Attenuated total reflection (ATR) probe tips

Abstract

This document relates to various features of a physical probe tip, such as an ATR probe tip, used in an optical system, such as can employ an ATR probe. The probe tip can be used for touching to a location of target tissue (or other sample) for illuminating the location of target tissue and measuring an absorption or other response signal that can be acquired in response to illumination of the target tissue by the illumination signal. The response signal can include mid-infrared spectral components that can be measured and compared against a reference template or against a machine-learning statistical learning model that can be trained based on similar spectra.

Description

ATTENUATED TOTAL REFLECTION (ATR) PROBE TIPSCLAIM OF PRIORITY

[0001] This application claims priority to U.S. Provisional Application Serial No. 63 / 591,999, titled “ATTENUATED TOTAL REFLECTION (ATR) PROBE TIPS” to Douglas J. Cohen et al., filed October 20, 2023, which is incorporated by reference herein in its entirety.CROSS-REFERENCE TO RELATED PATENT DOCUMENTS AND INCORPORATION BY REFERENCE

[0002] This patent application is related to:1. U.S. Patent No. 11,678,802;2. U.S. Patent Application No. 17 / 658,489;3. U.S. Patent No. 11,540,722; and4. U.S. Patent No. 11,607,135; wherein each of these patent documents (1), (2), (3), and (4) is hereby incorporated herein by reference.FIELD OF THE DISCLOSURE

[0003] This document pertains generally, but not by way of limitation, to an optical system for tissue analysis and classification, and more particularly but not by way of limitation to an Attenuated Total Reflection (ATR) probe and ATR probe tip configurations.BACKGROUND

[0004] Infrared (IR) spectroscopy can be performed on a small amount of tissue and is sensitive to molecular-level biochemical changes. It is nondestructive, involving no labeling or staining. Many other techniques require the patient or resected tissues to be subjected to labeling by nanoparticles, drugs, antibiotics, fluorescent dyes, radioactivity, quantum dots, fixation, etc. IR spectroscopy has great potential to identify tumors and distinguishtumor types. IR spectroscopy results can help to provide objective information to the pathologist, dermatologist, and oncologist, informing histopathological judgments.

[0005] An attenuated total reflection (ATR) probe is a probe that uses an internally reflecting beam of light inside a crystal producing an evanescent wave at the crystal's reflecting surface. The evanescent wave penetrates a wavelength or so (~10 pm) into the region outside of the crystal, but it is still collected with the reflected light at the probe's detector. An ATR probe records an IR spectrum of whatever is touched by the probe tip, which in this case is tissue. There exist many commercial Fourier Transform IR Attenuated Total Reflection (FTIR-ATR) probes that are used with commercial FTIR spectrometers.SUMMARY OF THE DISCLOSURE

[0006] This disclosure relates to various features of a physical probe tip, such as an ATR probe tip, used in an optical system, such as can employ an ATR probe. The probe tip can be used for touching to a location of target tissue (or other sample) for illuminating the location of target tissue and measuring an absorption or other response signal that can be acquired in response to illumination of the target tissue by the illumination signal. The response signal can include mid-infrared spectral components that can be measured and compared against a reference template or against a machinelearning statistical learning model that can be trained based on similar spectra. Creating a configuration that can help increase or maximize the absorption of the illumination light into the target tissue, while maintaining power specifications through the system, can involve a balance of materials, physical shape, and light path. The probe tip can be employed either “ / / / vivo" or “ex vivo" with the tissue sample. Increasing or maximizing the absorption of the illumination light into the target tissue, increasing or maximizing the response signal, or doing both, can help provide a suitable Signal-To-Noise-Ratio (SNR) of the system that can help aid successful operation of the system.

[0007] In some aspects, this disclosure is directed to a probe tip configured for discriminating tissue of a specimen, the probe tip comprising: a crystal having a curvilinear outer surface configured for contacting a target tissue; an input optical pathway optically coupled with the crystal, wherein the input optical pathway is configured to receive a light signal from a light source; and an output optical pathway optically coupled with the crystal, wherein the output optical pathway is configured to receive, via the crystal, a response signal from the target tissue.

[0008] In some aspects, this disclosure is directed to a system including an infrared (IR) source and configured for discriminating tissue of a specimen, the system comprising a probe tip as described in this disclosure, wherein the probe is used to obtain a portion of an IR spectrum from the specimen in response to illuminations using a specified subset of IR wavelengths provided by the IR source over a first measurement time period; an IR detector, wherein the IR detector receives the portion of the IR spectrum from the probe; and a computing device comprising a processor and a memory in communication with the processor, the memory including computer-executable instructions, wherein the computing device receives a signal representative of a detected portion of the IR spectrum from the IR detector and the computer-executable instructions cause the processor to evaluate the obtained portion of IR spectrum using one or more metrics, wherein the one or more metrics discriminate normal tissue of the specimen from abnormal tissue of the specimen.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] In the drawings, which are not necessarily drawn to scale, like numerals may describe similar components in different views. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

[0010] FIG. l is a block diagram illustrating an example of portions of a system that can be used for spectroscopic analysis.

[0011] FIGS. 2A and 2B depict an example of portions of a hemispherical ATR probe tip arrangement.

[0012] FIGS. 3 A and 3B depict an example of portions of a half-disk ATR probe tip arrangement.

[0013] FIG. 4A depicts an example of portions of an arch-shaped ATR probe tip arrangement.

[0014] FIG. 4B depicts a conceptual example of a two-bounce ray trace using an arch-shaped ATR probe tip arrangement, such as in FIG. 4A.

[0015] FIGS. 5A and 5B depict portions of another example of an archshaped ATR probe tip arrangement.

[0016] FIGS. 6 A and 6B depict portions of another example of an archshaped ATR probe tip arrangement.

[0017] FIG. 7 depicts an example of portions of an ATR probe tip arrangement with a curvilinear outer surface that includes an ellipsoid.

[0018] FIG. 8 depicts portions of another example of an arch-shaped ATR probe tip arrangement.

[0019] FIG. 9 depicts portions of another example an arch-shaped ATR probe tip arrangement.

[0020] FIG. 10 depicts portions of an example of an ATR probe tip arrangement with an asymmetrically shaped crystal.

[0021] FIG. 11 depicts portions of another example an arch-shaped ATR probe tip arrangement.

[0022] FIG. 12 depicts portions of another example an arch-shaped ATR probe tip arrangement.

[0023] FIG. 13 depicts portions of another example an arch-shaped ATR probe tip arrangement.

[0024] FIG. 14 depicts portions of another example an ATR probe tip arrangement.

[0025] FIG. 15 depicts portions of another example an ATR probe tip arrangement.

[0026] FIG. 16 depicts portions of an example of an ATR probe tip arrangement without optical fibers.

[0027] FIG. 17 depicts portions of another example of an ATR probe tip arrangement without optical fibers.

[0028] FIG. 18 depicts an example of portions of a frustrum ATR probe tip crystal arrangement.

[0029] FIG. 19 depicts an example of using mirrors (e.g., instead of optical fibers) to incouple or outcouple light into or out of the ATR probe crystal.

[0030] FIG. 20 depicts an example of a configuration that does not require a crystal, but instead can use metal or other mirrors causing a bouncing of light that can lead to a wave created that can be absorbed by the tissue and therefore measured.

[0031] FIG. 21 depicts an example of portions of a flat crystal with grooves ATR probe tip crystal arrangement, such as which can also optionally include polished mirrors.

[0032] FIG. 22 depicts another example of portions of a flat crystal with grooves ATR probe tip crystal arrangement, such as which can also optionally include polished mirrors.

[0033] FIG. 23 depicts an example of portions of a truncated cone ATR probe tip crystal arrangement.

[0034] FIG. 24 depicts another example of portions of a truncated cone ATR probe tip crystal arrangement.

[0035] FIG. 25 depicts an example of portions of a truncated cone with an angled input ATR probe tip crystal arrangement.DETAILED DESCRIPTION

[0036] This document relates to various features of a physical probe tip, such as an ATR probe tip, used in an optical system, such as can employ an ATR probe. The probe tip can be used for touching to a location of target tissue (or other sample) for illuminating the location of target tissue and measuring an absorption or other response signal that can be acquired inresponse to illumination of the target tissue by the illumination signal. The response signal can include mid-infrared spectral components that can be measured and compared against a reference template or against a machinelearning statistical learning model that can be trained based on similar spectra. Creating a configuration that can help increase or maximize the absorption of the illumination light into the target tissue, while maintaining power specifications through the system, can involve a balance of materials, physical shape, and light path. The probe tip can be employed either “ / / / vivo" or “ex vivo" with the tissue sample. Increasing or maximizing the absorption of the illumination light into the target tissue, increasing or maximizing the response signal, or doing both, can help provide a suitable Signal-To-Noise-Ratio (SNR) of the system that can help aid successful operation of the system.

[0037] More details of examples of the proposed ATR probe crystal tip are described below. a. Tissue has a refractive index in the range of 1.39 - 1.57, such as with a typical value of 1.4 and air has a refractive index of 1.0. b. An approach to configuring an ATR crystal probe tip is to configure the ATR crystal probe tip to help make it “universal,” that is, to work with any target substance. Such a “universal” configuration of an ATR crystal probe tip, however, is not necessarily specially configured or optimized to work with biological tissue. In such a “universal” approach, the ATR crystal probe tip can be configured to work with air as the target object being measured. c. By contrast to a “universal” approach, the present approach can help provide an ATR crystal probe tip that can be configured specifically to work on tissue with its higher-than-air refractive index. The present approach can include, among other things, using an ATR crystal probe tip material that can include or consist of zinc selenide (ZnSe), zinc sulfide (ZnS), calcium fluoride (CaF2),or another high refractive index material.d. The various examples described herein can be configured to help to improve or optimize light bounces and evanescent waves that are created at the ATR crystal probe tip being touched to a target location of tissue. This can help obtain better absorption of the illuminating light into the target tissue, which, in turn, will help the resulting response be read optimally by the optical tissue classification system. e. Certain probe designs can include a fiber loop (e.g., single, double, or triple loops of an optical fiber), a crystal shape of a cylinder with a cone on top, a frustrum not optimized for tissue (e.g., different angles than what is beneficial for light bouncing when the tip is used for tissue). In certain approaches, a fiber loop can be made from silver halide. But silver halide degrades with exposure to visible light over time. This makes silver halide a poor material for a medical device to be used in a medical office, because the usable life of the material will be short while the cost of the material will be high. f. One or more optical fibers can be arranged or located, such as in relation to the crystal ATR probe tip of a particular configuration, such as to help create the best evanescent waves through the crystal, or to obtain the most bounces of light within the targeted tissue. This can help to create or optimize an opportunity for obtaining absorption spectra that can be effectively measured by the system employing a particular crystal ATR probe tip arrangement. g. A “ring mode” can also be provided for a given crystal ATR probe tip arrangement. The ring mode can be incorporated into a crystal ATR probe tip. The ring mode can be created when a fiber optic input and a fiber optic output are respectively mounted or otherwise located sufficiently close to an edge of the crystal of the ATR probe tip. The ring mode can be effective at bouncing the light around the outside edge of the crystal ATR probe tip and creating the evanescent waves suitable for absorption into the tissue sample. h. To explain the ring mode more fully, it can be noted that attenuated total reflectance (ATR) happens each time an internal reflection of thelight in a crystal occurs. This means that the light in the crystal does not transmit outside the crystal. Instead, the light in the crystal reflects from the surface of the crystal and back into the crystal itself. This creates an evanescent wave on the surface of the crystal. In a spherical crystal lens, this happens along the rounded edge of the crystal. If the light is introduced into the crystal at the appropriate angle, such as by a fiber optic input to the crystal, the light will make many iterative bounces in which the light skirts along the edge of the crystal lens. This is the ring mode, which causes attenuated total reflectance, and creates an evanescent wave along the entire outside of the spherical crystal lens.This can help make the entire outside of the crystal lens more sensitive to absorbance measurements being made in response to the illumination.

[0038] Examples of various configurations are listed below, and can include integrating or including multiple or all of the above aspects, such as to help achieve a maximum result.

[0039] FIG. l is a block diagram illustrating an example of portions of a system 100 that can be used for spectroscopic analysis. In some examples, the system 100 can include a Fourier Transform Infrared (FTIR) spectroscopy system that is configured to perform a spectroscopic analysis of a sample 102, e.g., specimen. In other examples, the system 100 is configured to classify or characterize a sample 102, e.g., target tissue, such as for cancer detection. In some examples, the sample 102 includes in vivo tissue, resected tissue, skin, and the like. In other examples, the sample 102 is not biological tissue.

[0040] The system 100 can include a light source 104, e.g., fixed or tunable, such as to illuminate the sample 102 with electromagnetic energy, such as for eliciting one or more of an absorption, scattering, reflection, fluorescence, Raman, or other response signal of interest from the sample 102. In an illustrative example, the light source 104 can include a laser system, e.g., fixed or tunable, such as which can include a single or multiple (e.g., two) Quantum Cascade Lasers (QCLs), such as can issue illuminationpulses at specified wavenumbers, such as to cover a range between 1340 and 1870 such as in 54 steps of 10 cm1for each of the two QCLs. In some examples, the QCL is a tunable mid-infrared laser with a reduced set of selected IR wavelengths that have been optimized for detecting the chemical and molecular signatures of tissue specific lesions to include, but not limited to, cancer, preneoplasia, intracellular accumulations (e.g. steatosis), inflammation, and wound healing.

[0041] The light source 104 can be coupled via an optical coupler 106 into Attenuated Total Reflection (ATR) probe tip 108, where the probe tip 108 includes an input optical fiber 110 and a crystal 112, and where the crystal 112 can be located against or near the sample 102. In an example, the optical coupler 106 can include an optocoupler, such as with a focal length of f=50 mm, such as with an SMA connector. Various examples of various ATR probe tips 108 are shown and described below. The light source 104 generates selected wavelengths of infrared (IR) light, such as mid-IR light, that are provided to the sample 102 via the probe tip 108 and the input optical fiber 110. The probe tip 108 is used to obtain an IR spectrum of the sample 102 in response to the provided IR wavelengths. In this manner, the probe tip 108 can perform IR spectroscopy on the sample 102 using the selected IR wavelengths.

[0042] The crystal 112 is configured to transmit IR light and has a refractive index greater than biological tissue, where the refractive index of biological tissue has a typical range of 1.33 to 1.5. For example, the crystal can have a refractive index of about 1.6 or greater. Examples of suitable crystals 112 include calcium fluoride (CaF2), zinc selenide (ZnSe), and zinc sulfide (ZnS). In some examples, a surface of the crystal 112 is polished.

[0043] The probe tip 108 further includes an output optical fiber 114 configured to receive a response signal from the sample 102, such as a target tissue or other specimen, via the crystal 112. Optical fibers are examples of optical pathways. Other examples include refractive or diffractive focusing optics as well as free space, among others.

[0044] The crystal of the probe tip 108 is distinguishable from an optical fiber. Crystals like zinc selenide (ZnSe), zinc sulfide (ZnS), and calcium fluoride (CaF?) have a rigid, highly ordered crystalline structure, where atoms are arranged in a repeating lattice. This structured arrangement gives them distinct optical and mechanical properties, such as specific refractive indices and hardness, making them ideal for precise optical components like lenses and prisms. In contrast, optical fibers are composed of a cylindrical core and cladding made from glass (silica) or plastic, with the core having a slightly higher refractive index than the cladding. This difference enables total internal reflection, allowing light to be guided along the fiber even through bends and twists, offering flexibility that crystals lack due to their brittle, rigid structure.

[0045] The response signal can be communicated from the sample 102 via the ATR probe tip 108 and the output optical fiber 114 to a photodetector 116 (also referred to as a “detector”) for being detected and transduced into an electrical response signal representative of the optical response signal from the probe tip 108. In this manner, the IR spectrum is passed from the probe tip 108 to the photodetector 116, e.g., an IR detector, via the output optical fiber 114.

[0046] The resulting electrical response signal, e.g., the signal representative of the detected IR spectrum, can be buffered or amplified and communicated from the photodetector 116 to a signal processor 118, such as for sampling, digitization, and storage into a memory buffer of the signal processor 118. In some examples, the signal processor 118 includes a digital oscilloscope. In an example, the digital oscilloscope can include a Picoscope 4224, which can provide a deep memory.

[0047] The buffered digital response samples can be communicated from the signal processor 118 to a computer 120, such as can include processor circuitry that can be configured to include or provide digital signal processing and memory circuitry 122. The digital signal processing (DSP) circuitry 122 can receive the buffered digital response samples from thesignal processor 118 and can process the digital response samples such as to perform signal processing and spectroscopic analysis on the sample 102, e.g., tissue or other specimen. The computer 120 evaluates the obtained IR spectrum using one or more metrics, where the one or more metrics discriminate normal tissue of the sample 102 from abnormal tissue of the sample 102, for example. The computer 120 can also be configured to include or provide a microcontroller 124, such as can be used to control the light source 104.

[0048] Additional information regarding techniques for discrimination of tissue, for example, using a probe can be found in U.S. Patent No.11,607,135 titled “Low noise response detection using optical probe” to Coe, Jr. et al., and in U.S. Patent No. 11,678,802 titled “System and method for the discrimination of tissues using a fast infrared cancer probe” to Coe et al., the entire contents of each being hereby incorporated by reference in their entirety.

[0049] FIGS. 2A and 2B depict an example of portions of a hemispherical ATR probe tip arrangement. The probe tip 200 is an example of the probe tip 108 of FIG. 1. FIG. 2A depicts a front view of the probe tip 200. FIG. 2B depicts a side view of the probe tip 200. The probe tip 200 includes a crystal 202 having a curvilinear outer surface 204 configured for contacting a sample, such as a target tissue. In FIG. 2A, the curvilinear outer surface 204 is included as an outer surface of a hemispherical shape.

[0050] Curvilinear refers to a convex surface that is smoothly curved, encompassing both symmetrical and asymmetrical shapes. This includes but is not limited to, configurations such as hemispheres, ellipsoids, arches, and other geometries in which the curvature is configured and specified to help optimize interaction with the sample, e.g., target tissue, by increasing or maximizing light absorption and response signal acquisition. In symmetrical examples of probe tip crystals, the curvilinearity can be defined in terms of a single radius of curvature. In examples such as the hemispherical shape ofFIG. 2 A, the radius of curvature R is constant and equal to the radius of the sphere (or half the diameter D).

[0051] In some examples, the diameter D is less than about 5 millimeters (mm). In some examples, the dimension Y is the radius R. In other examples, the dimension Y can be a function of D, e.g., more or less than ’ / 2D.

[0052] The probe tip 200 can further include an input optical fiber 206 optically coupled with the crystal 202 and configured to receive a light signal from a light source, such as a light signal from the light source 104 of FIG. 1. The probe tip 200 can also further include an output optical fiber 208 optically coupled with the crystal 202 and configured to receive, via the crystal 202, a response signal from the sample. The spacing between the input optical fiber 206 and the output optical fiber 208 (the fiber spacing) can be adjusted such as to optimize light through the crystal 202. Optical fibers are examples of optical pathways. Other examples include refractive, diffractive, or other focusing optics as well as free space, among others.

[0053] The crystal 202 includes at least one flat surface 210 to which the input optical fiber 206 and / or the output optical fiber 208 is optically coupled. In some examples, the input optical fiber 206 (and / or the output optical fiber 208) is optically coupled with the flat surface 210 of the crystal 202 via direct contact. In other examples, one or more intermediary optical components can be positioned between the end of the input optical fiber 206 (and / or the output optical fiber 208) and the flat surface 210 of the crystal 202, thereby ensuring optimal light transfer and interaction with the sample 102. For example, one or more focusing optics, such as a lens or diffractive optics, such as a grating, can be positioned between the distal end of an optical fiber and the crystal 202. One or more such intermediary optical components can be pre-positioned within a package, e.g., packaged into a ferrule or the like, such as to allow the package carrying the intermediary optical components to be secured to the crystal 202 and at least one of the input optical fiber 206 or the output optical fiber 208.

[0054] The configuration of FIGS. 2A and 2B gets away from a trapezoid or cone shape of an ATR crystal in favor of using a hemisphere that can employ a ring mode similar to that of a spherical crystal lens.

[0055] FIGS. 3 A and 3B depict an example of portions of a half-disk ATR probe tip arrangement. The probe tip 300 is an example of the probe tip 108 of FIG. 1. FIG. 3 A depicts a front view of the probe tip 300. FIG. 3B depicts a side view of the probe tip 300. The probe tip 300 includes a crystal 302 having a curvilinear outer surface 304 configured for contacting a sample, such as a target tissue. In FIG. 3 A, the curvilinear outer surface 304 includes a curved outer peripheral portion of a half-disk shape (or “semicircular disk”).

[0056] In some examples, the diameter D is less than about 5 millimeters (mm). In some examples, the dimension Y is the radius R. In other examples, the dimension Y can be a function of D, e.g., more or less than ’ / 2D.

[0057] The probe tip 300 further includes an input optical fiber 306 optically coupled with the crystal 302 and configured to receive a light signal from a light source, such as a light signal from the light source 104 of FIG. 1. The probe tip 300 also includes an output optical fiber 308 optically coupled with the crystal 302 and configured to receive, via the crystal 302, a response signal from the sample. The spacing between the optical fibers can be adjusted to optimize light through the crystal.

[0058] The crystal 302 includes at least one flat surface 310 to which the input optical fiber 306 and / or the output optical fiber 308 is optically coupled, such as at locations that are near an outer peripheral edge of the semi-circular periphery of the half-disk shape. In some examples, the input optical fiber 306 (and / or the output optical fiber 308) is optically coupled with the flat surface 310 of the crystal 302 via direct contact. In other examples, one or more intermediary optical components can be positioned between the end of the input optical fiber 306 (and / or the output optical fiber 308) and the flat surface 310 of the crystal 302, thereby ensuring optimallight transfer and interaction with the sample 102. For example, one or more focusing optics, such as a lens or diffractive optics, such as a grating, can be positioned between the distal end of an optical fiber and the crystal 302.

[0059] The half-disk configuration of FIGS. 3 A and 3B can have a thickness “t” that is greater than the diameter of the input and output optical fibers. This configuration can potentially be easy to use because of the directionality of the semi-circular peripheral surface. The semi-circular peripheral surface need not extend for a full 180 degrees, but can include a smaller or larger peripheral sweep. Stated differently, the disk need not be a perfect cut of a circular disk into two exactly equally sized semi-circular disks.

[0060] FIG. 4A depicts an example of portions of an arch-shaped ATR probe tip arrangement. The probe tip 400 is an example of the probe tip 108 of FIG. 1. The probe tip 400 includes a crystal 402 having a curvilinear outer surface 404 configured for contacting a sample, such as a target tissue. In FIG. 4A, the curvilinear outer surface 404 is included as a peripheral surface in an arch shape.

[0061] The arch shape is defined by two radii, namely outer radius R1 and inner radius R2. In some examples, R1 is 2.5 mm and R2 is 1.5 mm. In other examples, R1 is 2.0 mm and R2 is 1.0 mm. In yet other examples, R1 is 1.5 mm and R2 is 0.5 mm.

[0062] The probe tip 400 further includes an input optical fiber 406 optically coupled with the crystal 402 and configured to receive a light signal from a light source, such as a light signal from the light source 104 of FIG. 1. The probe tip 400 also includes an output optical fiber 408 optically coupled with the crystal 402 and configured to receive, via the crystal 402, a response signal from the sample. The spacing between the optical fibers can be adjusted to optimize light through the crystal. The crystal 402 includes one or more of a flat surface 410 and a flat surface 412 to which the input optical fiber 406 and / or the output optical fiber 408 is optically coupled.

[0063] This configuration can be advantageous in that it can mimic a fiber loop tip ATR probe, but can do so without the visible light degradation. The arch tip material can include or consist of zinc selenide, for example, which is a material that will hold up well in a medical office use environment. The arch shape configuration has advantages like those of the half disk configuration, but the arch configuration can also be helpful to get the reverse bounce of the light on the inside of the arch, such as to help increase potential absorbance.

[0064] FIG. 4B depicts a conceptual example of a two-bounce ray trace using an arch-shaped ATR probe tip arrangement, such as shown in FIG. 4A. In the example shown, a 5 mm radius arch is shown. Ray tracing simulates how light travels through different media, such as the crystal 402, or reflects off surfaces, such as the surfaces defined by the two radii R1 and R2 of FIG. 4A, so as to predict how they will behave in a given optical system. In the two-bounce ray trace of FIG. 4B, light rays reflect off the two surfaces of the arch-shaped crystal 402 before reaching the output optical fiber 408 of FIG. 4A. FIG. 4B depicts the ring mode. As the light gets closer to the left edge of the crystal, the number of bounces in response to the light increases. In addition, light is not lost by hitting the back of the arch.

[0065] FIGS. 5A and 5B depict portions of another example of an archshaped ATR probe tip arrangement. The probe tip 500 is an example of the probe tip 108 of FIG. 1 using the arch-shaped crystal 402 of FIG. 4 A. FIG. 5A depicts a front view of the probe tip 500. FIG. 5B depicts a side view of the probe tip 500.

[0066] The probe tip 500 includes a hemispherically shaped support 502 coupled with the arch-shaped crystal 402. The hemispherically shaped support 502 is preferably non-transmissive (e.g., opaque) to mid-infrared light, such as wavelengths ranging from approximately 3 to 8 micrometers (pm).

[0067] In a non-limiting example, a zinc selenide arched-shaped crystal 402 can be mounted on a fused silica hemispherical shape, which can helpprovide structural support to the crystal 402. In some examples, calcium fluoride can be used as the hemispherically shaped support 502, such as with a zinc selenide crystal 402.

[0068] It can be desirable for the index of refraction of the hemispherically shaped support 502 to be different, e.g., lower, than the index of refraction of the crystal 402, because light will then totally internally reflect on the back side of the crystal 402, which will help the bounces on the front side.

[0069] In some examples, the crystal 402 has a thickness of about 2 mm. The arch shape is defined by two radii, namely outer radius R1 and inner radius R2. In some examples, R1 is 4.0 mm and R2 is 3.0 mm. In other examples, R1 is 3.5 mm and R2 is 2.5 mm. In yet other examples, R1 is 3.0 mm and R2 is 2.0 mm. In yet other examples, R1 is 2.5 mm and R2 is 1.5 mm. In yet other examples, R1 is 2.0 mm and R2 is 1.0 mm.

[0070] FIGS. 6 A and 6B depict portions of another example of an archshaped ATR probe tip arrangement. The probe tip 600 is an example of the probe tip 108 of FIG. 1 using the arch-shaped crystal 402 of FIG. 4 A. FIG. 6A depicts a front view of the probe tip 600. FIG. 6B depicts a side view of the probe tip 600.

[0071] The probe tip 600 includes a cylindrically shaped support 602 coupled with the crystal 402. The cylindrically shaped support 602 is preferably non-transmissive (e.g., opaque) to mid-infrared light, such as wavelengths ranging from approximately 3 to 8 pm.

[0072] In a non-limiting example, a zinc selenide arched-shaped crystal 402 can be mounted on a fused silica cylindrically shaped support, which can help provide structural support to the crystal 402. In some examples, calcium fluoride can be used as the cylindrically shaped support 602, such as with a zinc selenide crystal 402.

[0073] It can be desirable for the index of refraction of the cylindrically shaped support 602 to be different, e.g., lower, than the index of refraction of the crystal 402, because light will then totally internally reflect on the back side of the crystal 402, which will help the bounces on the front side.

[0074] In some examples, the crystal 402 has a thickness of about 2 mm. The arch shape is defined by two radii, namely outer radius R1 and inner radius R2. In some examples, R1 is 4.0 mm and R2 is 3.0 mm. In other examples, R1 is 3.5 mm and R2 is 2.5 mm. In yet other examples, R1 is 3.0 mm and R2 is 2.0 mm. In yet other examples, R1 is 2.5 mm and R2 is 1.5 mm. In yet other examples, R1 is 2.0 mm and R2 is 1.0 mm.

[0075] FIG. 7 depicts an example of portions of an ATR probe tip arrangement with a curvilinear outer surface that is included as an outer surface of an ellipsoid. The probe tip 700 is an example of the probe tip 108 of FIG. 1. The probe tip 700 includes a crystal 702 having a curvilinear outer surface 704 configured for contacting a sample, such as a target tissue. In FIG. 7, the curvilinear outer surface 704 can be included as part of an ellipsoid shape, e.g., non-spherical.

[0076] The probe tip 700 further includes an input optical fiber 706 optically coupled with the crystal 702 and configured to receive a light signal from a light source, such as a light signal from the light source 104 of FIG. 1. The probe tip 700 also includes an output optical fiber 708 optically coupled with the crystal 702 and configured to receive, via the crystal 702, a response signal from the sample. The spacing between the optical fibers can be adjusted to optimize light through the crystal.

[0077] The crystal 702 includes at least one flat surface 710 to which the input optical fiber 706 and / or the output optical fiber 708 is optically coupled, such as at locations that are near an outer peripheral edge of the ellipsoid. In some examples, the input optical fiber 706 (and / or the output optical fiber 708) is optically coupled with the flat surface 710 of the crystal 702 via direct contact. In other examples, one or more intermediary optical components can be positioned between the end of the input optical fiber 706 (and / or the output optical fiber 708) and the flat surface 710 of the crystal 702, thereby ensuring optimal light transfer and interaction with the sample 102. For example, one or more focusing optics, such as a lens or diffractiveoptics, such as a grating, can be positioned between the distal end of an optical fiber and the crystal 702.

[0078] This configuration can create an opportunity for multiple bounce locations. In addition, this configuration can create an opportunity for unique ring mode generation.

[0079] FIG. 8 depicts portions of another example of an arch-shaped ATR probe tip arrangement. The probe tip 800 is an example of the probe tip 108 of FIG. 1, where the crystal 802 is an ellipsoidal arch. The crystal 802 has a curvilinear outer surface 804 configured for contacting a sample, such as a target tissue. The curvilinear outer surface 804 can be included as part of an ellipsoidal arch.

[0080] The probe tip 800 further includes an input optical fiber 806 optically coupled with the crystal 802 and configured to receive a light signal from a light source, such as a light signal from the light source 104 of FIG. 1. The probe tip 800 also includes an output optical fiber 808 optically coupled with the crystal 802 and configured to receive, via the crystal 802, a response signal from the sample. The spacing between the optical fibers can be adjusted to optimize light through the crystal. The crystal 802 includes one or more of a flat surface 810 and a flat surface 812 to which the input optical fiber 806 and / or the output optical fiber 808 is optically coupled.

[0081] This configuration can help create an opportunity to increase or maximize bounces of the light within the elliptical arch ATR probe tip 800.

[0082] FIG. 9 depicts portions of another example of an arch-shaped ATR probe tip arrangement. The probe tip 900 is an example of the probe tip 108 of FIG. 1. The probe tip 900 is similar to the probe tip 800 of FIG. 8, with the addition of a support 902 to which the ellipsoidal arch shaped crystal 802 is coupled.

[0083] The support 902 is preferably non-transmissive (e.g., opaque) to mid-infrared light, such as wavelengths ranging from approximately 3 to 8 pm. In a non-limiting example, a zinc selenide arched-shaped crystal support 902 can be mounted on a fused silica support 902, which can helpprovide structural support to the crystal 802. In some examples, calcium fluoride can be used as a support, such as with a zinc selenide crystal 802.

[0084] It can be desirable for the index of refraction of the support 902 to be different, e.g., lower, than the index of refraction of the crystal 802, because then light will totally internally reflect on the back side of the crystal 802, which will help the bounces on the front side.

[0085] To this point the probe tip designs described above have included symmetrically shaped crystals. In other configurations, the crystals can be asymmetrically shaped, such as shown in FIGS. 10-12, which are asymmetrical versions of the symmetrical probe tips shown in FIGS. 7-9, respectively.

[0086] FIG. 10 depicts portions of an example of an ATR probe tip arrangement with an asymmetrically shaped crystal. The probe tip 1000 is an example of the probe tip 108 of FIG. 1.

[0087] The probe tip 1000 further includes an input optical fiber 1006 optically coupled with the crystal 1002 and configured to receive a light signal from a light source, such as a light signal from the light source 104 of FIG. 1. The crystal 1002 has a curvilinear outer surface 1004 configured for contacting a sample, such as a target tissue. The curvilinear outer surface 1004 is included as an outer surface of an asymmetrical ellipsoid shape, such as an ellipsoid with a combined partial sphere or other asymmetrical shape. This configuration can be a three-dimensional (3D) arrangement, similar to a hemisphere but non-symmetrical.

[0088] The probe tip 1000 also includes an output optical fiber 1008 optically coupled with the crystal 1002 and configured to receive, via the crystal 1002, a response signal from the sample. The spacing between the optical fibers can be adjusted to optimize light through the crystal.

[0089] The crystal 1002 includes at least one flat surface 1010 to which the input optical fiber 1006 and / or the output optical fiber 1008 is optically coupled, such as at locations that are near an outer peripheral edge of the ellipsoid. In some examples, the input optical fiber 1006 (and / or the outputoptical fiber 1008) is optically coupled with the flat surface 1010 of the crystal 1002 via direct contact. In other examples, one or more intermediary optical components can be positioned between the end of the input optical fiber 1006 (and / or the output optical fiber 1008) and the flat surface 1010 of the crystal 1002, thereby ensuring optimal light transfer and interaction with the sample 102. For example, one or more focusing optics, such as a lens or diffractive optics, such as a grating, can be positioned between the distal end of an optical fiber and the crystal 1002.

[0090] This configuration can help create an opportunity to configure one or more bounce locations, such as to help improve or optimize use. This configuration offers some unique potential to maximize light bouncing around the crystal.

[0091] FIG. 11 depicts portions of another example an arch-shaped ATR probe tip arrangement. The probe tip 1100 is an example of the probe tip 108 of FIG. 1, where the curvilinear outer surface 1104 of the crystal 1102 is an outer peripheral portion of an asymmetrical ellipsoidal arch, such as an ellipsoidal arch with a combined partial sphere or other asymmetrical shape.

[0092] The probe tip 1100 further includes an input optical fiber 1106 optically coupled with the crystal 1102 and configured to receive a light signal from a light source, such as a light signal from the light source 104 of FIG. 1. The probe tip 1100 also includes an output optical fiber 1108 optically coupled with the crystal 1102 and configured to receive, via the crystal 1102, a response signal from the sample. The spacing between the optical fibers can be adjusted to optimize light through the crystal. The crystal 1102 includes one or more of a flat surface 1110 and a flat surface 1112 to which the input optical fiber 1106 and / or the output optical fiber 1108 is optically coupled.

[0093] FIG. 12 depicts portions of another example an arch-shaped ATR probe tip arrangement. The probe tip 1200 is an example of the probe tip 108 of FIG. 1. The probe tip 1200 is similar to the probe tip 1100 of FIG. 11,with the addition of a support 1202 to which the asymmetrical ellipsoidal arch shaped crystal 1102 is coupled.

[0094] The support 1202 is preferably non-transmissive to mid-infrared light, such as wavelengths ranging from approximately 3 to 8 pm. In a nonlimiting example, a zinc selenide arched-shaped crystal 1102 can be mounted on a fused silica support 1202, which can help provide structural support to the crystal 1102. In some examples, calcium fluoride can be used as a support, such as with a zinc selenide crystal 1102.

[0095] It can be desirable for the index of refraction of the support 1202 to be different, e.g., lower, than the index of refraction of the crystal 1102, because light will then totally internally reflect on the back side of the crystal 1102, which will help the bounces on the front side.

[0096] FIG. 13 depicts portions of another example an arch-shaped ATR probe tip arrangement. The probe tip 1300 is an example of the probe tip 108 of FIG. 1. The probe tip 1300 includes a crystal 1302 having a curvilinear outer surface 1304 configured for contacting a sample, such as a target tissue 1306. The curvilinear outer surface 1304 is included an outer peripheral surface of an arch-shape.

[0097] In this configuration, arch-shaped crystal 1302 includes a first leg 1308 and a second leg 1310, each with length L. The legs are straight portions of crystal that extend away from each end of the arch-shaped portion of the crystal 1302. Use of the two legs can move the discontinuity between the crystal 1302 and the input optical fiber 1312 and the output optical fiber 1314 by the length L of the first leg 1308 and the second leg 1310, respectively, thereby potentially helping to improve performance. The arch can optionally be accompanied by a shaped insert within the interior curvature of the arch, such as to help provide mechanical support.

[0098] FIG. 14 depicts portions of another example an ATR probe tip arrangement. Although the probe tip 1400 shown includes a crystal 1402 having an arch shaped curvilinear outer surface 1404, the techniques of FIG. 14 are applicable to all the shapes of crystals described in this disclosure.The probe tip 1400 includes a support 1412 coupled with the crystal 1402 for structural support.

[0099] The probe tip 1400 shown includes an input focusing optic 1406 positioned between the input optical pathway, namely the input optical fiber 1408, and the crystal 1402. Examples of focusing optics include lenses and diffractive optics, such as gratings. In the example shown, there is no focusing optic positioned between the crystal 1402 and the output optical pathway, namely the output optical fiber 1410.

[0100] In the example shown, the input focusing optic 1406 is positioned closer to the input optical fiber 1408 than to the crystal 1402, whereas the output optical fiber 1410 is in direct contact with the crystal 1402.

[0101] FIG. 15 depicts portions of another example an ATR probe tip arrangement. The probe tip 1500 of FIG. 15 is similar to the probe tip 1400 of FIG. 14, with the addition of an output focusing optic 1502 positioned between the output optical pathway, namely the output optical fiber 1410, and the crystal 1402. The probe tip 1500 includes a support 1412 coupled with the crystal 1402 for structural support.

[0102] In the example shown, the input focusing optic 1406 is positioned closer to the input optical fiber 1408 than to the crystal 1402. In contrast, the output focusing optic 1502 is positioned closer to the crystal 1402 than to the output optical fiber 1410.

[0103] A lens, for example, between the crystal and at least one of the input or output optical fibers can be used to help focus light from or to an optical fiber in an optimum way into or out of the crystal (of any shape-disk, arch, hemisphere, etc.) to help increase or maximize evanescent wave creation. Like the input lens, an output lens can also improve SNR, and can be added, or used in lieu of, the input lens.

[0104] In addition to or instead of an input lens, a liquid-crystal (LC) beamsteerer can be provided. The LC beamsteerer can include an electrode to receive an electrical control signal. The control signal applied to the electrode can be established or varied, such as to set or adjust a direction oflight output from the beamsteerer into the ATR probe tip crystal. Properly setting or adjusting an input direction of light into the ATR probe tip crystal can help increase a number of light bounces in the crystal. An increased number of light bounces in the crystal will correspond to an increase in absorption of light from the ATR probe tip crystal into the tissue sample.

[0105] Optionally, an amount of light absorption into the tissue sample can be measured using the ATR probe tip crystal, and such measured light absorption can be used as a feedback control signal for controlling the beamsteerer to adjust the direction of light output from the beamsteerer and into the ATR probe tip crystal. This can optionally be performed in a closed-loop fashion to increase or maximize the light bounces in the crystal, the light absorption from the crystal into the tissue sample, or both. Similar beamsteering can optionally be provided at the output of ATR probe crystal, in addition to or instead of using the output lens.

[0106] As mentioned above, optical fibers are examples of optical pathways. Other examples of optical pathways include focusing optics as well as free space, some of which are shown in FIGS. 16 and 17.

[0107] FIG. 16 depicts portions of an example of an ATR probe tip arrangement without optical fibers. The probe tip 1600 of FIG. 16 is similar to the probe tip 1500 of FIG. 15, but neither the input optical pathway nor the output optical pathway includes optical fibers. The probe tip 1600 includes an input focusing optic 1406 coupled between the input optical pathway 1602 and the crystal 1402, with no optical fiber in the input optical pathway 1602. There is no optical fiber positioned in the output optical pathway 1604. In the example shown, there is also no output focusing optic positioned between the crystal 1402 and the output optical pathway 1604. The probe tip 1600 includes a support 1412 coupled with the crystal 1402 for structural support.

[0108] For example, a lens between the crystal and at least one of the light source or light detector can be used to help focus light from or to the crystal (of any shape-disk, arch, hemisphere, etc.) to help increase or maximizeevanescent wave creation. Like the input lens, an output lens can also improve SNR, and can be added, or used in lieu of, the input lens.

[0109] FIG. 17 depicts portions of another example of an ATR probe tip arrangement without requiring optical fibers. The probe tip 1700 of FIG. 16 is similar to the probe tip 1600 of FIG. 16, where neither the input optical pathway nor the output optical pathway includes optical fibers. However, the probe tip 1700 includes focusing optics in both the input and output optical pathways. The probe tip 1700 includes an input focusing optic 1406 coupled between the input optical pathway 1602 and the crystal 1402, with no optical fiber in the input optical pathway 1602. In addition, the probe tip 1700 includes an output focusing optic 1502 positioned between the output optical pathway 1604 and the crystal 1402.

[0110] FIG. 18 depicts an example of portions of a frustrum ATR probe tip crystal arrangement. The probe tip 1800 includes a crystal 1802 shaped as a frustrum. The crystal 1802 includes a height X, a base Y, and a top Z with non-limiting example dimensions of 1.08 mm, 3.0 mm, and 1.49 mm, respectively.

[0111] This configuration is different from certain ATR crystal approaches in that the angle 0 can be optimized for tissue, for optical fiber placement, or both. In an example, using an angle 0 = 55 degrees is optimized for tissue.

[0112] FIG. 19 depicts an example of using mirrors (e.g., instead of optical fibers) to incouple or outcouple light into or out of the ATR probe crystal. The probe tip 1900 includes a crystal 1902 and an input optical fiber 1904 and an output optical fiber 1906. In some examples, the crystal 1902 can be a frustrum (or truncated cone). In some such examples, a base of the frustrum can be configured to be in contact with the sample. In other examples, a circular disk can be used instead of the frustrum.

[0113] The probe tip 1900 includes an input mirror 1908 to incouple light into the crystal 1902 from the input optical pathway, e.g., the input optical fiber 1904. Similarly, the probe tip 1900 includes an output mirror 1910 tooutcouple light from the crystal 1902 to the output optical pathway, e.g., the output optical fiber 1906.

[0114] FIG. 20 depicts an example of a configuration that does not require a crystal, but instead can use metal or other mirrors causing a bouncing of light that can lead to a wave created that can be absorbed by the tissue and therefore measured. The probe tip 2000 includes a reflective material 2002, such as metal or mirrors. The reflective material 2002 defines an internal cavity 2004, such as including air. In the non-limiting example shown, the internal cavity 2004 is a frustrum, but other shapes can be used.

[0115] A light signal is applied via an input optical pathway, such as an input optical fiber 2006, and reflects off of the reflective surfaces 2008 and into the tissue 2010. Response signals from the tissue 2010 are reflected off the reflective surfaces 2008 and into the output optical pathway, such as the output optical fiber 2012.

[0116] FIG. 21 depicts an example of portions of a flat crystal with grooves ATR probe tip crystal arrangement, such as which can also optionally include polished mirrors. The probe tip 2100 includes reflective material 2102, such as metal or mirrors. The reflective material 2102 defines an internal cavity 2104, such as including air. In the non-limiting example shown, the internal cavity 2104 is generally frustrum-shaped, but other shapes can be used.

[0117] A light signal is applied via an input optical pathway, such as an input optical fiber 2106, and reflects off of the reflective surfaces 2108 and into the tissue 2110. The reflective surfaces 2108 shown are a flat mirror. Response signals from the tissue 2110 are reflected off the reflective surfaces 2108 and into the output optical pathway, such as the output optical fiber 2112.

[0118] A circular disk 2114 or other crystal can include grooves on a first surface opposing a second surface that contacts the tissue 2110 to be analyzed. The grooves can help in receiving or providing light at an appropriate angle, such as to or from an optical fiber via one or more flat orcurved (e.g., ellipsoidal) polished mirrors (shown in FIG. 21). The grooves can help form an evanescent wave along the top surface that contacts the tissue sample to be analyzed. If the grooves were not present, if the light strikes the crystal at above the critical angle for total internal reflection, such incident light would just reflect away and never touch the tissue.

[0119] FIG. 22 depicts another example of portions of a flat crystal with grooves ATR probe tip crystal arrangement, such as which can also optionally include polished mirrors. The probe tip 2200 of FIG. 21 is similar to the probe tip 2100 of FIG. 21 except that the reflective material 2102 includes reflective surfaces 2202 that define an internal cavity 2204 having a generally ellipsoidal shape, such as using ellipsoidal mirrors.

[0120] FIG. 23 depicts an example of portions of a truncated cone ATR probe tip crystal arrangement. The probe tip 2300 includes a crystal 2302 positioned within an internal cavity 2304 defined by a reflective material 2306. The crystal 2302 is frustrum-shaped.

[0121] A light signal is applied via an input optical pathway, such as an input optical fiber 2308, and reflects off of the reflective surfaces 2310 and into the tissue 2312 via the crystal 2302. The reflective surface 2310 is a flat mirror. Response signals from the tissue 2312 are reflected off the reflective surfaces 2310, via the crystal 2302, and into the output optical pathway, such as the output optical fiber 2314.

[0122] Such an arrangement can be used to help bounce light angularly into the crystal, such that it creates a maximum evanescent wave that can be absorbed by the tissue. The light can be received from or provided to an optical fiber via one or more flat or curved (e.g., ellipsoidal) polished mirrors (shown in FIG. 24).

[0123] FIG. 24 depicts another example of portions of a truncated cone ATR probe tip crystal arrangement. The probe tip 2400 of FIG. 24 is similar to the probe tip 2300 of FIG. 23 except that the reflective material 2306 includes reflective surfaces 2402 that define an internal cavity 2404 having an ellipsoidal shape, such as using ellipsoidal mirrors.

[0124] FIG. 25 depicts an example of portions of a truncated cone with an angled input ATR probe tip crystal arrangement. The probe tip 2500 can employ a crystal 2502 having a cone or frustrum shape in contact with tissue 2504, and the input optical fiber 2506 and the output optical fiber 2508 can be angled with respect to the crystal 2502.

[0125] The crystal 2502 can be any geometric shape or asymmetrical shape, with the optical fibers coming in at an angle with respect to a planar interface between crystal and tissue. The probe tip 2500 includes a support 2510 to provide structural support to at least the crystal 2502.

[0126] For various ATR probe tip configurations described above with respect to FIGS. 2-25, to support the crystal configuration, the fiber optics sizing and location can be optimized, which is different from certain other approaches to ATR crystal probe tips. For example, fiber optimization location techniques can include empirically determining the best locations for an input optical fiber, an output optical fiber, or both.

[0127] In addition, various techniques can determine the best combination of input optical fiber and output optical fiber. One approach is to use equal or identical input and output optical fibers. Another approach can include using a larger diameter input optical fiber and a relatively smaller diameter output optical fiber. Another approach can include using a larger — even significantly larger — diameter output optical fiber and a relatively smaller- diameter input optical fiber.

[0128] Other probe tip arrangements can include a two-dimensional (2D) version of the 3D arrangements shown and described above, e.g., by using a “slice” of a corresponding 3D version. For example, a 2D frustum or 2D cavity may work about as well as the 3D ones. Flat mirrors can be easier to use than curved 3D ones to steer the diverging light from an optical fiber.

[0129] Further, photonic crystals, which are ordered arrays of holes or recesses in a material, can be used. The size and spacing of the holes determine the transmission range; the material composition matters much less.

[0130] Finally, the optical fiber can be removed, such that the illumination light output by a laser or other light sources can mesh perfectly to the crystal.Various Notes

[0131] Each of the non-limiting claims or examples described herein may stand on its own, or may be combined in various permutations or combinations with one or more of the other examples.

[0132] The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention may be practiced. These embodiments are also referred to herein as “examples.” Such examples may include elements in addition to those shown or described. However, the present inventors also contemplate examples in which only those elements shown or described are provided. Moreover, the present inventors also contemplate examples using any combination or permutation of those elements shown or described (or one or more claims thereof), either with respect to a particular example (or one or more claims thereof), or with respect to other examples (or one or more claims thereof) shown or described herein.

[0133] In the event of inconsistent usages between this document and any documents so incorporated by reference, the usage in this document controls.

[0134] In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In this document, the terms “including” and “in which” are used as the plain- English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that includes elements in addition to those listed after such a term ina claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

[0135] Method examples described herein may be machine or computer- implemented at least in part. Some examples may include a computer- readable medium or machine-readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods may include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code may include computer readable instructions for performing various methods. The code may form portions of computer program products. Further, in an example, the code may be tangibly stored on one or more volatile, non-transitory, or non-volatile tangible computer- readable media, such as during execution or at other times. Examples of these tangible computer-readable media may include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact discs and digital video discs), magnetic cassettes, memory cards or sticks, random access memories (RAMs), read only memories (ROMs), and the like.

[0136] The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more claims thereof) may be used in combination with each other. Other embodiments may be used, such as by one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to comply with 37 C.F.R. § 1.72(b), to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosedembodiment. Thus, the following claims are hereby incorporated into the Detailed Description as examples or embodiments, with each claim standing on its own as a separate embodiment, and it is contemplated that such embodiments may be combined with each other in various combinations or permutations. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

CLAIMSWhat is claimed is:

1. A probe tip configured for discriminating tissue of a specimen, the probe tip comprising: a crystal having a curvilinear outer surface configured for contacting a target tissue; an input optical pathway optically coupled with the crystal, wherein the input optical pathway is configured to receive a light signal from a light source; and an output optical pathway optically coupled with the crystal, wherein the output optical pathway is configured to receive, via the crystal, a response signal from the target tissue.

2. The probe tip configured of claim 1, wherein the input optical pathway includes an input optical fiber, and wherein the output optical pathway includes an output optical fiber.

3. The probe tip configured of claim 1, comprising at least one of: an input focusing optic positioned between the input optical pathway and the crystal; and an output focusing optic positioned between the output optical pathway and the crystal.

4. The probe tip configured of claim 1, wherein the crystal has a refractive index greater than biological tissue.

5. The probe tip configured of claim 4, wherein the crystal is configured to transmit infrared light.

6. The probe tip configured of claim 1, wherein the crystal includes at least one flat surface to which the input optical pathway is optically coupled.

7. The probe tip configured of claim 1, wherein the curvilinear outer surface is included as a outer surface of a hemispherical shape.

8. The probe tip configured of claim 1, wherein the curvilinear outer surface includes a curved outer peripheral portion of a half-disk shape.

9. The probe tip configured of claim 1, wherein the curvilinear outer surface is included as a peripheral surface in an arch shape.

10. The probe tip configured of claim 9, wherein the crystal is coupled with a hemispherically shaped support.

11. The probe tip configured of claim 9, wherein the crystal is coupled with a cylindrically shaped support.

12. The probe tip configured of claim 1, wherein the curvilinear outer surface is included as an outer surface of an ellipsoid.

13. The probe tip configured of claim 1, wherein the curvilinear outer surface is included as part of an ellipsoidal arch.

14. The probe tip configured of claim 13, wherein the crystal is coupled with a support.

15. The probe tip configured of claim 1, wherein the curvilinear outer surface is included as an outer surface of an asymmetrical ellipsoid.

16. The probe tip configured of claim 1, wherein the curvilinear outer surface included as outer peripheral portion of an asymmetrical ellipsoidal arch.

17. The probe tip configured of claim 16, wherein the crystal is coupled with a support.

18. A system including an infrared (IR) source and configured for discriminating tissue of a specimen, the system comprising:a probe tip as recited in any of claims 1-17, wherein the probe tip is used to obtain a portion of an IR spectrum from the specimen in response to illuminations using a specified subset of IR wavelengths provided by the IR source over a first measurement time period; an IR detector, wherein the IR detector receives the portion of the IR spectrum from the probe; and a computing device comprising a processor and a memory in communication with the processor, the memory including computerexecutable instructions, wherein the computing device receives a signal representative of a detected portion of the IR spectrum from the IR detector and the computer-executable instructions cause the processor to evaluate the obtained portion of IR spectrum using one or more metrics, wherein the one or more metrics discriminate normal tissue of the specimen from abnormal tissue of the specimen.

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