Liquid chip detection system and method for analyzing one or more analytes

Abstract

The liquid-phase chip detection system and method for analyzing one or more analytes provided by the present invention apply an electric field to the particles to be analyzed in a detection zone via electrodes, causing the particles to undergo an electrochemiluminescence reaction, emitting a reporter light signal related to the analyte bound to the particles. A detection device then detects the reporter light signal to obtain reporter light signal data, which is then processed by a processing device to obtain the analyte content. Because the electrochemiluminescence reaction is used, no excitation light source is required when detecting the reporter light signal, eliminating background noise from the light source. This improves the sensitivity and accuracy of the reporter light signal detection, thereby also improving the sensitivity and accuracy of the analyte detection.

Description

Technical Field

[0001] The present invention relates to the field of biochip detection technology, and in particular to a liquid chip detection system and a method for analyzing one or more analytes. Background Art

[0002] Liquid-phase suspension chip technology is a cutting-edge molecular detection technology that integrates fluidics, microparticle synthesis, molecular hybridization, and efficient digital signal processing. Its principle is to integrate known molecules (DNA, RNA, peptides, proteins, small molecules, etc.) onto the surface of one or more microparticles to form a probe array, capture one or more analytes in the sample, and couple the analytes with one or more luminescent substances (fluorescent dyes, fluorescent groups or fluorescent microparticles, Raman spectroscopy characteristic molecules, etc.) for labeling. The luminescent substances are then stimulated with an excitation light source to emit light, which is then detected using optical methods. As a new biomolecule detection technology, liquid-phase suspension chip technology offers significant advantages for biomolecule detection, such as high throughput, fast speed, and low cost. However, its detection sensitivity and accuracy still need to be improved. Summary of the Invention

[0003] The present application provides a liquid chip detection system and a method for analyzing one or more analytes to improve the accuracy of analyte detection.

[0004] According to a first aspect, the present application provides a liquid phase chip detection system, comprising:

[0005] a light source configured to illuminate particles to be analyzed in a detection zone to generate a coded light signal related to the type of particles to be analyzed; wherein the detection zone is configured to provide a detection location for one or more particles to be analyzed; the particles to be analyzed are arranged in a single layer in the detection zone; and the particles to be analyzed are bound to an analyte;

[0006] The electrodes are used to apply an electric field to the particles to be analyzed in the detection zone, so as to cause the particles to undergo electrochemiluminescence reaction and emit a reporter light signal related to the analyte bound to the particles to be analyzed;

[0007] a detection device, configured to detect the coded optical signal and the report optical signal, convert the coded optical signal into coded optical signal data, and convert the report optical signal into report optical signal data;

[0008] A processing device is used to process the coded light signal data to obtain the type of the particle to be analyzed indicated by the coded light signal; according to the type of the particle to be analyzed, the reporting light signal data belonging to the same type of particle to be analyzed is processed to obtain the content of the analyte bound to the particle to be analyzed.

[0009] In the detection system, a particle to be analyzed is bound to an analyte; the coded light signal comprises a fluorescent signal; and the light source irradiates the particle to be analyzed in the detection area to generate the coded light signal, comprising:

[0010] The light source illuminates the particles to be analyzed in the detection area, and stimulates the particles to be analyzed to emit coded light signals.

[0011] In the detection system, the detection area is also used to accommodate a buffer solution, and the buffer solution is used to realize and / or promote the electrochemiluminescence reaction.

[0012] In the detection system, the detection area is an imaging room, and the detection system further includes:

[0013] A sampling needle, used to draw a sample to be analyzed by relying on the power provided by the fluid power source; the sample to be analyzed is a solution containing one or more particles to be analyzed;

[0014] The fluid power source is used to provide power to transport the sample to be analyzed sucked by the sampling needle to the imaging chamber, and to provide power to discharge waste liquid; the sampling needle, the imaging chamber and the fluid power source are connected.

[0015] The detection system further includes a receiving device for accommodating and fixing the microfluidic chip; the detection area is arranged on the microfluidic chip, and the microfluidic chip also includes a sample addition port, and the sample addition port and the detection area are connected through a microfluidic channel and / or a microvalve; the sample addition port is used to add a biological sample, and the one or more particles to be analyzed are obtained by reacting the biological sample with a reagent in the microfluidic chip, and the reagent includes one or more particles.

[0016] In the detection system, the detection area is a detection cup.

[0017] In the detection system, the detection device detects the coded light signal and the report light signal, converts the coded light signal into coded light signal data, and converts the report light signal into report light signal data, including:

[0018] The detection device filters the coded light signal emitted from the target area in the detection zone, and then images the filtered light signal to obtain a filtered image. Each filtered image contains the image signal of a wavelength band of the particles to be analyzed in the target area. All image signals of each particle to be analyzed together constitute the coded light signal data of the particle to be analyzed.

[0019] After the particles to be analyzed undergo an electrochemiluminescence reaction and emit the reporter light signal, imaging the target area in the detection zone to obtain a reporter image containing images of all particles to be analyzed in the target area;

[0020] The processing device processes the coded light signal data to obtain the type of the particle to be analyzed indicated by the coded light signal; based on the type of the particle to be analyzed, the reporting light signal data belonging to the same type of particle to be analyzed is processed to obtain the content of the analyte bound to the particle to be analyzed, including:

[0021] The processing device decodes the coded light signal data based on the image signal of each particle to be analyzed in the target area in the filtered image and the corresponding band of the image signal to obtain the type of each particle to be analyzed in the target area; based on the position of a particle to be analyzed in the filtered image and the corresponding position and image brightness of the particle to be analyzed in the report image, the content of the analyte bound to the particle to be analyzed is obtained.

[0022] The detection system further includes a particle confinement device; the particle confinement device is used to confine the particles to be analyzed in the detection area into a single layer arrangement to facilitate detection.

[0023] In the detection system, the particles to be analyzed are magnetic in a magnetic field, and the particle confinement device constrains the particles to be analyzed in the detection area into a single layer arrangement through magnetic force, and fixes the particles to be analyzed in the detection area through magnetic force.

[0024] According to a second aspect, the present application provides a method for analyzing one or more analytes, comprising the following steps:

[0025] A light source illuminates particles to be analyzed in a detection zone to generate a coded light signal; the coded light signal is related to the type of particles to be analyzed; the detection zone contains one or more particles to be analyzed; wherein the particles to be analyzed are arranged in a single layer in the detection zone; and the particles to be analyzed are bound to an analyte;

[0026] The electrodes apply an electric field to the particles to be analyzed in the detection area, causing the particles to undergo an electrochemiluminescence reaction and emit a reporter light signal related to the analyte bound to the particles to be analyzed;

[0027] The detection device detects the coded optical signal and the report optical signal, converts the coded optical signal into coded optical signal data, and converts the report optical signal into report optical signal data;

[0028] The processing device processes the coded light signal data to obtain the type of the particle to be analyzed indicated by the coded light signal; according to the type of the particle to be analyzed, the reporting light signal data belonging to the same type of particle to be analyzed is processed to obtain the content of the analyte bound to the particle to be analyzed.

[0029] According to the liquid-phase chip detection system and method for analyzing one or more analytes described in the above-mentioned embodiments, an electric field is applied to the particles to be analyzed in the detection zone via electrodes, causing the particles to undergo an electrochemiluminescence reaction, emitting a reporter light signal related to the analyte bound to the particles. A detection device then detects the reporter light signal to obtain reporter light signal data, which is then processed by a processing device to determine the analyte content. Because the reporter light signal is detected using an electrochemiluminescence reaction, no excitation light source is required, resulting in no background noise from the light source. This improves the accuracy of the reporter light signal detection, and consequently, the accuracy of the analyte detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 A schematic structural diagram of an embodiment of a liquid phase chip detection system provided by the present invention;

[0031] Figure 2 This is a structural block diagram of an embodiment of a liquid phase chip detection system provided by the present invention;

[0032] Figure 3 A flow chart of an embodiment of a method for analyzing one or more analytes provided by the present invention;

[0033] Figure 4 A schematic diagram of the liquid circuit subsystem of an embodiment of the liquid chip detection system provided by the present invention;

[0034] Figure 5 A schematic diagram of the liquid circuit of another embodiment of the liquid circuit subsystem in the liquid chip detection system provided by the present invention;

[0035] Figure 6 This is a schematic diagram of the principle of using a microfluidic chip for sample injection in the liquid chip detection system provided by the present invention;

[0036] Figure 7 A schematic diagram of the microfluidic path of the microfluidic chip in the liquid chip detection system provided by the present invention;

[0037] Figure 8 A schematic diagram of an embodiment of a detection device in the liquid chip detection system provided by the present invention;

[0038] Figure 9 This is a schematic diagram of another embodiment of the detection device in the liquid chip detection system provided by the present invention. DETAILED DESCRIPTION

[0039] The present invention will be further described in detail below through specific embodiments with reference to the accompanying drawings.

[0040] The liquid chip detection system provided by the present invention can analyze (detect) one or more analytes and is applicable to various detection equipment, such as liquid chip detectors, which can be used for in vitro diagnosis, immunoassay, molecular diagnosis, etc.

[0041] like Figure 1 and Figure 2 As shown, the detection system includes: a detection area 11, a processing device 20, a detection device 30, a light source 40 and an electrode 50. The detection device 30, the light source 40 and the electrode 50 are all electrically connected to the processing device 20.

[0042] The detection zone 11 is used to provide a detection location for one or more particles to be analyzed f. The particles to be analyzed are arranged in a single layer in the detection zone 11. For example, the detection zone 11 may be provided with a flat plate, on which the particles to be analyzed are arranged in a single layer. The surface of the plate can be flat, with the particles to be analyzed dispersed thereon; the surface of the plate can also have multiple micropores, with each micropore accommodating a particle to be analyzed, with each particle to be analyzed being effectively immobilized by the micropores. The particles to be analyzed are bound to an analyte. In this embodiment, each particle to be analyzed is bound to a single analyte. The detection zone 11 is also used to accommodate a buffer solution. The buffer solution can be an electrochemical reaction solution for achieving an electrochemiluminescence reaction, or it can be an electrochemical reaction solution for promoting an electrochemiluminescence reaction. The single layer arrangement of the particles to be analyzed in the detection zone 11 can be achieved by gravity, such as sedimentation, or by confinement, such as by an electric or magnetic field. In this embodiment, the detection system further includes a particle confinement device 60. The particle confinement device 60 is electrically connected to the processing device 20 and controlled by the processing device 20.

[0043] The particle confinement device 60 is used to confine the particles to be analyzed in the detection area 11 into a single layer arrangement for easy detection. There are many ways to confine, such as the particles are charged and confined into a single layer by an electric field. In this embodiment, the particles to be analyzed are magnetic particles bound to the analyte, that is, the particles to be analyzed have magnetism in the magnetic field. The particle confinement device 60 confines the particles to be analyzed in the detection area 11 into a single layer arrangement by magnetic force and fixes the particles to be analyzed in the detection area 11 by magnetic force. The particle confinement device 60 is generally an electromagnetic coil or a permanent magnet, or a permanent magnet with an electromagnetic coil or an iron core with an electromagnetic coil. The particle confinement device 60 can be arranged below the detection area 11.

[0044] The light source 40 is used to illuminate the detection area 11, specifically, to illuminate the particles to be analyzed in the detection area 11, to generate a coded light signal. The light source 40 can be arranged above the detection area 11, for example, illuminating the detection area 11 at a certain angle. The number of light sources 40 can be one or more, for example, the light sources 40 are arranged in pairs, with the two light sources 40 in the pair located on either side of the detection area 11. The coded light signal is related to the type of particle to be analyzed. The coded light signal can refer to the code of the particle to be analyzed, thereby obtaining the analyte corresponding to the code. One code corresponds to one particle to be analyzed, that is, to one analyte. The analyte can be a variety of biochemical markers such as nucleic acids, antigens, antibodies, hormones, carbohydrates, antibiotics, bacteria, or viruses. By encoding the particles, it is easier to analyze a variety of analytes. The light source 22 can be a static light source, or a point scanning or line scanning light source. The coded light signal can be a fluorescent signal. The light source 40 illuminates the particles to be analyzed in the detection area 11, exciting the particles to be analyzed to emit the coded light signal. In other words, the light source 40 is an excitation light source. The coded light signal can also be scattered light, that is, the light source 40 is used as an illumination light source, and is encoded according to the particle size and / or shape, etc. The light source 40 illuminates the particles to obtain the scattered light of each particle, and then the size and / or shape of each particle is obtained through the scattered light, thereby decoding.

[0045] Electrode 50 is used to apply an electric field to the particles to be analyzed in detection zone 11, for example, using an anode electrode, causing the particles to undergo an electrochemiluminescence reaction, emitting a reporter light signal related to the analyte bound to the particles. Electrode 50 is positioned on one side of the flattened particles to be analyzed. The particles to be analyzed can be arranged in a single layer on electrode 50 or in a single layer in the detection zone and in contact with electrode 50. Electrode 50 contacts the buffer and the particles to be analyzed to facilitate electron exchange. Electrode 50 can specifically be an electrode plate, a layer of coated electrode, or a microelectrode column positioned on one side of the flattened particles to be analyzed. This embodiment uses an electrode plate, and the surface of the electrode plate in contact with the particles to be analyzed can be flat or have multiple micropores. The electrochemiluminescence reaction is triggered and controlled by electrode 50, making it easy to control. No excitation light source is required for detecting the reporter light signal, resulting in no background noise from the light source. This improves the sensitivity and accuracy of the reporter light signal detection, and thus the sensitivity and accuracy of the analyte detection.

[0046] The detection device 30 is used to detect the coded light signal and the reporter light signal, converting the coded light signal into coded light signal data and the reporter light signal into report light signal data. The coded light signal data is processed to obtain the type of analyte indicated by the coded light signal. The report light signal data is processed to obtain the content of the analyte indicated by the report light signal. The detection device 30 may include at least one of a single-point photosensitive detector (photodetector), a linear array photosensitive detector, and a planar array photosensitive detector.

[0047] The detection system of the present invention may include a detection device body (not shown), in which the detection device 30, light source 40, electrode 50, and particle confinement device 60 may be disposed. The detection system of the present invention also includes a power supply device for supplying power to various electrical appliances in the detection system.

[0048] The processing device 20 is used to process each functional module (such as Figure 2 30, 40, 50, 60, etc.) are controlled to realize the analysis of the particles to be analyzed. For example, the processing device 20 processes the coded light signal data to obtain the type of particles to be analyzed referred to by the coded light signal. Since the present invention adopts liquid chip technology, various particles have their corresponding codes, and one code corresponds to one analyte. For example, encoding is performed according to different combinations of luminescent substances (such as fluorescent substances), encoding is performed according to different shapes and sizes of particles, etc., and the processing device 20 decodes the coded light signal data to obtain what kind of analytes are contained in the particles to be analyzed. Furthermore, the processing device 20 processes the report light signal data belonging to the same type of particles to be analyzed according to the type of particles to be analyzed, and obtains the content of the analyte bound to the particles to be analyzed. Generally, the higher the content, the greater the light intensity of the report light signal. The report light signal data of each particle to be analyzed are processed so that the final content is statistically significant and the content is accurate and reliable.

[0049] The processing device 20 can be a processor. The processor can be located within the detection device itself, meaning that the detection device itself can control the detection device itself, detect particles, and perform subsequent data processing and analysis. Of course, the processor can also be located outside the detection device itself. For example, if the detection system also includes a computer, the processor can be the processor within the computer. In other words, the computer can control the detection device itself to perform particle detection, and the computer can perform subsequent data processing and analysis.

[0050] like Figure 3 As shown, the process of the detection system analyzing one or more analytes is as follows:

[0051] Step 1: The detection area 11 obtains the particles to be analyzed. This step involves how to inject the sample. The present invention provides three injection methods corresponding to three different structures, which are described below one by one.

[0052] Method 1 uses the liquid path subsystem to inject samples, that is, the detection system also includes the liquid path subsystem. The detection area 11 is an imaging chamber, and the imaging chamber is a part of the liquid path subsystem, such as Figure 4 As shown, the liquid path subsystem further includes: a first gating device, a second gating device 12, a fluid power source 10, a sample aspiration position b, a waste liquid discharge position c and a liquid aspiration position d.

[0053] The sample aspiration position b is used to provide a sample to be analyzed, which contains one or more particles to be analyzed. The sample aspiration position b refers to the location where the sampling needle aspirates the sample. In one embodiment, this location can be a fixed facility, such as a recessed slot for placing the sample container 13 to provide the sample to be analyzed. Alternatively, the sample aspiration position b can be a container itself, which is used to hold the sample to be analyzed. In some embodiments, the sample aspiration position b can also be a coordinate location. When the sample needs to be aspirated, the sampling needle and / or sample container 13 are moved to this location to collect the sample.

[0054] The sample to be analyzed is stored in the sample container 13. Specifically, the sample is stored in the sample container 13 in the form of a liquid, and the sample contains one or more particles to be analyzed. The particles to be analyzed can be encoded by particle shape, particle pattern (for example, any pattern can be etched on the surface of the particle), particle size, fluorescence spectrum or Raman spectrum, etc. The size of the particle can be in the range of nanometers to micrometers, and can be microparticles of various shapes. For example, the particle can be a microsphere, and the particle size can be in the range of nanometers to micrometers. In this embodiment, the particle to be analyzed is combined with an analyte, a fluorescent substance used for encoding, and a substance used for electrochemiluminescence reaction (for example, ruthenium terpyridine). The fluorescent substance is usually a fluorescent dye, quantum dots or up-conversion luminescent materials, etc. The fluorescent substance can emit fluorescence under the excitation of a light source. It is used as a substance for electrochemiluminescence reaction.

[0055] The waste liquid discharge position c is the location where waste liquid is discharged. In one embodiment, this location can be a fixed facility, such as a recessed slot for placing the waste liquid recovery device 14. In another example, the waste liquid discharge position c can also be a container for storing waste liquid. In some embodiments, the waste liquid discharge position c can also be a coordinate position. When waste liquid needs to be discharged, the sampling needle and / or the waste liquid recovery device moves to this position to collect the cleaning liquid.

[0056] The liquid aspiration position d is the location for aspirating cleaning fluid. In one embodiment, this location can be a fixed facility, such as a recessed slot for placing the cleaning fluid container 15 to provide cleaning fluid. Alternatively, the liquid aspiration position d can be a container itself for containing cleaning fluid. In some embodiments, the liquid aspiration position d can also be a coordinate position. When cleaning fluid is required, the sampling needle and / or cleaning fluid container is moved to this position to collect the cleaning fluid.

[0057] The entrance of the imaging chamber 11 is selectively connected to the sample container 13, the waste liquid recovery device 14 and the cleaning liquid container 15 through the first gating device. That is, the first gating device is used to selectively connect one of the sample container 13, the waste liquid recovery device 14 and the cleaning liquid container 15 to the entrance of the imaging chamber 11. The first gating device includes a sampling needle a, which is used to draw the sample to be analyzed by relying on the power provided by the fluid power source 10. The first gating device drives the sampling needle a to communicate with the sample container 13, drives the sampling needle a to communicate with the waste liquid recovery device 14, and drives the sampling needle a to communicate with the cleaning liquid container 15 to achieve gating, such as Figure 4 The first gating device can also be gated by valve J, as shown. Figure 5 shown.

[0058] The fluid power source 10 is selectively connected to the outlet of the imaging chamber 11 and the cleaning liquid container through the second gating device 12. That is, the second gating device 12 is used to selectively connect one of the outlet of the imaging chamber 11 and the cleaning liquid container 15 to the fluid power source 10.

[0059] The fluid power source 10 is used to provide power to transport the sample to be analyzed, drawn up by the sampling needle a, to the imaging chamber 11 and to drain waste fluid. The fluid power source 10 can be a device such as a pump that propels fluid, particularly liquid, through a pipeline. The fluid power source 10 is electrically connected to the processing device 20. When the first and second gating devices are activated, the sampling needle a, the imaging chamber 11, and the fluid power source 10 are in communication.

[0060] This method uses a liquid subsystem to aspirate samples, and the process is fast and reliable.

[0061] Method 2 uses a microfluidic chip for sample injection, and the detection device body also includes a receiving device for accommodating and fixing the microfluidic chip; the detection area 11 is set on the microfluidic chip. Figure 6 As shown, the microfluidic chip also includes a sample injection port 110, which is connected to the detection area 11 through a microfluidic channel and / or a microvalve. The microfluidic channel and the microvalve are pipes (usually grooves) and valves arranged in the microfluidic chip. The cross-sectional dimensions of the microfluidic channel can be centimeters or less, usually micrometers or millimeters. The microvalve is adapted to the microfluidic channel in size. The microfluidic channel and the microvalve are specifically used in conventional ways and will not be described in detail.

[0062] The sample injection port 110 is used to inject biological samples. One or more particles to be analyzed are obtained by reacting the biological sample with a reagent in the microfluidic chip. The reagent includes one or more particles.

[0063] For details, see Figure 7 , Figure 7The figure shows a microfluidic circuit on a microfluidic chip. The detection device body may also include an air storage chamber 140, which is located inside or outside the microfluidic chip and is used to drive the movement of biological samples and / or liquids in the microfluidic chip to achieve biological sample reaction and / or detection. This method of driving liquid flow is a pressure-driven microfluidic method. Of course, centrifugal force-driven microfluidics, droplet microfluidics, digital microfluidics (such as electrowetting microfluidics), capillary force-driven microfluidics, and other methods can also be used, and the present invention does not limit them.

[0064] The microfluidic chip can also be provided with a sample filter 150 for filtering out substances in the biological sample that interfere with the detection. The sample filter 150 can be provided between the sample injection port 11 and the reaction area 121. Figure 7 In the illustrated embodiment, the sample filter 150 is disposed at the sample loading port 110 and is filtered immediately after the sample is loaded. For example, if the biological sample is blood, after the blood enters the microfluidic path of the microfluidic chip through the sample loading port 110, the sample filter 150 filters out blood cells and other substances that interfere with the detection, thereby facilitating subsequent detection.

[0065] The microfluidic chip can also be provided with a reaction zone 120, where the biological sample and the reagent react to obtain one or more particles to be analyzed. The reaction zone 120 and the detection zone 11 can be the same area or different areas.

[0066] A diluent storage area 160 may also be provided between the sample injection port 110 and the reaction area 120. The diluent storage area 160 stores diluent for diluting biological samples and / or reagents. The diluent storage area 160 may be provided inside the microfluidic chip or outside the microfluidic chip, connected to the microfluidic path of the microfluidic chip via an interface provided on the microfluidic chip.

[0067] The detection system also includes a reagent storage area disposed within and / or outside the microfluidic chip. The reagent storage area includes particle-coated reagents and / or electrochemical labeling reagents, buffer solutions, and the like. The coating material in the particle-coated reagents and the analyte-binding material in the electrochemical labeling reagents can be various biochemical molecules, such as nucleic acids, antigens, antibodies, hormones, carbohydrates, and antibiotics. The particle-coated reagents can be stored in the reagent storage area in a dry or gel form. In this case, the reagent storage area and the reaction area 120 can be in the same area or share a portion of the same area. Of course, the particle-coated reagents can also be stored in the reagent storage area in a liquid or gel form. In this case, the reagent storage area and the reaction area 120 can be separate areas, and the reagent storage area can be located between the injection port 110 and the reaction area 120. To accommodate the detection of multiple analytes, the reagent storage area can store multiple particle-coated reagents in the same area. Of course, the reagent storage area can also store multiple particle-coated reagents separately.

[0068] Particle coating reagents mainly include particles that are encoded and can bind to capture molecules, which can be biomolecules, etc. Electrochemical labeling reagents are used to bind to the analyte and emit light when triggered by a subsequent electric field.

[0069] Similarly, the electrochemical labeling reagent can be stored in a dry or gel form in the reagent storage area. In this way, the reagent storage area and the reaction area 120 can be the same area or share a portion of the area. Of course, the electrochemical labeling reagent can also be stored in the reagent storage area in a liquid or gel form. In this way, the reagent storage area and the reaction area 120 can be different areas. To cope with the detection of multiple analytes, the reagent storage area can store multiple electrochemical labeling reagents in the same area. Of course, the reagent storage area can also store multiple electrochemical labeling reagents separately.

[0070] The detection system also includes: a waste liquid tank 170 and a cleaning liquid storage area 190, which are arranged inside and / or outside the microfluidic chip. The detection system also includes a cleaning area 180 arranged inside the microfluidic chip. The reaction area 120, the waste liquid tank 170, the cleaning area 180, the detection area 11, the cleaning liquid storage area 190, etc. can be arranged in sequence along the direction of movement of the particles to be analyzed. The waste liquid tank 170 is used to store waste liquid and is provided with one or more air holes. The cleaning area 180 is an area for cleaning the particles to be analyzed after the reaction. The cleaning liquid storage area 190 stores cleaning liquid.

[0071] The electrode 50 can be arranged in the detection area 11 inside the microfluidic chip. The microfluidic chip is provided with a contact interface electrically connected to the electrode 50. The detection device body supplies power to the electrode 50 through the contact interface.

[0072] The detection device body is also provided with a particle drive device and a temperature control device. Both the particle drive device and the temperature control device are electrically connected to the processing device 20. The particle drive device is used to drive the movement of magnetic particles before the reaction between the biological sample and the reagent is completed to accelerate the reaction between the analyte in the biological sample and the magnetic particles in the reagent, and / or to drive the movement of the particles to be analyzed to transfer the particles to be analyzed. The temperature control device is used to precisely control the temperature of areas with required temperatures, such as controlling the temperature of the reaction zone 120 to the temperature required for the reaction between the biological sample and the reagent during the reaction.

[0073] Since the liquid path is set in the microfluidic chip and the microfluidic chip is very small, this method can greatly reduce the volume of the detection device itself, which is conducive to the miniaturization and portability of the device.

[0074] Method 3 uses a test cup for sample introduction. In other words, in this method, the detection area 11 is the test cup, specifically the bottom of the test cup. Specifically, the user adds the biological sample and a reagent containing the aforementioned particles to the test cup. After reaction within the test cup, one or more particles to be analyzed are obtained. After cleaning, the particles are then deposited or the particle confinement device 60 is used to arrange all the particles in a single layer at the bottom of the test cup, allowing subsequent testing to proceed.

[0075] Step 2: The light source 40 illuminates the particles to be analyzed in the detection area 11 to generate coded light signals. The specific process has been described above and will not be repeated here.

[0076] In step 3, electrode 50 applies an electric field to the particles in detection zone 11, causing them to undergo electrochemiluminescence (ECL) and emit a reporter light signal related to the analyte bound to the particles. The coded light signal and the reporter light signal are generated using different principles, so they do not affect each other. Step 2 can be performed first, followed by step 3, or step 3 can be performed first, followed by step 2.

[0077] Step 4. The detection device 30 detects the coded light signal and the reporter light signal, converts the coded light signal into coded light signal data, and converts the reporter light signal into reporter light signal data. Specifically, the detection device 30 filters the coded light signal emitted by the target area in the detection zone 11, and after filtering, images are formed to obtain a filtered image. A filtered image contains an image signal of a wavelength band of the particles to be analyzed in the target area, and all image signals of each particle to be analyzed together constitute the coded light signal data of the particle to be analyzed. After the particles to be analyzed undergo an electrochemiluminescence reaction and emit a reporter light signal, the detection device 30 images the target area in the detection zone 11 and obtains a reporter image containing images of all particles to be analyzed in the target area. The target area can be the entire detection area 11 or a portion of the detection area 11.

[0078] There are many ways to implement the detection device 30 to filter the coded light, for example Figure 8As shown, the detection device 30 includes a photosensitive detector (photodetector) 31 and a filter switching device 32. The filter switching device 32 and the photosensitive detector 31 are sequentially arranged on the optical path (the propagation path of light) of the coded light signal. The filter switching device 32 is used to allow light of different wavelengths (bands) to pass through, and includes a plurality of imaging filters 321, wherein the imaging filters 321 involved in filtering are arranged on the optical path between the detection area 11 and the photosensitive detector 31, thereby allowing light of a certain wavelength (band) to enter the photosensitive detector 31. By switching the imaging filters in the optical path, light of different wavelengths can enter the photosensitive detector 31 separately. For example, the filter switching device 32 can be a filter wheel, which includes a wheel and a plurality of imaging filters arranged in a circular array on the wheel, wherein the imaging filters involved in filtering are located on the optical path between the detection area 11 and the photosensitive detector 31. The imaging filter is used to filter the coded fluorescence of the particle f to be analyzed, for example, allowing only fluorescence of a single wavelength (band) to pass through, so that the photodetector 31 can image the fluorescence and obtain a corresponding filtered image. The rotating wheel rotates to switch the imaging filter 321, which can detect the fluorescence signal of another wavelength (band), and the photodetector 31 can then image the corresponding filtered image. The photodetector 31 can be at least one of a single-point photodetector, a linear array photodetector, and a planar array photodetector. The photodetector 31 can be an avalanche photodiode (APD), a photomultiplier tube (PMT), or a camera. The detection area can be scanned by moving the photodetector 31 to obtain a corresponding image. The detection area can be scanned by the light source 40 to obtain a corresponding image. Alternatively, a planar array photodetector can be used to directly image the detection area to obtain a corresponding image. A camera can also be used as a planar array photodetector. In addition, the detection device 30 can include one or more photodetectors of each type.

[0079] For example Figure 9 As shown, the detection device 30 includes a photosensitive detector 31 and a spectrometer 33. The number of photosensitive detectors 31 is usually multiple, and the spectrometer 33 can be one or more to meet the detection requirements of various analytes. The spectrometer 33 is used for spectrometry. Each spectrometer 33 can be connected in series and parallel to split the coded light signal according to the different wavelengths (bands) to obtain multiple light signals. Each light signal corresponds to a coded light of a band used for encoding, and a photosensitive detector 31 is set on the light path of each light signal obtained by spectrometry. The photosensitive detector 31 performs imaging to obtain a corresponding filtered image. The spectrometer 33 can use a dichroic mirror. A filter 34 can also be set between the spectrometer 33 and the photosensitive detector 31 to filter out interference from other light signals (such as light from a light source).

[0080] In step 5, the processing device 20 processes the coded light signal data to obtain the type of particle to be analyzed indicated by the coded light signal. Based on the type of particle to be analyzed, the reporting light signal data belonging to the same type of particle to be analyzed is processed to obtain the amount of analyte bound to the particle to be analyzed. Specifically, the processing device 20 decodes the coded light signal data based on the image signal of each particle to be analyzed in the target region and the corresponding wavelength band of the image signal in the filtered image, thereby obtaining the type of each particle to be analyzed in the target region. Based on the position of a particle to be analyzed in the filtered image and its corresponding position and image brightness in the reporting image, the amount of analyte corresponding to the particle to be analyzed is obtained. For example, magnetic polystyrene microspheres with a diameter of 6 μm are encoded using red and orange fluorescent dyes. Each dye is divided into 10 equal parts based on fluorescence intensity, forming 100 different magnetic fluorescent encoded microspheres of 10*10, each of which is coupled to 100 different probe molecules for biological detection. This shows that the present invention can detect a large number of analytes at once as needed. After filtering out the light from the light source 40 and the orange light, the target area is imaged to obtain an image of the particles emitting red light in the target area (filtered image), and by processing the image, the brightness level of the red light emitted by each particle can be known. Similarly, after filtering out the light from the light source 40 and the red light, the target area is imaged to obtain an image of the particles emitting orange light in the target area (filtered image), and by processing the image, the brightness level of the orange light emitted by each particle can be known. Since the position of the same particle in these two images is the same, the processing device 20 can decode it by combining the brightness level of the red light emitted by the particle and the brightness level of the orange light emitted. Similarly, the position of the same particle in the filtered image and the report image is the same, so the brightness level of the particle's electrochemical luminescence can be obtained. By comprehensively analyzing the luminescence of the same particles in the entire target area, the content of the analyte can be obtained.

[0081] In summary, the present invention combines electrochemiluminescence with liquid phase chip detection, which has higher sensitivity and accuracy than traditional liquid phase chips and higher detection throughput than traditional electrochemiluminescence detection.

[0082] The above examples are used to illustrate the present invention, which are only used to help understand the present invention and are not intended to limit the present invention. Those skilled in the art can make several simple deductions, modifications or substitutions based on the concept of the present invention.

Claims

1. A liquid phase chip detection system, characterized in that: include: a light source configured to illuminate particles to be analyzed in a detection zone to generate a coded light signal related to the type of particles to be analyzed; wherein the detection zone is configured to provide a detection location for one or more particles to be analyzed; the particles to be analyzed are arranged in a single layer in the detection zone; and the particles to be analyzed are bound to an analyte; The electrodes are used to apply an electric field to the particles to be analyzed in the detection zone, so as to cause the particles to undergo electrochemiluminescence reaction and emit a reporter light signal related to the analyte bound to the particles to be analyzed; A detection device, configured to detect the coded light signal and the reporter light signal, convert the coded light signal into coded light signal data, and convert the reporter light signal into reporter light signal data, comprising: filtering the coded light signal emitted from a target area in a detection zone, imaging the filtered light signal to obtain a filtered image, wherein each filtered image comprises an image signal of a wavelength band of particles to be analyzed in the target area, and all image signals of each particle to be analyzed together constitute the coded light signal data of the particle to be analyzed; and imaging the target area in the detection zone after the particles to be analyzed undergo an electrochemiluminescence reaction to emit the reporter light signal, to obtain a reporter image comprising images of all particles to be analyzed in the target area; A processing device is used to process the coded light signal data to obtain the type of particle to be analyzed indicated by the coded light signal; and according to the type of particle to be analyzed, process the report light signal data belonging to the same type of particle to be analyzed to obtain the content of the analyte bound to the particle to be analyzed, including: decoding the coded light signal data according to the image signal of each particle to be analyzed in the target area in the filtered image in which it is located and the corresponding band of the image signal to obtain the type of each particle to be analyzed in the target area; and obtaining the content of the analyte bound to the particle to be analyzed according to the position of the particle to be analyzed in the filtered image and the corresponding position and image brightness of the particle to be analyzed in the report image.

2. The detection system according to claim 1, wherein: A particle to be analyzed is bound to an analyte; the coded light signal comprises a fluorescent signal; and the light source irradiates the particle to be analyzed in a detection region to generate the coded light signal, comprising: The light source illuminates the particles to be analyzed in the detection area, and stimulates the particles to be analyzed to emit coded light signals.

3. The detection system according to claim 1, wherein: The detection zone is further used to contain a buffer, which is used to achieve and / or promote the electrochemiluminescence reaction.

4. The detection system according to claim 1, wherein: The detection area is an imaging chamber, and the detection system further includes: A sampling needle, used to draw a sample to be analyzed by relying on the power provided by the fluid power source; the sample to be analyzed is a solution containing one or more particles to be analyzed; The fluid power source is used to provide power to transport the sample to be analyzed sucked by the sampling needle to the imaging chamber and provide power to discharge waste liquid; the sampling needle, the imaging chamber and the fluid power source are connected.

5. The detection system according to claim 1, wherein: The microfluidic chip further comprises a receiving device for accommodating and fixing the microfluidic chip; the detection area is arranged on the microfluidic chip, and the microfluidic chip further comprises a sample addition port, the sample addition port and the detection area are connected via a microfluidic channel and / or a microvalve; the sample addition port is used for adding a biological sample, and the one or more particles to be analyzed are obtained by reacting the biological sample with a reagent in the microfluidic chip, and the reagent includes one or more particles.

6. The detection system according to claim 1, wherein: The detection area is a detection cup.

7. The detection system according to claim 1, wherein: It also includes a particle confinement device; the particle confinement device is used to confine the particles to be analyzed in the detection area into a single layer arrangement to facilitate detection.

8. The detection system according to claim 7, wherein: The particles to be analyzed have magnetism in a magnetic field. The particle confinement device confines the particles to be analyzed in the detection area into a single layer arrangement through magnetic force, and fixes the particles to be analyzed in the detection area through magnetic force.

9. A method for analyzing one or more analytes, characterized in that: The steps include: A light source illuminates particles to be analyzed in a detection zone to generate a coded light signal; the coded light signal is related to the type of particles to be analyzed; the detection zone contains one or more particles to be analyzed; wherein the particles to be analyzed are arranged in a single layer in the detection zone; and the particles to be analyzed are bound to an analyte; The electrodes apply an electric field to the particles to be analyzed in the detection area, causing the particles to undergo an electrochemiluminescence reaction and emit a reporter light signal related to the analyte bound to the particles to be analyzed; The detection device detects the coded light signal and the reporter light signal, converts the coded light signal into coded light signal data, and converts the reporter light signal into reporter light signal data, including: filtering the coded light signal emitted by the target area in the detection zone, imaging after filtering to obtain a filtered image, wherein each filtered image includes an image signal of a wavelength band of the particles to be analyzed in the target area, and all image signals of each particle to be analyzed together constitute the coded light signal data of the particle to be analyzed; after the particles to be analyzed undergo an electrochemiluminescence reaction to emit the reporter light signal, imaging the target area in the detection zone to obtain a reporter image including images of all particles to be analyzed in the target area; The processing device processes the coded light signal data to obtain the type of the particle to be analyzed indicated by the coded light signal; based on the type of the particle to be analyzed, the processing device processes the report light signal data belonging to the same type of particle to be analyzed to obtain the content of the analyte bound to the particle to be analyzed, including: decoding the coded light signal data based on the image signal of each particle to be analyzed in the target area in the filtered image and the corresponding band of the image signal to obtain the type of each particle to be analyzed in the target area; based on the position of a particle to be analyzed in the filtered image, the corresponding position of the particle to be analyzed in the report image and the image brightness, obtaining the content of the analyte bound to the particle to be analyzed.

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