Blood coagulation factor activity detection system and method and storage medium

Abstract

The invention provides a blood coagulation factor activity detection system and method and a storage medium, and the system comprises a quantum dot fluorescent probe array module which comprises a plurality of quantum dot fluorescent probes and is used for identifying and marking different blood coagulation factors in a blood sample; the laser module is used for emitting laser beams with various preset wavelengths to the blood sample, and the various preset wavelengths are matched with excitation wavelengths of different quantum dots; the signal capturing module is used for continuously capturing a fluorescence signal corresponding to each quantum dot fluorescence probe and transmitting the fluorescence signal to the activity detection module in real time; and the activity detection module is used for recording fluorescence change signals corresponding to different blood coagulation factors, labeling blood coagulation factor types for the fluorescence change signals, and inputting an activity prediction model to obtain activity levels of different blood coagulation factors. The multi-quantum-dot fluorescent probe can efficiently detect the activity of various blood coagulation factors, and the comprehensiveness and accuracy of blood coagulation factor activity detection are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical activity detection, and in particular to a coagulation factor activity detection system, method and storage medium. Background Art

[0002] Coagulation factors are various protein components involved in the blood coagulation process. As an important part of medical diagnosis, the detection of coagulation factor activity is of great significance for the prevention, diagnosis and treatment of various diseases. In recent years, with the rapid development of nanotechnology, quantum dots, as a new type of fluorescent nanomaterial, have become ideal fluorescent probe materials in the field of biomedical detection due to their excellent optical properties, such as high luminous efficiency, good photostability and widely adjustable emission spectrum. Especially in the detection of coagulation factor activity, quantum dot fluorescent probes have demonstrated the ability of non-invasive, high-sensitivity and high-specificity detection.

[0003] However, the current quantum dot-based coagulation factor activity technology is still in the laboratory research stage and has not yet been widely used in clinical practice, mainly because of the wide variety of coagulation factors, complex functions, and the difficulty of a single quantum dot fluorescent probe to achieve comprehensive detection of all relevant coagulation factor activities. In addition, issues such as the behavior, safety, and stability of quantum dots in vivo also need further study. Therefore, the existing coagulation factor activity detection technology is difficult to comprehensively detect a variety of complex coagulation factors, affecting the comprehensiveness and accuracy of the detection, and is unable to provide high-sensitivity and high-specificity detection of coagulation factor activity, limiting subsequent health status assessment and personalized management. Summary of the invention

[0004] In order to provide a basic understanding of some aspects of the disclosed embodiments, a brief summary is given below. The summary is not an extensive review, nor is it intended to identify key / critical components or delineate the scope of protection of these embodiments, but rather serves as a prelude to the detailed description that follows.

[0005] In view of the above-mentioned shortcomings of the prior art, the present invention discloses a coagulation factor activity detection system, method and storage medium, which are used to solve the technical problem that the coagulation factor activity detection technology in the prior art is difficult to comprehensively and accurately detect the activities of multiple complex coagulation factors.

[0006] In the first aspect, the present application provides a coagulation factor activity detection system, which includes: a quantum dot fluorescent probe array module, including a plurality of quantum dot fluorescent probes, each of the quantum dot fluorescent probes carrying ligands and quantum dots corresponding to different coagulation factors, for identifying and marking different coagulation factors in a blood sample; a laser module, for emitting a plurality of laser beams of specific wavelengths to the blood sample according to the excitation wavelengths of different quantum dots, and each quantum dot has a one-to-one correspondence with the laser beam of a specific wavelength; a signal capture module, for continuously capturing the fluorescence signal corresponding to each of the quantum dot fluorescent probes, and transmitting it to the activity detection module in real time; the activity detection module, for recording the fluorescence change signals corresponding to different coagulation factors, and marking the coagulation factor type for each of the fluorescence change signals, inputting the signals into the activity prediction model, and obtaining the activity levels of different coagulation factors.

[0007] In one embodiment of the present invention, the quantum dot fluorescent probe includes: an identification unit carrying the ligand and used to specifically bind to the target coagulation factor corresponding to the ligand; a separation unit for separating the target coagulation factor from the blood sample; and a fluorescent unit carrying the quantum dots and used to specifically label the separated target coagulation factor so that the target coagulation factor releases photons under the excitation of the laser beam to form a corresponding target fluorescence signal.

[0008] In one embodiment of the present invention, the signal capture module is an optical detection module, and the optical detection module includes: a filter unit, including multiple filters, each of the filters is used to correspond to the fluorescence signal corresponding to one of the quantum dot fluorescent probes; a photomultiplier tube unit, including multiple photomultiplier tubes, each of the photomultiplier tubes is used to release electrons according to one of the fluorescence signals, and multiply the electrons to obtain and output current signals; a first analysis unit, used to analyze the wavelength of each of the fluorescence signals, and determine the first mapping relationship between each of the current signals and the coagulation factor type; a first communication unit, used to transmit each of the current signals and the first mapping relationship to the activity detection module in real time.

[0009] In one embodiment of the present invention, the activity detection module includes: a first receiving unit, used to receive the first mapping relationship, and to receive and record each of the current signals in real time to form current change signals corresponding to different coagulation factors; a first processing unit, used to perform a first preprocessing operation on each of the current change signals, and to label each of the current change signals with the type of coagulation factor according to the first mapping relationship, wherein the first preprocessing operation includes at least denoising and smoothing; a first feature extraction unit, used to extract the numerical features of each of the current change signals after preprocessing and labeling, wherein the numerical features include at least peak value, rising rate, falling rate and time to reach the peak value; a first prediction unit, used to input each of the current change signals after preprocessing and labeling and the corresponding numerical features into a first activity prediction model to obtain the activity levels of different coagulation factors, wherein the first activity prediction model is trained based on a data set of current change signals that label the activity levels of different coagulation factors.

[0010] In one embodiment of the present invention, the multiple quantum dot fluorescent probes are multi-color quantum dot fluorescent probes, and quantum dot fluorescent probes of different colors are used to identify and mark different coagulation factors. The signal capture module is an imaging detection module; the imaging detection module includes: a camera unit, used to collect fluorescent images of quantum dot fluorescent probes of different colors in the blood sample, each of the fluorescent images characterizing the distribution and fluorescence intensity of quantum dot fluorescent probes of different colors; a second analysis unit, used to analyze the color of each of the fluorescent images and determine the second mapping relationship between each of the fluorescent images and the coagulation factor type; a second communication unit, used to transmit each of the fluorescent images and the second mapping relationship to the activity detection module in real time.

[0011] In one embodiment of the present invention, the activity detection module includes: a second receiving unit, used to receive the second mapping relationship, and to receive and record each of the fluorescence images in real time to form a fluorescence image change set corresponding to different coagulation factors; a second processing unit, used to perform a second preprocessing operation on each of the fluorescence images in each of the fluorescence image change sets, and to label the type of the coagulation factor for each of the fluorescence image change sets according to the second mapping relationship, wherein the second preprocessing operation at least includes background removal, denoising, enhancement and segmentation; a second feature extraction unit, used to extract image features of each of the fluorescence image change sets after preprocessing and labeling, wherein the image features at least include fluorescence distribution change features and fluorescence intensity change features; a second prediction unit, used to input each of the fluorescence image change sets after preprocessing and labeling and the corresponding image features into a second activity prediction model to obtain the activity levels of different coagulation factors, wherein the second activity prediction model is trained based on the fluorescence image change sets that label the activity levels of different coagulation factors.

[0012] In one embodiment of the present invention, the system also includes: an early warning module, which is used to match the activity level with a preset activity level range, and generate an early warning signal and trigger an early warning when the activity level does not fall within the activity level range; a risk assessment module, which is used to input the activity level into a coagulation function risk prediction model, perform a coagulation function risk assessment, and obtain a risk assessment result, wherein the coagulation function risk prediction model is trained based on an activity level data set with a coagulation function risk level marked; a report generation and export module, which is used to generate a test report based on the test time, the activity level and the risk assessment result, and provides a report export function to realize the export of the test report; a visualization module, which is used to visualize the fluorescence change signal, the activity level, the early warning signal, the risk assessment result and the test report; a data communication module, which is used to remotely transmit the activity level, the early warning signal, the risk assessment result and the test report to a medical information technology platform for remote access by medical professionals.

[0013] In one embodiment of the present invention, the system also includes an integrated management module, which includes: a calibration unit, which is used to calibrate the quantum dot fluorescent probe array module and the laser module according to a preset time period to ensure the detection accuracy of the system; a quality control unit, which is used to monitor the operating status of the system and generate an error report when the operating status is abnormal, and trigger a maintenance procedure; an update unit, which is used to receive detection accuracy feedback and determine the number of feedbacks in the detection accuracy feedback whose accuracy is less than a preset accuracy threshold, and when the feedback number is greater than the preset number threshold, update the activity prediction model for training.

[0014] In a second aspect, the present application provides a method for detecting the activity of coagulation factors, the method comprising: using a quantum dot fluorescent probe array to identify and label different coagulation factors in a blood sample, wherein the quantum dot fluorescent probe array comprises a plurality of quantum dot fluorescent probes, each of the quantum dot fluorescent probes carries ligands and quantum dots corresponding to different coagulation factors; emitting a plurality of laser beams of specific wavelengths to the blood sample according to the excitation wavelengths of different quantum dots, each quantum dot having a one-to-one correspondence with the laser beam of specific wavelength, so that different quantum dot fluorescent probes release photons under the excitation of the laser beam to form a plurality of fluorescence signals; continuously capturing and recording the fluorescence signals corresponding to each of the quantum dot fluorescent probes to obtain fluorescence change signals corresponding to different coagulation factors; labeling each of the fluorescence change signals with the type of coagulation factor, and inputting each of the labeled fluorescence change signals into an activity prediction model to obtain the activity levels of different coagulation factors, wherein the activity prediction model is trained based on a data set of fluorescence change signals that label the activity levels of different coagulation factors.

[0015] In a third aspect, the present application provides a computer-readable storage medium, characterized in that computer-readable instructions are stored thereon, and when the computer-readable instructions are executed by a processor of a computer, the computer executes the coagulation factor activity detection method as described in the first aspect.

[0016] As described above, the coagulation factor activity detection system, method and storage medium provided by the embodiments of the present invention have the following beneficial effects:

[0017] It integrates a quantum dot fluorescent probe array module, a laser module, a signal capture module and an activity detection module. The quantum dot fluorescent probe array module includes a variety of quantum dot fluorescent probes, each of which carries ligands and quantum dots corresponding to different coagulation factors, which are used to identify and label different coagulation factors in blood samples. The laser module is used to emit laser beams of multiple specific wavelengths to the blood sample according to the excitation wavelength of different quantum dots. Each quantum dot has a one-to-one correspondence with the laser beam of a specific wavelength. The signal capture module is used to continuously capture the fluorescence signal corresponding to each quantum dot fluorescent probe and transmit it to the activity detection module in real time. The activity detection module is used to record the fluorescence change signals corresponding to different coagulation factors, and to annotate the coagulation factor type for each fluorescence change signal, input the activity prediction model, and obtain the activity levels of different coagulation factors. Through a variety of quantum dot fluorescent probes, high-sensitivity and high-specificity detection of coagulation factor activity is achieved, thereby ensuring the reliability of the activity detection results. At the same time, a variety of quantum dot fluorescent probes can simultaneously label and distinguish a variety of coagulation factors, and efficiently detect the activity of a variety of coagulation factors, thereby not only realizing a panoramic monitoring of coagulation factor activity, but also reducing the errors introduced by multiple tests, thereby ensuring the accuracy of the activity detection results.

[0018] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The drawings herein are incorporated into the specification and constitute a part of the specification, showing embodiments consistent with the present application, and together with the specification, are used to explain the principles of the present application. Obviously, the drawings described below are only some embodiments of the present application, and for those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative work. In the drawings:

[0020] Figure 1 is a schematic diagram of an implementation environment of a coagulation factor activity detection system shown in an exemplary embodiment of the present application;

[0021] Figure 2is a block diagram of a coagulation factor activity detection system shown in an exemplary embodiment of the present application;

[0022] Figure 3 is a block diagram of a specific coagulation factor activity detection system shown in an exemplary embodiment of the present application;

[0023] Figure 4 is a block diagram of another specific coagulation factor activity detection system shown in an exemplary embodiment of the present application;

[0024] Figure 5 is a complete block diagram of a coagulation factor activity detection system shown in an exemplary embodiment of the present application;

[0025] Figure 6 It is a flow chart of a method for detecting the activity of a coagulation factor shown in an exemplary embodiment of the present application. DETAILED DESCRIPTION

[0026] The following will describe the embodiments of the present invention with reference to the accompanying drawings and preferred embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention. It should be understood that the preferred embodiments are only for illustrating the present invention, not for limiting the scope of protection of the present invention.

[0027] It should be noted that the illustrations provided in the following embodiments are only used to illustrate the basic concept of the present invention in a schematic manner, and thus the illustrations only show components related to the present invention rather than being drawn according to the number, shape and size of components in actual implementation. In actual implementation, the type, quantity and proportion of each component may be changed arbitrarily, and the component layout may also be more complicated.

[0028] In the following description, numerous details are discussed to provide a more thorough explanation of the embodiments of the present invention. However, it is obvious to those skilled in the art that the embodiments of the present invention can be implemented without these specific details. In other embodiments, well-known structures and devices are shown in the form of block diagrams rather than in detail to avoid making the embodiments of the present invention difficult to understand.

[0029] For the activity of coagulation factors, quantum dot fluorescent probes have demonstrated the ability to detect non-invasively, with high sensitivity and high specificity. However, the inventors of this application have found that the quantum dot-based coagulation factor activity technology is still in the laboratory research stage and has not yet been widely used in clinical practice. This is mainly because coagulation factors are of various types and complex functions, and a single quantum dot fluorescent probe is difficult to achieve comprehensive detection of the activity of all relevant coagulation factors. In addition, issues such as the behavior, safety and stability of quantum dots in organisms also need further study. Therefore, the existing coagulation factor activity detection technology is difficult to comprehensively detect a variety of complex coagulation factors, which affects the comprehensiveness and accuracy of the detection, and cannot provide high-sensitivity and high-specificity detection of coagulation factor activity, which limits subsequent health status assessment and personalized management.

[0030] Therefore, see Figure 1 , Figure 1 FIG. 1 is a schematic diagram of an implementation environment of a coagulation factor activity detection system shown in an exemplary embodiment of the present application. Figure 1 As shown, the implementation environment may include a coagulation factor activity detection system 110 and a computer device 120 for detecting the activity of coagulation factors. The computer device 120 may be at least one of a desktop graphics processing unit (GPU) computer, a GPU computing cluster, a neural network computer, etc. The coagulation factor activity detection system 110 integrates a quantum dot fluorescent probe array module, a laser module, a signal capture module, and an activity detection module. Through a variety of quantum dot fluorescent probes, high sensitivity and high specificity detection of coagulation factor activity are achieved, ensuring the reliability of the activity detection results. At the same time, a variety of quantum dot fluorescent probes can simultaneously label and distinguish a variety of coagulation factors, and efficiently detect the activity of a variety of coagulation factors, which not only realizes a panoramic monitoring of coagulation factor activity, but also reduces the errors introduced by multiple detections, ensuring the accuracy of the activity detection results.

[0031] See also Figure 2 , Figure 2 is a block diagram of a coagulation factor activity detection system shown in an exemplary embodiment of the present application. The method can be applied to Figure 1 It should be understood that the method can also be applied to other exemplary implementation environments and be specifically executed by devices in other implementation environments, and this embodiment does not limit the implementation environment to which the method is applicable.

[0032] like Figure 2As shown, in an exemplary embodiment, the coagulation factor activity detection system 200 includes at least a quantum dot fluorescent probe array module 210, a laser module 220, a signal capture module 230 and an activity detection module 240, which are described in detail as follows:

[0033] The quantum dot fluorescent probe array module 210 includes a plurality of quantum dot fluorescent probes, each of which carries ligands and quantum dots corresponding to different coagulation factors, and is used to identify and label different coagulation factors in a blood sample.

[0034] It should be noted that quantum dots are nano-scale semiconductor particles that can absorb and emit light of specific wavelengths. Each quantum dot corresponds to a specific excitation wavelength due to its size and composition. Therefore, different types of quantum dots require laser beams of different wavelengths to be effectively excited. Quantum dot fluorescent probes use quantum dots as fluorescent markers. Quantum dots of each size and composition have their own specific excitation wavelengths and emission wavelengths. In order to effectively excite a specific quantum dot fluorescent probe and make it emit light, a laser wavelength that matches the quantum dot is required.

[0035] In this embodiment, the coagulation factors include coagulation factor I (fibrinogen), coagulation factor II (prothrombin), coagulation factor III (tissue factor), coagulation factor IV (calcium ion) and coagulation factor V, etc. In view of the specificity of coagulation factors, a series of multiple quantum dot fluorescent probes with different emission wavelengths are designed and synthesized, that is, according to the number and type of coagulation factors to be detected, a corresponding number of quantum dot fluorescent probes are prepared, and each quantum dot fluorescent probe corresponds to detecting a coagulation factor. To ensure the selective binding of the probe to the coagulation factor, each quantum dot fluorescent probe carries a ligand (antibody or aptamer, etc.) and quantum dots that can selectively bind to the coagulation factor detected accordingly, so that the probe can simultaneously label and distinguish multiple coagulation factors, thereby realizing multi-target detection.

[0036] It should also be noted that the binding ability, selectivity and sensitivity of the probe to coagulation factors can be verified through in vitro experiments. At the same time, the synthesis conditions and surface modification strategies of the probe can be optimized, and the performance of the quantum dot fluorescent probe array can be evaluated and optimized to obtain the best detection performance.

[0037] In a possible embodiment, the synthesis of multiple quantum dots includes: using the SILAR (Successive Ionic Layer Adsorption and Reaction) method to synthesize multiple quantum dots with different emission wavelengths, and synthesizing quantum dots with uniform size and stable optical properties by precisely controlling reaction conditions, such as precursor concentration, reaction temperature and time. Specifically, it includes: 1. Substrate preparation, using a nano-gold or nano-silver coating substrate with enhanced fluorescence effect, the coating thickness is 5-10nm, and using plasma cleaning technology, using oxygen plasma to clean the substrate to ensure that there are no impurities on the surface; 2. Precursor solution preparation, selecting non-toxic and stable zinc acetate and sodium sulfide as precursor materials, accurately adjusting the pH value of the precursor solution to 8.5, and using dilute sodium hydroxide solution for fine-tuning; 3. SILAR deposition, in the SILAR process, using microwaves (such as a frequency of 2.45GHz and a power of 100W) to accelerate ion adsorption, Use ultrasonic waves (e.g., frequency of 40kHz, power of 50W) to enhance the uniformity of the reaction, and set the deposition cycle to complete the SILAR deposition (e.g., each deposition cycle includes 1 minute of adsorption and 1 minute of reaction, repeated 10-20 cycles); 4. Intelligent quantum dot growth control, use a spectrometer to monitor the growth of quantum dots in real time, and automatically adjust the concentration of the precursor solution (±0.01M), immersion time (±5 seconds) and reaction temperature (±1°C) according to the monitoring results; 5. Post-processing and characterization: First, laser annealing, such as using a laser with a wavelength of 532nm and a power density of 1W / cm 2 , annealing time is 10 minutes, and then characterize the equipment, such as using high-resolution transmission electron microscopy (resolution <0.1nm) and atomic force microscopy (resolution <0.01nm) for morphology and performance evaluation; 6. High-precision quantum dot preparation, using photolithography technology to define the position of quantum dots, using etching technology to form micro-nano structures, positioning accuracy <1μm, selecting silicon wafers with high flatness and low fluorescence background as substrates, and synthesizing a variety of quantum dots; 7. Comprehensive performance test, using a fluorescence spectrophotometer to test the emission wavelength and fluorescence intensity of quantum dots, conducting fluorescence spectrum tests, testing the fluorescence stability of quantum dots at room temperature, completing stability tests, using TR-PL (Time-Resolved Photoluminescence, time-resolved fluorescence spectroscopy) technology to test the fluorescence lifetime of quantum dots, completing lifetime tests, applying single-molecule spectroscopy technology to evaluate the uniformity and monodispersity of quantum dots, completing uniformity and monodispersity tests.

[0038] In one possible embodiment, the preparation of quantum dot fluorescent probe arrays includes: surface functional modification of quantum dots, selective introduction of biological molecules with high affinity to coagulation factors, such as antibodies or aptamers, and fixation on the surface of quantum dots by chemical bonding or physical adsorption. In this way, the quantum dot fluorescent probe array has the ability to specifically identify coagulation factors. Specifically including: 1. Pretreatment of the quantum dot surface, ultrasonic cleaning of the quantum dots with 1% sodium dodecyl sulfate solution to remove surface impurities, and then treating the quantum dots with 0.1M thioglycolic acid solution to enhance its binding ability with biological molecules; 2. Selection of biological recognition molecules, for specific coagulation factors, select verified high-affinity antibodies or ligands to ensure that their Kd (binding constant) with the target factor is less than 10^-9M; 3. Coupling of biological molecules and quantum dots, using EDC / NHS chemical cross-linking method (protein coupling technology) , fix the biorecognition molecule on the surface of quantum dots through covalent bonds, the concentrations of EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) and NHS (N-hydroxysuccinimide) can be 10 mg / ml and 25 mg / ml respectively, and the coupling reaction is carried out at room temperature (25°C), the pH value is adjusted to 7.4, and the reaction time is about 2 hours; 4. Post-treatment and purification, use an ultracentrifuge, such as centrifugation at a speed of 10000 rpm for 10 minutes to remove unbound biomolecules and impurities, and use PBS (phosphate buffered saline) to buffer The quantum dots are washed with flushing liquid for multiple times, and centrifuged after each wash. Finally, the quantum dot solution is filtered through a filter membrane to ensure that all large particle impurities are removed; 5. Verification of the effect of functional modification: Through fluorescence spectroscopy analysis, the specific recognition ability of the functionally modified quantum dots for the target coagulation factor is verified to ensure that there is no non-specific binding, and the specific recognition ability verification is completed. Coagulation factor solutions of different concentrations are used to react with the quantum dot probe, and the sensitivity of the probe is evaluated by flow cytometry to complete the sensitivity verification. The quantum dot probe is placed in different biological environments (such as plasma, serum, etc.), and its stability is evaluated by fluorescence spectroscopy analysis to complete the stability verification; 6. Array integration and packaging: design a preset array pattern, such as an 8x12 microarray, each dot has a diameter of 100μm, and use micro-nano processing technology, such as photolithography and etching technology, to accurately integrate the quantum dot fluorescent probe on a glass or silicon wafer substrate, and cover the array surface with a thin layer of biocompatible polymer film (such as polydimethylsiloxane PDMS) to protect the probe and improve its stability in practical applications. At the same time, ensure that the fluorescence performance of the probe is not affected during the packaging process.

[0039] In one possible embodiment, the prepared quantum dot fluorescent probe array is characterized and its performance is evaluated. The morphology and size distribution of the quantum dots are observed using TEM, and the fluorescence emission wavelength and intensity are measured using a fluorescence spectrometer. At the same time, in vitro experiments are performed to verify the binding ability and selectivity of the probe to coagulation factors.

[0040] In a possible embodiment, the vessel containing the blood sample may be a microfluidic chip, which integrates the above-mentioned multiple quantum dot fluorescent probes for rapid and uniform mixing and reaction of the blood sample and for achieving panoramic real-time detection of coagulation factor activity.

[0041] As a possible embodiment, the design of the microfluidic chip should ensure the stability and repeatability of the sample during the detection process. The microfluidic chip has multiple reaction chambers for achieving rapid mixing and reaction of blood samples and quantum dot fluorescent probes. The stability and repeatability of the sample during the detection process are ensured by optimizing the chip structure and fluid control. Specifically, the microfluidic chip includes at least a chip substrate, a sample inlet, a quantum dot fluorescent probe reservoir, a mixing chamber, a reaction chamber, a waste liquid outlet and an optical detection window. All components are integrated on the chip substrate and interconnected through microchannels.

[0042] For example, a substrate made of PDMS (polydimethylsiloxane) material is selected, with a size of 50mm×50mm×2mm; the sample inlet is set in the middle of the left side of the chip, and the mesh aperture is 50μm; the quantum dot fluorescent probe reservoir is adjacent to the right side of the sample inlet, with a volume of 0.5μL, and a micro solenoid valve is used; the mixing chamber is set at the intersection of the sample flow channel and the probe flow channel, with a size of 2mm×2mm×0.5mm, and the micro vortex generator in the mixing chamber has a diameter of 1mm and a height of 0.2mm; multiple reaction chambers are set, arranged downstream of the mixing chamber and arranged in parallel, each reaction chamber has a volume of 0.2μL, and a biocompatible coating is set, such as polyethylene glycol; the waste liquid outlet is set in the middle of the right side of the chip; the optical detection window is set above each reaction chamber, the material is transparent PDMS or glass, and the size is the same as the reaction chamber size.

[0043] In the coagulation factor activity test, the blood sample is injected from the sample inlet, filtered through the screen and then enters the mixing chamber. The micro solenoid valve controls the quantum dot fluorescent probe to be released from the liquid reservoir into the mixing chamber. The blood sample and the probe are mixed in the mixing chamber by a micro vortex generator. The mixed liquid is diverted to multiple parallel reaction chambers for reaction. After the reaction is completed, the waste liquid is discharged through the waste liquid outlet. The optical detection window allows real-time monitoring of the fluorescence signal in each reaction chamber.

[0044] As a possible embodiment, the microfluidic chip is provided with a micro temperature control system, including a micro heater and a temperature sensor. The micro heater is located at the bottom of the chip and has adjustable power. The temperature sensor is located near the reaction chamber and has an accuracy of ±0.1°C to control the detection temperature. The micro fluid control system can be programmable to precisely control the fluid flow and set the mixing ratio of the sample and the probe, the reaction time, etc. The microfluidic chip is modularly designed with detachable components for easy replacement or expansion, and standardized interfaces to ensure compatibility between different components.

[0045] In one embodiment, see Figure 3 or Figure 4 ,in, Figure 3 is a block diagram of a specific coagulation factor activity detection system shown in an exemplary embodiment of the present application, Figure 4 This is a block diagram of another specific coagulation factor activity detection system shown in an exemplary embodiment of the present application. The quantum dot fluorescent probe comprises at least: an identification unit 211, which carries a ligand and is used to specifically bind to a target coagulation factor corresponding to the ligand; a separation unit 212, which is used to separate the target coagulation factor from the blood sample; and a fluorescent unit 213, which carries quantum dots and is used to specifically label the separated target coagulation factor, so that the target coagulation factor releases photons under the excitation of the laser beam to form a corresponding target fluorescence signal.

[0046] In this embodiment, the recognition group in the recognition unit 211 is connected to the fluorophore in the fluorescent unit 213. The quantum dot fluorescent probe cooperates with the component recognition unit 211, the separation unit 212 and the fluorescent unit 213, so that different quantum dot fluorescent probes can produce significant fluorescence signal changes when interacting with different coagulation factors, thereby realizing the detection of target molecules.

[0047] The laser module 220 is used to emit laser beams of multiple specific wavelengths to the blood sample according to the excitation wavelengths of different quantum dots, and each quantum dot has a one-to-one correspondence with the laser beam of a specific wavelength.

[0048] In this embodiment, the laser module 220 includes an excitation light source that can emit laser beams of multiple specific wavelengths according to the excitation wavelengths of multiple quantum dots, so that each quantum dot can be excited to emit fluorescent signals of different wavelengths, and high-precision detection of multiple targets can be achieved at the same time. In this way, not only the detection efficiency is greatly improved, but also the errors introduced by multiple detections are reduced, thereby ensuring the accuracy and reliability of the detection results.

[0049] In this embodiment, the excitation light source emits light of a specific wavelength through an optical fiber or directly illuminates the optical detection window above the reaction chamber of the microfluidic chip. The wavelength and intensity of the light source can be adjusted to accommodate different types of quantum dots.

[0050] The signal capture module 230 is used to continuously capture the fluorescence signal corresponding to each quantum dot fluorescent probe and transmit it to the activity detection module in real time.

[0051] In this embodiment, after each quantum dot fluorescent probe is mixed with a blood sample, it passes through laser beams of multiple specific wavelengths, and the quantum dots in the various quantum dot fluorescent probes are excited to emit fluorescent signals of different wavelengths. The signal capture module 230 captures the fluorescent signal corresponding to each quantum dot fluorescent probe, which represents the signal of different coagulation factor activities.

[0052] In one embodiment, please continue to refer to Figure 3 The signal capture module 230 is an optical detection module, which includes: a filter unit 231, including multiple filters, each filter is used to correspond to the fluorescence signal corresponding to a quantum dot fluorescent probe; a photomultiplier tube unit 232, including multiple photomultiplier tubes, each photomultiplier tube is used to release electrons according to a fluorescence signal, and multiply the electrons to obtain and output a current signal; a first analysis unit 233, used to analyze the wavelength of each fluorescence signal, and determine the first mapping relationship between each current signal and the type of coagulation factor; a first communication unit 234, used to transmit each current signal and the first mapping relationship to the activity detection module in real time.

[0053] In this embodiment, the blood sample is contained in a microfluidic chip, which integrates microfluidic technology, quantum dot fluorescent probe technology and optical detection technology. It can comprehensively analyze the blood sample in a short time, monitor the corresponding fluorescence signals of multiple coagulation factors in real time and convert them into current signals, thereby realizing panoramic real-time monitoring of the activity of multiple coagulation factors.

[0054] In this embodiment, the constructed optical detection module integrates components such as a filter unit 231, a photomultiplier tube unit 232, a first analysis unit 233 and a first communication unit 234, wherein the filter unit 231 has a plurality of filters located between the excitation light source and the photomultiplier tube of the photomultiplier tube unit 232. The filter unit 231 selectively transmits fluorescent signals of a specific wavelength and blocks other unnecessary wavelengths. The photomultiplier tube unit 232 converts the fluorescent signals into electrical signals for amplification and processing. The electrical signals can be collected, recorded and analyzed. Because the wavelengths of the fluorescent signals emitted by different quantum dots are different, the wavelengths of the fluorescent signals are analyzed by the first analysis unit 233 to determine the one-to-one correspondence between each current signal and the type of coagulation factor, and the current signals and the first mapping relationship are transmitted to the activity detection module 240 in real time through the first communication unit 234, so that the activity detection module 240 analyzes each current signal to determine the activity level of each coagulation factor.

[0055] In this embodiment, the photomultiplier tube has high gain and low noise characteristics. The use of the photomultiplier tube can ensure the sensitivity and accuracy of the detection of each fluorescent signal and electrical signal.

[0056] It should also be noted that the system's detection performance of coagulation factor activity in high and low concentration ranges can be improved through the design of wide dynamic range detection technology, that is, by optimizing the design of the optical detection module and the signal processing algorithm. Specifically, a high dynamic range photodetector can be used, an adaptive signal amplification circuit can be designed, and the system can be calibrated and performance tested using standard samples to verify the accuracy and reliability of the system in a wide dynamic range. In response to the needs of wide dynamic range detection, the signal processing algorithm is optimized, such as using a nonlinear fitting algorithm to process the relationship between signal intensity and concentration, introducing a dynamic threshold for signal discrimination, etc. In this way, the detection performance of the system in high and low concentration ranges can be significantly improved, so that the system can adapt to the needs of coagulation factor activity detection in different concentration ranges, and provide more comprehensive and flexible data support for clinical and scientific research.

[0057] In one embodiment, please continue to refer to Figure 4 The multiple quantum dot fluorescent probes are multi-color quantum dot fluorescent probes, and quantum dot fluorescent probes of different colors are used to identify and mark different coagulation factors. The signal capture module 230 is an imaging detection module; the imaging detection module includes: a camera unit 235, which is used to collect fluorescent images of quantum dot fluorescent probes of different colors in a blood sample, and each fluorescent image represents the distribution and fluorescence intensity of quantum dot fluorescent probes of different colors; a second analysis unit 236, which is used to analyze the color of each fluorescent image and determine the second mapping relationship between each fluorescent image and the type of coagulation factor; a second communication unit 237, which is used to transmit each fluorescent image and the second mapping relationship to the activity detection module in real time.

[0058] It should be noted that after different colors of quantum dot fluorescent probes are used to identify and mark various coagulation factors, after being excited by a laser beam, different colors of quantum dots emit fluorescent signals of different colors, such as green, yellow and red.

[0059] In this embodiment, the blood sample is contained in a microfluidic chip, which integrates microfluidic technology, quantum dot fluorescent probe technology and imaging detection technology. It can comprehensively analyze the blood sample in a short time and monitor the distribution and fluorescence intensity of quantum dot fluorescent probes of different colors corresponding to different coagulation factors in real time. In this way, through multi-color quantum dot fluorescent probes, panoramic real-time monitoring of the activity of multiple coagulation factors is achieved, as well as high-sensitivity and high-specificity detection of coagulation factor activity, while ensuring the accuracy and reliability of the activity detection results.

[0060] In this embodiment, the built imaging detection module integrates components such as camera unit 235, second analysis unit 236 and second communication unit 237, wherein the camera unit 235 includes components such as high-sensitivity camera, optical lens, filter set, etc. The camera unit 235 can collect fluorescence images of quantum dot fluorescent probes of different colors in the blood sample. Because each fluorescence image characterizes the distribution and fluorescence intensity of quantum dot fluorescent probes of different colors, the color of each fluorescence image is analyzed by the second analysis unit 236 to determine the one-to-one correspondence between each fluorescence image and the type of coagulation factor, and each fluorescence image and the second mapping relationship are transmitted to the activity detection module in real time through the second communication unit 237, so that the activity detection module 240 analyzes each fluorescence image and determines the activity level of each coagulation factor. In this way, an imaging detection module suitable for capturing multicolor quantum dot fluorescence signals is constructed. It has high resolution, high sensitivity and real-time imaging capabilities, which further ensures the reliability and accuracy of coagulation factor activity detection.

[0061] In this embodiment, the built imaging detection module is used to capture and image the fluorescent signal, and the imaging effect is optimized by adjusting the wavelength and intensity of the excitation light source, the transmission wavelength range of the filter set, and the exposure time and gain of the camera. Specifically, the imaging detection module is started and initialized. All equipment self-checks normally, and the automatic calibration function is introduced. By shooting a standard fluorescent plate, the camera exposure time (such as 50ms), white balance (such as R: 1.0, G: 1.0, B: 1.0), sensitivity (such as 800), etc. are calibrated to ensure the accuracy and repeatability of imaging. According to the excitation and emission spectral characteristics of the multicolor quantum dot fluorescent probe, adjust the wavelength and intensity of the excitation light source, such as 488nm (blue light), 635nm (red light), etc., adjust the transmission wavelength range of the filter group, such as 650-700nm (red channel), to maximize the transmission of fluorescent signals and shield background noise, set the camera exposure time to 100ms and the gain to 2 to obtain clear, high-contrast fluorescent images, and finally start the imaging instrument to capture the fluorescent signal. By continuous shooting, the dynamic changes of the fluorescent signal are recorded in real time to obtain a series of fluorescent images.

[0062] It should also be noted that the multi-color quantum dot fluorescent probe and imaging detection module in this embodiment can integrate the in vivo dynamic imaging function. Through the in vivo dynamic imaging technology, the dynamic changes of coagulation factors in the body can be observed in real time, providing patients with a more comprehensive health status assessment and personalized management plan.

[0063] In a possible embodiment, the dynamic changes of coagulation factors in a living body are observed in real time through in vivo dynamic imaging technology, including: introducing the prepared multicolor quantum dot fluorescent probe into the body of an experimental animal by intravenous injection or local application, so as to ensure that the probe can accurately reach the target tissue or organ and bind to it, specifically preparing multicolor quantum dot fluorescent probes with specific functions, the surfaces of these probes are modified with ligands or antibodies that specifically bind to target biomarkers (such as specific proteins, receptors or enzymes), and quantum dots of red, green, blue and other colors are used, so that different biomarkers or cell types can be distinguished during imaging, and the multicolor quantum dot fluorescent probes with specific functions are prepared by intravenous injection or local application, so as to ensure that the probe can accurately reach the target tissue or organ and bind to it, and the probes can be used to observe the dynamic changes of coagulation factors in a living body in real time, and the dynamic changes of coagulation factors in a living body in real time can be observed by intravenous injection or local application, and the probes can be used to observe the dynamic changes of coagulation factors in a living body in real time, and the dynamic changes of coagulation factors in real time can be observed by intravenous injection or local application, and the probes can be used to observe the dynamic changes of coagulation factors ... The multicolor quantum dot fluorescent probe is introduced into the living body by intravenous injection. To ensure that the probe can accurately reach and concentrate on the target tissue or organ, targeted delivery technology is used, such as modifying the probe with specific ligands or antibodies (such as antibodies against tumor markers), and highly sensitive in vivo imaging instruments such as FMT (fluorescence molecular tomography) or OCT (optical coherence tomography) are used to distinguish and track quantum dots of different colors, collect fluorescence signals at different time points, and monitor the distribution and dynamic changes of multicolor quantum dot fluorescent probes in the living body in real time to form different fluorescence images. The activity of various coagulation factors is analyzed through the changes in fluorescence images. Subsequently, by comparing the data of different experimental groups (such as different disease model groups) and control groups (such as healthy groups), the biological mechanisms under specific physiological or pathological conditions, such as the growth, metastasis or inflammatory response of tumors, are revealed.

[0064] As a possible embodiment, it is necessary to evaluate the biocompatibility and safety of multicolor quantum dot fluorescent probes, and to evaluate the potential toxicity risk through blood biochemical indicators and histopathological examination. Biodegradable materials (such as polylactic acid-co-glycolic acid) can be used to prepare multicolor quantum dot fluorescent probes to reduce potential toxicity risks.

[0065] The activity detection module 240 is used to record the fluorescence change signals corresponding to different coagulation factors, and to label each fluorescence change signal with the type of coagulation factor, and input the signal into the activity prediction model to obtain the activity levels of different coagulation factors.

[0066] In this embodiment, since multiple coagulation factor activity tests are performed simultaneously and different coagulation factor activity characteristics are different, the coagulation factor type is first labeled for each fluorescence change signal so that the fluorescence change signal corresponds to the coagulation factor type one by one, and then the signal is input into the activity prediction model to predict the coagulation factor activity. In this way, the accuracy of the activity test results is effectively improved by combining the activity prediction model for prediction.

[0067] In one embodiment, please continue to refer to Figure 3The activity detection module 240 at least includes: a first receiving unit 241, which is used to receive the first mapping relationship, and to receive and record each current signal in real time to form a current change signal corresponding to different coagulation factors; a first processing unit 242, which is used to perform a first preprocessing operation on each current change signal, and to label each current change signal with a coagulation factor type according to the first mapping relationship, wherein the first preprocessing operation at least includes denoising and smoothing; a first feature extraction unit 243, which is used to extract the numerical features of each current change signal after preprocessing and labeling, wherein the numerical features at least include a peak value, a rising rate, a falling rate and a time to reach a peak value; a first prediction unit 244, which is used to input each current change signal after preprocessing and labeling and the corresponding numerical features into a first activity prediction model to obtain the activity levels of different coagulation factors, wherein the first activity prediction model is trained based on a data set of current change signals that label the activity levels of different coagulation factors.

[0068] In this embodiment, when the signal detection module 230 is an optical detection module, the current change signals corresponding to different coagulation factors are analyzed to obtain the activity levels of multiple coagulation factors.

[0069] In this embodiment, a median filtering method is used for denoising, for example, the window size is set to 5 data points, which effectively removes background noise and outliers; a moving average method is used for smoothing, for example, the window size is 10 data points, which reduces data fluctuations, thereby ensuring the quality of the current change signal. Then, the key features of the current change signal, such as the peak value, the rate of rise, the rate of decline, and the time to reach the peak value, are extracted, wherein the rate of rise and the rate of decline are obtained by calculating the slope of the signal, so that the model can more accurately predict the activity levels of multiple coagulation factors through the extraction of multiple data features. In addition, a random forest algorithm is selected, and the first activity prediction model for coagulation factor activity detection is established according to the training of the current change signal data set with different coagulation factor activity levels marked. In this way, the prediction is combined with the activity prediction model to effectively improve the accuracy of the activity detection results.

[0070] In one embodiment, please continue to refer to Figure 4The activity detection module 240 at least includes: a second receiving unit 245, which is used to receive the second mapping relationship, and to receive and record each fluorescent image in real time to form a fluorescent image change set corresponding to different coagulation factors; a second processing unit 246, which is used to perform a second preprocessing operation on each fluorescent image in each fluorescent image change set, and to label the type of coagulation factor for each fluorescent image change set according to the second mapping relationship, wherein the second preprocessing operation at least includes background removal, denoising, enhancement and segmentation; a second feature extraction unit 247, which is used to extract image features of each fluorescent image change set after preprocessing and labeling, wherein the image features at least include fluorescence distribution change features and fluorescence intensity change features; a second prediction unit 248, which is used to input each fluorescent image change set after preprocessing and labeling and the corresponding image features into a second activity prediction model to obtain the activity levels of different coagulation factors, wherein the second activity prediction model is trained based on the fluorescent image change set that labels the activity levels of different coagulation factors.

[0071] In this embodiment, when the signal detection module 230 is an imaging detection module, the fluorescence image change sets corresponding to different coagulation factors are analyzed to obtain the activity levels of multiple coagulation factors.

[0072] In this embodiment, the foreground and background are distinguished by setting grayscale or color thresholds, and background removal is performed. The BM3D (Block-Matching and 3D filtering) denoising algorithm is used. The algorithm combines the advantages of non-local mean and transform domain filtering, and can effectively remove Gaussian noise and salt and pepper noise in the image. The adaptive contrast enhancement technology is applied to dynamically adjust the degree of enhancement according to the contrast of the local area of ​​the image. The semantic segmentation method based on deep learning is used to train the neural network model to achieve accurate segmentation of the fluorescence signal, thereby improving the quality of each fluorescence image. Then, by comparing the fluorescence images at different time points (such as 30 seconds, 1 minute, 2 minutes, etc.), the fluorescence distribution change characteristics (expressed in pixel number, shape or area) and the fluorescence intensity change characteristics (expressed in relative fluorescence units) in the fluorescence image change concentration are extracted. By extracting multiple image features, the model can more accurately predict the activity levels of multiple coagulation factors. In addition, a random forest algorithm was selected to train a set of fluorescence image changes that annotated different levels of coagulation factor activity, and a second activity prediction model for coagulation factor activity detection was established. In this way, the time series fluorescence images were combined with the activity prediction model for prediction, and the dynamic changes of coagulation factors were tracked, which effectively improved the accuracy of the activity detection results.

[0073] In one embodiment, see Figure 5 , Figure 5 FIG. 1 is a complete block diagram of a coagulation factor activity detection system shown in an exemplary embodiment of the present application. Figure 5As shown, the system also includes at least: an early warning module 250, which is used to match the activity level with a preset activity level range, and generate an early warning signal and trigger an early warning when the activity level does not fall within the activity level range; a risk assessment module 260, which is used to input the activity level into a coagulation function risk prediction model, perform a coagulation function risk assessment, and obtain a risk assessment result, wherein the coagulation function risk prediction model is obtained by training an activity level data set with annotated coagulation function risk levels; a report generation and export module 270, which is used to generate a test report according to the test time, activity level and risk assessment result, and provides a report export function to realize the export of the test report; a visualization module 280, which is used to visualize the fluorescence change signal, activity level, early warning signal, risk assessment result and test report; a data communication module 290, which is used to remotely transmit the activity level, early warning signal, risk assessment result and test report to a medical information technology platform for remote access by medical professionals.

[0074] In this embodiment, the early warning module 250 sets the activity level threshold to ±10% of the normal range, and when the predicted result exceeds this range, the early warning mechanism is triggered. The risk assessment module 260 can perform a coagulation function risk assessment based on the activity level of each coagulation factor. The report generation and export module 270 can automatically generate a test report containing information such as the test time, activity level and risk assessment results, and provide a report export function, which can be connected to a cloud server to realize the sharing of the test report. In the visualization module 280, a user interface based on the Web (World Wide Web) is developed, and JavaScript and D3.js libraries are used to realize real-time data visualization, displaying the change trend curve of the fluorescence change signal, the activity level of various coagulation factors, the early warning signal risk assessment results and the test report. The data communication module 290 can remotely transmit the activity level, early warning signal, risk assessment results and test reports to the medical information technology platform for remote access by medical professionals, wherein the medical information technology platform can be various software systems, hardware equipment and mobile terminals used in hospitals or medical institutions, etc. Medical professionals can further review the test results and provide medical advice or health management advice to patients through remote access. 。

[0075] In one embodiment, please continue to participate Figure 5The system at least includes an integrated management module 2100, which includes: a calibration unit, which is used to calibrate the quantum dot fluorescent probe array module and the laser module according to a preset time period to ensure the detection accuracy of the system; a quality control unit, which is used to monitor the operating status of the system, and generate an error report when the operating status is abnormal, and trigger a maintenance procedure; an update unit, which is used to receive detection accuracy feedback, and determine the number of feedbacks in the detection accuracy feedback whose accuracy is less than a preset accuracy threshold, and when the number of feedbacks is greater than the preset number threshold, update the activity prediction model for training.

[0076] In this embodiment, the calibration unit can calibrate the quantum dot fluorescent probe array module and the laser module according to a preset time period to ensure the detection accuracy of the system, wherein the calibration process includes cleaning and calibration using standard samples, firstly ensuring that the quantum dot fluorescent probe array and the laser path are free of dust or other contaminants, and secondly using blood with a known activity level to calibrate the quantum dot fluorescent probe array module and the laser module, thereby adjusting the quantum dot type, the wavelength of the laser beam emitted by the laser module, etc. The quality control unit can monitor the operating status of the system to generate an error report when the system operating status is abnormal, and trigger a maintenance procedure to timely overhaul the system; the update unit can receive detection accuracy feedback, wherein the detection accuracy feedback includes detection opinions or suggestions fed back by users, and detection accuracy obtained by accuracy verification, and introduces an online learning mechanism. When it is determined that the number of feedbacks with an accuracy less than a preset accuracy threshold in the detection accuracy feedback is greater than a preset number threshold, the activity prediction model is updated and trained to adapt to the changes in different populations and coagulation factor activity, and improve the prediction accuracy. In this way, the realization of panoramic instant detection of coagulation factor activity is further promoted.

[0077] The above-mentioned coagulation factor activity detection system integrates a quantum dot fluorescent probe array module, a laser module, a signal capture module and an activity detection module, wherein the quantum dot fluorescent probe array module includes a plurality of quantum dot fluorescent probes, each of which carries a ligand and a quantum dot corresponding to a different coagulation factor, and is used to identify and label different coagulation factors in a blood sample; the laser module is used to emit a plurality of laser beams of specific wavelengths to the blood sample according to the excitation wavelength of different quantum dots, and each quantum dot has a one-to-one correspondence with a laser beam of a specific wavelength; the signal capture module is used to continuously capture the fluorescence signal corresponding to each quantum dot fluorescent probe and transmit it to the Activity detection module, the activity detection module is used to record the fluorescence change signals corresponding to different coagulation factors, and to mark the coagulation factor type for each fluorescence change signal, input the activity prediction model, and obtain the activity levels of different coagulation factors. Through a variety of quantum dot fluorescent probes, high-sensitivity and high-specificity detection of coagulation factor activity is achieved, ensuring the reliability of activity detection results. At the same time, a variety of quantum dot fluorescent probes can simultaneously label and distinguish a variety of coagulation factors, and efficiently detect the activity of a variety of coagulation factors, which not only realizes panoramic monitoring of coagulation factor activity, but also reduces errors introduced by multiple tests, ensuring the accuracy of activity detection results.

[0078] In this way, in the embodiments of the present application, the technologies of quantum dot synthesis, surface functionalization, microfluidic chip design, optical detection and image processing are combined to meet the urgent needs of clinical medicine, drug development, basic medical research and personalized health management for the detection of coagulation factor activity.

[0079] See also Figure 6 , Figure 6 FIG. 1 is a flow chart of a method for detecting the activity of a coagulation factor shown in an exemplary embodiment of the present application. The method can be applied to Figure 1 The implementation environment shown is a schematic diagram. It should be understood that the method may also be applicable to other exemplary implementation environments, and this embodiment does not limit the implementation environment to which the system is applicable.

[0080] like Figure 6 As shown, in an exemplary embodiment, the method for detecting the activity of coagulation factors includes at least steps S610 to S640, which are described in detail as follows:

[0081] Using quantum dot fluorescent probe arrays to identify and label different coagulation factors in blood samples, wherein the quantum dot fluorescent probe array includes a plurality of quantum dot fluorescent probes, each of which carries ligands and quantum dots corresponding to different coagulation factors;

[0082] According to the excitation wavelengths of different quantum dots, laser beams of multiple specific wavelengths are emitted to the blood sample. Each quantum dot has a one-to-one correspondence with the laser beam of a specific wavelength, so that different quantum dot fluorescent probes release photons under the excitation of the laser beam to form multiple fluorescent signals;

[0083] Continuously capture and record the fluorescence signal corresponding to each quantum dot fluorescent probe to obtain the fluorescence change signals corresponding to different coagulation factors;

[0084] Each fluorescence change signal is labeled with the type of coagulation factor, and each labeled fluorescence change signal is input into an activity prediction model to obtain the activity level of different coagulation factors, wherein the activity prediction model is trained based on a data set of fluorescence change signals that label the activity levels of different coagulation factors.

[0085] It should be noted that the coagulation factor activity detection method provided in the above embodiment and the coagulation factor activity detection system provided in the above embodiment belong to the same concept, and the contents of each step have been described in detail in the system embodiment and will not be repeated here.

[0086] The present application also provides a computer-readable storage medium on which a computer program is stored. When the computer program is executed by a processor of a computer, the computer executes the above-mentioned coagulation function health management method. The computer-readable storage medium may be included in an electronic device, or may exist independently without being assembled into the electronic device.

[0087] It should be noted that the computer-readable medium shown in the embodiment of the present application can be a computer-readable signal medium or a computer-readable storage medium or any combination of the above two. The computer-readable storage medium can be, for example, an electrical, magnetic, optical, electromagnetic, infrared, or semiconductor system, device or device, or any combination of the above. More specific examples of computer-readable storage media can include, but are not limited to: an electrical connection with one or more wires, a portable computer disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM), a flash memory, an optical fiber, a portable compact disk read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the above. In the present application, a computer-readable signal medium may include a data signal propagated in a baseband or as part of a carrier wave, wherein a computer-readable computer program is carried. This propagated data signal can take a variety of forms, including but not limited to an electromagnetic signal, an optical signal, or any suitable combination of the above. A computer-readable signal medium may also be any computer-readable medium other than a computer-readable storage medium, which may send, propagate or transmit a program for use by or in conjunction with an instruction execution system, apparatus or device. A computer program contained on a computer-readable medium may be transmitted using any appropriate medium, including but not limited to: wireless, wired, etc., or any suitable combination of the above.

[0088] The flowcharts and block diagrams in the accompanying drawings illustrate the possible architecture, functions and operations of the systems, methods and computer program products according to various embodiments of the present invention. Among them, each box in the flowchart or block diagram can represent a module, a program segment, or a part of the code, and the above-mentioned module, program segment, or a part of the code contains one or more executable instructions for implementing the specified logical function. It should also be noted that in some alternative implementations, the functions marked in the box can also occur in a different order from the order marked in the accompanying drawings. For example, two boxes represented in succession can actually be executed substantially in parallel, and they can sometimes be executed in the opposite order, depending on the functions involved. It should also be noted that each box in the block diagram or flowchart, and the combination of boxes in the block diagram or flowchart, can be implemented with a dedicated hardware-based system that performs a specified function or operation, or can be implemented with a combination of dedicated hardware and computer instructions.

[0089] The units involved in the embodiments of the present invention may be implemented by software or hardware, and the units described may also be arranged in a processor. The names of these units do not, in some cases, limit the units themselves.

[0090] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the technology may modify or change the above embodiments without violating the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by a person of ordinary skill in the art without departing from the spirit and technical ideas disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. A coagulation factor activity detection system, characterized in that: The system comprises: A quantum dot fluorescent probe array module, including a plurality of quantum dot fluorescent probes, each of which carries ligands and quantum dots corresponding to different coagulation factors, for identifying and marking different coagulation factors in a blood sample; A laser module, used for emitting laser beams of multiple specific wavelengths to the blood sample according to the excitation wavelengths of different quantum dots, wherein each quantum dot has a one-to-one correspondence with the laser beam of a specific wavelength; A signal capture module, used to continuously capture the fluorescence signal corresponding to each of the quantum dot fluorescent probes, and transmit it to the activity detection module in real time; The activity detection module is used to record the fluorescence change signals corresponding to different coagulation factors, and to mark the type of coagulation factor for each of the fluorescence change signals, and input them into the activity prediction model to obtain the activity levels of different coagulation factors.

2. The coagulation factor activity detection system according to claim 1, characterized in that: The quantum dot fluorescent probe comprises: a recognition unit, carrying the ligand, for specifically binding to a target coagulation factor corresponding to the ligand; A separation unit, used for separating the target coagulation factor from the blood sample; The fluorescent unit carries the quantum dots and is used to specifically label the separated target coagulation factor, so that the target coagulation factor releases photons under the excitation of the laser beam to form a corresponding target fluorescence signal.

3. The coagulation factor activity detection system according to claim 1, characterized in that: The signal capture module is an optical detection module, and the optical detection module includes: A filter unit, comprising a plurality of filters, each of which is used to transmit a corresponding fluorescence signal corresponding to one of the quantum dot fluorescent probes; A photomultiplier tube unit, comprising a plurality of photomultiplier tubes, each of which is used to release electrons according to one of the fluorescent signals, and multiply the electrons to obtain and output a current signal; a first analysis unit, configured to analyze the wavelength of each of the fluorescence signals to determine a first mapping relationship between each of the current signals and the type of coagulation factor; The first communication unit is used to transmit each of the current signals and the first mapping relationship to the activity detection module in real time.

4. The coagulation factor activity detection system according to claim 3, characterized in that: The activity detection module comprises: A first receiving unit, configured to receive the first mapping relationship, and to receive and record each of the current signals in real time to form current change signals corresponding to different coagulation factors; a first processing unit, configured to perform a first preprocessing operation on each of the current change signals, and to label each of the current change signals with the type of the coagulation factor according to the first mapping relationship, wherein the first preprocessing operation at least includes denoising and smoothing; A first feature extraction unit, used for extracting numerical features of each current change signal after preprocessing and labeling, wherein the numerical features at least include a peak value, a rising rate, a falling rate and a time to reach the peak value; The first prediction unit is used to input each of the current change signals after preprocessing and labeling and the corresponding numerical features into a first activity prediction model to obtain the activity levels of different coagulation factors, wherein the first activity prediction model is trained based on a data set of current change signals that label the activity levels of different coagulation factors.

5. The coagulation factor activity detection system according to claim 1, characterized in that: The multiple quantum dot fluorescent probes are multicolor quantum dot fluorescent probes, and quantum dot fluorescent probes of different colors are used to identify and label different coagulation factors, and the signal capture module is an imaging detection module; The imaging detection module comprises: A camera unit, used for collecting fluorescence images of quantum dot fluorescent probes of different colors in the blood sample, each of the fluorescence images representing the distribution and fluorescence intensity of the quantum dot fluorescent probes of different colors; a second analysis unit, configured to analyze the color of each of the fluorescent images to determine a second mapping relationship between each of the fluorescent images and the type of coagulation factor; The second communication unit is used to transmit each of the fluorescent images and the second mapping relationship to the activity detection module in real time.

6. The coagulation factor activity detection system according to claim 5, characterized in that: The activity detection module comprises: A second receiving unit is used to receive the second mapping relationship, and receive and record each of the fluorescent images in real time to form a fluorescent image change set corresponding to different coagulation factors; A second processing unit, configured to perform a second preprocessing operation on each of the fluorescence images in each of the fluorescence image variation sets, and to label the type of the coagulation factor on each of the fluorescence image variation sets according to the second mapping relationship, wherein the second preprocessing operation at least includes background removal, denoising, enhancement, and segmentation; A second feature extraction unit, used to extract image features of each of the fluorescence image change sets after preprocessing and annotation, wherein the image features at least include fluorescence distribution change features and fluorescence intensity change features; The second prediction unit is used to input the preprocessed and labeled fluorescence image change sets and the corresponding image features into a second activity prediction model to obtain the activity levels of different coagulation factors, wherein the second activity prediction model is trained based on the fluorescence image change sets that annotate the activity levels of different coagulation factors.

7. The coagulation factor activity detection system according to any one of claims 1 to 6, characterized in that: The system further comprises: an early warning module, for matching the activity level with a preset activity level range, and generating an early warning signal and triggering an early warning when the activity level does not fall within the activity level range; a risk assessment module, used for inputting the activity level into a coagulation function risk prediction model, performing coagulation function risk assessment, and obtaining a risk assessment result, wherein the coagulation function risk prediction model is trained based on an activity level data set with annotated coagulation function risk levels; A report generation and export module, used to generate a test report according to the test time, the activity level and the risk assessment result, and provide a report export function to realize the export of the test report; A visualization module, used for visually displaying the fluorescence change signal, the activity level, the warning signal, the risk assessment result and the detection report; A data communication module is used to remotely transmit the activity level, the warning signal, the risk assessment result and the test report to a medical information technology platform for remote access by medical professionals.

8. The coagulation factor activity detection system according to claim 7, characterized in that: The system also includes a comprehensive management module, which includes: A calibration unit, used to calibrate the quantum dot fluorescent probe array module and the laser module according to a preset time period to ensure the detection accuracy of the system; A quality control unit, for monitoring the operating state of the system, and generating an error report when the operating state is abnormal, and triggering a maintenance procedure; An updating unit is used to receive detection accuracy feedback, determine the number of feedbacks in the detection accuracy feedback whose accuracy is less than a preset accuracy threshold, and when the number of feedbacks is greater than the preset number threshold, update the activity prediction model for training.

9. A method for detecting the activity of coagulation factors, characterized in that: The method comprises: Using a quantum dot fluorescent probe array to identify and label different coagulation factors in a blood sample, wherein the quantum dot fluorescent probe array includes a plurality of quantum dot fluorescent probes, each of which carries ligands and quantum dots corresponding to different coagulation factors; According to the excitation wavelengths of different quantum dots, laser beams of multiple specific wavelengths are emitted to the blood sample, and each quantum dot has a one-to-one correspondence with the laser beam of specific wavelength, so that different quantum dot fluorescent probes release photons under the excitation of the laser beam to form multiple fluorescent signals; Continuously capturing and recording the fluorescence signal corresponding to each of the quantum dot fluorescent probes to obtain fluorescence change signals corresponding to different coagulation factors; Each of the fluorescence change signals is labeled with the type of coagulation factor, and each of the labeled fluorescence change signals is input into an activity prediction model to obtain the activity levels of different coagulation factors, wherein the activity prediction model is trained based on a data set of fluorescence change signals that label the activity levels of different coagulation factors.

10. A computer-readable storage medium, characterized in that: Computer-readable instructions are stored thereon, and when the computer-readable instructions are executed by a processor of a computer, the computer is caused to execute the method for detecting the activity of coagulation factors as claimed in claim 9.

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