High-flux spectrum type surface plasma resonance detection system and detection method

Abstract

The invention discloses a high-flux spectrum type surface plasma resonance detection system and a detection method. The system sequentially comprises a light source module, a light beam shaping module, a spatial light modulation module, an SPR sensing module, an optical processing module, a light splitting module, a wavelength selection module and a signal detection module from the light source module to the signal detection module. The spatial light modulation technology of the digital micromirror is combined with the SPR high-throughput detection technology, and high-throughput, high-sensitivity and wide-dynamic-range SPR signal detection is realized by utilizing the characteristics of high resolution, programmability and integration of the digital micromirror. In order to ensure high sensitivity and wide dynamic range while improving the detection flux, the high-resolution light modulation function of the digital micromirror is combined with the optical structure design, so that the spatial multiplexing and wavelength modulation detection functions of a plurality of sensing sites can be realized; meanwhile, a single-point detector is adopted to replace a traditional CCD detector to realize spectral signal measurement, so that the sensitivity and the dynamic measurement range of SPR signals are improved.

Description

Technical Field

[0001] This invention relates to the field of SPR optical signal detection technology, specifically to a high-throughput spectral surface plasmon resonance detection system and method. Background Technology

[0002] Surface plasmon resonance (SPR) is a physical optical phenomenon and an optical technique used to characterize changes in the refractive index of a surface. SPR technology allows for real-time observation of surface phenomena such as molecular interactions and thin film formation. As a high-precision, label-free, and real-time response detection method, it has been widely applied in research fields such as life sciences, biology, pharmacology, and analytical chemistry.

[0003] In terms of detection methods, SPR sensors have four modulation types: angle modulation, wavelength modulation, phase modulation, and intensity modulation. Among them, angle modulation detection is widely used in commercial instruments. Compared with angle modulation detection, wavelength modulation detection has some other significant advantages, such as simple instrument structure, wide refractive index measurement range, and ease of integration with other detection technologies.

[0004] With the continuous development of modern life science technology, increasingly higher demands are being placed on SPR detection technology. The most pressing requirement is to increase throughput, i.e., processing large amounts of analytical data. To improve throughput, several manufacturers have launched commercial multi-channel SPR instruments. These instruments offer excellent performance, very high measurement accuracy, and integrate powerful sample introduction devices with a high degree of automation, enabling simultaneous detection of SPR signal changes across multiple channels. However, the instruments and consumables are very expensive, and the increased throughput is limited, often restricting their practical application. Summary of the Invention

[0005] In view of this, embodiments of the present invention provide a high-throughput spectral surface plasmon resonance detection system and detection method.

[0006] The first aspect of the present invention provides a high-throughput spectral surface plasmon resonance detection system, which includes, in sequence from the light source module to the signal detection module: a light source module, a beam shaping module, a spatial light modulation module, an SPR sensing module, an optical processing module, a beam splitting module, a wavelength selection module, and a signal detection module; The light source module is used to generate an initial light signal; The beam shaping module is used to shape the initial optical signal into a parallel optical signal; The spatial light modulation module is used to select the optical signal of the target area from the parallel light signal and transmit it to the SPR sensing module; The SPR sensing module is used to place the array of chips under test, and uses the light signal of the target area to detect the SPR spectral signal of the target area of ​​the chip under test to obtain the SPR reflected light signal. The optical processing module is used to denoise the SPR reflected light signal to obtain a denoised SPR light signal. The beam splitting module is used to perform spectral expansion on the SPR denoised optical signal to obtain an SPR multi-wavelength optical signal. The wavelength selection module is used to select the target wavelength of the SPR optical signal for output in the SPR multi-wavelength optical signal; The signal detection module is used to collect SPR optical signals at the target wavelength and output spectral data.

[0007] Furthermore, the light source module generates broadband light covering the visible light region as an initial optical signal output; the wavelength range of the initial optical signal is not less than 380 nm-780 nm.

[0008] Furthermore, the beam shaping module includes a collimating lens and an adjustable aperture; the collimating lens is a cylindrical lens used to adjust the diverging initial light signal into a parallel light signal; the adjustable aperture is used to adjust the beam size of the parallel light signal.

[0009] Furthermore, the spatial light modulation module includes a first digital micromirror; the first digital micromirror is used to retain the light signal of the target area and transmit it to the SPR sensing module according to the first control command, and to shield the light signal of other areas; The target area in the first control command is determined based on the sensing sites of the chip array under test.

[0010] Furthermore, the SPR sensing module includes a polarizer and a triangular prism; the polarizer is used to adjust the light signal to a horizontal polarization state; a chip array under test is placed on the triangular prism, and the sensing sites in the target area of ​​the chip array under test undergo total internal reflection and SPR phenomenon after being illuminated by the light signal, and generate an SPR reflected light signal output carrying SPR information.

[0011] Furthermore, the optical processing module includes a bandpass filter, a first cylindrical lens, and a second cylindrical lens; The bandpass filter is used to filter out optical signals in other bands except the target band in the SPR reflected optical signal to obtain the SPR denoised optical signal; The first cylindrical lens and the second cylindrical lens are used to converge and shape the SPR denoised optical signal.

[0012] Furthermore, the beam splitting module includes a diffraction grating and a first converging lens; the diffraction grating is used to perform beam splitting processing on the SPR denoised optical signal, so that optical signals of different wavelengths are spatially separated to obtain SPR multi-wavelength optical signals. The first converging lens is a spherical lens, used to control the emission of SPR multi-wavelength optical signals toward the wavelength selection module.

[0013] Furthermore, the wavelength selection module includes a second digital micromirror; the second digital micromirror is used to retain the SPR light signal of the target wavelength and transmit it to the signal detection module according to the second control command, while shielding light signals of other wavelengths.

[0014] Furthermore, the signal detection module includes a second converging lens, a focusing lens, and a single-point detector; the second converging lens is a spherical lens, used to control the emission of the SPR light signal of the target wavelength towards the focusing lens; the focusing lens is a cylindrical lens, used to focus the SPR light signal of the target wavelength onto the single-point detector; the single-point detector is used to detect the light intensity value of the SPR light signal of the target wavelength, and summarizes the light intensity values ​​corresponding to each wavelength SPR light signal to form a spectral curve, which serves as the spectral information of the corresponding sensing site of the chip array under test.

[0015] Another aspect of this invention discloses a high-throughput spectral surface plasmon resonance detection method, applied to the aforementioned high-throughput spectral surface plasmon resonance detection system, comprising the following steps: A first control command indicating the target area is sent to the first digital micromirror in the spatial light modulation module, causing the first digital micromirror to retain the light signal of the target area and transmit it to the SPR sensing module; The second control command is sent to the second digital micromirror in the wavelength selection module to retain the SPR light signal of different target wavelengths one by one, so that the single-point detector of the signal detection module can measure the light intensity value corresponding to the SPR light signal of different wavelengths and summarize it into the spectral information of the corresponding sensing site of the chip array under test. The step of changing the target area indicated in the first control command and returning to the first digital micromirror in the spatial light modulation module to send the first control command indicating the target area is used to obtain the spectral information of other sensing sites of the chip array under test until all sensing sites of the chip array under test have been measured.

[0016] This invention also discloses a computer program product or computer program, which includes computer instructions stored in a computer-readable storage medium. A processor of a computer device can read the computer instructions from the computer-readable storage medium and execute the computer instructions, causing the computer device to perform the aforementioned method.

[0017] The embodiments of the present invention have the following beneficial effects: The present invention provides a high-throughput spectral surface plasmon resonance (SPR) detection system and method, which combines the spatial light modulation technology of digital micromirrors with SPR high-throughput detection technology. It utilizes the high resolution, programmability, and integrated characteristics of digital micromirrors to achieve high-throughput, high-sensitivity, and wide dynamic range SPR signal detection. To ensure high sensitivity and wide dynamic range while improving detection throughput, the present invention combines the high-resolution light modulation function of digital micromirrors with a precise optical structure design, enabling spatial multiplexing of multiple sensing sites and wavelength modulation detection. Simultaneously, a single-point detector replaces the traditional CCD detector for spectral signal measurement, thereby improving the sensitivity and dynamic measurement range of the SPR signal.

[0018] Additional aspects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description or may be learned by practice of the invention. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is a schematic diagram of the optical structure of a high-throughput spectral surface plasmon resonance detection system according to the present invention; Figure 2 This is a schematic diagram of the device principle of a digital micromirror. Figure 3 This is a schematic diagram of the steps involved in a high-throughput spectroscopic surface plasmon resonance detection method.

[0021] Reference numerals: 1-LED light source, 2-collimating lens, 3-adjustable aperture, 4-first digital micromirror, 5-polarizer, 6-triangular prism, 7-chip array, 8-bandpass filter, 9-first cylindrical lens, 10-second cylindrical lens, 11-diffraction aperture, 12-first converging lens, 13-second digital micromirror, 14-second converging lens, 15-focusing lens, 16-single-point detector. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0023] SPR (Self-Range Phosphoric Interaction) detection technology, as a high-precision, label-free, and real-time response method, has been widely applied in research fields such as life sciences, biology, pharmacology, and analytical chemistry. Due to its advantages such as real-time detection of biomolecular interactions, convenience, higher resolution than traditional methods, no need for labeling, and low sample requirements, SPR detection has become a mature method for detecting biomolecular interactions and is widely used in life science fields such as proteomics, cell signaling, receptor / ligand, antibody / antigen molecule fishing, immune recognition, cancer research, and new drug screening. It is used for real-time dynamic monitoring of interactions between proteins, nucleic acids, and drug molecules / target proteins. Due to its unique advantages, SPR detection technology is increasingly becoming a leading technology for biomolecular interaction analysis.

[0024] In terms of detection methods, SPR sensors have four modulation types: angle modulation, wavelength modulation, phase modulation, and intensity modulation. Among them, angle modulation detection is widely used in commercial instruments. Compared with angle modulation detection, wavelength modulation detection has some other significant advantages, such as simple instrument structure, wide refractive index measurement range, and ease of integration with other detection technologies.

[0025] Therefore, introducing CCD imaging technology into SPR instruments to achieve SPR imaging measurement (SPRi detection technology) is a good solution to improve SPR detection throughput. SPRi combines SPR detection with CCD imaging technology, using a CCD imaging sensor to replace the traditional single-channel photodetector to increase detection throughput. However, the actual detection throughput is limited by chip spotting technology, image resolution, and sensor chip fabrication process.

[0026] It is evident that currently commercially available channel-type SPR instruments suffer from limited throughput and high cost, often limiting their practical application. While SPRi technology can significantly improve throughput, the low signal-to-noise ratio, narrow dynamic range, and inter-pixel crosstalk inherent in image sensors result in lower sensitivity and dynamic range compared to channel-type SPR instruments, making it impossible to simultaneously meet the requirements of high throughput, high sensitivity, and wide dynamic range detection.

[0027] A digital micromirror device (DMD) is a spatial light modulation device composed of millions of independently controllable high-speed digital optical reflection switches. For example... Figure 1 As shown, each optical reflector switch is a micromirror that can deflect back and forth between two angles (corresponding to digital values ​​0 and 1, respectively), thereby realizing the optical switching control function of a single pixel. Due to its compact structure, high resolution, high speed, low cost, and programmability, the DMD is very suitable for the design of various optical instruments.

[0028] Based on this, the first embodiment of the present invention provides a high-throughput spectral surface plasmon resonance detection system, which includes, in sequence from the light source module to the signal detection module: a light source module, a beam shaping module, a spatial light modulation module, an SPR sensing module, an optical processing module, a beam splitting module, a wavelength selection module, and a signal detection module.

[0029] The system comprises the following modules: a light source module to generate an initial optical signal; a beam shaping module to shape the initial optical signal into a parallel optical signal; a spatial light modulation module to select the optical signal of the target region from the parallel optical signal and transmit it to the SPR sensing module; an SPR sensing module to place the array of chips under test and to use the optical signal of the target region to detect the SPR spectral signal of the target region of the chip under test, thereby obtaining the SPR reflected optical signal; an optical processing module to denoise the SPR reflected optical signal, thereby obtaining the SPR denoised optical signal; a beam splitting module to perform spectral expansion on the SPR denoised optical signal, thereby obtaining the SPR multi-wavelength optical signal; a wavelength selection module to select the target wavelength SPR optical signal from the SPR multi-wavelength optical signal for output; and a signal detection module to collect the SPR optical signal of the target wavelength and output spectral data.

[0030] A schematic diagram of the optical architecture of this invention is shown below. Figure 2 As shown, this invention presents a unique DMD-based spatial multiplexing and wavelength scanning structure for multiple sensing sites. It leverages the high resolution, programmability, and integrated characteristics of the DMD to achieve high-throughput, high-sensitivity, and wide dynamic range SPR signal detection. To ensure high sensitivity and wide dynamic range while increasing detection throughput, this invention utilizes the high-resolution optical modulation function of the DMD, combined with a precise optomechanical structure design, to achieve spatial multiplexing and wavelength modulation detection for multiple sensing sites. Simultaneously, a single-point detector replaces the traditional CCD detector for spectral signal measurement, thereby improving the sensitivity and dynamic measurement range of the SPR signal.

[0031] The structure and function of each module in the embodiments of the present invention are described in detail below: Light Source Module: In this embodiment of the invention, the light source module is a combination of an LED broadband light source and a pinhole aperture. The LED broadband light source generates a broadband beam with a wavelength range covering at least the visible light band of 380 nm to 780 nm. The pinhole aperture is positioned in the output optical path of the LED broadband light source. Its function is to shape the broadband beam emitted by the LED into a point light source, providing an initial light source for subsequent optical paths and helping to improve beam quality and ensure the stability of the system's detection reference.

[0032] Beam shaping module: In this embodiment of the invention, it sequentially includes a collimating lens and an adjustable aperture disposed on the output optical path of the pinhole aperture. The collimating lens is used to convert the diverging beam from the pinhole aperture into a parallel beam. The adjustable aperture is disposed in the optical path of this parallel beam, and its aperture is adjustable to limit and adjust the diameter of the parallel beam, making it match the effective area size of the subsequent spatial light modulation device (i.e., the first digital micromirror), thereby ensuring that the illumination range accurately covers the target modulation area and providing ideal beam conditions for subsequent spatial light selection.

[0033] Spatial light modulation module: In this embodiment of the invention, the spatial light modulation module is implemented using a first digital micromirror. The first digital micromirror comprises millions of independently controllable micromirror units, each of which can switch between two preset deflection angles (e.g., +12° and -12°). The effective photosensitive area of ​​the first digital micromirror is pre-divided into multiple sub-regions, each sub-region spatially corresponding to a different sensing site on the sensing chip. Therefore, by applying a first control signal to the first digital micromirror, the micromirror units of the target sub-region are switched to an "on" deflection angle, while the micromirror units of the non-target sub-regions are switched to an "off" deflection angle. This allows for the spatial selective reflection of beams corresponding to specific sensing sites from the incident parallel beam, thereby achieving time-division multiplexing detection of multiple sensing sites. The specific detection throughput can be flexibly adjusted by controlling the number of sub-regions using the first control signal.

[0034] SPR Sensing Module: In this embodiment of the invention, the SPR sensing module sequentially includes a polarizer and a triangular prism. The polarizer is positioned in the beam path selected by the spatial light modulation module, and its function is to adjust the incident beam into specific horizontally polarized light (TM polarized light) to meet the conditions for exciting surface plasmon resonance. A sensor chip array is mounted on the triangular prism, and its bottom surface is optically coupled to the metal thin film of the sensor chip array, either directly or indirectly. Specifically, the surface of the metal thin film of the sensor chip array is constructed as an array containing multiple detection sites. When horizontally polarized light meeting the resonance conditions is incident on the surface of the sensor chip, total internal reflection occurs, exciting surface plasmon waves. Therefore, the intensity and spectral characteristics of the reflected beam change with the refractive index of the medium on the metal thin film surface, thereby modulating the interaction information of the analyte into the reflected light signal.

[0035] Optical Processing Module: In this embodiment of the invention, the optical processing module sequentially includes a bandpass filter and a cylindrical lens group. The bandpass filter is disposed in the reflected light path of the SPR sensing module to filter out stray light outside the target wavelength range (e.g., 420 nm to 700 nm), effectively suppressing background noise. The cylindrical lens group includes a first cylindrical lens and a second cylindrical lens, whose function is to converge and shape the reflected beam after filtering, to compensate for possible optical path offset caused by spatial light selection, and to adjust the beam to a specific spot shape suitable for subsequent beam splitting module reception, thereby ensuring optical signal quality and transmission efficiency, and providing optimized light input conditions for subsequent spectral analysis.

[0036] Spectrometer Module: In this embodiment of the invention, the spectrometer module sequentially includes a diffraction grating and a first converging lens. The diffraction grating is disposed in the optical path of the beam emitted from the optical processing module, and its function is to spatially disperse the incident broadband composite beam according to wavelength using the diffraction effect. The first converging lens is disposed in the subsequent optical path of the diffraction grating, and is used to converge the beams of different wavelengths after dispersion and image them onto the micromirror array plane of the second digital micromirror, thereby forming a clear spectral band spatially expanded in wavelength order at its image plane, providing the necessary optical conditions for the precise wavelength positioning of the subsequent wavelength selection module.

[0037] Wavelength Selection Module: In this embodiment of the invention, the wavelength selection module employs a second digital micromirror to achieve wavelength selection. The second digital micromirror is positioned within the optical path of the spectral band expanded by wavelength in space by the beam splitting module, with the column direction of its micromirror array aligned with the wavelength distribution direction of the spectral band. By applying a second control signal to the second digital micromirror, specific columns or combinations of micromirror units are switched to an "on" deflection angle, while the remaining micromirror units are switched to an "off" deflection angle. This allows for the spatial selective reflection of beams corresponding to specific narrow wavelengths from the incident continuous spectral band. By sequentially changing the positions of the "on" micromirror columns, a wavelength scanning function without mechanical movement can be achieved. The scanning range and resolution of the second digital micromirror can be flexibly configured via the second control signal.

[0038] Signal Detection Module: In this embodiment of the invention, the signal detection module sequentially includes a second converging lens, a focusing lens, and a single-point detector. The second converging lens is positioned in the optical path of the single-wavelength beam emitted from the wavelength selection module, used for initial convergence of the beam. The focusing lens is positioned in the subsequent optical path of the converging lens, used for secondary focusing of the initially converged beam, forming a tiny light spot whose size precisely matches the photosensitive surface of the single-point detector. The photosensitive surface of the single-point detector is precisely positioned at the focal point of the aforementioned focusing lens, used to convert the received optical signal into a corresponding electrical signal. The intensity of this electrical signal characterizes the SPR response intensity of the target region of the chip array under test at the corresponding wavelength. Finally, by summing the SPR response intensities at each wavelength, a spectral curve characterizing the SPR response intensity of the target region of the chip array under test can be formed. Spectral SPR can acquire a complete reflection spectrum curve, not just intensity changes at a single angle or wavelength. By analyzing the shift of the resonant wavelength (i.e., the spectral valley) or the change in the entire spectral shape, richer information can be obtained. For example, it can improve the accuracy and sensitivity of detection, help distinguish between specific binding and non-specific adsorption, and simultaneously obtain information such as the dynamics of molecular interactions, affinity (binding constant), and concentration in a single experiment, providing a more powerful tool for life science research and bioanalysis.

[0039] Traditional SPR sensors typically detect only one or a few sample interactions at a time. This invention employs a chip array combined with spatial light modulation techniques such as DMD to simultaneously perform parallel or rapid sequential detection of dozens or even hundreds of samples or analytes. This significantly reduces the time required to acquire large amounts of data, making it particularly suitable for applications requiring large-scale, rapid screening in fields such as drug screening, proteomics, and clinical diagnostics, thus significantly improving the efficiency and throughput of research and testing.

[0040] The overall structure of this invention has no moving parts, which simplifies the design of the optical system and makes the optical structure of the instrument more compact. This not only reduces the size of the instrument but also lowers its cost.

[0041] The second embodiment of this invention discloses a high-throughput spectral surface plasmon resonance detection method, applied to a high-throughput spectral surface plasmon resonance detection system of the first embodiment. For example... Figure 3 As shown, it includes the following steps: S1. Send a first control command indicating the target area to the first digital micromirror in the spatial light modulation module, so that the first digital micromirror retains the light signal of the target area and transmits it to the SPR sensing module; S2. Send a second control command to the second digital micromirror in the wavelength selection module to retain SPR light signals of different target wavelengths one by one, so that the single-point detector of the signal detection module can measure the light intensity values ​​corresponding to the SPR light signals of different wavelengths and summarize them into the spectral information of the corresponding sensing sites of the chip array under test. S3. Change the target area indicated in the first control command, return to the step of sending the first control command indicating the target area to the first digital micromirror in the spatial light modulation module, obtain the spectral information of other sensing sites of the chip array under test, until all sensing sites of the chip array under test have been measured.

[0042] This invention, through a first control command and a second control command, enables the coordinated operation of a first digital micromirror and a second digital micromirror, achieving overall SPR measurement of the chip array under test. First, the micromirror array of the first digital micromirror is pre-divided into several sub-regions, each sub-region spatially corresponding to a sensing site on the chip. Simultaneously, the column direction of the micromirror array of the second digital micromirror is aligned with the wavelength distribution direction of the dispersed spectrum, with each column or combination of columns corresponding to a specific narrow wavelength.

[0043] During measurement, a sub-region of the first digital micromirror is fixed in the "on" state to select a sensing site to be measured. Subsequently, the second digital micromirror is controlled by sequentially switching the position of its "on" micromirror array to select different wavelengths of light signals to enter the detector, thereby completing the full-spectrum scan of the selected site and generating a complete SPR spectral curve.

[0044] Subsequently, the "on" state sub-region of the first digital micromirror is switched to the next sensing site according to a preset sequence by the first control command, and the wavelength scanning process of the second digital micromirror is repeated. This cycle is repeated until all preset sub-regions on the first digital micromirror are traversed, so that the SPR spectral data of each sensing site on the entire chip array can be acquired efficiently and without mechanical movement.

[0045] This embodiment also provides a computer program product that, when run on a computer, causes the computer to perform the aforementioned related steps to realize the high-throughput spectral surface plasmon resonance detection method provided in the above embodiment.

[0046] Those skilled in the art will understand that modules in the device of the embodiments of the present invention can be adaptively modified and placed in one or more devices different from those embodiments. Modules, units, or components in the embodiments of the present invention can be combined into a single module, unit, or component, and further, they can be divided into multiple sub-modules, sub-units, or sub-components. Except where at least some of such features and / or processes or units are mutually exclusive, any combination can be used to combine all features disclosed in this specification (including the corresponding claims, abstract, and drawings) and all processes or units of any method or device so disclosed. Unless expressly stated otherwise, each feature disclosed in this specification (including the corresponding claims, abstract, and drawings) may be replaced by an alternative feature that serves the same, equivalent, or similar purpose.

[0047] Through the above description of the embodiments, those skilled in the art will understand that, for the sake of convenience and brevity, only the division of the above functional modules is used as an example. In actual applications, the above functions can be assigned to different functional modules as needed, that is, the internal structure of the device can be divided into different functional modules to complete all or part of the functions described above.

[0048] Furthermore, the various embodiments in this specification are described in a progressive manner, and the same or similar parts between the various embodiments can be referred to mutually. In particular, for embodiments such as apparatus and devices, since they are basically similar to the method embodiments, the relevant parts can be referred to the description of the method embodiments. The apparatus, devices, and other embodiments described above are merely illustrative, and the modules, units, etc., described as separate components may or may not be physically separate, that is, they may be located in one place or distributed in multiple places, such as nodes in a system network. Specifically, some or all of the modules and units can be selected according to actual needs to achieve the purpose of the above-described embodiment solutions. Those skilled in the art can understand and implement this without creative effort.

[0049] In the description of this specification, references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0050] Furthermore, the terms "first," "second," etc., used in the embodiments of this invention are for descriptive purposes only and should not be construed as indicating or implying relative importance, or implicitly specifying the number of technical features indicated in this embodiment. Therefore, features defined with terms such as "first" and "second" in the embodiments of this invention can explicitly or implicitly indicate that the embodiment includes at least one of those features. In the description of this invention, the word "multiple" means at least two or more, such as two, three, four, etc., unless otherwise explicitly specified in the embodiments.

[0051] In embodiments of the present invention, the terms "comprising," "including," or any other variations thereof are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element. Furthermore, components, features, and elements with the same names in different embodiments of the present invention may have the same meaning or different meanings, the specific meaning of which must be determined by its interpretation in that specific embodiment or further in conjunction with the context of that specific embodiment.

[0052] Although embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present invention. Other embodiments of the present invention will readily conceive of by considering the specification and practicing the invention. This application is intended to cover any variations, uses, or adaptations of the invention that follow the general principles of the invention and include common knowledge or customary techniques in the art not disclosed herein. The specification and embodiments are to be considered exemplary only, and the true scope and spirit of the invention are indicated by the following claims.

Claims

1. A high-throughput spectroscopic surface plasmon resonance detection system, characterized in that, The light source module, in sequence with the signal detection module, includes: light source module, beam shaping module, spatial light modulation module, SPR sensing module, optical processing module, beam splitting module, wavelength selection module, and signal detection module. The light source module is used to generate an initial light signal; The beam shaping module is used to shape the initial optical signal into a parallel optical signal; The spatial light modulation module is used to select the optical signal of the target area from the parallel light signal and transmit it to the SPR sensing module; The SPR sensing module is used to place the array of chips under test, and uses the light signal of the target area to detect the SPR spectral signal of the target area of ​​the chip under test to obtain the SPR reflected light signal. The optical processing module is used to denoise the SPR reflected light signal to obtain a denoised SPR light signal. The beam splitting module is used to perform spectral expansion on the SPR denoised optical signal to obtain an SPR multi-wavelength optical signal. The wavelength selection module is used to select the target wavelength of the SPR optical signal for output in the SPR multi-wavelength optical signal; The signal detection module is used to collect SPR optical signals at the target wavelength and output spectral data.

2. The high-throughput spectroscopic surface plasmon resonance detection system according to claim 1, characterized in that, The light source module generates broadband light covering the visible light region as the initial light signal output; the wavelength range of the initial light signal is not less than 380 nm-780 nm.

3. The high-throughput spectroscopic surface plasmon resonance detection system according to claim 1, characterized in that, The beam shaping module includes a collimating lens and an adjustable aperture; the collimating lens is a cylindrical lens used to adjust the diverging initial light signal into a parallel light signal; the adjustable aperture is used to adjust the beam size of the parallel light signal.

4. The high-throughput spectroscopic surface plasmon resonance detection system according to claim 1, characterized in that, The spatial light modulation module includes a first digital micromirror; the first digital micromirror is used to retain the light signal of the target area and transmit it to the SPR sensing module according to the first control command, and to shield the light signal of other areas; The target area in the first control command is determined based on the sensing sites of the chip array under test.

5. The high-throughput spectral surface plasmon resonance detection system according to claim 1, characterized in that, The SPR sensing module includes a polarizer and a triangular prism; the polarizer is used to adjust the light signal to a horizontal polarization state; a chip array under test is placed on the triangular prism, and the sensing sites in the target area of ​​the chip array under test undergo total internal reflection and SPR phenomenon after being illuminated by the light signal, and generate an SPR reflected light signal output carrying SPR information.

6. The high-throughput spectroscopic surface plasmon resonance detection system according to claim 1, characterized in that, The optical processing module includes a bandpass filter, a first cylindrical lens, and a second cylindrical lens; The bandpass filter is used to filter out optical signals in other bands except the target band in the SPR reflected optical signal to obtain the SPR denoised optical signal; The first cylindrical lens and the second cylindrical lens are used to converge and shape the SPR denoised optical signal.

7. The high-throughput spectroscopic surface plasmon resonance detection system according to claim 1, characterized in that, The beam splitting module includes a diffraction grating and a first converging lens; the diffraction grating is used to perform beam splitting processing on the SPR denoised optical signal, so that optical signals of different wavelengths are spatially separated to obtain SPR multi-wavelength optical signals. The first converging lens is a spherical lens, used to control the emission of SPR multi-wavelength optical signals toward the wavelength selection module.

8. The high-throughput spectroscopic surface plasmon resonance detection system according to claim 1, characterized in that, The wavelength selection module includes a second digital micromirror; the second digital micromirror is used to retain the SPR light signal of the target wavelength and transmit it to the signal detection module according to the second control command, and to shield light signals of other wavelengths.

9. A high-throughput spectroscopic surface plasmon resonance detection system according to claim 1, characterized in that, The signal detection module includes a second converging lens, a focusing lens, and a single-point detector. The second converging lens is a spherical lens used to control the emission of the SPR light signal of the target wavelength towards the focusing lens. The focusing lens is a cylindrical lens used to focus the SPR light signal of the target wavelength onto the single-point detector. The single-point detector is used to detect the light intensity value of the SPR light signal of the target wavelength, and summarizes the light intensity values ​​corresponding to each wavelength SPR light signal to form a spectral curve, which serves as the spectral information of the corresponding sensing site of the chip array under test.

10. A high-throughput spectroscopic surface plasmon resonance detection method, applied to a high-throughput spectroscopic surface plasmon resonance detection system as described in any one of claims 1-9, characterized in that, Includes the following steps: A first control command indicating the target area is sent to the first digital micromirror in the spatial light modulation module, causing the first digital micromirror to retain the light signal of the target area and transmit it to the SPR sensing module; The second control command is sent to the second digital micromirror in the wavelength selection module to retain the SPR light signal of different target wavelengths one by one, so that the single-point detector of the signal detection module can measure the light intensity value corresponding to the SPR light signal of different wavelengths and summarize it into the spectral information of the corresponding sensing site of the chip array under test. The step of changing the target area indicated in the first control command and returning to the first digital micromirror in the spatial light modulation module to send the first control command indicating the target area is used to obtain the spectral information of other sensing sites of the chip array under test until all sensing sites of the chip array under test have been measured.

Images