Systems and methods for calibrating a sample positioning system using spectral measurements

Abstract

An example calibration system calibrates motion of a sample positioning system included in a spectroscopy system by determining one or more positions associated with one or more features of a calibration sample supported by the sample positioning system based on one or more spectral measurements output by the spectroscopy system. The calibration system generates calibration data for calibrating motion of the sample positioning system along x and y axes of the sample positioning system based on the one or more positions.

Description

Technical Field

[0001] This description generally relates to methods and systems for spectroscopy, and more specifically to sample positioning systems included in spectroscopy systems that use spectral measurements for calibration. Background of the Invention

[0002] Spectroscopy is a technique used to identify the properties of a sample (e.g., a gaseous, liquid, and / or solid sample) by directing light onto the sample and detecting the light leaving the sample using a photosensitive detector. The detected light (such as changes in wavelength) is analyzed to provide information about the sample's composition, its chemical bonds, and / or other characteristics. This chemical analysis can be performed using infrared light, Raman scattering light, or other types of light.

[0003] As an illustrative example, in Raman spectroscopy, when illumination light is incident on a sample, the molecular bonds in the sample material can be excited by the incident light, and radiation can be emitted that can be detected as scattered light. The Rayleigh component of the scattered light corresponds to the light emitted when the molecules relax from the excited state to the ground state. In some cases, molecules relax to different vibrational or rotational levels in the ground state. This produces Raman scattering components at Stokes and anti-Stokes frequencies. Samples composed of multiple molecular species can produce such Raman scattering spectra. The Raman scattering components can be detected and analyzed to determine information about the sample composition.

[0004] In some cases, samples are positioned relative to illumination light, such as by a sample positioning system, to perform spectroscopic measurements (e.g., Raman spectroscopy). For example, the sample positioning system may be configured to receive the sample at one or more locations and move (e.g., along the x, y, and / or z axes) to position one or more locations relative to the focus of the illumination light to illuminate the sample at those locations. In some cases, due to variations in the motion of the sample positioning system (e.g., due to manufacturing variability) and / or the positioning of the sample, the sample may not be properly aligned with the focus of the illumination light, which can lead to variations, inaccuracies, and / or degraded quality of the acquired spectral data. Therefore, it may be necessary to calibrate the motion of the sample positioning system. Summary of the Invention

[0005] The following description presents a simplified overview of one or more aspects of the methods and systems described herein to provide a basic understanding of such aspects. This overview is not a comprehensive summary of all aspects covered, and is not intended to identify key or decisive elements of all aspects, nor to define the scope of any or all aspects. Its sole purpose is to present some concepts of one or more aspects of the methods and systems described herein in a simplified form as an introduction to the more detailed descriptions presented below.

[0006] In some examples, a method for a sample positioning system for calibrating a spectral system includes: determining a first position associated with a first feature of a calibration sample supported by the sample positioning system based on one or more spectral measurements output by the spectral system, wherein the sample positioning system is configured to translate the calibration sample along x-axis and y-axis to position the calibration sample for performing the one or more spectral measurements, wherein the first position represents the coordinates of the first feature on the x-axis and y-axis of the sample positioning system; determining one or more additional positions associated with one or more additional features of the calibration sample based on one or more additional spectral measurements output by the spectral system, the one or more additional positions representing one or more additional coordinates of the one or more additional features relative to the first position on the x-axis and y-axis; and generating calibration data for calibrating the motion of the sample positioning system on the x-axis and y-axis based on the first position and the one or more additional positions.

[0007] In some examples, the spectral system includes: a sample positioning system configured to move a sample along the x-axis and y-axis of the sample positioning system; a source and a detector for performing spectral measurements on the sample; a memory for storing instructions; and one or more processors communicatively coupled to the memory and configured to execute the instructions to perform a process including: performing one or more spectral measurements on a calibration sample; determining a first position associated with a first feature of the calibration sample based on the one or more spectral measurements, wherein the first position represents the coordinates of the first feature along the x-axis and y-axis; performing one or more additional spectral measurements on the calibration sample; determining one or more additional positions associated with one or more additional features of the calibration sample based on the one or more additional spectral measurements, wherein the one or more additional positions represent one or more additional coordinates of the one or more additional features along the x-axis and y-axis; generating calibration data for calibrating the motion of the sample positioning system along the x-axis and y-axis based on the first position and the one or more additional positions; positioning the sample using the sample positioning system based on the calibration data; and performing spectral measurements on the sample.

[0008] In some exemplary embodiments, the calibration plate includes a first set of at least three holes, each of which has a first aperture and a non-deep focus-related reference material; and a second set of at least three holes, each of which has a second aperture and a depth-of-focus-related reference material. Attached Figure Description

[0009] The accompanying drawings illustrate various embodiments and are part of the specification. The illustrated embodiments are merely examples and do not limit the scope of this disclosure. Throughout the drawings, the same or similar reference numerals denote the same or similar elements.

[0010] Figure 1A schematic diagram of an exemplary spectroscopic system, including a sample positioning system, is shown.

[0011] Figure 2 An exemplary implementation of the sample positioning system is shown.

[0012] Figure 3 A perspective view of an exemplary embodiment of a sample holder used with a sample positioning system is shown.

[0013] Figure 4A It shows Figure 3 A top view of the sample holder.

[0014] Figure 4B It shows along Figure 4A The line IV-IV intercepted Figure 3 A cross-sectional view of the sample holder.

[0015] Figure 5A and Figure 5B An exemplary embodiment of the motion of the sample positioning system is shown.

[0016] Figure 6A A top view illustrating an exemplary implementation of a calibration sample used for calibrating a sample positioning system is shown.

[0017] Figure 6B It shows along Figure 6A The line VI-VI cut Figure 6A A perspective cross-sectional view of the calibration sample.

[0018] Figure 6C It shows along Figure 6A The line VI-VI cut Figure 6A A side sectional view of the calibration sample.

[0019] Figure 7 An exemplary embodiment of a calibration sample positioned within a sample positioning system is shown.

[0020] Figure 8 An exemplary method for calibrating a sample positioning system is shown.

[0021] Figures 9A to 9C An exemplary embodiment of a spectral measurement that can be acquired by a spectral system including a sample positioning system is shown.

[0022] Figure 10 An exemplary embodiment of a calibration sample skewed from its intended position on the x and y axes is shown.

[0023] Figure 11 An exemplary embodiment of a calibration sample deviated from its intended position on the z-axis is shown. Detailed Implementation

[0024] This document describes a system and method for calibrating a sample positioning system in a spectroscopic system. The sample positioning system is configured to move a sample along the x-axis and y-axis of the sample positioning system to position the sample for performing spectroscopic measurements using the spectroscopic system. For example, based on one or more spectral measurements received from the spectroscopic system, a first position is associated with a first feature of the calibration sample supported by the sample positioning system. The first position represents the coordinates of the first feature along the x-axis and y-axis of the sample positioning system. Based on one or more additional spectral measurements received from the spectroscopic system, one or more additional positions are determined associated with one or more additional features of the calibration sample. These one or more additional positions represent one or more additional coordinates of the one or more additional features on the x-axis and y-axis of the sample positioning system. Based on the first position and these one or more additional positions, calibration data for calibrating the movement of the sample positioning system along the x-axis and y-axis is generated. In this way, the sample can be accurately positioned based on the calibration data for spectroscopic measurements.

[0025] In one example, calibration data may include calibration values ​​that represent the differences associated with a first expected position of a first position relative to a first feature on the x and y axes, and one or more additional positions relative to one or more additional features on the x and y axes.

[0026] In some examples, the motion of the sample positioning system is further calibrated on the z-axis. For illustration, a second position is determined based on one or more spectral measurements received from the spectral system, associated with a second feature of a calibration sample supported by the sample positioning system included in the spectral system, such that the second position further represents the coordinates of the first feature on the z-axis of the sample positioning system. Based on the second position, calibration data for calibrating the motion of the sample positioning system on the x, y, and z axes can be generated.

[0027] In some examples, multiple first features are included in the calibration sample for calibrating the sample positioning system along the XY axes. The sample positioning system is configured to translate the sample in the XY plane of the sample positioning system. Multiple second features are included in the calibration sample for calibrating the sample positioning system along the Z-axis. By translating the sample along the Z-axis, the distance between the sample and the light source used for spectral measurements is adjusted.

[0028] The calibration sample can extend along the length (Y-axis) and width (X-axis) of the calibration sample plane. In the intended position, the XY plane of the calibration system is aligned with the XY plane of the sample positioning system. However, as... Figure 10 and Figure 11As shown, the XY plane of the calibration sample can be deflected from the XY plane of the sample positioning system. The calibration system can be a calibration plate. The plate can be a plate according to the Laboratory Automation and Screening Association (SLAS) standard.

[0029] Each first feature can be positioned close to a corresponding second feature, such that the second position of the second feature represents the position / coordinate of the first feature on the z-axis. In some examples, the distance between the first and second features is within 10 mm. The first feature may include an aperture with a diameter ranging from 0.01 mm to 1.5 mm. The second feature may include a depth-of-focus reference material. In some examples, the first feature may be identical to the second feature, such that the same feature can be used for calibration in all three axes.

[0030] Depth-correlated reference materials emit light in a different wavelength range than the illumination light. Thus, the position of the focal point of the illumination light relative to the depth-correlated reference material can be determined based on the light emitted from it. For example, the depth-correlated reference material generates a Raman signal in response to illumination. Using a thin layer of depth-correlated reference material, calibration along the z-axis can be achieved.

[0031] In some examples, a non-depth-of-focus-dependent reference material can be added to the features used for XY calibration (such as the first feature) to cause the illumination light to scatter.

[0032] In some examples, the spectral system includes a focusing lens for focusing light generated from the source onto the sample, and the position of the focal point of the light along the Z-axis of the sample positioning system is adjusted by adjusting the relative position between the focusing lens and the sample.

[0033] In one example, the focusing lens can be motorized. The sample positioning system can move the sample along the X and Y axes, but not along the Z axis of the sample positioning system. Adjusting the relative position between the focusing lens and the sample involves adjusting the focusing lens via a motor. In this way, the sample positioning system is rigid along the Z axis, which ensures high precision and high resolution of focus movement along the Z axis.

[0034] In some examples, the sample positioning system is configured to translate the sample along each of the X, Y, and Z axes of the sample positioning system. A focusing lens used to focus light generated from the light source onto the sample may be fixed relative to the sample positioning system. Adjusting the relative position between the focusing lens and the sample involves translating the sample along the Z-axis using the sample positioning system.

[0035] In some examples, the first and second positions correspond to adjacent holes in a board according to the SLAS standard.

[0036] In some examples, the one or more spectroscopic measurements include detecting light emitted from a calibration sample, such as light scattered and / or generated from the calibration sample in response to illumination. The light emitted from the calibration sample may include Raman characteristics (i.e., a Raman signal). One or more spectra are acquired through the spectroscopic measurements. In some examples, the location of the calibration sample is determined based on the peak signal intensity of the spectrum.

[0037] In some examples, calibration data represent one or more of the skewness, offset, or proportion of the calibration sample associated with the sample positioning system.

[0038] In some examples, the sample positioning system is calibrated based on calibration data, enabling the calibrated system to perform measurement procedures on the sample of interest. For example, the measurement procedure may include performing one or more spectroscopic measurements using the calibrated sample positioning system to determine one or more properties of the sample of interest (e.g., identification, structure, chemical bonding, concentration, etc.). In some examples, calibration data is stored in a data storage device of the sample positioning system, allowing the calibration data to be accessed from the data storage device for calibrating the movement of the sample positioning system during measurement procedures.

[0039] In some examples, the calibration sample includes a plate comprising a first set of at least three wells and a second set of at least three wells. Each well in the first set of at least three wells may include aperture- and non-depth-of-focus-dependent reference material for determining calibration data associated with the x and y axes of the sample positioning system. Each well in the second set of at least three wells may include aperture- and depth-of-focus-dependent reference material for determining calibration data associated with the z-axis of the sample positioning system.

[0040] In some examples, the calibration sample can be integrated into the sample positioning system. For instance, features of the calibration sample can be embedded in the sample positioning system. In this way, the calibration sample is included in the sample positioning system.

[0041] The systems and methods described herein can provide various benefits, including one or more advantages over conventional systems and methods used for calibrating sample positioning systems. For example, calibrating the motion of a sample positioning system using spectral measurements, relative to calibrating the motion based on visual inspection, allows for more accurate and / or efficient calibration of the sample positioning system (e.g., calibrating the motion of the sample positioning system based on a location with a good spectral signal that corresponds to the focal point of the illuminating light). Furthermore, calibrating the motion of a sample positioning system using spectral measurements allows the sample positioning system to provide more accurate and / or repeatable spectral measurements of the sample and reduces variability associated with the sample positioning system (e.g., between different sample positioning systems).

[0042] Various embodiments will now be described in more detail with reference to the accompanying drawings. The systems and methods described herein may provide one or more of the benefits described above, as well as various additional and / or alternative benefits that will become apparent herein.

[0043] In some specific implementations, the systems and methods for calibrating sample positioning systems, as described herein, can be used in conjunction with Raman spectroscopy systems. Therefore, Raman spectroscopy systems will now be described. However, the Raman spectroscopy systems described herein are illustrative and not limiting. The systems and methods described herein may be operated as part of or in combination with the Raman spectroscopy systems described herein and / or any other suitable optical spectroscopy systems, including infrared spectroscopy systems, ultraviolet spectroscopy systems, or optical emission spectrometers.

[0044] Figure 1 An exemplary Raman spectroscopy system 100 (“spectroscopy system 100”) is shown. Spectroscopy system 100 includes a light source 102, a sample positioning system 104, a spectrometer 106, and a controller 108. Spectroscopy system 100 may include additional or alternative components that may be used in a particular implementation. In some examples, spectroscopy system 100 is implemented as a microscope, such as a Raman microscope.

[0045] Light source 102 is configured to generate light 110 for illuminating sample 112 stored within sample positioning system 104. In some examples, the light 110 generated by light source 102 includes monochromatic light (e.g., light having a substantially constant wavelength and / or frequency), such as light in the visible range (e.g., light having wavelengths from about 380 nanometers (nm) to about 700 nm), light in the near-infrared range (e.g., light having wavelengths from about 700 nm to about 2500 nm), and / or light in the near-ultraviolet range (e.g., light having wavelengths from about 200 nm to about 400 nm). Light source 102 is implemented by any suitable light source configured to generate light 110, such as a laser (e.g., a continuous-wave laser, a pulsed laser, etc.), including but not limited to a 780 nm diode laser, a 633 nm HeNe laser, and / or a 532 nm solid-state laser.

[0046] In some examples, the light 110 generated by the light source 102 is manipulated by one or more optical devices to direct the light 110 toward the sample 112 within the sample positioning system 104. As shown, the light 110 generated by the light source 102 is directed toward a beam splitter 114, which is configured to split the light 110 into a transmitted beam portion and a reflected beam portion. The transmitted beam portion is directed toward a focusing lens 116, which is configured to focus the transmitted beam portion toward the sample 112. Other suitable optical devices may also be used to manipulate the light 110 toward the sample 112, such as one or more of filters (e.g., laser filters, notch filters, tunable filters, edge filters, neutral density filters, etc.), lenses (e.g., focusing lenses, collimating lenses, beam-collecting lenses, etc.) or mirrors.

[0047] Sample positioning system 104 is configured to receive sample 112. Sample 112 is configured to store one or more analytes for detection and analysis by spectral system 100. Sample positioning system 104 may be further configured to position sample 112 relative to light 110 (e.g., the focal point of light 110) such that one or more analytes within sample 112 are illuminated by light 110. For illustration, sample positioning system 104 may be configured to support one or more samples 112, each sample storing one or more analytes at one or more locations within sample positioning system 104, and to move these one or more locations relative to one or more optics (e.g., focusing lens 116) and / or light source 102 (e.g., left, right, forward, backward, toward, and / or away from) to position the one or more analytes stored by the one or more samples 112 at the focal point of light 110 (e.g., to excite the molecular bonds of the one or more analytes at those locations). In some cases, sample 112 includes multiple features such that sample positioning system 104 can be configured to store each analyte at a different location within sample positioning system 104. Therefore, sample positioning system 104 can be configured to move sample 112 at different locations to sequentially align each analyte of interest with light 110 to perform spectroscopic measurements on each analyte of interest.

[0048] As an illustrative example, sample 112 may be implemented as a plate having a first feature and a second feature, the first feature being configured to store a first analyte at a first location, and the second feature being configured to store a second analyte at a second location spaced apart from the first location. Sample positioning system 104 may be configured to support sample 112 and move such that the first location is aligned with light 110 to induce illumination of the first analyte stored at the first feature and perform a spectral measurement associated with the first analyte. Sample positioning system 104 may then be moved such that the second location is aligned with light 110 to induce illumination of the second analyte stored at the second feature and perform a spectral measurement associated with the second analyte. Sample positioning system 104 may continue to move sample 112 to illuminate additional analytes of interest. An example movement of sample positioning system 104 is described in more detail below. Furthermore, although... Figure 1 The sample positioning system 104 is shown to be separate from the optics (e.g., beam splitter 114 and focusing lens 116) and the light source 102, but one or more optics (e.g., beam splitter 114 and focusing lens 116) and / or the light source 102 may alternatively be included in whole or in part within the sample positioning system 104.

[0049] The one or more analytes stored in sample 112 may include, for example, chemical analytes (e.g., molecules, ions, etc.) and / or biological analytes (e.g., metabolites, proteins, lipids, etc.) for detection and analysis by spectroscopic system 100. For example, when sample 112 is irradiated by light 110, the molecular bonds in one or more analytes in sample 112 are excited by the light 110, and in response, scattered light 118 with multiple wavelengths (e.g., by Raman scattering) is emitted, which are shifted to wavelengths different from the irradiating light 110. Based on the shift of the wavelength and / or frequency of the scattered light 118 emitted from sample 112 relative to the irradiating light 110 received by sample 112, spectroscopic system 100 may determine one or more properties (e.g., recognition, structure, chemical bonds, concentration, etc.) of the one or more analytes included in sample 112.

[0050] Therefore, the scattered light 118 is directed toward the spectrometer 106 for detection and analysis. In some examples, the scattered light 118 emitted from the sample 112 is directed to the spectrometer 106 by one or more optics, which may include the same optics and / or additional optics used to direct the light 110 toward the sample 112. As shown, a focusing lens 116 is configured to focus the scattered light 118 toward a filter 120 configured to allow the scattered light 118 having a desired wavelength range (such as wavelengths beyond those included in the light 110) to pass through the filter 120 to reach the spectrometer 106. Other suitable optics may also be used to direct at least a portion of the scattered light 118 toward the spectrometer 106, such as one or more of a beam splitter, a filter (e.g., a laser filter, a notch filter, a tunable filter, an edge filter, a neutral density filter, etc.), a lens (e.g., a focusing lens, a collimating lens, a focusing lens, etc.), or a mirror.

[0051] As shown, the spectrometer 106 includes a grating 122, a wavelength filter 124, and a detector 126. The grating 122 is implemented by any suitable grating (e.g., a holographic grating, a transmission grating, a reflection grating, etc.) or other dispersive element configured to disperse scattered light 118 into multiple component wavelengths 128 (e.g., wavelengths 128-1 to 128-3) included in the scattered light 118. Each wavelength 128 may include a specific wavelength and / or a continuous wavelength range included in the scattered light 118. The grating 122 is also configured to guide the multiple separated wavelengths 128 toward the wavelength filter 124. For example, the multiple wavelengths 128 of the scattered light 118 separated by the grating 122 are guided from the grating 122 in different directions (e.g., at different angles) such that each wavelength 128 included in the multiple wavelengths 128 is received at a different region of the wavelength filter 124 relative to the other wavelengths 128.

[0052] Wavelength filter 124 is configured to receive a plurality of wavelengths 128 and selectively direct one or more wavelengths of interest (e.g., one or more wavelengths that can be used to determine one or more properties of one or more analytes in sample 112) included in the plurality of wavelengths 128 toward detector 126, while filtering the remaining wavelengths included in the plurality of wavelengths 128 (e.g., the filtered wavelengths are not directed toward detector 126). Wavelength filter 124 may be implemented by a digital micromirror device (DMD), a liquid crystal filter, or any other suitable filter device configured to selectively direct the wavelengths 128 of scattered light 118 toward detector 126.

[0053] Detector 126 is configured to receive light directed toward it by wavelength filter 124, and to detect or measure the intensity of light at each wavelength 128 received by detector 126. Detector 126 may be implemented by any suitable optical detector, such as, but not limited to, one or more of a photodiode, charge-coupled device (CCD), or single-channel detector. Detector 126 may also be configured to generate a signal representing the intensity of light at wavelength 128 detected by detector 126, and output this signal to controller 108. Detector 126 may detect Raman signals.

[0054] Spectrometer 106 may include additional or alternative components that may serve a particular implementation, such as one or more optical devices (e.g., entrance slits, lenses, filters, mirrors, etc.) configured to direct light toward grating 122, wavelength filter 124, and / or detector 126. As an illustrative example, spectrometer 106 may include a collimating lens configured to direct light to grating 122, a focusing lens configured to direct light to wavelength filter 124, and / or a light-collecting lens configured to direct light to detector 126.

[0055] Controller 108 is communicatively coupled to light source 102, sample positioning system 104, wavelength filter 124, and detector 126, and is configured to control the operation of the light source, sample positioning system, wavelength filter, and detector. For example, controller 108 may be configured to control the operation of various hardware components included in light source 102, sample positioning system 104, wavelength filter 124, and detector 126. For illustration, controller 108 may be configured to control one or more parameters (e.g., intensity, wavelength, frequency, timing, etc.) of light 110 generated and emitted by light source 102 and / or the movement of sample positioning system 104 to align sample 112 with the light 110 used for illumination. Controller 108 may be further configured to selectively control the wavelength 128 of scattered light 118 filtered by wavelength filter 124, receive signals output by detector 126, and / or determine one or more properties of the one or more analytes included in sample 112 based on the signals received by detector 126.

[0056] The controller 108 may also include and / or provide a user interface configured to enable interaction between the user of the sample positioning system 104, the spectrometer 106, and / or the controller 108. The user can interact with the controller 108 via the user interface through tactile, visual, auditory, and / or other sensory communication.

[0057] Controller 108 may include any suitable hardware (e.g., processor, circuitry, etc.) and / or software that can serve a particular implementation. Although Figure 1The controller 108 is shown to be separate from the sample positioning system 104 and the spectrometer 106, but the controller 108 may alternatively be wholly or partially included within the sample positioning system 104 and / or the spectrometer 106. In some examples, the controller 108 includes a computing device communicatively coupled to the sample positioning system 104 and / or the spectrometer 106 via a wired connection (e.g., cable), a wireless connection, and / or a network (e.g., a local area network, a wireless network (e.g., Wi-Fi), a wide area network, the Internet, a cellular data network, etc.).

[0058] Figure 2 An exemplary embodiment of a sample positioning system 104 within a spectroscopic system 100 is shown. As shown, the sample positioning system 104 includes a sample support 200 having a recess 202 formed therein and configured to receive a sample (e.g., sample 112) for storing one or more analytes. The sample positioning system 104 further includes a substrate 206 and an opening 208 formed therethrough. The sample positioning system 104 includes a first actuator for translating the sample support 200 along the x-axis of the sample positioning system 104 and a second actuator for translating the sample support 200 along the y-axis of the sample positioning system 104. In some examples, the sample positioning system 104 may translate the sample only in the XY plane but not along the z-axis of the sample positioning system 104. In some examples, the sample positioning system 104 may translate the sample along each of the X, Y, and Z axes of the sample positioning system. The sample positioning system 104 is configured to receive light (e.g., light 110) generated by a light source (e.g., light source 102) and guide it through opening 208 toward sample support 200 (and sample 112 supported by sample support 200). In some examples, the base 204 of the spectral system 100 may accommodate one or more optics (e.g., beam splitter 114 and focusing lens 116) such that the base 204 can be configured to receive light generated by the light source and guide it through opening 208 toward sample support 200.

[0059] The sample positioning system 104 is configured to move the sample support 200 relative to the substrate 206 (e.g., the sample support 200 may move left, right, forward, backward, toward and / or away from the substrate 206) to align the various positions of the sample support 200 (and the sample 112 supported by the sample support 200) with the opening 208. The sample positioning system 104 may include additional or alternative components that may be used in a particular implementation, such as one or more motors configured to move the sample support 200 relative to the opening 208 and / or a controller configured to cause movement of the sample support 200 relative to the opening 208. Additionally or alternatively, the sample support 200 may be integrated with the sample, such that the sample support 200 is configured to directly receive one or more analytes (e.g., not receiving the individual sample 112). In some examples, the sample support may be integrated with the sample positioning system.

[0060] Figures 3 to 4B An exemplary embodiment 300 of a sample that can be implemented or is similar to a sample 112 for use with the sample positioning system 104 is shown. For example, Figure 3 A perspective view of sample 300 is shown. Figure 4A A top view of sample 300 is shown, and Figure 4B It shows along Figure 4A A cross-sectional view of sample 300 taken from line IV-IV.

[0061] As shown, sample 300 is realized by sample plate 302 having a plurality of holes 304 (e.g., holes 304-1 to 304-n) formed therein. Each hole 304 is formed by an opening extending from the top surface 306 of sample plate 302 toward the bottom surface 308 of sample plate 302. Thus, each hole 304 is configured to receive and retain one or more analytes within each hole 304. At least a portion of sample plate 302 (e.g., at least the portion of sample plate 302 extending the holes 304 to the bottom surface 308) may be made of any suitable material (e.g., polypropylene, polycarbonate, etc.) configured to allow light (e.g., light 110 and / or scattered light 118) to pass through sample plate 302 toward and / or from the holes 304 (e.g., to illuminate and / or emit light from one or more analytes stored within the holes 304).

[0062] like Figure 4AAs shown, the holes 304 of sample 300 are arranged in a grid configuration forming multiple rows (e.g., indicated by letters A to H) and columns (e.g., indicated by numbers 1 to 12). In some examples, the holes 304 of sample 300 are arranged according to a standard grid configuration (such as the SLAS standard) (e.g., the holes 304 are formed within sample 300 according to one or more predefined parameters, such as the standard number of holes 304, the diameter of holes 304, the depth of holes 304, the spacing between holes 304, the spacing from the edge of sample 300, the tolerances associated with holes 304, the ratio between rows and columns of holes 304, etc.). As an illustrative example, the holes 304 of sample 300 are arranged according to the SLAS standard for an orifice plate with 96 holes (e.g., the holes 304 are arranged in 8 rows and 12 columns, and spaced approximately 9 mm from center to center). For one or more well plates, such as those with 6, 12, 24, 48, 96, 192, 384, 768, or 1536 wells, the wells 304 can alternatively be arranged according to any other suitable SLAS standard. Thus, the wells 304 are spaced apart such that each well 304 can be configured to store an analyte at a different location relative to another analyte stored in a different well 304.

[0063] Other suitable standards, configurations, and / or parameters for the aperture 304 may be available for the sample 300. For example, the aperture 304 may have any shape (e.g., circular, rectangular, square, etc.) and be arranged in any number of rows and / or columns. In some examples, the arrangement of the aperture 304 on the sample 300 may be customizable and / or specified based on user input (e.g., the aperture 304 may be arranged in a non-standard configuration). For illustration, a user may interact with a user interface (e.g., associated with controller 108) to specify the arrangement and / or location of the aperture 304 on the sample 300. Furthermore, in addition to or in place of the aperture 304, the sample 300 may include other suitable features for storing the sample 112 (e.g., beads, etc.), and / or the sample 300 may include another suitable type of sample holder instead of the sample plate 302.

[0064] Figure 5A and Figure 5B An exemplary embodiment of the motion of a calibration sample positioning system 104 for performing spectroscopic measurements on an analyte (e.g., sample 300) held in a SLAS plate is shown. The X, Y, and Z coordinates are the coordinates of the sample positioning system 104. For example, Figure 5AAn exemplary embodiment 500 in which sample 300 is positioned within sample positioning system 104 is shown. As shown, sample 300 is received within recess 202 of sample support 200, wherein top surface 306 of sample 300 faces outward to allow one or more holes 304 of sample 300 to receive one or more analytes. Sample support 200 may receive sample 300 in an initial position (e.g., sample support 200 is positioned toward the left and rear edges of substrate 206, wherein holes 304 of sample 300 are not aligned with openings 208 of substrate 206).

[0065] The sample support 200 of the sample positioning system 104 is configured to move based on calibration data to align one or more holes 304 with openings 208 of the substrate 206, so that one or more analytes stored within the one or more holes 304 are illuminated by light (e.g., light 110) to perform spectroscopic measurements on the one or more analytes of the sample 300. For illustration, Figure 5B An exemplary embodiment 502 of a sample support 200 is shown, which is moved to align the first aperture 304-1 with the opening 208. For example, the sample support 200 is moved from an initial position relative to the substrate 206 along the y-axis (e.g., to the right) (as shown by arrow 504) and along the x-axis (e.g., forward) (as shown by arrow 506) to move the sample 300 to align the first aperture 304-1 with the opening 208 (e.g., the center of the first aperture 304-1 is aligned with the focal point of light 110). When the first aperture 304-1 is aligned with the opening 208, the sample positioning system 104 can be configured to guide light 110 through the opening 208 toward the first aperture 304-1 to illuminate one or more analytes stored in the first aperture 304-1, and to emit scattered light 118 from the one or more analytes stored in the first aperture 304-1 through the opening 208 (e.g., to be detected by detector 126).

[0066] Therefore, the sample positioning system 104 is configured to move the sample support 200 and / or the sample 300 to the left and / or right relative to the substrate 206 along the y-axis, and to move the sample support and / or the sample forward and / or backward relative to the substrate 206 along the x-axis, so as to align any corresponding hole 304 of the sample 300 with the opening 208 for irradiation. Other suitable configurations for the movement of the sample positioning system 104 (e.g., to move the sample support 200 and / or the sample 300) may be used.

[0067] The sample positioning system 104 can be configured to move the sample support 200 to align another aperture 304 of the sample 300 with the opening 208 so as to illuminate another analyte with light 110. For illustration, the sample positioning system 104 can move the sample support 200 rearward along the x-axis from a first position to a second position, in which the first aperture 304-1 of the sample 300 (e.g., located in row A and column 1) is aligned with the opening 208, and in the second position, the other aperture 304-12 of the sample 300 (e.g., located in row A and column 12) is aligned with the opening 208. To move from the first position to the second position, the sample positioning system 104 can move the sample support 200 and / or the sample 300 along the x-axis by a distance corresponding to a desired distance between the first aperture 304-1 and the other aperture 304-12. The sample positioning system 104 can be further configured to move along the x-axis and y-axis to an additional position, in which the additional aperture 304 is aligned with the opening 208.

[0068] The movement of the sample positioning system 104 has been calibrated to adequately position the sample support 200 and / or the sample 300 in alignment with the opening 208 in order to provide accurate spectral measurements. For example, the movement of the sample positioning system 104 (e.g., the sample support 200 and / or the sample 300) may not correspond to the expected distance and / or position between the openings 304, such as due to differences between the sample positioning systems 104 (e.g., manufacturing variability), and / or the focal point of light guided by the sample positioning system 104 toward the opening 304 may not correspond to the expected position of the focal point, such as due to differences between the sample positioning systems 104.

[0069] In some examples, a sample (e.g., sample 300) and / or a calibration sample are used to calibrate the movement of the sample positioning system 104. For illustration, a calibration sample may be inserted into the sample positioning system 104 to calibrate the movement of the sample positioning system 104 and then removed from the sample positioning system 104 to allow a sample (e.g., sample 300) to be inserted into the sample positioning system 104 for storing one or more analytes and performing spectroscopic measurements on the sample (e.g., one or more analytes stored by the sample).

[0070] In some examples, calibration samples can be integrated into the sample positioning system. For instance, these features can be positioned at the corners of the sample support to calibrate the sample positioning system. This eliminates the need for additional calibration samples separate from the sample positioning system.

[0071] Figures 6A to 6C An exemplary embodiment 600 of a calibration sample used to calibrate the motion of the sample positioning system 104 is shown. For example, Figure 6A A top view of calibration sample 600 is shown. Figure 6B It shows along Figure 6A A perspective cross-sectional view of the calibration sample 600 taken from line VI-VI, and Figure 6C It shows along Figure 6A A side sectional view of calibration sample 600 taken from line VI-VI.

[0072] As shown in the figure, the calibration sample 600 is implemented as a calibration plate 602, which is configured to be received within a recess 202 of the sample support 200. For example, the calibration plate 602 may have the same size as a plate according to the SLAS standard. The calibration plate 602 includes a first set of non-depth-dependent holes 604 (e.g., non-depth-dependent holes 604-1 to 604-4) extending within the calibration plate 602 and a second set of depth-dependent holes 606 (e.g., depth-dependent holes 606-1 to 606-4). Each hole included in the first set of non-depth-dependent holes 604 is formed by an opening extending from the top surface 608 of the calibration plate 602 toward the bottom surface 610 of the calibration plate 602. Each hole included in the first set of non-depth-dependent holes 604 includes a first aperture 612 (e.g., first apertures 612-1 to 612-4) extending from each non-depth-dependent hole 604 to the bottom surface 610 of the calibration plate 602. In the example shown, the size of each first aperture 612 is set to be smaller than each non-depth-dependent aperture 604 included in the first set of non-depth-dependent apertures 604. In some examples, each first aperture 612 may be sized based on the amplitude of the wavelength of light to be transmitted through the first aperture 612 and / or based on the size of the aperture (e.g., aperture 304) to be used with the sample positioning system 104 for storing samples. In some examples, each first aperture 612 includes a diameter of about 0.01 mm to about 1.5 mm, such as about 0.2 mm.

[0073] Each aperture included in the first set of non-depth-dependent apertures 604 further includes a non-focus-dependent reference material 614 (e.g., polystyrene, etc.). For example, the non-focus-dependent reference material 614 may be configured to emit scattered light (e.g., scattered light 118) when illuminated by light (e.g., light 110), regardless of the depth of the calibration plate 602 relative to the focal point of the light (e.g., the calibration plate 602 may be located anywhere along the z-axis relative to the substrate 206 so that the non-focus-dependent reference material 614 emits scattered light 118). Therefore, the non-focus-dependent reference material 614 included in the first set of non-depth-dependent apertures 604 can be used to calibrate the movement of the sample positioning system 104 along the x-axis and y-axis (e.g., independent of the z-axis).

[0074] In the example shown, the first set of non-depth-dependent holes 604 includes four holes located at different corners of the calibration plate 602. Additionally or alternatively, each hole included in the first set of non-depth-dependent holes 604 may correspond to a hole in a plate according to the SLAS standard. For example, the first non-depth-dependent hole 604-1 may be located at a first corner of the calibration plate 602 to correspond to hole 304 of sample 300 in row A and column 1. The second non-depth-dependent hole 604-2 may be located at a second corner of the calibration plate 602 to correspond to hole 304 of sample 300 in row A and column 12. The third non-depth-dependent hole 604-3 may be located at a third corner of the calibration plate 602 to correspond to hole 304 of sample 300 in row H and column 1. The fourth non-depth-dependent hole 604-4 may be located at a fourth corner of the calibration plate 602 to correspond to hole 304 of sample 300 in row H and column 12. This placement of the holes included in the first set of non-depth-related holes 604 allows for the calibration of the movement of the sample positioning system 104 along the entire surface of the calibration sample 600 and / or sample 300. Other suitable configurations of the holes included in the first set of non-depth-related holes 604 (e.g., spacing, size, position, etc.) can be used to fully calibrate the movement of the sample positioning system 104 between the holes. For example, at least two holes (e.g., located at opposite corners of the calibration plate 602) and / or at least three holes (e.g., located at three different corners of the calibration plate 602) can be used.

[0075] Similarly, each hole included in the second set of depth-correlated holes 606 is formed by an opening extending from the top surface 608 of the calibration plate 602 toward the bottom surface 610 of the calibration plate 602. Each hole included in the second set of depth-correlated holes 606 includes a second aperture 616 (e.g., second apertures 616-1 to 616-4) extending from each hole to the bottom surface 610 of the calibration plate 602. In the example shown, the size of each second aperture 616 is set to be smaller than each depth-correlated hole 606 included in the second set of depth-correlated holes 606. In some examples, the size of each second aperture 616 may be set based on the amplitude of the wavelength of light to be transmitted through the second aperture 616 and / or based on the size of the hole 304 to be used with the sample positioning system 104. Furthermore, the size of each second aperture 616 may be set to be larger than each first aperture 612 in the first set of non-depth-correlated holes 604.

[0076] Each aperture included in the second set of depth-correlated apertures 606 further includes a depth-correlated reference material 618 (e.g., silicon, silicon dioxide, etc.). For example, the depth-correlated reference material 618 may be configured to emit scattered light (e.g., scattered light 118) based on the depth of the calibration plate 602 relative to the focal point of the light when the depth-correlated reference material 618 is illuminated with light (e.g., light 110). (E.g., the calibration plate 602 is positioned at a specific location relative to the substrate 206 along the z-axis so that the depth-correlated reference material 618 emits scattered light.) Therefore, the depth-correlated reference material 618 included in the second set of depth-correlated apertures 606 can be used to calibrate the movement of the sample positioning system 104 along the z-axis.

[0077] In the example shown, the second set of depth-correlated holes 606 includes four holes located at different corners of the calibration plate 602 and offset from the corresponding holes of the first set of non-depth-correlated holes 604. For example, each hole included in the second set of depth-correlated holes 606 may be offset from the corresponding hole included in the first set of non-depth-correlated holes 604 by a distance of approximately 10 mm. Additionally or alternatively, each hole included in the second set of depth-correlated holes 606 may correspond to an adjacent hole in a plate according to the SLAS standard. For illustration, the first depth-correlated hole 606-1 may be located at a first corner of the calibration plate 602 to correspond to hole 304 of sample 300 in row A and column 2. The second depth-correlated hole 606-2 may be located at a second corner of the calibration plate 602 to correspond to hole 304 of sample 300 in row A and column 11. The third depth-correlated hole 606-3 may be located at a third corner of the calibration plate 602 to correspond to hole 304 of sample 300 in row H and column 2. The fourth depth-related hole 606-4 may be located at the fourth corner of the calibration plate 602 to correspond to the hole 304 of the sample 300 in row H and column 11.

[0078] This placement of the holes included in the second set of depth-correlated holes 606 allows for calibration of the movement of the sample positioning system 104 along the z-axis and the x and y axes associated with the first set of non-depth-correlated holes 604. In some examples, the position of each hole included in the second set of depth-correlated holes 606 along the z-axis may correspond to the position of a corresponding hole included in the first set of non-depth-correlated holes 604 along the z-axis (e.g., the position of the first non-depth-correlated hole 604-1 may be calibrated along the z-axis based on the position of the first depth-correlated hole 606-1).

[0079] Other suitable configurations (e.g., spacing, size, position, etc.) of the holes included in the second set of depth-related holes 606 can be used to adequately calibrate the movement of the sample positioning system 104. For example, at least two holes (e.g., located at opposite corners of the calibration plate 602) or at least three holes (e.g., located at three different corners of the calibration plate 602) can be used. Additionally or alternatively, at least a portion of the holes included in the second set of depth-related holes 606 may overlap at least a portion of the corresponding holes included in the first set of non-depth-related holes 604. For illustration, non-depth-of-focus reference material 614 and depth-of-focus reference material 618 may be provided in the same hole, such that only one set of holes can be provided. Alternatively, the second set of depth-related holes 606 including the depth-of-focus reference material 618 may be omitted from the calibration sample 600 (e.g., in cases where the movement of the sample positioning system 104 is not calibrated relative to the z-axis). In some examples, in addition to or in place of the first set of non-depth-dependent holes 604 and / or the second set of depth-dependent holes 606, the calibration sample 600 may include other suitable features for providing non-depth-of-focus-dependent reference material 614 and / or depth-of-focus-dependent reference material 618. Furthermore, the calibration sample 600 may include other suitable types of sample holders in place of the calibration plate 602.

[0080] As an illustrative example, Figure 7 A specific embodiment 700 of a calibration sample 600 positioned within a sample support 200 of a sample positioning system 104 is shown. As shown, the sample support 200 is positioned to align a first non-depth-dependent aperture 604-1, included in a first set of non-depth-dependent apertures 604, with an opening 208 in a substrate 206. Therefore, light 110 transmitted through the opening 208 by the focusing lens 116 is configured to be focused toward a non-depth-of-focus reference material 614 through a first aperture 612-1 of the first non-depth-of-focus aperture 604-1. The non-depth-of-focus reference material 614 may be configured to emit scattered light in response to illumination by light 110 that can be detected (e.g., by a detector 126). The sample support 200 may be further moved to align a first depth-of-focus aperture 606-1, included in a second set of depth-of-focus apertures 606, with an opening 208 in a substrate 206. Therefore, the light 110 transmitted through the opening 208 by the focusing lens 116 is configured to be focused toward the depth-of-focus reference material 618 through the second aperture 616-1 of the first depth-of-focus aperture 606-1. The depth-of-focus reference material 618 may be configured to emit scattered light in response to illumination by the light 110, which can be detected (e.g., by the detector 126), such as when the depth-of-focus reference material 618 is positioned at a desired distance (e.g., at the focal point of the light 110) relative to the substrate 206 and / or the focusing lens 116 along the z-axis.

[0081] Figure 8An exemplary method 800 is shown for a sample positioning system (e.g., sample positioning system 104) that uses spectral measurements to calibrate a spectral system (e.g., spectral system 100). Although Figure 8 The illustration shows exemplary operations according to one embodiment, but other embodiments may omit, add, reorder, and / or modify them. Figure 8 Any of the operations shown. Figure 8 One or more of the operations shown can be performed by the spectral system 100, the sample positioning system 104, any components included therein, and / or any specific implementation thereof.

[0082] As shown in the figure, method 800 includes, at operation 802, determining a first position associated with a first feature of a calibration sample (e.g., calibration sample 600) supported by a sample positioning system, based on one or more spectral measurements output by a spectral system. The first feature of the calibration sample may include one or more of the following: an aperture (e.g., non-depth-dependent aperture 604 and / or depth-dependent aperture 606), an aperture diameter (e.g., a first aperture 612 and / or a second aperture 616), or a focal point (e.g., associated with non-depth-of-focus reference material 614 and / or depth-of-focus reference material 618). In some examples, the first feature includes the center of an aperture in a plate according to a SLAS standard. The first position is a position relative to the sample positioning system.

[0083] A sample positioning system (e.g., sample support 200) is configured to translate the calibration sample along the x and y axes of the sample positioning system to position the calibration sample for performing one or more spectral measurements to determine a first location of a first feature. For example, the first location represents the coordinates of the first feature along the x and y axes of the sample positioning system. The first location may be determined based on the peak signal intensity of one or more spectral measurements associated with the first feature. For example, the first location is the position where the strongest peak signal intensity is detected. In some examples, an algorithm such as the simplex algorithm may be used to determine the peak signal intensity.

[0084] As an illustrative example, a first feature of the calibration sample may have a first intended location (e.g., along the x and y axes of the sample positioning system). The first intended location may be determined based on the geometry of the calibration sample (such as the SLAS standard) and / or specified by user input. The sample positioning system is movable to align the first intended location of the first feature with openings (e.g., opening 208) of the sample positioning system configured to direct light (e.g., light 110) toward the calibration sample. For illustration, the first feature may include a first non-depth-dependent aperture 604-1, such that the intended location of the center of the first non-depth-dependent aperture 604-1 is positioned along the x and y axes within the intended focal point of the light. A spectral system may perform spectral measurements associated with the first feature at the first intended location. For illustration, the spectral system may generate light that is directed through the openings of the sample positioning system to illuminate a non-depth-dependent reference material 614 within the first non-depth-dependent aperture 604-1. When the first feature (e.g., the first non-depth-dependent aperture 604-1) is sufficiently aligned with the focal point of light at the first intended location, the light generated by the spectral system illuminates the material associated with the first feature (e.g., the non-depth-dependent reference material 614), such that the material can be configured to emit light (e.g., scatter light), which can be detected by a detector of the spectral system (e.g., detector 126) to obtain a spectral signal. Alternatively, if the first feature is not aligned with the focal point of light at the aperture and / or the first intended location, the light generated by the spectral system may not illuminate the material associated with the first feature, making it impossible to obtain a spectral signal, and / or the light generated by the spectral system may not sufficiently illuminate the material associated with the first feature, such that the light emitted by the material may provide a weak spectral signal (e.g., with a small peak).

[0085] The sample positioning system can be further moved incrementally along the x-axis and / or y-axis to move the first feature relative to the opening around a first intended position, and one or more spectral measurements can be performed by a spectral system to acquire a spectral signal associated with the first feature at each increment. For illustration, the sample positioning system can be moved to incrementally position the first feature of the calibration sample around the first intended position according to a pattern (e.g., a box pattern, a circular pattern, a Z-shaped pattern, etc.). At each increment, spectral measurements can be performed to acquire a spectral signal at each increment. The peak signal intensity (e.g., peak amplitude and / or centroid) of each spectral signal can be determined for each spectral measurement associated with the first feature. A spectral signal with a maximum peak signal intensity (e.g., higher than the peak signal intensity of another spectral signal) can correspond to the first feature properly aligned with the opening and / or the focal point of light transmitted through the opening of the sample positioning system. Therefore, the first position of the first feature can be determined based on the position of the sample positioning system in which a spectral signal with a higher peak signal intensity relative to another peak signal intensity is acquired. For example, the first position can represent coordinates along the x-axis and y-axis corresponding to the position of the calibration sample aligned with the opening and / or the focal region of light. In some examples, the first position may include the distance offset of the first position relative to the first expected position (e.g., along the x-axis and / or y-axis).

[0086] As an illustrative example, Figures 9A to 9C An exemplary spectral signal 900 (e.g., spectral signals 900-1 to 900-3) is shown, associated with a first characteristic of a calibration sample that can be acquired by a spectral system. As shown in the figure... Figure 9A A first spectral signal 900-1 with a first peak signal intensity 902-1 is depicted, such as at the centroid of the spectral signal 900. Figure 9B A second spectral signal 900-2 with a second peak signal intensity 902-2 higher than the first peak signal intensity 902-1 is depicted. For example, the second spectral signal 900-2 can be acquired after the sample positioning system is moved incrementally relative to the position of the sample positioning system in which the first spectral signal 900-1 is acquired. Figure 9C A third spectral signal 900-3 is depicted, having a third peak signal intensity 902-3 higher than the second peak signal intensity 902-2. For example, the third spectral signal 900-3 can be acquired after the sample positioning system is moved incrementally relative to the position of the sample positioning system in which the second spectral signal 900-2 is acquired. Based on such a spectral signal 900, it can be determined that the third spectral signal 900-3 has a maximum peak signal intensity 902 relative to the first spectral signal 900-1 and the second spectral signal 900-2, such that the position of the spectral measurement system in which the third spectral signal 900-3 is acquired can be used to determine the first position of the first feature.

[0087] In some examples, the first position of a first feature can be determined based on a peak signal intensity exceeding a threshold. For example, the threshold can be configured to indicate that the first feature of the calibration sample is adequately aligned with respect to the aperture and / or focused area of ​​light (e.g., to provide accurate spectral measurements of the sample stored in a sample holder at a position corresponding to the first position). For illustration, the first position of the first feature can be determined as the first expected position when the peak signal intensity of the spectral signal acquired at the first expected position exceeds the threshold. Alternatively, when the peak signal intensity of the spectral signal acquired at the first expected position is below the threshold, the sample positioning system can be moved incrementally around the first expected position, such as until another peak signal intensity of another spectral signal exceeds the threshold. Thus, the first position can be determined based on the position of the sample positioning system where the peak signal intensity exceeds the threshold.

[0088] Additionally or alternatively, the sample positioning system can be moved along the x-axis and y-axis until the spectral measurement converges to the maximum peak signal intensity. For illustration, a spectral signal can be acquired as the sample positioning system increments in a first direction along the x-axis and / or y-axis. If the peak signal intensity of the spectral signal increases, the sample positioning system can continue to increment in the first direction. Alternatively, if the peak signal intensity of the spectral signal decreases, the sample positioning system can increment in a second, opposite direction until the maximum peak signal intensity is determined.

[0089] Return to reference Figure 8 Method 800 further includes, at operation 804, determining one or more additional locations associated with one or more additional features of the calibration sample based on one or more additional spectral measurements output by the spectral system. The one or more additional features of the calibration sample may include one or more of the following: apertures (e.g., additional apertures included in the first set of non-depth-dependent apertures 604 and / or the second set of depth-dependent apertures 606), aperture diameters (e.g., the first aperture 612 and / or the second aperture 616), or focal points (e.g., associated with non-depth-of-focus reference materials 614 and / or depth-of-focus reference materials 618). In some examples, the one or more additional features include the center of an aperture in a plate according to the SLAS standard.

[0090] The one or more additional locations may represent one or more additional coordinates of the one or more additional features along the x-axis and y-axis (such as relative to a first location). For example, a spectroscopic system may be configured to move a sample positioning system (e.g., sample support 200) along the x-axis and y-axis to position a calibration sample for performing one or more additional spectral measurements to determine one or more additional locations of the one or more additional features. In some examples, the one or more additional locations may be determined based on the peak signal intensity of one or more additional spectral measurements associated with the one or more additional features, such as by using an algorithm (e.g., a simplex algorithm).

[0091] As an illustrative example, additional features of the calibration sample may have additional expected positions (e.g., along the x and y axes) based on SLAS standards and / or specified by user input. The sample positioning system is movable to align the additional expected positions of the additional features with openings in the sample positioning system configured to guide light toward the calibration sample. For illustration, the additional feature may include a second non-depth-dependent aperture 604-2, such that the additional expected position of the center of the second non-depth-dependent aperture 604-2 is positioned within the expected focal point of the light along the x and y axes. A spectral system may perform spectral measurements associated with the additional feature at the additional expected positions. For illustration, the spectral system may generate light that is guided through the openings of the sample positioning system. With the additional feature adequately aligned with the openings and / or the focal point of the light at the additional expected positions, the light generated by the spectral system illuminates the material associated with the additional feature of the calibration sample (e.g., non-depth-dependent reference material 614). The material associated with the additional feature may be configured to emit light (e.g., scattered light 118), which can be detected by a detector of the spectral system (e.g., detector 126) to obtain a spectral signal. Alternatively, if the light is not focused on the additional feature and the opening and / or at the intended location of the additional feature, the light generated by the spectral system may not illuminate the material associated with the additional feature, making it impossible to obtain a spectral signal, and / or the light emitted by the material associated with the additional feature may provide a weak spectral signal (e.g., with a small peak).

[0092] The sample positioning system can be further moved incrementally along the x-axis and / or y-axis to move the additional feature relative to the opening around an additional desired position, and one or more additional spectral measurements can be performed by the spectral system to acquire the spectral signal associated with the additional feature at each increment. For illustration, the sample positioning system can be moved to incrementally position the additional feature of the calibration sample around the additional desired position according to a pattern (e.g., a box pattern, a circular pattern, a Z-shaped pattern, etc.). The peak signal intensity (e.g., peak amplitude and / or centroid) of each spectral signal can be determined for each spectral measurement associated with the additional feature at each increment. The spectral signal with the maximum peak signal intensity (e.g., higher than the peak signal intensity of another spectral signal) can correspond to the additional feature properly aligned with the opening and / or the focal point of light transmitted through the opening of the sample positioning system. Therefore, the additional position of the additional feature can be determined based on the position of the sample positioning system in which a spectral signal with a higher peak signal intensity relative to another peak signal intensity is acquired.

[0093] In some examples, the additional location of an additional feature can be determined based on a peak signal intensity exceeding a threshold. For example, the threshold can be configured to indicate that the additional feature of the calibration sample is adequately aligned with the aperture and / or focus of light (e.g., to provide accurate spectral measurements of the sample stored in a sample holder at a location corresponding to the additional location). For illustration, the additional location of the additional feature can be determined as the additional expected location when the peak signal intensity of the spectral signal acquired at the additional expected location exceeds the threshold. Alternatively, when the peak signal intensity of the spectral signal acquired at the additional expected location is below the threshold, the sample positioning system can be moved incrementally around the additional expected location, such as until another peak signal intensity of another spectral signal exceeds the threshold. Thus, the additional location can be determined based on the location of the sample positioning system where the peak signal intensity exceeds the threshold. In some examples, the additional location may include a distance (e.g., along the x-axis and / or y-axis) offset of the additional location relative to the additional expected location and / or the first location.

[0094] Additionally or alternatively, the sample positioning system can be moved along the x-axis and y-axis until the additional spectral measurement converges to the maximum peak signal intensity. For illustration, a spectral signal can be acquired as the sample positioning system increments in a first direction along the x-axis and / or y-axis. If the peak signal intensity of the spectral signal increases, the sample positioning system can continue to increment in the first direction. Alternatively, if the peak signal intensity of the spectral signal decreases, the sample positioning system can increment in a second, opposite direction until the maximum peak signal intensity is determined.

[0095] In some examples, the spectral system may continue to move the sample positioning system and perform additional spectral measurements associated with additional features of the calibration sample (e.g., the remaining holes included in the first set of non-depth-related holes 604) to determine the additional location of the additional features.

[0096] Method 800 further includes, at operation 806, generating calibration data for calibrating the motion of the sample positioning system along the x-axis and y-axis based on the first position and the one or more additional positions. In some examples, the calibration data may include calibration values ​​representing differences associated with a first expected position of the first position relative to a first feature along the x-axis and y-axis, and differences associated with one or more additional expected positions of the one or more additional positions relative to the one or more additional features along the x-axis and y-axis. Such differences may include one or more of skew, offset, or scaling associated with calibrating the sample and / or the sample positioning system. Calibration values ​​may be represented by any suitable metric, such as one or more discrete values ​​(e.g., coordinates, distance, orientation, angle, slope, etc.).

[0097] As an illustrative example, Figure 10 A specific implementation 1000 of a calibration sample 600 is shown, deviated from its intended position 1002 (e.g., when the calibration sample 600 is inserted together with the sample support 200 of the sample positioning system 104 without any difference). As shown, the calibration plate 602 of the calibration sample 600 is deviated along the x-axis (e.g., as shown by ΔX) and along the y-axis (e.g., as shown by ΔY). Based on the intended position 1002, intended positions 1004 of one or more features of the calibration sample 600 may be determined, such as according to SLAS criteria and / or as specified by user input. For example, each intended position 1004 corresponds to the intended position of a corresponding hole included in the first set of non-depth-related holes 604, such as according to a standard distance between holes. Based on spectral measurements, actual positions 1006 (e.g., positions 1006-1 to 1006-4) may be determined for each corresponding hole included in the first set of non-depth-related holes 604.

[0098] For illustration, the one or more calibration values ​​may include one or more of the following: the distance along the x-axis between the first expected position 1004-1 of the first non-depth-related hole 604-1 and the first position 1006-1 of the first non-depth-related hole 604-1; the distance along the y-axis between the first expected position 1004-1 and the first position 1006-1; the total distance between the first expected position 1004-1 and the first position 1006-1; the angle between the x-axis and another axis extending between the first expected position 1004-1 and the first position 1006-1; or the angle between the y-axis and another axis extending between the first expected position 1004-1 and the first position 1006-1.

[0099] Such calibration values ​​may additionally or alternatively be determined for additional positions 1006 (such as between the second expected position 1004-2 of the second non-depth-related hole 604-2 and the second position 1006-2 of the second non-depth-related hole 604-2, between the third expected position 1004-3 of the third non-depth-related hole 604-3 and the third position 1006-3 of the third non-depth-related hole 604-3, and / or between the fourth expected position 1004-4 of the fourth non-depth-related hole 604-4 and the fourth position 1006-4 of the fourth non-depth-related hole 604-4). In some examples, calibration data associated with additional positions 1006 (e.g., second positions 1004-2, third positions 1004-3, and fourth positions 1004-4) is provided relative to additional expected positions 1004 (e.g., second positions 1006-2, third positions 1006-3, and fourth positions 1006-4), such as offsets relative to additional expected positions 1004. Additionally or alternatively, calibration data associated with additional positions 1006 may be provided relative to first positions 1006-1, such as offsets relative to first positions 1006-1. This one or more calibration values ​​may additionally or alternatively include the slope of one or more lines (e.g., as shown by dashed lines) between the two positions 1006, the slope of one or more expected lines (e.g., as shown by solid lines) between the two expected positions 1004, and / or the angle between the lines and the respective expected lines. Other suitable differences may also be included in the calibration data.

[0100] In some examples, the sample positioning system is configured to move along the x and y axes but not along the z axis. In these cases, the motion of the sample positioning system is calibrated only along the x and y axes. Alternatively, the sample positioning system can be configured to move along the z axis in addition to the x and y axes. In these examples, the motion of the sample positioning system can be further calibrated along the z axis. In some examples, the optics used to guide light toward the sample can be adjusted to adjust the focus of the light along the z axis. For example, Figure 1 and Figure 7 The focusing lens 116 can be motorized to move the focal point of the illuminating light along the z-axis. For example, based on one or more spectral measurements received from the spectral system, a second position associated with a second feature of a calibration sample supported by the sample positioning system can be determined. In some examples, the second position may further represent the coordinates of the first feature along the z-axis. Based on the second position, calibration data for calibrating the movement of the sample positioning system along the z-axis can be generated. Similar to determining the first position (XY) of the first feature, the focus can be adjusted along the z-axis while acquiring the spectral signal. The second position can then be determined at the location where the strongest peak signal intensity is detected.

[0101] As an illustrative example, Figure 11An illustrative embodiment 1100 of a calibration sample 600 is shown, deviating from its intended position 1102 along the z-axis (e.g., as indicated by ΔZ) (e.g., when the calibration sample 600 is inserted together with the sample support 200 of the sample positioning system 104 without any difference). As shown, one or more intended positions 1104 (e.g., intended positions 1104-1 to 1104-2) can be determined based on the intended position 1102, such as according to SLAS criteria and / or as specified by user input. For example, each intended position 1104 corresponds to the intended position of a corresponding hole included in the second set of depth-correlated holes 606. Based on spectral measurements, actual positions 1106 (e.g., positions 1106-1 to 1106-2) are determined, for example, for each corresponding hole included in the second set of depth-correlated holes 606.

[0102] For illustration, the one or more calibration values ​​may include one or more of the z-axis distances between the first expected position 1104-1 of the first depth-related hole 606-1 and the first position 1106-1 of the first depth-related hole 606-1. Such one or more calibration values ​​may additionally or alternatively be determined for additional positions 1106 (e.g., between the second expected position 1104-2 of the second depth-related hole 604-2 and the second position 1106-2 of the second depth-related hole 606-2, etc.). The one or more calibration values ​​may additionally or alternatively include the slope of one or more lines (e.g., as shown by dashed lines) between the two positions 1106, the slope of one or more expected lines (e.g., as shown by solid lines) between the two expected positions 1104, and / or the angle between the lines and the respective expected lines.

[0103] In some examples, the position 1106 associated with a second feature of the calibration sample 600 (e.g., holes included in the second set of depth-dependent holes 606) represents the position 1006 associated along the z-axis with a first feature of the calibration sample 600 (e.g., holes included in the first set of non-depth-dependent holes 604). For illustration, the first position 1106-1 associated with a first depth-dependent hole 606-1 along the z-axis may correspond to the first position 1006-1 associated with a corresponding first non-depth-dependent hole 604-1 along the z-axis. Similarly, the second position 1106-2 associated with a second depth-dependent hole 606-2 along the z-axis may correspond to the second position 1006-2 associated with a corresponding second non-depth-dependent hole 604-2 along the z-axis, and so on.

[0104] Return to reference Figure 8Method 800 further includes, at operation 808, positioning a sample (e.g., sample 112, sample 300) based on calibration data using a sample positioning system for performing spectroscopic measurements on the sample (e.g., one or more analytes included in the sample). For example, the calibration data may be applied to the sample positioning system, such as for a measurement procedure to generate one or more spectroscopic measurements using the sample positioning system. For example, after generating the calibration data, the calibration sample 600 may be removed from the sample positioning system 104. Another sample (such as sample 300) may be inserted into a sample support 200 of the sample positioning system 104, which may include one or more features (e.g., orifices 304) for receiving one or more analytes. The sample positioning system 104 may be moved (e.g., via controller 108) to position the orifices 304 of the sample 300 containing one or more samples of interest, which have openings 208 to illuminate one or more analytes and acquire one or more spectroscopic measurements associated with the one or more analytes (e.g., as shown in the image). Figure 5A and Figure 5B (As shown). When the sample positioning system 104 is moved, its movement is calibrated according to calibration data. As an illustrative example, if the analyte of interest is contained within a first hole 304-1 of the sample 300 corresponding to a first non-depth-related hole 604-1 of the calibration sample 600, the sample positioning system 104 may be moved to a first position 1006-1 (e.g., instead of the first expected position 1004-1). Furthermore, the actual positions of other holes 304 of the sample 300 located within the sample positioning system 104 can be derived based on the calibration data, such that the sample positioning system 104 is moved to the actual positions of the holes 304 (e.g., along the x-axis, y-axis, and / or z-axis) rather than the expected positions of the holes 304 to resolve discrepancies associated with the sample positioning system 104.

[0105] In some embodiments, one or more of the systems, components, and / or processes described herein may be implemented and / or performed by one or more suitably configured computing devices. To this end, one or more of the systems and / or components described above may include, or be implemented by, any computer hardware and / or computer implementation instructions (e.g., software) embodied on, or implemented by, at least one non-transitory computer-readable medium configured to perform one or more of the processes described herein. Specifically, system components may be implemented on one physical computing device or on more than one physical computing device. Therefore, system components may include any number of computing devices and may employ any number of computer operating systems.

[0106] In some embodiments, one or more processes described herein may be implemented at least in part as instructions embodied in a non-transitory computer-readable medium and executable by one or more computing devices. Typically, a processor (e.g., a microprocessor) receives instructions from a non-transitory computer-readable medium (e.g., memory, etc.) and executes those instructions, thereby performing one or more processes, including one or more processes described herein. Such instructions may be stored and / or transmitted using any of a variety of known computer-readable media.

[0107] Computer-readable media (also known as processor-readable media) include any non-transitory medium that contributes to providing data (e.g., instructions, such as computer program products embodied on a computer-readable medium) that can be read by a computer (e.g., by the computer's processor). Such media can take many forms, including but not limited to non-volatile and / or volatile media. Non-volatile media may include, for example, optical discs or magnetic disks and other permanent storage. Volatile media may include, for example, dynamic random access memory (“DRAM”), which typically constitutes main memory. Common forms of computer-readable media include, for example, magnetic disks, hard disks, magnetic tapes, any other magnetic media, optical disc read-only memory (“CD-ROM”), digital video discs (“DVD”), any other optical media, random access memory (“RAM”), programmable read-only memory (“PROM”), electrically erasable programmable read-only memory (“EPROM”), FLASH-EEPROM, any other memory chip or cassette disk, or any other tangible medium that is computer-readable.

[0108] The advantages and features of this disclosure are further described in the following statements:

[0109] 1. A method for a sample positioning system for calibrating a spectral system, the method comprising: determining a first position associated with a first feature of a calibration sample supported by the sample positioning system based on one or more spectral measurements output by the spectral system, wherein the sample positioning system is configured to translate the calibration sample along an x-axis and a y-axis of the sample positioning system to position the calibration sample for performing the one or more spectral measurements, wherein the first position represents coordinates of the first feature on the x-axis and the y-axis; determining one or more additional positions associated with one or more additional features of the calibration sample based on one or more additional spectral measurements output by the spectral system, the one or more additional positions representing one or more additional coordinates of the one or more additional features along the x-axis and the y-axis; and generating calibration data based on the first position and the one or more additional positions for calibrating the motion of the sample positioning system along the x-axis and the y-axis.

[0110] 2. The method according to any one of the foregoing statements, the method further comprising: determining, based on the one or more spectral measurements output by the spectral system, a second position associated with a second feature of the calibration sample supported by the sample positioning system included in the spectral system, the second position further representing the coordinates of the first feature along the z-axis; and further generating, based on the second position, calibration data for calibrating the motion of the sample positioning system along the x-axis, the y-axis, and the z-axis.

[0111] 3. The method according to any one of the foregoing statements, wherein the calibration data includes calibration values ​​representing differences associated with a first expected position of the first position relative to the first feature along the x-axis and the y-axis, and one or more additional expected positions of the one or more additional positions relative to the one or more additional features along the x-axis and the y-axis.

[0112] 4. The method according to any one of the foregoing statements, wherein the first location is determined based on the peak signal intensity of the one or more spectral measurements, and the one or more additional locations are determined based on the peak signal intensity of the one or more additional spectral measurements.

[0113] 5. The method according to any one of the foregoing statements, the method further comprising applying the calibration data to the sample positioning system for a measurement procedure to generate one or more spectral measurements using the spectral system.

[0114] 6. The method according to any one of the foregoing statements, wherein the calibration sample comprises a calibration plate, the calibration plate comprising: a first group of at least three wells, each well in the first group of at least three wells having a first aperture and non-deep focus related reference material, wherein the first feature and the one or more additional features correspond to one or more wells in the first group of at least three wells; and a second group of at least three wells, each well in the second group of at least three wells having a second aperture and depth-of-focus related reference material, wherein the second feature corresponds to one or more wells in the second group of at least three wells.

[0115] 7. The method according to any one of the foregoing statements, wherein each of the at least three holes in the second group is offset from the corresponding hole in the first group of at least three holes at different corners of the calibration plate, and the offset distance is within 10 mm.

[0116] 8. The method according to any one of the foregoing statements, wherein the calibration plate is of the same size as a plate according to the Laboratory Automation and Screening Association (SLAS) standard.

[0117] 9. A spectroscopic system comprising: a sample positioning system configured to move a sample along an x-axis and a y-axis of the sample positioning system; a source and a detector for performing spectroscopic measurements on the sample; a memory for storing instructions; and one or more processors communicatively coupled to the memory and configured to execute the instructions to perform a process comprising: performing one or more spectroscopic measurements on a calibration sample; determining a first position associated with a first feature of the calibration sample based on the one or more spectroscopic measurements, wherein the first position represents coordinates of the first feature along the x-axis and the y-axis; performing one or more additional spectroscopic measurements on the calibration sample; determining one or more additional positions associated with one or more additional features of the calibration sample based on the one or more additional spectroscopic measurements, wherein the one or more additional positions represent one or more additional coordinates of the one or more additional features along the x-axis and the y-axis; generating calibration data for calibrating the movement of the sample positioning system along the x-axis and the y-axis based on the first position and the one or more additional positions; positioning the sample using the sample positioning system based on the calibration data; and performing spectroscopic measurements on the sample.

[0118] 10. The spectral system according to any one of the foregoing statements, wherein the process further comprises: determining a second position associated with a second feature of the calibration sample based on the one or more spectral measurements, the second position further representing the coordinates of the first feature along the z-axis of the sample positioning system; and further generating, based on the second position, the calibration data for calibrating the motion of the sample positioning system along the x-axis, the y-axis, and the z-axis.

[0119] 11. The spectral system according to any one of the preceding statements, wherein the first feature includes a first aperture, and wherein the second feature includes a depth-of-focus-correlated reference material located behind a second aperture larger than the first aperture.

[0120] 12. The spectral system according to any one of the foregoing statements, wherein the distance between the second position and the first position in the XY plane of the calibration sample is within 10 mm.

[0121] 13. The spectral system according to any one of the foregoing statements, wherein the first position and the second position at least partially overlap.

[0122] 14. The spectral system according to any one of the foregoing statements, wherein the calibration sample comprises a calibration plate according to the Laboratory Automation and Screening Association (SLAS) standard, and the first feature and the second feature are disposed at the positions of adjacent holes in the calibration plate.

[0123] 15. The spectral system according to any one of the foregoing statements, wherein the calibration sample comprises a plate, the plate comprising a first group of at least three wells and a second group of at least three wells, each well in the first group of at least three wells having an aperture and non-deep focus related reference material for determining the calibration data along the x-axis and the y-axis, and the first feature and the one or more additional features corresponding to one or more wells in the first group of at least three wells, each well in the second group of at least three wells having an aperture and depth-of-focus related reference material for determining the calibration data along the z-axis, and the second feature corresponding to one well in the second group of at least three wells.

[0124] 16. The spectral system according to any one of the preceding statements, wherein each of the at least three holes in the second set is offset from the corresponding hole in the first set of at least three holes at a different corner of the plate.

[0125] 17. The spectral system according to any one of the foregoing statements, wherein determining the first position based on the spectral measurement comprises determining the first position based on the peak signal intensity of one or more spectra from the spectral measurement, and wherein determining the one or more additional positions based on the one or more additional spectral measurements comprises determining the additional positions based on the peak signal intensity of one or more additional spectra from the additional spectral measurements.

[0126] 18. The spectroscopic system according to any one of the foregoing statements, wherein the first feature and the one or more additional features are each associated with the pore size of the calibration sample.

[0127] 19. The spectral system according to any one of the foregoing statements, wherein the calibration data includes calibration values ​​representing differences associated with a first expected position of the first position relative to the first feature along the x-axis and the y-axis, and one or more additional expected positions of the one or more additional positions relative to the one or more additional features along the x-axis and the y-axis.

[0128] 20. The spectral system according to any one of the foregoing statements, wherein the difference associated with the first position relative to the first feature along the x-axis and the y-axis and the one or more additional positions relative to the one or more additional features along the x-axis and the y-axis includes one or more of a skew, offset, or scaling associated with the calibration sample.

[0129] 21. The spectral system according to any one of the foregoing statements, wherein the calibration data is generated further based on a first expected position of the first feature and one or more additional expected positions of the one or more additional features.

[0130] 22. The spectroscopic system according to any one of the foregoing statements, wherein the first feature and the one or more additional expected positions are determined based on the positions of the first feature and the one or more additional features on the calibration sample.

[0131] 23. The spectral system according to any one of the foregoing statements, wherein the calibration sample has the same size as a plate according to the Laboratory Automation and Screening Association (SLAS) standard.

[0132] 24. The spectral system according to any one of the foregoing statements, wherein the first feature includes a first aperture corresponding to the center of a hole in the plate according to the SLAS standard.

[0133] 25. The spectral system according to any one of the foregoing statements, wherein the first feature includes an aperture with a diameter of 0.01 mm to 1.5 mm.

[0134] 26. The spectral system according to any one of the foregoing statements, the spectral system further comprising a lens for focusing light generated from the source onto the calibration sample, wherein the position of the focal point of the light along the z-axis is adjusted by adjusting the relative position between the lens and the calibration sample.

[0135] 27. The spectral system according to any one of the foregoing statements, wherein adjusting the relative position between the lens and the calibration sample includes adjusting the position of the lens, and wherein the sample positioning system does not move the calibration sample along the z-axis.

[0136] 28. The spectroscopic system according to any one of the foregoing statements, wherein the calibration sample is integrated into the sample positioning system.

[0137] 29. The spectral system according to any one of the foregoing statements, wherein the sample positioning system moves along the x-axis and the y-axis but not along the z-axis.

[0138] 30. A Raman spectroscopy system comprising a spectral system according to any one of the foregoing statements, wherein the spectral system is the Raman spectroscopy system.

[0139] 31. A calibration plate comprising: a first group of at least three holes, each hole in the first group of at least three holes having a first aperture and a non-deep focus-related reference material; and a second group of at least three holes, each hole in the second group of at least three holes having a second aperture and a depth-of-focus-related reference material.

[0140] 32. The calibration plate according to any one of the foregoing statements, wherein each of the at least three holes in the second set is offset from the corresponding hole in the first set of at least three holes at different corners of the plate.

[0141] 33. The calibration plate according to any one of the foregoing statements, wherein the offset distance is within 10 mm.

[0142] 34. The calibration plate according to any one of the foregoing statements, wherein each of the at least three holes in the second group at different corners of the calibration plate at least partially overlaps with a corresponding hole in the at least three holes in the first group.

[0143] 35. The calibration plate according to any one of the foregoing statements, wherein the second aperture is larger than the first aperture.

[0144] 36. The calibration plate according to any one of the foregoing statements, wherein the first aperture comprises a diameter of 0.01 mm to 1.5 mm.

[0145] 37. The calibration plate according to any one of the foregoing statements, wherein each of the at least three wells in the second set is offset from the corresponding well in the at least three wells in the first set, in accordance with the Laboratory Automation and Screening Association (SLAS) standard.

[0146] 38. The calibration plate according to any one of the foregoing statements, wherein the calibration plate is of the same size as a plate according to the Laboratory Automation and Screening Association (SLAS) standard.

[0147] 39. The calibration plate according to any one of the foregoing statements, wherein the first set of at least three wells and the second set of at least three wells comprise the center of the well locations of the plate according to the Laboratory Automation and Screening Association (SLAS) standard.

[0148] Those skilled in the art will recognize that, although various exemplary embodiments have been described with reference to the accompanying drawings in the foregoing description, it will be apparent that various modifications and alterations can be made thereto, and additional embodiments can be implemented, without departing from the scope of the invention as set forth in the appended claims. For example, certain features of one embodiment described herein may be combined with or substituted for features of another embodiment described herein. Therefore, the description and drawings should be considered illustrative rather than restrictive.

Claims

1. A method for calibrating a sample positioning system for a spectroscopic system, the method comprising: A first position is determined based on one or more spectral measurements output by the spectral system, which is associated with a first feature of a calibration sample supported by the sample positioning system, wherein the sample positioning system is configured to translate the calibration sample along the x-axis and y-axis of the sample positioning system to position the calibration sample for performing the one or more spectral measurements, wherein the first position represents the coordinates of the first feature on the x-axis and the y-axis; One or more additional locations associated with one or more additional features of the calibration sample are determined based on one or more additional spectral measurements output by the spectral system, the one or more additional locations representing one or more additional coordinates of the one or more additional features along the x-axis and the y-axis; and Based on the first position and the one or more additional positions, calibration data is generated for calibrating the motion of the sample positioning system along the x-axis and the y-axis.

2. The method according to claim 1, further comprising: A second position is determined based on one or more spectral measurements output by the spectral system, and is associated with a second feature of the calibration sample supported by the sample positioning system included in the spectral system. The second position further represents the coordinates of the first feature along the z-axis. Further, based on the second position, calibration data is generated for calibrating the motion of the sample positioning system along the x-axis, y-axis, and z-axis.

3. The method according to claim 2, wherein the calibration sample comprises a calibration plate, the calibration plate comprising: A first group of at least three holes, each of the first group of at least three holes having a first aperture and a non-deep-focus related reference material, wherein the first feature and the one or more additional features correspond to one or more holes in the first group of at least three holes; and The second group has at least three holes, each of which has a second aperture and depth-of-focus related reference material, wherein the second feature corresponds to one or more holes in the second group of at least three holes.

4. The method of claim 3, wherein each of the at least three holes in the second group is offset from the corresponding hole in the first group of at least three holes at different corners of the calibration plate, and the offset distance is within 10 mm.

5. The method of claim 3, wherein the calibration plate is the same size as a plate according to the Laboratory Automation and Screening Association (SLAS) standard.

6. The method of claim 1, wherein the calibration data includes calibration values ​​representing differences associated with a first expected position of the first position relative to the first feature along the x-axis and the y-axis, and one or more additional expected positions of the one or more additional positions relative to the one or more additional features along the x-axis and the y-axis.

7. The method of claim 1, wherein the first location is determined based on the peak signal intensity of the one or more spectral measurements, and the one or more additional locations are determined based on the peak signal intensity of the one or more additional spectral measurements.

8. The method of claim 1, further comprising applying the calibration data to the sample positioning system for a measurement procedure to generate one or more spectral measurements using the spectral system.

9. A spectroscopic system, the spectroscopic system comprising: A sample positioning system configured to move a sample along the x-axis and y-axis of the sample positioning system; A source and a detector, the source and the detector being used to perform spectroscopic measurements on the sample; The memory is used to store instructions; and One or more processors, communicatively coupled to the memory and configured to execute the instructions to perform a process including: Perform one or more spectral measurements on the calibration sample; A first location associated with a first feature of the calibration sample is determined based on the one or more spectral measurements, wherein the first location represents the coordinates of the first feature along the x-axis and the y-axis; Perform one or more additional spectroscopic measurements on the calibration sample; Based on the one or more additional spectral measurements, one or more additional locations are determined that are associated with one or more additional features of the calibration sample, the one or more additional locations representing one or more additional coordinates of the one or more additional features along the x-axis and the y-axis; Based on the first position and the one or more additional positions, calibration data is generated for calibrating the motion of the sample positioning system along the x-axis and the y-axis; The sample is located using the sample positioning system based on the calibration data; as well as Spectroscopic measurements were performed on the sample.

10. The spectroscopic system of claim 9, wherein the process further comprises: A second position associated with a second feature of the calibration sample is determined based on the one or more spectral measurements, the second position further representing the coordinates of the first feature along the z-axis of the sample positioning system; and Further, based on the second position, calibration data is generated for calibrating the motion of the sample positioning system along the x-axis, y-axis, and z-axis.

11. The spectral system of claim 10, wherein the first feature includes a first aperture, and wherein the second feature includes a depth-of-focus reference material located behind a second aperture larger than the first aperture.

12. The spectral system of claim 10, wherein the distance between the second position and the first position in the XY plane of the calibration sample is within 10 mm.

13. The spectral system of claim 10, wherein the calibration sample comprises a calibration plate according to the Laboratory Automation and Screening Association (SLAS) standard, and the first feature and the second feature are disposed at the positions of adjacent holes in the calibration plate.

14. The spectral system of claim 10, wherein the calibration sample comprises a plate comprising a first group of at least three wells and a second group of at least three wells, each well in the first group of at least three wells having an aperture and non-deep focus-dependent reference material for determining the calibration data along the x-axis and the y-axis, and the first feature and the one or more additional features corresponding to one or more wells in the first group of at least three wells, each well in the second group of at least three wells having an aperture and depth-of-focus-dependent reference material for determining the calibration data along the z-axis, and the second feature corresponding to one well in the second group of at least three wells.

15. The spectral system of claim 10, further comprising a lens for focusing light generated from the source onto the calibration sample, wherein the focal point of the light along the z-axis is adjusted by adjusting the relative position between the lens and the calibration sample.

16. The spectral system of claim 15, wherein adjusting the relative position between the lens and the calibration sample includes adjusting the position of the lens, and wherein the sample positioning system does not move the calibration sample along the z-axis.

17. The spectral system of claim 9, wherein the calibration data includes calibration values ​​representing differences associated with a first expected position of the first position relative to the first feature along the x-axis and the y-axis, and one or more additional expected positions of the one or more additional positions relative to the one or more additional features along the x-axis and the y-axis.

18. The spectral system of claim 9, wherein the first feature comprises an aperture with a diameter of 0.01 mm to 1.5 mm.

19. The spectroscopic system of claim 9, wherein the calibration sample is integrated into the sample positioning system.

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