Methods for noise suppression during optical measurements

Abstract

Techniques for noise suppression during optical measurements, associated instruments, associated methods, and associated non-transitory computer-readable media are generally provided. Some techniques described herein are particularly suitable for use in suppressing noise in optical data indicating an optical signal received from a probe while the probe is at least partially inserted into a container and while the container is undergoing agitation. Some instruments described herein are configured for noise suppression during optical measurements as described herein. Some methods described herein perform noise suppression during optical measurements as described herein. Some non-transitory computer- readable-media described herein include processor-executable instructions for noise suppression during optical measurements as described herein.

Description

[0001] S2164.70013US00

[0002] BA2411-US-PRO

[0003] METHODS FOR NOISE SUPPRESSION DURING OPTICAL MEASUREMENTS

[0004] RELATED APPLICATIONS

[0005] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No.: 63 / 728,990, filed December 6, 2024, under Attorney Docket No.: S2164.70013US00, and entitled “METHODS FOR NOISE SUPPRESSION DURING OPTICAL MEASUREMENTS,” which is incorporated herein by reference in its entirety.

[0006] FIELD

[0007] Techniques for suppressing noise during optical measurements, associated instruments, associated methods, and associated non-transitory computer-readable media are generally described.

[0008] BACKGROUND

[0009] Sensors may be employed to optically detect characteristics of a sample under test. For example, a probe may be inserted into a container to obtain an optical signal indicating characteristics of a liquid sample held by the container.

[0010] Accordingly, new techniques for noise suppression during optical measurements, associated instruments, and methods of use thereof would be beneficial.

[0011] SUMMARY

[0012] The present disclosure generally describes techniques for suppressing noise during optical measurements, associated instruments, associated methods, and associated non- transitory computer-readable media. 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.

[0013] In some embodiments an instrument is provided. The instrument comprises a probe configured to transmit light while the probe is at least partially inserted into a container and while the container is undergoing agitation, an optical detector configured to receive, from the probe over time, an optical signal, and a processor operatively coupled to memory. The optical signal comprises a first portion of the light reflected by an interface internal to the probe and a second portion of the light reflected by an end of the probe. The processor is configured to obtain optical data based on electrical signals produced by the optical detector over time indicating intensity of the optical signal and filter fixed-frequency components S2164.70013US00

[0014] BA2411-US-PRO from the optical data to produce filtered optical data, the fixed-frequency components corresponding to reflection of the light from a surface of the container.

[0015] In some embodiments, a method is provided. The method comprises transmitting, by a probe, while the probe is at least partially inserted into a container and the container is undergoing agitation, light, receiving, by an optical detector of an instrument over time, from the probe of the instrument, an optical signal, obtaining, by a processor of the instrument operatively coupled to memory of the instrument, optical data based on electrical signals produced by the optical detector over time indicating intensity of the optical signal, and filtering, by the processor, fixed-frequency components from the optical data to produce filtered optical data. The optical signal comprises a first portion of the light reflected by an interface internal to the probe and a second portion of the light reflected by an end of the probe. The fixed-frequency components corresponding to reflection of the light from a surface of the container.

[0016] In some embodiments, a non-transitory computer-readable medium is provided. The non-transitory computer-readable medium has instructions stored thereon that, when executed by a processor operatively coupled to memory, cause the processor to perform a method. The method comprises obtaining optical data based on electrical signals produced by an optical detector of an instrument over time indicating intensity of an optical signal and filtering, by the processor, fixed-frequency components from the optical data. The optical signal is received by the optical detector from a probe of the instrument while the probe is at least partially inserted into a container while the container is undergoing agitation. The optical signal comprises a first portion of light transmitted by the probe and reflected by an interface internal to the probe and a second portion of the light reflected by an end of the probe. The fixed-frequency components correspond to reflection of the light from a surface of the container.

[0017] Other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments of the disclosure 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. S2164.70013US00

[0018] BA2411-US-PRO

[0019] BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Non-limiting embodiments of the present disclosure 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 disclosure shown where illustration is not necessary to allow those of ordinary skill in the art to understand the disclosure. In the figures:

[0021] FIG. 1 shows one non-limiting example of an instrument including processing circuitry configured to suppress noise during an optical measurement, in accordance with some embodiments;

[0022] FIG. 2 shows one non-limiting example of a system including an instrument including processing circuitry configured to suppress noise during an optical measurement, in accordance with some embodiments;

[0023] FIG. 3 shows one non-limiting example of a container including a plurality of container portions, in accordance with some embodiments;

[0024] FIG. 4A shows a non-limiting example of an optical signal including a first portion of transmitted light reflected from an interface internal to a probe and a second portion of transmitted light reflected from an end of the probe, in accordance with some embodiments;

[0025] FIG. 4B shows a non-limiting example of relative light intensity vs. wavelength for the optical signal of FIG. 4 A, in accordance with some embodiments;

[0026] FIG. 5A shows a non-limiting example of an optical signal including a first portion of transmitted light reflected from the interface internal to the probe of FIG. 4A and a second portion of transmitted light reflected from the end of the probe having a species immobilized thereon, in accordance with some embodiments;

[0027] FIG. 5B shows a non-limiting example of relative light intensity vs. wavelength for the optical signal of FIG. 5 A, in accordance with some embodiments;

[0028] FIG. 6 shows a non-limiting example of measurement data flow in an instrument described herein, in accordance with some embodiments;

[0029] FIG. 7 shows amplitude over time for a non-limiting example of optical data received from an optical detector and for the same optical data filtered to remove noise, in accordance with some embodiments;

[0030] FIG. 8A shows amplitude over frequency up to 40 Hz for the optical data and the fdtered optical data of FIG. 7, in accordance with some embodiments; S2164.70013US00

[0031] BA2411-US-PRO

[0032] FIG. 8B shows amplitude over frequency up to 1 Hz for the filtered optical data of FIG. 7, in accordance with some embodiments;

[0033] FIG. 9A shows amplitude over time for a non-limiting example of optical data received from an optical detector indicating content of optical signals received from a plurality of probes, in accordance with some embodiments;

[0034] FIG. 9B shows amplitude over time for the same optical data as shown in FIG. 9A fdtered to remove noise, in accordance with some embodiments;

[0035] FIG. 9C shows root- mean- squared (RMS) content of the optical data and filtered optical data shown in FIGs. 9A and 9B, respectively, in accordance with some embodiments;

[0036] FIG. 10 shows a non-limiting example method of noise suppression during an optical measurement, in accordance with some embodiments; and

[0037] FIG. 11 shows non-limiting example processing circuitry that may be configured to suppress noise during an optical measurement, in accordance with some embodiments.

[0038] DETAILED DESCRIPTION

[0039] Techniques for noise suppression during optical measurements, associated instruments, associated methods, and associated non-transitory computer-readable media are generally provided. Some techniques described herein are particularly suitable for use in suppressing noise in optical data indicating an optical signal received from a probe while the probe is at least partially inserted into a container and while the container is undergoing agitation. Some instruments described herein are configured for noise suppression during optical measurements as described herein. Some methods described herein perform noise suppression during optical measurements as described herein. Some non-transitory computer- readable-media described herein include processor-executable instructions for noise suppression during optical measurements as described herein.

[0040] In some embodiments, suppression of noise from optical measurements provides a more accurate optical data stream that is more conducive to downstream analysis. Advantageously, this may allow for more accurate characterization of a sample being measured using a sensitive probe. For example, periodic reflections (e.g., from agitation of the container holding the sample) that may be undesirably included in an optical signal obtained from a probe may be filtered out to make the remainder of the optical signal (e.g., indicating characteristics of a sample contacted with the probe) easier to process.

[0041] In some embodiments, noise suppression in an optical measurement may target fixed- frequency components corresponding to reflection of light that is transmitted by a probe and S2164.70013US00

[0042] BA2411-US-PRO reflected from a surface of a container into which the probe is at least partially inserted while the container is undergoing agitation. For example, the probe may provide an optical signal to an optical detector over time, which may include reflections from the container having a fixed oscillatory period due to agitation of the container into which the probe is inserted. For instance, reflections from the container may peak periodically in the optical signal, corresponding to periodic agitation of the container, which may cause a particular portion of the container to be illuminated by the probe and reflect light back into the probe at a fixed point in time within each period of agitation.

[0043] In some embodiments, a processor operatively coupled to memory may be configured to filter fixed-frequency components from optical data indicating intensity of an optical signal received from a probe. For example, the processor may be configured to obtain optical data based on electrical signals produced by an optical detector, which in turn may be configured to receive the optical signal from the probe over time. For instance, the processor may be configured to filter the optical data to produce filtered optical data that suppresses (e.g., mitigates and / or omits entirely) the fixed-frequency components. Advantageously, suppressing fixed-frequency components using processing components internal to an instrument (e.g., internal to an instrument further including the probe and optical detector) improves the quality of measurement data to be output from the instrument (e.g., for data communication and / or visualization), which may optionally be performed in real time. It should be appreciated that, while noise being suppressed from an optical signal output from an instrument may enter the optical signal during the optical measurement process, the process of noise suppression need not be performed during the optical measurement process or shortly thereafter (e.g., in real-time).

[0044] In some embodiments, noise suppression techniques described herein may be adapted for a probe configured to provide an optical signal that includes a first portion of light that is transmitted by the probe and reflected by an interface internal to the probe and a second portions of the light that is transmitted by the probe and reflected by an end of the probe. For example, characterization of a sample (e.g., a species immobilized to the end of the probe) may be determined based on interference between the first portion of the light and the second portion of the light (e.g., based on the optical data indicating intensity of the optical signal). For instance, the relative intensities of the first portion of the light and the second portion of the light may be indicated in spectral content of the optical signal.

[0045] FIG. 1 shows one non-limiting example of an instrument 100 configured to suppress noise during an optical measurement, in accordance with some embodiments. S2164.70013US00

[0046] BA2411-US-PRO

[0047] As shown in FIG. 1, the instrument 100 includes a probe 110, an optical detector 120, and a processor 130. In some embodiments, the probe 110 may be configured to produce an optical signal 118 that the optical detector 120 may be configured to receive, and the processor 130 may be configured to obtain optical data 122 based on electrical signals produced by the optical detector 120 indicating content of the optical signal. In some embodiments, the processor 130 may be configured to output measurement data, which may include filtered optical data 132 as shown in FIG. 1. For example, the filtered optical data 132 may include content from the optical data 122 and omit noise that the processor 130 may be configured to suppress, as described further herein.

[0048] In some embodiments, the probe 110 may be configured to transmit light. For example, the probe 110 may include an optical waveguide 116 configured to propagate light toward the container and / or to propagate the optical signal to the optical detector, such as using total internal reflection along a length of the probe 110. For instance, the instrument 100 may include a light source from which the probe 110 may be configured to receive and transmit light, such as via a cable configured to transmit the light from the light source to the probe 110. In other embodiments, the probe 110 may be configured to transmit light received from an external component (e.g., a light source of a surrounding system that includes and / or interfaces with the instrument 100).

[0049] In some embodiments, the optical detector 120 may be configured to receive the optical signal 118 from the probe 110 over time, the optical signal 118 including light reflected by the probe 110. For example, the optical signal 118 may comprise a first portion Pl of the light reflected by an interface 114 internal to the probe 110 and a second portion P2 of the light reflected by the end 112 of the probe 110. For example, the interface 114 may be a boundary between different materials within the probe 110, such as materials having different refractive indices such that the boundary reflects the transmitted light back down the probe 110. Similarly, the end 112 of the probe may be configured as a boundary between material of the probe 110 and material beyond the end 112 of the probe 110, which may have different refractive indices such that the boundary reflects the transmitted light back down the probe 110. In some embodiments, the optical detector 120 may include a spectrometer configured to produce electrical signals over time indicating spectral content of the optical signal 118, such as a spectral distribution of intensity of the optical signal over time. For example, as described further herein, the portions Pl and P2 may interfere to produce different optical signal intensities over the spectrum of the optical signal 118, which may indicate the relative intensities of the portions Pl and P2. S2164.70013US00

[0050] BA2411-US-PRO

[0051] In some embodiments, the instrument 100 may further include a cable configured to transmit the optical signal 118 from the probe 110 to the optical detector 120. For example, the cable may include an optical fiber cable configured to propagate the optical signal 118 from the probe 110 to the optical detector 120. For instance, the cable may be included in the instrument 100, and / or may be included in a system that includes or is configured to interface with the instrument 100. In some embodiments, the optical detector 120 may have a port configured to receive a cable from the probe 110 to receive the optical signal 118.

[0052] In some embodiments, the probe 110 may be configured to transmit (or at least capable of transmitting) light while the probe 110 is at least partially inserted into a container 102. For example, the optical signal 118 produced by the probe 110 when at least partially inserted into the container 102 may indicate characteristics of a liquid 104 held by the container 102. For instance, the liquid 104 may include a species to be measured based on the optical signal 118 produced by the probe 110 while the probe end 112 contacts the liquid 104. In some embodiments, the second portion P2 of the light may be reflected by an interface between the probe end 112 and a species immobilized on the probe 110. In some embodiments, the instrument 100 may be configured to insert the probe 110 into the container 102. For example, the instrument 100 may include and / or be configured to interface with a motor that is configured to insert the probe 110 into the container 102.

[0053] In some embodiments, the probe 110 may be configured to transmit (or at least capable of transmitting) light while the container 102 is undergoing agitation 108a, 108b. For example, the container 102 may be agitated (e.g., by an agitator not shown in FIG. 1) periodically to move the liquid 104 within the container 102, which may prevent species in the liquid 104 from settling in a location where the species would not be detected using the probe 110. As shown in FIG. 1, agitation 108a may occur in a direction that is transverse (e.g., orthogonal) with respect to a direction in which the probe 110 is inserted into the container 102, and / or agitation 108b may occur in a direction that is substantially parallel to the direction in which the probe 110 is inserted into the container.

[0054] In some embodiments, the processor 130 may be operatively coupled to memory and configured to obtain the optical data 122 based on electrical signals produced by the optical detector 120 over time indicating intensity of the optical signal 118. For example, the optical data 122 may include the electrical signals, and / or the optical data 122 may indicate content of the electrical signals. In some embodiments, the processor 130 may be in electrical communication with the optical detector 120 to receive the optical data 122 including the electrical signals directly, and / or the processor 130 may be configured to receive the optical S2164.70013US00

[0055] BA2411-US-PRO data 122 from an intermediary component that receives the electrical signals from the optical detector 120. According to various embodiments, the processor 130 and optical detector 120 may be connected directly or indirectly (e.g., via an intermediary component) via traces on a circuit board on which the processor 130 and optical detector 120 are mounted and / or via electrical connectors on circuit boards on which the processor 130 and optical detector 120 are mounted, respectively. According to various embodiments, the processor 130 may include a general-purpose central processing unit (CPU), a graphics processing unit (GPU) (e.g., configured for enhanced parallel processing with respect to some CPUs), and / or an application specific integrated circuit (ASIC) and / or field-programmable gate array (FPGA) configured for digital signal processing. In some embodiments, the processor 130 may be operatively coupled to memory configured to store configuration instructions and / or parameters (e.g., predetermined thresholds and / or settings), e.g., for detecting contact between the probe 110 and the liquid surface 106.

[0056] In some embodiments, the processor 130 may be further configured to filter fixed- frequency components from the optical data 122 to produce the filtered optical data 132, the fixed- frequency components corresponding to reflection of the light from a surface 106 of the container 102. For example, as shown in FIG. 1, the optical signal 118 may (e.g., inadvertently) include a third portion P3 of the light reflected by the container surface 106, which may appear in the optical signal within the fixed-frequency components. In some embodiments, the fixed-frequency components may correspond to a frequency of the agitation 108a, 108b (e.g., and harmonics thereof) of the container 102. For example, the agitation 108a, 108b may cause reflections from the container surface 106 to appear periodically at the frequency of the agitation 108a, 108b (and harmonics thereof), which may inadvertently result in the third portion P3 of the light reflected from the container surface 106 to be present in the optical signal 118. For instance, the frequency of the agitation 108a, 108b (e.g., 1000 RPM, which is about 16.6 Hz) may be less than one-half of a sample rate at which the optical detector 120 is configured to observe the optical signal 118 (e.g., 40 Hz), such that the frequency of the agitation 108a, 108b is low enough to be captured in the electrical signals produced by the optical detector 120 indicating content of the optical signal 118. In some embodiments, the processor 130 may be configured to apply a notch filter to the optical data 122, with notches of the notch filter being based on the frequency of agitation 108a, 108b of the container 102, as described further herein.

[0057] In some embodiments, the optical data 122 may comprise a first set of optical measurements received by the processor 130 from the optical detector 120, and the S2164.70013US00

[0058] BA2411-US-PRO instrument 100 may be configured to output the filtered optical data 132 at least in part while the processor 130 receives a next set of optical measurements from the optical detector 120. For example, the first set of optical measurements may include a plurality of frames at a sample rate of the optical detector, and at least some frames of the next set of optical measurements may be received (e.g., represented in optical data 122) at the processor 130 while at least some of the filtered optical data 132 is being output. For instance, the processor 130 may be configured to receive the optical data 122 and filter out fixed- frequency components of the optical data 122 in real-time, though embodiments described herein are not so limited.

[0059] In some embodiments, the processor may be further configured to determine interference between the first portion Pl of the light and the second portion P2 of the light based on the optical data 122. For example, the first portion Pl and the second portion P2 of the light may interfere to cause different relative intensities over the spectrum of the optical signal 118, from which the processor 130 may be configured to determine the relative intensities and thus interference of the respective reflections. In some embodiments, the processor 130 may be configured to determine the interference based on results of crosscorrelation of spectral content of portions of the optical data 122 sampled over time. For example, the optical data 122 may indicate spectral samples of the optical signal 118, each of which may indicate intensity of the optical signal over wavelength at a given time, and the processor 130 may be configured to cross-correlate spectral samples of the optical signal 118 to determine the interference based on spectral changes of the optical signal 118 over time (e.g., between spectral samples).

[0060] In some embodiments, the processor may be further configured to identify fixed- frequencies at which to filter out fixed-frequency components of the optical data 122 based on correlated samples of the optical signal 118. For example, the processor 130 may be configured to receive and cross-correlate spectral samples of the optical signal 118 (e.g., of the optical data 122), in which periodic reflections from the container surface 106 due to container agitation 108a, 108b may be present and identified by concentration of amplitude at a fixed-frequency. For instance, in cross-correlating spectral samples of the optical signal 118, the fixed-frequency of the container agitation 108a, 108b may be transformed into a different but still fixed frequency, which the processor 130 may be configured to identify and set for filtering out the fixed-frequency components from the optical data 122. In other embodiments, the processor 130 may be configured to filter out fixed-frequency components S2164.70013US00

[0061] BA2411-US-PRO at the known fixed frequency of container agitation 108a, 108b (e.g., 1000 RPM, which is about 16.6 Hz).

[0062] FIG. 2 shows one non-limiting example of a system 200 including an instrument 100 configured to suppress noise during an optical measurement, in accordance with some embodiments.

[0063] As shown in FIG. 2, the system 200 further includes a controller 210, a light source 220, a motor 230, a container agitator 240, a display 250, and a data communication interface 260. For example, the controller 210 may be configured to operate the light source 220 to transmit light to the probe 110, operate the motor 230 to insert the probe 110 into a container (e.g., 102 in FIG. 1), and / or operate the container agitator 240 to agitate the container (e.g., 108a, 108b in FIG. 1). For instance, the controller 210 may include a processor (e.g., as described herein for processor 130). In FIG. 2, the light source 220, motor 230, and container agitator 240 are part of the system 200 that includes the instrument 100, though in other embodiments the instrument 100 may alternatively or additionally include a light source, motor, and / or container agitator.

[0064] In some embodiments, the instrument 100 may be further configured to output, to a user interface and / or via a data communication interface, filtered optical data (e.g., 132). For example, in FIG. 2, the processor 130 of the instrument 100 is shown configured to output the filtered optical data 132 to the controller 210, which in turn may be configured to output the filtered optical data 132 to the display 250 for displaying to a user (e.g., in a user interface displayed on the display 250) and / or to the data communication interface 260 (e.g., a universal serial bus (USB)). For instance, the filtered optical data 132 may suppress noise from fixed-frequency components when visualized on the display 250 and / or when processed downstream by a device that receives the measurement data 132 via the data communication interface 260.

[0065] FIG. 3 shows one non-limiting example of a container 300 including a plurality of container portions 302, in accordance with some embodiments.

[0066] In some embodiments, the container 300 may be configured as described herein for the container 102. For example, each portion 302 of the container 300 may be configured to hold liquid, undergo agitation, and receive an inserted probe (e.g., 110), which may be configured to produce an optical signal indicating characteristics of the liquid as described herein (e.g., including undesired reflections from the container portion 302). In some embodiments, the portions 302 may be configured similarly to one another, such as having a same volume. In some embodiments, the portions 302 may be connected together (e.g., S2164.70013US00

[0067] BA2411-US-PRO formed integrally) as the container 300, whereas in other embodiments, the portions 302 may be separate and held together (e.g., by an underlying tray).

[0068] In some embodiments, a plurality of probes (e.g., 110) may be inserted into a respective subset of the container portions 302 (e.g., along an insertion direction normal to the illustrated openings of the container portions 302). For example, a motor (e.g., 230) of an instrument (e.g., 100) that includes the probe and / or of a system (e.g., 200) that includes the instrument may be configured to move (or at least capable of moving) the probes in a direction normal to the illustrated openings of the container portions 302 to insert the probes into the container portions 302, respectively. It should be appreciated that insertion of probes into the container portions 302 might alternatively or additionally be achieved by moving the container portions 302 relative to the probes, as embodiments described herein are not so limited.

[0069] In some embodiments, a plurality of probes may be further configured to be (or at least capable of being) moved (e.g., by an instrument and / or system including the instrument) between a first subset of the container portions 302 and a second subset of the container portions 302 (e.g., which may alternatively or additionally hold liquid). For example, prior to or after insertion of the probes into the first subset of the container portions 302, the probes may be translated (e.g., in a translation direction transverse and / or orthogonal to the direction of insertion into the container portions 302) toward the second subset of the container portions 302 for insertion. For instance, insertion of the probes into liquid (e.g., 104) held by the first subset of the container portions 302 may bind species to the probe ends (e.g., 112), and translating the probes to the second subset of the container portions 302 holding liquid (e.g., 104) and inserting the probe ends into the second subset of the container portions 302 to contact the liquid may disassociate the species that were bound to the probe ends.

[0070] In some embodiments, fewer probes may be included in an instrument than container portions 302 of a container 300, with the probes being translated between and inserted into subsets of container portions 302. In other embodiments, the same number or more probes than container portions 302 may be included, such as by inserting a different group of probes into a subset of container portions 302 after translating the previously inserted group of probes to another subset of container portions 302 for insertion, and / or by not inserting all probes into container portions 302 at any given time. It should be appreciated that probes may be inserted only into one respective subset of the container portions 302, as embodiments described herein are not so limited. S2164.70013US00

[0071] BA2411-US-PRO

[0072] FIG. 4A shows a non-limiting example of an optical signal including a first portion of transmitted light reflected from an interface 414 internal to a probe 410 and a second portion of transmitted light reflected from an end 412 of the probe 410, in accordance with some embodiments.

[0073] In some embodiments, the probe 410 may be configured to transmit light and to reflect light from the interface 414 and from the probe end 412, such as described herein for the probe 110.

[0074] FIG. 4B shows a non-limiting example of relative light intensity vs. wavelength for the optical signal of FIG. 4A, in accordance with some embodiments.

[0075] In some embodiments, the probe 410 may be configured to transmit broadband light and produce an optical signal including reflected portions of light that interfere to produce different relative intensities over the spectrum with respect to the transmitted light. For example, in FIG. 4A, the probe 410 is shown transmitting white light, whereas FIG. 4B shows the resulting optical signal having non-uniform intensity over the spectrum due to interference between the portions of reflected light. For instance, the relative intensities at various wavelengths over the spectrum may provide an indication of presence or absence of a particular species (e.g., a bound species and / or a liquid surface), an amount of a particular species, and / or an identity of a species at the probe end 412. In some embodiments, the probe 410 may be configured as a biolayer interferometry (BLI) probe.

[0076] FIG. 5A shows a non-limiting example of an optical signal including a first portion of transmitted light reflected from the interface 414 internal to the probe 410 and a second portion of transmitted light reflected from the end 412 of the probe 410 having a species 420 immobilized thereon, in accordance with some embodiments.

[0077] As shown in FIG. 5 A, a species 420 is bound to the probe end 412, such as may occur when the probe end 412 is treated with a binding entity and inserted into liquid including the species 420.

[0078] FIG. 5B shows a non-limiting example of relative light intensity vs. wavelength for the optical signal of FIG. 5A, in accordance with some embodiments.

[0079] As shown in FIG. 5B, the relative intensities of the optical signal over the spectrum are different with respect to the optical signal of FIG. 4B, such as due to the impact of the bound species 420 on the amount of light reflected from the probe end 412 in the optical signal of FIG. 4B as compared to the optical signal of FIG. 4A in which no species 420 is bound. S2164.70013US00

[0080] BA2411-US-PRO

[0081] FIG. 6 shows a non-limiting example of measurement data flow in an instrument described herein, in accordance with some embodiments.

[0082] In some embodiments, the instrument 600 may be configured as described herein for the instrument 100, such as including an optical detector 620 and processor 630, which may be configured as described herein for the optical detector 120 and processor 130, respectively. Also shown in FIG. 6 is memory 640 operatively coupled to processor 630, which may be configured as transitory and / or non-transitory memory.

[0083] In some embodiments, the processor 630 may be configured to obtain optical data 622 at least in part by receiving, from the optical detector 620, optical measurements 621 observed by the optical detector 620 over time and cross-correlating the optical measurements 621. For example, in FIG. 6, processor 630 is shown receiving optical measurements 621 from optical detector 620, storing the optical measurements 621 in memory 640, and cross-correlating a first optical measurement Ml of the optical measurements 621 and a second optical measurement M2 of the optical measurements 621 to obtain the optical data 622. For instance, the processor 630 is shown executing a storage process 642 to store the optical measurements 621 in the memory 640, loading the first optical measurement Ml and the second optical measurement M2 from the memory 640, and executing a cross-correlation process 644 on the first measurement Ml and the second optical measurement M2.

[0084] In some embodiments, the optical measurements 621 may include respective spectral samples of an optical signal (e.g., 118) received by the optical detector 620 from a probe (e.g., 110). For example, the spectral samples may indicate, at a given time, relative intensity of portions of light (e.g., reflected from an internal probe interface and a probe end, respectively) in an optical signal received by the optical detector 620. For instance, the spectral samples may include electrical signals (e.g., digital representations of analog signals) generated by the optical detector over a spectrum of wavelengths indicating intensity of light received at a plurality of discrete points along the spectrum. In some embodiments, crosscorrelation of the spectral samples may indicate an overall change in spectral content over time in the optical signal. For example, a cross-correlation of a pair of spectral samples may indicate quantitatively an extent of wavelength shift in relative intensity peaks between the spectral samples.

[0085] In some embodiments, the processor 630 may be configured to filter fixed-frequency components of the optical data 622 to produce filtered optical data 632. For example, the processor 630 may be configured to apply a notch filter to the fixed-frequency components of S2164.70013US00

[0086] BA2411-US-PRO the optical data 622, which may include light reflected from a surface (e.g., 106) of a container (e.g., 102) into which the probe (e.g., 110) is inserted. For instance, the fixed- frequency components may include a frequency of agitation of the container and harmonics thereof. In some embodiments, the fixed-frequency components of the optical data 622 may correspond to, but differ in frequency from, a frequency of agitation of the container and harmonics thereof. For example, in cross-correlating optical measurements 621 over time, the resulting optical data 622 may transform spectral content from the optical measurements 621. For instance, where the optical measurements 621 include spectral samples received at a sample rate (e.g., 40 Hz), the spectral content of the optical data 622 resulting from crosscorrelation may have a bandwidth of 40 Hz, and the fixed-frequency components may include frequencies within that bandwidth that do not align with the frequency of agitation and harmonics thereof.

[0087] In some embodiments, the processor 630 may be further configured to determine the frequency or frequencies of the fixed-frequency components to be filtered (e.g., during a calibration process) by cross-correlating spectral samples (e.g., having known or expected content) and identifying fixed-frequencies in one or more sets of cross-correlated spectral samples that have at least a threshold amplitude (e.g., normalized to other frequencies in the band) or difference in amplitude with respect to neighboring frequencies (e.g., relative peaks). Alternatively or additionally, in some embodiments, the frequency or frequencies of the fixed-frequency components may be predetermined and set in memory (e.g., 640).

[0088] In some embodiments, the processor 630 may be configured to determine a frequency or frequencies of fixed-frequency components to be filtered based on values input to the instrument (or to a system that includes the instrument) by a user. For example, where the frame rate of the optical detector and the frequency of agitation of the container are input by a user, a frequency famay be determined using the following equation: where ac is the frame rate of the optical detector (in Hz), round is a function that takes any number as an input and outputs the nearest integer, and fnis the nth integer harmonic of the frequency sc of agitation of the container in rotations per minute (RPM). In this example, the Nyquist frequency for the frame rate ac may be equal to The nth integer harmonic fnmay be defined by the following equation: r

[0089] ^■= n’SC S2164.70013US00

[0090] BA2411-US-PRO

[0091] As an illustrative example, where the frame rate ac is 40 Hz and the frequency of agitation of the container sc is 1000 RPM, the first four harmonics (i.e., n=l to n=4) may be 16.67 Hz, 33.33 Hz, 50 Hz, and 66.67 Hz, respectively, and the corresponding frequencies for fixed- frequency components to be filtered out may be 16.67 Hz, 6.67 Hz, 10 Hz, and 13.33 Hz, respectively. It should be appreciated that the above equations are not limited to determining a frequency or frequency based on user inputs, as the above equations may be alternatively or additionally applied where values are predetermined (e.g., stored in memory) and / or determined in another way.

[0092] While the processor 630 is described as configured to receive optical measurements 621 for a single probe, it should be appreciated that the processor 630 may be configured to receive optical measurements for a plurality of probes, such as when the optical detector 620 is configured to receive optical measurements 621 from the plurality of probes, and / or where the processor 630 is configured to receive optical measurements 621 from a plurality of optical detectors each configured to receive an optical signal from one or more probes.

[0093] While only a first optical measurement Ml and a second optical measurement M2 are shown being cross-correlated in FIG. 6, it should be appreciated that any number of optical measurements 621 received over time from the optical detector 620 may be cross-correlated, such as 3, 4, or 5 optical measurements 621. For example, including additional spectral samples in cross-correlation may further emphasize strict or substantially strict increases and / or decreases in wavelength of peak relative intensity of an optical signal over time. For instance, a strict increase may occur over each of a set of cross-correlated spectral samples whereas a substantially strict increase may occur over a majority of a set of cross-correlated spectral samples.

[0094] While the processor 630 is shown executing the storage process 642, cross-correlation process 644, and filter process 646 in FIG. 6, it should be appreciated that instructions for these processes may be distinct or at least partially combined with one another in storage and / or at time of execution, as organization of the process flow may vary. Moreover, it should be appreciated that these processes may be performed sequentially, simultaneously, and / or at least partially simultaneously (e.g., cross-correlation may begin by loading the first measurement data Ml prior to reception and / or storage of the second measurement data M2).

[0095] FIG. 7 shows amplitude over time for optical data received from an optical detector and for the same optical data filtered to remove noise, in accordance with some embodiments.

[0096] In some embodiments, the optical data (“Original”) shown in FIG. 7 may be obtained by cross-correlating spectral samples received from an optical detector (e.g., 120) over time S2164.70013US00

[0097] BA2411-US-PRO indicating content of an optical signal received from a probe (e.g., 110), and the filtered optical data (“Filtered”) shown in FIG. 7 may be obtained by filtering out fixed-frequency components corresponding to reflection of light from a surface (e.g., 106) of a container (e.g., 104) into which the probe is inserted.

[0098] As shown in FIG. 7, the filtered optical data have a significantly smaller peak-to-peak amplitude of oscillation than the optical data while having substantially the same central operating point about which the oscillations occur. For example, the reduction in peak-to- peak amplitude may correspond to removing oscillations at fixed-frequencies corresponding to reflections from a container surface, which may not contribute to downstream processing of the data closer to or at the central operating point about which the oscillations occur.

[0099] FIG. 8A shows amplitude over frequency up to 40 Hz for the optical data and the filtered optical data of FIG. 7, in accordance with some embodiments.

[0100] As shown in FIG. 8A, the optical data and filtered optical data have frequency content from 0 Hz to 40 Hz, and the optical data shows peaks in content around 5 Hz, 10 Hz, 16 Hz, and 17 Hz that are significantly reduced in the filtered optical data. For example, these frequencies may be subject to one or more notch filters applied by a processor (e.g., 130) that reduces content in fixed-frequency components in the filtered optical data as compared to the optical data. For instance, these fixed-frequencies may correspond to a frequency of agitation of the container and harmonics thereof, as transformed by the cross-correlation process.

[0101] FIG. 8B shows amplitude over frequency up to 1 Hz for the filtered optical data of FIG. 7, in accordance with some embodiments.

[0102] As shown in FIG. 8B, the filtered optical data exhibits a sharp falloff in amplitude from a peak at 0 Hz, indicating that substantially all of the content of the filtered optical data may occur at or close to 0 Hz. For example, content of the optical data at or close to 0 Hz may be substantially unimpacted by notch filters applied to fixed-frequency components corresponding to reflections from a surface of a container.

[0103] FIG. 9A shows amplitude over time for optical data received from an optical detector indicating content of optical signals received from a plurality of probes, in accordance with some embodiments. FIG. 9B shows amplitude over time for the same optical data as shown in FIG. 9A filtered to remove noise, in accordance with some embodiments. FIG. 9C shows root-mean-squared (RMS) content of the optical data and filtered optical data shown in FIGs. 9A and 9B, respectively, in accordance with some embodiments.

[0104] In FIG. 9A, optical data for 8 channels (“Chi,” “Ch2,” “Ch3,” “Ch4,” “Ch5,” “Ch6,” “Ch7,” “Ch8,”) is plotted over time. In some embodiments, the optical may be obtained in the S2164.70013US00

[0105] BA2411-US-PRO manner described herein in connection with FIG. 7. For example, each trace may be obtained by cross-correlating spectral samples received from an optical detector (e.g., 120) over time indicating content of an optical signal received from a respective probe (e.g., 110). According to various embodiments, the same optical detector may be used and / or separate optical detectors may be used.

[0106] In FIG. 9B, filtered optical data for the 8 channels of FIG. 9A is plotted over time. In some embodiments, the filtered optical data may be obtained as described herein in connection with FIG. 7. For example, the filtered optical data shown for each channel may be obtained by filtering out fixed-frequency components from an optical signal of that channel corresponding to reflection of light from a surface (e.g., 106) of a container (e.g., 104) into which the respective probe is inserted. According to various embodiments, the same fixed- frequency components may be removed from multiple channels and / or different fixed- frequency components may be removed from multiple channels, respectively.

[0107] As in the example of FIG. 7, the filtered optical data for each channel in FIG. 9B is shown having a significantly smaller peak-to-peak amplitude of oscillation than the optical data for the corresponding channel while having substantially the same central operating point about which the oscillations occur.

[0108] As shown in FIG. 9C, the filtered optical data for each channel shows a reduction in RMS content with respect to the optical data for that channel, and the reduction is greater in channels having higher filtered optical data (e.g., indicating a greater change in spectral content over time via cross-correlation of samples).

[0109] FIG. 10 shows a non-limiting example method 1000 of noise suppression during an optical measurement, in accordance with some embodiments.

[0110] In some embodiments, method 1000 may be performed using an instrument described herein, such as instrument 100. For example, method 1000 is shown in FIG. 10 including a step 1002 of transmitting light, a step 1004 of receiving an optical signal, a step 1006 of obtaining optical data (e.g., 122), and a step 1008 of filtering the optical data. For example, step 1002 may include a probe (e.g., 110) transmitting light, step 1004 may include an optical detector (e.g., 120) receiving the optical signal from the probe, step 1006 may include a processor (e.g., 130) obtaining the optical data based on electrical signals produced by the optical detector over time indicating intensity of the optical signal, and step 1008 may include the processor filtering fixed-frequency components from the optical data to produce filtered optical data (e.g., 132), the fixed-frequency components corresponding to reflection of the light from a surface (e.g., 106) of a container (e.g., 102) into which the probe is inserted. For S2164.70013US00

[0111] BA2411-US-PRO instance, these steps may be performed as has been described herein for instruments and / or systems that include instruments.

[0112] FIG. 11 shows a non-limiting example processing circuitry 1100 that may be configured to suppress noise during an optical measurement, in accordance with some embodiments.

[0113] In some embodiments, suppression of noise in an optical measurement as described herein may be performed using processing circuitry 1100 (e.g., implemented using components mounted on and / or coupled to a substrate of an instrument). Processing circuitry 1100 may include one or more processors 1102 and one or more articles of manufacture that comprise non-transitory computer-readable storage media (e.g., memory 1104 and one or more non-volatile storage media 1106). The processor 1102 may control writing data to and reading data from the memory 1104 and the non-volatile storage device 1106 in any suitable manner, as the aspects of the disclosure provided herein are not limited in this respect. To perform any of the functionality described herein, the processor 1102 may execute one or more processor-executable instructions stored in one or more non-transitory computer- readable storage media (e.g., the memory 1104), which may serve as non-transitory computer-readable storage media storing processor-executable instructions for execution by the processor 1102.

[0114] In some embodiments, any method or method steps described herein as being performed by a processor may be stored as processor-executable instructions in a non- transitory computer-readable medium. For example, where processing steps to be executed by a processor are based on or in response to received data or signals (e.g., from an optical detector), the instructions may specify a format and / or type of content of the received data or signals designating those data or signals as the subject of the processing steps.

[0115] While several embodiments of the present disclosure 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 disclosure. 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 disclosure is / are used. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many S2164.70013US00

[0116] BA2411-US-PRO equivalents to the specific embodiments of the disclosure 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 disclosure may be practiced otherwise than as specifically described and claimed. The present disclosure 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 disclosure.

[0117] 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.

[0118] 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.”

[0119] 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.

[0120] 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 S2164.70013US00

[0121] BA2411-US-PRO

[0122] “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0123] 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.

[0124] 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.

[0125] 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 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.

Claims

S2164.70013US00BA2411-US-PROCLAIMS1. An instrument, comprising: a probe configured to transmit light while the probe is at least partially inserted into a container and while the container is undergoing agitation; an optical detector configured to receive, from the probe over time, an optical signal comprising: a first portion of the light reflected by an interface internal to the probe; and a second portion of the light reflected by an end of the probe; and a processor operatively coupled to memory and configured to: obtain optical data based on electrical signals produced by the optical detector over time indicating intensity of the optical signal; and filter fixed-frequency components from the optical data to produce filtered optical data, the fixed-frequency components corresponding to reflection of the light from a surface of the container.

2. The instrument of claim 1, wherein the probe comprises an optical waveguide configured to propagate the light toward the container and to propagate the optical signal to the optical detector.

3. The instrument of claim 1 or 2, wherein the processor is configured to obtain the optical data at least in part by: receiving, from the optical detector, a first optical measurement observed by the optical detector at a first time; receiving, from the optical detector, a second optical measurement observed by the optical detector at a second time following the first time; and cross-correlating the first optical measurement with the second optical measurement to produce the optical data.

4. The instrument of any one of claims 1 to 3, wherein the optical detector comprises a spectrometer and the electrical signals indicate a spectral distribution of intensity of the optical signal over time.

5. The instrument of any one of claims 1 to 4, wherein the fixed-frequency components correspond to a frequency of the agitation and harmonics thereof.S2164.70013US00BA2411-US-PRO6. The instrument of claim 5, wherein the optical detector is configured to observe the optical signal at a sample rate and the frequency of the agitation is less than one-half of the sample rate.

7. The instrument of any one of claims 1 to 6, wherein the instrument is configured to output, to a user interface and / or via a data communication interface, the filtered optical data.

8. The instrument of any one of claims 1 to 7, wherein: the optical data comprises a first set of optical measurements received by the processor from the optical detector; and the instrument is configured to output the filtered optical data at least in part while the processor receives a next set of optical measurements from the optical detector.

9. The instrument of any one of claims 1 to 8, wherein the second portion of the light is reflected by an interface between the end of the probe and a species immobilized on the probe.

10. The instrument of any one of claims 1 to 9, wherein the processor is further configured to determine interference between the first portion of the light and the second portion of the light based on the optical data.

11. The instrument of claim 10, wherein the processor is configured to determine the interference based on results of cross-correlation of spectral content of portions of the optical data sampled over time.

12. A method, comprising: transmitting, by a probe of an instrument, while the probe is at least partially inserted into a container and the container is undergoing agitation, light; receiving, by an optical detector of the instrument over time, from the probe of the instrument, an optical signal comprising: a first portion of the light reflected by an interface internal to the probe; and a second portion of the light reflected by an end of the probe;S2164.70013US00BA2411-US-PRO obtaining, by a processor of the instrument operatively coupled to memory of the instrument, optical data based on electrical signals produced by the optical detector over time indicating intensity of the optical signal; and filtering, by the processor, fixed-frequency components from the optical data to produce filtered optical data, the fixed-frequency components corresponding to reflection of the light from a surface of the container.

13. The method of claim 12, further comprising, by an optical waveguide of the probe: propagating the light toward the container; and propagating the optical signal to the optical detector.

14. The method of claim 12 or 13, wherein obtaining the optical data comprises: receiving, by the processor from the optical detector, a first optical measurement observed by the optical detector at a first time; receiving, by the processor from the optical detector, a second optical measurement observed by the optical detector at a second time following the first time; and cross-correlating, by the processor, the first optical measurement with the second optical measurement.

15. The method of any one of claims 12 to 14, wherein the optical detector comprises a spectrometer and the electrical signals indicate a spectral distribution of intensity of the optical signal over time.

16. The method of any one of claims 12 to 15, wherein the fixed-frequency components correspond to a frequency of the agitation and harmonics thereof.

17. The method of claim 16, wherein the optical detector observes the optical signal at a sample rate and the frequency of the agitation is less than one-half of the sample rate.

18. The method of any one of claims 12 to 17, further comprising outputting, by the instrument, to a user interface and / or via a data communication interface, the filtered optical data.

19. The method of claim 18, wherein:S2164.70013US00BA2411-US-PRO the optical data comprises a first set of optical measurements received by the processor from the optical detector; and outputting the filtered optical data is performed at least in part while the processor receives a next set of optical measurements from the optical detector.

20. The method of any one of claims 12 to 19, wherein the second portion of the light is reflected by an interface between the end of the probe and a species immobilized on the probe.

21. The method of any one of claims 12 to 20, further comprising, by the processor, determining interference between the first portion of the light and the second portion of the light based on the optical data.

22. The method of claim 21, wherein determining the interference is based on results of cross-correlation of spectral content of portions of the optical data sampled over time.

23. A non-transitory computer-readable medium having instructions stored thereon that, when executed by a processor operatively coupled to memory, cause the processor to perform a method, the method comprising: obtaining optical data based on electrical signals produced by an optical detector of an instrument over time indicating intensity of an optical signal, the optical signal received by the optical detector from a probe of the instrument while the probe is at least partially inserted into a container while the container is undergoing agitation, the optical signal comprising: a first portion of light transmitted by the probe and reflected by an interface internal to the probe; and a second portion of the light reflected by an end of the probe; and filtering, by the processor, fixed-frequency components from the optical data corresponding to reflection of the light from a surface of the container.

24. The non-transitory computer-readable medium of claim 23, wherein obtaining the optical data comprises: receiving, from the optical detector, a first optical measurement observed by the optical detector at a first time;S2164.70013US00BA2411-US-PRO receiving, from the optical detector, a second optical measurement observed by the optical detector at a second time following the first time; and cross-correlating the first optical measurement with the second optical measurement.

25. The non-transitory computer-readable medium of claim 23 or 24, wherein the fixed- frequency components correspond to an agitation frequency of the container and harmonics thereof.

26. The non-transitory computer-readable medium of claim 25, wherein the optical detector observes the optical signal at a sample rate and the agitation frequency is less than one-half of the sample rate.

27. The non-transitory computer-readable medium of any one of claims 23 to 26, wherein the optical detector comprises a spectrometer and the electrical signals indicate a spectral distribution of intensity of the optical signal over time.

28. The non-transitory computer-readable medium of any one of claims 23 to 27, wherein filtering the fixed-frequency components from the optical data comprises applying a bandstop filter comprising stop bands containing the fixed-frequency components.

29. The non-transitory computer-readable medium of any one of claims 23 to 28, wherein the second portion of the light is reflected by an interface between the end of the probe and a species immobilized on the probe.

30. The non-transitory computer-readable medium of any one of claims 23 to 29, wherein the method further comprises determining interference between the first portion of the light and the second portion of the light based on the optical data.

31. The non-transitory computer-readable medium of claim 30, wherein determining the interference is based on results of cross-correlation of spectral content of portions of the optical data sampled over time.

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