Spectrometers for interferometry applications

Abstract

Spectrometers, associated instruments, and associated methods are generally provided. Some spectrometers described herein are particularly suitable for use in detecting light supplied thereto by a probe via a cable. Some instruments described herein comprise a spectrometer described herein. Some methods described herein are performed in a spectrometer and / or instrument described herein.

Description

[0001] SPECTROMETERS FOR INTERFEROMETRY APPLICATIONS

[0002] RELATED APPLICATIONS

[0003] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 63 / 703,440, filed October 4, 2024, and entitled “Spectrometers for Interferometry Applications,” and to U.S. Provisional Application No. 63 / 805,814, filed May 14, 2025, and entitled “Spectrometers for Interferometry Applications,” each of which is incorporated herein by reference in its entirety for all purposes.

[0004] FIELD

[0005] Spectrometers for interferometry applications, associated instruments, and associated methods, are generally described.

[0006] BACKGROUND

[0007] Spectrometers may be employed to detect light generated during optical measurements. However, some spectrometers may collect too little light to allow for optical signals to be detected rapidly and / or may be unduly sensitive to thermal fluctuations and / or misalignment of one or more components therein.

[0008] Accordingly, new spectrometers, associated instruments, and methods of use thereof would be beneficial.

[0009] SUMMARY

[0010] The present disclosure generally describes spectrometers, associated instruments, and methods. The subject matter described herein involves, in some cases, interrelated products, alternative solutions to a particular problem, and / or a plurality of different uses of one or more systems and / or articles.

[0011] Paragraph 1: In some embodiments, a spectrometer is provided. The spectrometer comprises a transmissive collimator positioned to collimate light supplied by a probe via a cable, a diffraction grating positioned to disperse light collimated by the transmissive collimator, and an optical detector. The cable comprises a fiber bundle comprising a plurality of fibers. At least one of the fibers in the plurality of fibers is in optical communication with an optical fiber present in the probe. The light supplied by the probe comprises light reflected from an interface internal to the probe and light reflected from the end of the probe.

[0012] 1

[0013] #14429996vl Paragraph 2: In some embodiments, a method is provided. The method comprises transmitting light supplied by a probe through a cable, collimating the light by transmitting the light through a transmissive collimator, dispersing the light by reflecting it from a diffraction grating, and detecting the light with an optical detector. The cable comprises a fiber bundle comprising a plurality of fibers. At least one of the fibers in the plurality of fibers is in optical communication with an optical fiber present in the probe. The light transmitted through the probe comprises light reflected from an interface internal to the probe and light reflected from the end of the probe.

[0014] Paragraph 3: In some embodiments, an instrument is provided. The instrument comprises a light source configured to emit light, a cable configured to transmit the emitted light, and a spectrometer. The cable comprises a fiber bundle comprising a plurality of fibers. At least one of the fibers in the plurality of fibers is configured to be in optical communication with an optical fiber present in a probe. The spectrometer comprises a transmissive collimator configured to collimate the light supplied by the probe via the cable, a diffraction grating positioned to disperse light collimated by the lens / collimator, and an optical detector. The light comprises light reflected from an interface internal to the probe and light reflected from the end of the probe.

[0015] Paragraph 4: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the diffraction grating is reflective.

[0016] Paragraph 5: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the light comprises light having a variety of wavelengths.

[0017] Paragraph 6: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the optical detector is a multi-channel optical detector.

[0018] Paragraph 7: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the fiber bundle is a furcated fiber bundle.

[0019] Paragraph 8: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the fiber bundle is a fiber-optic bundle.

[0020] Paragraph 9: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the fibers in the fiber bundle are multimode fibers.

[0021] Paragraph 10: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the fibers in the fiber bundle allow for multiplexing and / or for the performance of measurements from multiple light sources.

[0022] Paragraph 11: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the probe is an optical probe.

[0023] 2

[0024] #14429996vl Paragraph 12: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises a lens.

[0025] Paragraph 13: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises two or more lenses.

[0026] Paragraph 14: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises a lens having an adjustable focal length.

[0027] Paragraph 15: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises a lens having a fixed focal length.

[0028] Paragraph 16: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises an adjustable liquid lens.

[0029] Paragraph 17: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises an adjustable focusing lens.

[0030] Paragraph 18: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises a liquid crystal lens.

[0031] Paragraph 19: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises a zoom lens.

[0032] Paragraph 20: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises a tunable acoustic gradient lens.

[0033] Paragraph 21: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, at least a portion of the light supplied by the probe is transmitted through the transmissive collimator.

[0034] Paragraph 22: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator comprises at least one cylindrically shaped lens.

[0035] Paragraph 23: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the transmissive collimator, diffraction grating, and / or optical detector are mounted on the same substrate.

[0036] Paragraph 24: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the substrate comprises glass, fused quartz, and / or a ceramic.

[0037] Paragraph 25: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the substrate has a thickness of greater than or equal to 1 mm and less than or equal to 15 mm.

[0038] 3

[0039] #14429996vl Paragraph 26: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, a thermally insulating material is disposed on and / or adjacent to at least one wall of an enclosure of the spectrometer.

[0040] Paragraph 27: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, a thermally insulating material is disposed on and / or adjacent to two or more walls of an enclosure of the spectrometer.

[0041] Paragraph 28: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the spectrometer is positioned in a bank of spectrometers comprising two or more adjacent spectrometers and / or the instrument comprises a bank of spectrometers comprising two or more spectrometers.

[0042] Paragraph 29: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, an insulating material is disposed on and / or adjacent to at least one side of the bank of spectrometers.

[0043] Paragraph 30: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the instrument further comprises a heating element disposed on and / or adjacent to at least one wall of an enclosure of the spectrometer and / or at least one side of the bank of spectrometers.

[0044] Paragraph 31: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the instrument further comprises a temperature sensor configured to measure the temperature within the spectrometer and / or within one or more spectrometers in the bank of spectrometers.

[0045] Paragraph 32: In some embodiments, in a spectrometer, method or instrument of any preceding Paragraph, the thermally insulating material comprises silicone foam.

[0046] Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and / or inconsistent disclosure, the present specification shall control. If two or more documents incorporated by reference include conflicting and / or inconsistent disclosure with respect to each other, then the document having the later effective date shall control.

[0047] BRIEF DESCRIPTION OF THE DRAWINGS

[0048] 4

[0049] #14429996vl Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures:

[0050] FIG. 1 shows one non-limiting example of a spectrometer, in accordance with some embodiments;

[0051] FIG. 2 shows a ray diagram for the spectrometer shown in FIG. 1, in accordance with some embodiments;

[0052] FIG. 3 shows one non-limiting example of an instrument comprising a spectrometer, in accordance with some embodiments;

[0053] FIG. 4 shows an exemplary method, in accordance with some embodiments;

[0054] FIG. 5 shows one non-limiting example of a plurality of fibers in a cable taking the form of a fiber-optic bundle and the associated bundle x- and y-axes, in accordance with some embodiments;

[0055] FIG. 6 shows an exemplary transmissive collimator and its x- and y-axes, in accordance with some embodiments;

[0056] FIGs. 7 and 8 show non-limiting examples of probes, in accordance with some embodiments;

[0057] FIG. 9 depicts schematically one example of a process by which light comprising both an amount of the light that has been reflected from an interface internal to a probe and an amount of light that has been reflected from the end of a probe can be generated, in accordance with some embodiments;

[0058] FIG. 10A shows a non-limiting example of a spectrometer with a thermally insulating material disposed on walls of an enclosure thereof, in accordance with some embodiments;

[0059] FIG. 10B shows a non-limiting example of a bank of spectrometers with a thermally insulating material disposed on sides thereof, in accordance with some embodiments;

[0060] FIG. IOC shows a non-limiting example of a spectrometer with a thermally insulating material disposed on walls of an enclosure thereof, a heating element disposed on a wall thereof, and a temperature sensor, in accordance with some embodiments;

[0061] 5

[0062] #14429996vl FIG. 10D shows a non-limiting example of a bank of spectrometers with a thermally insulating material disposed on sides thereof, a heating element disposed on a side thereof, and a temperature sensor, in accordance with some embodiments;

[0063] FIGs. 11 and 12 show changes in the beam diameter with defocus at two different wavelengths (575 nm and 775 nm, respectively) for fiber bundles including fibers having centers positioned up to ± 200 microns away from the intersection of the bundle x- and y- axes, in accordance with some embodiments;

[0064] FIG. 13 depicts thermal expansion coefficients of glass, aluminum, copper, and stainless steel, in accordance with some embodiments;

[0065] FIGs. 14 and 15 show wavelength shifts in measured interference patterns as a function of time, in accordance with some embodiments;

[0066] FIG. 16 depicts an exemplary arrangement of three fibers in a cable comprising three fibers, in accordance with some embodiments;

[0067] FIG. 17 depicts an exemplary arrangement of four fibers in a cable comprising four fibers, in accordance with some embodiments;

[0068] FIG. 18 shows the optical pathway of light into and through a spectrometer, in accordance with some embodiments.

[0069] FIG. 19A shows wavelengths shifts in interference patterns measured as a function of time in uninsulated spectrometers, in accordance with some embodiments;

[0070] FIG. 19B shows wavelength shifts in interference patterns measured as a function of time in insulated spectrometers, in accordance with some embodiments;

[0071] FIG. 20 depicts an exemplary arrangement of components of a spectrometer comprising an enclosure, a thermally insulating material disposed on one or more walls of the enclosure, a heating element disposed on one wall of the enclosure, and a temperature sensor, in accordance with some embodiments;

[0072] FIGs. 21 A and 2 IB depict an exemplary arrangement of a bank of spectrometers with a thermally insulating material disposed on multiple sides thereof, in accordance with some embodiments; and

[0073] FIGs. 22A-22C depict an exemplary instrument comprising a temperature control system comprising fans, metal enclosures allowing for isolated thermal conduction, and heat- isolated mountings, and a bank of spectrometers comprising a thermally insulating material disposed on multiple sides thereof, in accordance with some embodiments.

[0074] DETAILED DESCRIPTION

[0075] 6

[0076] #14429996vl Spectrometers, associated instruments, and associated methods are generally provided. Some spectrometers described herein are particularly suitable for use in detecting light supplied thereto by a probe via a cable. Some instruments described herein comprise a spectrometer described herein. Some methods described herein are performed in a spectrometer and / or instrument described herein.

[0077] In some embodiments, a spectrometer has one or more features that enhance the collection of light from a cable. Advantageously, this may allow for measurements to be performed in instances where less light is supplied by a probe to the cable and / or for measurements to be performed in a relatively rapid manner. One non-limiting example of such a feature is a transmissive collimator positioned to collimate light supplied by a cable and / or transmit light supplied by a cable to a diffraction grating with a relatively high efficiency. Desirably, the transmissive collimator may be positioned relatively close to the location at which the probe (or a component in optical communication with a probe, such as a cable) supplies light to the spectrometer, reducing the lateral distance over which the light will spread (i.e., the beam diameter) for any particular beam divergence, thereby reducing light that is lost and not collected due to such beam divergence.

[0078] In some embodiments, a spectrometer has one or more features that enhance thermal stability. Advantageously, this may reduce instability associated with thermal fluctuations and / or may enhance the precision of measurements performed using the spectrometer. In some embodiments, enhanced thermal stability may assist with maintaining a stable spectral baseline and / or enhance spectral stability during thermal fluctuations. It is also possible for enhanced thermal stability to allow for the use of a spectrometer described herein under varying laboratory and / or field conditions.

[0079] One non-limiting example of such a feature is the mounting of one or more of the components of the spectrometer (e.g., all components thereof) on substrates having relatively low thermal expansion coefficients. Such substrates may exhibit little change in dimension upon being exposed to thermal fluctuations.

[0080] Another non-limiting example of such a feature is the inclusion of a transmissive collimator taking the form of a lens having an adjustable focal length. In such embodiments, the focal length of a lens may be adjusted. It should also be noted that lenses having adjustable focal lengths may also desirably be suitable for compensating for misalignments (e.g., due to tilt of one or more components, such as an optical detector) and / or beam broadening unrelated to thermal fluctuations. For instance, lenses having adjustable focal lengths may, in some instances, be able to compensate for misalignment of one or more

[0081] 7

[0082] #14429996vl components of a probe or a cable in optical communication with a probe (e.g., one or more fibers therein for probes and / or cables comprising such fibers) and / or for the inherent beam broadening that occurs in fiber bundles comprising multiple fibers having centers spatially separated in one or more directions. The use of lenses may also be desirable because lenses may cause less stray light to be generated than would be if reflective elements, such as mirrors, were employed instead to collimate light.

[0083] In some embodiments, a spectrometer has one or more features that enhance the evenness of light collection across various channels (e.g., for various wavelengths and / or for various spectrometers in an instrument). Advantageously, this may allow for the measurement of light intensity as a function of wavelength to be measured with more precision and / or reproducibility. One example of such a feature is a transmissive collimator taking the form of a lens having an adjustable focal length as described above. When such a lens is present, the focal length of the lens may be adjusted to compensate for chromatic aberrations, thereby enhancing the evenness of light collection.

[0084] In some embodiments, a spectrometer has relatively few components and / or relatively few optical components (e.g., the optical components therein may consist of a transmissive collimator, a diffraction grating, and an optical detector). Advantageously, such spectrometers may occupy a reduced footprint (which may be desirable for use in instruments for which compactness is desirable and / or when it is desirable for multiple spectrometers to be positioned in a single instrument), may be relatively facile to manufacture, and / or may exhibit reduced cost in comparison to spectrometers comprising more components and / or more optical components.

[0085] In some embodiments, a spectrometer provides a desirably high frame readout (e.g., about 10 times higher than some other spectrometers). High frame readouts may be beneficial because they may allow for collection of a sufficient amount of light to obtain a good quality interferogram in less time. High frame readouts may be further facilitated by the use of bright light sources, such as LEDs.

[0086] FIG. 1 shows one non-limiting example of a spectrometer, and FIG. 2 shows a ray diagram for this spectrometer. In FIG. 1, the spectrometer 100 comprises a transmissive collimator 102, a diffraction grating 104, and an optical detector 106. Also shown in FIG. 1 is a cable 108 that is in optical communication with a probe (not shown). The cable can receive light from the probe and / or transmit light supplied by the probe (e.g., to the optical detector).

[0087] 8

[0088] #14429996vl As can be seen in FIG. 2, in the spectrometer shown in FIGs. 1 and 2, the light 210 supplied by the cable undergoes beam divergence prior to impinging on the transmissive collimator. The transmissive collimator is positioned to collimate this light, as can be seen from the collimated light 212 that exits the transmissive collimator in FIG. 2.

[0089] As can also be seen in FIG. 2, in the spectrometer shown in FIGs. 1 and 2, the collimated light 212 that exits the transmissive collimator is transmitted such that it impinges on the diffraction grating. The diffraction grating is positioned to disperse this light, as can be seen from the dispersed light 214 that reflects from the diffraction grating in FIG. 2. It should be noted that spectrometers described herein may comprise a reflective diffraction grating, like the diffraction grating shown in FIG. 2, and / or may comprise a transmissive diffraction grating (not shown). Similarly, in some embodiments, a spectrometer described herein comprises a spherical diffraction grating, like the diffraction grating shown in FIG. 2, and in some embodiments, a spectrometer described herein comprises a flat diffraction grating (e.g., a flat, reflective diffraction grating).

[0090] Finally, in the spectrometer shown in FIGs. 1 and 2, the light 214 dispersed by the diffraction grating impinges on the optical detector, allowing for detection thereof. Because the diffraction grating disperses the light, light of different wavelengths dispersed by the diffraction grating impinges on the optical detector at different locations. This allows the intensity of different wavelengths of light to be measured facilely by the optical detector. Therefore, and without wishing to be bound by any particular theory, spectrometers having the design shown in FIGs. 1 and 2 may be particularly suitable for applications in which it is desirable to detect the variation of light intensity with wavelength, such as interferometry applications.

[0091] It should be understood that, although FIG. 2 depicts collimation by the transmissive collimator of all of the light supplied by the cable, dispersion by the diffraction grating of all of the collimated light, and impingement on the optical detector of all of the dispersed light, it is also possible for some of the light not to undergo one or more of these processes. For instance, in some embodiments, some light supplied by the cable does not impinge on the transmissive collimator, some of the light transmitted through the transmissive collimator remains uncollimated, some of the light transmitted through the transmissive collimator (collimated or not) does not impinge on the diffraction grating, some of the light impinging on the diffraction grating is not dispersed, and / or some of the light dispersed by the diffraction grating does not impinge on the optical detector. In such embodiments, at least a portion of the light may impinge on the transmissive collimator, at least a portion of the light 9

[0092] #14429996vl transmitted through the transmissive collimator may become collimated, at least a portion of the light transmitted through the transmissive collimator (collimated or not) may impinge on the diffraction grating, at least a portion of the light impinging on the diffraction grating may be dispersed, and / or at least a portion of the light dispersed by the diffraction may impinge on the optical detector.

[0093] In some embodiments, an instrument comprising a spectrometer is provided. In such embodiments, the spectrometer may have one or more features shown in FIGs. 1 and 2. FIG. 3 shows one non-limiting example of such an instrument. The instrument 316 shown in FIG. 3 comprises a spectrometer 300, a cable 308, and a light source 318. The light source may be configured to emit light. For instance, the light source may be configured to emit light that is ultimately transmitted to the cable (e.g., via a second, different cable or by the same optical cable, to and through a probe, and then to the cable). Such light may, prior to being transmitted to the cable and / or after being transmitted to a probe, be reflected from an interface internal to the probe and / or be reflected from the end of the probe.

[0094] FIG. 4 shows one exemplary method 420 comprising the steps 422-430. Such steps may be performed in a spectrometer, such as a spectrometer having one or more features in common with the spectrometer shown in FIGs. 1 and 2, and / or an instrument, such as an instrument having one or more features in common with the instrument shown in FIG. 3. The first, optional step 422 of the method 420 comprises transmitting light through a probe. The light may comprise light reflected from an interface internal to the probe and light reflected from the end of the probe. The step 424 comprises transmitting the light through a cable. In other words, the probe may supply light to a cable that is then transmitted through the cable. The cable may transmit the light from the probe to a spectrometer. The step 426 of the method 420 comprises collimating the light. The light may be collimated by transmitting it through a transmissive collimator, such as the transmissive collimator shown in FIGs. 1 and 2. The step 428 of the method 420 comprises dispersing the light. This may be accomplished by reflecting it from (or transmitting it through) a diffraction grating, such as the diffraction grating shown in FIGs. 1 and 2. Finally, the step 430 of the method 420 comprises detecting the light. This may be accomplished with an optical detector, such as the optical detector shown in FIGs. 1 and 2.

[0095] In some embodiments, a method described herein may be performed as part of an assay. For instance, light that is detected may be detected during an assay and / or may be employed to determine the result of an assay. As one example, an assay may comprise determining whether a species is present in a sample by immobilizing the species, if present,

[0096] 10

[0097] #14429996vl on the end of a probe and determining whether the species is present and / or the amount of the species based on the interference of light reflected from an interface internal to the probe and light reflected from the end of the probe.

[0098] A variety of suitable transmissive collimators may be employed in the spectrometers, instruments, and methods described herein. In some embodiments, a transmissive collimator is a lens and / or comprises one or more lenses (e.g., two or more lenses). Lenses having fixed focal lengths or adjustable focal lengths may be employed for this purpose. Non-limiting examples of suitable lenses include adjustable liquid lenses, adjustable focusing lenses, liquid crystal lenses, zoom lenses, and tunable acoustic gradient lenses. In some embodiments, a collimator comprises one or more cylindrically shaped lenses.

[0099] As described in further detail below, some cables comprise a plurality of fibers that form a bundle. In some such embodiments, a transmissive collimator is arranged such that the fiber bundle is positioned in a focal point of the transmissive collimator. It is also possible for a transmissive collimator having an adjustable focal length to be adjustable such that the adjusted focal length is positioned so that the fiber bundle is positioned in its focal point. For instance, the transmissive collimator may have a focal length that can be adjusted towards or away from the transmissive collimator in the direction of its optical axis.

[0100] A variety of suitable optical detectors may be employed in the spectrometers, instruments, and methods described herein. In some embodiments, a spectrometer comprises a multi-channel optical detector and / or a method comprises detecting light with a multichannel optical detector. The different channels may be used to detect different wavelengths of light. Advantageously, this may allow for the intensities of multiple wavelengths of light to be detected simultaneously, which may allow for measurements to be made more rapidly. It is also possible for a spectrometer to comprise multiple single-channel optical detectors and / or for a method to comprise detecting light with multiple single-channel detectors. In such embodiments, each single-channel detector may be employed to detect a different wavelength.

[0101] Non-limiting examples of suitable types of optical detectors include photon-counting devices, spectrophotometers, spectrometers (e.g., infrared spectrometers), polarization detectors, photodiodes, CCD / CMOS sensors, and imaging sensors. In some embodiments, an optical detector comprises a sensor, such as a CMOS sensor, having a relatively fast read time (e.g., less than 4 ms, less than 1 ms, and / or less than 0.5 ms, and, optionally, greater than 0 ms and / or greater than 0.1 ms). In some embodiments, an optical detector is capable of generating good quality interference patterns at a relatively high rate (e.g., greater than 500 11

[0102] #14429996vl Hz, greater than 750 Hz, and / or greater than 1 kHz, and, optionally, less than 10 kHz, or less than 5 kHz).

[0103] Optical detectors described herein may be configured to and / or capable of detecting a variation of light intensity over one or more periods of time. For instance, such optical detectors may be able to make relatively rapid measurements of light intensity and / or measure light intensity over a relatively short period of time. It is also possible for some optical detectors to be configured to and / or capable of detecting a light intensity arising from a plurality of locations (e.g., each associated with a fluid and / or a sample of a fluid). In some embodiments, an optical detector is configured to and / or capable of detecting the intensity of light as a function of position (which, in turn, may allow for the detection of the intensity of light as a function of the angle from which it reflected from the probe), detecting the intensity of light as a function of wavelength, and / or detecting the intensity of light across a restricted angular range.

[0104] In some embodiments, a spectrometer described herein is enclosed in an enclosure. In such embodiments, the enclosure may have one or more properties that optically isolates the spectrometer from light external thereto and not supplied thereto via a cable. For instance, the enclosure may be opaque to more one or more wavelengths of light (e.g., one or more wavelengths of light that the spectrometer is capable of detecting and / or configured to detect). The opacity may be such that the intensity of light transmitted through the enclosure to the spectrometer may be sufficiently low such that the spectrometer detects no light when not supplied with light via a cable and / or such that any light that it does detect takes the form of a baseline that can be facilely differentiated from any light supplied thereto via the cable (e.g., that has an intensity of less than 5%, less than 2%, less than 1%, less than 0.75%, less than 0.5%, less than 0.2%, or less than 0.1% of light supplied thereto via a cable during the measurement of light intensity).

[0105] In some embodiments, an enclosure enclosing a spectrometer has one or more features that reduce or eliminate the reflection of light from the spectrometer to a cable and / or a probe that supplies the spectrometer with light (and / or is capable of and / or configured to do so). It is also possible for one or more features of a spectrometer enclosed by the enclosure (e.g., a diffraction grating positioned therein, a transmissive collimator positioned therein, an optical detector positioned therein) to have one or more such features. Advantageously, spectrometers having such a design may exhibit reduced or no reflection of the light that is supplied by the probe or the cable thereto back into the probe or the cable. Such reflected

[0106] 12

[0107] #14429996vl light may undesirably interfere with light being supplied by the probe or the cable to the spectrometer, resulting in unwanted noise.

[0108] In some embodiments, an enclosure comprises a plurality of walls arranged in a manner that reduces or eliminates the above-described reflection. Such walls may be positioned such that light incident thereon that is supplied by a cable or probe reflects therefrom in a direction other than back to the probe or the cable. Similarly, other components of the spectrometer (e.g., diffraction gratings, transmissive collimators, optical detectors) that are in the optical pathway of light supplied by a probe or a cable thereto may be positioned such that light incident thereon along this optical pathway is reflects therefrom in a direction other than back to the probe or the cable or back along this optical pathway in the reverse direction.

[0109] In some embodiments, an enclosure comprises a plurality of walls that have one or more features that promote light absorption and / or diffuse reflection of light. It is also possible for one or more other components of the spectrometer (e.g., diffraction gratings, transmissive collimators, optical detectors) to have such features. The absorption of light may be promoted by light- absorbing coatings (e.g., coatings comprising one or more lightabsorbing components, such as light- absorbing particles). The diffuse reflection of light may be promoted by surface texture (e.g., surface roughness sufficient to cause diffuse reflection).

[0110] A variety of suitable light sources may be present in the instruments described herein. Non-limiting examples of suitable types of light sources include incandescent bulbs and / or lamps (e.g., xenon flash lamps, tungsten halogen lamps, mercury lamps, arc lamps), LEDs, and laser diodes. In some embodiments, an instrument comprises a light source that is part of a plate reader. Light sources may emit white light and / or light at a variety of wavelengths.

[0111] In some embodiments, a light source is present in a light source system further comprising one or more additional components. As one example, a light source may be present in a light source system that comprises two or more light sources (e.g., two or more LEDs).

[0112] As noted above, in some embodiments, a spectrometer and / or instrument described herein is capable of operating and / or configured to operate in conjunction with a probe. Similarly, a method described herein may comprise transmitting light through a probe. The probe may supply light to the spectrometer (e.g., via a cable). In some embodiments, a probe has one or more features that facilitate the supply of such light to the spectrometer. Lor instance, a probe may be capable of transmitting and / or configured to transmit light from a light source (e.g., via a cable placing the light source in optical communication with the

[0113] 13

[0114] #14429996vl probe) through the probe and / or to the end of the probe. As another example, a probe may be capable of transmitting and / or configured to transmit light (e.g., light reflected from an interface internal to the probe, light reflected from the end of the probe) through the probe and to a spectrometer (e.g., via a cable placing the probe in optical communication with the spectrometer). As a third example, a probe may comprise one or more features (e.g., one or more structural features) that assist with generating the type of light to be detected by the spectrometer.

[0115] The probes described herein may have a variety of suitable designs. Some probes described herein are optical probes. Such probes may be part of one or more optical pathways present in an instrument described herein (e.g., between a light source and an environment external to the probe) and / or may be configured to transmit light. In some embodiments, a probe is transparent to and / or may transmit light at a plurality of wavelengths (e.g., visible wavelengths, infrared wavelengths, near infrared wavelengths, wavelengths of light emitted by a light source, wavelengths of light that an optical detector is capable of detecting and / or configured to detect). Some probes comprise one or more polished ends to facilitate transmission. Such polished ends may be perpendicular to the optical axis of the probe.

[0116] In some embodiments, a probe is a fiber-optic probe and / or comprises one or more fibers, such as one or more optical fibers.

[0117] It is also possible for a probe (and / or a fiber therein) to be in optical communication (or be configured to be and / or capable of being in such optical communication) with one or more fiber-optic cables and / or cables comprising two or more fibers. Such cables may transmit light from a light source to a probe (and / or a fiber therein) and / or from a probe (and / or a fiber therein) to an optical detector. This may be accomplished when at least one of the fibers in the cable is in optical communication with an optical fiber present in the probe. In such embodiments, it is also possible for the cable to comprise two or more fibers in optical communication with the optical fiber present in the probe and / or to comprise one or more further fibers not in optical communication with the optical fiber present in the probe. The latter fibers may transmit light from a light source to an optical detector that does not pass through the probe and / or transmit one or more other types of reference signals.

[0118] In some embodiments, a probe and / or a cable may comprise a fiber bundle, such as a fiber-optic bundle and / or a furcated fiber bundle. Fiber bundles may comprise a plurality of fibers. When present, fibers in a probe and / or a cable may be single mode or multimode. In some embodiments, a probe and / or a cable comprises one or more apertures through which 14

[0119] #14429996vl light may be transmitted. For instance, a probe and / or a cable may comprise a plurality of fibers and / or optical fibers, and the terminus of each optical fiber may serve as an aperture through which light may be transmitted. When present, the apertures may be positioned on a side of the probe and / or the cable opposite a side on which any optical detector systems and / or light sources are positioned. In such embodiments, the probe and / or the cable may serve to transmit light from a light source to an aperture and / or to transmit light from an aperture to a spectrometer described herein.

[0120] The probes and cables described herein may comprise fibers (e.g., optical fibers) having a variety of suitable diameters. In some embodiments, a probe or a cable comprises a fiber (e.g., an optical fiber) having a core with a diameter of greater than or equal to 150 microns, greater than or equal to 200 microns, greater than or equal to 300 microns, greater than or equal to 400 microns, greater than or equal to 500 microns, greater than or equal to 600 microns, greater than or equal to 700 microns, greater than or equal to 800 microns, greater than or equal to 900 microns, greater than or equal to 1000 microns, greater than or equal to 1100 microns, greater than or equal to 1200 microns, greater than or equal to 1300 microns, greater than or equal to 1400 microns, greater than or equal to 1500 microns, greater than or equal to 1600 microns, greater than or equal to 1700 microns, greater than or equal to 1800 microns, or greater than or equal to 1900 microns. In some embodiments, a probe or a cable comprises a fiber (e.g., an optical fiber) having a core with a diameter of less than or equal to 2000 microns, less than or equal to 1900 microns, less than or equal to 1800 microns, less than or equal to 1700 microns, less than or equal to 1600 microns, less than or equal to 1500 microns, less than or equal to 1400 microns, less than or equal to 1300 microns, less than or equal to 1200 microns, less than or equal to 1100 microns, less than or equal to 1000 microns, less than or equal to 900 microns, less than or equal to 800 microns, less than or equal to 700 microns, less than or equal to 600 microns, less than or equal to 500 microns, less than or equal to 400 microns, less than or equal to 300 microns, or less than or equal to 200 microns. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 150 microns and less than or equal to 2000 microns, or greater than or equal to 400 microns and less than or equal to 2000 microns). Other ranges are also possible.

[0121] The probes and cables described herein may comprise a variety of suitable amounts of fibers and / or optical fibers. In some embodiments, a probe or a cable comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more fibers and / or optical fibers.

[0122] In some embodiments, a probe or a cable comprises a plurality of fibers and / or optical fibers (e.g., a plurality of fibers and / or optical fibers forming a bundle) that are arranged such

[0123] 15

[0124] #14429996vl that x- and y-axes can be drawn though horizontal and vertical centerlines of the area occupied by all of the plurality of fibers together. Such horizontal and vertical lines may be referred to as the “bundle x-axis,” and “bundle y-axis,” respectively. They may also define a plane perpendicular the optical axes of the fibers. FIG. 5 shows one non-limiting example of a plurality of fibers in a cable taking the form of a fiber-optic bundle and the associated bundle x- and y-axes. In some embodiments, the bundle x-axis and bundle y-axis of a probe may intersect at a point through which an optical axis of the probe passes perpendicularly. This optical axis of the cable and the optical axis of a transmissive collimator also employed in the spectrometer may be coincident lines.

[0125] In FIG. 5, it can be seen that one or more fibers present in a probe or a cable may have centers that are offset from the bundle x- and / or y-axes. It can also be seen that fibers present in a probe or a cable may have centers that are offset from each other along the bundle x- and / or y-axes and / or that the fibers present in the probe or a cable may extend laterally across the bundle x- and / or y-axes. This offset may result in the optical axes of these fibers being misaligned with the optical axis of a collimator also present in the spectrometer. This misalignment may result in reduced collection of light by certain types of collimators (e.g., reflective collimators) and / or incomplete collimation of light supplied therefrom to a collimator. As described elsewhere herein, for these reasons, it may be desirable to employ a collimator that is able to compensate for this misalignment, such as a transmissive collimator positioned relatively close to the probe or cable and / or comprising a lens having an adjustable focal length. It may also be desirable to employ a transmissive collimator positioned and / or adjusted such that one or more portions of the fiber bundle (e.g., the intersection of the bundle x- and / or y-axes, a center of a fiber) is positioned in the focal point of the transmissive collimator.

[0126] It should be noted that the geometries and dimensions shown in FIG. 5 are exemplary. Some probes and cables may comprise a plurality of fibers and / or optical fibers having a geometry and / or arrangement having one or more features that are the same as those shown in FIG. 5 and some probes and cables may comprise a plurality of fibers and / or optical fibers having a geometry and / or arrangement differing from those shown in FIG. 5 in one or more ways. For instance, a probe or cable may comprise fibers that are arranged to form two rows (as in FIGs 5), or may comprise fibers and / or optical fibers that are arranged to form a different number of rows. Additionally, a probe or cable may comprise fibers and / or optical fibers that are arranged differently within a row than the rows of FIG. 5, rows that are offset differently from the rows shown in FIG. 5, and / or in designs lacking identifiable rows.

[0127] 16

[0128] #14429996vl Similarly, rows of fibers and / or optical fibers may include the same numbers of fibers (e.g., optical fibers) shown in FIG. 5 or may contain more or fewer fibers. As another example, it should be understood that the fiber dimensions, core dimensions, cladding dimensions, and coating dimensions shown in FIG. 5 are exemplary. Some fibers and / or optical fibers may have one or more such dimensions and some fibers may have one or more dimensions that differ from such dimensions. Additionally, some fibers and / or optical fibers may lack a coating.

[0129] In some embodiments, x- and y-axes can be drawn though horizontal and vertical centerlines of the area occupied by a transmissive collimator. Such horizontal and vertical lines may be referred to as the “transmissive collimator x-axis,” and “transmissive collimator y-axis,” respectively. They may also define a plane perpendicular the optical axes of the transmissive collimator. FIG. 6 shows an exemplary transmissive collimator and its x- and y- axes.

[0130] In some embodiments, a probe or cable comprises fibers (e.g., optical fibers) that have centers that are greater than or equal to 0 microns, greater than or equal to 50 microns, greater than or equal to 100 microns, greater than or equal to 150 microns, or greater than or equal to 200 microns from a transmissive collimator y-axis. In some embodiments, a probe or cable comprises fibers that have centers that are less than or equal to 230 microns, less than or equal to 200 microns, less than or equal to 150 microns, less than or equal to 100 microns, or less than or equal to 50 microns from a transmissive collimator y-axis. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 0 microns and less than or equal to 230 microns). Other ranges are also possible.

[0131] When a probe or cable comprises more than one fiber, each fiber independently may have a center having a distance to a transmissive collimator y-axis that is in one or more of the above-referenced ranges.

[0132] In some embodiments, a probe or cable comprises fibers (e.g., optical fibers) that have centers that are greater than or equal to 0 microns, greater than or equal to 50 microns, greater than or equal to 100 microns, greater than or equal to 150 microns, greater than or equal to 200 microns, greater than or equal to 250 microns, greater than or equal to 300 microns, greater than or equal to 350 microns, greater than or equal to 400 microns, greater than or equal to 450 microns, greater than or equal to 500 microns, or greater than or equal to 550 microns from the transmissive collimator x-axis. In some embodiments, a probe or cable comprises fibers that have centers that are less than or equal to 580 microns, less than or equal to 550 microns, less than or equal to 500 microns, less than or equal to 450 microns,

[0133] 17

[0134] #14429996vl less than or equal to 400 microns, less than or equal to 350 microns, less than or equal to 300 microns, less than or equal to 250 microns, less than or equal to 200 microns, less than or equal to 150 microns, less than or equal to 100 microns, or less than or equal to 50 microns from the transmissive collimator y-axis. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 0 microns and less than or equal to 580 microns). Other ranges are also possible.

[0135] When a probe or cable comprises more than one fiber, each fiber independently may have a center having a distance to a transmissive collimator x-axis that is in one or more of the above-referenced ranges.

[0136] In some embodiments, a probe or a cable comprises a fiber bundle, and the fibers in the fiber bundle allow for multiplexing and / or for the performance of measurements from multiple light sources. As one example, in some embodiments, a probe or a cable comprises a fiber bundle in which some of the fibers receive light from one light source and / or one location and other fibers receive light from a different light source system and / or a different location. For instance, a cable may comprise some fibers that receive light from a light source (e.g., light that has not passed through a probe) and some fibers receive light from the probe. As a second example, in some embodiments, a probe or a cable comprises a fiber bundle in which some of the fibers supply light to one location and some fibers supply light to another location. For instance, a cable may comprise some fibers that supply light from a light source to a spectrometer along an optical pathway that does not pass through a probe and some fibers that supply light from the light source to the probe.

[0137] It is also possible for a probe to comprise further optics (e.g., in addition to fibers and / or optical fibers) that assist with the transmission of light. As an example, a probe may comprise a lens and / or a pinhole. When present, these components may assist with near-field imaging. In some embodiments, a probe comprises a transmissive collimator that is configured to collect and transmit light to the probe and / or a component thereof. As an example, the transmissive collimator may be configured to collect and transmit light to an axis along the center and / or optical axis of the probe, along the center and / or optical axis of an optical fiber present in the probe, and / or along the center and / or optical axis of a bundle (e.g., a fiberoptic bundle) present in the probe.

[0138] In some embodiments, a probe comprises one or more components that allow it to be optically coupled to a light source, a spectrometer as described herein, and / or a component thereof (e.g., an optical cable). As an example, in some embodiments, a probe comprises a component, such as a plastic hub, that is compatible with an SMA connector (e.g., an

[0139] 18

[0140] #14429996vl SMA905 connector), a BNC connector, a connector with push, lock, and / or twist functionality, and / or a compression spring. In some embodiments, a probe is coupled to an optical cable via a ferrule. The ferrule may comprise optical fibers comprising polished tips, which may facilitate optical communication with the probe. In some embodiments, a probe is capable of being and / or configured to be optically coupled to an optical cable that comprises one or more components to assist with strain relief at the location of the coupling.

[0141] In some embodiments, a probe may be positioned in a housing and / or an instrument described herein comprises a housing in which the probe is positioned, configured to be positioned, and / or capable of being positioned. The housing may mechanically support the probe, may fix the position of the probe (e.g., via mating, a pressurized fit, clamps, a holder, an adhesive, etc.), and / or may be configured to translate and / or be capable of translating the probe. In some embodiments, a housing is configured such that a probe may be reversibly inserted into and / or removed therefrom.

[0142] In some embodiments, a probe (and / or one or more fibers present in a probe) comprises an interface internal thereto. As described above, such probes may be particularly suitable for generating light comprising an amount of light that has been reflected from this interface and an amount of type of light that has been reflected from the end of the probe. When present, such interfaces may extend across the entirety of a probe and / or fiber crosssection (e.g., the cross-section perpendicular to the axis along which light is transmitted through the probe, the cross-section perpendicular to the long axis of the probe). Interfaces internal to probes and / or fibers may have a variety of suitable designs. In some embodiments, a probe and / or fiber comprises an internal interface that takes the form of an interface between an interior portion of the probe and / or fiber and a coating disposed on the interior portion of the probe and / or fiber. FIG. 7 shows one non-limiting embodiment of a probe having such a design. The probe 732 shown in FIG. 7 includes an internal interface 734 between the interior portion of the probe 736 and the coating 738 disposed on the interior portion of the probe.

[0143] In some embodiments, a probe and / or fiber comprises a coating disposed on an interior portion of the probe and / or fiber and one or more further portions of the probe and / or fiber disposed on the coating. As one example, in some embodiments, a probe and / or fiber further comprises a second coating disposed on the coating disposed on the interior portion of the probe and / or fiber. The second coating may be formed from the same material as the interior portion of the probe and / or fiber. FIG. 8 shows one example of such a probe. In

[0144] FIG. 8, the probe 832 includes a second coating 840 disposed on the coating 838. This probe

[0145] 19

[0146] #14429996vl also includes an internal interface 834 between the interior portion of the probe 836 and the coating 838. As another example, in some embodiments, one or more species are immobilized on the probe (not shown), such as on the end of the probe.

[0147] Probes, fibers, internal interfaces thereto, and coatings may have a variety of suitable shapes. For instance, a probe, a fiber, an internal interface, and / or a coating may have a hexagonal and / or a round cross-section.

[0148] The various components of the probes and fibers described herein may have a variety of suitable compositions. In some embodiments, one or more portions of a probe and / or fiber (e.g., an interior portion, a coating, a second coating disposed on a coating disposed on an interior portion, the entirety of the probe) comprises a glass. Non-limiting examples of suitable glasses include SiCh and Ta2Os. In some embodiments, a probe and / or fiber comprises an interior portion and / or a second coating comprising SiCh and a coating comprising Ta2Os. In some embodiments, one or more portions of a probe and / or fiber (e.g., an interior portion, a coating, a second coating disposed on a coating disposed on an interior portion, the entirety of the probe) comprises a polymer. Non-limiting examples of suitable polymers include polystyrene and polyethylene.

[0149] The coatings described herein may have a variety of suitable thicknesses. In some embodiments, one or both of the coatings (and / or both coatings together) have a thickness of greater than or equal to 50 nm, greater than or equal to 100 nm, greater than or equal to 200 nm, greater than or equal to 500 nm, greater than or equal to 750 nm, greater than or equal to 1 micron, greater than or equal to 2 microns, greater than or equal to 3 microns, or greater than or equal to 4 microns. In some embodiments, one or both of the coatings (and / or both coatings together) have a thickness of less than or equal to 5 microns, less than or equal to 4 microns, less than or equal to 3 microns, less than or equal to 2 microns, less than or equal to 1 micron, less than or equal to 750 nm, less than or equal to 500 nm, less than or equal to 200 nm, or less than or equal to 100 nm. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 50 nm and less than or equal to 5 microns, greater than or equal to 100 nm and less than or equal to 5 microns, or greater than or equal to 500 nm and less than or equal to 1 micron). Other ranges are also possible.

[0150] In some embodiments, a probe and / or fiber comprises a surface that is functionalized, that has a surface chemistry that assists with the performance of an assay, and / or has a surface chemistry that assists with the immobilization of a species thereon. The surface functionalization and / or chemistry may promote the immobilization thereon of reaction products that are typically generated during assays. For instance, the surface 20

[0151] #14429996vl functionalization and / or chemistry may promote the immobilization of one or more species generated during the assay thereon. It is also possible for a surface functionalization and / or chemistry to promote the immobilization thereon of one or more species that may be present in an environment with which the probe and / or fiber is in contact. In some embodiments, and as described above, a probe and / or fiber comprises a surface on which one or more species that are reagents are immobilized. The reagent(s) may be immobilized on the probe and / or fiber in a variety of suitable manners. As an example, the reagent(s) may be bonded to the probe and / or fiber. The bonding may comprise covalent bonding, ionic bonding, polar bonding, van der Waals bonding, hydrophobic bonding, and / or hydrogen bonding.

[0152] A variety of suitable reagents may be immobilized on the probes and fibers described herein. Some reagents may be species that are capable of engaging in one or more chemical reactions (e.g., one or more chemical reactions that may take place during an assay that the probe is employed to facilitate). For instance, a probe and / or fiber may comprise a reagent that is capable of bonding with another species (e.g., covalently, ionically, by polar interactions, by van der Waals interactions, hydrophobically, by hydrogen bonding, by complexing), absorbing another species, adsorbing another species, catalyzing a reaction of another species and / or between two or more species, decomposing (e.g., upon exposure to another species), undergoing a conformational shift, and / or catalyzing a reaction. In some embodiments, one or more of the previously described chemical reactions may cause the species with which the reagent reacts to become immobilized thereon. Selected non-limiting examples of suitable reagents include biomolecules (e.g., proteins, glycoproteins, peptides, nucleic acids (e.g., DNA, RNA, mRNA), antibodies (e.g., antibodies for exosomes, such as anti-CD63 and / or anti-CD9, antibodies for proteins, antibodies for viruses, antibodies for virus-like particles), antibody fragments, antigens, polysaccharides, carbohydrates, hormones, streptavidin, glutathione), ligands (e.g., ligands for proteins, such as protein A), small molecules, viruses, cells, inorganic compounds (e.g., aminopropylsilane), sequestration compounds, capsids, bacteria resins (e.g., Ni-NTA), plasmids, nutrient components, metabolics, metabolic byproducts, and combinations thereof. Non-limiting examples of proteins include protein A, protein G, protein L, and lectin. One non-limiting example of a combination of two or more of the previously described reagent types is a reagent that comprises protein A and an antibody to an exosome and / or a virus. The antibody may be immobilized on protein A immobilized on a probe and / or fiber surface and may be capable of immobilizing an exosome and / or a virus. In such embodiments, as well as others, two or

[0153] 21

[0154] #14429996vl more reagents are immobilized on a probe and / or fiber (and, in some embodiments, one or more such reagents may be a combination of two or more reagents).

[0155] In some embodiments, a species immobilized on a surface of a probe and / or fiber is suitable for engaging in a chemical and / or biological reaction that comprises binding. It is also possible for a probe and / or fiber to be suitable for engaging in a chemical and / or biological reaction that does not comprise binding. When present, binding may comprise a reaction between a target and a binding partner that specifically binds to the target (e.g., an agent or molecule that specifically binds to the target). Binding may also comprise immobilizing a target on the binding partner. In some embodiments, the binding partner may specifically bind to an epitope on the target molecule. Non-limiting examples of specific pairs of binding partners and targets include an antibody and an antigen, an antibody fragment and an antigen, an antibody and a hapten, an antibody and a peptide, an antibody and a small molecule, an antigen and a fusion protein, an antibody fragment and a hapten, an enzyme and an enzymatic substrate, an enzyme and an inhibitor, an enzyme and a cofactor, a binding protein and a substrate, a carrier protein and a substrate, a protein and a small molecule, lecithin and a carbohydrate, a receptor and a hormone, a receptor and an effector, complementary strands of nucleic acid, a protein in combination with a nucleic acid repressor and an inducer, a ligand and a cell surface receptor, a virus and a ligand, and a receptor and a ligand.

[0156] Non-limiting examples of antibodies that may be binding partners or antibodies include intact (i.e., full-length) polyclonal and monoclonal antibodies, antigen-binding fragments of polyclonal and monoclonal antibodies (such as Fab, Fab', F(ab')2, or Fv), single chains (scFv) mutants of single chains, fusion proteins comprising an antibody portion, humanized antibodies, chimeric antibodies, diabodies, linear antibodies, single chain antibodies, multispecific antibodies (e.g., bispecific antibodies), and modified configurations of the immunoglobulin molecule that comprise an antigen recognition site of the required specificity. Non-limiting examples of antibodies falling into the last category include glycosylation variants of antibodies, amino acid sequence variants of antibodies, and covalently modified antibodies. Additionally, a binding partner may be an antibody of any class, such as IgD, IgE, IgG, IgA, or IgM (or subclass thereof, e.g., IgGl, IgG2, IgG3, IgG4, IgAl and / or IgA2).

[0157] An antigen may be a molecule or a portion of a molecule that can have antibodies generated against it. Antigens may be peptides, polysaccharides and / or lipids. Some antigens

[0158] 22

[0159] #14429996vl may originate from within the body (a “self-antigen”), and some antigens may originate from the external environment (a “non-self-antigen”).

[0160] In some embodiments, antibodies suitable for performing a chemical and / or biological reaction specifically bind to epitopes on their target molecules. An epitope (which may be referred to as an antigenic determinant) may be the part of the antigen recognized (or bound by) an antibody. For example, the epitope may be the specific piece of the antigen to which an antibody binds. The part of an antibody that binds to the epitope may be referred to as a paratope. An epitope may be a conformational epitope (composed of discontinuous amino acids or sections of the antigen) or a linear epitope (composed of continuous amino acids). Some proteins may share segments of high sequence homology and / or structural similarity. These similar proteins may have common epitopes (in other words, the epitopes on different antibodies may be bound by the same antibody). Further, a protein that has been processed differentially (such as a protein that has gone a further enzymatic process) may share some, but not all, epitopes with its pre-processing form. Non-limiting examples of different epitopes that may be added or removed during processing include N-terminal signal peptides (as seen, for example, on pre-pro-peptides) and changes seen when an inactive protein (e.g., a pro-peptide) is turned into an active form by post-translational modification.

[0161] When an antibody specifically binds to an epitope, it may engage in a binding reaction that is capable of discriminating between a target molecule and a non-target molecule. For example, a binding partner may specifically bind to a target molecule with greater than or equal to 2-fold, with greater than or equal to 4-fold, greater than or equal to 5- fold, greater than or equal to 6-fold, greater than or equal to 7-fold, greater than or equal to 8- fold, greater than or equal to 9-fold, greater than or equal to 10-fold, greater than or equal to 20-fold, greater than or equal to 25-fold, greater than or equal to 50-fold, or greater than or equal to 100-fold greater affinity than to a non-target molecule.

[0162] The binding affinity of an antibody may be parametrized by its affinity (KD). The KD is the ratio of the dissociation constant to the association constant (Ko=Kd / Ka). In some embodiments, a binding partner described herein has an affinity (KD) of less than or equal to 10'5M, less than or equal to 10'6M, less than or equal to 10'7M, less than or equal to 10'8M, less than or equal to 10'9M, less than or equal to IO'10M, less than or equal to 10'11M, or less than or equal to 10'12M. An increased affinity KD corresponds to a decreased dissociation constant Kd or an increased association constant (Ka). Higher affinity binding of a binding partner (e.g., an antibody) to a first molecule relative to a second molecule can be indicated by a higher Ka(or a smaller numerical value of KD and / or Kd) for binding to the first target 23

[0163] #14429996vl than the Ka(or numerical value of KD and / or Ka) for binding to the second target. In such cases, the antibody has a specificity for the first molecule (e.g., a protein in a first conformation or mimic thereof) relative to the second molecule (e.g., the same protein in a second conformation or mimic thereof, or a second protein). Differences in binding affinity (e.g., specificity) can be greater than or equal to 1.5-fold, greater than or equal to 2-fold, greater than or equal to 3-fold, greater than or equal to 4-fold, greater than or equal to 5-fold, greater than or equal to 10-fold, greater than or equal to 15-fold, greater than or equal to 20- fold, greater than or equal to 37.5-fold, greater than or equal to 50-fold, greater than or equal to 70-fold, greater than or equal to 80-fold, greater than or equal to 90-fold, greater than or equal to 100-fold, greater than or equal to 500-fold, greater than or equal to 1000-fold, greater than or equal to 10,000-fold, greater than or equal to 105-fold.

[0164] In some embodiments, a reagent may be immobilized on a surface of a probe and / or fiber via a covalent bond. Prior to such immobilization, the surface of the probe and / or fiber may be functionalized such that it comprises a plurality of functional groups suitable for forming such covalent bonds. For instance, the surface of the probe and / or fiber may be functionalized by reaction with a bifunctional reagent comprising a siloxane group that facilitates attachment to the probe and / or fiber and a functional group that facilitates the formation of a covalent bond with the reagent to be immobilized on the probe and / or fiber. As another example, the surface of the probe and / or fiber may be exposed to a plasma or other treatment that generates functional groups in situ that facilitate the formation of a covalent bond with the reagent to be immobilized on the probe and / or fiber. Non-limiting examples of suitable types of functionals group that facilitate the formation of a covalent bond with the reagent to be immobilized on the probe and / or fiber include hydroxyls, amines, and carboxyls.

[0165] Light detected by spectrometers and instruments described herein and / or pursuant to methods described herein may (e.g., light supplied by a probe) may comprise light reflected from an interface internal to the probe and / or light reflected from the end of the probe. Such light may comprise both types of light, light interference between these two types of light (e.g., interference between light supplied to the probe by a common light source but traveling through optical pathways having different optical path lengths), the absence of either or both such type of light, and / or the absence of such interference. As two examples, light supplied by a probe may comprise interference between light that is reflected from two different interfaces associated with a probe and / or a species immobilized on a probe (e.g., an interface between an interior portion of a probe and a coating disposed on the internal portion of the 24

[0166] #14429996vl probe, an interface between the species and the probe, an interface between the species and an environment external to the probe, an interface at the end of the probe) or the absence of such interference. Light comprising light reflected from an interface internal to the probe and light reflected from the end of the probe may be indicative of the amount and / or type of a species immobilized on the end of the probe.

[0167] Light that is reflected from an interface associated with a probe may be supplied to a probe from a light source. Such a light source may be optically coupled to a probe such that light is transmitted from the light source and across the probe (e.g., parallel to an optical axis of the probe). Upon reaching an end of the probe, the light may be transmitted out of the probe and / or may reflect from an interface between the probe and an environment external to the probe (and / or from the end of the probe). If there is a species immobilized on the probe, some light may reflect from the interface between the probe and the species and / or some light may be transmitted through the species. The species may also change the effective refractive index at the end of the probe and / or change the effective optical path length of the light transmitted through the probe. Light transmitted through the species will then encounter the environment with which the species is in contact. Some light encountering this environment may be transmitted into the environment with which the species is in contact (e.g., an environment external to the probe) and / or may reflect from the interface between the environment and the species.

[0168] It is also possible for probe described herein to have one or more internal interfaces at which reflection may occur. For instance, some probes may comprise one or more internal interfaces at which reflection can occur, such as an interface between a coating and an interior portion of the probe on which the coating is disposed.

[0169] Light reflected from one or more of the above-described locations (and / or any further locations) may travel back through the probe. If light is reflected from multiple locations (e.g., at an interface between the probe and a species immobilized on the probe, at an interface between a species immobilized on the probe and an environment external to the probe, at an interface between a coating disposed on an interior portion of the probe and a species immobilized on the probe, at an interface between an interior portion of the probe and a coating disposed thereon, from the end of the probe), such light may interfere which each other. Light interference may cause the intensity of the interfered light to be higher or lower depending on whether the interference is positive or negative, which may depend on the phase shift between the multiple sources of interfering light. The phase shift may depend on the differences in the path lengths traveled by the light prior to interfering, the refractive 25

[0170] #14429996vl index of the material(s) through which the light passes prior to interfering, and / or on the wavelength of light. Thus, in some embodiments, light supplied by a probe and / or detected by an optical detector comprises light having a variety of wavelengths. Additionally, obtaining information about the intensity of interfered light across a variety of wavelengths may provide information about the presence or absence of a layer comprising a species immobilized on a probe, the thickness of such a layer, and / or the refractive index of such a layer. This information may be employed to determine the presence, absence, and / or amount of the species immobilized on the probe.

[0171] FIG. 9 depicts schematically one example of a process by which light comprising both an amount of the light that has been reflected from an interface internal to a probe and an amount of light that has been reflected from the end of a probe can be generated. As shown in FIG. 9, light that travels down a probe may reflect from an interface between a coating disposed on an interior portion of a probe and from an interface between a species immobilized on the probe and an environment external to the probe. The phase shift between these two sources of reflected light may depend on the amount of the species immobilized on the probe and on the wavelength of the reflected light, which may affect the intensity of the reflected light measured. Analysis of the intensity of the reflected light as a function of wavelength may therefore be employed to determine an amount of the species immobilized on the probe. As shown in FIG. 9, the intensity of the reflected light as a function of wavelength may form an interference pattern, and a change in the magnitude of the phase shift between light reflecting from two interfaces described herein may cause a wavelength shift of such an interference pattern.

[0172] Detection of light may be performed at one or more discrete points in time or over a period of time. Additionally, such detection may be performed in a manner that yields a single data point (e.g., an endpoint, the average intensity of light at a particular wavelength as measured over a period of time, the average intensity of light at a particular wavelength as computed by averaging a plurality of measurements of light intensity, the intensity of light at a particular wavelength as determined from a single measurement) and / or a plurality of data points. The plurality of data points may describe the variation of the light intensity over time (e.g., in a kinetic measurement), the variation of the light intensity as a function of position, and / or the variation of the light intensity as a function of wavelength. The plurality of data points may be obtained from different measurements that take place over different (overlapping or non-overlapping) periods of time.

[0173] 26

[0174] #14429996vl In some embodiments, detecting light over time comprises detecting its variation over time. The variation may comprise an increase, a decrease, or a lack of variation. In some embodiments, the variation comprises the first derivative of the intensity of the light at one or more wavelengths. The variation in the intensity of the light (and / or one or more wavelengths thereof) over a period of time may be determined from multiple measurements made over the period of time that yield multiple values of the light intensities over the period of time.

[0175] In some embodiments, light detected by a spectrometer and / or pursuant to a method described herein comprises visible light. It is also possible for the light to comprise infrared light. Additionally, the light may be and / or comprise polarized light or unpolarized light.

[0176] In some embodiments, one or more components of a spectrometer and / or instrument (e.g., a transmissive collimator, a diffraction grating, an optical detector) described herein are mounted on a substrate having a particular thermal expansion coefficient, such as a relatively low thermal expansion coefficient. These components of the spectrometer and / or instrument may be mounted on the same substrate (e.g., on a single substrate having a relatively low thermal expansion coefficient). One non-limiting example of a substrate having a relatively low thermal conductivity and a relatively low thermal expansion coefficient is a substrate comprising glass, consisting essentially of glass, and / or consisting of glass. Other nonlimiting examples of suitable substrates include substrates comprising, consisting essentially of, and / or consisting of fused quartz and / or ceramics.

[0177] In some embodiments, one or more of the above-listed components (e.g., a transmissive collimator, a diffraction grating, and / or an optical detector) are mounted on a substrate having a thermal expansion coefficient of less than or equal to 15 pm / (m * °C).

[0178] In some embodiments, one or more components of a spectrometer and / or instrument (e.g., a transmissive collimator, a diffraction grating, an optical detector) described herein have thermal expansion coefficients that are relatively similar to those of substrates on which they are mounted. For instance, in some embodiments, one or more such components are mounted on a substrate having the same composition, and therefore the same thermal expansion coefficient.

[0179] Substrates on which spectrometer and / or instrument components are mounted may have a variety of suitable thicknesses. In some embodiments, a substrate on which a spectrometer is mounted has a thickness of greater than or equal to 1 mm, greater than or equal to 2 mm, greater than or equal to 5 mm, greater than or equal to 7.5 mm, greater than or equal to 10 mm, or greater than or equal to 12.5 mm. In some embodiments, a substrate on 27

[0180] #14429996vl which a spectrometer is mounted has a thickness of less than or equal to 15 mm, less than or equal to 12.5 mm, less than or equal to 10 mm, less than or equal to 7.5 mm, less than or equal to 5 mm, or less than or equal to 2 mm. Combinations of the above-referenced ranges are also possible (e.g., greater than or equal to 1 mm and less than or equal to 15 mm). Other ranges are also possible.

[0181] When a spectrometer and / or an instrument comprises two or more substrates, each substrate may independently have a thickness in one or more of the above-referenced ranges.

[0182] In some embodiments, a spectrometer and / or instrument as described herein may comprise a thermally insulating material. For example, in some embodiments, the thermally insulating material may be disposed on and / or adjacent to one or more walls of an enclosure of a spectrometer. When present, the thermally insulating material may be external to the wall(s) of the enclosure.

[0183] Spectrometers comprising thermally insulating materials may have several advantages over spectrometers that do not comprise thermally insulating materials. For example, without wishing to be bound by a particular theory, it is believed that a thermally insulating material may advantageously reduce thermal fluctuations within the spectrometer and / or reduce the sensitivity of the temperature internal to the enclosure to thermal fluctuations external to the enclosure. Reducing thermal fluctuations within the spectrometer may desirably minimize thermal expansion and / or contraction of components of the spectrometer. Reducing thermal fluctuations in the spectrometer may also advantageously prevent and / or reduce fluctuations of the internal temperature distribution within the spectrometer, which it is believed may improve the accuracy of measurements made using the spectrometer.

[0184] In some embodiments, instruments comprising one or more spectrometers that comprise thermally insulating materials may have several advantages over instruments that do not comprise thermally insulating materials. For example, without wishing to be bound by a particular theory, it is believed that a thermally insulating material may advantageously reduce temperature variation and / or internal temperature distribution variation among the spectrometers within the instrument (e.g., by reducing the transmission of variations in temperature external to the spectrometers’ enclosures to environments internal thereto). It is believed that such a reduction in temperature variation and / or internal temperature distribution variation may allow for the spectrometers within the instrument to produce consistent measurements (e.g., measurements without significant differences between the spectrometers).

[0185] 28

[0186] #14429996vl In some embodiments, the walls of an enclosure enclosing a spectrometer are formed from a material other than a thermally insulating material, and a thermally insulating material is disposed thereon. This may advantageously allow for the walls to be formed from a material with one or more desirable properties (e.g., reduced reflectivity, low transparency) that is not necessarily thermally insulating. For instance, in some embodiments, the walls of the enclosure may be formed from metal.

[0187] As described below, an instrument and / or spectrometer may comprise a thermally insulating material having a variety of desirable properties. The properties of the thermally insulating material may vary based on the design of the instrument and / or spectrometer, and / or based on the desired applications in which the instrument and / or spectrometer may be used. For example, in some embodiments, a relatively thin and / or compact thermally insulating material and / or a thermally insulating material having a relatively low thermal conductivity may be particularly desirable.

[0188] In some embodiments, as described above, a thermally insulating material may be disposed on and / or adjacent to one or more walls of an enclosure of a spectrometer. For example, in some embodiments, the thermally insulating material may be disposed on and / or adjacent to one of the walls of the enclosure, two of the walls of the enclosure, three of the walls of the enclosure, four of the walls of the enclosure, five of the walls of the enclosure, or more. In some embodiments, the thermally insulating material may be disposed on and / or adjacent to all of the walls of the enclosure. For example, in the non-limiting embodiment shown in FIG. 10A, the enclosure of the spectrometer 1001 comprises six walls, and thermally insulating material 1002 is disposed on two of the six walls. Thermally insulating material 1002 could be disposed on and / or adjacent to any combination of the walls of the enclosure of the spectrometer 1001. As shown in FIG. 10A, thermally insulating material disposed on a wall of an enclosure may be disposed on a side of the wall external to the environment enclosed by the enclosure.

[0189] The thermally insulating material may be disposed directly on the wall(s) of an enclosure or may be indirectly disposed on such wall(s). For instance, one or more intervening layers (e.g., an adhesive) may be positioned between the wall(s) of the enclosure on which the thermally insulating material is disposed and the thermally insulating material.

[0190] In some embodiments, two or more spectrometers may be placed adjacent to each other. In some embodiments, a grouping of two or more spectrometers placed adjacent to each other may be referred to as a bank of spectrometers. The sides of the bank of spectrometers may be made up of the externally-facing walls of enclosures of the 29

[0191] #14429996vl spectrometers contained therein. For example, as shown in FIG. 10B, a bank of spectrometers 1050 may comprise side 1051 comprising walls 1010a and 1010b of the enclosures of the spectrometers 1001a and 1001b contained therein.

[0192] In some embodiments, a thermally insulating material may be disposed on (e.g., directly, indirectly) and / or adjacent to one or more walls of the enclosures of each spectrometer within the bank of spectrometers, as described above. In some embodiments, a thermally insulating material may be disposed on and / or adjacent to an entire side of the bank of spectrometers (e.g., the thermally insulating material may be shared by two adjacent spectrometers in the bank of spectrometers). For example, as shown in FIG. 10B, the bank of spectrometers 1050 comprises six sides, and the thermally insulating material 1020 is disposed on two of the six sides of the bank of spectrometers 1050. Thermally insulating material 1020 may be disposed on and / or adjacent to any combination of the sides of the bank of spectrometers. In some embodiments in which the thermally insulating material is disposed on and / or adjacent to an entire side of the bank of spectrometers, the thermally insulating material may be a continuous thermally insulating material.

[0193] In some embodiments, a gap may be left between two adjacent spectrometers in a bank of spectrometers (e.g., gap 1060 shown in FIG. 10B). In some embodiments, the gap may be filled with air and / or may facilitate convective cooling of the spectrometers.

[0194] A thermally insulating material may have any of a variety of suitable properties. For example, in some embodiments, a thermally insulating material may have an advantageously low thermal conductivity. For example, in some embodiments, the thermally insulating material may have a thermal conductivity of greater than or equal to 0.02 W / mK and less than or equal to 0.05 W / mK. Thermally insulating materials having such low thermal conductivities may be especially suitable for applications in which a high degree of temperature stability is desired.

[0195] In some embodiments, a thermally insulating material may have an advantageously low thermal conductivity, as described above, and / or an advantageously high thickness. In some embodiments, the thermally insulating material may have an advantageously high R value, where the R value is defined as the thickness of the thermally insulating material divided by the thermal conductivity of the thermally insulating material. For example, a silicone foam having a thermal conductivity of 0.06 W / mK and a thickness of 1 / 8 inch would have an R value of 0.3. Increasing the thickness of the thermally insulating material and / or decreasing its thermal conductivity may advantageously lead to the thermally insulating material having a higher R value.

[0196] 30

[0197] #14429996vl A thermally insulating material may have any of a variety of suitable compositions. For example, in some embodiments, the thermally insulating material comprises foam (e.g., silicone foam, polyurethane foam), an aerogel (e.g., an aerogel comprising glass), fiberglass, and / or neoprene.

[0198] A thermally insulating material may have any of a variety of suitable thicknesses. In some embodiments, the thickness of the thermally insulating material may be chosen based on the application of interest, design considerations, and / or the composition and / or thermal conductivity of the thermally insulating material, which may be any of the compositions and / or thermal conductivities described above. Likewise, in some embodiments, the composition and / or thermal conductivity of the thermally insulating material may be chosen based on the thickness of the thermally insulating material. For example, in some embodiments, if a thermally insulating material having a thickness of approximately 1 / 8 inch is chosen due to design considerations, a material having a particular thermal conductivity may be chosen for the thermally insulating material in order to achieve a particular R value, as described above. In some embodiments, in which space considerations may require the use of a particularly thin thermally insulating material (e.g., a thermally insulating material having a thickness of less than 1 / 8 inch), it may be necessary to use a thermally insulating material having a lower thermal conductivity in order to achieve the same R value as a thicker thermally insulating material.

[0199] In some embodiments, the thermally insulating material may have a suitably low flammability. For example, in some embodiments, the thermally insulating material may have a flammability rating of V-0 under the UL 94 standard.

[0200] In some embodiments, an instrument and / or a spectrometer as described herein may comprise a heating element and / or a sensing element (e.g., a temperature sensor). In some embodiments, a heating element may be disposed on and / or adjacent to one or more sides of an enclosure of a spectrometer. For example, as shown in FIG. IOC, a heating element 1030 may be disposed on one wall of an enclosure of spectrometer 1001. In some embodiments, the heating element may advantageously allow for the maintenance of a consistent temperature within the spectrometer, particularly when a thermally insulating material is disposed on at least one wall of the enclosure of the spectrometer. This may be achieved by maintaining the spectrometer at a relatively constant temperature that is higher than the temperature of one or more other locations in an instrument in which the spectrometer is positioned.

[0201] 31

[0202] #14429996vl In some embodiments, an instrument and / or a spectrometer as described herein may comprise a temperature sensor. In some embodiments, the temperature sensor may be configured to measure and / or capable of measuring the temperature within the spectrometer. In some embodiments, as shown in FIG. IOC, a temperature sensor 1031 may be placed on and / or adjacent to a wall of an enclosure of the spectrometer 1001. In some embodiments, the temperature sensor may advantageously allow for the monitoring and / or regulation of the temperature within the spectrometer. In some embodiments, the temperature sensor may allow for the continuous monitoring and / or regulation of the temperature within the spectrometer. In some embodiments, the temperature sensor may be connected to a heating element disposed on and / or adjacent to at least one wall of the enclosure of the spectrometer, as described above. In some embodiments, the temperature sensor and heating element may be configured to operate and / or capable of operating in concert to maintain a desired temperature within the spectrometer (e.g., via a controller).

[0203] In some embodiments, a heating element and / or sensor as described above may be included in each spectrometer in a bank of spectrometers. In some embodiments, the heating element and / or temperature sensor may be shared by a group of spectrometers within the bank of spectrometers. For example, in some embodiments, a heating element may be shared by a subset of the spectrometers within the bank of spectrometers. In some embodiments, the heating element and / or temperature sensor may be shared by all spectrometers within the bank of spectrometers. For example, in the non-limiting embodiment shown in FIG. 10D, the heating element 1070 may be disposed on a wall of the enclosure of adjacent spectrometers 1001a and 1001b, while the temperature sensor 1071 may be shared by the two adjacent spectrometers 1001a and 1001b.

[0204] In some embodiments, temperature variations within a spectrometer, bank of spectrometers, and / or instrument as described herein may be reduced and / or minimized by conditioning and / or regulating airflow within the spectrometer, bank of spectrometers, and / or instrument.

[0205] In some embodiments, temperature variations within a spectrometer, bank of spectrometers, and / or instrument as described herein may be reduced and / or minimized by thermally insulating the entire instrument (e.g., the instrument comprising one or more spectrometers and / or banks of spectrometers). In some embodiments, insulating the entire instrument may comprise zoned temperature control within the instrument based on the thermal requirements of various components therein, such as spectrometers, banks of spectrometers, samples therein (e.g., samples disposed in multiwell plates), probes, probe 32

[0206] #14429996vl housings, and / or other components. In some embodiments, airflow within the instrument may be segregated, for example to mitigate possible adverse effects on sensitive samples (such as evaporation) that may arise from locally high temperatures within the instrument.

[0207] In some embodiments, temperature variations within a spectrometer, bank of spectrometers, and / or instrument as described herein may be reduced and / or minimized through the use of a controller (e.g., a PID controller) to perform active temperature regulation of the spectrometer, bank of spectrometers, and / or instrument. In some embodiments, active thermal control may allow for precise spatial and temperature control of the spectrometer, bank of spectrometers, and / or instrument.

[0208] In some embodiments, temperature variations within a spectrometer, bank of spectrometers, and / or instrument as described herein may be reduced and / or minimized by disposing phase change materials (PCMs) on and / or adjacent to one or more walls of an enclosure of the spectrometer, one or more sides of the bank of spectrometers, and / or one or more portions of the instrument. In some embodiments, phase change materials may allow for passive temperature regulation, thereby buffering the spectrometer, bank of spectrometers, and / or instrument against temperature fluctuations.

[0209] EXAMPLE 1

[0210] This Example demonstrates the desirability of employing a lens having an adjustable focal length to compensate for the presence of multiple fibers in an optical probe.

[0211] FIGs. 11 and 12 show changes in the beam diameter with defocus at two different wavelengths (575 nm and 775 nm, respectively) for fiber bundles including fibers having centers positioned up to ± 200 microns away from the intersection of the bundle x- and y- axes. These beam diameters were obtained at five different values of defocus (-200 microns, -100 microns, 0 microns, 100 microns, and 200 microns). As can be seen from these Figures, the presence of multiple fibers in a probe can result in undesirable beam broadening. Such beam broadening can be compensated for by adjusting the focal length of a lens having such an adjustable focal length so that the light impinging thereon is appropriately collimated.

[0212] EXAMPLE 2

[0213] This Example provides the thermal conductivity and thermal expansion coefficients for three different materials.

[0214] The thermal expansion coefficients of glass, aluminum, copper, and stainless steel are shown in FIG. 13. As can be seen from FIG. 13, glass has a desirably low thermal expansion

[0215] 33

[0216] #14429996vl coefficient in comparison to these metals. This indicates that glass may be a desirable substrate for mounting one or more components of a spectrometer described herein (e.g., a transmissive collimator, a diffraction grating, an optical detector).

[0217] EXAMPLE 3

[0218] This Example compares the performance of spectrometers having the design shown in FIGs. 1 and 2 to a commercially available USB4000 spectrometer available from Ocean Optics.

[0219] The USB4000 spectrometer included an aluminum enclosure to which all optical components were attached. The spectrometers having the design shown in FIGs. 1 and 2 included a glass substrate to which all optical components were attached.

[0220] Each spectrometer was positioned in an instrument described herein further comprising a light source and a probe. First, each instrument was turned off and remained turned off overnight. The next morning, each instrument was turned on and employed to detect, over time, light comprising light reflected from an interface internal to the probe and light reflected from the end of the probe. Without wishing to be bound by any particular theory, it is believed that turning on the instruments caused the instruments to generate heat, changing the temperature inside the spectrometers. It is believed that it took approximately 40 minutes for the temperatures inside the instruments to stabilize after the instruments were turned on.

[0221] FIG. 14 shows the wavelength shift in the interference pattern between the light reflected from the interface internal to the probe and light reflected from the end of the probe as a function of time for the USB4000 spectrometer after the instrument in which it was positioned was turned on. FIG. 15 shows this same wavelength shift detected as a function of time for the spectrometers having the design shown in FIGs. 1 and 2 after the instruments in which they were positioned were turned on. From these Figures, it can be seen that the spectrometers having the design shown in FIGs. 1 and 2 measured smaller wavelength shifts prior to the achievement of thermal equilibrium than the USB4000 spectrometer. It can also be seen that the spectrometers having the design shown in FIGs. 1 and 2 measured signals that were more predictable and exhibited less drift during warm-up than those measured by the USB4000 spectrometer. This data indicates that the spectrometer shown in FIGs. 1 and 2 exhibits performance that is improved and more consistent than the performance of the USB4000 spectrometer.

[0222] 34

[0223] #14429996vl Without wishing to be bound by any particular theory, it is believed that this difference in performance is due to the different materials to which the optical components in the different spectrometers were attached. It is also believed that aluminum can expand and twist upon exposure to heat of the magnitude generated during instrument warm-up while glass exhibits relative dimensional stability upon exposure to such heat. Additionally, it is believed that the expansion and twisting of the aluminum enclosure present in the USB4000 spectrometer results in unexpected wavelength shifts and an unpredictable amplitude of the wavelength shifts measured thereby during instrument warm-up. Finally, it is believed that the spectrometers having the design shown in FIGs. 1 and 2 exhibit comparatively lower amplitude and higher predictability wavelength shifts upon instrument warm-up.

[0224] EXAMPLE 4

[0225] This Example depicts exemplary arrangements of fibers in the probes and cables described herein.

[0226] FIG. 16 depicts an exemplary arrangement of three fibers in a cable comprising three fibers. FIG. 17 depicts an exemplary arrangement of four fibers in a cable comprising four fibers. In both of these Figures, the fibers are cladded and have a 300-micron core and a 330- micron outer diameter.

[0227] EXAMPLE 5

[0228] This Example depicts the optical pathway of light into and through an exemplary spectrometer.

[0229] FIG. 18 shows the optical pathway of the light into and through the spectrometer. The light is supplied by the cable external to the spectrometer and then enters the spectrometer and impinges on the diffraction grating. As can be seen from the circled component of the optical pathway, the diffraction grating desirably reflects this light away from the cable.

[0230] EXAMPLE 6

[0231] This Example compares the performance of spectrometers comprising a thermally insulating material disposed on one or more walls thereof with spectrometers that do not comprise a thermally insulating material disposed on one or more walls thereof.

[0232] In Experiment 1, eight uninsulated spectrometers were positioned in an instrument described herein comprising a light source and a probe. In Experiment 2, two banks of four

[0233] 35

[0234] #14429996vl spectrometers, each comprising silicone foam insulation having a thickness of 1 / 8” disposed on five of the six sides of the bank of spectrometers and a heating element disposed on the sixth side, were positioned in an instrument described herein comprising a light source and a probe. In each Experiment, the instrument was turned on and employed to detect, over time, light comprising light reflected from an interface internal to the probe and light reflected from the end of the probe.

[0235] FIG. 19A shows the wavelength shift in the interference pattern between the light reflected from the interface internal to the probe and light reflected from the end of the probe as a function of time in each of the uninsulated spectrometers in Experiment 1, and FIG. 19B shows this same wavelength shift detected as a function of time in each of the spectrometers within the insulated banks in Experiment 2. From these Figures, it can be seen that Experiment 2 had significantly improved signal tightness (i.e., significantly less variation in measurements among the spectrometers) compared to Experiment 1. Without wishing to be bound by any particular theory, it is believed that this difference in performance is due to the decreased thermal variations across the spectrometers in Experiment 2 due to the presence of the thermally insulating materials.

[0236] EXAMPLE 7

[0237] This Example depicts exemplary arrangements of components of spectrometers and banks of spectrometers described herein.

[0238] FIG. 20 depicts an exemplary arrangement of components of a spectrometer comprising an enclosure as described herein, comprising a thermally insulating material disposed on one or more walls of the enclosure, a heating element disposed on one wall of the enclosure, and a temperature sensor configured to measure a temperature within the spectrometer.

[0239] FIGs. 21 A and 2 IB depict an exemplary arrangement of a bank of spectrometers comprising four spectrometers, with a thermally insulating material disposed on multiple sides thereof.

[0240] FIGs. 22A-22C depict an exemplary instrument comprising a temperature control system comprising fans, metal enclosures allowing for isolated thermal conduction, and heat- isolated mountings. The instruments shown in FIGS. 22A-22C also comprise a bank of spectrometers comprising four spectrometers, comprising a thermally insulating material disposed on multiple sides thereof.

[0241] 36

[0242] #14429996vl While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the functions and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the teachings of the present invention is / are used. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and / or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and / or methods, if such features, systems, articles, materials, kits, and / or methods are not mutually inconsistent, is included within the scope of the present invention.

[0243] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0244] The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.” The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0245] 37

[0246] #14429996vl As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0247] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0248] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

[0249] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially 38

[0250] #14429996vl of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

[0251] 39

[0252] #14429996vl

Claims

CLAIMSWhat is claimed is:

1. A spectrometer, comprising: a transmissive collimator positioned to collimate light supplied by a probe via a cable, wherein the cable comprises a fiber bundle comprising a plurality of fibers, and wherein at least one of the fibers in the plurality of fibers is in optical communication with an optical fiber present in the probe; a diffraction grating positioned to disperse light collimated by the transmissive collimator; and an optical detector, wherein the light supplied by the probe comprises light reflected from an interface internal to the probe and light reflected from the end of the probe.

2. A method, comprising: transmitting light supplied by a probe through a cable, wherein the cable comprises a fiber bundle comprising a plurality of fibers, and wherein at least one of the fibers in the plurality of fibers is in optical communication with an optical fiber present in the probe; collimating the light by transmitting the light through a transmissive collimator; dispersing the light by reflecting it from a diffraction grating; and detecting the light with an optical detector, wherein the light transmitted through the probe comprises light reflected from an interface internal to the probe and light reflected from the end of the probe.

3. An instrument, comprising: a light source configured to emit light; a cable configured to transmit the emitted light, wherein the cable comprises a fiber bundle comprising a plurality of fibers, and wherein at least one of the fibers in the plurality of fibers is configured to be in optical communication with an optical fiber present in a probe; a spectrometer, comprising: a transmissive collimator configured to collimate the light supplied by the probe via the cable; a diffraction grating positioned to disperse light collimated by the transmissive collimator; and40#14429996vlan optical detector, wherein the light comprises light reflected from an interface internal to the probe and light reflected from the end of the probe.

4. A spectrometer as in claim 1, wherein the diffraction grating is reflective.

5. A spectrometer as in claim 1, wherein the light comprises light having a variety of wavelengths.

6. A spectrometer as in claim 1, wherein the optical detector is a multi-channel optical detector.

7. A spectrometer as in claim 1, wherein the fiber bundle is a furcated fiber bundle.

8. A spectrometer as in claim 1, wherein the fiber bundle is a fiber-optic bundle.

9. A spectrometer as in claim 1, wherein the fibers in the fiber bundle are multimode fibers.

10. A spectrometer as in claim 1, wherein the fibers in the fiber bundle allow for multiplexing and / or for the performance of measurements from multiple light sources.

11. A spectrometer as in claim 1, wherein the probe is an optical probe.

12. A spectrometer as in claim 1, wherein the transmissive collimator comprises a lens.

13. A spectrometer as in claim 1, wherein the transmissive collimator comprises two or more lenses.

14. A spectrometer as in claim 1, wherein the transmissive collimator comprises a lens having an adjustable focal length.

15. A spectrometer as in claim 14, wherein the transmissive collimator comprises a lens having a fixed focal length.41#14429996vl16. A spectrometer as in claim 14, wherein the transmissive collimator comprises an adjustable liquid lens.

17. A spectrometer, instrument, or method as in any preceding claim, wherein the transmissive collimator comprises an adjustable focusing lens.

18. A spectrometer as in claim 1, wherein the transmissive collimator comprises a liquid crystal lens.

19. A spectrometer as in claim 1, wherein the transmissive collimator comprises a zoom lens.

20. A spectrometer as in claim 1, wherein the transmissive collimator comprises a tunable acoustic gradient lens.

21. A spectrometer as in claim 1, wherein at least a portion of the light supplied by the probe is transmitted through the transmissive collimator.

22. A spectrometer as in claim 1, wherein the transmissive collimator comprises at least one cylindrically shaped lens.

23. A spectrometer as in claim 1, wherein the transmissive collimator, diffraction grating, and / or optical detector are mounted on the same substrate.

24. A spectrometer as in claim 23, wherein the substrate comprises glass, fused quartz, and / or a ceramic.

25. A spectrometer as in claim 23, wherein the substrate has a thickness of greater than or equal to 1 mm and less than or equal to 15 mm.

26. A spectrometer as in claim 1, wherein a thermally insulating material is disposed on and / or adjacent to at least one wall of an enclosure of the spectrometer.42#14429996vl27. A spectrometer as in claim 1, wherein a thermally insulating material is disposed on and / or adjacent to two or more walls of an enclosure of the spectrometer.

28. A spectrometer as in claim 1, wherein the spectrometer is positioned in a bank of spectrometers comprising two or more adjacent spectrometers.

29. A spectrometer as in claim 28, wherein an insulating material is disposed on and / or adjacent to at least one side of the bank of spectrometers.

30. A spectrometer as in claim 28, further comprising a heating element disposed on and / or adjacent to at least one wall of an enclosure of the spectrometer and / or at least one side of the bank of spectrometers.

31. A spectrometer as in claim 28, further comprising a temperature sensor configured to measure the temperature within the spectrometer and / or within one or more spectrometers in the bank of spectrometers.

32. A spectrometer as in claim 26, wherein the thermally insulating material comprises silicone foam.43#14429996vl

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