Detection chip, detection device, detection system and detection method

Abstract

A detection chip is provided, a detection device that supports detection of multiple different types of the detection chips, and a corresponding detection method, as well as a detection system including the detection device, a client device, and one or more servers. The detection device includes: a detection device configured to detect data in a reaction area of the detection chip; an analysis device configured to analyze a detection result based on the detected data; and a control device configured to couple and decouple the detection chip, where the detection chip includes multiple different types.

Description

Technical Field

[0001] The present disclosure relates to biological detection. More specifically, the present disclosure relates to a detection chip for detecting biological samples, a corresponding detection device, a detection system including the detection device, and a corresponding detection method. Background Art

[0002] There are many challenges in the fields of biomedical analysis, environmental detection, food and drug safety, etc. The demands for on-site sampling analysis, rapid detection, and self-testing by non-professional users have put forward higher requirements for inspection and quarantine analysis means and equipment. To meet these continuously emerging new demands, it is necessary to develop miniaturized and integrated inspection and quarantine devices. Detection chips have emerged as the times require. Summary of the Invention

[0003] Existing detection devices of the detection chip type generally only support a single detection chip. And due to the principle differences of detection technologies for different detection chips, different detection devices are required to support different detection chips, so as to realize the detection functions of different health parameters. Therefore, there are problems such as high dispersion of detection devices, poor consistency between detection results, low accuracy, different operations of each device being not conducive to efficient operation, and high overall price. In addition, the digital degree of detection results is low, which is not conducive to users' query, long-term record and tracking. The correlation between each detection result data may not be clear enough, and the interpretation of detection results also needs to be improved.

[0004] Embodiments of the present invention at least partially solve one or more of the above-mentioned problems.

[0005] According to the first aspect of the embodiments of the present invention, a detection chip is provided, including: a sample injection area configured to receive a sample to be detected, a pretreatment area communicable with the sample injection area and configured to pretreat the sample to be detected, the pretreatment including filtration, quantification, and dilution, a reagent area configured to pre-store reagents required for detection in a freeze-dried or liquid pre-embedded form, a mixing area communicable with the pretreatment area and the reagent area and configured to mix the sample to be detected and the corresponding reagents, and a reaction area communicable with the mixing area and configured to cause the sample to be detected to react under certain conditions for detection; one or more closed cavities, wherein one or more of the sample injection area, the pretreatment area, the reagent area, the mixing area, and the reaction area are located in the one or more closed cavities, an elastic device, the elastic device being part of the housing forming the cavity, the elastic device being capable of changing the air pressure in the cavity under the extrusion of an extrusion device, thereby realizing the movement and the mixing, and / or a gas pump interface, the gas pump outside the detection chip realizing the movement and the mixing through the movement of gas via the gas pump interface; wherein the detection chip includes one of the following types: a biochemical detection chip for detecting biochemical indicators, an immunoassay detection chip for detecting immune indicators, a molecular detection chip for detecting molecular indicators, a cell detection chip for detecting cell indicators, and a coagulation detection chip for detecting coagulation indicators.

[0006] In one embodiment, for the detection chips for biochemical and molecular detection, the area through which the sample to be detected passes is made of a material with no protein adsorption ability; for the detection chips for immunoassay detection, the area through which the sample to be detected passes is made of a material with protein adsorption ability.

[0007] In one embodiment, the conditions include lighting conditions and the detection includes optical detection or image detection.

[0008] In one embodiment, the conditions include power-on conditions and the detection includes electrical detection.

[0009] According to the second aspect of the embodiments of the present invention, a detection device is provided for supporting the above-mentioned detection chip, including: a detection device configured to detect data in the reaction area; an analysis device configured to analyze a detection result based on the detected data; and a control device configured to couple and decouple at least one of the detection chips, wherein the detection chips include multiple different types.

[0010] In one embodiment, the detection device further includes a storage device configured to store the detected data; wherein the analysis device further analyzes the detection result based on the detected data of multiple detection chips in the storage device.

[0011] In one embodiment, the detection device further includes a condition providing device, where the conditions include: suitable lighting conditions, suitable power supply conditions, and / or suitable temperature conditions.

[0012] In one embodiment, the control device is further configured to: in response to receiving a user instruction, control the detection process and / or send the detection result to the user via the user interface.

[0013] In one embodiment, the control device is further configured to implement one or more of the following: motion control of the detection chip, temperature control, magnetic component control, and power control.

[0014] In one embodiment, the analysis device is further configured to analyze the detection result based on a machine learning model.

[0015] In one embodiment, the detection device is a portable detection device.

[0016] According to the third aspect of the embodiments of the present invention, there is provided a detection system including the detection device as described above. The detection system further includes: a client device configured to, when running, send an instruction to the detection device based on a user input, and receive the detection result sent by the detection device and present it to the user; and one or more servers configured to provide support for the detection device and / or the client.

[0017] In one embodiment, the client device is further configured to perform one or more of the following: provide guidance to the user, where the guidance relates to one or more of the following aspects: chip selection, device connection, sample collection, operation process, quality control, and chip detection; calibrate the detection result based on the data stored in one or more of the servers accessible to it; interpret the detection result of the detection device, where interpreting the detection result of the detection device includes one or more of the following: the change in the detection result compared to the historical detection results from the same source, the possible reasons behind the change, the possible reasons behind the abnormal detection result, and suggestions for the user.

[0018] In one embodiment, the server is further configured to perform one or more of the following: based on the detection result of the detection device, provide continuous metric management to the user via the client device, where the metric management includes one or more of the following: regularly reminding the user to perform the detection of one or more metrics, analyzing the user's historical detection results, presenting the metric development trend, and making suggestions to the user.

[0019] In one embodiment, the metric management is provided based on a machine learning model or big data analysis.

[0020] According to a fourth aspect of an embodiment of the present invention, there is provided a detection method for the above-mentioned detection device, the method comprising the following steps: performing coupling with the detection chip; after inputting a sample to be detected, controlling the movement of the sample to be detected in the detection chip and the mixing with the reagent; providing conditions required for detection; performing detection on the sample to be detected mixed with the reagent under the conditions to obtain detection data; and analyzing based on the detection data to obtain a detection result.

[0021] In one embodiment, analysis is further performed based on other detection results from the same source to obtain the detection result.

[0022] In one embodiment, the detection method further comprises the step of sending the detection result to the client device for one or more of the following: display, interpretation, and calibration, where the interpretation includes one or more of the following: changes in the detection result compared to historical detection results from the same source, possible reasons behind the changes, possible reasons behind abnormal detection results, and suggestions for the user.

[0023] In one embodiment, one or more of the steps are performed in response to receiving an indication from the client device.

[0024] When the detection chip according to an embodiment of the present invention performs detection, it can not only liberate human labor, but also be conducive to precise control, reduce operation errors. At the same time, the sealing of the cavity can reduce external interference and contamination. By designing a single detection device to support multiple different types of detection chips, the overall cost can be greatly reduced. At the same time, using the same condition providing device and detection device to detect each detection chip is conducive to the unification of detection data standards, thereby achieving the consistency of detection results, and helping to realize the comprehensive analysis of the detection results of multiple detection chips stored locally. Through the combination of the detection chip and the detection device, as well as the auxiliary functions of the client device and the server, a health service system covering the three-dimensional integration of inspection, diagnosis, and treatment and suitable for mobile health management, especially the application scenario of home health management, can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Embodiments of the present invention will now be described in more detail by way of non-limiting examples with reference to the accompanying drawings, which are merely illustrative and where the same reference numerals always refer to the same parts. In the drawings:

[0026] Figure 1 A schematic diagram of a detection system according to an embodiment of the present invention is shown;

[0027] Figure 2Shows a schematic block diagram of a detection device according to an embodiment of the present invention;

[0028] Figure 3 Shows a schematic optical path diagram of optical detection according to an embodiment of the present invention;

[0029] Figure 4a Shows a schematic diagram of a detection chip according to an embodiment of the present invention;

[0030] Figure 4b Shows a schematic diagram of a detection chip according to another embodiment of the present invention;

[0031] Figure 5 Shows a flowchart according to an embodiment of the present invention;

[0032] Figure 6 Shows the schematic function of the detection system according to an embodiment of the present invention in individual fields. Detailed implementation manners

[0033] Various exemplary embodiments of the present invention will now be described more fully with reference to the accompanying drawings. However, it should be understood that the specific structural and functional details disclosed herein are merely representative. The exemplary embodiments may be embodied in many alternative forms and should not be construed as limited to the specific exemplary embodiments set forth herein. In addition, for the sake of simplicity and clarity in the context, detailed descriptions of well-known structures and methods are omitted to avoid unnecessary details and possible confusion.

[0034] Currently, in the field of biochip detection, due to differences in the principles of detection technologies, different detection devices are usually required to be used with different detection chips to achieve the detection function of different health parameters. As a result, the detection devices have a high degree of dispersion, the consistency between detection results is poor, and the degree of digitization is low, which is not conducive to users' querying and long-term record tracking. Moreover, the correlation between the detection result data is not clear, which is not conducive to subsequent interpretation and analysis. Therefore, in this field, the ability to evaluate the comprehensive health status and predict diseases by interpreting and analyzing detection results needs to be improved.

[0035] Based on the above analysis, the present invention proposes a detection system 100, which is schematically shown in Figure 1 The detection system 100 includes a detection device 101 and a detection chip 104 that can be used on the detection device 101, and optionally further includes a client device 102 and a server 103.

[0036] Exemplarily, the detection chip 104 can be various different types of detection chips for detecting different indicators and different parameters. For example, a biochemical detection chip 1041 for detecting biochemical indicators, an immunological detection chip 1042 for detecting immunological indicators, a molecular detection chip 1043 for detecting molecular indicators, a cell detection chip 1044 for detecting cell indicators, a coagulation detection chip 1045 for detecting coagulation indicators, etc. Further, the biochemical detection chip 1040 includes a chronic disease detection chip with blood glucose and total cholesterol as detection indicators; the immunological detection chip 1042 includes an inflammation and myocardial infarction detection chip with C-reactive protein and troponin I as detection indicators; the molecular detection chip 1043 includes an infectious disease detection chip with hepatitis B virus as a detection indicator; the detection device 101 can read, analyze, and transmit data generated on one or more different detection chips 104. In the case of reading, analyzing, and transmitting data generated on multiple different detection chips 104, the detection device 101 can perform reading, analyzing, and transmitting simultaneously, or can perform reading, analyzing, and transmitting successively.

[0037] The above detection chip 104 can be used on the detection device 101. The detection device 101 can be used to couple (mechanically and electronically) with different types of detection chips 104 simultaneously or successively to achieve the detection of the sample to be tested under the control of the detection device 101.

[0038] The client device 102 can provide an interaction interface for the user, which is configured to achieve the following during operation: sending an instruction to the detection device based on the user input, and receiving the detection result sent by the detection device and presenting it to the user. In one example, the client device 102 is configured to provide guidance to the user, and the guidance relates to one or more of the following aspects: chip selection, device connection, sample collection, operation process, quality control, and chip detection. In one example, the client device 102 is further configured to calibrate the detection result based on the data stored in one or more of the servers 103 accessible to it. In one example, the client device 102 is configured to interpret the detection result of the detection device 101, which requires the client device 102 itself to be configured with a certain function of interpreting the detection result (such as for diverse indicators such as glucose, blood lipids, uric acid, blood, etc.). For example, the change in the detection result compared to the historical detection results from the same source, the possible reasons behind this change (such as the user's diet and exercise, etc.) and / or suggestions (such as suggestions for diet and exercise towards a healthy development), and also, for example, in the case of an abnormal detection result, the possible reasons behind the abnormality (such as lack of sleep, lack of water, hunger, etc.) and / or (such as suggestions for eliminating the abnormality), and so on. Thus, the operation of the user can be greatly facilitated through the client device 102.

[0039] The detection system 100 optionally includes one or more servers (e.g., located in the cloud), which are configured to provide support for the detection device 101 and / or the client 102. In one example, the above interpretation of the client device 102 is based on the big data provided by the server 103 accessible to it, or based on the machine learning model provided by the server 103 accessible to it. In one example, the server 103 is further configured to: based on the detection results of the detection device, via the client device, provide continuous metric management to the user, for example, regularly remind the user to perform the detection of one or more metrics, analyze the user's historical detection results, present the metric development trend, and give suggestions to the user. Optionally, the metric management can also be provided based on a machine learning model or big data analysis.

[0040] Thus, through the combination of the detection chip 104 and the detection device 101, as well as the auxiliary functions of the client device 102 and the server 103, Figure 1 the system 100 shown can be compatible with functions such as biochemical detection, immunoassay, and molecular detection, providing a health service system that covers the three dimensions of examination, diagnosis, and treatment and is suitable for mobile health management, especially for the application scenario of home health management.

[0041] Figure 2 FIG. shows a schematic block diagram of a detection device 101 according to an embodiment of the present invention. The detection device 101 includes a condition providing device 201, a detection device 202, an analysis device 203, and a control device 204. Optionally, the detection device 101 further includes a storage device 204 and a communication device 205.

[0042] The condition providing device 201 is configured to provide the conditions required for detection for the detection chip 104 under specific circumstances, such as appropriate lighting conditions, power supply conditions, and / or temperature conditions, etc. It should be noted, however, that only an example is given here, and not all detections require the provision of certain conditions. Exemplarily, the condition providing device 201 may include a light source to provide appropriate lighting for the optical detection of the reaction results on the detection chip. The light source can be a monochromatic light source or a polychromatic light source. The light source can be, for example, a laser, an inorganic light-emitting diode, an organic light-emitting diode, a fluorescent lamp, etc. Optionally, the condition providing device 201 can simultaneously include the above-mentioned multiple light sources to support the simultaneous detection of detection chips with different light source condition requirements. Optionally, the condition providing device 201 can simultaneously provide multiple groups of the same light source to support the simultaneous detection of multiple detection chips with the same light source condition requirements. The above optional configurations can promote the parallel processing of the detection chips and greatly improve the detection efficiency. Optionally, the condition providing device 201 can also include a collimation structure, such as a lens, cooperating with the light source to adjust the divergence and convergence degree of the light source. Figure 3An embodiment of obtaining data on the detection chip 104 by optical detection in the detection device 101 is schematically shown. The point light source 3011 emits light, which is collimated by the lens 3012 to obtain a collimated light beam L1. The collimated light beam L1 is reflected by the semi-transmissive and semi-reflective mirror 3022 to obtain a reflected light beam L2. The reflected light beam L2 is projected onto the reaction area on the detection chip 104, and a result light beam L3 is generated through absorption, reflection, etc. of the reaction sample in the reaction area. The result light beam L3 is projected onto the photoelectric sensor 3024 through the semi-transmissive and semi-reflective mirror 3022 and is converted into an electrical signal here. Optionally, before the result light beam L3 is projected onto the photoelectric sensor 3024, it can also pass through the filter 3023 to filter out the light beam components irrelevant to the wavelength to be detected to avoid interference with the detection result and improve the detection accuracy. It should be understood that Figure 3 This is merely an illustrative example of optical detection. In various other possible implementations, the light source can be a parallel light source, there can be multiple lenses, and the arrangement of the lenses and the optical path can adopt various different schemes according to needs.

[0043] In addition, by way of example, the condition providing device 201 may include a power supply device and corresponding circuits (such as electrodes, etc.), which can be connected to the corresponding electrical interfaces of the detection chip to provide the power supply conditions required for electrical detection.

[0044] The detection device 202 is configured to detect data in the reaction area on the detection chip 104, such as optical signal data, electrical signal data, etc. By way of example, the detection device 202 may include various optical sensors, such as phototubes, photomultiplier tubes, photoresistors, photodiodes, phototransistors, photovoltaic cells, etc., which can convert the optical results on the detection chip into electrical signals for further analysis and processing. For example, the detection device 202 can detect the intensity, wavelength, etc. of the received optical signal and generate a changing electrical signal accordingly. Optionally, the detection device 202 may also include an image sensor, such as a camera, which can convert the optical image on the detection chip into an electrical signal in a corresponding proportional relationship with the optical image. In addition, by way of example, the detection device 202 may include electrical detection devices, such as ammeters, voltmeters, etc., to detect the electrical signals directly generated on the detection chip, such as electric field strength, etc.

[0045] The analysis device 203 is configured to analyze the detection result based on the detected data. The analysis device 203 can receive the detected data from the detection device 202 and perform analysis and processing. By way of example, the analysis device 203 can be configured to compare the detected data with pre-determined reference data, thereby outputting an analysis result, such as the type of substance contained in the detection sample and / or the concentration of the substance contained in the detection sample.

[0046] Optionally, the analysis device 203 can also calibrate the detection result according to the statistics-based calibration data. Further, the analysis device 203 can be configured to further process the analysis result to output the detection result. For example, the analysis result can potentially indicate possible health risks and / or medical advice.

[0047] In addition, the analysis device 203 can be further configured to analyze the detection result based on the detection data of multiple detection chips (such as stored locally). For example, it can obtain the detection data of multiple chips of the same type and output the statistical situation of relevant indicators, or it can obtain the detection data of multiple chips of different types and output the detection result by comprehensively analyzing multiple indicators. In addition, the analysis device 203 can be further configured to analyze the detection result based on a machine learning model.

[0048] The control device 204 is configured to couple and decouple at least one detection chip 104, where the detection chips include multiple different types, such as the biochemical detection chip, immunoassay chip, molecular detection chip, cell detection chip, coagulation detection chip, etc. described in the reference Figure 1 For example, the control device 204 can control the mechanical and electrical coupling of the detection chip 104 with the detection device 102 in response to a user instruction or a trigger signal generated due to the insertion or removal of the detection chip 104.

[0049] The control device 204 can be further configured to: in response to receiving a user instruction (such as via the client device 102), control the detection process and / or present the detection result to the user via a user interface (such as the display screen of the client device 102, or the display screen of the detection device 101 itself, Figure 2 not shown). The detection process includes one or more of the following: detection start, detection pause, detection abort, detection end, detection delay, etc.

[0050] The control device 204 is also configured to cooperate with relevant structures on the detection chip 104 to control the movement of substances in the chip. In one example, the detection chip 104 includes one or more enclosed cavities 403 and an elastic device (not shown) that is part of the outer shell forming the cavities 403. The detection device 101 may include a motor (such as a linear motor, a rotating shaft motor, etc.) and an appropriate mechanical lever, which cooperate with the elastic device (such as a silicone pad, etc.) at a corresponding position on the chip. By controlling the degree of deformation of the elastic device, the air pressure in the cavity 403 is changed, thereby achieving one or more of the following for substances (such as fluids) in the chip: forward driving, backward contraction, forward and backward movement, and thorough mixing of substances, etc. In another example, the detection device 101 may include an air pump and corresponding gas channels, which cooperate with the air pump interface at a corresponding position on the detection chip 104. By operating the air pump to draw air or blow air, the movement of the gas in the detection chip 104 is controlled, and further one or more of the following for substances (such as fluids) in the detection chip 104 are controlled: forward driving, backward contraction, forward and backward movement, and thorough mixing of substances, etc.

[0051] In addition, the control device 204 can also be configured to implement one or more of the following: motion control of the detection chip 104, temperature control, magnetic component control, power control, etc. Exemplarily, as described above, the control device 204 can control the coupling and decoupling of the detection chip 104, as well as the movement and mixing of substances in the detection chip 104; the control device 204 may include a heating module (such as a resistive heating, induction heating, infrared heating element, etc.), a temperature detection module (such as a thermocouple, a thermistor, etc.), and optionally a heat dissipation module arranged near the position where the detection chip 104 is coupled in place, to control the temperature around the chip according to the needs of the detection program, thereby obtaining the temperature required for detection; the control device 204 may include a magnet such as an electromagnet or a permanent magnet to control the movement of relevant magnetic substances by turning on and off the electromagnet or moving the magnet in the case where the detection chip involves a magnetosensitive reaction, and, for example, the control device 203 can also control the power supply to the detection chip 104, such as supplying power to the electrodes of the chip 104, etc.

[0052] The storage device 204 can be configured to store relevant data and instructions. The relevant data includes detected data, reference data, calibration data, etc. The instructions include instructions of programs used for analyzing and processing the detected data, etc. The storage device 204 may include one or more computer-readable storage media, such as volatile storage media (RAM) and non-volatile storage media such as flash memory, mechanical hard disks, solid-state drives, etc., removable and non-removable storage media.

[0053] The communication device 205 may be configured to communicate with the client device 102 and / or the server 103 either wired (e.g., via a cable) or wirelessly (e.g., via Bluetooth, WIFI, etc.) in a suitable manner, so as to obtain user instructions from the client device 102, send analysis and detection results to the client device 102, and / or obtain available data or application programs from the server 103, send analysis and detection results to the server 103, etc. It should be understood that the communication device 205 may be configured to communicate with the client device 102 and the server 103 in the same or different manners.

[0054] The reference data and / or calibration data used by the analysis device may be manually input via a user interface ( Figure 2 not shown in the figure), or may be stored on the storage device 204. The calibration data may be obtained by detecting the same sample (e.g., dividing the same sample into two parts) using a reference chip and a detection chip, and processing their respective analysis results. The reference data, calibration data, and / or machine learning model used by the analysis device may also be obtained from the server 103 through the communication device 205, such as the server 103 located in the cloud.

[0055] In addition, through the integrated and miniaturized design of related devices, the detection device 101 can be a portable detection device. A portable detection device is relative to large, heavy, and fixed devices, and refers to a detection device with a relatively small volume and a weight that can be borne by an adult (for example, less than 30 kg) and is convenient to carry. Exemplarily, various elements involved such as the light source, lens, power source, sensor, motor, air pump, etc. mentioned above can be miniaturized as much as possible under the condition of meeting the detection requirements. The related circuits and circuit components can be arranged as integrated circuits, and the involved processing and calculations can be completed in a single microprocessor. Exemplarily, for the biochemical detection chips, immunoassay chips, molecular detection chips, etc. mentioned above, the driving methods (such as coupling and decoupling), the movement and mixing methods of substances, the data acquisition methods of detection, etc. can be unified, which is beneficial to the miniaturization or lightweight of the detection device. Also, through the optimized design of the related circuits, control algorithms, etc. in the detection device 101, the low-power operation of the device can be achieved to achieve a longer standby and usage time with a limited battery capacity. Exemplarily, the detection device 101 can be configured to automatically enter the standby state when there is no operation for a period of time (such as 1 minute, 3 minutes, 5 minutes, etc.). Optionally, the detection device 101 can include a device such as a photovoltaic cell that can convert light energy into electrical energy and store it to supply power to the detection device, thus avoiding frequent charging or battery replacement. It should be understood that the various devices, modules, functions, etc. described above can be embodied as software, hardware, firmware, or a combination thereof. And, without departing from the present disclosure, the functionality of each device or module can be implemented in a single device or module, implemented in multiple devices or modules, or implemented as a part of other devices or modules. The reference to a specific device or module is only regarded as a reference to the appropriate device or module for providing the described functionality, rather than indicating a strict logical or physical structure or organization.

[0056] It should be understood that the detection device of the embodiment of the present invention is not limited to only supporting Figure 1 the detection chips with various functions illustrated in the figure, but can support all possible detection chips, and they can all detect indicators based on such a principle: the sample to be detected reacts under certain conditions (with a certain reagent) and can be detected through detection.

[0057] By designing a single detection device to support multiple different types of detection chips, the overall cost can be greatly reduced. At the same time, using the same condition-providing device and detection device to detect each detection chip is beneficial to the unification of the data standards of detection, thereby achieving the consistency of detection results, and helping to realize the comprehensive analysis of the detection results of multiple detection chips stored locally.

[0058] Figure 4aA perspective view of a removable detection chip 104 is shown. The detection chip 104 includes a plurality of cavities 403 (which can also be one), the plurality of cavities 403 are enclosed as a whole, can be communicated through channels 402, and include at least one sample injection area 401 configured to receive a sample to be detected.

[0059] Optionally, the plurality of cavities 403 include a pretreatment area 404, which can be communicated with the sample injection area 401 and is configured to pretreat the sample to be detected. The pretreatment includes filtration, quantification, dilution, etc. For example, for an immunoassay chip, when detecting troponin I, the pretreatment area 404 can include a blood filtration membrane, where the blood filtration membrane can separate liquid from cells through physical pore sizes to achieve separation of plasma and red blood cells, and the red blood cells stay on the blood filtration membrane, thereby reducing the interference of red blood cells on the test results.

[0060] The plurality of cavities 403 further include a reagent area 408 configured to pre-store the reagents required for detection, for example, in the form of freeze-dried or liquid pre-embedded seals. For different detection chips, different reagents need to be pre-stored for different detection indicators. Exemplarily, for a biochemical detection chip, an enzyme-phenol mixed reagent can be pre-stored for glucose; for an immunoassay chip, colloidal gold particles labeled with troponin I antibody can be pre-stored for troponin I, and a fluorescent label and buffer can be pre-stored for C-reactive protein; for a molecular detection chip, hepatitis B virus (HBV) DNA (i.e., HBV-DNA) polymerase and a fluorescent dye can be pre-stored for hepatitis B virus (HBV); and so on. The plurality of cavities 403 further include a mixing area 405, which can be communicated with the pretreatment area 404 and the reagent area 408 and is configured to mix the pretreated sample to be detected and the corresponding reagents. For example, in the example of a biochemical detection chip, the glucose content can be detected. After the sample enters the mixing area 405, the enzyme-phenol mixed reagent is injected from the reagent area 408. Glucose produces gluconic acid and hydrogen peroxide under the action of peroxidase (POD), and hydrogen peroxide makes o-tolidine generate a blue substance under the action of peroxidase. The absorbance of this blue substance is at 625 nm.

[0061] In the example of the immunoassay chip, the content of troponin I can be detected. After the sample enters the mixing zone 405, colloidal gold particles labeled with anti-troponin I antibodies are injected from the reagent zone 408. The anti-human troponin I antibodies are labeled on the surface of the colloidal gold particles by utilizing the characteristics of homogeneous colloidal gold particles. It is a mixture of monoclonal antibodies of multiple clones with different immune active sites. When troponin I is present in the mixing zone 405, the antibodies on the surface of the colloidal gold particles will capture the corresponding antigen and form an antigen-antibody complex, thereby causing local aggregation or accumulation of the colloidal gold particles, and shifting the transmission spectrum of the homogeneous colloidal gold reagent from red to blue. This shift is mainly reflected by the decrease in absorbance at 540 nm and the increase in absorbance at 660 nm. In addition, in the example of the immunoassay chip, C-reactive protein can also be detected. When the sample flows to the mixing zone 405, a fluorescent label and a buffer solution are injected into the mixing zone 405 via the reagent zone 408 to specifically react with the sample, and then the mixed solution is transported to the reaction zone 406.

[0062] In the example of the molecular detection chip, hepatitis B virus (HBV) can be detected. When the sample enters the mixing zone 405, a hepatitis B virus DNA (i.e., HBV-DNA) polymerase reagent and a fluorescent dye are injected from the reagent zone 408. The hepatitis B virus can be amplified under the action of the polymerase and stained with the fluorescent dye. The sample to be detected is a serum sample obtained by preprocessing a blood sample.

[0063] The multiple cavities 403 further include a reaction zone 406, which can communicate with the mixing zone 405 and is configured to enable the sample to be detected to react under certain conditions for detection. For example, in the example of the biochemical detection chip for detecting the glucose content, after the mixed liquid flows to the reaction zone 406, the temperature of the reaction zone 406 is controlled by the control device 204 of the detection device 101 to keep it at about 37 °C to promote the occurrence of the reaction. Subsequently, the absorbance value of the solution at 625 ± 10 nm is detected by the detection device 202 and the analysis device 203 to quantitatively detect the glucose content.

[0064] In the example of the immunoassay chip for detecting troponin I, the fully mixed liquid flows to the reaction zone 406 through the channel 402, and the detection device 202 and the analysis device 203 are used to record the absorbance value of the solution at 540 ± 10 nm, thereby quantitatively detecting the troponin I antigen.

[0065] In the example of the immunoassay chip for detecting C-reactive protein, the mixed solution flowing to the reaction zone 406 has more fluorescent labels (such as EU mentioned below) 3+chelating agent), and thus emits a high-intensity fluorescence intensity, which reflects the concentration value of the C-reactive protein sample.

[0066] In one example, the mixing zone 405 and the reaction zone 406 are the same zone. This can reduce the chip volume and is also beneficial to the portable design of the detection device.

[0067] In one embodiment, the detection chip 104 includes one or more enclosed cavities 403 and an elastic device that is part of the outer shell forming the cavities 403, wherein one or more of the sample injection zone, pretreatment zone, reagent zone, mixing zone, and reaction zone are located in the one or more enclosed cavities 403 (usually forming an enclosed cavity as a whole, in which one or more zones and the channels between the multiple zones are located, but it is also possible that a single zone forms a cavity, such that multiple zones correspond to multiple different cavities, connected by channels. By "enclosed", it is isolated from the outside of the chip, but it does not mean that there is no connection inside the chip). The elastic device can change the air pressure in the cavity 403 under the extrusion of an extrusion device (not shown, generally provided by a supporting detection device), thereby realizing one or more of the following for the sample to be detected and the reagent in the detection chip 104: forward driving, backward contraction, forward and backward movement, and sufficient mixing of substances, etc. Alternatively or optionally, the detection chip 104 includes a gas pump interface, and a gas pump outside the detection chip realizes one or more of the following for the substances (such as fluids) in the detection chip 104 through the movement of gas via the gas pump interface: forward driving, backward contraction, forward and backward movement, and sufficient mixing of substances, etc. The gas pump can be provided by a supporting detection device.

[0068] Optionally, the detection chip 104 further includes a waste liquid hole 407. The waste liquid hole 407 is usually closed and is opened when waste liquid needs to be discharged (for example, under the control of a supporting detection device). In one example, the detection device includes a waste liquid collection area, which is coupled to the waste liquid hole 407 and can collect the waste liquid after detection to prevent contamination and backflow.

[0069] In one embodiment, in the detection chip 104 based on electrical detection, as Figure 4bAs shown, an electrode 409 is connected to the reaction area shown. In one example, an electrode channel is fabricated on the substrate of the detection chip by hot pressing or in-situ polymerization, and a functional carbon paste material is filled in the electrode channel as the electrode 409. During the detection process, for example, under the action of an electric field, components in the sample can be separated based on their different mobilities, and the components to be detected in the separated sample (e.g., under the control of the supporting detection device) reach the reaction cell in sequence and are detected. According to the detection chip of the embodiments of the present disclosure, functional areas that are integrally enclosed but have different functions are provided and different functional areas are connected (e.g., connected through microchannels), realizing integrated operations such as sample pretreatment, mixing, and reaction, reducing manual operation steps. For example, one-key detection can be achieved without excessive manual control, which not only liberates human labor but also facilitates precise control, reduces operation errors. At the same time, the sealing of the cavity can reduce external interference and contamination.

[0070] In one embodiment, the detection chip includes multiple substrates: a channel substrate, a cover substrate, etc. The multiple substrates can be formed of different materials respectively, or can be formed of the same material, and different methods such as double-sided tape, solvent bonding, UV glue bonding, ultrasonic bonding, laser bonding, etc. can be used to combine the multiple substrates together.

[0071] In one embodiment, the reagent in the reagent area is configured as follows:

[0072] Different reagents are used for different detection chips. In one example, in biochemical detection projects, detection reagents for glucose and total cholesterol are used. The selection of detection reagents will be evaluated in the following aspects: evaluate the specificity and enzyme activity of glucose oxidase, cholesterol esterase, cholesterol oxidase, and catalase; evaluate the light absorption performance of different chromogenic substrates; evaluate the influence of different buffer systems on the reaction. For example, when detecting C-reactive protein, the corresponding buffer can be Tris-HCL buffer. The buffer is a chemical component in the solution that maintains the relative stability of pH and can "neutralize" the added acid or base. Therefore, it is necessary to evaluate the influence of Tris-HCL buffer on the reaction; evaluate the reagent performance from dimensions such as the linear range, linear fitting degree, and repeatability of the chromogenic reaction. In another example, in immunoassay projects, the selection of detection reagents will be evaluated in the following aspects: evaluate the performance of CRP and cTnI antigen-antibody pairs from dimensions such as the detection limit LoD, linear range, and specificity. At the same time, different selections and evaluations will be made on the formulations of the coating solution, dilution solution, and washing solution. In still another example, in molecular detection projects, for example, for hepatitis B virus, a corresponding virus extraction kit is selected. Considering the complexity of liquid control in the flow channel, a nucleic acid extraction scheme without organic solvents will be preferred. Different nucleic acid extraction schemes will be evaluated for nucleic acid extraction efficiency by fluorescence quantitative PCR. In the example of the detection chip for hepatitis B detection, the PCR amplification scheme will evaluate both fluorescence quantitative PCR and isothermal amplification LAMP. Primers will be designed, and the amplification efficiency, reaction specificity, and sensitivity will be evaluated. The selection of amplification enzymes will be evaluated from dimensions such as amplification speed, anti-inhibitor ability, and hot start performance. The PCR amplification mentioned above refers to the Polymerase Chain Reaction (also known as: polymerase chain reaction). PCR is a method for in vitro enzymatic synthesis of specific DNA fragments. It consists of a cycle of high-temperature denaturation, low-temperature annealing (renaturation), and appropriate-temperature extension reactions, which are cycled to rapidly amplify the target DNA, with the characteristics of strong specificity, high sensitivity, simple operation, and time-saving.

[0073] Reagents generally require stabilizers. The long-term storage of protein reagents is involved in biochemical, immunoassay, molecular detection chips, etc., and stabilizers for different enzymes, antibodies, and other protein reagents need to be configured. The stabilizer uses common components, and the performance of the stabilizer is evaluated by the accelerated method. Thus, the formulation of the stabilizer is adjusted to achieve the expectation.

[0074] The detection chip may also involve the freeze-drying storage process of reagents, such as biochemical detection chips, immunoassay detection chips, and molecular detection chips. Different freeze-drying methods and processes can be configured according to different reagents, different morphological requirements after freeze-drying of reagents, and in combination with the formulations of different stabilizers.

[0075] In one embodiment, the detection chip will detect the result through an optical signal, for example, by using the optical detection described regarding Figure 3 In one example, for a biochemical detection chip with glucose as the detection index, as described above, a color reaction will occur in the reaction zone 406, so that the detection index in the sample can be quantified by measuring the absorption at a specific visible light wavelength. In another example, an immunoassay method called time-resolved fluorescence analysis can be adopted. It labels antigens or antibodies with lanthanide elements. According to the luminescence characteristics of lanthanide element chelates, time-resolved fluorescence analysis is used to measure fluorescence, and two parameters, wavelength and time, are detected simultaneously for signal resolution, which can effectively exclude the interference of non-specific fluorescence and greatly improve the analysis sensitivity. The immunoassay chip will quantify the detection index in the sample through this detection method. For example, Eu 3+ chelating agent can be used as a fluorescent label for detecting C-reactive protein. The absorption wavelength range in the fluorescence spectrum of the Eu 3+ chelating agent is relatively wide. Under the excitation of light with a wavelength of 230-370 nm, a fluorescence signal of 610 nm is emitted. Optionally, in this embodiment, a 360 nm filter (i.e., filter 3023) can be used to filter the light to avoid interference with the results. In yet another example, a molecular detection method called molecular fluorescence analysis can be adopted. When the molecules of a substance absorb light energy, they emit a fluorescence spectrum in the ultraviolet, visible (infrared) region. Qualitative and quantitative analysis of the substance is carried out based on the characteristics and intensity of its spectrum. This analysis method is molecular fluorescence analysis. The molecular detection chip will quantify the detection index in the sample through the fluorescence value (for example, excitation wavelength 488 nm / emission wavelength 535 nm). Various different detection chips can be designed uniformly. For example, the reaction zones of various different detection chips based on optical detection can be designed to be located at the same position of each detection chip to simplify the design of the detection device, so that the condition providing device of the detection device, such as a light source, can be arranged without considering the light requirements at different positions.

[0076] In one embodiment, the material of the chip is a polymer plastic-based material. Its advantage is that it is conducive to batch processing and has a low cost. In one example, for example, the cavities and their connecting channels through which the sample and reagent pass in the biochemical detection chip and the molecular detection chip are made of materials with no protein adsorption ability, while for example, the immunoassay chip, especially its reaction zone, is set to use materials with high protein adsorption ability.

[0077] In one embodiment, the detection chip is manufactured by using the method of PDMS casting and machining, for example, to manufacture the detection chip in the test stage. Its advantage is that rapid manufacturing can be achieved.

[0078] Figure 5Shows a flowchart according to an embodiment of the present invention. The method is used for Figure 1 the detection device 102 and includes the following steps:

[0079] In S501, the detection device 101 performs coupling with the detection chip 104. In S502, after inputting the sample to be tested, the detection device 101 controls the movement of the sample to be tested in the detection chip 104 and its mixing with the reagent. In S503, if necessary, the detection device 101 provides the conditions required for detection. In S504, the detection device 101 performs detection on the sample to be tested mixed with the reagent under the said conditions to obtain data. In a further example, the detection device 101 also performs analysis based on other detection results from the same source to obtain the said detection result. In S505, the detection device 101 performs analysis based on the detected data to obtain the detection result. In S506, the detection device 101 sends the said detection result to the client device 102 for one or more of the following: display, interpretation, and calibration, where the interpretation includes one or more of the following: the changes in the said detection result compared with the historical detection results from the same source, the possible reasons behind the changes, the possible reasons behind the abnormal detection results, and suggestions for the user. In one embodiment, one or more of the above steps are performed by the detection device 101 in response to receiving an instruction from the client device 102.

[0080] Figure 6 Shows the schematic functions of the detection system according to an embodiment of the present invention in the application in the field of medical health. In the embodiment, using the detection device described in this application and cooperating with the corresponding detection chip, various samples can be detected, such as finger blood, saliva, nasopharyngeal extract, genital extract, urine, etc., and various detection indicators in the samples can be detected, such as WBC (white blood cell), SAA (serum amyloid A), CRP (C-reactive protein), PCT (procalcitonin), BNP (B-type natriuretic peptide), cTnl (cardiac troponin), D-Dimer (D-dimer), Glu (urine glucose), ChoL (total cholesterol), TG (triglyceride), K+, Na+, ALT (alanine aminotransferase), RSV (respiratory syncytial virus), CMV (cytomegalovirus), EB (Epstein-Barr virus), HPV (human papillomavirus), HIV (human immunodeficiency virus), hCG (human chorionic gonadotropin), Torch (Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus), KET (urinary ketone body), pH, etc. Thus, the detection system 100 can be used for various functions, such as cardiovascular and cerebrovascular health detection, health management, metabolic health detection, respiratory system health detection, reproductive health monitoring, prenatal and postnatal health detection, kidney index monitoring, white blood cell detection, and so on.

[0081] It should be understood that regardingFigure 5 The samples, detection indicators, and functions shown are merely examples in the application in the field of medical health. The present invention is by no means limited to this, but is intended to include various other samples, detection indicators, and functions that can be understood by those skilled in the art. Various technologies can be described herein in the general context of software-hardware elements or program modules. Generally, these modules include routines, programs, objects, elements, components, data structures, etc. that perform specific tasks or implement specific abstract data types. The terms "module", "function", and "component" used herein generally refer to software, firmware, hardware, or a combination thereof. The features of the technologies described herein are platform-independent, meaning that these technologies can be implemented on various computing platforms with various processors.

[0082] Although the present disclosure has been described in connection with some embodiments, it is not intended to be limited to the specific forms set forth herein. By studying the specification, the drawings, and the appended claims, those skilled in the art can make modifications to the embodiments of the present invention without departing from the scope of the present disclosure. The scope of the present disclosure is limited only by the appended claims. Additionally, although individual features may be included in different claims, these may possibly be advantageously combined, and including them in different claims does not imply that the combination of features is not feasible and / or advantageous. The order of features in the claims does not imply that the features must work in any specific order. Furthermore, in the claims, the word "comprising" does not exclude other elements, and the indefinite article "a" or "an" does not exclude a plurality. The reference numerals in the claims are merely exemplary and should not be construed as limiting the scope of the claims in any way.

Claims

1. A detection chip, comprising: a sample injection area configured to receive a sample to be detected, a pretreatment area communicable with the sample injection area and configured to pretreat the sample to be detected, the pretreatment including filtration, quantification, and dilution, a reagent area configured to pre-store reagents required for detection in the form of freeze-dried or liquid pre-embedding, a mixing area communicable with the pretreatment area and the reagent area and configured to mix the sample to be detected and the corresponding reagent, and a reaction area communicable with the mixing area and configured to cause the sample to be detected to react under certain conditions for detection; one or more closed cavities, wherein one or more of the sample injection area, pretreatment area, reagent area, mixing area, and reaction area are located in the one or more closed cavities, a closed elastic device, the elastic device being part of the housing forming the cavity, the elastic device being capable of changing the air pressure in the cavity under the extrusion of an extrusion device, thereby achieving the movement and the mixing, and / or an air pump interface, and an air pump outside the detection chip realizes the movement and the mixing through the movement of gas via the air pump interface; wherein the detection chip includes one of the following types: a biochemical detection chip for detecting biochemical indicators, an immunoassay detection chip for detecting immune indicators, a molecular detection chip for detecting molecular indicators, a cell detection chip for detecting cell indicators, and a coagulation detection chip for detecting coagulation indicators; wherein for the detection chips for biochemical and molecular detection, the area through which the sample to be detected passes is made of a material having no protein adsorption ability; for the immunoassay detection chips, the area through which the sample to be detected passes is made of a material having protein adsorption ability.

2. The detection chip according to claim 1, wherein, the conditions include light conditions and the detection includes optical detection or image detection, and the conditions include power-on conditions and the detection includes electrical detection.

3. A detection device for supporting the detection chip according to claim 1, comprising: a detection device configured to detect data in the reaction area; an analysis device configured to analyze a detection result based on the detected data; and a control device configured to couple and decouple the detection chip, wherein the detection chip includes multiple different types.

4. The detection device according to claim 3, further comprising a storage device configured to store the detected data; wherein the analysis device further analyzes the detection result based on the detected data of multiple detection chips in the storage device.

5. The detection device according to claim 3, wherein the control device is further configured to: in response to receiving a user instruction, control the detection process and / or send the detection result to the user via a user interface.

6. The detection device according to claim 3, wherein the control device is further configured to implement one or more of the following: movement control of the detection chip, temperature control, magnetic component control, and power control.

7. The detection device according to claim 3, wherein the analysis device is further configured to analyze the detection result based on a machine learning model.

8. A detection system including the detection device as described in claim 3, the detection system further including: A client device, which is configured to, when running, implement: sending an instruction to the detection device based on a user input, and receiving a detection result sent by the detection device and presenting it to the user; and One or more servers, which are configured to provide support for the detection device and / or the client.

9. The detection system as described in claim 8, wherein the client device is further configured to perform one or more of the following: providing guidance to the user, the guidance relating to one or more of the following aspects: chip selection, device connection, sample collection, operation process, quality control, and chip detection; Calibrating the detection result based on data stored in the one or more servers accessible thereto; Interpreting the detection result of the detection device, wherein interpreting the detection result of the detection device includes one or more of the following: changes in the detection result compared to historical detection results from the same source, possible reasons behind the changes, possible reasons behind abnormal detection results, suggestions for the user.

10. The detection system as described in claim 9, wherein the server is further configured to perform one or more of the following: based on the detection result of the detection device, via the client device, providing continuous metric management to the user, the metric management including one or more of the following: regularly reminding the user to perform detection of one or more metrics, analyzing the user's historical detection results, presenting the trend of metric development, and making suggestions to the user.

11. The detection system as described in claim 10, wherein the metric management is provided based on a machine learning model or big data analysis.

12. A detection method for the detection device of claim 3, the method including the following steps: Performing coupling with the detection chip; After inputting a sample to be detected, controlling the movement of the sample to be detected in the detection chip and its mixing with the reagent; Providing the conditions required for detection; Performing detection on the sample to be detected mixed with the reagent under the conditions to obtain detection data; and Analyzing based on the detection data to obtain a detection result.

13. The detection method as described in claim 12, wherein It also analyzes based on other detection results from the same source to obtain the detection result.

14. The detection method as described in claim 12 further includes the step of: Sending the detection result to the client device for one or more of the following: display, interpretation, and calibration, wherein The interpretation includes one or more of the following: changes in the detection result compared to historical detection results from the same source, possible reasons behind the changes, possible reasons behind abnormal detection results, suggestions for the user.

15. The detection method as described in claim 14, wherein one or more of the steps are performed in response to receiving an instruction from the client device.

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