Surface plasmon resonance imaging device, method, control system and storage medium

Through the motor control system of the telecentric light source and the angle modulation component, the uniformity of the incident light intensity is adjusted, which solves the detection speed and data quality problems of the surface plasmon resonance imaging device and realizes fast and accurate detection.

CN115508275BActive Publication Date: 2025-09-12CHANGSHA UNIVERSITY
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Patent Information

Application Number
CN202110630755.X
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2021-06-07
Publication Date
2025-09-12
Estimated Expiration
2041-06-07

AI Technical Summary

Technical Problem

The imaging data quality limitations of existing surface plasmon resonance imaging devices make it difficult for the detection speed to meet the needs of rapid detection. The reflected light intensity unevenness and noise have serious impacts, and the existing calibration steps are complex and time-consuming.

Method used

A telecentric light source and angle modulation component are combined with a motor control system to adjust the telecentric angle of the incident light so that the incident light intensity at all sample points on the microarray chip is equal, omitting the standard sample or light intensity calibration step.

Benefits of technology

It achieves rapid detection without complex calibration steps, reduces operation complexity and detection time, and improves detection speed and accuracy.

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Abstract

The present application is applicable to the field of surface plasmon resonance technology and provides a surface plasmon resonance imaging device, method, control system, and storage medium. The surface plasmon resonance imaging device includes a light source system, a detection system, a sample injection system, an imaging system, and a control system. The light source system includes a telecentric light source, a first motor, and an angle modulation component. The detection system includes a coupler and a microarray chip. The sample injection system includes a sample injection pool. The imaging system includes a first array detector. The first motor is mechanically connected to the angle modulation component, and the control system is electrically connected to the first motor and the first array detector, respectively. The control system is used to control the first motor to drive the angle modulation component to move, thereby adjusting the telecentric angle of the incident light generated by the telecentric light source so that the intensity of the incident light at all sample points on the microarray chip is equal, eliminating the need for measurement steps such as standard sample calibration or standard light intensity calibration, thereby meeting rapid detection requirements.
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Description

Technical Field

[0001] The present application belongs to the field of surface plasmon resonance (SPR) technology, and in particular relates to a surface plasmon resonance imaging device, method, control system, and storage medium. Background Art

[0002] When a polarized light beam of a certain wavelength and incident angle passes through a coupler and strikes the interface between a metal and a dielectric, internal reflection occurs. This excitation of an evanescent wave at the interface transfers the beam's energy, causing a sharp attenuation of the reflected light intensity. This phenomenon is known as surface plasmon resonance, and the corresponding incident angle is called the resonance angle. When the incident beam is parallel and the angle of incidence is fixed near the resonance angle, a device that detects the spatial distribution of the reflected light intensity using a first array detector to detect changes in the refractive index or thickness of the medium within a specific area is called a surface plasmon resonance imaging (SPRi) device. Unlike techniques that use luminescent markers for optical measurement, SPRi devices enable real-time refractive index measurements of the sample under test without the need for luminescent markers. The measurement data can be stored as videos, images, or other formats, facilitating subsequent analysis and traceability. Furthermore, by preparing a microarray within the metal surface area being examined by the SPRi device and monitoring the average intensity of each sample point in the microarray, high-throughput detection of the sample under test can be achieved. Due to these advantages, SPRi devices are widely used in fields such as food safety, environmental monitoring, drug screening, and medical diagnostics. With the increase in detection indicators and the number of samples to be tested, the demand for using SPRi devices to quickly detect samples is constantly expanding.

[0003] However, due to limitations in imaging data quality, the detection speed of existing SPRi devices is difficult to meet demand. Most existing SPRi devices use a light source with a Gaussian spatial intensity distribution to obliquely incident on a coupler, resulting in differences in the intensity of the incident light at different spatial locations within the metal surface area. This difference, combined with fluctuations in the brightness of the light source and the shot noise of the array detector, leads to changes in the local light intensity. This not only causes uneven intensity of the reflected light at different sample points within the microarray, but is also the main source of noise in the intensity measurement of the reflected light within a single sample point. To eliminate the impact of uneven reflected light intensity, existing SPRi devices typically use measurement steps such as standard sample calibration or standard light intensity calibration. These steps are complex to operate, require a lot of time, and are not conducive to achieving rapid detection. Summary of the Invention

[0004] In view of this, embodiments of the present application provide a surface plasmon resonance imaging device, method, control system, and storage medium to address the problem that existing surface plasmon resonance imaging devices are limited by imaging data quality and the detection speed is difficult to meet requirements.

[0005] A first aspect of an embodiment of the present application provides a surface plasmon resonance imaging device, comprising a light source system, a detection system, a sample injection system, an imaging system, and a control system, wherein the light source system comprises a telecentric light source, a first motor, and an angle modulation component; the detection system comprises a coupler and a microarray chip; the sample injection system comprises a sample injection pool; and the imaging system comprises a first array detector;

[0006] The first motor is mechanically connected to the angle modulation component, and the control system is electrically connected to the first motor and the first array detector respectively;

[0007] The control system is used to control the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source so that the intensity of the incident light at all sample points of the microarray chip is equal.

[0008] A second aspect of the embodiments of the present application provides a surface plasmon resonance imaging method, which is implemented based on the surface plasmon resonance imaging device described in the first aspect of the embodiments of the present application. The method includes:

[0009] The first motor is controlled to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source, so that the intensity of the incident light at all sample points of the microarray chip is equal.

[0010] A third aspect of an embodiment of the present application provides a control system, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein when the processor executes the computer program, the steps of the surface plasmon resonance imaging method provided in the first aspect of the embodiment of the present application are implemented.

[0011] A fourth aspect of the embodiments of the present application provides a computer-readable storage medium, which stores a computer program. When the computer program is executed by at least one processor, it implements the steps of the surface plasmon resonance imaging method provided in the first aspect of the embodiments of the present application.

[0012] The surface plasmon resonance imaging device provided in the first aspect of an embodiment of the present application includes a light source system, a detection system, an injection system, an imaging system and a control system. The light source system includes a telecentric light source, a first motor and an angle modulation component. The detection system includes a coupler and a microarray chip. The injection system includes an injection pool. The imaging system includes a first array detector. The first motor is mechanically connected to the angle modulation component, and the control system is electrically connected to the first motor and the first array detector respectively. The control system is used to control the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source so that the intensity of the incident light at all sample points on the microarray chip is equal, without the need for measurement steps such as standard sample calibration or standard light intensity calibration. At the same time, the operation complexity and the time required for detection are reduced, and the needs of rapid detection can be met.

[0013] It can be understood that the beneficial effects of the second to fourth aspects mentioned above can be found in the relevant description of the first aspect mentioned above, and will not be repeated here. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the embodiments or descriptions of the prior art. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0015] Figure 1 Schematic diagram of the structure of a surface plasmon resonance imaging device provided in an embodiment of the present application;

[0016] Figure 2 Schematic diagram of the structure of the sample injection system provided in the embodiment of the present application;

[0017] Figure 3 Schematic diagram of the preparation effect diagram, the second image, and the calibration result of the second image provided in an embodiment of the present application;

[0018] Figure 4 is a schematic diagram of the calibration result of the second image provided in an embodiment of the present application;

[0019] Figure 5 is a schematic diagram of the calibration result of the second image provided in an embodiment of the present application;

[0020] Figure 6 is a schematic diagram of the refractive index of the sample to be tested provided in the embodiment of the present application;

[0021] Figure 7 is a schematic diagram of the refractive index of the sample to be tested provided in the embodiment of the present application;

[0022] Figure 8is a schematic diagram of the refractive index of the sample to be tested provided in the embodiment of the present application;

[0023] Figure 9 It is a structural diagram of the control system provided in an embodiment of the present application. DETAILED DESCRIPTION

[0024] In order to help those skilled in the art better understand the present invention, the following will clearly describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work should fall within the scope of protection of the present invention.

[0025] The terms "comprising" and "including" and any variations thereof in the specification of this application and the accompanying drawings are intended to cover non-exclusive inclusions. For example, a process, method, system, product, or device that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units that are not listed, or may optionally include other steps or units that are inherent to these processes, methods, products, or devices. In addition, the terms "first," "second," and "third," etc. are used to distinguish different objects, rather than to describe a specific order.

[0026] like Figure 1 As shown, the embodiment of the present application provides a surface plasmon resonance imaging device, including a light source system, a detection system, a sample injection system, an imaging system and a control system 5. The light source system includes a telecentric light source 11, a first motor 12 and an angle modulation component 13. The detection system includes a coupler 21 and a microarray chip 22. The sample injection system includes a sample injection pool 31. The imaging system includes a first array detector 41.

[0027] The first motor 12 is mechanically connected to the angle modulation component 13, and the control system is electrically connected to the first motor 12 and the first array detector 41 respectively;

[0028] The control system is used to control the first motor 12 to drive the angle modulation component 13 to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source 11 so that the intensity of the incident light at all sample points of the microarray chip 22 is equal.

[0029] In applications, the telecentric light source can be implemented by an LED or a laser. The laser can be any type of tunable laser, for example, a Fabry-Perot laser, a distributed feedback semiconductor laser, a distributed Bragg reflector laser, a vertical-cavity surface-emitting laser, and an external cavity tuned semiconductor laser. The control system can adjust the wavelength of the incident light emitted by the laser by adjusting the operating temperature, bias current, or bias voltage of the laser chip. The wavelength of the incident light can be set according to actual needs. For example, the wavelength of the incident light ranges from 450 nm (nanometers) to 1000 nm, and can specifically be 450 nm, 660 nm, or 980 nm.

[0030] In application, the first motor can be any type of micro motor, such as a micro DC servo motor, as needed. The angle modulation component is provided on the first motor. When the first motor rotates, the angle modulation component is driven to move, thereby automatically adjusting the telecentric angle of the telecentric light source. The angle modulation component can be implemented by any type of optical path adjustment component, such as a combination of a knob and a reflector. The first motor drives the knob to rotate to adjust the reflection angle of the reflector, thereby adjusting the telecentric angle of the telecentric light source. The rotational accuracy of the first motor's driving knob can be set according to actual needs, for example, less than or equal to 0.1°. Figure 1 exemplarily shown in FIG. 1 , the angle modulation component 13 includes a knob.

[0031] like Figure 1 As shown, in one embodiment, the light source system further includes a narrowband filter 14 and a polarizer 15 . After the incident light passes through the narrowband filter 14 and the polarizer 15 , it has a single wavelength and a single polarization state.

[0032] In applications, the center wavelength of a narrowband filter is equal to the wavelength of the incident light emitted by a telecentric light source. The narrowband filter is used to filter out other light in the incident light with wavelengths different from its center wavelength, such as stray light introduced during the transmission of the incident light. The entire light source system can be implemented using a telecentric lens with an adjustable telecentricity angle.

[0033] In application, the positions between the light source system and the detection system are relatively fixed so that the incident light can be incident on the microarray chip. The incident angle can be any acute angle, for example, 53°, 65° or 79°.

[0034] In applications, incident light is coupled to the metal surface of the microarray chip via a coupler. The coupler can be implemented by a glass prism or a waveguide element. The glass prism can be made of optical glass with high light transmittance according to actual needs, such as ZF3 glass, BK7 glass, etc. Figure 1 The coupler 21 is exemplarily shown as a triangular glass prism, and the microarray chip 22 is arranged on one surface of the coupler 21.

[0035] In one embodiment, the preparation method of the microarray chip is:

[0036] performing ultrasonic cleaning on the glass substrate for a first preset time using a mixture of ethanol and ether in a preset volume ratio to clean the surface of the glass substrate;

[0037] placing the glass substrate in an electron beam evaporation apparatus and evacuating the apparatus to reduce the pressure in the apparatus to a preset pressure;

[0038] Depositing chromium with a first preset thickness as an adhesion layer and zinc sulfide with a second preset thickness as an adhesion enhancement layer on the surface of the glass substrate at a first preset rate;

[0039] Depositing gold having a third preset thickness on the surface of the glass substrate at a second preset rate as a metal surface for exciting surface plasmon resonance;

[0040] Soaking the glass substrate in a mercapto acid solution of a first preset concentration for a second preset time to form a monomolecular self-assembled layer;

[0041] A biomolecule spotter is used to spot a preset biomolecule microarray of a second preset concentration on the surface of the glass substrate to obtain a microarray chip, wherein each spot of the microarray chip has a preset diameter and a preset shape.

[0042] In application, the preset parameters in the preparation method of the microarray chip can be set according to actual needs, for example:

[0043] The preset volume ratio ranges from 1:1 to 1:10, and can specifically be 1:2, 1:4, or 1:10;

[0044] The first preset duration is greater than or equal to 30 minutes, and specifically can be 30 minutes, 2 hours, or 4 hours;

[0045] The preset air pressure value is less than or equal to 10 -5 mTorr (mTorr), specifically 10 -7 mTorr, 10 -6 mTorr or 10 - 5 mTorr;

[0046] The first preset rate is less than or equal to 0.1 nm / s (nanometers per second), specifically 0.01 nm / s or 0.03 nm / s;

[0047] The first preset thickness ranges from 0.5 nm (nanometers) to 2.5 nm, and specifically can be 1.5 nm or 2.5 nm;

[0048] The second preset thickness ranges from 0.5 nm to 3 nm, and may specifically be 1 nm, 2 nm, or 3 nm;

[0049] The second preset rate is greater than or equal to 0.01 nm / s, specifically 0.01 nm / s, 0.03 nm / s or 0.08 nm / s;

[0050] The third preset thickness ranges from 40 nm to 70 nm, and may specifically be 45 nm or 50 nm;

[0051] The first preset concentration is greater than or equal to 0.1 mM (mmol / L), specifically 1 mM or 1.5 mM;

[0052] The carbon chain length of the mercapto acid in the mercapto acid solution ranges from 3 to 15, specifically 8, 11 or 13;

[0053] The second preset duration is greater than or equal to 30 minutes, specifically 24 hours;

[0054] The second predetermined concentration is greater than or equal to 1 mM, 1.5 mM or 2 nM;

[0055] The preset biomolecule may be a protein, a nucleic acid fragment, a polypeptide molecule, a tissue section, a cell, etc., and may specifically be bovine serum albumin;

[0056] The preset diameter is greater than or equal to 10 μm (micrometer), specifically 50 μm or 100 μm;

[0057] The preset shape may be a circle or a quasi-circle, for example, an ellipse.

[0058] In use, the sample injection well is positioned on the side of the microarray chip where the metal surface resides. When a sample is introduced into the sample injection well, the incident light undergoes internal reflection at the interface between the sample and the metal surface, simultaneously exciting an evanescent wave at the interface and transferring light energy. This causes the intensity of the reflected light reflected from the interface to decay sharply relative to the incident light. The standard sample can be deionized water, and the sample to be tested can be a glycerol solution composed of a mixture of deionized water and glycerol. The mass fraction of glycerol in the glycerol solution ranges from 0.25% to 1%, and specifically can be 0.2%, 0.5%, or 1%.

[0059] In a specific embodiment, the preparation method of the microarray chip is:

[0060] The glass substrate was ultrasonically cleaned for 2 h using a mixture of ethanol and ether at a volume ratio of 1:4 to clean the surface of the glass substrate;

[0061] Place the glass substrate in the electron beam evaporation instrument and evacuate the air to reduce the pressure in the electron beam evaporation instrument to 10 -6 mTorr;

[0062] 2.5 nm of chromium as an adhesion layer and 2 nm of zinc sulfide as an adhesion enhancement layer were evaporated on the surface of the glass substrate at a rate of 0.1 nm / s.

[0063] 45 nm of gold was evaporated on the surface of a glass substrate at a rate of 0.01 nm / s as a metal surface for exciting surface plasmon resonance;

[0064] The glass substrate was immersed in a 1 mM mercapto acid solution with a carbon chain length of 11 for 24 h to form a monomolecular self-assembled layer;

[0065] A 1 mM bovine serum albumin microarray was formed by spotting on the surface of a glass substrate using a biomolecule spotter to obtain a microarray chip. Each spot on the microarray chip was a circle with a diameter of 100 μm.

[0066] In another specific embodiment, the preparation method of the microarray chip is:

[0067] The glass substrate was ultrasonically cleaned for 30 min using a mixture of ethanol and ether with a volume ratio of 1:2 to clean the surface of the glass substrate;

[0068] Place the glass substrate in the electron beam evaporation instrument and evacuate the air to reduce the pressure in the electron beam evaporation instrument to 10 -5 mTorr;

[0069] 1.5 nm of chromium as an adhesion layer and 1 nm of zinc sulfide as an adhesion enhancement layer were evaporated on the surface of the glass substrate at a rate of 0.03 nm / s.

[0070] 50 nm of gold was evaporated on the surface of the glass substrate at a rate of 0.03 nm / s as a metal surface for exciting surface plasmon resonance;

[0071] The glass substrate was immersed in a 1.5 mM mercapto acid solution with a carbon chain length of 8 for 24 h to form a monomolecular self-assembled layer;

[0072] A 1.5 mM bovine serum albumin microarray was formed by spotting on the surface of a glass substrate using a biomolecule spotter to obtain a microarray chip. Each spot on the microarray chip was a circle with a diameter of 50 μm.

[0073] In another specific embodiment, the preparation method of the microarray chip is:

[0074] The glass substrate was ultrasonically cleaned for 4 h using a mixture of ethanol and ether at a volume ratio of 1:10 to clean the surface of the glass substrate;

[0075] Place the glass substrate in the electron beam evaporation instrument and evacuate the air to reduce the pressure in the electron beam evaporation instrument to 10 -7 mTorr;

[0076] 1.5 nm of chromium as an adhesion layer and 3 nm of zinc sulfide as an adhesion enhancement layer were evaporated on the surface of the glass substrate at a rate of 0.01 nm / s.

[0077] 50 nm of gold was evaporated on the surface of the glass substrate at a rate of 0.08 nm / s as a metal surface for exciting surface plasmon resonance;

[0078] The glass substrate was immersed in a 2 mM solution of mercapto acid with a carbon chain length of 13 for 24 h to form a monomolecular self-assembled layer;

[0079] A 2 mM bovine serum albumin microarray was formed by spotting on the surface of a glass substrate using a biomolecule spotter to obtain a microarray chip. Each spot on the microarray chip was a circle with a diameter of 100 μm.

[0080] like Figure 1 As shown in FIG2 , in one embodiment, the injection system further includes a three-way valve 32 , an injection pump 33 and a waste liquid bottle 34 ;

[0081] After the standard sample enters the three-way valve 32 through the first selection end 321 of the three-way valve 32 or the sample to be tested enters the three-way valve 32 through the second selection end 322 of the three-way valve 32, it first enters the sampling pump 33 through the pipeline 331, and then enters the sampling pool 31 through the sampling port of the sampling pool 31. After the first array detector 41 completes surface plasmon resonance imaging, it enters the waste liquid bottle 34 through the sampling outlet of the sampling pool 31 for recovery.

[0082] In application, the three-way valve can be a manual valve manually controlled by the user, or it can be an electrically controlled valve electrically connected to the control system and controlled by the control system. The control system inputs the standard sample or the sample to be tested into the injection pool by controlling one of the two selection ends of the three-way valve to open at the same time. The pipeline can be set according to actual needs, for example, a polyethylene (Polyethylene of raised temperature resistance, PE) pipeline. The injection pump can be a manual pump manually controlled by the user, or it can be an electrically controlled pump electrically connected to the control system and controlled by the control system. Its specific type can be set according to actual needs, for example, a plunger pump. The duration of the standard sample or the sample to be tested being passed into the injection pool can be set according to actual needs, for example, greater than or equal to 50s.

[0083] like Figure 1 As shown, in one embodiment, the imaging system further includes a beam splitter 42 and a second array detector 43;

[0084] The control system is also electrically connected to the second array detector 43;

[0085] The reflected light from all sample points is split into a first reflected light and a second reflected light by a beam splitter 42 and then emitted to a first array detector 41 and a second array detector 43 respectively.

[0086] The control system 5 is specifically used for:

[0087] Controlling the first motor 12 to drive the angle modulation component 13 to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source 11;

[0088] Acquire a first image of the microarray chip 22 through the second array detector 43;

[0089] Obtaining a ratio of the mean square error of the intensities of all pixels in the first image to the mean intensity;

[0090] When the ratio is not equal to the preset threshold, the control returns to the first motor 12 to drive the angle modulation component 13 to move until the ratio is equal to the preset threshold. When the ratio is equal to the preset threshold, the intensity of the incident light at all sample points of the microarray chip 22 is equal.

[0091] In the application, after each adjustment of the telecentric angle, the control system calculates the ratio of the mean square error of the intensity of all pixels in the first image to the mean intensity, and then determines whether the ratio is equal to a preset threshold. If so, the telecentric angle adjustment is stopped; otherwise, the telecentric angle adjustment is continued until the ratio is equal to the preset threshold. The preset threshold can be set to the minimum value that the ratio can reach or slightly greater than the minimum value according to actual needs. The minimum value can be determined by the method that when the ratio cannot be reduced after repeated adjustment of the telecentric angle, the ratio is considered to have reached the minimum value.

[0092] In application, the beam splitter can be realized by any optical device with a beam splitting function, and its splitting ratio can be selected according to actual needs. For example, the beam splitter can be a semi-transparent and semi-reflective mirror. When the transmitted light is incident on the first array detector and the reflected light is incident on the second array detector, the transmittance and reflection ratio of the semi-transparent and semi-reflective mirror for the incident light with a wavelength of 660nm can be 50%:50%, the transmittance and reflection ratio for the incident light with a wavelength of 450nm can be 60%:40%, and the transmittance and reflection ratio for the incident light with a wavelength of 980nm can be 70%:30. %; when the transmitted light is incident on the second array detector and the reflected light is incident on the first array detector, the transmittance and reflection ratio of the semi-transparent and semi-reflective mirror for the incident light with a wavelength of 660nm can be 50%:50%, the transmittance and reflection ratio for the incident light with a wavelength of 450nm can be 40%:60%, and the transmittance and reflection ratio for the incident light with a wavelength of 980nm can be 30%:70%. That is, the proportion of the light beam incident on the first array detector should be greater than or equal to the proportion of the light beam incident on the second array detector, so as to improve the accuracy of surface plasmon resonance imaging.

[0093] In applications, the first array detector and the second array detector can be implemented using photoelectric conversion devices such as photodiodes, phototransistors, and photomultiplier tubes, for example, charge-coupled device (CCD) sensors or complementary metal oxide semiconductor (CMOS) sensors. The size of each pixel in the first array detector and the second array detector can be selected based on actual needs. For example, the size of each pixel in the first array detector is greater than or equal to 10um×10um, specifically 30um×30um, 50um×50um, or 100um×100um; the size of each pixel in the second array detector is less than or equal to 10um, specifically 3um×3um, 5um×5um, or 10um×10um.

[0094] like Figure 1 As shown, in one embodiment, the imaging system further includes a second motor 44, and the first array detector 41 is mechanically connected to the second motor 44;

[0095] The control system 5 is further configured to control the second motor 44 to adjust the position of the receiving surface of the first array detector 41 so that the receiving surface of the first array detector 41 receives the reflected light reflected by all the sample points.

[0096] In practice, due to limitations in data processing methods, the uneven intensity of reflected light across all sample points reduces the contrast of the measured image, making it impossible to accurately locate each sample point within the microarray using software algorithms. This requires manual point-finding based on experience. This not only relies on large-scale equipment such as a host computer for installing a non-real-time operating system, increasing computation time and cost, but also is complex to operate and inaccurate, making it difficult to apply to accurate and rapid detection scenarios. Therefore, a control system controls the second motor to adjust the position of the first array detector so that it receives reflected light from all sample points. This eliminates the need for manual point-finding based on experience, reduces computation time and cost, and is simple to operate and highly accurate, meeting the needs of rapid detection.

[0097] In use, the imaging system and the detection system are relatively fixed in position so that the reflected light, at an acute angle, can be fully received by the receiving surface of the first array detector. The reflection angle can be any acute angle, for example, 53°, 65°, or 79°. Specifically, the light source system, the detection system, and the imaging system are relatively fixed in position so that the incident angle of the incident light and the reflection angle of the reflected light are equal, and the angle between the normal to the receiving surface of the first array detector and the normal to the bottom surface of the coupler is equal to the reflection angle.

[0098] In practice, the second motor is a two-degree-of-freedom motor used to drive the receiving surface of the first array detector to move in two mutually perpendicular directions within the receiving surface. The second motor can be any type of micromotor, such as a micro DC servo motor, as needed. The displacement accuracy of the second motor can be set as needed, for example, to less than or equal to 10 μm.

[0099] In application, the control system can be a central processing unit (CPU), or other general-purpose processors, digital signal processors (DSP), application-specific integrated circuits (ASIC), field-programmable gate arrays (FPGA), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor can be a microprocessor or any conventional processor, for example, a control card with a chip model of STM32F407 or STM32F103. The control system can be connected to other components by any wired communication method, for example, connected to the first motor and the second motor by a serial interface, and connected to the first array detector and the second array detector by a serial bus.

[0100] like Figure 1 As shown, in one embodiment, the light source system further includes a first temperature controller 16 disposed at the telecentric light source 11, and the first temperature controller 16 is used to control the temperature of the telecentric light source 11;

[0101] The injection system further includes a second temperature controller 35 disposed at the injection pool 31 . The second temperature controller 35 is used to control the temperature of the injection pool 31 .

[0102] In application, the first temperature controller and the second temperature controller can be implemented by any device with heating and cooling functions, for example, they can be implemented by thermocouples, control circuits, cooling plates and cooling fans, etc., where the thermocouples can be equivalently replaced by heating wires.

[0103] based on Figure 1 The structure of the surface plasmon resonance imaging device shown in FIG. Figure 1 or Figure 3 As shown, in one embodiment, the control system 5 is specifically used to:

[0104] The second array detector 43 acquires a second image of all sample points (eg Figure 3 (b)

[0105] Get the preparation effect diagram of all sample points (such as Figure 3 (as shown in (a));

[0106] According to the second image and the preparation effect diagram, calibrate all the sample points in the second image;

[0107] According to the calibration results, the positions of all sample points on the receiving surface of the second array detector 43 are obtained (eg Figure 3 (c)

[0108] Acquire a third image of all sample points through the first array detector 41;

[0109] According to the third image, positions of all sample points on the receiving surface of the first array detector 41 are obtained;

[0110] Obtaining the position difference between the position of all sample points on the receiving surface of the first array detector 41 and the position of all sample points on the receiving surface of the second array detector 43;

[0111] According to the position difference, the second motor 44 is controlled to adjust the position of the receiving surface of the first array detector 41 so that the receiving surface of the first array detector 41 receives the reflected light reflected by all the sample points.

[0112] In application, the preparation effect diagram is a printed effect diagram of the microarray chip prepared by the above-mentioned preparation method. The preparation effect diagram should at least include all sample points, and may also include a margin area located around the area where all sample points are located. The starting point, end point, horizontal margin, and vertical margin of the margin area can be set according to actual needs. By converting the positions of all sample points in the second image from the image coordinate system to the second array detector coordinate system, the positions of all sample points on the receiving surface of the second array detector can be obtained; by converting the positions of all sample points in the third image from the image coordinate system to the first array detector coordinate system, the positions of all sample points on the receiving surface of the first array detector can be obtained; by converting the position difference from the first array detector coordinate system to the second motor coordinate system, the second motor can be controlled to adjust the position of the receiving surface of the first array detector according to the position difference, so that the receiving surface of the first array detector can ultimately receive the reflected light reflected by all sample points.

[0113] based on Figure 1 The structure of the surface plasmon resonance imaging device shown in FIG. Figure 1 or Figure 3 As shown, the control system 5 is specifically used for:

[0114] After the standard sample is introduced into the sample injection pool 31, the second image of the microarray chip 22 is acquired by the second array detector 43;

[0115] Obtain four design parameters for the preparation effect diagram, including the coordinates of the starting point of the preparation effect diagram, the coordinates of the end point, the difference between the horizontal coordinates of the corner point closest to the starting point and the starting point (offsetx), and the difference between the vertical coordinates of the corner point and the starting point (offsety);

[0116] According to the second image, the preparation effect diagram and the four design parameters, a compression ratio between the second image and the effect diagram and coordinates of all sample points in the preparation effect diagram are obtained;

[0117] The coordinates of all sample points in the second image are obtained according to the difference offsetx between the horizontal coordinates of the corner point and the starting point, the difference offsety between the vertical coordinates of the corner point and the starting point, the compression ratio, and the coordinates of all sample points in the prepared effect image, so as to calibrate all sample points in the second image.

[0118] In application, by switching the three-way valve to the first selection end, a standard sample, such as deionized water, can be introduced into the injection pool. The compression ratio includes the ratio of the length of the preparation effect image to the second image in the horizontal axis direction and the ratio of the width of the preparation effect image to the second image in the vertical axis direction.

[0119] In one embodiment, the coordinates of any point in the second image are expressed as follows:

[0120]

[0121] Wherein, (x, y) is the coordinate of any sample point in the second image, (a, b) is the coordinate of any sample point in the preparation effect image, offsetx is the difference between the horizontal coordinates of the corner point and the starting point, offsety is the difference between the vertical coordinates of the corner point and the starting point, ratex is the ratio of the length of the preparation effect image and the second image in the horizontal direction, and ratey is the ratio of the width of the preparation effect image and the second image in the vertical direction.

[0122] based on Figure 1 In one embodiment of the structure of the surface plasmon resonance imaging device shown, the control system is specifically used to:

[0123] After calibrating all sample points in the second image, obtaining the coordinates of the center of gravity of all sample points in the second image;

[0124] The coordinates of all sample points in the second image are replaced with the coordinates of the corresponding centers of gravity to obtain the corrected coordinates of all sample points in the second image.

[0125] In the application, all sample points calibrated in the second image may not completely match all actual sample points in the second image. Therefore, it is necessary to automatically calibrate the coordinates obtained by calibration. Ideally, all calibrated sample points coincide with all actual sample points, the area where the sample points are located is white, and the center of gravity of the sample points coincides with the center of the circle. When the calibration effect is not ideal, the difference between the center of gravity of the sample point and the center of the circle represents the direction that should be corrected. At this time, the coordinates of the corrected sample point can be obtained by replacing the coordinates of the center of the circle with the coordinates of the center of gravity of the sample point. The formula for calculating the center of gravity of the sample point is as follows:

[0126]

[0127]

[0128] Among them, (x c ,y c ) represents the centroid coordinates of the sample point, M 00 represents the zero-order moment of the second image V, M 10 and M 01 Represents the first-order moment of the second image V, V(i,j) represents the grayscale value of the pixel with coordinates (i,j) in the second image V, I is the maximum horizontal coordinate of the pixel in the second image V, and J is the maximum vertical coordinate of the pixel in the second image V.

[0129] In an application, after automatic calibration, the positioning accuracy of a sample point can be measured by using the ratio of the number of white pixels in all sample points to the number of all pixels in all sample points.

[0130] Figure 3 (c) exemplarily shows a schematic diagram of the calibration result of the second image when the size of each pixel in the first array detector is 100um×100um and the size of each pixel in the second array detector is 10um×10um.

[0131] Figure 4 exemplarily shows a schematic diagram of the calibration result of the second image when the size of each pixel in the first array detector is 50um×50um and the size of each pixel in the second array detector is 5um×5um.

[0132] Figure 5 exemplarily shows a schematic diagram of the calibration result of the second image when the size of each pixel in the first array detector is 30um×30um and the size of each pixel in the second array detector is 3um×3um.

[0133] based on Figure 1 In the structure of the surface plasmon resonance imaging apparatus shown in FIG. 1 , in one embodiment, the control system 5 is further configured to:

[0134] Adjusting the sensitivity coefficient of the first array detector 41 to a preset sensitivity coefficient;

[0135] adjusting the bias of the first array detector 41;

[0136] Acquire a fourth image of all sample points through the first array detector 41;

[0137] When the pixel values ​​corresponding to all the sample points in the fourth image are not all zero, the bias of the first array detector 41 is adjusted again until the pixel values ​​corresponding to all the sample points in the fourth image are all zero.

[0138] In application, in order to improve the sensitivity of the first array detector, its sensitivity coefficient needs to be adjusted. The preset sensitivity coefficient can be set according to actual needs, for example, 0.00292, 0.00298, or 0.00583. After adjusting the bias of the first array detector, a fourth image of all sample points is acquired through the first array detector, and the pixel values ​​corresponding to all sample points in the fourth image are detected to see whether they are all 0. If so, the bias adjustment is stopped to complete the bias calibration. If not, the bias of the first array detector is adjusted again, and a fourth image of all sample points is acquired through the first array detector, and the pixel values ​​corresponding to all sample points in the fourth image are detected to see whether they are all 0. This cycle is repeated until the pixel values ​​corresponding to all sample points in the fourth image are all 0.

[0139] based on Figure 1 In the structure of the surface plasmon resonance imaging apparatus shown in FIG. 1 , in one embodiment, the control system 5 is further configured to:

[0140] At a preset moment in a preset sampling process, a fifth image of all sample points is acquired by the first array detector 41, wherein the preset sampling process is as follows: after the standard sample is introduced into the sampling pool 21 for a third preset time, the sample to be tested having a preset mass fraction is introduced into the sampling pool 31 for a fourth preset time, and then the standard sample is introduced into the sampling pool 31 for a fifth preset time. The preset moment is the moment when the sample to be tested is introduced into the sampling pool 31 for a sixth preset time, and the sixth preset time is less than the fourth preset time.

[0141] According to the fifth image, the refractive index of the sample to be measured is obtained.

[0142] In the application, the standard sample can be deionized water, and the sample to be tested can be a glycerol solution. The preset parameters in the preset injection process can be set according to actual needs, for example:

[0143] The value range of the third preset time length is greater than or equal to 50s, and can be specifically 50s, 200s or 300s;

[0144] The preset mass fraction ranges from 0.25% to 1%, and can specifically be 0.25%, 0.5% or 1%.

[0145] The value range of the fourth preset time length is greater than or equal to 50s, and can be specifically 100s, 200s or 300s. Correspondingly, the sixth preset time length can be specifically 50s, 100s or 150s.

[0146] The value range of the fifth preset time length is greater than or equal to 50s, and specifically can be 50s, 100s or 300s.

[0147] In a specific embodiment, the preset injection process is:

[0148] The three-way valve 32 is switched to the first gate end 321, and deionized water is introduced into the sample injection pool 21 for 200 seconds. The three-way valve 32 is then switched to the second gate end 322, and a 0.5% glycerol solution is introduced into the sample injection pool 31 for 200 seconds. The three-way valve 32 is then switched to the first gate end 321 again, and deionized water is introduced into the sample injection pool 31 for 200 seconds. At the moment when the glycerol solution is introduced into the sample injection pool 31 for 100 seconds, a fifth image of all sample points is acquired by the first array detector 41.

[0149] Figure 6 Schematic diagram of the refractive index of the sample to be measured obtained based on this embodiment is exemplarily shown in FIG.

[0150] In another specific embodiment, the preset injection process is:

[0151] The three-way valve 32 is switched to the first gate end 321, and deionized water is introduced into the sample injection pool 21 for 50 seconds. The three-way valve 32 is then switched to the second gate end 322, and a 0.5% glycerol solution is introduced into the sample injection pool 31 for 100 seconds. The three-way valve 32 is then switched to the first gate end 321, and deionized water is introduced into the sample injection pool 31 for 100 seconds. At the moment when the glycerol solution is introduced into the sample injection pool 31 for 50 seconds, a fifth image of all sample points is acquired by the first array detector 41.

[0152] Figure 7 Schematic diagram of the refractive index of the sample to be measured obtained based on this embodiment is exemplarily shown in FIG.

[0153] In another specific embodiment, the preset injection process is:

[0154] The three-way valve 32 is switched to the first gate end 321, and deionized water is introduced into the sample injection pool 21 for 300 seconds. The three-way valve 32 is then switched to the second gate end 322, and a 0.25% glycerol solution is introduced into the sample injection pool 31 for 300 seconds. The three-way valve 32 is then switched to the first gate end 321, and deionized water is introduced into the sample injection pool 31 for 300 seconds. At the moment when the glycerol solution has been introduced into the sample injection pool 31 for 150 seconds, a fifth image of all sample points is acquired by the first array detector 41.

[0155] Figure 8 Schematic diagram of the refractive index of the sample to be measured obtained based on this embodiment is exemplarily shown in FIG.

[0156] The surface plasmon resonance imaging device provided in the embodiments of the present application can make the intensity of incident light at all sample points on a microarray chip equal, eliminating the need for measurement steps such as standard sample calibration or standard light intensity calibration. This also reduces operational complexity and detection time, thus meeting the need for rapid detection.

[0157] The control system controls the second motor to adjust the position of the first array detector so that the first array detector receives reflected light from all sample points. This eliminates the need for manual point-finding methods based on experience, reduces calculation time and economic costs, and is easy to operate with high accuracy, meeting rapid detection requirements.

[0158] like Figure 9 As shown, in one embodiment, the control system 5 provided by the embodiment of the present application includes: at least one processor 51 ( Figure 9 Only one processor is shown in the figure), a memory 52, and a computer program 53 stored in the memory 52 and executable by at least one processor 51. When the processor 51 executes the computer program 53, the surface plasmon resonance imaging method in the above embodiment is implemented. The method includes the following steps:

[0159] Step S1, controlling the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source, so that the intensity of the incident light at all sample points on the microarray chip is equal.

[0160] In one embodiment, step S1 includes:

[0161] Step S11, controlling the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source;

[0162] Step S12: acquiring a first image of all sample points of the microarray chip by a second array detector;

[0163] Step S13: obtaining the ratio of the mean square error of the intensities of all pixels in the first image to the average intensity;

[0164] Step S14: When the ratio is not equal to the preset threshold, return to controlling the first motor to drive the angle modulation component to move until the ratio is equal to the preset threshold. When the ratio is equal to the preset threshold, the intensity of the incident light at all sample points of the microarray chip is equal.

[0165] In one embodiment, the surface plasmon resonance imaging method further comprises:

[0166] Step S2: controlling the second motor to adjust the position of the receiving surface of the first array detector so that the receiving surface of the first array detector receives the reflected light reflected by all the sample points.

[0167] In one embodiment, step S2 includes:

[0168] Step S21, acquiring a second image of all sample points through a second array detector;

[0169] Step S22, obtaining preparation effect diagrams of all sample points;

[0170] Step S23: calibrate all sample points in the second image according to the second image and the preparation effect diagram;

[0171] Step S24: Obtain the positions of all sample points on the receiving surface of the second array detector according to the calibration results;

[0172] Step S25: Acquire a third image of all sample points through the first array detector;

[0173] Step S26: Obtaining positions of all sample points on the receiving surface of the first array detector according to the third image;

[0174] Step S27, obtaining the position difference between the position of all sample points on the receiving surface of the first array detector and the position of all sample points on the receiving surface of the second array detector;

[0175] Step S28: Control the second motor to adjust the position of the receiving surface of the first array detector according to the position difference, so that the receiving surface of the first array detector receives the reflected light reflected by all the sample points.

[0176] In one embodiment, step S21 includes:

[0177] Step S211: After a standard sample is introduced into the sample injection pool, a second image of all sample points is acquired by a second array detector;

[0178] Step S23 includes:

[0179] Step S231, obtaining four design parameters of the preparation effect diagram of all sample points of the microarray chip, the four design parameters including the coordinates of the starting point of the preparation effect diagram, the coordinates of the cutoff point, the difference between the abscissa of the corner point closest to the starting point and the starting point, and the difference between the ordinate of the corner point and the starting point;

[0180] Step S232: Obtain a compression ratio between the second image and the effect diagram and coordinates of all sample points in the preparation effect diagram according to the second image, the preparation effect diagram, and the four design parameters;

[0181] Step S233: Obtain the coordinates of all sample points in the second image according to the difference between the horizontal coordinates of the corner point and the starting point, the difference between the vertical coordinates of the corner point and the starting point, the compression ratio, and the coordinates of all sample points in the preparation effect image, so as to calibrate all sample points in the second image.

[0182] In one embodiment, after step S23, the following steps are included:

[0183] Step S24, obtaining the coordinates of the center of gravity of all sample points in the second image;

[0184] Step S25 : Replace the coordinates of all sample points in the second image with the coordinates of the corresponding centers of gravity to obtain corrected coordinates of all sample points in the second image.

[0185] In one embodiment, the surface plasmon resonance imaging method further comprises:

[0186] Step S3, adjusting the sensitivity coefficient of the first array detector to a preset sensitivity coefficient;

[0187] Step S4, adjusting the bias of the first array detector;

[0188] Step S5: acquiring a fourth image of all sample points through the first array detector;

[0189] Step S6: When the pixel values ​​corresponding to all the sample points in the fourth image are not all 0, return to adjusting the bias of the first array detector until the pixel values ​​corresponding to all the sample points in the fourth image are all 0.

[0190] In one embodiment, the surface plasmon resonance imaging method further comprises:

[0191] Step S7: Acquire a fifth image of all sample points by the first array detector at a preset time in a preset sampling process, wherein the preset sampling process is as follows: after the standard sample is introduced into the sampling pool for a third preset time, the sample to be tested having a preset mass fraction is introduced into the sampling pool for a fourth preset time, and then the standard sample is introduced into the sampling pool for a fifth preset time, and the preset time is the time when the sample to be tested is introduced into the sampling pool for a sixth preset time, and the sixth preset time is less than the fourth preset time.

[0192] Step S8: Obtain the refractive index of the sample to be measured according to the fifth image.

[0193] It should be noted that the execution process of the above steps is based on the same concept as the surface plasmon resonance imaging device embodiment of the present application. Its specific functions and technical effects can be found in the surface plasmon resonance imaging device embodiment section and will not be repeated here.

[0194] In applications, in some embodiments, the memory can be an internal storage unit of a terminal device, such as a hard disk or memory of the terminal device. In other embodiments, the memory can also be an external storage device of the terminal device, such as a plug-in hard disk equipped with the terminal device, a Smart Media Card (SMC), a Secure Digital (SD) card, a Flash Card, etc. Furthermore, the memory can also include both the internal storage unit of the terminal device and an external storage device. The memory is used to store an operating system, application programs, a boot loader, data, and other programs, such as the program code of a computer program. The memory can also be used to temporarily store data that has been output or is about to be output.

[0195] Those skilled in the art will appreciate that the above embodiments are merely examples of surface plasmon resonance imaging devices and do not constitute a limitation of the present invention. Surface plasmon resonance imaging devices may include more or fewer components than shown, or combinations of certain components, or different components. For example, they may also include input / output devices, network access devices, timers, and the like. The input / output devices may include the aforementioned human-computer interaction devices, and may also include a display screen for displaying the operating parameters of the terminal device. The network access device may include a communication module for communication between the terminal device and a user terminal.

[0196] In applications, the display screen can be a thin film transistor liquid crystal display (TFT-LCD), a liquid crystal display (LCD), an organic electroluminesence display (OLED), a quantum dot light emitting diode (QLED) display screen, a seven-segment or eight-segment digital tube, etc.

[0197] In applications, the communication module can be configured as any device capable of directly or indirectly communicating with the client over long distances, either wired or wirelessly, according to actual needs. For example, the communication module can provide communication solutions for network devices, including wireless local area networks (WLAN) (such as Wi-Fi networks), Bluetooth, Zigbee, mobile communication networks, global navigation satellite systems (GNSS), frequency modulation (FM), near field communication (NFC), and infrared (IR). The communication module can include an antenna, which can have only one element or an antenna array comprising multiple elements. The communication module can receive electromagnetic waves through the antenna, frequency modulate and filter the electromagnetic wave signals, and then send the processed signals to the processor. The communication module can also receive signals to be transmitted from the processor, frequency modulate and amplify them, and then convert them into electromagnetic waves for radiation via the antenna.

[0198] It should be noted that the information interaction, execution process, etc. between the above-mentioned devices / modules are based on the same concept as the method embodiment of this application. Their specific functions and technical effects can be found in the method embodiment section and will not be repeated here.

[0199] Those skilled in the art can clearly understand that, for the convenience and brevity of description, only the division of the above-mentioned functional modules is used as an example for illustration. In actual applications, the above-mentioned functions can be distributed and completed by 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. The functional modules in the embodiment can be integrated into a processing module, or each module can exist physically alone, or two or more modules can be integrated into one module. The above-mentioned integrated modules can be implemented in the form of hardware or in the form of software functional modules. In addition, the specific names of the functional modules are only for the convenience of distinguishing each other and are not used to limit the scope of protection of this application. The specific working process of the modules in the above-mentioned system can refer to the corresponding process in the aforementioned method embodiment, which will not be repeated here.

[0200] An embodiment of the present application further provides a computer-readable storage medium storing a computer program. When the computer program is executed by a processor, the steps in the above-mentioned surface plasmon resonance imaging method embodiment can be implemented.

[0201] An embodiment of the present application provides a computer program product. When the computer program product is run on a control system, the steps in the above-mentioned surface plasmon resonance imaging method embodiment can be implemented.

[0202] If the integrated module is implemented as a software functional module and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the present application can implement all or part of the process of the above-mentioned method embodiment by instructing the relevant hardware through a computer program. The computer program can be stored in a computer-readable storage medium. When executed by a processor, the computer program can implement the steps of each of the above-mentioned method embodiments. The computer program includes computer program code, which can be in source code form, object code form, executable file, or some intermediate form. The computer-readable medium can at least include: any entity or device capable of carrying computer program code to the camera terminal device, recording medium, computer memory, read-only memory (ROM), random access memory (RAM), electrical carrier signal, telecommunication signal, and software distribution medium. Examples include a USB flash drive, a mobile hard drive, a magnetic disk, or an optical disk.

[0203] In the above embodiments, the description of each embodiment has its own focus. For parts that are not described or recorded in detail in a certain embodiment, reference can be made to the relevant description of other embodiments.

[0204] Those skilled in the art will appreciate that the modules and algorithm steps of each example described in conjunction with the embodiments disclosed herein can be implemented in electronic hardware, or a combination of computer software and electronic hardware. Whether these functions are performed in hardware or software depends on the specific application and design constraints of the technical solution. Professional and technical personnel can use different methods to implement the described functions for each specific application, but such implementation should not be considered beyond the scope of this application.

[0205] In the embodiments provided in this application, it should be understood that the disclosed terminal devices and methods can be implemented in other ways. For example, the terminal device embodiments described above are merely illustrative. For example, the module division is merely a logical function division. In actual implementation, there may be other division methods, such as multiple modules or components can be combined or integrated into another system, or some features can be ignored or not executed. In addition, the mutual coupling or direct coupling or communication connection shown or discussed can be an indirect coupling or communication connection through some interface, device or module, which can be electrical, mechanical or other forms.

[0206] The modules described as separate components may or may not be physically separate, and the components shown as modules may or may not be physical modules, that is, they may be located in one place or distributed across multiple network modules. Some or all of the modules may be selected to achieve the purpose of the present embodiment according to actual needs.

[0207] The above-described embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present application, and should all be included in the scope of protection of the present application.

Claims

1. A surface plasmon resonance imaging device, characterized in that: It includes a light source system, a detection system, a sample injection system, an imaging system and a control system. The light source system includes a telecentric light source, a first motor and an angle modulation component. The detection system includes a coupler and a microarray chip. The sample injection system includes a sample injection pool. The imaging system includes a first array detector. The first motor is mechanically connected to the angle modulation component, and the control system is electrically connected to the first motor and the first array detector respectively; The control system is used to control the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source so that the intensity of the incident light at all sample points of the microarray chip is equal; The imaging system further includes a beam splitter and a second array detector; The control system is also electrically connected to the second array detector; The reflected light reflected from all the sample points is split into a first reflected light and a second reflected light by the beam splitter, and then emitted to the first array detector and the second array detector respectively; The control system is specifically used for: controlling the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source; Acquire a first image of all the sample points through the second array detector; Obtaining a ratio of the mean square error of the intensities of all pixels in the first image to the mean intensity; When the ratio is not equal to the preset threshold, the control returns to the first motor to drive the angle modulation component to move until the ratio is equal to the preset threshold. When the ratio is equal to the preset threshold, the intensity of the incident light at all sample points of the microarray chip is equal.

2. The surface plasmon resonance imaging apparatus according to claim 1, wherein The imaging system further includes a second motor, the first array detector being mechanically connected to the second motor; The control system is further configured to control the second motor to adjust the position of the receiving surface of the first array detector so that the receiving surface of the first array detector receives the reflected light reflected by all the sample points.

3. The surface plasmon resonance imaging apparatus according to claim 2, wherein: The control system is further specifically used for: Acquire a second image of all the sample points through the second array detector; Obtaining preparation effect diagrams of all the sample points; calibrating all the sample points in the second image according to the second image and the preparation effect diagram; Obtaining positions of all sample points on a receiving surface of the second array detector according to the calibration result; Acquire a third image of all the sample points through the first array detector; Obtaining positions of all the sample points on a receiving surface of the first array detector according to the third image; Obtaining position differences between positions of all the sample points on the receiving surface of the first array detector and positions of all the sample points on the receiving surface of the second array detector; According to the position difference, the second motor is controlled to adjust the position of the receiving surface of the first array detector so that the receiving surface of the first array detector receives the reflected light reflected by all the sample points.

4. The surface plasmon resonance imaging apparatus according to claim 3, wherein: Acquiring the second image of all the sample points by the second array detector includes: After a standard sample is introduced into the sample injection pool, a second image of all the sample points is acquired by the second array detector; The step of calibrating all sample points in the second image according to the second image and the preparation effect diagram includes: Obtaining four design parameters of the preparation effect diagram, the four design parameters including the coordinates of the starting point of the preparation effect diagram, the coordinates of the end point, the difference between the abscissa of the starting point and the corner point closest to the starting point among all the sample points, and the difference between the ordinates of the corner point and the starting point; Obtaining, according to the second image, the preparation effect diagram, and the four design parameters, a compression ratio between the second image and the effect diagram, and coordinates of all sample points in the preparation effect diagram; The coordinates of all the sample points in the second image are obtained according to the difference between the abscissas of the corner point and the starting point, the difference between the ordinates of the corner point and the starting point, the compression ratio, and the coordinates of all the sample points in the preparation effect image, so as to calibrate all the sample points in the second image.

5. The surface plasmon resonance imaging apparatus according to claim 4, wherein: The control system is also used to: After calibrating all the sample points in the second image, obtaining coordinates of the centers of gravity of all the sample points in the second image; The coordinates of all the sample points in the second image are replaced by the coordinates of the corresponding centers of gravity to obtain corrected coordinates of all the sample points in the second image.

6. The surface plasmon resonance imaging apparatus according to any one of claims 1 to 5, wherein: The control system is also used to: Adjusting the sensitivity coefficient of the first array detector to a preset sensitivity coefficient; adjusting the bias of the first array detector; Acquire a fourth image of all the sample points through the first array detector; When the pixel values ​​corresponding to all the sample points in the fourth image are not all 0, the bias of the first array detector is adjusted again until the pixel values ​​corresponding to all the sample points in the fourth image are all 0.

7. The surface plasmon resonance imaging apparatus according to any one of claims 1 to 5, wherein: The control system is also used to: At a preset moment in a preset sampling process, a fifth image of all the sample points is acquired by the first array detector, wherein the preset sampling process is: after the standard sample is passed into the sampling pool for a third preset time, the sample to be tested with a preset mass fraction is passed into the sampling pool for a fourth preset time, and then the standard sample is passed into the sampling pool for a fifth preset time, and the preset moment is the moment when the sample to be tested is passed into the sampling pool for a sixth preset time, and the sixth preset time is less than the fourth preset time; The refractive index of the sample to be measured is obtained according to the fifth image.

8. The surface plasmon resonance imaging apparatus according to any one of claims 1 to 5, wherein: The light source system further includes a first temperature controller provided on the telecentric light source, the first temperature controller being used to control the temperature of the telecentric light source; The injection system further includes a second temperature controller disposed on the injection pool, and the second temperature controller is used to control the temperature of the injection pool.

9. The surface plasmon resonance imaging apparatus according to any one of claims 1 to 5, wherein: The preparation method of the microarray chip is: performing ultrasonic cleaning on the glass substrate for a first preset time using a mixture of ethanol and ether in a preset volume ratio to clean the surface of the glass substrate; placing the glass substrate in an electron beam evaporation apparatus and evacuating the apparatus to reduce the pressure in the apparatus to a preset pressure; Depositing chromium with a first preset thickness as an adhesion layer and zinc sulfide with a second preset thickness as an adhesion enhancement layer on the surface of the glass substrate at a first preset rate; Depositing gold having a third preset thickness on the surface of the glass substrate at a second preset rate as a metal surface for exciting surface plasmon resonance; Soaking the glass substrate in a mercapto acid solution of a first preset concentration for a second preset time to form a monomolecular self-assembled layer; A biomolecule spotter is used to spot a preset biomolecule microarray of a second preset concentration on the surface of the glass substrate to obtain a microarray chip, wherein each spot of the microarray chip has a preset diameter and a preset shape.

10. A surface plasmon resonance imaging method, characterized in that: Based on the surface plasmon resonance imaging device of claim 1, the method comprises: controlling the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source, so that the intensity of the incident light at all sample points of the microarray chip is equal; The imaging system further includes a beam splitter and a second array detector; The control system is also electrically connected to the second array detector; The reflected light reflected from all the sample points is split into a first reflected light and a second reflected light by the beam splitter, and then emitted to the first array detector and the second array detector respectively; The controlling the first motor to drive the angle modulation component to move to adjust the telecentric angle of the incident light generated by the telecentric light source so that the intensity of the incident light at all sample points on the microarray chip is equal includes: controlling the first motor to drive the angle modulation component to move, so as to adjust the telecentric angle of the incident light generated by the telecentric light source; Acquire a first image of all the sample points through the second array detector; Obtaining a ratio of the mean square error of the intensities of all pixels in the first image to the mean intensity; When the ratio is not equal to the preset threshold, the control returns to the first motor to drive the angle modulation component to move until the ratio is equal to the preset threshold. When the ratio is equal to the preset threshold, the intensity of the incident light at all sample points of the microarray chip is equal.

11. The surface plasmon resonance imaging method according to claim 10, wherein: The imaging system further includes a second motor, the first array detector being mechanically connected to the second motor; The method further comprises: The second motor is controlled to adjust the position of the receiving surface of the first array detector so that the receiving surface of the first array detector receives the reflected light reflected by all the sample points.

12. The surface plasmon resonance imaging method according to claim 11, wherein: The controlling the second motor to adjust the position of the receiving surface of the first array detector so that the receiving surface of the first array detector receives the reflected light reflected by all the sample points includes: Acquire a second image of all the sample points through the second array detector; Obtaining preparation effect diagrams of all the sample points; calibrating all the sample points in the second image according to the second image and the preparation effect diagram; Obtaining positions of all sample points on a receiving surface of the second array detector according to the calibration result; Acquire a third image of all the sample points through the first array detector; Obtaining positions of all the sample points on a receiving surface of the first array detector according to the third image; Obtaining position differences between positions of all the sample points on the receiving surface of the first array detector and positions of all the sample points on the receiving surface of the second array detector; According to the position difference, the second motor is controlled to adjust the position of the receiving surface of the first array detector so that the receiving surface of the first array detector receives the reflected light reflected by all the sample points.

13. The surface plasmon resonance imaging method according to claim 12, wherein: Acquiring the second image of all the sample points by the second array detector includes: After a standard sample is introduced into the sample injection pool, a second image of all the sample points is acquired by the second array detector; The step of calibrating all sample points in the second image according to the second image and the preparation effect diagram includes: Obtaining four design parameters of the preparation effect diagram, the four design parameters including the coordinates of the starting point of the preparation effect diagram, the coordinates of the end point, the difference between the abscissa of the starting point and the corner point closest to the starting point among all the sample points, and the difference between the ordinates of the corner point and the starting point; Obtaining, according to the second image, the preparation effect diagram, and the four design parameters, a compression ratio between the second image and the effect diagram, and coordinates of all sample points in the preparation effect diagram; The coordinates of all the sample points in the second image are obtained according to the difference between the abscissas of the corner point and the starting point, the difference between the ordinates of the corner point and the starting point, the compression ratio, and the coordinates of all the sample points in the preparation effect image, so as to calibrate all the sample points in the second image.

14. The surface plasmon resonance imaging method according to claim 13, wherein: After calibrating all the sample points in the second image, the method further comprises: Obtaining coordinates of the centers of gravity of all sample points in the second image; The coordinates of all the sample points in the second image are replaced by the coordinates of the corresponding centers of gravity to obtain corrected coordinates of all the sample points in the second image.

15. The surface plasmon resonance imaging method according to any one of claims 10 to 14, wherein: The method further comprises: Adjusting the sensitivity coefficient of the first array detector to a preset sensitivity coefficient; adjusting the bias of the first array detector; Acquire a fourth image of all the sample points through the first array detector; When the pixel values ​​corresponding to all the sample points in the fourth image are not all 0, the bias of the first array detector is adjusted again until the pixel values ​​corresponding to all the sample points in the fourth image are all 0.

16. The surface plasmon resonance imaging method according to any one of claims 10 to 14, wherein: The method further comprises: At a preset moment in a preset sampling process, a fifth image of all the sample points is acquired by the first array detector, wherein the preset sampling process is: after the standard sample is passed into the sampling pool for a third preset time, the sample to be tested with a preset mass fraction is passed into the sampling pool for a fourth preset time, and then the standard sample is passed into the sampling pool for a fifth preset time, and the preset moment is the moment when the sample to be tested is passed into the sampling pool for a sixth preset time, and the sixth preset time is less than the fourth preset time; The refractive index of the sample to be measured is obtained according to the fifth image.

17. A control system comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein: When the processor executes the computer program, the steps of the surface plasmon resonance imaging method according to any one of claims 10 to 16 are implemented.

18. A computer-readable storage medium, characterized in that The computer-readable storage medium stores a computer program, and when the computer program is executed by at least one processor, the steps of the surface plasmon resonance imaging method according to any one of claims 10 to 16 are implemented.

Citation Information

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