Microfluid sample detection device and microfluid sample detection system

Abstract

The utility model provides a microfluid sample detection device which comprises a fluid inlet, a microfluid channel, a fluid outlet, a reaction area, a liquid collecting area, a pump body and a valve body, the valve body comprises a substrate, a double-sided colloid and a flexible diaphragm, a cavity is formed between the upper surface of the plastic substrate and the lower surface of the flexible diaphragm, the cavity is opened when the flexible diaphragm is loosened, and the cavity is closed when the flexible diaphragm is tensioned; the valve body comprises a first valve body, a second valve body, a third valve body and a fourth valve body, the second valve body and the third valve body are arranged between the pump body and the microfluid channel and located on the downstream portion of the first valve body, and the working states of the third valve body and the fourth valve body are opposite. Moreover, the parallel scheme further comprises a conductive system composed of electrodes, the conductive system at least comprises two electrodes, and the electrode sensing ends are located at the two ends of the reaction area respectively. The microfluidic sample detection device is loaded in a detection device to form a microfluidic sample detection system.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical devices, in particular to a microfluidic sample detection device and a microfluidic sample detection system. BACKGROUND

[0002] With the continuous development of intelligent technology, people's life, work and study increasingly use intelligent devices, and use intelligent technology to improve the quality of life and increase the efficiency of learning and work.

[0003] Microfluidic chip is a scientific technology that manipulates fluid in micron scale space as the main feature, has the ability to miniaturize the basic functions of biological and chemical laboratories to a few square centimeter chip, and is also called chip laboratory. At present, the mainstream form of microfluidic chip is formed by a network of microchannels, and the controllable fluid penetrates the entire system to realize various functions of conventional chemical or biological laboratories. The basic characteristics and greatest advantage of microfluidic chip are flexible combination and scale integration of various unit technologies on a small controllable platform. It is very suitable for the design of point-of-care testing (POCT) products. However, the materials commonly used to make microfluidic chips include glass and organic polymers such as polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), polycarbonate (PC), and hydrogel. The processing and manufacturing environment, including air temperature, air humidity, and particle density in various media used in the process. Higher environmental requirements for chip manufacturing generally need to be achieved in a clean room. Clean room technology is closely related to the success of the microfluidic chip manufacturing process. Depending on the manufacturing method, the clean room standard needs to reach 10,000 or 1,000 or even 100. For example, the manufacturing technology of high polymer microfluidic chip mainly includes hot pressing method, molding method, injection molding method, laser ablation method, LIGA method, etc. However, the equipment used in the prior art is expensive and the steps are complex, not only strict requirements and high operating costs for the environmental quality during the process, but also low yield per batch, so the cost of the manufactured products is generally high. There is still a certain gap between the production capacity and cost requirements of point-of-care testing (POCT) products, which limits the popularization of microfluidic technology in the POCT industry.

[0004] At present, there is no effective solution to the above problems. SUMMARY

[0005] The utility model provides a kind of microfluidic sample detection device, including fluid inlet, microfluidic channel and fluid outlet, and reaction zone, liquid collection area, pump body, valve body;Valve body includes substrate, double-sided adhesive and flexible diaphragm, cavity is formed between the upper surface of plastic substrate and the lower surface of flexible diaphragm, cavity opens when flexible diaphragm relaxes, cavity closes when flexible diaphragm is nervous;Valve body includes first valve body, second valve body, third valve body and fourth valve body, second valve body and third valve body are located between pump body and microfluidic channel and located downstream of first valve body, the working state of third valve body and fourth valve body is opposite.

[0006] Further, microfluidic channel includes first region and second region, at least first region or second region is reaction zone, and pump body can drive microfluidic sample from first region into second region.

[0007] Further, microfluidic channel includes first region, second region and third region, at least first region or second region or third region is reaction zone, and pump body can drive microfluidic sample from first region into second region, and then into third region.

[0008] In another embodiment, it further includes conductive system composed of electrode, and the conductive system includes at least two electrodes, and electrode sensing end is located at both ends of reaction zone.

[0009] Preferably, the conductive system includes at least three electrodes, and electrode sensing end is located at both ends of first region and second region, at least first region or second region is reaction zone, when pump body and microfluidic channel are communicated through second valve body and / or third valve body, pump body can drive microfluidic sample from first region into second region. Further, the conductive system includes at least four electrodes, and electrode sensing end is located at both ends of first region, second region and third region, at least first region or second region or third region is reaction zone, when pump body and microfluidic channel are communicated through second valve body and / or third valve body, pump body can drive microfluidic sample from first region into second region, and then into third region.

[0010] In another embodiment, electrode sensing end of two electrodes is located upstream of third valve body; or electrode sensing end of two electrodes is located downstream of third valve body; or electrode sensing end of two electrodes is located upstream of third valve body and downstream of third valve body.

[0011] In another embodiment, reaction zone is located upstream of third valve body; or reaction zone is located downstream of third valve body; or third valve body is within the range of reaction zone.

[0012] In another embodiment, first region is located upstream of third valve body; or first region is located downstream of third valve body; or third valve body is within the range of first region.

[0013] In another embodiment, a start electrode is also included, the start electrode having a sensing end positioned upstream of the second valve body and cooperatively defining a start zone with the sensing end of the first electrode downstream of the second valve body.

[0014] The utility model also provides a microfluid sample detection system, including detection equipment and above-mentioned microfluid sample detection device, microfluid sample detection device is loaded in detection equipment, and detection equipment and microfluid detection device electrode electric connection / signal connection.

[0015] Further, the microfluid sample detection device is electrically connected to the detection equipment electrode through an electric contact pin.

[0016] The utility model has the advantages of: 1, microfluid sample detection device simple structure is easy to produce and manufacture, can be applied to various methodological in vitro diagnostic products, and can carry out single detection, multi-in-one combination detection, and even can combine electrochemical detection and photochemical detection method to the same microfluid sample detection device;2, the liquid receiving area in microfluid sample detection device is located at the most downstream of microfluid channel, and there is no problem of polluting detection equipment;3, a pump body is equipped with two valve bodies in microfluid sample detection device, can provide more control mode for the flow of microfluid sample, and the application range can be further widened. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1-1 One of the microfluid detection device embodiments of the utility model.

[0018] Figure 1-2 The second microfluid detection device embodiment of the utility model.

[0019] Figure 1-3 The third microfluid detection device embodiment of the utility model.

[0020] Figure 1-4 The fourth microfluid detection device embodiment of the utility model.

[0021] Figure 2 The fifth microfluid detection device embodiment of the utility model.

[0022] Figure 3-1 The sixth microfluid detection device embodiment of the utility model.

[0023] Figure 3-2 The seventh microfluid detection device embodiment of the utility model.

[0024] Figure 4-1 The eighth microfluid detection device embodiment of the utility model.

[0025] Figure 4-2The ninth embodiment of the microfluidic detection device of the present invention.

[0026] Figure 5 This invention provides a combined implementation of a microfluidic detection device.

[0027] Figure 6 One of the schematic diagrams of the microfluidic detection device module of the present invention.

[0028] Figure 7 The second schematic diagram of the microfluidic detection device module of the present invention.

[0029] Figure 8 The third schematic diagram of the microfluidic detection device module of the present invention.

[0030] Figure 9 Example 6: Results of the accuracy study of the product of the present invention.

[0031] Figure 10 Example 6A: Results of a study on the accuracy of traditional products.

[0032] Figure 11 Example 6B: Results of a study on the accuracy of conventional products. Detailed Implementation

[0033] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0034] Microfluidic detection device

[0035] like Figure 1-1 As shown, one of the microfluidic detection devices for implementing the present invention includes a fluid inlet 11, a fluid outlet 12, a microfluidic channel 13, a liquid collection zone 14, a reaction zone 131, a pump body 41, and a valve body.

[0036] The fluid inlet 11 is used to add the microfluid sample to be tested, the fluid outlet 12 is communicated with the environment, the microfluid channel 13 is between the fluid inlet and the fluid outlet, the microfluid sample to be tested enters from the fluid inlet and flows in the microfluid channel, the volume of the microfluid sample that is pushed forward in the microfluid channel is greater than the volume of the gas that is discharged from the fluid outlet. The collection area 14 is downstream of the microfluid channel and also downstream of the reaction area, and is used to receive the microfluid sample after the reaction, the fluid outlet is located at the outlet of the collection area and is communicated with the environment, the environment refers to the external environment of the microfluid detection device of the present application, which can be the environment provided in the system of the present application, or can be the same as the environment outside the system of the present application. The fluid outlet allows gas or liquid to flow out, in most embodiments, the fluid outlet is a gas outlet, only allowing gas to flow out, liquid cannot flow out; in a small part of the embodiments, the fluid outlet is a gas and liquid outlet, allowing both gas and liquid to flow out.

[0037] The reaction area 131 is in the microfluid channel between the fluid inlet and the fluid outlet, in other words, the reaction area is partially coincident with the microfluid channel. The microfluid sample to be tested is designed to react with the fixed pre-prepared reagent in the reaction area during the process of flowing in the microfluid channel, at this time, the reaction area is the most downstream area.

[0038] Pump body 41 is used to passively drive the flow of microfluidic samples in the microfluidic channel. In other words, by controlling the pressure applied to the pump body, a driving force can be provided for the flow of the microfluidic sample. This driving force drives the microfluidic sample to enter the microfluidic channel from the fluid inlet, and can further drive the microfluidic sample to continue flowing downstream. The pressure value applied to the pump body can be preset and associated with the travel position of the microfluidic sample after entering the microfluidic channel. That is, when the preset pressure value applied to the pump body is a certain value, the microfluidic sample is at a certain position in the microfluidic channel. This design can be used to confirm the successful addition of the microfluidic sample and to determine that the microfluidic sample has entered a certain area. The valve body includes valve body 31, valve body 32, valve body 33, and valve body 33. Valve body 31, located downstream of the fluid inlet, is used to control the opening and closing between the fluid inlet and the microfluidic channel. It is in the open state until the microfluidic sample has completely entered the microfluidic channel. Valve body two (322) and valve body three (33) are located downstream of valve body one and are situated between the pump body and the microfluidic channel. They control the connection or disconnection between the pump body and the microfluidic channel. When valve body two and / or valve body three are open, the pump body and the microfluidic channel are fluidly connected. In other words, valve body two and valve body three control the pump body, determining whether the pump body provides driving force to the microfluidic sample. Valve body two and valve body three can be simultaneously open for a period of time, but cannot be simultaneously open indefinitely. Valve body three is located downstream of valve body two, while valve body two is upstream of the reaction zone. Valve body three can be either upstream or downstream of the reaction zone; that is, the reaction zone can be located in the microfluidic channel between valve body two and valve body three, or in the microfluidic channel downstream of valve body three. Valve body one and valve body three jointly determine the volume of the final microfluidic sample participating in the reaction, or, conversely, valve body two and valve body three jointly determine the volume of the final microfluidic sample participating in the reaction. Valve four is located at the fluid outlet and is used to control the connection between the liquid collection area and the external environment. The operating states of valves three and four are opposite; that is, when valve three is open, valve four is closed, and vice versa. When valve three is open and valve four is closed, the pump body and the microfluidic channel are connected, and the pump body can passively drive the microfluidic sample to flow towards the fluid outlet. When valve three is open, valve two can also be opened simultaneously to drive the microfluidic sample towards the fluid outlet. However, valve two must be closed before the tip of the microfluidic sample approaches it to prevent the sample from entering the pump body through valve two. Similarly, valve three must be closed before the tip of the microfluidic sample approaches it to prevent the sample from entering the pump body through valve three.

[0039] In some embodiments, the valve body is composed of a plastic substrate and a flexible diaphragm, the plastic substrate includes an upper surface and a lower surface, a groove is formed on the upper surface of the plastic substrate by laser, etching or other methods, the flexible diaphragm includes an upper surface and a lower surface, the upper surface of the plastic substrate and the lower surface of the flexible diaphragm are bonded together by adhesive material, the upper surface of the plastic substrate and the lower surface of the flexible diaphragm are in contact and partially joined, a cavity is formed between the upper surface of the plastic substrate and the lower surface of the flexible diaphragm, the cavity is through when the flexible diaphragm is in a relaxed state, i.e. the valve body is in an open state, and the cavity is not through when the flexible diaphragm is under pressure, i.e. the valve body is in a closed state.

[0040] In other embodiments, the valve body is composed of a plastic substrate, a double-sided adhesive and a flexible diaphragm, the plastic substrate includes an upper surface and a lower surface, the double-sided adhesive includes a hollow, the flexible diaphragm includes an upper surface and a lower surface, the upper surface of the plastic substrate, the double-sided adhesive and the lower surface of the flexible diaphragm are pressed together to be bonded, a cavity is formed between the upper surface of the plastic substrate and the lower surface of the flexible diaphragm, the cavity is open when the flexible diaphragm is relaxed, and the cavity is closed when the flexible diaphragm is tense; the valve body includes a first valve body and a second valve body, the second valve body is located downstream of the first valve body, and the working states of the first valve body and the second valve body are opposite; the lock body is located downstream of the second valve body.

[0041] As shown in Figure 1-2 Fig. 2, for the second microfluidic detection device of the present application, on the basis of the first microfluidic detection device, a conductive system composed of electrodes is further included. The conductive system includes two electrodes, electrode one 51 and electrode two 52, wherein electrode one further includes electrode contact one 511 and electrode sensing end one 512, electrode two further includes electrode contact two 521 and electrode sensing end two 522, and electrode sensing end one 512 and electrode sensing end two 522 are respectively located at the two ends of the reaction zone 131, i.e. electrode sensing end one is located at the starting end of the reaction zone, and electrode sensing end two is located at the terminal end of the reaction zone, as shown in Figure 1-2 (a) both electrode sensing end one and electrode sensing end two are located downstream of the second valve body and between the second valve body and the third valve body, i.e. upstream of the third valve body, at this time the reaction zone is between the second valve body and the third valve body, i.e. upstream of the third valve body; as shown in Figure 1-2 (b) both electrode sensing end one and electrode sensing end two are located downstream of the third valve body, at this time the reaction zone is downstream of the third valve body; as shown in Figure 1-2 (c) electrode sensing end one is located downstream of the second valve body and upstream of the third valve body, and electrode sensing end two is located downstream of the third valve body, at this time the third valve body is within the range of the reaction zone. As shown in Figure 1-3As shown, to implement the third microfluidic detection device of the present invention, based on the first microfluidic detection device, the second microfluidic detection device, or other subsequent microfluidic detection devices, it further includes a microfluidic channel branch 132, a branch outlet 121, and electrodes 53, 54, 531, 532, 541, and 542, wherein the branch outlet is a gas outlet, allowing only gas to flow out.

[0042] like Figure 1-4 As shown, a fourth microfluidic detection device for implementing the present invention further includes a frame-shaped electrode 501, an electrode frame-shaped region 5011, and a frame-shaped contact 5012, based on the first, second, third, or other subsequent microfluidic detection devices. Alternatively, based on the first, second, third, or other subsequent microfluidic detection devices, only the electrode frame-shaped region 5011 is included.

[0043] like Figure 2 As shown, to implement the fifth microfluidic detection device of the present invention, based on the second microfluidic detection device, the conductive system further includes electrode five 55, that is, the electrode system includes three electrodes, electrode five including electrode contact five 551 and electrode sensing end five 552. Region one 1311 and region two 1312 are formed in the microfluidic channel, at this time, region two is the downstream region. Wherein, region one is a reaction zone, or region two is a reaction zone, or both regions one and two are reaction zones. When the pump body and the microfluidic channel are connected through valve body two and / or third valve body, that is, the pump body can be connected to the microfluidic channel alone through the third valve body, or connected to the microfluidic channel through the second valve body and the third valve body together, or connected to the microfluidic channel through the second valve body, then the pump body can drive the microfluidic sample to enter region one and region two sequentially. Electrode sensing end one is located at the beginning of region one, electrode sensing end two is located at the end of region one and also the beginning of region two, and electrode sensing end five is located at the end of region two. Electrode sensing ends one, two, and five are all located downstream of valve body two. The positional relationship of electrode sensing ends one and two relative to valve body two and valve body three is as follows: Figure 1-2 The same as in [the previous text]. See reference [the previous text]. Figure 1-2 As shown in (a), region one is located upstream of valve body three; refer to Figure 1-2 As shown in (b), region one is located downstream of valve body three; refer to Figure 1-2 As shown in (c), valve body three is within the area of ​​region one.

[0044] like Figure 3-1As shown, for the sixth microfluidic detection device of the present invention, based on the fifth microfluidic detection device, the conductive system further includes electrode six 56, that is, the electrode system includes four electrodes, electrode six includes electrode contact six 561 and electrode sensing end six 562. Region one 1311, region two 1312 and region three 1313 are formed in the microfluidic channel, at this time, region three is the downstream region. Among them, region one is a reaction zone, or region two is a reaction zone, or region three is a reaction zone, or any two of region one, region two and region three are reaction zones, or region one, region two and region three are all reaction zones. When the pump body and the microfluidic channel are connected through valve body two and / or valve body three, the pump body can drive the microfluidic sample to enter region one, region two and region three in sequence. Electrode sensing end one is located at the starting end of region one, electrode sensing end two is located at the ending end of region one and is also the starting end of region two, electrode sensing end six is ​​located at the ending end of region two and is also the starting end of region three, and electrode sensing end five is located at the ending end of region three.

[0045] Furthermore, it also includes electrode seven, which comprises electrode contact seven and electrode sensing end seven. Regions one, two, three, and four are formed within the microfluidic channel. That is, electrode sensing end five is located at both the end of region three and the beginning of region four, while electrode sensing end seven is located at the end of region four. At this point, region four is the downstream region. Region one is a reaction zone, or region two is a reaction zone, or region three is a reaction zone, or region four is a reaction zone, or any two or three of regions one, two, three, and four are reaction zones, or all four regions are reaction zones. When the pump body and the microfluidic channel are connected via valve body two and / or valve body three, the pump body can drive the microfluidic sample sequentially into regions one, two, three, and four.

[0046] like Figure 3-2 As shown, this is a seventh microfluidic detection device implementing the present invention. Based on the fifth microfluidic detection device, it further includes a frame electrode 501, an electrode frame region 5011, and a frame contact 5012, or only includes the electrode frame region 5011. The microfluidic detection device is formed by bonding a substrate and a coating. The frame electrode is printed on the substrate, and the electrode frame region is printed on the coating and protrudes from the coating. When the substrate and the coating are bonded together, the electrode frame region and the microfluidic channels in the substrate together form an area for the accumulation of pre-placed reagents. The two horizontally parallel sides of the electrode frame region can serve as the electrode sensing ends of the frame electrode.

[0047] like Figure 4-1As shown in the figure, on the basis of any one of the microfluidic detection devices one to seven or other subsequent microfluidic detection devices, the eighth microfluidic detection device for implementing the present application includes electrode one 51, electrode contact one 511, electrode sensing end one 512, electrode eight 58, electrode contact eight 581, electrode sensing end eight 582, the electrode sensing end eight is located downstream of the valve body one and upstream of the valve body two, the electrode sensing end one is located downstream of the electrode sensing end eight, the electrode sensing end one, the electrode sensing end eight and the microfluidic channel jointly enclose to form an activation zone, the activation zone is close to the microfluidic inlet, the electrode sensing end eight is the starting end of the activation zone, and the electrode sensing end one is the terminal end of the activation zone. Alternatively, as shown in the figure, the electrode sensing end eight can also be located upstream of the valve body one and downstream of the fluid inlet. Figure 4-2

[0048] The microfluidic detection devices one to eight can be copied and combined to form new microfluidic detection devices, and the combined microfluidic detection device only retains one fluid inlet. For example, the microfluidic detection device one is copied and combined to form a microfluidic detection device including two microfluidic detection devices one but only retaining one fluid inlet, or the microfluidic detection device five and the microfluidic detection device seven are both copied and combined to form a microfluidic detection device including two microfluidic detection device five units and two microfluidic detection device seven units but only retaining one fluid inlet.

[0049] Figure 5 As shown in the figure, the combined microfluidic detection device for implementing the present application combines the microfluidic detection device five, the microfluidic detection device three based on the microfluidic detection device five, and two microfluidic detection devices seven to form a microfluidic detection device only retaining one fluid inlet.

[0050] Microfluidic detection device

[0051] As shown in the figure, the combined microfluidic detection device for implementing the present application combines the microfluidic detection device five, the microfluidic detection device three based on the microfluidic detection device five, and two microfluidic detection devices seven to form a microfluidic detection device only retaining one fluid inlet. Figure 6 Figure 7 Figure 8 As shown in the figure, the structure schematic diagram of the microfluidic detection equipment for implementing the present application includes a main control board, a display screen, a load position, a magnetic module, a temperature module, an optical module, an electrical module, an actuator, a battery, a power supply interface, and a timer. In the specific implementation, the optical module and the electrical module at least include one of them; the magnetic module, the temperature module, and the display screen are optional designs, which can be included in the microfluidic detection equipment or not included in the microfluidic detection equipment.

[0052] ​​​​The power interface provides power for the operation of the detection device and can charge a battery that helps the detection device to operate normally without power access, thus achieving the portability of the detection device. After the detection device is turned on, the detection device is placed into the detection device. After the microfluidic sample detection device is accurately placed on the load position of the detection device, the load position generates a loaded signal and transmits it to the main control board. The detection device and the detection device complete the signal connection, and the main control board commands the detection device to start running. In another embodiment, the main control board can be prompted to command the detection device to start running by clicking a button on the detection device.

[0053] The at least one reaction waiting time countdown in the timer is to determine a fixed time period for the reaction of the microfluidic sample in the microfluidic channel. In another embodiment, the microfluidic sample loading waiting time countdown can also be set in the timer, and the time when the detection device and the detection device complete the signal connection is taken as the starting point of the loading waiting time countdown. When the time in the timer is up, it is determined that the microfluidic sample to be tested has been successfully added. When the timer is used to determine that the sample has been successfully added, it is not necessary to use the above-mentioned optical detection unit to determine that the sample has been successfully added. In another embodiment, the microfluidic sample arrival time countdown to the fixed region (such as the reaction area) can also be set in the timer, and the countdown starts when the microfluidic sample starts to flow. When the countdown is over, the microfluidic sample arrives at the fixed region.

[0054] The actuator provides pressure for the pump body of the detection device. After the detection device is accurately placed on the load position of the detection device, pressure is provided for the pump body, and the pump body is compressed to drive part or all of the gas in the pump body to flow out of the detection device; the pressure provided for the pump body is maintained, and when the microfluidic sample to be tested contacts the fluid inlet, the pump body is released to drive the microfluidic sample to flow and enter the microfluidic channel; and after the microfluidic sample to be tested is successfully added to the microfluidic channel, pressure is provided for the pump body, and the pump body is compressed to drive the microfluidic sample to flow towards the downstream region of the microfluidic channel. The downstream region here refers to, for example, the processing area, the reaction area, the detection area, etc. In some embodiments, the pressure value applied by the actuator to the pump body can be pre-set and associated with the position of the microfluidic sample in the microfluidic channel after the microfluidic sample enters the microfluidic channel, that is, when the pressure value applied to the pump body is pre-set to a certain value, the microfluidic sample in the microfluidic channel is just at a certain position. This design can be used to confirm that the microfluidic sample has been successfully added, and to determine that the microfluidic sample has entered a certain region. For example, when the pressure value applied by the actuator reaches a certain value, the microfluidic sample flows to the reaction area. In such an embodiment, the countdown of the microfluidic sample arrival time to the fixed region in the above-mentioned timer can not be set. The actuator provides pressure for the valve body to close the valve body to close the microfluidic channel, or releases the pressure to open the valve body to make the microfluidic channel pass through.

[0055] The optical module includes a light detection unit, which detects the reaction result of the microfluid sample to be tested, and the detection result is displayed on the display screen after being processed by the main control board. Alternatively, the optical module also includes a photoelectric conversion unit, and the detection result is displayed on the display screen after being processed by the main control board after being converted into an electrical signal by the photoelectric conversion unit.

[0056] In another aspect, the optical module is also used to determine whether the microfluid sample to be tested has been successfully added to the detection device. The light detection unit continuously detects the light reflection state of the same position of the microfluid channel at different time points and converts it into an electrical signal by the photoelectric conversion unit, and the main control board determines that the microfluid sample to be tested has been successfully added.

[0057] The electrical module includes an electrical connector and an electrical detection unit. The electrical connector provides a matched electrical pin for the electrode contact in the microfluid detection device. The microfluid detection device has as many electrical pins as the electrode contact. The main control board commands the electrical detection unit to output a continuous weak electrical signal (the stop output time is after the successful addition of the microfluid sample to be tested is completed). In the case of a break, it cannot be detected. When the detection device has been accurately placed on the load position of the detection equipment, the electrode contact on the detection device is matched with the electrical pin on the electrical connector, indicating that the detection device and the detection equipment have completed the electrode electrical connection. The electrical module determines that the microfluid sample to be tested has been successfully added by detecting the electrical signal between the electrodes. Alternatively, since the time of a microfluid sample of a certain volume passing through a microfluid channel of a certain size is determined, the addition of the microfluid sample to be tested is determined to be successful by setting the addition waiting time of the microfluid sample in the timer in advance, and taking the time when the detection device and the detection equipment complete the signal connection as the addition waiting time starting point. When the time in the timer passes, it is determined that the microfluid sample to be tested has been successfully added.

[0058] After the microfluid sample to be tested completes the reaction, the electrical detection unit of the electrical module detects the current generated by the electron transfer. The current signal passes through electrode one and electrode two, and is transmitted to the main control board of the detection equipment through the corresponding electrical pins of electrode contact one and electrode contact two. The main control board processes and displays the detection result on the display screen.

[0059] The magnetic module includes a magnet and a magnetic shield. The magnet is fixed near the downstream region of the microfluid channel in the detection device, and the magnet is isolated from the downstream region of the microfluid channel by the magnetic shield. When the microfluid sample to be tested enters the downstream region of the microfluid channel and the microfluid sample to be tested needs to be subjected to magnetic adsorption separation, the main control board commands the magnetic shield to move so that the magnetic field generated by the magnet acts on the microfluid sample to be tested.

[0060] The temperature module includes a heating unit. The heating unit is fixed near the downstream region of the microfluid channel in the detection device. The main control board commands the heating unit to provide the required processing temperature for the microfluid sample to be tested, or to provide the required reaction temperature.

[0061] Microfluidic sample extraction system

[0062] The microfluidic sample detection device is loaded into a microfluidic sample detection apparatus to form a microfluidic sample detection system, the detection apparatus is electrically connected with the electrodes of the microfluidic detection device, the detection apparatus determines that the signal connection with the microfluidic detection device is completed through the loading signal of the loading position received by the main control board, or the detection apparatus determines that the electrode electrical connection with the microfluidic detection device is completed through the signal formed by the electrode contact and the electrical contact pin on the electrical connector.

[0063] The microfluidic detection device is prepared into a microfluidic detection device for detecting blood ketone, red blood cells are used as the first target object, the reagent prepositioned in the first region is a magnetic particle combined with an anti-red blood cell antibody, β-hydroxybutyric acid is used as the second target object, and the reagent prepositioned in the second region is a preparation containing β-hydroxybutyric acid oxidoreductase and an electron medium. In this case, the first region and the second region are both reaction regions. The microfluidic detection device for detecting blood ketone is loaded into a detection apparatus to form a microfluidic sample detection system.

[0064] The above detection is repeated 10 times respectively using the blood sample to be detected containing 1 mmol / L, 2 mmol / L, 4 mmol / L, 6 mmol / L and 7 mmol / L of β-hydroxybutyric acid, and the detection result values are obtained. A biochemical standard instrument is used as a control, and the same blood sample to be detected is detected 10 times on an existing A brand traditional electrochemical blood glucose detection product with excellent performance and a B brand traditional electrochemical blood glucose detection product with general performance, and the detection result values are obtained. As shown in Table 1, it can be seen from Table 1 that the standard deviation and the coefficient of variation are obviously reduced compared with the B traditional brand product and the A brand traditional product, which indicates that the discrete degree of the detection result data of the application is lower, and the repeatability of the measured β-hydroxybutyric acid content in the blood sample is smaller. The data in Table 1 is researched for accuracy and plotted as shown in Figure 9 、 Figure 10 and Figure 11 , the R 2 of the application is obviously greater than that of the B traditional brand product with general performance, and greater than the R 2 of the traditional brand product with excellent performance, which indicates that the measured β-hydroxybutyric acid content in the blood sample is closer to the true value, and the accuracy is higher than that of the existing product with excellent performance.

[0065] Table 1 Comparison of experimental results of Example 6

[0066]

[0067] The above examples are only used to more clearly illustrate the technical solutions of the present application, and therefore only serve as examples, and cannot limit the protection scope of the present application.

[0068] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs; the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application; the terms "comprising," "comprises" and "including" as used herein are synonymous with and meant to have the same meaning as the term "including"; the description and drawings of the present application are merely exemplary and explanatory thereof, and the scope of the application is not limited thereto. In the description of the present application, the technical terms "first", "second", "third", "fourth" and the like are only used to distinguish different objects, and cannot be understood as indicating or implying relative importance or implicitly indicating the number, specific order or primary and secondary relationship of the technical features indicated. In the description of the embodiments of the present application, the meaning of "a plurality of" is two or more, unless otherwise explicitly specified.

[0069] Reference herein to "an embodiment", "one embodiment" or "an implementation" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the application. The appearance of the phrase in various places in the specification does not necessarily all refer to the same embodiment, nor is it necessarily independent or alternative embodiments to other embodiments.

[0070] The above embodiments are only used to illustrate the technical solutions of the present application, and not to limit it; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacement to part or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application, and they should all be covered in the scope of the claims and the description of the present application. In particular, as long as there is no structural conflict, each technical feature mentioned in each embodiment can be combined in any way. The present application is not limited to the specific embodiments disclosed herein, but includes all technical solutions falling within the scope of the claims.

Claims

1. A microfluidic sample detection device, comprising a fluid inlet, a microfluidic channel, and a fluid outlet, as well as a reaction zone, a liquid collection zone, a pump body, and a valve body; the valve body comprises a substrate, a double-sided adhesive, and a flexible diaphragm, wherein a cavity is formed between the upper surface of the plastic substrate and the lower surface of the flexible diaphragm, the cavity opening when the flexible diaphragm is relaxed and closing when the flexible diaphragm is tense; the valve body comprises a first valve body, a second valve body, a third valve body, and a fourth valve body, wherein the second valve body and the third valve body are disposed between the pump body and the microfluidic channel and downstream of the first valve body, and the third valve body and the fourth valve body operate in opposite states.

2. The microfluidic sample detection device according to claim 1, characterized in that, The microfluidic channel includes a first region and a second region, at least the first region or the second region is a reaction zone, and the pump can drive the microfluidic sample from the first region into the second region.

3. The microfluidic sample detection device according to claim 2, characterized in that, The microfluidic channel includes a first region, a second region, and a third region. At least the first region, the second region, or the third region is a reaction zone. The pump can drive the microfluidic sample from the first region into the second region and then into the third region.

4. The microfluidic sample detection device according to claim 1, characterized in that, It also includes a conductive system composed of electrodes, the conductive system comprising at least two electrodes, with the electrode sensing ends located at opposite ends of the reaction zone.

5. A microfluidic sample detection device according to claim 4, characterized in that, The conductive system includes at least three electrodes, with the electrode sensing ends located at the two ends of the first region and the second region, respectively. At least the first region or the second region is a reaction zone. When the pump body and the microfluidic channel are connected through the second valve body and / or the third valve body, the pump body can drive the microfluidic sample from the first region into the second region.

6. The microfluidic sample detection device according to claim 5, characterized in that, The conductive system includes at least four electrodes, with the electrode sensing ends located at the two ends of the first region, the second region, and the third region, respectively. At least the first region, the second region, or the third region is a reaction zone. When the pump body and the microfluidic channel are connected through the second valve body and / or the third valve body, the pump body can drive the microfluidic sample from the first region into the second region, and then into the third region.

7. A microfluidic sample detection device according to claim 4, characterized in that, The electrode sensing ends of both electrodes are located upstream of the third valve body; or the electrode sensing ends of both electrodes are located downstream of the third valve body; or one electrode sensing end of the two electrodes is located upstream of the third valve body and the other is located downstream of the third valve body.

8. A microfluidic sample detection device according to claim 1 or 4, characterized in that, The reaction zone is located upstream of the third valve body; or the reaction zone is located downstream of the third valve body; or the third valve body is located within the reaction zone.

9. A microfluidic sample detection device according to claim 2, 3, 5, or 6, characterized in that, The first region is located upstream of the third valve body; or the first region is located downstream of the third valve body; or the third valve body is within the range of the first region.

10. A microfluidic sample detection device according to any one of claims 1-7, characterized in that, It also includes a start-up electrode, the sensing end of which is located upstream of the second valve body and together with the sensing end of the first electrode downstream of the second valve body, forms a start-up area in the microfluidic channel.

11. A microfluidic sample detection system, comprising a detection device and a microfluidic sample detection apparatus as described in any one of claims 1-10, wherein the microfluidic sample detection apparatus is mounted in the detection device, and the detection device is electrically / signally connected to the electrodes of the microfluidic sample detection apparatus.

12. A microfluidic sample detection system according to claim 11, characterized in that, The microfluidic sample detection device is electrically connected to the electrodes of the detection equipment via electrical contacts.

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