Multimode RF transceiver advances WEDGE radio system

Wireless communications are evolving at an ever-increasing rate. Systems suchas GSM, EDGE and CDMA are being augmented with 3G and Wi-Fi capabilities,making an efficient and cost-effective multimode solution essential. The RF transceiver is a key ingredient of any multimode solution. Its design presents several challenges that are magnified when distinctly different modes such as GSM and WCDMA must both be hosted. This article examines some of the challenges related to multimode transceiver design, and presents a highly integrated, multimode RF transceiver solution that addresses the needs of GSM, EDGE and WCDMA.

 

Wireless standards necessarily pursue a dual path of consolidation
and expansion, as if this were a law of nature. Market
forces demand this. Wi-Fi solution providers were quick to integrate
802.11a/g with their 802.11b solutions. GSM solutions necessarily
integrated EDGE. In the same manner, combined GSM-EDGEWCDMA
solutions are also unavoidable.
These same market forces drive the multimode aspect of transceiver
design as well as the multiband perspective. Solutions that were
acceptable for single- or dual-band applications may not be acceptable
for triple- and quad-band service where external component cost and
size become unacceptable. Transceiver designers must be increasingly
forward-looking in anticipation of these factors, while at the same time
employ measured restraint so that present customer demands are well
served in the near-term. The discussion that follows focuses on attaining
some of the more demanding requirements that are commensurate with
a highly integrated GSM-EDGE-WCDMA transceiver solution, and the
role these requirements play in transceiver architecture selection.

 

Receiver considerations
Industry-favored solutions for GSM-EDGE have converged to
primarily one of two choices for the receive architecture: a) directconversion
or b) low-IF. Aside from complexity and low-cost features
that these architectures provide, several technical issues have warranted
these choices.
GSM-EDGE requires IP2 performance on the order of 50 dBm or
more when referred to the antenna input. This requirement amplifies
the already challenging issues pertaining to dc offsets in the receiver.
Direct-conversion receivers struggle with this problem more than
low-IF receivers since the dc component falls directly within the
receive bandwidth. The dc offset is also time varying because it is
driven by dynamic adjacent-channel interferers. It also is affected
by local oscillator (LO) leakage, low-noise amplifier (LNA) gain, and
temperature.
CMOS designs must also contend with fairly severe 1/f noise in
the sensitive IQ gain stages that immediately follow the downconversion
mixer. Detailed 1/f noise parameters depend significantly
on oxide thickness and channel length. RF CMOS technologies
in the 130 nm to 180 nm realm generally exhibit 1/f corner
frequencies on the order of several hundred kHz, thereby making the
low-IF architecture attractive for this reason. Issues of dc offset
are not eliminated entirely with the low-IF architecture, but the
severity is reduced.

 

image

 

Most WCDMA receivers have adopted
the zero-IF architecture.Owing to WCDMA’s
much wider modulationbandwidth, dc
offset issues are moreeasily addressed than
for GSM-EDGE. The bandwidth argument
also reduces the 1/fnoise issue because
(i) its impact on the overall receive signalto-
noise ratio (SNR) is considerably less,
and (ii) this noise is spread across multiple chips of the WCDMA waveform where it can be
effectively tracked out by the baseband signal processing if desired.
One of the major problems facing WCDMA receiver design pertains
to transmitter leakage that falls through the duplexer filtering into the LNA input.
This leakage adversely impacts attaining receiver
IP2 and IP3 requirements, and normally requires band-specific SAW
filters to be used between the LNA outputs and the mixer input.
In WCDMA low-band, the transmit signal is offset from the receive
signal by a scant 45 MHz whereas the offset is increased to 190
MHz for the IMT band near 2 GHz. These offsets combined with the
required filter attenuation that is needed make the on-chip filtering
option quite challenging. Since the filter follows immediately after
the LNA, its insertion loss must be reasonable or else additional
constraints are imposed on the LNA gain. As shown in Figure 1, the ratio
of inductor-Q to filter-Q must be at least a factor of four in order to
have a reasonably small insertion loss.

image

 

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To View the complete Article from Jim Crawford, Please Visit his Website HERE

Radio Architectures, Pt 3: Intermodulation and Intercept Points

Intermodulation and Intercept Points
The mixer generates intermediate freqeuency (IF) signals that result from the sum and difference of the LO and RF signals combined in the mixer:

These sum and difference signals at the IF port are of equal amplitude, but generally only the difference signal is desired for processing and demodulation so the sum frequency (also known as the image signal: see Fig. 8-11) must be removed, typically by means of IF bandpass or lowpass filtering.

A secondary IF signal, which can be called f*IF, is also produced at the IF port as a result of the sum frequency reflecting back into the mixer and combining with the second harmonic of the LO signal.

Mathematically, this secondary signal appears as:

This secondary IF signal is at the same frequency as the primary IF signal. Unfortunately, differences in phase between the two signals typically result in uneven mixer conversion-loss response. But flat IF response can be achieved by maintaining constant impedance between the IF port and following component load (IF filter and amplifier) so that the sum frequency signals are prevented from re-entering the mixer. In terms of discrete components, some manufacturers offer constant-impedance IF bandpass filters that serve to minimize the disruptive reflection of these secondary IF signals. Such filters attenuate the unwanted sum frequency signals by absorption. Essentially, the return loss of the filter determines the level of the sum frequency signal that is reflected back into the mixer.

If a mixer’s IF port is terminated with a conventional IF filter, such as a bandpass or lowpass type, the sum frequency signal will re-enter the mixer and generate intermodulation distortion. One of the main intermodulation products of concern is the two-tone, third-order product, which is separated from the IF by the same frequency spacing as the RF signal. These intermodulation frequencies are a result of the mixing of spurious and harmonic responses from the LO and the input RF signals:

But by careful impedance matching of the IF filter to the mixer’s IF port, the effects of the sum frequency products and their intermodulation distortion can be minimized.

EXAMPLE: Intermodulation and Intercept Points
To get a better understanding of intermodulation products, let’s consider the simple case of two frequencies, say f1 and f2. To define the products, we add the harmonic multiplying constants of the two frequencies. For example, the second order intermodulation products are (f1 +f2); the third order are (2f1 ‘f2); the fourth order are (2f1 +f2); the fifth order are (3f1 ‘f2); etc. If f1 and f2 are two frequencies of 100 kHz and 101 kHz (that is, 1 kHz apart) then we get the intermodulation products as shown in Table 8-1.

From the table it becomes apparent that only the odd order intermodulation products are close to the two fundamental frequencies of f1 and f2. Note that one third order product (2f1‘f2) is only 1 kHz lower in frequency than f1 and another (2f2 ‘f1) is only 1 kHz above f2. The fifth order product is also closer to the fundamentals than corresponding even order products.

These odd order intermodulation products are of interest in the first mixer state of a superheterodyne receiver. As we have seen earlier, the very function of a mixer stage—namely, forming an intermediate lower frequency from the sum/difference of the input signal and a local oscillatory—results in the production of nonlinearity. Not surprisingly, the mixer stage is a primary source of unwanted intermodulation products. Consider this example: A receiver is tuned to a signal on 1000 kHz but there are also two strong signals, f1on 1020 kHz and f2 on 1040 kHz. The closest signal is only 20 kHz away.

Our IF stage filter is sharp with a 2.5-kHz bandwidth, which is quite capable of rejecting the unwanted 1020-kHz signal. However, the RF stages before the mixer are not so selective and the two signals f1 and f2 are seen at the mixer input. As such, intermodulation components are readily produced, including a third order intermodulation component (2f1 ‘f2) at (2-1020’1040)=1000 kHz. This intermodulation product lies right on our input signal frequency! Such intermodulation components or out-of-band signals can easily cause interference within the working band of the receiver.

In terms of physical measurements, the two-tone, third-order intermodulation is the easiest to measure of the intermodulation interferences in an RF system. All that is needed is to have two carriers of equal power levels that are near the same frequency. The result of this measurement is used to determine the third-order intermodulation intercept point (IIP3), a theoretical level used to calculate third-order intermodulation levels at any total power level significantly lower than the intercept point.

The next Silicon Valley

The next Silicon Valley? You’re kidding, right?

Google the phrase, and you’ll find an archive of old stories with titles like "India likely to be the next Silicon Valley," "Could the next Silicon Valley be in a developing country?" "Is Vietnam the next Silicon Valley?" Or my favorite: "Could Silicon Valley be the next Detroit?"

Long the preeminent high-tech center in North America and the world, Silicon Valley saw unrivaled success that has proved very tough to clone or import. The Valley has done a great job over the years of attracting and retaining global talent and local capital, and of building world-class tech companies around brilliant ideas.

But as last week’s General Motors bankruptcy shows, the U.S. industrial base is undergoing wrenching change. And on the technology front, R&D in everything from electronics to solar tech is increasingly being done outside of Silicon Valley. Technology innovation itself has become globalized.

As history has shown, tough economic times don’t halt the evolution of technologies and their applications. On the contrary, tech innovation can drive economic recovery and strengthen competitiveness. Consequently, such innovation has become a national imperative in many nations around the world.

Last week, the International Association of Science Parks (IASP) held its annual conference. The event, hosted in Raleigh, N.C., by Research Triangle Park, drew more than 700 delegates from more than 40 countries, representing all quarters of the global innovation economy. As one delegate from the Berlin Adlershof tech cluster put it, "The hard-core tech sector is doing very well."

Like Silicon Valley, regional tech centers from Brazil to Bangalore are finding that technology development thrives in an environment of creative intellectual energy that offers a networked economy, proximity to research institutions and universities, unique intellectual property development, a diverse base of high-tech talent, access to investment capital and infrastructure. As IASP delegates would attest, these attributes are now characteristic of many metropolitan regions around the world.

Innovation hubs

Innovation hubs and science parks are no longer limited to a few select locations. In today’s economy, innovative businesses and regions are appearing and flourishing by making global connections, tapping into virtual opportunities, breaking down local jurisdictions and building regional innovation engines–what IASP keynoters termed "future knowledge ecosystems."

By some estimates, in as little as 10 years virtually all jobs will have a technology component. Highly skilled workers can choose where they want to live, work and play. An epic battle is on among regions globally to attract and retain them.

Ironically, as the worst economic downturn in modern times unfolds, thousands of talented professionals, engineers, scientists and students from around the world are leaving Silicon Valley, or are having difficulty staying in or entering the United States.

According to a recent Business Week article, "Foreign students who graduate from U.S. universities with degrees in science and engineering are increasingly leaving the U.S. to pursue job opportunities in their home countries." The article quotes a Duke University report, released in March and titled "Losing the World’s Best and Brightest," that warns, "The departure of these foreign nationals could represent a significant loss for the U.S. science and engineering workforce, where these immigrants have played increasingly larger roles over the past three decades."

Craig Barrett, the recently retired chairman of Intel, despaired of the United States’ stemming those losses.

In a December 2007 article in the Washington Post, Barrett noted: "The European Union has taken steps that the U.S. Congress can’t seem to muster the courage to take. By proposing simple changes in immigration policy, EU politicians served notice that they are serious about competing with the United States and Asia to attract the world’s top talent to live, work and innovate in Europe.

"With Congress gridlocked on immigration, it’s clear that the next Silicon Valley will not be in the United States."

Maybe not. But as tech development centers in places like China, the Gulf states, India, Israel, Korea, Russia, South America, Southeast Asia and Taiwan become stronger links in the new, complex technology innovation chain, the current Silicon Valley might create a new future for itself as the granddaddy of the "knowledge ecosystem," securing its place as it gingerly looks over its shoulder.

Radio Architectures, Pt 2: Receivers, LOs, and Mixers

By Christopher Bowick

The following is excerpted from Chapter 8 from a new edition of the book, RF Circuit Design, 2e by Christopher Bowick. You Can buy the book HERE

Moving up the scale in complexity, we come to the next evolutionary RF architecture: the tuned-radio-frequency (TRF) receiver (see Fig. 8-6). This early design was one of the first to use amplification techniques to enhance the quality of the signal reception. A TRF receiver consisted of several RF stages, all simultaneously tuned to the received frequency before detection and subsequent amplification of the audio signal. Each tuned stage consisted of a bandpass filter –which need not be an LC tank filter but could also be a Surface Acoustic Wave (SAW) filter or a dielectric cavity filter– with an amplifier to boost the desired signal while reducing unwanted signals such as interference.

The final stage of the design is a combination of a diode rectifier and audio amplifier, collectively known as a grid-leak detector. In contrast to other radio architectures, there is no translation in frequency of the input signals, and no mixing of these input signals with those from a tunable LO. The original input signal is demodulated at the detector stage. On the positive side, this simple architecture does not generate the image signals that are common to other receiver formats using frequency mixers, such as superheterodynes.

The addition of each LC filter-amplifier stage in a TRF receiver increases the overall selectivity. On the downside, each such stage must be individually tuned to the desired frequency since each stage has to track the previous stage. Not only is this difficult to do physically, it also means that the received bandwidth increases with frequency. For example, if the circuit Q was 50 at the lower end of the AM band, say 550 kHz, then the receiver bandwidth would be 500/50 or 11 kHz–a reasonable value. However at the upper end of the AM spectrum, say 1650 kHz, the received bandwidth increases to 1650/50 or 33 kHz.

As a result, the selectivity in a TRF receiver is not constant, since the receiver is more selective at lower frequencies and less selective at higher frequencies. Such variations in selectivity can cause unwanted oscillations and modes in the tuned stages. In addition, amplification is not constant over the tuning range. Such shortcomings in the TRF receiver architecture have led to more widespread adoption of other receiver architectures, including direct-conversion and superheterodyne receivers, for many modern wireless applications.

Direct-Conversion Receiver
A way to overcome the need for several individually tuned RF filters in the TRF receiver is by directly converting the original signal to a much lower baseband frequency. In the direct conversion receiver (DCR) architecture, frequency translation is used to change the high input frequency carrying the modulated information into a lower frequency that still carries the modulation but which is easier to detect and demodulate. This frequency translation is achieved by mixing the input RF signal with a reference signal of identical or near-identical frequency (see Fig. 8-7). The nonlinear mixing of the two signals results in a baseband signal prior to the detection or demodulating stage of the front-end receiver.

The reference signal is generated by a local oscillator (LO). When an input RF signal is combined in a nonlinear device, such as a diode or field-effect-transistor (FET) mixer, with an LO signal, the result is an intermediate-frequency (IF) signal that is the sum or difference of the RF and LO signals.

When the LO signal is chosen to be the same as the RF input signal, the receiver is said to have a homodyne (or “same frequency”) architecture and is also known as a zero-IF receiver. Conversely, if the reference signal is different from the frequency to be detected, then it’s called a heterodyne (or “different frequency”) receiver. The terms superheterodyne and heterodyne are synonyms (“super” means “higher” or “above” not “better”).

In either homodyne or heterodyne approaches, new frequencies are generated by mixing two or more signals in a nonlinear device, such as a transistor or diode mixer. The mixing of two carefully chosen frequencies results in the creation of two new frequencies, one being the sum of the two mixed frequencies and the other being the difference between the two mixed signals.

The lower frequency is called the beat frequency, in reference to the audio “beat” that can be produced by two signals close in frequency when the mixing product is an actual audio-frequency (AF) tone. For example, if a frequency of 2000 Hz and another of 2100 Hz were beat together, then an audible beat frequency of 100 Hz would be produced. The end result is a frequency shifting from a higher frequency to lower—and in the case of RF receivers—baseband frequency.

Direct conversion or homodyne (zero-IF) receivers use an LO synchronized to the exact frequency of the carrier in order to directly translate the input signals to baseband frequencies. In theory, this simple approach eliminates the need for multiple frequency downconversion stages along with their associated filters, frequency mixers, and LOs. This means that a fixed RF filter can be used after the antenna, instead of multiple tuned RF filters as in the TRF receiver. The fixed RF filter can thus be designed to have a higher Q.

In direct-conversion design, the desired signal is obtained by tuning the local oscillator to the desired signal frequency. The remaining unwanted frequencies that appear after downconversion stay at the higher frequency bands and can be removed by a lowpass filter placed after the mixer stage.

If the incoming signal is digitally encoded, then the RF receiver uses digital filters within a DSP to perform the demodulation. Two mixers are needed to retain both the amplitude and phase of the original modulated signal: one for the in-phase (I) and another for a quadrature (Q) baseband output. Quadrature downconversion is needed since two sidebands generally form around any RF carrier frequency. As we have already seen, these sidebands are at different frequencies. Thus, using a single mixer, for a digitally encoded signal, would result in the loss of one of the sidebands. This is why an I/Q demodulator is typically used for demodulating the information contained in the I and Q signal components.

Unfortunately, many direct-conversion receivers are susceptible to spurious LO leakage, when LO energy is coupled to the I/Q demodulator by means of the system antenna or via another path. Any LO leakage can mix with the main LO signal to generate a DC offset, possibly imposing potentially large DC offset errors on the frequency-translated baseband signals. Through careful design, LO leakage in a direct-conversion receiver can be minimized by maintaining high isolation between the mixer’s LO and RF ports.

Perhaps the biggest limitation of direct-conversion receivers is their susceptibility to various noise sources at DC, which creates a DC offset. The sources of unwanted signals typically are the impedance mismatches between the amplifier and mixer. As noted earlier in this chapter, improvements in IC integration via better control of the semiconductor manufacturing process have mitigated many of the mismatch-related DC offset problems.

Still another way to solve DC offset problems is to downconvert to a center frequency near, but not at, zero. Near-zero IF receivers do just that, by downconverting to an intermediate frequency (IF) which preserves the modulation of the RF signal by keeping it above the noise floor and away from other unwanted signals. Unfortunately, this approach creates a new problem, namely that the image frequency and the baseband beat signals that arise from inherent signal distortion, can both fall within the intermediate band. The image frequencies, to be covered later, can be larger than the desired signal frequency, thus causing resolution challenges for the analog-to-digital converter.

Superheterodyne Receivers
In contrast to the simplicity of the direct-conversion receiver, the superheterodyne receiver architecture often incorporates multiple frequency translation stages along with their associated filters, amplifiers, mixers, and local oscillators (see Fig. 8-8).

But in doing so, this receiver architecture can achieve unmatched selectivity and sensitivity. Unlike the direct-conversion receiver in which the LO frequencies are synchronized to the input RF signals, a superheterodyne receiver uses an LO frequency that is offset by a fixed amount from the desired signal. This fixed amount results in an intermediate frequency (IF) generated by mixing the LO and RF signals in a nonlinear device such as a diode or FET mixer.

Generating local oscillators
The LO is often a phase-locked voltage-controlled oscillator (VCO) capable of covering the frequency range of interest for translating incoming RF signals to a desired IF range. In recent years, a number of other frequency-stabilization techniques, including analog fractional-N frequency synthesis and integer-N frequency synthesis as well as direct-digital-synthesis (DDS) approaches, have been used to generate the LO signals in wireless receiver architectures for frequency translation.

Any LO approach should provide signals over a frequency band of interest with the capability of tuning in frequency increments that support the system’s channel bandwidths. For example, a system with 25-kHz channels is not well supported by a synthesized LO capable of tuning in minimum steps of only 1 MHz. In addition, the LO should provide acceptable single-sideband (SSB) phase-noise performance, specified at an offset frequency that coincides with the system’s channel spacing. Referring to an LO’s SSB phase noise offset 1MHz from the carrier will not provide enough information about the phase noise that is closer to the carrier and that may affect communications systems performance in closely spaced channels. Phase noise closer to the carrier is typically specified at offset frequencies of 1 kHz or less.

The LO source should also provide adequate drive power for the front-end mixers. In some cases, an LO buffer amplifier may be added to increase the signal source’s output to the level required to achieve acceptable conversion loss in the mixer. And for portable applications, the power supply and power consumption of the LO become important considerations when planning for a power budget.

Mixers
Mixers are an integral component in any modern radio front end (see Fig. 8-9). Frequency mixers can be based on a number of different nonlinear semiconductor devices, including diodes and field-effect transistors (FETs). Because of their simplicity and capability of operation without DC bias, diode mixers have been prevalent in many wireless systems. Mixers based on diodes have been developed in several topologies, including single-ended, single-balanced, and double-balanced mixers. Additional variations on these configurations are also available, such as image-reject mixers and harmonic mixers which are typically employed at higher, often millimeter-wave, frequencies.

The simplest diode mixer is the single-ended mixer, which can be formed with an input balanced-unbalanced (balun) transformer, a single diode, an RF choke, and a lowpass filter. In a single diode mixer, insertion loss results from conversion loss, diode loss, transformer loss. The mixer sideband conversion is nominally 3 dB, while the transformer losses (balun losses) are about 0.75 dB on each side, and there are diode losses because of the series resistances of the diodes.

The equivalent circuit of a diode consists of a series resistor and a time-variable electronic resistor. Moving up slightly in complexity, a single-ended mixer consists of a single diode, input matching circuitry, balanced-unbalanced (balun) transformer or some other means for injecting a mixing signal with the RF input signal, and a lowpass or bandpass filter to pass desired mixer products and reject unwanted signal components.

Single-ended mixers are inexpensive and often used in low-cost detectors, such as motion detectors. The input balun must be highly selective to prevent radiation of the LO signal back into the RF port and out of the antenna. Although the behavior of the diode changes with LO level, it can be matched for impedance at a particular frequency, such as the LO frequency, to achieve fairly consistent conversion-loss performance and flatness.

The desired frequency converted signals are available at the IF port; the filter eliminates the unwanted high-frequency signal components generated by the mixing process. The LO drive level can be arbitrary, although different types of mixers and their diodes generally dictate an optimum LO drive level for mixer operation. The dimensions of the diode will dictate the frequency of operation, allowing use through millimeter wave frequencies if the diode is made sufficiently small.

Some single-ended mixers use an anti-parallel diode pair in place of the single diode to double the LO frequency and use the second harmonics of the LO’s fundamental frequency, somewhat simplifying the IF filtering requirements. The trade-off involves having to supply higher LO power in order to achieve sufficient mixing power by means of the LO’s second-harmonic signals.

A single-balanced mixer uses two diodes connected back to back. In the back-to-back configuration, noise components from the LO or RF that are fed into one diode are generated in the opposite sense in the other diode and tend to cancel at the IF port.

A double-balanced mixer is typically formed with four diodes in a quad configuration (see Fig. 8-10). The quad configuration provides excellent suppression of spurious mixing products and good isolation between all ports. Because of the symmetry, the LO voltage is sufficiently isolated from the RF input port and no RF voltage appears at the LO port. With a sufficiently large LO drive level, strong conduction occurs in alternate pairs of diodes, changing them from a low to high resistance state during each half of the LO’s frequency cycle.

Because the RF voltage is distributed across the four diodes, the 1-dB compression point is higher than that of a single-balanced mixer, although more LO power is needed for mixing. The conversion loss of a double-balanced mixer is similar to that of a single-balanced mixer, although the dynamic range of the double-balanced mixer is much greater due to the increase in the intercept point (recall IP discussion from earlier chapters).

By incorporating FET or bipolar transistors into monolithic IC mixer topologies, it is possible to produce active mixers with conversion gain rather than conversion loss. In general, this class of mixer can be operated with lower LO drive levels than passive FET or diode mixers, although active mixers will also distort when fed with excessive LO drive levels.

For RF front ends, wireless receivers, or even complete transceivers fabricated using monolithic IC semiconductor processes, the Gilbert cell mixer is a popular topology for its combination of low power consumption, high gain, and wide bandwidth. Originally designed as an analog four-quadrant multiplier for small-signal applications, the Gilbert-cell mixer can also be used in switching-mode operation for mixing purposes. Because it requires differential signals, the Gilbert-cell mixer is usually implemented with input and output transformers in the manner of double-balanced mixers.

Understand Radio Architectures, Part 1

The fundamental operation of an RF front end is fairly straightforward: it detects and processes radio waves that have been transmitted with a specific known frequency or range of frequencies and known modulation format. The modulation carries the information of interest, be it voice, audio, data, or video.

The receiver must be tuned to resonate with the transmitted frequency or frequencies in order to detect them. Those received signals are then filtered from all surrounding signals and noise and amplified prior to a process known as demodulation, which removes the desired information from the radio waves that carried it.

These three steps—filtering, amplification and demodulation—detail the overall process. But actual implementation of this process (i.e., designing the physical RF receiver printed-circuit board (PCB)) depends upon the type, complexity, and quantity of the data being transmitted. For example, designing an RF front end to handle a simple amplitude-modulated (AM) signal requires far less effort and hardware (and even software) than building an RF front end for the latest third-generation (3G) mobile telecommunications handset.

Because of the enhanced performance of analog components due to IC process improvements and decreasing costs of more powerful digital-signal-processing (DSP) hardware and software functions, the ways that different RF front-end architectures are realized has changed over the years. Still, the basic requirements for an RF front end, such as the frequency range and type of carrier to be received, the RF link budget, and the power, performance, and size restrictions of the front-end design, remain relatively the same in spite of the differences in radio architectures.

Let’s start by looking at the simplest of radio architectures or implementations.

AM Detector Receivers
One of the basic RF receiver architectures for detecting a modulated signal is the amplitude modulation (AM) detector receiver (see Fig. 8-2). The name comes from the fact that information like speech and music could be converted into amplitude (voltage) modulated signals riding on a carrier wave. Such an RF signal could be de-modulated at the receiving end by means of a simplediode detector. All that is needed for a basic AM receiver—like a simple crystal radio—is an antenna, RF filter, detector, and (optional) amplifier to boost the recovered information to a level suitable for a listening device, such as a speaker or headphones.

The antenna, which is capacitive at the low frequencies used for AM broadcasting, is series matched with an inductor to maximize current through both, thus maximizing the voltage across the secondary coil. A variable capacitance filter may be used to select the designed frequency band (or channel) and to block any unwanted signals, such as noise. The filtered signal is then converted to demodulate the AM signal and recover the information. Fig. 8-3 represents a schematic version of the block diagram shown in Fig. 8-2.

The heart of the AM architecture is the detector demodulator. In early crystal radios, the detector was simply a fine metal wire that contacted a crystal of galena (lead sulfide), thus creating a point contact rectifier or “crystal detector.” In these early designs, the fine metal contact was often referred to as a “catwhisker.” Although point-contact diodes are still in use today in communication receivers and radar, most have been replaced by pn-junction diodes, which are more reliable and easier to manufacture.

For a simpleAM receiver, the detector diode acts as a half-wave rectifier to convert or rectify a received AC signal to a DC signal by blocking the negative or positive portion of thewaveform (see Fig. 8-4).A half-wave rectifier clips the input signal by allowing either the positive or negative half of theAC wave to pass easily through the rectifier, depending upon the polarity of the rectifier.

A shunt inductor is typically placed in front of the detector to serve as an RF choke. The inductor maintains the input to the detector diode at DC ground while preserving a high impedance in parallel with the diode, thus maintaining the RF performance.

In a simple detector receiver, the AM carrier wave excites a resonance in the inductor/tuned capacitor (LC) tank subcircuit. The tank acts like a local oscillator (LO) to the current through the diode is proportional to the amplitude of the resonance and this gives the baseband signal (typically analog audio).

The baseband signal may be in either analog or digital format, depending upon the original format of the information used to modulate the AM carrier.As we shall see, this process of translating a signal down or up to the baseband level becomes a critical technique in most modern radios. The exception is time domain or pulse position modulation. Interestingly, this scheme dates back to the earliest (spark gap) radio transmitters. It’s strange how history repeats itself. Another example is that the earliest radios were digital (Morse code), than analog was considered superior (analog voice transmission), now digital is back!

The final stage of a typical AM detector system is the amplifier, which is needed to provide adequate drive levels for an audio listening device, such as a headset or speaker. One of the disadvantages of the signal diode detector is its poor power transfer efficiency. But to understand this deficiency, you must first understand the limitation of the AM design that uses a halfwave rectifier at the receiver. At transmission from the source, the AM signal modulation process generates two copies of the information (voice or music) plus the carrier. For example, consider an AM radio station that broadcasts at a carrier frequency of 900 kHz. The transmission might be modulated by a 1000-Hz (1-kHz) signal or tone. The RF front end in an AM radio receiver will pick up the 900-kHz carrier signal along with the 1-kHz plus and minus modulation around the carrier, at frequencies of 901 and 899 kHz, respectively (see Fig. 8-5). The modulation frequencies are also known as the upper and lower sideband frequencies, respectively.

But only one of the sidebands is needed to completely demodulate the received signal. The other sideband contains duplicate information. Thus, the disadvantages of AM transmissions are twofold: (1) for a given information bandwidth, twice that bandwidth is needed to convey the information, and (2) the power used to transmit the unused sideband is wasted (typically, up to 50% of the total transmitted power).

Naturally, there are other ways to demodulate detector-based receiver architectures. We have just covered an approach used in popular AM receivers. Replacing the diode detector with another detector type would allow us to detect frequency-modulated (FM) or phase-modulated (PM) signals, this latter modulation commonly used in transmitting digital data. For example, many modern telecommunication receivers rely heavily on phaseshift keying (PSK), a form of phase (angle) modulation. The phrase “shift keying” is an older expression (from the Morse code era) for “digital.”

All detector circuits are limited in their capability to differentiate between adjacent signal bands or channels. This capability is a measure of the selectivity of the receiver and is a function of the input RF filter to screen out unwanted signals and to pass (select) only the desired signals. Selectivity is related to the quality factor or Q of the RF filter. A high Q means that the circuit provides sharp filtering and good differentiation between channels—a must for modern communication systems.

Unfortunately, tuning the center carrier frequency of the filter across a large bandwidth while maintaining a high differentiation between adjacent channels is very difficult at the higher frequencies found in today’s mobile devices. Selectivity across a large bandwidth is complicated by a receiver’s sensitivity requirement, or the need to need to detect very small signals in the presence of system noise—noise that comes from the earth (thermal noise), not just the receiver system itself. The sensitivity of receiving systems is defined as the smallest signal that leads to an acceptable signal-to-noise ratio (SNR).

Receiver selectivity and sensitivity are key technical performance measures (TPMs) and will be covered in more detail in this chapter. At this point, it is sufficient to note that the AM diode detector architecture is limited in selectivity and sensitivity.

Part 2 of this article will cover direct-conversion, and superheterodyne receiver configurations.

Printed with permission from Newnes, a division of Elsevier. Copyright 2008. “RF Circuit Design, 2e” by Christopher Bowick. For more information about this title and other similar books, please visit www.newnespress.com.

What’s in an RF Front End?

The following is excerpted from Chapter 8 from a new edition of the book, RF Circuit Design, 2e by Christopher Bowick. Order the Book here http://www.rfengineer.net/rf-books/

The RF front end is generally defined as everything between the antenna and the digital baseband system. For a receiver, this “between” area includes all the filters, low-noise amplifiers (LNAs), and down-conversion mixer(s) needed to process the modulated signals received at the antenna into signals suitable for input into the baseband analog-to-digital converter (ADC). For this reason, the RF front end is often called the analog-to-digital or RF-to-baseband portion of a receiver.

Radios work by receiving RF waves containing previously modulated information sent by a RF transmitter. The receiver is basically a low noise amplifier that down converts the incoming signal. Hence, sensitivity and selectivity are the primary concerns in receiver design.

Conversely, a transmitter is an up converts an outgoing signal prior to passage through a high power amplifier. In this case, non-linearity of the amplifier is a primary concern. Yet, even with these differences, the design of the receiver front end and transmitter back end share many common elements—like local oscillators. In this chapter, we’ll concentrate our efforts on understanding the receiver side.

Thanks to advances in the design and manufacture of integrated circuits (ICs), some of the traditional analog IF signal processing tasks can be handled digitally. These traditional analog tasks, like filtering and up-down conversion, can now be handled by means of digital filters and digital signal processors (DSPs). Texas Instruments have coined the term digital radio processors for this type of circuit.

This migration of analog into digital circuits means that the choice of what front-end functions are implemented by analog and digital means generally depends on such factors as required performance, cost, size, and power consumption. Because of the mix of analog and digital technologies, RF front end chips using mixed-signal technologies may also be referred to as RF-to-digital or RF-to-baseband (RF/D) chips.

Why is the front end so important? It turns out that this is arguably the most critical part of the whole receiver. Trade-offs in overall system performance, power consumption, and size are determined between the receiver front end and the ADCs in the baseband (middle end). In more detail, the analog front end sets the stage for what digital bit-error-rate (BER) performance is possible at final bit detection. It is here that the receiver can, within limits, be designed for the best potential signal to noise ratio (SNR).

Higher Levels of Integration
Look inside any modern mobile phone, multimedia device, or home-entertainment control system that relies on the reception and/or transmission of wireless signals and you’ll find an RF front end. In the RIM Blackberry PDA, for example, the communication system consists of both a transceiver chip and RF front-end module (see Fig. 8-1).

8-1. Tear down of modern mobile device reveals several RF front-end chips. (Courtesy of iSuppli)

The front-end module incorporates several integrated circuits (ICs) that may be based on widely different semiconductor processes, such as conventional silicon CMOS and advanced silicon germanium (SiGe) technologies. Functionally, such multichip modules provide most if not all of the analog signal processing—filtering, detection, amplification and demodulation via a mixer. (The term “system-in-package” or SIP is a synonym for multichip module or MCM.)

Multichip front-end modules demonstrate an important trend in RF receiver design, namely, ever-increasing levels of system integration required to squeeze more functionality into a single chip. The reasons for this trend—especially in consumer electronics—come from the need for lower costs, lower power consumption (especially in mobile and portable products), and smaller product size.

Still, regardless of the level of integration, the basic RF architecture remains unchanged: signal filtering, detection, amplification and demodulation. More specifically, a modulated RF carrier signal couples with an antenna designed for a specific band of frequencies.

The antenna passes the modulated signals along to the RF receiver’s front end. After much conditioning in the front-end circuitry, the modulation or information portion of the signal—now in the form of an analog baseband signal—is ready for analog-to-digital conversion into the digital world. Once in the digital realm, the information can be extracted from the digitized carrier waveforms and made available as audio, video, or data.

Before the advent of such tightly integrated modules, each functional block of the RF front end was a separate component, designed separately. This means that there were separate components for the RF filter, detector, mixer-demodulator, and amplifier. More importantly, this meant that all of these physically independent blocks had to be connected together.

To prevent signal attenuation and distortion and to minimize signal reflections due to impedance differences between function blocks, components were standardized for a characteristic impedance of 50 ohms, which was also the impedance of high-frequency test equipment. The 50-ohm coaxial cable interface was a trade-off that minimized signal attenuation while maximizing power transfer—signal energy—between the independently designed RF filter, LNA, and mixer.

Before higher levels of functional integration and thus lower costs could be achieved, it was necessary to design and manufacture these RF functional blocks using standard semiconductor processes, such as silicon CMOS IC processes.

Unfortunately, one of the drawbacks of CMOS technology can be the difficulty in achieving a 50-ohm input impedance. Still, it is only necessary to have the 50-ohm matched input and output impedances when the connection lines between the sub-circuits is long compared to the wavelength of the carrier wave. For ICs and MCMs at GHz frequencies, connections lines are short, so 50-ohm between sub-circuits isn’t a problem. It is necessary to somehow get to 50 ohms to connect to the (longer) printed circuit board traces.

This is but one example of the changes that have taken place with modern integrated front ends. We will not cover all the changes here. Instead, we’ll focus on the important design parameters that can affect the design of an RF front end, including the signal-to-noise ratio (SNR), receiver sensitivity, receiver and channel filter selectivity, and even the bit resolution of the ADC (covered later). This high-level description of the RF front end reveals not only the basic functioning but also the potential system trade-offs that must be considered.

Part 2 will take a look at several different radio architectures: detector, direct-conversion, and superheterodyne receiver configurations.

Printed with permission from Newnes, a division of Elsevier. Copyright 2008. “RF Circuit Design, 2e” by Christopher Bowick. For more information about this title and other similar books, please visit www.newnespress.com.

RF-Induced Hyperthermia – Need Help Building This

On of our readers needs help building one of these.

US Patent Application # 20060190063

Enhanced Systems and Methods for RF-Induced Hyperthermia

24 August 2006
US Cl. 607/101
Intl Cl. A61F 2/00 20060101 A61F002/00

Abstract — A method of inducing hyperthermia in at least a portion of a target area–e.g., a tumor or a portion of a tumor or targeted cancerous cells–is provided. Targeted RF absorption enhancers, e.g., antibodies bound to RF absorbing particles, are introduced into a patient. These targeted RF absorption enhancers will target certain cells in the target areas and enhance the effect of a hyperthermia generating RF signal directed toward the target area. The targeted RF absorption enhancers may, in a manner of speaking, add one or more RF absorption frequencies to cells in the target area, which will permit a hyperthermia generating RF signal at that frequency or frequencies to heat the targeted cells.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefits of, provisional application Ser. No.: 60/569,348 filed on May 7, 2004, which is entitled System and Method For RF-Induced Hyperthermia, and which is incorporated herein by reference. This application is also a continuation in part of and claims priority to non-provisional application Ser. No. 10/969,477 filed on Oct. 8, 2004, which is also entitled System and Method for RF-Induced Hyperthermia, and which is incorporated herein by reference. This application is also related to U.S. patent application Ser. No. ______, filed herewith and entitled Systems and Methods for Combined RF-Induced Hyperthermia and Radioimmunotherapy and filed herewith and related to U.S. patent application Ser. No. ______, filed herewith and entitled Systems and Methods for RF-Induced Hyperthermia Using Biological Cells and Nanoparticles as RF Enhancer Carriers, both of which are incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention relates generally to the field of radio frequency (RF) circuits, and more specifically to an RF transmitter and receiver system and method for inducing hyperthermia in a target area.

BACKGROUND OF THE INVENTION

[0003] Hyperthermia is characterized by a very high fever, especially when induced artificially for therapeutic purposes. RF electromagnetic energy is electromagnetic energy at any frequency in the radio spectrum from 9000 Hz to 3 THz (3000 GHz). It is known in the art to use contact antennas to direct RF electromagnetic radiation to intentionally induce hyperthermia in human tissue for therapeutic purposes, e.g., destroying diseased cells (e.g., U.S. Pat. No. 4,800,899). There are also several other prior art RF heating devices described in various publications (e.g., the Thermotron RF-8 system, Yamamoto Viniter Co. of Osaka, Japan, and the KCTPATEPM system, Russia, and U.S. Pat. No. 5,099,756; Re. 32,066; and U.S. Pat. No. 4,095,602 to LeVeen).

SUMMARY OF THE INVENTION

[0004] In accordance with one exemplary embodiment of the present invention, a method of inducing hyperthermia in at least a portion of a target area–e.g., a tumor or a portion of a tumor or targeted cancerous cells–is provided. In this first exemplary method, targeted RF absorption enhancers, e.g., antibodies bound to RF absorbing particles, are introduced into a patient. These targeted RF absorption enhancers will target certain cells in the target areas and enhance the effect of a hyperthermia generating RF signal directed toward the target area. The targeted RF absorption enhancers may, in a manner of speaking, add one or more artificial RF absorption frequencies to cells in the target area, which will permit a hyperthermia generating RF signal at that frequency or frequencies to heat the targeted cells.

[0005] In accordance with another exemplary embodiment of the present invention, another method of inducing hyperthermia in at least a portion of a target area is provided. In this second exemplary method RF absorption enhancers (targeted and/or non-targeted) are introduced into a patient and a multifrequency hyperthermia generating RF signal is directed toward the target area. The multifrequency hyperthermia generating RF signal may be a frequency modulated (FM) signal having parameters selected to correspond to a sample of particles being used as energy absorption enhancer particles in the RF absorption enhancers. For example, the center frequency of an FM hyperthermia generating signal may correspond to a resonant frequency of nominally sized particles used as energy absorption enhancer particles and the modulation of the FM hyperthermia generating signal may correspond to a size tolerance of the particles.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exemplary high-level block diagram of a non-invasive RF system for inducing hyperthermia in a target area;

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FIG. 2 is an exemplary medium-level block diagram of an RF system for inducing hyperthermia in a target area;

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FIGS. 3, 3A, 4, 5 and 6 are exemplary embodiments of transmission heads and reception heads on either side of a target areas;

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FIG. 7 is an exemplary high-level flowchart of an embodiment of a RF methodology for inducing hyperthermia in a target area;

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FIG. 8 is an exemplary medium level flow chart of an embodiment of an RF methodology for inducing hyperthermia in a target area;

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FIG. 9 is an exemplary medium level flow chart of an embodiment of an RF methodology for inducing in-vitro hyperthermia in a target area;

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FIG. 10 is an exemplary medium level flow chart of an embodiment of a magnetic methodology for separating cells;

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FIGS. 11, 12A, and 12B are high-level schematic block diagrams of exemplary RF systems;

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FIG. 13 is a front/left perspective schematic view of another exemplary transmission head;

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FIG. 14 is a left side schematic view of the exemplary transmission head of FIG. 13;

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FIG. 15 is a left side schematic view of an exemplary pair of heads of FIG. 13 arranged as an exemplary transmitter head and receiver head;

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FIG. 16 is a front/left perspective schematic view of yet another exemplary transmission head;

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FIG. 17 is a left side schematic view of the exemplary transmission head of FIG. 16;

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FIG. 18 is a left side schematic view of an exemplary pair of heads of FIG. 16 arranged as an exemplary transmitter head and receiver head;

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FIGS. 19, 20, 21A, 21B, 22A, and 22B are schematic diagrams showing various exemplary configurations of transmitter heads and receiver heads;

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FIG. 23 is a medium-level schematic block diagram of an exemplary RF generator;

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FIGS. 24-29 are schematic circuit diagrams of exemplary tuned circuit RF absorbing particles for RF absorption enhancers; and

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FIGS. 30-33 are schematic illustrations of exemplary implementations of tuned circuit RF absorbing particles for RF absorption enhancers.

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DETAILED DESCRIPTION

[0024] In the accompanying drawings which are incorporated in and constitute a part of the specification, exemplary embodiments of the invention are illustrated, which, together with a general description of the invention given above, and the detailed description given below, serve to example principles of the invention.

[0025] Referring to the drawings, and initially to FIG. 1, there is shown a first exemplary embodiment of a non-invasive RF system 100 for inducing hyperthermia in a target area 106. System 100 comprises an RF transmitter 102 in circuit communication with a transmission head 104 and an RF receiver 110 in circuit communication with a reception head 108. “Circuit communication” as used herein is used to indicate a communicative relationship between devices. Direct electrical, optical, and electromagnetic connections and indirect electrical, optical, and electromagnetic connections are examples of circuit communication. Two devices are in circuit communication if a signal from one is received by the other, regardless of whether the signal is modified by some other device. For example, two devices separated by one or more of the following–transformers, optoisolators, digital or analog buffers, analog integrators, other electronic circuitry, fiber optic transceivers, or even satellites–are in circuit communication if a signal from one reaches the other, even though the signal is modified by the intermediate device(s). As a final example, two devices not directly connected to each other (e.g. keyboard and memory), but both capable of interfacing with a third device, (e.g., a CPU), are in circuit communication.

[0026] In exemplary system 100, the RF transmitter 102 generates an RF signal 120 at a frequency for transmission via the transmission head 104. Optionally, the RF transmitter 102 has controls for adjusting the frequency and/or power of the generated RF signal and/or may have a mode in which an RF signal at a predetermined frequency and power are transmitted via transmission head 104. In addition, optionally, the RF transmitter 102 provides an RF signal with variable amplitudes, pulsed amplitudes, multiple frequencies, etc.

[0027] The RF receiver 110 is in circuit communication with the reception head 108. The RF receiver 110 is tuned so that at least a portion of the reception head 108 is resonant at the frequency of the RF signal 120 transmitted via the transmission head 104. As a result, the reception head 108 receives the RF signal 120 that is transmitted via the transmission head 104.

[0028] The transmission head 104 and reception head 108 are arranged proximate to and on either side of a general target area 106. General target 106 is general location of the area to be treated. The general target area 106 is any target area or type of cells or group of cells, such as for example, tissue, blood cells, bone marrow cells, etc. The transmission head 104 and reception head 108 are preferably insulated from direct contact with the general target area 106. Preferably, the transmission head 104 and reception head 108 are insulated by means of an air gap 112. Optional means of insulating the transmission head 104 and reception head 108 from the general target area 106 include inserting an insulating layer or material 310 (FIG. 3), such as, for example, Teflon.RTM. between the heads 104, 108 and the general target area 106. Other optional means include providing an insulation area on the heads 104, 108, allowing the heads to be put in direct contact with the general target area 106. The transmission head 104 and the reception head 108, described in more detail below, may include one or more plates of electrically conductive material.

[0029] The general target area 106 absorbs energy and is warmed as the RF signal 120 travels through the general target area 106. The more energy that is absorbed by an area, the higher the temperature increase in the area. Generally, the general target area 106 includes a specific target area 130. Specific target area 130 includes the tissue or higher concentration of cells, such as, for example, a tumor, that are desired to be treated by inducing hyperthermia. Preferably, the general target area is heated to for example, to between 106.degree. and 107.degree.. Thus, preferably, the specific target area 130 receives higher concentrations of the RF signal 120 then the general target area 106. As a result, the specific target area 130 absorbs more energy, resulting in a higher temperature in the specific target area 130 than in the surrounding general target area 106.

[0030] Energy absorption in a target area can be increased by increasing the RF signal 120 strength, which increases the amount of energy traveling through the general target area 106. Other means of increasing the energy absorption include concentrating the signal on a localized area, or specific target area 130, and/or enhancing the energy absorption characteristics of the target area 130.

[0031] One method of inducing a higher temperature in the specific target area 130 includes using a reception head that is smaller than the transmission head. The smaller reception head picks up more energy due to the use of a high-Q resonant circuit described in more detail below. Optionally, an RF absorption enhancer 132 is used. An RF absorption enhancer is any means or method of increasing the tendency of the specific target area 130 to absorb more energy from the RF signal. Injecting an aqueous solution is a means for enhancing RF absorption. Aqueous solutions suitable for enhancing RF absorption include, for example, water, saline solution, aqueous solutions containing suspended particles of electrically conductive material, such as metals, e.g., iron, various combination of metals, e.g., iron and other metals, or magnetic particles. These types of RF enhancers (i.e., non-targeted “general RF enhancers”) are generally directly introduced into the target area. Other exemplary general RF enhancers are discussed below, e.g., aqueous solutions of virtually any metal sulfate (e.g., aqueous solutions of iron sulfate, copper sulfate, and/or magnesium sulfate, e.g., aqueous solutions (about 5 mg/kg of body mass), copper sulfate (about 2 mg/kg of body mass), and magnesium sulfate (about 20 mg/kg of body mass)), other solutions of virtually any metal sulfate, injectable metal salts (e.g., gold salts), and RF absorbing particles attached to other non-targeted carriers. Preferably, these types of RF enhancers may be directly injected into the target area by means of a needle and syringe, or otherwise introduced into the patient.

[0032] Other means of enhancing RF absorption include providing targeted RF enhancers, such as antibodies with associated RF absorption enhancers, such as metal particles. The antibodies (and other targeting moieties, discussed below) target and bind to specific target cells in the target area 130. Generally, antibodies (and other targeting moieties) can be directed against any target, e.g., tumor, bacterial, fungal, viral, parasitic, mycoplasmal, histocompatibility, differentiation and other cell membrane antigens, pathogen surface antigens, toxins, enzymes, allergens, drugs and any biologically active molecules. Binding RF enhancing particles to the antibodies (and other carriers having at least one targeting moiety) permits the injection of the antibodies (and other carriers having at least one targeting moiety) into the patient and the targeting of specific cells and other specific targets. Once a high enough concentration of RF enhancers 132 are attached to the target cells, the RF signal 120 is passed through the specific target area 130. The RF enhancers induce the absorption of more energy, creating a localized temperature in the specific target area 130 that is higher than the temperature created in the general target area 106. In addition, a combination of antibodies (and other carriers having at least one targeting moiety) bound to different metals (and other RF absorbing particles, discussed below) can be used allowing for variations in the RF absorption characteristics in localized areas of the target areas. These variations in RF absorption characteristics permit intentional uneven heating of the specific target area 130.

[0033] Targeted RF enhancers and general RF enhancers can be used to improve current RF capacitive heating devices as well as current RF ablation devices. Antibodies bound to metals, which can act as RF absorption enhancers in accordance with the teachings of the present application, can be obtained through commercially available channels.

[0034] Targeted RF enhancers and general RF enhancers are applicable for both in-vivo and in-vitro applications. In one in-vitro application the targeted RF enhancers and/or general RF enhancers are in introduced into the target area prior to the target area being removed from the patient. After the targeted RF enhancers and/or general RF enhancers bind to the target area, the target area is removed from the patient and treated with one or more RF signals. In another in-vitro application the target area is removed from the patient before the RF enhancers are introduced into the target area. Once the target area is in a suitable vessel, the targeted RF enhancers and/or general RF enhancers are introduced into the target area. The target area is then treated with one or more RF signals.

[0035] Optionally, multiple frequency RF signals 120 are used. Multiple frequency RF signals can be used to treat target areas. Multiple frequency RF signals allow the energy absorption rate and absorption rate in different locations of the target area to be more closely controlled. The multiple frequency signals can be combined into one signal, or by use of a multi-plated transmission head, or multiple transmission heads, can be directed at one or more specific regions in the target area. This is useful for treating target areas that have specific regions of various shapes, thicknesses and/or depths. Similarly, pulsed RF signals, variable frequency RF signals and other combinations or variations of the RF signals can be used to more precisely control and target the heating of the specific target areas. These and other methods of increasing RF absorption can be used independently or in any number of combinations to increase the energy absorption rate of the specific target area 130.

[0036] In addition, antibodies (or other targeting moieties) bound with magnetic particles (i.e., magnetic targeted RF enhancers) can be steered to specific locations using magnets or magnetic resonant imaging (MRI) machines. Thus, the magnetic targeted RF enhancers can be directed toward specific target area or target cells. Furthermore, once the magnetic targeted RF enhancers bind to the specific target cells, the target cells can be separated from the other cells by use of a magnetic force. The magnetic force can be either an attracting force, or a repelling force. Magnets or MRI machines can also be used to steer injected (or otherwise introduced) magnetic particles to specific locations. The magnetic general RF enhancers discussed above may also be directed toward a specific target area or target cells using a magnetic force from, e.g., a magnet or MRI machine.

[0037] Additionally, in accordance with the teachings above, a target of RF induced hyperthermia may be specific target cells and need not be limited to a specific region of a body. Certain cancers, e.g., blood cancers, do not necessarily manifest themselves in a localized region. As discussed above, targeted RF enhancers, will target specific cells and need not be localized. In the case of blood cancers, such as lymphoma, leukemia, and multiple myeloma, such targeted RF absorption enhancers (e.g., targeting moieties bound to RF absorbing particles) can be introduced into a patient and then a selected region of the body (or perhaps the entire body) can be irradiated with RF energy, with the RF absorption enhancers bound to the cells heating up and heating those cells more than cells without RF absorption enhancers bound to them.

[0038] The above discussion recites several different types of exemplary RF absorption enhancers for enhancing the RF absorption of a target area (which may be a tumor or a portion of a tumor or target cells or some other target), such as (i) solutions and/or suspensions introduced into a target area to enhance RF heating of the target area (general RF absorption enhancers) and (ii) antibodies (or other targeting moieties) bound to RF absorbing particles that are introduced into a patient and that target specific target cells to enhance RF heating of the targeted cells (targeted RF absorption enhancers). As discussed above, these and other RF absorption enhancers may be used independently or in any number of combinations to increase RF absorption of a target area. The targeted RF absorption enhancers discussed herein can be thought of as effectively changing the resonant frequency of the target cells, i.e., adding another, artificial frequency to the target cells (which may be a resonant frequency of RF absorbing particles), because the RF absorbing particles, which are bound to target cells via the targeting moieties, will absorb more RF energy and heat more quickly than the target cells will at that frequency. Thus, instead of trying to determine one or more resonant frequencies of target cells, the targeted RF absorption enhancers used in accordance with the systems and methods of the present invention may be used to effectively add an artificial frequency or frequencies to the target cells at whatever artificial frequency or frequencies are desired to create hyperthermia.

[0039] The targeted RF absorption enhancers discussed above have a portion that binds to one or more targets and an associated portion that absorbs RF energy relatively well, e.g., a carrier having a targeting moiety and attached to an RF absorbing particle. The general RF absorption enhancers may also have an associated portion that absorbs RF energy relatively well e.g., a non-targeted carrier attached to an RF absorbing particle or RF absorbing particles in solution or suspension. Several examples given above of such RF absorbing particles listed above include particles of electrically conductive material, such as metals, iron, various combination of metals, irons and metals, or magnetic particles. Other examples are given below. Of course, these particles may be sized as so-called “nanoparticles” (microscopic particles whose size is measured in nanometers, e.g., 1-1000 nm) or sized as so-called “microparticles” (microscopic particles whose size is measured in micrometers, e.g., 1-1000 .mu.m). If these particles are to be injected (or otherwise introduced) intravenously, such particles are preferably small enough to be bound to and carried with the at least one carrier to a target cell (e.g., in the patient’s body) or target area (e.g., in the patient’s body) via the patient’s vascular system. In accordance with other exemplary embodiments of the present invention, other RF absorption enhancers may be used, e.g., using other carriers other than antibodies and/or using other RF absorbing particles than those specifically identified above.

[0040] Examples of such other carriers (both targeted and non-targeted) for RF absorption enhancers include any one or more of the following: biomolecules, biological cells, microparticle delivery systems, nanoparticle delivery systems, water-soluble polymers, other polymers, molecular or cellular proteomic or genomic structures, as well as other small particle constructs, including biological or robotic constructs, whether organic or from man-made materials, such as synthetic applied materials. Again, these carriers are attached to, or perhaps contain, RF absorbing particles to form RF absorption enhancers.

[0041] Exemplary biomolecules that may be used as carriers (both targeted and non-targeted) for RF absorption enhancers include any one or more of the following: organic molecules, nucleotides, proteins, antibodies, other specialized proteins, ligands, oligonucleotides, genetic material, nucleotides, DNA, RNA, viruses, retroviruses, organometallic molecules, proteins that are rapidly taken up by fast growing cells and tumors, transferrin, RGD (arg-gly-asp tripeptide) peptides, and NGR (asn-gly-arg tripeptide) peptides, folate, trasferrin, galactosamine, and GM-CSF (granulocyte macrophage colony stimulating factor). Herein, the term “organometallic molecule” (or just organometallics) means a molecule in which there is at least one bonding interaction (ionic or covalent, localized or delocalized) between one or more carbon atoms of an organic group or molecule and a main group, transition, lanthanide, or actinide metal atom (or atoms), and shall include organic derivatives of the metalloids (boron, silicon, germanium, arsenic, and tellurium), organic derivatives of all other metals and alloys, molecular metal hydrides; metal alkoxides, thiolates, amides, and phosphides; metal complexes containing organo-group 15 and 16 ligands; metal nitrosyls and similar others. Thus, in addition to being bound to separate RF absorbing particles to form RF absorption enhancers, some organometallic molecules may function as RF absorption enhancers by themselves, having both a carrier portion and an RF absorbing metallic portion. These organometallic molecules may be directly injected (or otherwise introduced) or may be attached to organic, biomolecular, biopolymer, molecular or cellular proteomic or genomic structures, or may be placed in biologic, robotic, or man-made synthetic applied materials. The application of organometallics in nuclear medicine (i.e. for the labeling of receptor binding biomolecules like steroid hormones or brain tracers) has been proposed in the literature. Technetium and radiogallium, typically used for medical imaging, can be modified with an organometallic. These biomolecules, organometallic technetium and organometallic radiogallium, could serve the dual function of imaging a tumor and be a radiofrequency enhancer because of their specific heat properties and imaging properties. Additionally, organometallic technetium and/or organometallic radiogallium may be bound to one or more different RF absorbing particles, e.g., bound to any one or more of virtually any of the RF absorbing particles described herein, to form RF absorption enhancers.

[0042] Exemplary biological cells (both targeted and non-targeted) that may be used as carriers for RF absorption enhancers include any one or more of the following: white blood cells, modified white cells, vaccine stimulated white cells, expanded white cells, T-cells, and tumor infiltrating lymphocytes (TILs). In general, these cells can be removed from a tumor or the circulating blood of a cancer patient and grown in tissue culture dishes or suspensions; thereafter, RF absorbing particles can be microinfused or absorbed into the cells to create RF absorption enhancers.

[0043] Exemplary microparticle and nanoparticle delivery systems (both targeted and non-targeted) that may be used as carriers for RF absorption enhancers include any one or more of the following: liposomes, immunoliposomes (liposomes bound to antibodies or antibody fragments or non-antibody ligand-targeting moieties), magnetic liposomes, glass beads, latex beads, other vesicles made from applied materials, organically modified silica (ORMOSIL) nanoparticles, synthetic biomaterial like silica modified particles and nanoparticles, other nanoparticles with the ability to take up DNA (or other substances) for delivery to cells, other nanoparticles that can act as a vector to transfer genetic material to a cell. Many of these can be directly taken up or otherwise internalized in the targeted cells. Liposomes are artificial microscopic vesicles used to convey substances–e.g., nucleic acids, DNA, RNA, vaccines, drugs, and enzymes–to target cells or organs. In the context of this application, liposomes may contain and carry RF absorbing particles (such as metal particles, organometalics, nanoparticles, etc.) to target cells or organs. These and other microparticle and nanoparticle delivery systems (both targeted and non-targeted) may be used to carry any one or combination of two or more of virtually any of the RF absorbing particles described herein, to form RF absorption enhancers. Exemplary polymers that may be used as carriers for RF absorption enhancers include any one or more of the following: dextran, albumin, and biodegradable polymers such as PLA (polylactide), PLGA polymers (polylactide with glycolide or poly(lactic acid-glycolic acid)), and/or hydroxypropylmethacrylamine (HPMA).

[0044] Other exemplary carriers for RF absorption enhancers include: molecular or cellular proteomic or genomic constructs, as well as other small particle constructs, including biological or robotic constructs, whether organic or from man-made materials, such as synthetic applied materials.

[0045] Targeted RF absorption enhancers are characterized by targeting and binding to target cells to thereby increase heating of target cells responsive to the RF signal by interaction between the RF signal and the targeted RF absorption enhancer. The target cells may be in an organ or a tumor or a portion of a tumor, or may be circulating or isolated cells, such as blood cells. Some targeted RF absorption enhancers may bind to the cell membrane or intracellular contents of (e.g., one or more biomolecules inside) the target cells. Some targeted RF absorption enhancers may bind to target cells by being taken up or otherwise internalized by the target cells. Some targeted RF absorption enhancers discussed herein can be thought of as effectively changing the resonant frequency of target cells, i.e., adding another, artificial frequency to the target cells (which may be a resonant frequency of RF absorbing particles), because the RF absorbing particles, which are bound to target cells via the targeting moieties, will absorb more RF energy and heat more quickly than the target cells will at that frequency. For targeted RF absorption enhancers, carriers with a targeting moiety for targeting and binding to a target cells (“targeted carriers”) are attached (either directly or indirectly) to any of the RF absorbing particles described herein and introduced into the patient prior to transmitting the RF signal to create hyperthermia. Some targeted carriers for RF absorption enhancers (e.g., antibodies, ligands, and TILs) inherently have targeting moieties for targeting some part of target cells. Other RF absorption enhancer carriers (e.g., liposomes) may need to be modified to be targeting carriers by attaching one or more target moieties for targeting some part of target cells, e.g., immunoliposomes, which are liposomes bound to antibodies or antibody fragments or non-antibody ligand-targeting moieties. Some targeted carriers (e.g., antibodies, ligands, and antibody fragments) target one or more “target biomolecules” of target cells and bind to the target cells. The term “target biomolecules” as used herein means a molecular structure within a target cell or on the surface of a target cell characterized by selective binding of one or more specific substances. The term “target biomolecules” includes, by way of example but not of limitation, cell surface receptors, tumor-specific markers, tumor-associated tissue markers, target cell markers, or target cell identifiers, such as CD markers, an interleukin receptor site of cancer cells, and other biomolecules to which another molecule, e.g. a ligand, antibody, antibody fragment, cell adhesion site, biopolymer, synthetic biomaterial, sugar, lipid, or other proteomic or genetic engineered constructs including recombinant technique, binds. Examples of targeted carriers and other targeting moieties that can be used to create targeted RF absorption enhancer carriers include: bivalent constructs, bispecific constructs, fusion proteins; antibodies; antibody fragments; non-antibody ligands; and non-antibody targeting moieties (e.g., GM-CSF which targets to GM-CSF receptor in leukemic blasts or Galactosamine which targets endothelial growth factor receptors in the vessels).

[0046] Tumors may produce antigens recognized by antibodies. There are currently trials of antibodies and antibody fragments for virtually all cancers and others are being developed. Tumors often express high levels and/or abnormal forms of glycoproteins and glycolipids. Antibodies are known to target these (e.g., Anti-MUC-1 for targeting breast or ovarian cancer). Oncofetal antigens are also produced by some tumors. Antibodies are known to target these (e.g., anti-TAG72 [anti-tumor-associated glycoprotein-72] for targeting colonrectal, ovarian and breast cancer or anti-CEA [anti-carcinoembryonic antigen] for targeting colon-rectal, small-cell lung and ovarian cancers). Tissue specific antigens have also been targeted. Antibodies are known to target these (e.g., anti-CD25 for targeting interleukin-2 receptor in cutaneous T-cell lymphoma). The rapid production of blood vessels in tumors presents another target. Antibodies are known to target these (anti-VEGR [anti-vascular endothelial growth-factor receptor] for targeting endothelial cells in solid tumors. These are but a few examples of the antibodies have already been used as ligands in targeted therapy to which the present RF enhancers could be attached. Any one or more of the RF absorbing particles disclosed herein can be attached (directly or indirectly) to any of these antibodies and antibody fragments (and any others) to form substances that may be used as targeted RF absorption enhancers in connection with hyperthermia generating RF signals in accordance with the teachings herein.

[0047] Other examples of known ligand antibodies are the monoclonal antibodytrastuzumab (Herceptin) which targets to ERBB2 receptor in cells that over-express this receptor such as breast and ovarian cancers or rituximab an anti-CD 20 which targets cell surface antigen in non-hodgkin’s lymphoma and other b-cell lymphoproliferative diseases. Any one or more of the RF absorbing particles can be attached (directly or indirectly) to any of these antibodies and antibody fragments (and any others) to form substances that may be used as targeted RF absorption enhancers in connection with hyperthermia generating RF signals in accordance with the teachings herein.

[0048] For general RF absorption enhancers, non-targeted carriers, such as certain biomolecules, oligonucleotides, certain cells (such as cells having general adhesive molecules on their surfaces that are less specific than ligands and antibodies, which general adhesive molecules may attach to many different types of cells), etc. may be attached (either directly or indirectly) to any of the RF absorbing particles described herein and injected (or otherwise introduced) prior to transmitting the RF signal to create hyperthermia. Nanoparticles having oligonucleotides attached thereto, such as DNA sequences attached to gold nanoparticles, are available from various sources, e.g., Nanosphere, Inc., Northbrook, Ill. 60062, U.S. Pat. No. 6,777,186.

[0049] RF absorbing particles are particles that absorb one or more frequencies of an RF electromagnetic signal substantially more than untreated cells in or proximate the target area. This permits the RF signal to heat the RF absorbing particle (or a region surrounding it or a cell near it) substantially more than untreated cells in or proximate the target area, e.g., heating the RF absorbing particles (or a region surrounding them or a cell near them) with the RF signal to a temperature high enough to kill target cells bound to them (or damage the membrane of target cells bound to them), while untreated cells in or proximate the target area are not heated with the RF signal to a temperature high enough to kill them. Exemplary target hyperthermia temperatures include values at about or at least about: 43.degree. C, 106.3.degree. F., 106.5.degree. F., and 106.7.degree. F., and 107.degree. F. It may also be desirable to generate a lower hyperthermia temperature (e.g., any temperature above 103.degree., or above 104.degree., or above 105.degree.) which may not directly cause necrosis from hyperthermia within the target area, but may kill or damage cells in the target area in combination with another therapy, e.g., chemotherapy and/or radiotherapy and/or radioimmunotherapy. Pulsed RF signals may produce very localized temperatures that are higher. Exemplary RF absorbing particles mentioned above include particles of electrically conductive material, such as gold, copper, magnesium, iron, any of the other metals, and/or magnetic particles, or various combinations and permutations of gold, iron, any of the other metals, and/or magnetic particles. Examples of other RF absorbing particles for general RF absorption enhancers and/or targeted RF absorption enhancers include: metal tubules, particles made of piezoelectric crystal (natural or synthetic), very small LC circuits (e.g., parallel LC tank circuits, FIGS. 24 and 30), tuned radio frequency (TRF) type circuits (e.g., a parallel LC tank circuit having an additional inductor with a free end connected to one of the two nodes of the tank circuit, FIGS. 27 and 31), other very small tuned (oscillatory) circuits (e.g., FIGS. 25, 26, 28, 29, and 32-33), hollow particles (e.g., liposomes, magnetic liposomes, glass beads, latex beads, other vesicles made from applied materials, microparticles, microspheres, etc.) containing other substances (e.g., small particles containing argon or some other inert gas or other substance that has a relatively high absorption of electromagnetic energy), particles of radioactive isotopes suitable for radiotherapy or radioimmunotherapy (e.g., radiometals, .beta.-emitting lanthanides, radionuclides of copper, radionuclides of gold, copper-67, copper-64, lutetium-177, yttrium-90, bismuth-213, rhenium-186, rhenium-188, actinium-225, gold-127, gold-128, In-111, P-32, Pd-103, Sm-153, TC-99m, Rh-105, Astatine-211, Au-199, Pm-149, Ho-166, and Thallium-201 thallous chloride), organometallics (e.g., those containing Technetium 99m and radiogallium), particles made of synthetic materials, particles made of biologic materials, robotic particles, particles made of man made applied materials, like organically modified silica (ORMOSIL) nanoparticles. These particles may be sized as so-called “nanoparticles” (microscopic particles whose size is measured in nanometers, e.g., 1-1000 nm) or sized as so-called “microparticles” (microscopic particles whose size is measured in micrometers, e.g., 1-1000 .mu.m). These particles are preferably small enough to be bound to and carried with the at least one biomolecule to a target cell via the patient’s vascular system. For example, gold nanospheres having a nominal diameter of 3-37 nm, plus or minus 5 nm may used as RF absorption enhancer particles. Some of the radioactive isotopes are inserted as “seeds” and may serve as RF absorption enhancers, e.g., palladium-103, to heat up a target area in the presence of an RF signal.

[0050] In the case of the particles of radioactive isotopes used for various treatments, e.g., to treat cancer, a multi-step combination therapy can be used in accordance with the teachings hereof. In a first phase, targeted carriers (either carriers with an inherent targeting moiety or non-targeting carriers with a targeting moiety attached thereto) are attached to one or more RF absorbing radionuclides, such as any of the radiometals mentioned herein, are introduced into the patient, target specific cells, and emissions (e.g., alpha emissions and/or beta emissions and/or Auger electron emissions) therefrom damage or kill the targeted cells. This first phase may include the introduction of other radiometal-labeled antibodies that may act as RF absorption enhancers but that do not have cell damaging emissions, e.g., radiometals used primarily for imaging. This first phase, in the context of certain antibodies and certain radioisotopes, is known to those skilled in the art. Thereafter, in a second phase according to the present invention, an RF signal is transmitted in accordance with the teachings herein to generate a localized hyperthermia at the targeted cells by using the radioisotope particles (which may be partially depleted) as RF absorption enhancing particles. Such a two-phase therapy may result in enhanced treatment effectiveness vis-a-vis traditional radioimmunotherapy with the addition of the second RF-induced hyperthermia phase. In the alternative, such a two-phase therapy may result in about the same treatment effectiveness vis-a-vis traditional radioimmunotherapy by using a lower dose of radioisotope emissions in the first phase (some radioisotopes can cause severe damage to tissue, e.g., bone marrow, during radiotherapy) with the addition of the second RF-induced hyperthermia phase. Between the two phases, one may wait for a predetermined period of time, e.g., a period of time based on the half-life of emissions from a particular radiometal used, or a period of time based on a patient recovery time after the first phase, or a period of time based on the ability of one or more non-targeted organs (e.g., the liver or kidneys) to excrete, metabolize, or otherwise eliminate the radioimmunotherapy compound(s). In this regard, it may be beneficial for this multiphase therapy to use radiometals or other RF absorbing radionuclides with a relatively high residualization in target cells. This may help prevent damage to non-targeted organs and cells by permitting them to excrete, metabolize, or otherwise eliminate the radioimmunotherapy compound(s) prior to coupling a hyperthermia generating RF signal using the radioimmunotherapy compound as an RF enhancer. For example, a patient treated with Yttrium-90 (Y-90) ibritumomab tiuxetan (Y-90 ZEVALIN.RTM.) (which is used to treat b-cell lymphomas and leukemias) in accordance with known protocols, and also perhaps injected with Indium-111 (In-111) ibritumomab tiuxetan (In-111 ZEVALIN.RTM.) (which is used for imaging in connection with rituximab treatments), may also thereafter have a hyperthermia-generating RF signal coupled through a body part to heat the cells targeted by the Y-90 ZEVALIN.RTM. and/or the (In-111 ZEVALIN.RTM.). Particles of radioactive isotopes used to treat cancer, either attached to biomolecules or not, can be obtained from various commercial sources. Radiometals can be attached to monoclonal antibodies, e.g., 90-Yttrium-ibritumomab tiuxetan [Zevalin] or 131-iodine-tositumomab (Bexxar) target anti-CD 20 antigens and are used for lymphomas. Radiofrequency can produce an added effect with these metals.

[0051] Very small LC circuits and other tuned (oscillatory) circuits were mentioned above as exemplary RF absorbing particles. The very small LC circuits and other tuned (oscillatory) circuits (FIGS. 24-29) may damage target cells with vibration (i.e., heating) when a signal at or near the resonant frequency of the tuned circuit is received. Additionally, or in the alternative, there may be direct radio frequency ablation to the cell from RF energy absorbed by tuned circuit RF absorbing particles, which current may be transferred to target cells via one or more metal connections of the tuned circuit particles to the cell membrane or cell itself (see the discussion below with respect to the at least one exposed electrical contact 2502 and the encapsulating electrically conducting material).

[0052] For purposes of the present application, virtually any of the carriers (targeted or non-targeted) for RF absorption enhancers described herein may be attached (either directly or indirectly) to virtually any RF absorbing particle described herein and/or virtually any combination of and/or permutation of any RF absorbing particles described herein to form any one or more RF absorption enhancers. For example, antibody carriers may be bound to (or otherwise carry) one or more piezoelectric crystals, tuned electronic circuits, tuned RF (TRF) circuits, TRF circuits having a rectifier D (FIG. 29), LC tank circuits, LC tank circuits having a rectifier D (FIG. 26), metallic particles, and/or metallic nanoparticles. As other examples, TIL carriers may be attached to or contain an organometallic or TRF or any other of the microscopic electronic circuit particles, RNA or DNA carriers may be attached to organometallic molecules acting as RF absorbers, antibody carriers may be attached to organometallic molecules acting as RF absorbers, metals (e.g., iron) may be attached to transferrin, liposomes may contain RF absorbing particles, immunoliposomes (liposomes bound to antibodies or antibody fragments or non-antibody ligand-targeting moieties) may contain RF absorbing particles, immunopolymers (microreservoirs) formed by linking therapeutic agents and targeting ligands to separate sites on water-soluble biodegradable polymers, such as HPMA, PLA, PLGA, albumin, and dextran, may be used to form RF absorption enhancers by attaching to an RF absorbing particle and a targeting moiety (antibody or non-antibody), those formed by the attachment of multivalent arrays of antibodies, antibody fragments, or other ligands to the liposome surface or to the terminus of hydropic polymers, such as polyethylene glycol (PEG), which are grafted at the liposome surface) may contain RF absorbing particles, dextran may have metallic particles and targeting peptides attached to it, polymers of HPMA can have targeting peptides and metallic particles attached, liposomes may carry metallic or thermally conductive synthetic biomaterials inside, immunoliposomes may carry metallic or thermally conductive synthetic biomaterials inside, monoclonal antibodies and metals, monoclonal antibodies and radioisotopes like Zevalin, antibody fragments and organometallics, antibody fragments and radioisotopes, fusion proteins and organometallics, fusion proteins and radioisotopes, bispecifics and metals or organometallics, bispecifics and bivalents constructs and radioisotopes. Since tumor penetration is often hampered by particle size, reductionistic engineering techniques that create smaller proteomic and genomic constructs and recombinations which are more tumor-specific will be able to carry RF absorption enhancers. As other examples, microparticle and nanoparticle delivery systems (both targeted and non-targeted) and any of the other carriers herein may carry two or more different RF absorbing particles, e.g., metallic particles of two different sizes, metallic particles and electronic circuits, metallic particles and an RF absorbing gas, electronic circuits and an RF absorbing gas, etc. Such combinations of RF absorbing particles may provide enhanced absorption at two different frequencies, e.g., two different resonant frequencies, or a resonant frequency and a frequency range (as one might see with a tuned RF circuit absorbing particle combined with a general particle, such as a metal particle), which may facilitate multi-level treatments at multiple tissue depths.

[0053] Additionally, virtually any of the foregoing RF absorbing particles may be partially encapsulated or fully encapsulated in a carrier or other encapsulating structure such as: glass beads, latex beads, liposomes, magnetic liposomes, other vesicles made from applied materials, etc. As exemplified by the tank circuit of FIG. 25 and the TRF circuit of FIG. 28, RF absorbing particles in the form of a tuned circuit may be partially encapsulated in an electrically insulating material 2500 (e.g., a glass or latex bead) and have at least one exposed electrical contact 2502 in circuit communication with the rectifier D for contact with biological material in the target area. In the alternative, RF absorbing particles in the form of a tuned circuit may be encapsulated in an electrically conducting material in circuit communication with the rectifier for contact with biological material in the target area. Similarly, as exemplified by the rectifying tank circuit of FIG. 26 and the rectifying TRF circuit of FIG. 29, RF absorbing particles having a rectifier D to rectify a received RF signal may be partially encapsulated in an electrically insulating material 2500 and have at least one exposed electrical contact 2502 in circuit communication with the rectifier D for contact with biological material in the target area to provide a path for rectified current to flow and perhaps damage cells and/or heat cells in the target area. In the alternative, RF absorbing particles having a rectifier to rectify a received RF signal may be encapsulated in an electrically conducting material in circuit communication with the rectifier for contact with biological material in the target area to provide a path for rectified current to flow and perhaps damage cells and/or heat cells in the target area. These may be fabricated using standard monolithic circuit fabrication techniques and/or thin film fabrication techniques. Various techniques for fabricating microscopic spiral inductors of FIGS. 24-29 using monolithic circuit fabrication techniques and/or thin film fabrication techniques are known, e.g., U.S. Pat. Nos. 4,297,647; 5,070,317; 5,071,509; 5,370,766; 5,450,263; 6,008,713; and 6,242,791. Capacitors and rectifiers D may also be fabricated using monolithic circuit fabrication techniques and/or thin film fabrication techniques (e.g., with a pair of conductive layers with a dielectric therebetween and a P-N junction, respectively). Thus, it is believed that the microscopic (preferably microparticle or nanoparticle) circuits of FIGS. 24-29 may be fabricated using known monolithic circuit fabrication techniques and/or thin film fabrication techniques. FIGS. 30-33 show exemplary embodiments of some exemplary tuned (oscillatory) circuit particles. FIG. 30 shows an exemplary embodiment 3000 of an LC particle of FIG. 25. The exemplary LC particle 3000 comprises a substrate 3002 carrying an inductor 3004 in circuit communication with a capacitor 3006 via conductive traces 3008, 3010. The inductor 3004 may be a spiral 3020 of electrically conductive material. The capacitor 3006 may be formed from two spaced plates 3022, 3024 of electrically conductive material with a dielectric (not shown) therebetween. Plate 3022 and conductive path 3008 are shown as at a lower level than plate 3024 and inductor 3020. Conductive path 3008 is connected to inductor 3020 with a via 3021. The encapsulating electrically insulating material 2500 in FIG. 20 may be implemented by a layer of electrically insulating material 3026 covering at least the inductor 3004 and the capacitor 3006 above in cooperation with the substrate 3002 below. The exposed electrical contact 2502 in FIG. 25 may be implemented as an exposed pad 3030 of conductive material. FIG. 31 shows an exemplary embodiment 3100 of a TRF circuit of FIG. 28. Particle 3100 may be the same as particle 3000, except particle 3100 has an additional inductor 3102. The inductor 3102 may be a spiral 3104 of electrically conductive material, in circuit communication by a via 3106 with the node 3008 connecting inductor 3004 and capacitor 3006. FIG. 32 shows an exemplary embodiment 3200 of a rectifying tank circuit 3200 of FIG. 26. Particle 3200 may be the same as particle 3000, except particle 3200 has a rectifier 3202. Rectifier 3202 may be implemented with a n-type semiconductor region (or a p-type region) 3204 in circuit communication with a p-type region (or an n-type region) 3206 as known to those in the art. The node 3010 connecting inductor 3004 and capacitor 3006 may be connected to rectifier 3202 at via 3208. Similarly, the exposed pad 3030 may be connected to rectifier 3202 at via 3210. FIG. 33 shows an exemplary embodiment 3300 of a rectifying TRF circuit of FIG. 28. Particle 3300 may be the same as particle 3100, except particle 3300 has a rectifier 3202. As with the rectifier in FIG. 32, rectifier 3202 may be implemented with an n-type semiconductor region (or a p-type region) 3204 in circuit communication with a p-type region (or an n-type region) 3206 as known to those in the art. The node 3010 connecting inductor 3004 and capacitor 3006 may be connected to rectifier 3202 at via 3208. Similarly, the exposed pad 3030 may be connected to rectifier 3202 at via 3210. The particles made of piezoelectric crystal can be obtained from various commercial sources, e.g., Bliley Technologies, Inc., Erie, Pa. Gases in the noble gas family, e.g., neon, argon, etc., exhibit relatively large excitation at relatively low RF signal strengths. The small particles containing argon can be obtained from various commercial sources.

[0054] Various means for getting the RF absorption enhancers of the present invention to the targeted cell site are contemplated. RF absorption enhancers may be introduced as part of a fluid directly into the tumor (e.g., by injection), introduced as part of such a fluid into the patient’s circulation (e.g., by injection), mixed with the cells outside the body (ex-vivo), inserted into target cells with micropipettes. Nanoparticle RF absorption enhancers may be introduced by aerosol inhalers, sublinqual and mucosal absorption, lotions and creams, and skin patches. RF absorption enhancers may be directly injected into a patient by means of a needle and syringe. In the alternative, they may be injected into a patient via a catheter or a port. They may be injected directly into a target area, e.g., a tumor or a portion of a tumor. In the alternative, they may be injected via an intravenous (IV) system to be carried to a target cell via the patient’s vascular system. RF absorption enhancers of the present invention may bind with the cell surface, bind to a target cell wall (e.g., those using monoclonal antibodies as a carrier) or be internalized by the cells (e.g., those using liposomes and nanoparticles as a carrier). Certain RF absorption enhancers of the present invention (e.g., those using TILs as a carrier) may be internalized by target cells. Additionally, it may be desirable to surgically-place certain RF absorption enhancers in a patient, e.g., metallic radioactive “seeds.”

[0055] RF hyperthermia generating signal may have a frequency corresponding to a selected parameter of an RF enhancer, e.g., 13.56 MHz, 27.12 MHz, 915 MHz, 1.2 GHz. Several RF frequencies have been allocated for industrial, scientific, and medical (ISM) equipment, e.g.: 6.78 MHz.+-.15.0 kHz; 13.56 MHz.+-.7.0 kHz; 27.12 MHz.+-.163.0 kHz; 40.68 MHz.+-.20.0 kHz; 915 MHz.+-.13.0 MHz; 2450 MHz.+-.50.0 MHz. See Part 18 of Title 47 of the Code of Federal Regulations. It is believed that hyperthermia generating RF signals at sequentially higher frequency harmonics of 13.56 MHz will penetrate into respectively deeper tissue, e.g., a hyperthermia generating RF signal at 27.12 MHz will penetrate deeper than at 13.56 MHz, a hyperthermia generating RF signal at 40.68 MHz will penetrate deeper than at 27.12 MHz, a hyperthermia generating RF signal at 54.24 MHz will penetrate deeper than at 40.68 MHz, a hyperthermia generating RF signal at 67.80 MHz will penetrate deeper than at 54.24 MHz, a hyperthermia generating RF signal at 81.36 MHz will penetrate deeper than at 67.80 MHz, and so on (up to higher RF frequencies that may heat the skin uncomfortably or burn the skin). The optimum depth level is selected based upon antibodies used, and the physical size of the patient, the location and depth of the target area, and the tumor involved. As discussed above, combinations of two or more different frequencies may be used, e.g., a lower frequency RF component (such as 13.56 MHz) and a higher frequency component (such as 40.68 MHz) to target different tissue depths with the same hyperthermia generating RF signal.

[0056] Some of the exemplary particles shown comprise a rectifier D, e.g., FIGS. 26, 29, 32 and 33. Any of the RF absorption enhancer particles disclosed herein may also comprise an associated rectifier or demodulator (e.g., a diode or crystal in circuit communication with an oscillatory circuit) on some or all of the particles to cause rectification of the RF signal and thereby generate a DC current to damage the target cell(s) (in the case of targeted RF absorption enhancers) and/or cells in the target area (in the case of general RF absorption enhancers). Thus, for example, the particles may have an LC tank circuit with a diode (FIG. 26), a TRF (Tuned Radio Frequency) type circuit implemented thereon with a diode (FIG. 29) or a piezoelectric crystal with a diode. Such RF absorption enhancer particles may require the patient to be grounded, e.g., with a grounded lead pad, to provide a current path for the rectified RF current. These examples immediately above may be thought of as being similar to a simple TRF crystal set, which was powered only by a received RF signal and could demodulate the received signal and generate enough energy to power a high-impedance earphone with no outside power source other than the signal from the radio station. With the particles of the present application, the addition of a diode to these circuits may cause DC currents to flow within the target area and/or within and/or between the target cells responsive to the RF signal causing additional heating effect to generate the desired hyperthermia temperature, e.g., 43.degree. C. The rectifier in any of these particles may be a single diode in either polarity (for half-wave rectification of the received RF signal) or a pair of diodes with opposite polarity (for full wave rectification of the RF signal).

[0057] Any of the RF absorbing particles described herein may be used alone or in virtually any combination of and/or permutation of any of the other particle or particles described herein. For example, it may be beneficial to use the same targeted carrier or targeting moiety with a plurality of different RF absorbing particles described herein for treatment of a target area. Similarly, any of the RF absorbing particles described herein may be used alone or in virtually any combination of and/or permutation of any of the targeting moieties or targeted carriers described herein. Similarly, it may be best for some target areas (e.g., some tumors) to use multiple different targeting moieties or targeted carriers in RF absorption enhancers, e.g., for a malignancy that may have different mutations within itself. Accordingly, virtually any combination or permutation of RF absorption enhancer targeting moieties or RF absorption enhancer targeted carriers may be attached to virtually any combination of and/or permutation of any RF absorbing particle or particles described herein to create RF absorption enhancers for use in accordance with the teachings herein.

[0058] Of the RF absorbing particles mentioned herein, some may be suitable for a 13.56 MHz hyperthermia-generating RF signal, e.g., gold nanoparticles, copper nanoparticles, magnesium nanoparticles, argon-filled beads, aqueous solutions of any of the metal sulfates mentioned herein, other hollow nanoparticles filled with argon, and any of the organometallics. RF absorption enhancers using these RF absorbing particles are also expected to be effective at slightly higher frequencies, such as those having a frequency on the order of the second or third harmonics of 13.56 MHz.

[0059] Some of the particles used in general RF absorption enhancers and/or targeted RF absorption enhancers may have one or more resonant frequencies associated therewith such that RF energy or other electromagnetic energy at that resonant frequency causes much greater heating of the particle than other frequencies. Thus, in accordance with the systems and methods of the present invention, it may be beneficial to match one or more resonant frequencies of RF absorption enhancer particles (general and/or targeted) with one or more of the electromagnetic frequencies being used to create hyperthermia. Additionally, the size of nanoparticles can vary to within certain manufacturing tolerances, with generally increased cost for a significantly smaller manufacturing tolerance. Thus, for a single frequency being used to create hyperthermia, there may be a nominal size of nanoparticles associated with that one frequency (e.g., a nominal size of nanoparticles having a resonant frequency at that frequency); however, the cost of manufacturing nanoparticles only at that one size might be prohibitively high. Consequently, from a cost standpoint, it might be beneficial (i.e., lower cost) to use nanoparticles with a larger size tolerance as RF absorption enhancer particles; however, the particles within a sample of nanoparticles with a larger size tolerance may have widely different resonant frequencies. Accordingly, it may be beneficial to use a frequency modulated (FM) signal to create hyperthermia with certain energy absorption enhancer particles. The parameters of the FM signal used to generate hyperthermia may be selected to correspond to the specific sample of particles being used as energy absorption enhancer particles. The center frequency of an FM hyperthermia generating signal may correspond to a resonant frequency of nominally sized particles used as energy absorption enhancer particles and the modulation of the FM hyperthermia generating signal may correspond to the size tolerance of the particles used as energy absorption enhancer particles. For example, a hyperthermia generating RF signal may be modulated with an FM signal having a frequency deviation of 300-500 KHz or more, and any particles having a resonant frequency within the FM deviation would vibrate and cause heating. Targeted RF absorption enhancer particles used in accordance with an FM signal used to generate hyperthermia can be thought of as effectively changing the resonant frequency range of the target cells, i.e., adding a resonant frequency range to the target cells. Thus, instead of trying to determine one or more resonant frequency ranges of target cells, in accordance with the systems and methods of the present invention the resonant frequency range of target cells may be effectively changed to whatever frequency range is desired to create hyperthermia. With all the embodiments described herein, one may select a frequency or frequency range for a signal used to generate hyperthermia that corresponds to a parameter of energy enhancing particles, or one may select energy enhancing particles corresponding to a frequency or frequency range for a signal used to generate hyperthermia. It may be beneficial to modify other existing thermotherapy devices to use the FM hyperthermia generating RF signal discussed herein. Similarly, it may be beneficial to modify other existing thermotherapy therapies to use the FM hyperthermia generating RF signal discussed herein.

[0060] Additionally, in any of the embodiments discussed herein, the RF signal used to generate hyperthermia may be a pulsed, modulated FM RF signal, or a pulse fixed frequency signal. A pulsed signal may permit a relatively higher peak-power level (e.g., a single “burst” pulse at 1000 Watts or more, or a 1000 Watt signal having a duty cycle of about 10% to about 25%) and may create higher local temperatures at RF absorption enhancer particles (i.e., higher than about 43.degree. C.) without also raising the temperature that high and causing detrimental effects to surrounding cells (for targeted enhancers) or surrounding areas (for general enhancers).

[0061] Several systems can be used to remotely determine temperature within a body using sensors or using radiographic means with infrared thermography and thermal MRI. Such remotely determined temperature may be used as feedback to control the power of the signal being delivered to generate hyperthermia. For example, a temperature remotely measured can be used as an input signal for a controller (e.g., a PID controller or a proportional controller or a proportional-integral controller) to control the power of the hyperthermia-generating signal to maintain the generated temperature at a specific temperature setpoint, e.g., 43.degree. C.

[0062] Similarly, the location of certain radioisotopes can be remotely determined using radiographic means for imaging of radioimmunotherapy. Accordingly, in any of the embodiments discussed herein, RF absorption enhancers may have substances (such as certain radioisotopes, quantum dots, colored dyes, fluorescent dyes, etc.) added or attached thereto that, when introduced with the RF absorption enhancers, can be used to remotely determine the location of RF absorption enhancers, i.e., the location of the substances can be determined and the location of RF absorption enhancers can be inferred therefrom. In the alternative, these substances can be introduced before or after RF absorption enhancers are introduced and used to remotely determine the location of the RF absorption enhancers. Examples of radioisotopes the location of which can be monitored in a body (e.g., with CT scanners, PET scanners, and other systems capable of detecting particles emitted by such substances) include: technetium 99m, radiogallium, 2FDG (18-F-2-deoxyglucose or 18-F-2-fluorodeoxyglucose) (for PET scans), iodine-131, positron-emitting Iodine 124, copper-67, copper-64, lutetium-177, bismuth-213, rhenium-186, actinium-225, In-111, iodine-123, iodine-131, any one or more of which may be added to RF absorption enhancers. Some of these, e.g., technetium 99m, radiogallium, 2FDG, iodine-131, copper-67, copper-64, lutetium-177, bismuth-213, rhenium-186, actinium-225, and In-111 may also absorb a significant amount of RF energy and therefore function as RF absorption enhancing particles, absorbing RF energy sufficient to raise the temperature of target cells or a target area to a desired temperature level and permitting remote location determination. Such determined location can be used to provide feedback of the location of general or targeted RF absorption enhancers to know which regions of an area or body will be heated by a hyperthermia generating RF signal. For example, the location of these particles (and by inference the location of targeted RF absorption enhancers) can be periodically determined, i.e., monitored, and the hyperthermia generating RF signal applied when enough of the targeted RF absorption enhancers are in a desired location. As another example, the location of these particles (and by inference the location of general or targeted RF absorption enhancers) can be periodically determined, i.e., monitored, and the hyperthermia generating RF signal ceased when the RF absorption enhancers have diffused too much or have moved from a predetermined location. Thus, the location of RF absorption enhancers may be determined via PET scanners, CT scanners, X-ray devices, mass spectroscopy or specialized CT scanners (e.g., Phillips Brilliance CT), and/or infrared, near infrared, thermal MRIs and other optical and/or thermal scanners. For PET scans, exemplary known imaging/treatment substances include: (a) antibodies (or targeting peptides) linked to PET radiometals linked to a cytoxic agent and (b) antibodies (or targeting peptides) linked to PET radiometals linked to beta emitting radionucleotides. In accordance with the teachings herein, one or more RF absorbing particles may be added to these substances (or in the alternative one or more RF absorbing particles may replace either the cytoxic agent or the beta emitting radionucleotides) for combined PET imaging with RF generated hyperthermia. Thus, these phage display antibodies attached to PET radiometals may also be attached to any one or more of the RF absorbing particles discussed herein. This combination of imaging and RF hyperthermia therapy may be accomplished with PET, infrared, near infrared, and MRI.

[0063] Imaging techniques can be used to guide the injection (or other introduction) of RF absorption enhancers into a tumor, e.g., a tumor or a portion of a tumor. After injection, a hyperthermia generating RF signal is applied to the target area and thermal imaging can be used to monitor the heat being generated by the RF signal and perhaps directly control the power of the RF signal. Thereafter, follow-up 3-D imaging using traditional methods can be used to determine the results of the hyperthermia. Additionally, imaging combinations are contemplated for imaging of RF absorption enhancers, e.g., using thermal imaging, colored dyes, quantum dots.

[0064] Several substances have been described as being injected into a patient, e.g., general RF absorption enhancers, targeted RF absorption enhancers, radioisotopes for remotely determining temperature, radioisotopes capable of being remotely located, etc. It is expected that some or all of these will be injected using a syringe with a needle. The needle may be removed from the patient after injection and before the RF signal is applied to generate hyperthermia. In the alternative, a needle used to inject one or more of the foregoing may be left in place and used as an RF absorption enhancer, i.e., a needle can be made from any number of selected that will heat in the presence of an RF signal. Thus, an ordinary needle may be used as an RF absorption enhancer. Additionally, a needle can be altered to resonate at a selected frequency of an RF hyperthermia-generating signal, which will cause it to heat faster. For example, the tip of a needle can be modified to include a quarter-wave coil, e.g., at the tip of the needle. For example, at an RF frequency of about 13.56 MHz, about six (6) turns of 22 or 24 gauge wire wrapped around the tip of a needle (and perhaps covered with an electrical insulator, e.g., an enamel coating) may greatly enhance RF absorption at the needle tip, effectively creating a hot spot at the tip of the needle subjected to an RF signal. Additionally, or in the alternative, a needle used to inject one or more RF absorption enhancers may have a temperature sensor at its tip in circuit communication with external circuitry to determine a temperature of a target region. As discussed above, this determined temperature may be used to control the power of the RF signal to maintain a desired temperature of a target region.

[0065] Viruses (and liposomes and perhaps other carriers) may also be used to improve receptivity of target cells and target areas to targeted RF absorption enhancers, e.g., by having a virus (and/or liposomes and/or another carrier) carry a gene (or other biomolecule) for production of a protein that would be incorporated on the surface of a target cell, making the target cell more identifiable and easily attached by a targeted RF enhancer. For example, a patient may be infected with a virus by removing the cells from the body, growing and increasing their number in a tissue culture, infecting the cells outside the body (ex-vivo), and then inserting them back into the patient. Or the virus may be introduced directly into the body (in-vivo) or into the tumor. Additionally, a virus with such a targeting gene may also be delivered to a target cell by other means, e.g., liposomes or microinfusion. Once the target cell produces the protein that is incorporated to the surface membrane, a dose of a targeted RF absorption enhancer is introduced into the body and the targeted carrier thereof will target and attach to the new protein on the target cell membrane. After waiting for a significant number of the targeted RF absorption enhancers to attach to the new protein, a hyperthermia generating RF signal is transmitted into the target area and the target cells are given a lethal dose of heat or a dose of heat to augment other therapies.

[0066] Referring once again to the figures, FIG. 2 illustrates an exemplary embodiment having an RF transmitter 200 in circuit communication with transmission head 218 that transmits an RF signal 270 through a target area 280 to a reception head 268 in circuit communication with an RF receiver 250. The RF transmitter 200 is a multi-frequency transmitter and includes a first RF signal generator 204. The first RF signal generator 204 generates a first signal at a first frequency F1, such as a 16 megahertz frequency. The first RF signal generator 204 is in circuit communications with band pass filter B.P. 1 206, which is in circuit communication with an RF combination circuit 212. Band pass filter B.P. 1 206 is a unidirectional band pass filter that prevents signals at other frequencies from reaching first RF signal generator 204.

[0067] RF transmitter 200 includes a second RF signal generator 208. Second RF signal generator 208 generates a second signal at a second frequency F2, such as, for example a 6 megahertz signal. Second signal generator 208 is in circuit communication with band pass filter B.P. 2 210, which is also in circuit communication with the RF combination circuit 212. Band pass filter B.P. 2 210 prevents signals at other frequencies from reaching second RF signal generator 208. Optionally, RF combination circuit 212 includes circuitry to prevent the first and second signals from flowing toward the other signal generators and thus eliminates the need for band pass filter B.P. 1 206 and band pass filter B.P. 2 210.

[0068] RF combination circuit 212 combines the first and second signal at frequency F1 and frequency F2 and outputs RF signal 270. Preferably, RF combination circuit 212 is in circuit communication with first meter 214. First meter 214 is used to detect the signal strength of RF signal 270. The RF signal 270 is transmitted via transmission head 218 through the target 280 to reception head 268. Optionally, plug type connectors 216, 266 are provided allowing for easy connection/disconnection of transmission head 218, and reception head 268 respectfully. Reception head 268 is preferably in circuit communications with a second meter 264. Second meter 264 detects the RF signal strength received by the reception head 268. The difference in RF signal strength between first meter 214 and second meter 264 can be used to calculate energy absorbed by the target area 280. Reception head 268 is also in circuit communication with an RF splitter 262. RF splitter 262 separates the RF signal 270 into back into its components, first signal at frequency F1 and second signal at frequency F2. RF splitter 262 is in circuit communication with band pass filter B.P. 1 256, which is in circuit communication with first tuned circuit 254. Similarly, RF splitter 262 is in circuit communication with band pass filter B.P. 2 260, which is in circuit communication with second tuned circuit 258. Optionally, band pass filter B.P. 1, 256 and band pass filter B.P. 2 260 can be replaced with a splitter or powered tee.

[0069] First tuned circuit 254 is tuned so that at least a portion of reception head 268 is resonant at frequency F1. Similarly, second tuned circuit 258 is tuned to that at least a portion of reception head 268 is resonant at frequency F2. Since the reception head 268 is resonant at frequencies F1 and F2 the RF signal 270 is forced to pass through the target area 280.

[0070] Optionally, an exemplary embodiment having an RF transmitter, similar to that illustrated above, that does not include an RF combination circuit is provided. Instead, the RF transmitter uses a multi-frequency transmission head. In this embodiment, one portion of the transmission head is used to transmit one frequency signal, and a second portion is used to transmit a second frequency signal. In addition, optionally, the reception head and resonant circuits are constructed without the need for a splitter, by providing a reception head having multiple portions wherein the specific portions are tuned to receive specific frequency signals. An example of such a transmission head in more detail illustrated below.

[0071] FIG. 2 illustrates another means for concentrating the RF signal on specific target area by using a larger transmission head then reception head. The RF signal 270 transmitted by larger transmission head 218 is received by reception head 268 in such a manner that the RF signal 270 is more concentrated near the reception head 268 than it is near the transmission head 218. The more concentrated the RF signal 270, the higher the amount of energy that can be absorbed by the specific area 282. Thus, positioning the larger transmission head on one side of the target area 280 and positioning the smaller reception head 268 on the other side of and near the specific target area 282 is a means for concentrating the RF signal 270 on the specific target area 282. Optionally, one or more of the tuned circuits 254, 258 in the RF receiver 250 are tuned to have a high quality factor or high “Q.” Providing a resonant circuit with a high “Q” allows the tuned head to pick up larger amounts of energy.

[0072] FIGS. 3-6 illustrate a number of exemplary transmitter head and reception head configurations. Additionally, the transmitter and receiver heads may be metallic plates. FIG. 3 illustrates a transmitter head 302 having a non-uniform thickness 314. Transmission head 302 is electrically insulated from target area 306 by an insulation layer 308 in contact with the target area. Similarly, reception head 304 is electrically insulated by insulation layer 310. Insulation layer 310 can be in direct contact with target area 306. Insulation layer 308, 310 provide additional means of electrically insulating the transmission head and reception heads from the target area. Reception head 304 also has non-uniform thicknesses 314 and 316. Receiver head 304 is smaller than transmission head 302 and has a smaller cross sectional area on its face. The smaller cross-sectional area of receiver head 304 facilitates in concentrating an RF signal in a specific target area.

[0073] FIG. 3A illustrates a face view of the exemplary embodiment of the transmission head 302 of FIG. 3. The transmission head 302 includes a plurality of individual transmission heads 314, 316. Transmission heads 314 provide for transmission of a signal at a first frequency, such as 4 megahertz. Transmission heads 316 provide for transmission of a signal at a second frequency, such as, for example 10 MHz, or 13.56 MHz or any of the lower harmonics of 13.56 MHz mentioned above, e.g., 27.12 MHz. Preferably, the transmission heads 314 and 316 are electrically insulated from one another. In addition, preferable the power output can be controlled to each transmission head, allowing for the power output to be increased or decreased in specific areas based upon the size, shape, or depth of the specific target area. Optionally, all of the transmission heads 314 provide the same power output, and transmission heads 316 provide the same power output.

[0074] Obviously the transmission head can contain any number of individual transmission heads. Moreover, the transmission heads can transmit signals at a plurality of frequency, and include, but are not limited to transmission heads that transmit signals at one, two, three, etc. different frequencies. All of which have been contemplated and are within the spirit and scope of the present invention.

[0075] FIG. 4 illustrates yet an additional exemplary embodiment. FIG. 4 illustrates transmission head 402 with a wavy surface 412 and reception head 404 having a wavy surface 414. Other useful surface configurations include bumpy, planer, non-uniform, mounded, conical and dimpled surfaces. Varied surface shapes allow for variable depths of heating control. The shape of receiving head 414 is thinner, narrower (not shown) and is selected based upon the size and shape of the specific target area 410 located in the general target area 406.

[0076] FIG. 5 illustrates an exemplary embodiment with a non-invasive transmission head 502 and an invasive needle 512. In this embodiment, end of needle 512 is located at least partially within general target area 506 and near specific target area 510. Needle 512 is preferably hollow and has extension members 514 within the needle 512. Once the end of needle 512 is located near the specific target area 510, the extension members 514 are extended and attach to the specific target area 510. Preferably, the specific target area 510 has been targeted with a large concentration of RF absorption enhancers 516. The target area 510, itself, becomes the reception head. The extension members 514 provide circuit communication with the resonant circuit and the target area 510 is resonant at the desired frequency. Providing multiple extension members provides for a more even heating of the specific target area 510. This embodiment allows the RF signal to be concentrated on small areas.

[0077] FIG. 6 illustrates yet another exemplary embodiment of transmission and reception heads. In this embodiment, transmission head 602 includes a first transmission head portion 604 and a second transmission head portion 606. The first and second transmission heads 602, 604 are electrically isolated from one another by an insulating member 608. Similarly, reception head 612 includes a first reception portion 614 and a second reception portion 16 that are electrically isolated from one another by an insulation member 618. Providing multiple transmission head portions that are electrically isolated from one another allows the use of multiple frequencies which can be used to heat various shapes and sizes of target areas. Different frequencies can be used to heat thicker and thinner portions of the target area, or deeper target areas allowing for a more uniform heating, or maximum desired heating, of the entire target area. Another exemplary embodiment (not shown) includes a plurality of concentric circles forming transmission head portions and are electrically isolated or insulated from each other.

[0078] FIG. 7 illustrates a high level exemplary methodology of for inducing hyperthermia in a target area 700. The methodology begins at block 702. At block 704 the transmission head is arranged. Arrangement of the transmission head is accomplished by, for example, placing the transmission head proximate to and on one side of the target area. At block 706 the reception head is arranged. Arrangement of the reception head is similarly accomplished by, for example, placing the reception head proximate to and on the other side of the target area so that an RF signal transmitted via the transmission head to the reception head will pass through the target area. At block 708 the RF signal is transmitted from the transmission head to the reception head. The RF signal passes through and warms cells in the target area. The methodology ends at block 710 and may be ended after a predetermined time interval and/in response to a determination that a desired heating has been achieved.

[0079] FIG. 8 illustrates an exemplary methodology for inducing hyperthermia in a target area 800. The methodology begins at block 802. At block 804 an RF transmitter is provided. The RF transmitter may be any type of RF transmitter allowing the RF frequency to be changed or selected. Preferably RF transmitter is a variable frequency RF transmitter. Optionally, the RF transmitter is also multi-frequency transmitter capable of providing multiple-frequency RF signals. Still yet, optionally the RF transmitter is capable of transmitting RF signals with variable amplitudes or pulsed amplitudes.

[0080] Preferably, a variety of different shapes and sizes of transmission and reception heads are provided. The transmission head is selected at block 806. The selection of the transmission head may be based in part on the type of RF transmitter provided. Other factors, such as, for example, the depth, size and shape of the general target area, or specific target area to be treated, and the number of frequencies transmitted may also be used in determining the selection of the transmission head.

[0081] The RF receiver is provided at block 808. The RF receiver may be tuned to the frequency(s) of the RF transmitter. At block 810, the desired reception head is selected. Similarly to the selection of the transmission head, the reception head is preferably selected to fit the desired characteristics of the particular application. For example, a reception head with a small cross section can be selected to concentrate the RF signal on a specific target area. Various sizes and shapes of the reception heads allow for optimal concentration of the RF signal in the desired target area.

[0082] The RF absorption in the target area is enhanced at block 812. The RF absorption rate may be enhanced by, for example, injecting an aqueous solution, and preferably an aqueous solution containing suspended particles of an electrically conductive material. Optionally, the RF absorption in the target area is enhanced by exposing the target cells to one or more targeted RF absorption enhancers, as discussed above.

[0083] Arrangement of the transmission head and reception head are performed at blocks 814 and 816 respectfully. The transmission head and reception heads are arranged proximate to and on either side of the target area. The transmission head and reception heads are insulated from the target area. Preferably the heads are insulated from the target area by means of an air gap. Optionally, the heads are insulated from the target area by means of an insulating material. The RF frequency(s) are selected at block 818 and the RF signal is transmitted at block 820. In addition to selecting the desired RF frequency(s) at block 818, preferably, the transmission time or duration is also selected. The duration time is set to, for example, a specified length of time, or set to raise the temperature of at least a portion of the target area to a desired temperature/temperature range, such as, for example to between 106.degree. and 107.degree., or set to a desired change in temperature. In addition, optionally, other modifications of the RF signal are selected at this time, such as, for example, amplitude, pulsed amplitude, an on/off pulse rate of the RF signal, a variable RF signal where the frequency of the RF signal varies over a set time period or in relation to set temperatures, ranges or changes in temperatures. The methodology ends at block 822 and may be ended after a predetermined time interval and/in response to a determination that a desired heating has been achieved.

[0084] FIG. 9 illustrates an exemplary in-vitro methodology of inducing hyperthermia in target cells 900. The exemplary in-vitro methodology 900 begins at block 902. At block 904, cells to be treated are extracted from a patient and placed in a vessel. The removed cells include at least one or more target cells and are extracted by any method, such as for example, with a needle and syringe. At block 906 antibodies bound with RF enhancers are provided and exposed to the extracted cells. The antibodies bound with RF enhancers attach to one or more of the target cells that are contained within the larger set of extracted cells.

[0085] An RF transmitter and RF receiver are provided at blocks 910 and 912 respectively. The transmission head is arranged proximate to and on one side of the target cells in the vessel at block 916. At block 918 the reception head is arranged proximate to and on the other side of the target cells. An RF signal is transmitted at block 918 to increase the temperature of the target cells to, for example, to between 106.degree. and 107.degree..

[0086] FIG. 10 illustrates an exemplary in-vitro methodology of separating cells 1000. The exemplary in-vitro methodology begins at block 1002. At block 1004, cells to be treated are extracted from a patient and placed in a vessel. The extracted cells include at least one or more target cells and are extracted by any method, such as for example, with a needle and syringe. At block 1006 targeting carriers (with either inherent targeting moieties or targeting moieties attached thereto) bound to magnetic particles (magnetic targeted RF absorption enhancers) are provided and exposed to the extracted cells. The magnetic targeted RF absorption enhancers attach to one or more of the target cells that are contained within the larger set of extracted cells. A magnetic coil is provided at block 1010 and energized at block 1012. The target cells that are bound to the targeting moieties are attracted by the magnetic field. The target cells bound to the targeting moieties are then separated from the other cells. The target cells can be separated by skimming the one or more target cells from the remaining cells, or retaining the one or more target cells in one area of the vessel and removing the other cells. The methodology ends at block 1020 after one or more of the target cells are separated from the other cells.

[0087] As shown in FIG. 11, an exemplary system 1100 according to the present invention may have an RF generator 1102 transmitting RF energy via a transmission head 1104 toward a target area 1106. The transmission head 1104 may have a plate 1108 operatively coupled to a coil or other inductor 1110. In such a configuration, the head 1104 may itself constitute or be components of a resonant circuit for transmission and/or reception of a hyperthermia-generating RF signal. The plate 1108 may be in circuit communication with the coil or other inductor 1110. The RF generator 1102 may be a commercial transmitter, e.g., the transmitter portion of a YAESU brand FT-1000MP Mark-V transceiver. A hyperthermia generating signal can be generated at about 13.56 MHz (one of the FCC-authorized frequencies for ISM equipment) by the transmitter portion of a YAESU brand FT-1000MP Mark-V transceiver by clipping certain blocking components as known to those skilled in the art. The RF generator 1102 and transmission head 1104 may have associated antenna tuner circuitry (not shown) in circuit communication therewith or integral therewith, e.g., automatic or manual antenna tuner circuitry, to adjust to the impedance of transmission head 1104 and the target area 1106 (and a receiver, if any). The transmitter portion of a YAESU brand FT-1000MP Mark-V transceiver has such integral antenna tuner circuitry (pressing a “Tune” button causes the unit to automatically adjust to the load presented to the RF generator portion). The RF generator 1202 and transmission head may have associated antenna tuner circuitry (not shown) in circuit communication therewith or integral therewith, e.g., automatic or manual antenna tuner circuitry, to adjust to the combined impedance of the target area 1206 and the receiver 1212, 1214 and compensate for changes therein. The transmitter portion of a YAESU brand FT-1000MP Mark-V transceiver has such integral antenna tuner circuitry. Various configurations for the plate 1108 and coil 1110 are possible, as exemplified below. A central axis of the coil, e.g., the central axis of a cylindrical inductor core, may be directed toward the target area.

[0088] As exemplified by FIG. 12A, an exemplary system 1200 according to the present invention may have an RF generator 1202 transmitting RF energy via a transmission head 1204 (which transmission head 1204 may have a plate 1208 operatively coupled to a coil or other inductor 1210) through a target area 1206 to a reception head 1212 coupled to a load 1214. The reception head 1212 may have a plate 1216 operatively coupled to a coil or other inductor 1218. The RF generator 1202 may be a commercial transmitter, e.g., the transmitter portion of a YAESU brand FT-1000MP Mark-V transceiver, which may be modified as discussed above to generate a 13.56 MHz signal. The RF generator 1202 and transmission head 1204 may have associated antenna tuner circuitry (not shown) in circuit communication therewith or integral therewith, e.g., automatic or manual antenna tuner circuitry, to adjust to the combined impedance of the transmission head 1204, the target area 1206, and the receiver 1212, 1214 and compensate for changes therein. The transmitter portion of a YAESU brand FT-1000MP Mark-V transceiver has such integral antenna tuner circuitry. The load 1214 may be as simple as a non-inductive resistive load (e.g., a grounded power resistor) providing a path for coupled RF energy to dissipate. Various configurations for the plates 1208, 1216 and coils 1210, 1218 are possible, as exemplified below.

[0089] As exemplified by FIG. 12B, an exemplary system 1220 according to the present invention may have a combined RF generator/load 1222 transmitting RF energy via the transmission head 1204 through the target area 1206 to the reception head 1212, which may also be coupled to the combined RF generator/load 1222. The combined RF generator/load 1222 may be a commercial transceiver, e.g., a YAESU brand FT-1000MP Mark-V transceiver, which has built-in automatic antenna tuner circuitry, which can automatically correct for the impedance of the transmission head 1204, the target area 1206, and the reception head 1212. For generating hyperthermia with an RF signal, the YAESU brand FT-1000MP Mark-V transceiver may not generate enough heat, depending on whether RF enhancers are used. Accordingly, the output may need to be amplified with a power amplifier prior to coupling via the transmission head through the target region to the reception head. The configurations of FIGS. 12A and 12B, having a transmission head and a reception head defining a target region therebetween, are favored at the time of the filing of the present application with respect to generating hyperthermia with an RF signal in a target region, e.g., in a tumor or portion of a tumor treated with RF enhancers.

[0090] As shown in FIGS. 13-14, an exemplary head 1300 (as a transmission head and/or as a reception head) may have a plate of conductive material 1302 operatively coupled to a coil or other inductor 1304, an axis of which inductor 1304 may extend generally perpendicular or substantially perpendicular with respect to a surface 1305 of the plate 1302. In such a configuration, the head 1300 may itself constitute or be components of a resonant circuit for transmission and/or reception of a hyperthermia-generating RF signal. The plate of conductive material 1302 may be a generally round plate made of flat, conductive material of substantially uniform thickness. The specific characteristics (surface area, thickness, material, etc.) of the plate 1302 may depend on the specific application and may depend greatly on the frequency or frequencies of electromagnetic radiation directed toward a target area. The plate 1302 may be made from, e.g., copper or silver-plated copper or bronze and should be thick enough to be self-supporting or supported by supporting structures (not shown). The surface area of the plate 1302 may depend on the size of the target area, with a larger plate being used for a larger target area. The surface area of the plate 1302 may depend on the frequency of hyperthermia generating RF signal being used, with lower frequencies, e.g., 13.56 MHz, using a larger plate than higher frequencies, e.g., 27.12 MHz or 40.68 MHz, to help tune to the frequency of hyperthermia generating RF signal being used.

[0091] Similarly, the specific characteristics (number of inductors, inductance of each inductor, overall length of each, material for each, material dimensions for each, number of windings for each, coil diameter for each, coil core material for each, etc.) of the inductor 1304 may depend on the specific application and may depend greatly on the frequency or frequencies of electromagnetic radiation directed toward a target area. At higher RF frequencies, (e.g., at about 100 MHz and higher) the inductor 1304 may be a simple straight length of electrical conductor. The inductor 1304 at lower RF frequencies (e.g., about 13.56 MHz) may be configured as a coil 1304 of electrically conductive material, as shown in the figures. If the inductor 1304 is a coil, the coil 1304 may be formed using a core 1306, which may have an axis, e.g., a central axis 1307, that is generally or substantially perpendicular to the surface 1305 of plate 1302. If a plurality of frequencies of electromagnetic radiation are directed toward a target area, a corresponding plurality of electrically insulated inductors may extend generally or substantially perpendicular from the surface 1305 toward the target area. Some or all of the plurality of electrically insulated inductors may be coils, some or all of which may be coaxial or even share a common core 1306. As shown in FIG. 13, the inductor 1304 may be spaced from a central point 1308 (e.g., a center of area or center of mass or axial center) of the plate by a distance 1309. Similarly, the axis 1307 of inductor 1304 may be spaced from the central point 1308 of the plate by a distance (not shown). As shown in FIG. 14, the head 1300 may have an associated electrical connector 1312 for being placed in circuit communication with either an RF generator (in the case of a transmission head) or a load (in the case of a reception head). As discussed below, the plate 1302 may be electrically connected to the inductor 1304 at a point 1310. In the alternative, the plate 1302 may be electrically insulated from the inductor 1304, which may permit the plate to be configured differently from the inductor 1304, e.g., permit the plate 1302 to be grounded or tuned independently of the inductor 1304. Thus, the connector 1312 may be in circuit communication with the plate 1302 and/or the inductor 1304 and the plate 1302 and the inductor 1304 may each have an associated connector. As discussed below, the other end 1314 of coil 1304 may be free or may be connected to a tuning circuit, e.g., a capacitor which may be a variable capacitor.

[0092] An exemplary head for use at a frequency of about 13.56 MHz may have a plate formed as an approximately circular shaped disk of flat copper that is about ten (10) inches thick electrically connected to an inductor that is a coil formed from about six (6) turns of 22 or 24 gauge wire would around a 1-inch hollow air core with the windings extending about three (3) inches from the surface of the plate.

[0093] As shown in FIG. 15, two of the exemplary heads 1300 of FIGS. 13-14 may be used as a transmission head 1300a and reception head 1300b pair. In this configuration, the transmission head 1300a may be in circuit communication with an RF generator via connector 1312a and reception head 1300b may be in circuit communication with a load via connector 1312b with RF electromagnetic energy being coupled from transmission head 1300a to reception head 1300b. As shown in FIG. 15, such a pair may be oriented to create an area 1500 bounded on different sides by the plates 1302a, 1302b and coils 1304a, 1304b. More specifically, the transmission head 1300a and reception head 1300b may be oriented with their plates 1302a, 1302b generally facing each other and their inductors spaced from each other and with their axes extending generally parallel to each other to create area 1500. Area 1500 thus is bounded by a side 1502a proximate plate 1302a, a side 1502b proximate plate 1302b, a side 1504a proximate inductor 1304a, and a side 1504b proximate inductor 1304b. Notice that in this configuration, the distal ends 1502a, 1502b of the inductors 1304a, 1304b are proximate an opposite location 1508b, 1508a of the opposite plate 1302b, 1302a, respectively, which creates an overlap of the inductors 1304a, 1304b that helps form the area 1500. It is expected that RF electromagnetic energy will be coupled from inductor 1304a to inductor 1304b in this side to side configuration. Similarly, it is also believed that RF electromagnetic energy will be coupled from plate 1302a to plate 1302b. Surprisingly, a pair of heads 1300a, 1300b tuned to substantially the same frequency (or harmonics thereof) can be arranged in a skewed configuration (with the plates not directly facing each other and the axes of the coils skewed) and separated by several feet of separation and still permit coupling of significant RF electromagnetic energy from head 1300a to head 1300b.

[0094] Another exemplary head configuration is shown in FIGS. 16-17, which shows exemplary head 1600 (as a transmission head and/or as a reception head). The head 1600 is similar in many ways to the head 1300 of FIGS. 13-14. Like head 1300, head 1600 may have a plate of conductive material 1602 operatively coupled to a coil or other inductor 1604, an axis of which inductor 1604 may extend generally perpendicular or substantially perpendicular with respect to a surface 1605 of the plate 1602. In such a configuration, the head 1300 may itself constitute or be components of a resonant circuit for transmission and/or reception of a hyperthermia-generating RF signal. Except as set forth below, all of the discussion above with respect to head 1300 also applies to the head 1600. If the inductor 1604 is a coil, the coil 1604 may be formed using a core 1606, which may have an axis, e.g., a central axis 1607, that is generally or substantially perpendicular to surface 1605 of plate 1602. Unlike head 1300, in head 1600, the axis 1607 of inductor 1604 is shown as being coaxial with a central point of the plate. Also note that the head 1600 has a coil 1604 that has more closely spaced coil windings than coil 1304 of head 1300, which permits coil 1604 to be shown as being shorter than coil 1304 in FIG. 13. As shown in FIG. 17, the head 1600 may have an associated electrical connector 1612 for being placed in circuit communication with either an RF generator (in the case of a transmission head) or a load (in the case of a reception head) with RF electromagnetic energy being coupled from transmission head 1300a to reception head 1300b. As discussed below, the plate 1602 may be electrically connected to the inductor 1604 at a point 1610. In the alternative, the plate 1602 may be electrically insulated from the inductor 1604, which may permit the plate to be configured differently from the inductor 1604, e.g., permit the plate 1602 to be grounded or tuned independently of the inductor 1604. Thus, the connector 1612 may be in circuit communication with the plate 1602 and/or the inductor 1604 and the plate 1602 and the inductor 1604 may each have an associated connector. As discussed below, the other end 1614 of coil 1604 may be free or may be connected to a tuning circuit, e.g., a capacitor which may be a variable capacitor. Again, except as noted above, all of the discussion above with respect to head 1300 also applies to the head 1600.

[0095] A pair of the exemplary heads 1600 of FIGS. 16-17 may be used as a transmission head 1600a and reception head 1300b pair, with the transmission head 1600a in circuit communication with an RF generator via connector 1612a and the reception head 1600b in circuit communication with a load via connector 1612b, with RF electromagnetic energy being coupled from transmission head 1600a to reception head 1600b. In such a configuration, the head 1600 may itself constitute or be components of a resonant circuit for transmission and/or reception of a hyperthermia-generating RF signal. Although a pair of heads 1600 may be arranged similar to as shown in FIG. 15, with a pair of inductors side to side and plates facing each other, head 1600 does not really lend itself to this configuration because inductor 1604 is significantly shorter than inductor 1304 and if put in this configuration, there would be a substantially smaller target area and significant portions of the opposite plates not directly facing each other. The head 1600 does lend itself to the configuration shown in FIG. 18 in which a pair of heads 1600a, 1600b are arranged in an “end-fired” configuration, i.e., the coils 1604a, 1604b are coaxial so that the ends of the coils are essentially aimed at each other. In the configuration of FIG. 18, the plates 1602a, 1602b face each other directly. RF electromagnetic energy is coupled from transmission head 1300a to reception head 1300b through an area 1800 between the heads 1600a, 1600b as discussed in more detail below. The central axis of the coils 1604a, 1604b, e.g., the central axis of a cylindrical inductor core, may be directed toward the target area.

[0096] FIG. 19 shows two heads 1600a, 1600b in the “end-fired” configuration of FIG. 18 with transmission head 1600a being in circuit communication with an RF generator via coaxial cable 1900 connected to connector 1312a and the reception head 1300b being in circuit communication with a load via a coaxial cable 1902 connected to connector 1312b, with RF electromagnetic energy being coupled from transmission head 1600a to reception head 1600b. A conductor 1904 within connector 1612a is in circuit communication with plate 1602a and coil 1604a. Similarly, a conductor 1906 within connector 1612b is in circuit communication with plate 1602b and coil 1604b. The shield layer of coaxial cables 1900, 1902 are grounded as shown schematically at 1910, 1912. It is believed that there is significant coupling of RF electromagnetic energy directly between the end-fired inductors 1604a, 1604b, as indicated schematically by the relatively closely spaced rays at 1920. It is also believed that there is additional coupling of RF electromagnetic energy between the plates 1602a, 1602b, although not at as significant a rate, as indicated schematically by the more widely spaced rays at 1930. Again, surprisingly, a pair of such heads 1600a, 1600b tuned to substantially the same frequency (or harmonics thereof) can be arranged in a skewed configuration (with the plates not directly facing each other and the axes of the coils skewed) and separated by several feet of separation and still permit coupling of significant RF electromagnetic energy from head 1600a to head 1600b.

[0097] FIG. 20 shows two heads 2000a, 2000b the same as the two heads 1600a, 1600b in the “end-fired” configuration of FIGS. 18 and 19, except that the heads 2000a, 2000b have plates 2002a, 2002b that are electrically insulated from inductors 2004a, 2004b and are grounded. Thus, in the configuration of FIG. 20, the inductor 2004a is in circuit communication with an RF generator via coaxial cable 1900 connected to connector 2012a and inductor 2004b is in circuit communication with a load via a coaxial cable 1902 connected to connector 2012b, with RF electromagnetic energy being coupled from inductor 2004a to inductor 2004b. A conductor 2040 within connector 2012a is in circuit communication with 2004a. Similarly, a conductor 2042 within connector 2012b is in circuit communication with coil 2004b. The shield layer of coaxial cables 1900, 1902 are grounded as shown schematically at 1910, 1912. Additionally, in this configuration, the plates 2002a, 2002b are grounded as shown schematically at 2044, 2046. It is believed that there is significant coupling of RF electromagnetic energy directly between the end-fired inductors 2004a, 2004b, as indicated schematically by the relatively closely spaced rays at 2020.

[0098] FIGS. 21A and 21B show schematically the end-fired coils 1604a, 1604b, 2004a, 2004b shown in FIGS. 18-20 coupling electromagnetic radiation 1920, 2020 from coil 1604a, 2004a to coil 1604b, 2004b. In FIG. 21A, the distal ends 1614a, 1614b, 2014a, 2014b of coils 1604a, 2004a, 1604b, 2004b are shown as being free. In the alternative, either or both of the distal ends 1614a, 2014a, 1614b, 2014b may be connected to active or passive circuitry to assist in coupling electromagnetic radiation 1920, 2020 from coil 1604a, 2004a to coil 1604b, 2004b, whether there is an associated plate 1602, 2002 or not. For example, either or both of the distal ends 1614a, 2014a, 1614b, 2014b of coils 1604a, 2004a, 1604b, 2004b may be in circuit communication with parallel capacitors C1, C2 as shown in FIG. 21B to assist in coupling electromagnetic radiation from coil to coil. Similarly, FIGS. 22A and 22B show schematically the side to side coils 1304a, 1304b shown in FIG. 15 coupling electromagnetic radiation 2200 from coil 1304a to coil 1304b. In FIG. 22A, the distal ends 1314a, 1314b of coils 1304a, 1304b are shown as being free. In the alternative, either or both of the distal ends 1614a, 1614b may be connected to active or passive circuitry to assist in coupling electromagnetic radiation 2200 from coil 1304a to coil 1304b, whether there is an associated plate 1302 or not. For example, either or both of the distal ends 1314a, 1314b, of coils 1604a, 1604b may be in circuit communication with parallel capacitors C3, C4 as shown in FIG. 22B to assist in coupling electromagnetic radiation from coil to coil. Side to side coils 1304a, 1304b without corresponding plates may be placed in a grounded cage, e.g., a Faraday cage such as a grounded bronze screen box, to prevent re-radiation away from each other, such as re-radiation along their central axes. The use of ungrounded plates in circuit communication with coils (e.g., FIGS. 13-19) tends to confine the RF energy between the plates, which might avoid the need for a Faraday shield. For example, for a pair of the exemplary heads described above (13.56 MHz; plates formed as an approximately circular shaped disk of flat copper that is about ten (10) inches thick electrically connected to a coil formed from about six (6) turns of 22 or 24 gauge wire would around a 1-inch hollow air core with the windings extending about three (3) inches from the surface of the plate) arranged in the configuration of FIG. 18 and tuned to the frequency being transmitted, with the plates spaced about 6” apart, transmitted RF seems to stay substantially within the confines of the plates using a neon bulb, as basic testing has indicated.

[0099] Any of the foregoing heads may be used for transmission and/or reception of a hyperthermia-generating RF signal.

[0100] FIG. 23 shows an exemplary RF generator 2300 in circuit communication with a transmission head 2302 coupling hyperthermia generating RF energy to a reception head 2304 through a target area 2306. The spacing between the transmission head 2302 and the reception head 2304 preferably, but not necessarily, may be adjusted to accommodate targets of different sizes. The transmission head 2302 and/or the reception head 2304 may have circuitry to accommodate differences in impedance between the transmission head 2302 and the reception head 2304 caused, e.g., by differences in spacing between the heads 2302, 2304 and/or different targets. Such circuitry may include automatic antenna matching circuitry and/or manually adjustable variable components for antenna matching, e.g., high-voltage, high-power RF variable capacitors. The reception head 2304 may be in circuit communication with a load 2308, which may be as simple as a non-inductive resistive load (e.g., a grounded power resistor) providing a path for coupled RF energy to dissipate. The transmission head 2302 and the reception head 2304 may each be in any of the various head configurations shown and/or described herein. The transmission head 2302 and/or the reception head 2304 may have an associated power meter, which may be used as feedback to adjust any manually adjustable variable components for antenna matching until a substantial amount of power being transmitted by transmission head 2302 is being received by the reception head 2304. In general, such power meters may be separate or integral with the RF generator, and/or the RF receiver, and/or the combined RF generator/receiver. If separate power meters are used, they may be located remotely with the transmission head 2302 and the reception head 2304 to facilitate contemporaneous adjustment and tuning of the transmission head 2302 and the reception head 2304.

[0101] The exemplary RF generator 2300 of FIG. 23 comprises a crystal oscillator 2320 that generates a signal 2322 at a power level of about 0.1 Watts at a selectable frequency to a preamplifier 2324. The signal 2322 may be modified before the preamplifier 2324 to have a variable duty cycle, e.g., to provide a pulsed RF signal at a variable duty cycle. As discussed above, it may be beneficial to use a frequency modulated (FM) RF signal to create hyperthermia with certain energy absorption enhancer particles. Accordingly, in addition, or in the alternative, signal 2322 may be modified before the preamplifier 2324 to be an FM signal. For example, pre-amp 2324 may be replaced with an amplifying FM exciter to modulate the signal 2322 with a selected modulation frequency and amplify the signal as pre-amp 2324. The parameters of the FM RF signal used to generate hyperthermia may be selected to correspond to the specific sample of particles being used as energy absorption enhancer particles. The center frequency of an FM hyperthermia generating RF signal may correspond to a resonant frequency of nominally sized particles used as energy absorption enhancer particles and the modulation of the FM hyperthermia generating RF signal may correspond to the size tolerance of the particles used as energy absorption enhancer particles, as discussed above.

[0102] The preamplifier 2324 amplifies the RF signal 2322 (or the modified signal 2322) and generates a signal 2326 at a power level of about 10 Watts to an intermediate power amplifier 2328. The intermediate power amplifier 2328 amplifies the RF signal 2326 and generates an RF signal 2330 at a power level of about 100 Watts to a power amplifier 2332. The power amplifier 2332 amplifies the RF signal 2330 and generates a selectable power RF signal 2334 at a selectable power level of 0.00 Watts to about 1000 Watts to the transmission head 2302. A power meter may be placed in circuit communication between the power amplifier 2332 and the transmission head 2302 to measure the RF power to the transmission head 2302. Similarly, a power meter may be placed in circuit communication between the reception head 2304 and the load 2306 to measure the RF power from the reception head 2304. The preamplifier 2324 may be a hybrid preamplifier. The intermediate power amplifier 2328 may be a solid state Class C intermediate power amplifier. The power amplifier 2332 may be a zero-bias grounding grid triode power amplifier, which are relatively unaffected by changes in output impedance, e.g., a 3CX15000A7 power amplifier.

[0103] The exemplary RF generator 2300 shown generates a high-power fixed-frequency hyperthermia generating RF signal at an adjustable power range of 0.00 Watts to about 1000 Watts. The exemplary RF generator 2300 shown may be modified to generate high-power fixed-frequency hyperthermia generating RF signals at selected frequencies or at an adjustable frequency, any of which may be pulsed or FM modulated. For example, a plurality of separate crystals, preamplifiers, and IPAs, each at a different frequency, e.g., 13.56 MHz, 27.12 MHz, 40.68 MHz, 54.24 MHz, 67.80 MHz, and 81.36 MHz (not shown) may be switchably connected to the power amplifier 2332 for generation of a high-power hyperthermia generating signal at a frequency selected from a plurality of frequencies.

[0104] While the present invention has been illustrated by the description of embodiments thereof, and while the embodiments have been described in some detail, it is not the intention of the applicant to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in the art. For example, any of the transmitter circuits and/or transceiver circuits described herein can be used with virtually any of the RF absorption enhancers (general and/or targeted), described herein, or with any combination or permutation thereof, or without any RF absorption enhancer. As another example, the RF signal (single frequency or FM modulated) may be modulated with another signal, such as, for example, a square wave (e.g. a 300-400 Hz square wave). Modulating the RF signal with a square wave may stimulate the tissue and enhance heating; square waves introduce harmonics that may enhance modulation utilized; and square waves may also be used to pulse the transmitted signal to change the average duty cycle. Another example includes total body induced hyperthermia to treat the patient’s entire body. In this example, the transmission and reception heads are as large as the patient and hyperthermia is induced in the entire body. Cooling the blood may be required to prevent overheating and can be accomplished in any manner. Additionally, the steps of methods herein may generally be performed in any order, unless the context dictates that specific steps be performed in a specific order. Therefore, the invention in its broader aspects is not limited to the specific details, representative apparatus and methods, and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of the applicant’s general inventive concept.


US Patent Application # 20050251234 (A1)

Systems and Methods for RF-Induced Hyperthermia Using Biological Cells and Nanoparticles as RF Enhancer Carriers

10 November 2005
John Kanzius, et al.
US Cl. 607/101
Intl Cl. A61F 002/00

Abstract — A method of inducing hyperthermia in at least a portion of a target area–e.g., a tumor or a portion of a tumor or targeted cancerous cells–is provided. Targeted RF absorption enhancers, e.g., tumor infiltrating lymphocytes (TILs) containing RF absorbing particles, are introduced into a patient. These targeted RF absorption enhancers will target certain cells in the target areas and enhance the effect of a hyperthermia generating RF signal directed toward the target area. The targeted RF absorption enhancers may, in a manner of speaking, add one or more RF absorption frequencies to cells in the target area, which will permit a hyperthermia generating RF signal at that frequency or frequencies to heat the targeted cells.


US Patent Application # 20050251233

System and method for RF-induced hyperthermia

John Kanzius, et al.
10 November 2005

Improving multi-carrier PA efficiency using envelope tracking

By Gerard Wimpenny, Nujira


Modern complex modulation schemes have the disadvantage of requiring linear power amplification, which compromises overall system efficiency because RF power amplifiers (PAs) are much less efficient when backed off from maximum power. The power amplifier and its associated components consume up to 50% of the overall power in a cellular basestation and account for a similar proportion of operating costs. Conventional techniques for improving PA efficiency are inherently narrowband, and are unable to span more than a single band. This article describes a technique based on envelope tracking that has been proven to offer a dramatic improvement in efficiency, from typically low 20% for a class AB amplifier to mid 40%, while offering multiband performance.

Manufacturers of cellular basestations are under considerable pressure on numerous fronts and need to innovate to survive. In particular, the demands on RF PA designers continue to increase. These demands arise from the following factors.

Firstly, the continued evolution of the UMTS and WiMAX standards, and further evolved standards such as Long Term Evolution (LTE), are generating challenging technical requirements, including the need to support a variety of different channel coding and modulation techniques (CDMA, OFDM, etc.), broader channel bandwidths, and high peak-to-average power (PAPR) modulation schemes.

Secondly, factors such as deregulation and the growth of new networks, particularly in parts of the world not yet well equipped with cellular networks, have created a requirement for basestations to support a wider range of frequency bands as new spectrum is released to meet urgent capacity demands.

Thirdly, environmental or ‘green’ issues, such as the desire to reduce both direct and indirect CO2 emissions, and equipment size, are also moving up the agenda. Several operators have pledged to work with suppliers to increase the energy efficiency of their networks. For example, Vodafone aims to improve the average energy efficiency of new network equipment by 33% by March 2008 compared with its 2006 figures. The savings, in both cost and carbon emissions, which could be made by realizing these improvements are huge. Vodafone has stated its intention to remove air conditioning units from sites where possible, which alone account for about 25% of network energy usage, and use remote radio heads where possible. But the removal of air conditioning units and the deployment of remote radio heads are only feasible if PA efficiency is greatly improved. Improving PA efficiency with high peak-to-average power (PAPR) systems is particularly challenging due to the need to use linear PAs to meet the critical RF performance criteria.

Finally, the increased level of competition on a global scale puts increasing pressure on design teams to use the latest and greatest technology in order to stay competitive, in turn leading to the need for faster design cycles. This, coupled with an equally strong need to contain development costs (again for competitive reasons) has meant that PA design teams need to focus on generic platforms which can be deployed into a number of different products with minimal or no change. A reduction in the number of design variants also allows improved inventory management.

In summary, the technical design challenges are increasing, and infrastructure vendors are under pressure to produce complex product families supporting different frequencies, power levels and standards, at lower prices, with shorter product development times, while at the same time achieving significant reductions in power consumption. The requirements of lower power consumption and streamlined inventory management are both critical factors driving the development of very high efficiency, RF frequency agnostic and modulation agnostic broadband PAs for wireless infrastructure.

The industry has devoted years of R&D effort to developing software defined radios (SDRs) to address these goals, but the engineers have been frustrated in their attempts to build equipment fulfilling all of the requirements because of the need to incorporate narrow band high power PAs and band specific front-end filters. Only recently have advances in PA technology made it possible to overcome one of these ‘final barriers’.

Flexible BTS architecture
Figure 1 shows a traditional basestation PA configuration. Flexible, wideband basestation architectures are already possible for the lower power RF circuitry, but are more difficult for the PA final stage. A short term solution is to make ‘band selectable’ PA modules but in the longer term multi-band PAs will be the preferred solution.

1. A conventional basestation PA configuration without envelope tracking

The efficiency of the PA is dependant on the ‘crest factor’, or peak/average power ratio (PAPR) of the signal being amplified. In a W-CDMA system, the PA is usually operating far below peak power, as the signal crest factor is typically 6.5 – 7.0dB. OFDM systems such as 3GPP LTE and WiMAX use even higher crest factors (typically 8.5 – 9.5dB) for improved spectral efficiency but this results in traditional PA designs having even lower efficiency.

It is difficult to achieve flexible, high efficiency, broadband PA designs by means of ‘RF only’ efficiency enhancement techniques, such as Doherty. A large number of variants are required to cover all the different frequencies, powers and PAPR values, as these designs have inherently narrow bandwidth. It also takes considerable development time to achieve high production yields, and it is difficult to maintain the efficiency as systems evolve to higher PAPR values.

Envelope tracking
The classic Class AB amplifier technology offers efficient operation when the RF envelope waveform is close to peak power, and with careful design this can be achieved over a relatively broad bandwidth. When amplifying high crest factor RF signals though, it is less efficient, typically in the range 15-25% for W-CDMA and WiMax. The reason for this is shown in Figure 2, where the solid blue curve represents drain efficiency vs. power output and the dashed curve is the probability distribution of instantaneous output power value. As can be seen, for much of the time the signal power lies well below the peak power and hence the device is operating at low efficiency.

2.Main curve shows drain efficiency vs. power output, and dashed curve shows the probability distribution of the instantaneous output power value

It is possible, however, to achieve a significant improvement in PA efficiency (and hence the efficiency of the entire network) without compromising bandwidth using envelope tracking (ET). Here the voltage supplied to the final RF stage power transistor is changed dynamically, synchronized with the RF signal passing through the device, to ensure that the output device remains in its most efficient operating region (in saturation). This technique can significantly increase the energy efficiency of 3G, WiMAX and DVB transmitters. With envelope tracking, the supply voltage is reduced from its maximum value so that it ‘tracks’ the signal envelope, and this reduces the energy dissipated as heat as shown in Figure 3. An ET amplifier operates at its optimum efficiency at all envelope levels, and hence offers greatly improved efficiency when operating with envelope varying signals, as shown in Figure 4.

3. Envelope tracking reduces the voltage difference between the supply voltage and the signal envelope, which determines the amount of energy dissipated as heat.

4. Efficiency locus when envelope tracking is applied

As well as reducing power consumption, the reduced heat-sinking requirements allow PAs to be smaller and more reliable. Lower base station power consumption also has beneficial effects further down the chain, allowing reductions in battery back-up requirements, for instance. ET is fully compatible with contemporary digital pre-distortion techniques, and does not significantly degrade system linearity.

While the principle of ET has been known for many years [1], it has not been commercialized until now because of the difficulty of implementing a power supply modulator capable of achieving the accuracy, bandwidth and noise specifications necessary for wideband signals such as multi carrier WCDMA, WiMAX or DVB operation. These parameters all relate directly to the detailed design of the power modulator, which has to track the rapidly varying envelope of the RF signal with very high accuracy, but also has to achieve high power conversion efficiency for the benefits of ET to be fully realized.

Figure 5 shows how Nujira’s High Accuracy Tracking (HAT) power modulator is used in conjunction with a PA. The only addition required to the standard basestation architecture described in Figure 1 is an envelope tracking interface to drive the HAT power modulator. The result is an efficient, flexible basestation architecture which preserves the standard PA footprint, signal interfaces and power supplies within a modular PA design, and moves one step closer to a ‘plug & play’ basestation.

5. Application of High Accuracy Tracking power modulator to the standard power amplifier architecture

The same ET approach is equally applicable for 2500MHz WiMAX, 850MHz CDMA2000, and 2100MHz or 900MHz W-CDMA, and can be used with LDMOS, GaAs FET, GaAs HBT or GaN based PAs. The emerging GaN technology offers not only high efficiency but also the possibility of implementing broadband designs; hence it is an excellent partner for envelope tracking.

Summary
The use of envelope tracking technology enables the efficiency of high crest factor RF PAs to be significantly increased, regardless of device technology, while preserving the benefits of high spectral efficiency possible with modern wireless communication standards such as WCDMA, WiMAX, LTE and DVB. Envelope tracking is also inherently RF frequency agnostic and opens up the possibility of future broadband ‘multi-band’ PAs.

Operators are now demanding radio equipment that offers high flexibility, small size and above all, high energy efficiency. The availability of broadband PAs with efficiencies approaching 50% is critical to meeting these needs, and envelope tracking is a key enabling technology. An essential element of any envelope tracking solution is the power supply modulator, and Nujira’s HAT technology is rapidly becoming established as the industry benchmark for high efficiency power amplifier performance.

References
1. Khan, L.R., “Single Sideband Transmission by Envelope Elimination and Restoration”, Proc. IRE, Vol.40, July 1952, pp803-806.