Radio frequency system and method for tissue discrimination

Abstract

Devices and methods are disclosed for characterizing tissue samples using radiofrequency (RF) analysis. RF reflection or transmission spectra are analyzed to determine dielectric and conductivity properties that correlate with tissue type. In some embodiments, one or more probe tips contact the tissue simultaneously or sequentially at different locations on the tissue samples, enabling spatially resolved RF spectral measurements across the sample. The system may include a positioner for translating probe tips relative to the sample, a carrier for holding a biopsy stylet or tissue substrate, and an analyzer for classifying tissue as healthy, benign, or malignant. The approach enables rapid, non-destructive discrimination of tissue types for diagnostic, therapeutic, or research applications.

Description

P50554W001RADIO FREQUENCY SYSTEM AND METHOD FOR TISSUE DISCRIMINATION BACKGROUND

[0001] The ability to distinguish between diseased and healthy tissue types (e.g., distinguish malignant, benign, and normal tissues) is valuable for a variety of diagnostic, therapeutic, and research applications. Prior art tissue characterization generally relies on trained specialists performing visual inspection of specially prepared tissue samples using microscopic imaging. An accurate, fast, non-destructive automatic tissue discrimination technique could perform useful intermediate screening, directing specialists, doctors, and researchers to specific tissue locations of interest.

[0002] It is generally understood that various tissue types exhibit characteristic frequencydependent dielectric properties, and a variety of techniques have been attempted to discriminate diseased from healthy tissue based on dielectric contrast at particular frequencies. One such method has been patented by the present inventor, and is disclosed in U.S. Pat. No. 7,725,151, entitled “Apparatus and Method for Near-Field Imaging of Tissue.” In that patent, a bundle of flush coaxial probe tips is brought into contact with tissue, the probe tips are excited with a multiplicity of frequencies, a one-sided near-field reflection and / or transmission coefficient spectrum is obtained at each position, and the results are translated into an image.SUMMARY OF ILLUSTRATIVE EMBODIMENTS

[0003] In some described embodiments, a method and apparatus probe the dielectric and conductivity properties of a tissue sample. Measurements are taken with the tissue sample located between a ground surface and a probe tip, with both substantially contacting the tissue sample. The probe tip can take the form of, e.g., an exposed coaxial cable fitting, where the ground sheath (and dielectric interposer) does not extend to the end of the center conductor, such that the center conductor is exposed in an air gap (containing the tissue sample) between the end of the coaxial ground sheath and the ground surface. It is believedP50554W001 that situating the tissue sample in this air gap allows it to influence a resonance characteristic between the inductance and capacitance in the air gap. Electromagnetic energy at a range of frequencies appropriate for discrimination is driven to the probe tip, and a reflection coefficient as a function of frequency is obtained. A peak resonance reflection coefficient (or other metric based on the reflection coefficient characterization) is obtained, and then used to characterize the tissue type at the position of the probe tip. The probe tip may be brought into contact with the tissue sample at a plurality of positions and / or orientations to characterize the tissue across the sample in one or more directions. Alternately or in addition, a probe may comprise a plurality of probe tips that contact the sample at multiple locations, allowing for multiple measurements to be taken without repositioning the sample and probe.

[0004] In some embodiments, the ground surface can be a biopsy stylet, advantageously allowing measurements to be taken on a tissue sample soon after the sample is obtained, or at least prior to disturbing the tissue sample. In some embodiments, an air gap calibration is performed at a position on the ground surface where there is no tissue and / or a calibration dielectric material. In some embodiments, a probe tip is an easily replaceable, expendable part of the system. In some embodiments, the exposed length of the center conductor is selected for a particular range of expected resonant frequencies. In some embodiments, this length is also related to a thickness of the tissue sample, and / or a range of excitation frequencies is adjusted for a thickness of the tissue sample. In some embodiments, x-y locations of a plurality of measurements are recorded and registered to a visual image of the tissue sample.

[0005] The foregoing general description of the illustrative implementations and the following detailed description thereof are merely exemplary aspects of the teachings of this disclosure and are not restrictive.P50554W001BRIEF DESCRIPTION OF THE DRAWINGS

[0006] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate one or more embodiments and, together with the description, explain these embodiments. The accompanying drawings have not necessarily been drawn to scale. Any values or dimensions illustrated in the accompanying graphs and figures are for illustration purposes only and may or may not represent actual or preferred values or dimensions. Where applicable, some or all features may not be illustrated to assist in the description of underlying features. In the drawings:

[0007] FIG. 1 illustrates a sideview of a biopsy stylet useful for obtaining a tissue sample;

[0008] FIG. 2A and FIG. 2B illustrate, in front (2A) and rear (2B) perspective view, a configuration of a coaxial terminator useful in an embodiment;

[0009] FIG. 3 contains a block diagram illustrating the components of a system embodiment, in a position to take a tissue measurement;

[0010] FIG. 4 shows components of an embodiment having a plurality of probe tips, in a position to take a plurality of tissue measurements;

[0011] FIG. 5 illustrates lateral translation of a probe tip across an elongated sample;

[0012] FIG. 6 illustrates measurements taken on a sample at a variety of probe tip angles;

[0013] FIG. 7 illustrates an experimental setup measuring a single sample comprising both healthy and tumor tissue, and the reflection coefficient measurements taken at different positions along the sample;

[0014] FIG. 8 plots reflection coefficient measurements for three different cancer tissue samples;

[0015] FIG. 9 plots reflection coefficient measurements for three different healthy liver tissue samples;P50554W001

[0016] FIG. 10 plots reflection coefficient measurements for three different healthy kidney tissue samples; and

[0017] FIG. 11 plots reflection coefficient measurements for kidney, liver, and ct26 cancer tissue samples.DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0018] The description set forth below in connection with the appended drawings is intended to be a description of various, illustrative embodiments of the disclosed subject matter.Specific features and functionalities are described in connection with each illustrative embodiment; however, it will be apparent to those skilled in the art that the disclosed embodiments may be practiced without each of those specific features and functionalities.

[0019] FIG. 1 depicts an end portion 100 of a standard biopsy stylet / needle, consisting of an inner stylet 102 that translates in and out of a sheath 106. The inner stylet 102 contains a cutout 104 that a physician manipulates to the position of a desired tissue sample from a subject, which is extracted positioned in the cutout by moving the outer sheath 106 over the cutout 104. In some embodiments, a probe tissue-measurement system according to an embodiment is adapted to accept a stylet directly for measurement of a sample as obtained, with the stylet functioning as a ground surface. In other embodiments, a tissue sample may be moved to a different ground substrate prior to measurement, and / or a different method may be used to obtain a tissue sample.

[0020] FIG. 2A and FIG. 2B illustrate a coaxial terminator 200 useful in an embodiment. In one measurement configuration, coaxial terminator 200 is an FMCN1400 SMA female connector stub terminal two-hole flange, available from Fairview Microwave, Inc. of Lewisville, TX. This part is typically mounted to a circuit board, with a dielectric core 202 seated through a ground plane of a circuit board, and a center conductor 204 passing through a dielectric of the circuit board and soldered to a trace on the opposite side. A ground flangeP50554W001206 is attached to the circuit board, and a thread end protrudes, for attachment of a coaxial cable. In the configurations below, however, dielectric core 202 and center conductor 204 are used as a probe in an air gap.

[0021] Although in a first embodiment, the entire probe tip assembly (as a fixed part of a coaxial terminator 200) screws directly onto a coaxial cable, in a production embodiment a probe tip may comprise an end portion that is easily replaceable by push-fit, twist- fit, snap- fit, or some other quick-engagement mechanism. The replaceable probe tip may be disposable or may have the ability to be sterilized and reused. Probe tips may also be spring- loaded and / or have load or deflection sensors to detect when the probe tip has engaged a sample.

[0022] Probe tips may have a selectable tip point size, varying from 100s of microns down to fractions of a micron. In the FIG. 2 depiction, center conductor 204 has a blunt tip and a 250- micron diameter. With sharper point size, it is expected that spatial resolution will increase, but signal-to-noise ratio will decrease. A skilled practitioner should be expected to select a point size appropriate for a particular measurement regime.

[0023] Probe length affects resonance. In the FIG. 2 depiction, the exposed probe tip is 1.27 mm long, and the unshielded dielectric (with center conductor inside) length is 3.18 mm. Generally, a thicker sample will call for a longer probe. Otherwise, probe length can be selected to produce a desired resonance range appropriate for a particular tissue discrimination problem. In systems with replaceable probe tips, different lengths may be interchangeable in the same system.

[0024] FIG. 3 shows, in block diagram form, a probe tissue-measurement system 300.System 300 comprises a positioner 302, a vector network analyzer 304, an evaluation unit 306, and a carrier 308. Positioner 302 and / or carrier 308 are translatable with respect to each other, under control of evaluation unit 306, in a z-axis, x-axis and / or a y-axis. Positioner 302P50554W001 comprises a mount for a probe tip 200, and provides for connection of the probe tip 200 to a coaxial cable / transmission line 312, which connects at its opposite end to the vector network analyzer 304. The evaluation unit 306 comprises a programmable computer / controller that communicates with the positioner 302 (and / or carrier 308 if that part is positionable under computer control) and the vector network analyzer 304. Carrier 308 securely holds a stylet 100 or other sampling device, or in some embodiments the sample rests directly on carrier 308, which provides a ground surface. Optionally, a digital imager 320 also connects to evaluation unit 306. Digital image 320 can be used to gather images of the tissue sample, register the position of samples taken with the probe tip to a plan view of the sample, and / or aid in positioning probe tip 200.

[0025] In some embodiments, a new measurement sequence begins with a reference measurement. The reference measurement process can comprise moving the probe tip 200 to a position where it is over the ground surface at a position where there is no sample and bringing the probe tip in contact with the ground surface to create a short circuit. Optionally, a reference dielectric with a known characteristic can be interposed as the position of the reference measurement. The vector network analyzer may be swept over a range of frequencies of interest and a reference voltage reflection coefficient spectrum is obtained.

[0026] Next, a series of measurements is taken of a tissue sample 310. For each measurement, the probe tip is translated to overlay a desired position on the tissue sample 310. The probe tip is then lowered into a position where it is in contact with the sample. The probe tip may be lowered slowly, with the network analyzer running, until a shift from a free- air reflection coefficient is detected. Alternately, a load cell in the positioner can sense a certain pressure, or a deflection of a spring positioner on the probe tip can be used to stop movement. The vector network analyzer is then swept over a range of frequencies of interest and a voltage reflection coefficient spectrum is obtained. The probe tip is then lifted andP50554W001 moved to a new position, where the process is repeated. Reference images may be recorded with camera 320 at various timestamps during the measurement sequence. The process for classifying the tissue sample at each position will be described after the following explanation of a few alternate embodiments for taking physical samples.

[0027] FIG. 4 shows an alternate embodiment 400, having a positioner 402 that holds a plurality of probe tips, from a left probe tip 400a to a right probe tip 400e. The plurality of probe tips are brought into contact with the tissue sample 310. Each probe tip can connect through a respective transmission line to a vector network analyzer (not shown), or a switching network can selectively connect different probes to a vector network analyzer in sequence. This embodiment has the advantage of simultaneously or sequentially collecting voltage reflection coefficient spectra across multiple locations in the sample without needing to move a single probe and / or sample. In some embodiments, one such multi-probe measurement with an adequate density of probe tips along the sample provides sufficient data for diagnosis. In other embodiments, after measurements have been taken with the plurality of probe tips, the positioner 402 is raised and translated to a new measurement position, preferably stepping a smaller distance than the spacing between the probe tips.

[0028] FIG. 5 illustrates a process 500 for scanning across a biopsy sample left to right. The stylet 100 may cause a different capacitive response near its edges, for which an adjustment can be applied based on past characterizations of known homogeneous samples.

[0029] FIG. 6 illustrates a process for making multiple measurements at one sample location, based on tilting of the stylet 100 / tissue sample 310 or probe tip 200. For some tissue samples and / or for some tissue types, tilting may produce a different measurement that aids in discrimination. Like in the FIG. 5 example, an adjustment can be applied based on past characterizations of known samples.P50554W001

[0030] Due to the configuration of the measurement system, the exposed conductor of the probe tip creates an inductance, and a capacitor exists between the probe tip and the ground surface, with the tissue sample acting as a dielectric material of the capacitor. As different tissue types also exhibit different electrical conductivities, the configuration of probe tip / tissue / ground surface creates an RCL resonator, with a resonant frequency dependent on the dielectric constant of the tissue under the probe tip, and a Q factor of the resonance determined by the electrical conductivity of the tissue sample. Because healthy tissue tends to have the lowest dielectric constant and lowest conductivity, it tends to form a resonance with a sharpest, deepest, and highest-frequency peak for a given configuration. Benign tumor tissue tends to have a dielectric constant only slightly greater than healthy tissue, but a greater conductivity, and thus tends to form a resonance with a shallower peak at a slightly lower frequency. Malignant tumor tissue has the highest dielectric constant, and a much greater conductivity, and thus tends to form a resonance with a dramatically shallower peak and a greater shift to lower frequency. As a probe tip is stepped across a margin between healthy and malignant tissue, a transition from sharp, deep, high-frequency to shallower, broader, and lower frequency resonance should be observable.

[0031] FIG. 7 illustrates portions of a particular experimental system 700 and experimental result. A stylet 100 such as depicted in FIG. 1 provides a ground surface, and a probe tip 200 such as shown in FIGs. 2A / 2B is used for measurements. The probe tip 200 and stylet 100 are shown shorted together for creation of a reference measurement.

[0032] A tissue sample 310 is shown disposed on stylet 100. One end of tissue sample 310 contains tumor cells, and the other end contains healthy cells. The tissue sample is less than 1 mm thick.

[0033] In an experiment, reflection coefficient measurements are taken along tissue sample 310 by placing probe tip 200 in contact with tissue sample 310 at a series of locations alongP50554W001 its length. Probe tip 200 is driven by a signal from a Keysight 8720 Vector Network Analyzer, which is swept over a frequency range from 8 GHz to 20 GHz. At the location of healthy tissue, a sharp resonance is measured that peaks at about 16.4 GHz. At the location of malignant tissue, a much shallower resonance peaks at about 15.8 GHz. As shown in the inset graph, the spectra for tumor tissue is repeatable at different locations along the sample.

[0034] Evaluation unit 306 (FIG. 3) calculates, e.g., a metric, provides a binary tumor / healthy-benign classification, or provides a probability of malignancy based on the reflection coefficient spectra produced at each probe tip location. A reference spectrum produced at a short-circuit location may be used to normalize the data prior to computing a metric. Other signal processing, such as a low-pass filter, may precede peak detection. The metric could be a vector, with one component dependent on the depth of the peak resonance, and another component dependent on the frequency of the peak resonance or the distance of the peak resonance frequency from, e.g., an expected peak resonance frequency for healthy tissue. Training data may be used to train a classifier to produce a binary result or probability of malignancy for each position along the sample, from the vector data. Alternately, the spectra for a set of training data, or features derived therefrom, can be fed to an artificial intelligence system to train it to recognize tissue types from spectral response differences.

[0035] FIGs. 8-10 show a different set of experimental results, obtained with an 8 mm probe tip on thicker tissue samples (generally 4-8 mm thick). In this experiment, samples of ct26 tumor tissue, healthy liver tissue, and healthy kidney tissue were subjected to the same measurement process. Results are presented for three ct26 sample points (FIG. 8), three liver sample points (FIG. 9), three kidney sample points (FIG. 10), and one of each compared against each other (FIG. 11). Each tissue type shows good repeatability, with kidney tissue showing on average a peak of 8.08 dB at 3.09 GHz, liver tissue showing on average a peak of 9.42 db at 3.09 GHz, and ct26 showing on average a 16.29 dB peak at 3.1375 GHz.P50554W001

[0036] Reference throughout the specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment of the subject matter disclosed. Thus, the appearance of the phrases “in one embodiment” or “in an embodiment” in various places throughout the specification is not necessarily referring to the same embodiment. Further, the particular features, structures or characteristics may be combined in any suitable manner in one or more embodiments. Further, it is intended that embodiments of the disclosed subject matter cover modifications and variations thereof.

[0037] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context expressly dictates otherwise. That is, unless expressly specified otherwise, as used herein the words “a,” “an,” “the,” and the like carry the meaning of “one or more.” Additionally, it is to be understood that terms such as “left,” “right,” “top,” “bottom,” “front,” “rear,” “side,” “height,” “length,” “width,” “upper,” “lower,” “interior,” “exterior,” “inner,” “outer,” and the like that may be used herein merely describe points of reference and do not necessarily limit embodiments of the present disclosure to any particular orientation or configuration.Furthermore, terms such as “first,” “second,” “third,” etc., merely identify one of a number of portions, components, steps, operations, functions, and / or points of reference as disclosed herein, and likewise do not necessarily limit embodiments of the present disclosure to any particular configuration or orientation.

[0038] Furthermore, the terms “approximately,” “about,” “proximate,” “minor variation,” and similar terms generally refer to ranges that include the identified value within a margin of 20%, 10% or preferably 5% in certain embodiments, and any values therebetween.

[0039] All of the functionalities described in connection with one embodiment are intended to be applicable to the additional embodiments described below except where expresslyP50554W001 stated or where the feature or function is incompatible with the additional embodiments. For example, where a given feature or function is expressly described in connection with one embodiment but not expressly mentioned in connection with an alternative embodiment, it should be understood that the inventors intend that that feature or function may be deployed, utilized or implemented in connection with the alternative embodiment unless the feature or function is incompatible with the alternative embodiment.

[0040] Reference has been made to illustrations representing methods and systems according to implementations of this disclosure. Aspects thereof may be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general -purpose computer, special purpose computer, or other programmable data processing apparatus and / or distributed processing systems having processing circuitry, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions / operations specified in the illustrations.

[0041] One or more processors can be utilized to implement various functions and / or algorithms described herein. Additionally, any functions and / or algorithms described herein can be performed upon one or more virtual processors. The virtual processors, for example, may be part of one or more physical computing systems such as a computer farm or a cloud drive.

[0042] Aspects of the present disclosure may be implemented by software logic, including machine readable instructions or commands for execution via processing circuitry. The software logic may also be referred to, in some examples, as machine readable code, software code, or programming instructions. The software logic, in certain embodiments, may be coded in runtime-executable commands and / or compiled as a machine-executable program orP50554W001 file. The software logic may be programmed in and / or compiled into a variety of coding languages or formats.

[0043] Aspects of the present disclosure may be implemented by hardware logic (where hardware logic naturally also includes any necessary signal wiring, memory elements and such), with such hardware logic able to operate without active software involvement beyond initial system configuration and any subsequent system reconfigurations (e.g., for different object schema dimensions). The hardware logic may be synthesized on a reprogrammable computing chip such as a field programmable gate array (FPGA) or other reconfigurable logic device. In addition, the hardware logic may be hard coded onto a custom microchip, such as an application-specific integrated circuit (ASIC). In other embodiments, software, stored as instructions to a non-transitory computer-readable medium such as a memory device, on-chip integrated memory unit, or other non-transitory computer-readable storage, may be used to perform at least portions of the herein described functionality.

[0044] Various aspects of the embodiments disclosed herein are performed on one or more computing devices, such as a laptop computer, vector network analyzer, spectrum analyzer, function generator, tablet computer, mobile phone or other handheld computing device, or one or more servers. Such computing devices include processing circuitry embodied in one or more processors or logic chips, such as a central processing unit (CPU), graphics processing unit (GPU), field programmable gate array (FPGA), application-specific integrated circuit (ASIC), or programmable logic device (PLD). Further, the processing circuitry may be implemented as multiple processors cooperatively working in concert (e.g., in parallel) to perform the instructions of the inventive processes described above.

[0045] The process data and instructions used to perform various methods and algorithms derived herein may be stored in non-transitory (i.e., non-volatile) computer-readable medium or memory. The claimed advancements are not limited by the form of the computer-readableP50554W001 media on which the instructions of the inventive processes are stored. For example, the instructions may be stored on CDs, DVDs, in FLASH memory, RAM, ROM, PROM, EPROM, EEPROM, hard disk or any other information processing device with which the computing device communicates, such as a server or computer.

[0046] These computer program instructions can direct a computing device or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable medium produce an article of manufacture including instruction means which implement the function / operation specified in the illustrated process flows.

[0047] The computing device, in some embodiments, further includes a display controller for interfacing with a display, such as a built-in display or LCD monitor. A general purpose I / O interface of the computing device may interface with a keyboard, a hand-manipulated movement tracked I / O device (e.g., mouse, virtual reality glove, trackball joystick, etc.), and / or touch screen panel or touch pad on or separate from the display.

[0048] Moreover, the present disclosure is not limited to the specific circuit elements described herein, nor is the present disclosure limited to the specific sizing and classification of these elements. For example, the skilled artisan will appreciate that the circuitry described herein may be adapted based on changes in battery sizing and chemistry or based on the requirements of the intended back-up load to be powered.

[0049] The functions and features described herein may also be executed by various distributed components of a system. For example, one or more processors may execute these system functions, where the processors are distributed across multiple components communicating in a network. The distributed components may include one or more client and server machines, which may share processing, in addition to various human interface and communication devices (e.g., display monitors, smart phones, tablets, personal digitalP50554W001 assistants (PDAs)). The network may be a private network, such as a LAN or WAN, or may be a public network, such as the Internet. Input to the system, in some examples, may be received via direct user input and / or received remotely either in real-time or as a batch process.

[0050] Although provided for context, in other implementations, methods and logic flows described herein may be performed on modules or hardware not identical to those described. Accordingly, other implementations are within the scope that may be claimed.

[0051] While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the present disclosures. Indeed, the novel methods, apparatuses and systems described herein can be embodied in a variety of other forms; furthermore, various omissions, substitutions and changes in the form of the methods, apparatuses and systems described herein can be made without departing from the spirit of the present disclosures. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the present disclosures.

Claims

P50554W001CLAIMSWhat is claimed is:

1. A device for characterizing a tissue sample comprising: a sample holder configured to hold a tissue sample for analysis; a probe tip configured to contact the tissue sample for analysis, the probe tip being electrically connected to a transmission line; a radiofrequency signal source configured to drive the transmission line with a plurality of radiofrequency signals; a radiofrequency detector configured to measure a response of the tissue sample to each of the plurality of radiofrequency signals and provide an output of a corresponding plurality of responses of the tissue sample; and an analyzer configured to correlate the output of the corresponding plurality of responses of the tissue sample with a tissue characteristic.

2. The device of claim 1, wherein a vector network analyzer comprises the radiofrequency signal source and the radiofrequency detector.

3. The device of claim 2, further comprising a positioner, wherein the probe tip is mounted to the positioner and the positioner is configured to move the probe tip relative to the sample holder.

4. The device of claim 2, further comprising a carrier, wherein the carrier comprises the sample holder or the sample holder is mounted to the carrier, and wherein the carrier is configured to move the sample holder relative to the probe tip.

5. The device of claim 1, further comprising a plurality of probe tips configured to contact the tissue sample for analysis, each probe tip being electrically connected to a corresponding transmission line.P50554W0016. The device of claim 5, further comprising a splitter to split the plurality radiofrequency signals among the probe tips such that each of the probe tips receive the same radiofrequency signal among the plurality of radiofrequency signals at substantially the same time.

7. The device of claim 5, further comprising a device for sequentially applying the plurality of radiofrequency signals among the probe tips.

8. The device of claim 5, wherein a vector network analyzer comprises the radiofrequency signal source and the radiofrequency detector.

9. The device of claim 5, further comprising a positioner, wherein the plurality of probe tips are mounted to the positioner and the positioner is configured to move the probe tip relative to the sample holder.

10. The device of claim 5, further comprising a carrier, wherein the carrier comprises the sample holder or the sample holder is mounted to the carrier, and wherein the carrier is configured to move the sample holder relative to the plurality of probe tips.

11. A method for characterizing a tissue sample, comprising: placing a first side of a tissue sample on a ground surface; bringing a probe tip into contact with a second side of the tissue sample, the probe tip electrically connected to a transmission line; driving the transmission line with a plurality of radiofrequency signals while recording a tissue response at each of the frequencies of the plurality of radiofrequency signals; and based at least on one or more characteristics of the tissue response at each of the frequencies of the plurality of radiofrequency signals, performing a classification of a tissue type of the tissue sample.P50554W00112. The method of claim 11, further comprising bringing a plurality of probe tips into contact with a plurality of points on the tissue sample, wherein each of the plurality of probe tips is electrically connected to a corresponding transmission line.

13. The method of claim 11, wherein the step of bringing the probe tip into contact with a second side of the tissue sample comprises moving the probe tip relative to the tissue sample.

14. The method of claim 11, wherein the step of bringing the probe tip into contact with a second side of the tissue sample comprises moving the tissue sample relative to the probe tip.

15. The method of claim 12, further comprising driving each of the corresponding transmission lines with each of the plurality of radiofrequency signals simultaneously.

16. The method of claim 12, further comprising driving each of the corresponding transmission lines with each of the plurality of radiofrequency signals sequentially.

17. The method of claim 11, wherein the step of bringing a probe tip into contact with a second side of the tissue sample comprises bringing the probe tip into contact with a first location of the tissue sample, followed by executing the driving, recording, and performing steps for the first location, then bringing the probe tip into contact with a second location of the tissue sample and repeating the driving, recording, and performing steps for the second location.

18. The method of claim 17, wherein bringing the probe tip into contact with the first and second locations comprises moving the probe tip relative to the tissue sample.

19. The method of claim 17, wherein bringing the probe tip into contact with the first and second locations comprises moving the tissue sample relative to the probe tip.

20. The method of claim 12, wherein the step of bringing a plurality of probe tips into contact with a plurality of points on the tissue sample comprises bringing the plurality of probe tips into contact with a first plurality of locations of the tissue sample, followed by executing the driving, recording, and performing steps for the first plurality of locations, thenP50554W001 bringing the plurality of probe tips into contact with a second plurality of locations of the tissue sample, followed by executing the driving, recording, and performing steps for the second plurality of locations.

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