A drug concentration detection chip and a drug concentration detection assembly

Abstract

The utility model relates to a kind of medicine concentration detection chip and medicine concentration detection assembly, comprising: chip body, detection area is equipped on chip body, and detection flow passage is equipped in detection area;The two ends of detection flow passage are communicated with liquid inlet flow passage and liquid outlet flow passage, and liquid inlet flow passage includes: liquid inlet, the first liquid inlet flow passage is communicated with liquid inlet, the other end of first liquid inlet flow passage is communicated with first buffer flow passage, the other end of first buffer flow passage is communicated with second buffer flow passage, and first buffer flow passage and second buffer flow passage are equipped with confluence cavity between, first buffer flow passage, confluence cavity and second buffer flow passage form the buffer area that cross section is v-shaped, and the other end of second buffer flow passage is communicated with detection flow passage by the third buffer flow passage of inclination arrangement.This utility model is respectively arranged buffer flow passage in the two ends of detection channel, avoid adding liquid flow rate too fast and cause liquid in detection area not to be able to contact with the nanometer hole channel array on PCB board fully and cause the liquid in each nanometer hole channel uneven and affect the problem of detection precision.

Description

Technical Field

[0001] This utility model relates to the field of detection chips, specifically to a drug concentration detection chip and a drug concentration detection component. Background Technology

[0002] Drug concentration detection is a core component of clinical medicine and pharmacy, its necessity stemming from the complex metabolic characteristics of drugs in the human body and the significant impact of individual differences on efficacy and safety. Current drug concentration detection technologies include immunoassay, chromatography, spectroscopy, and mass spectrometry. However, most of these methods require the use of microfluidic chips for detection, and the resulting data is then analyzed to determine the drug concentration.

[0003] For example, the invention patent application with publication number CN119246840A discloses a method for detecting blood drug concentration in clinical pharmacy, which includes capturing drug molecules in a blood sample based on a microfluidic chip, enabling a sensor to detect the drug molecules and their binding to the surface, and collecting highly sensitive blood drug response data.

[0004] For example, utility model patent CN109954525B discloses a three-phase layer microfluidic chip for simultaneously detecting the free drug concentration and total drug concentration in blood. It includes a cover plate and a base plate, which are bonded together to form a complete chip. The surface of the chip base plate has a first injection channel, a second injection channel, a third injection channel, a first collection channel, a second collection channel, a third collection channel, and a main channel connecting the above channels. During detection, a blood sample is introduced into the first injection channel, a PBS buffer solution is introduced into the second injection channel, and an organic solvent is introduced into the third channel. The three solutions flow in the chip to form a stable laminar flow. The organic solvent containing the extracted drug is obtained at the third collection channel, concentrated, and then injected into the detection instrument for detection. During detection, the flow rate ratio of the three solutions in the first, second, and third injection channels of the chip is 2–12:2–10:2–18.

[0005] The microfluidic chip disclosed in the above utility model has a simple structure and cannot be applied to high-throughput detection scenarios. Utility Model Content

[0006] The purpose of this invention is to provide a drug concentration detection chip and a drug concentration detection component, which can partially solve or alleviate the above-mentioned technical problems. It can be used with a PCB board with a nanopore array for high-throughput detection. Furthermore, it has buffer channels at both ends of the detection channel to avoid the problem that the liquid cannot fully contact the nanopore array of the PCB board in the detection area due to the excessively fast liquid flow rate, which would lead to uneven liquid distribution in each (or most) nanopore and affect the detection accuracy.

[0007] The technical solution of the present utility model to solve the above problems is as follows:

[0008] In the first aspect of the present utility model, there is provided a drug concentration detection chip, which includes: a chip body, a detection area is provided on the chip body, and a detection flow channel is provided in the detection area; both ends of the detection flow channel are connected with a liquid inlet flow channel and a liquid outlet flow channel, and the liquid inlet flow channel includes:

[0009] A liquid inlet, the liquid inlet is provided on the top of the chip body, the liquid inlet is connected with a first liquid inlet flow channel, the other end of the first liquid inlet flow channel is connected with a first buffer flow channel, the other end of the first buffer flow channel is connected with a second buffer flow channel, and a confluence chamber is provided between the first buffer flow channel and the second buffer flow channel. The first buffer flow channel and the second buffer flow channel are respectively arranged on both sides of the confluence chamber, so that the first buffer flow channel, the confluence chamber and the second buffer flow channel form a buffer area with a V-shaped cross section. The other end of the second buffer flow channel is connected with the detection flow channel through an inclined third buffer flow channel;

[0010] The liquid outlet flow channel includes: a liquid outlet, the liquid outlet is connected with a first liquid outlet flow channel, the other end of the first liquid outlet flow channel is connected with an inclined fourth buffer flow channel, and the other end of the fourth buffer flow channel is connected with the detection flow channel.

[0011] In some embodiments, the chip body includes a flow channel upper cover and a flow channel lower cover detachably connected to the flow channel upper cover. The liquid inlet, the first liquid inlet flow channel, the liquid outlet and the first liquid outlet flow channel are all provided on the flow channel upper cover;

[0012] Among them, the flow channel upper cover includes a first groove and a third groove, and the flow channel lower cover includes a second groove with a V-shaped cross section and a fifth buffer flow channel. When the flow channel upper cover and the flow channel lower cover are installed together and the first groove covers the second groove, the first groove and the second groove form the buffer area connected with the third buffer flow channel;

[0013] The third groove and the upper surface of the flow channel lower cover form a sixth buffer flow channel, so that the fifth buffer flow channel and the sixth buffer flow channel form the fourth buffer flow channel with a 乁-shaped cross section.

[0014] In some embodiments, a fourth groove is provided at the bottom of the chip body corresponding to the position of the detection area, and when the PCB board is installed with the chip body, the gap between the fourth groove and the PCB board forms the detection flow channel.

[0015] In some embodiments, the flow channel cover further includes: first protrusions symmetrically disposed on both sides of the detection area, and second protrusions communicating with the two first protrusions, wherein the first protrusions are arranged in a meandering manner, and the second protrusions are arranged along the edge of the flow channel cover;

[0016] The upper cover of the flow channel is provided with a first waste liquid tank arranged in a meandering pattern at the position corresponding to the first protrusion, and a second waste liquid tank is provided along the edge of the upper cover of the flow channel at the position corresponding to the second protrusion.

[0017] When the lower cover and the upper cover of the flow channel are combined, the first protrusion cooperates with the first waste liquid tank, the second protrusion cooperates with the second waste liquid tank, and the gap between the first protrusion and the bottom of the first waste liquid tank forms a first waste liquid channel; the gap between the second protrusion and the bottom of the second waste liquid tank forms a second waste liquid channel, and the first waste liquid channel communicates with the second waste liquid channel. In this case, one of the first waste liquid tanks is provided with a waste liquid inlet at the end near the outlet, and the other first waste liquid tank is provided with a waste liquid outlet at the end near the outlet.

[0018] In some embodiments, the upper cover of the flow channel includes an observation window disposed through the upper cover of the flow channel, the observation window corresponding to the position and shape of the detection area in the lower cover of the flow channel.

[0019] In some embodiments, the flow channel cover is rotatably provided with a knob device, the knob device including a knob body and a flow channel switch pressure plate disposed at the bottom of the knob body, the bottom of the flow channel switch pressure plate being provided with a flow channel communication groove.

[0020] Specifically, when the knob body is rotated to the first position, the liquid outlet is connected to the waste liquid inlet through the flow channel connecting groove. When the knob body is rotated to the second position, the flow channel connecting groove is offset, and the flow channel switch plate closes the liquid outlet.

[0021] In some embodiments, a limit strip is also provided at the bottom of the knob device, and correspondingly, two slots are provided on the upper cover of the flow channel;

[0022] When the limiting strip rotates to one of the slots, the knob body rotates to the first position;

[0023] When the limiting strip rotates to another slot, the knob body rotates to the second position.

[0024] In some embodiments, the knob body is provided with a flow channel switch knob and a rotation direction arrow on its surface.

[0025] In some embodiments, the flow channel switch knob is provided with a vent hole.

[0026] A second aspect of this invention is to provide a drug concentration detection component, comprising: the aforementioned drug concentration detection chip; a PCB board and a socket, wherein a nanopore array for detection is disposed in the reaction area of ​​the PCB board; a detection electrode is disposed on the socket; when the PCB board is mounted on the socket and the socket is mounted on the drug concentration detection chip, a detection flow channel is formed between the upper surface of the nanopore array disposed on the PCB board and the fifth groove at the bottom of the drug concentration detection chip, and the top of the detection electrode on the socket is located at the bottom of the manifold in the drug concentration detection chip.

[0027] Beneficial effects:

[0028] (1) The present invention sets up a detection channel in the detection area, and sets up an inlet channel and an outlet channel at both ends of the detection channel. The inlet channel includes a first buffer channel, a second buffer channel and a third buffer channel. A confluence cavity is provided between the first buffer channel and the second buffer channel, which are set at an inclination, thereby forming a buffer zone with a V-shaped cross-section. When the added liquid flows to this part, the presence of the confluence cavity makes it possible for even if the added liquid has a large flow rate, it will be buffered in the confluence cavity. Under the resistance of the second buffer channel set at an inclination upward, the liquid flow rate is reduced. Under the action of the third buffer channel, the decelerated liquid is appropriately accelerated, thereby ensuring that when the liquid enters the detection channel, the liquid can flow fully and evenly to the nanopore array on the PCB board in the detection area. This avoids the problem of uneven filling of liquid in each (or most) nanopores in the PCB board due to the excessively fast flow rate of the added liquid. It also eliminates the need to stop and observe whether the filling is uniform after adding some liquid before adding more liquid. In other words, the liquid addition speed is more flexible, and even if the addition speed is relatively fast, the uniformity of the liquid can be guaranteed due to the buffer channel design. That is, this utility model provides a microfluidic chip that can add liquid to a nanopore array on a PCB board and ensure the uniformity of the liquid in most (e.g., more than 80%) of the nanopores.

[0029] (2) An observation window is set up so that the test liquid can be observed in the flow channel. The connection and disconnection of the test flow channel and the waste liquid flow channel can be realized by the knob device. For example, during the test, the two flow channels can be disconnected by the knob device to avoid the waste liquid in the waste liquid flow channel flowing back into the test channel and causing pollution. When the waste liquid needs to be discharged, the two flow channels can be connected by the knob device so that the liquid in the test flow channel can flow into the waste liquid channel.

[0030] (3) Liquid needs to be added to the channel multiple times during the detection process. If the waste liquid needs to be sucked out using the suction chamber after each addition, the entire detection process will become cumbersome and inefficient. If a waste liquid tank is set up, on the one hand, when the liquid in the waste liquid tank exceeds the outlet of the waste liquid flow channel, it may cause the subsequent waste liquid to be unable to be discharged, or it may require increased pressure to flow, which makes the operation more complicated. On the other hand, when the amount of liquid in the waste liquid tank reaches a certain level, it will cause the center of gravity of the entire chip to shift or become unbalanced, thereby affecting the liquid distribution in the detection area and leading to inaccurate detection results. Therefore, in this application, by setting up a first waste liquid channel and a second waste liquid channel arranged in a roundabout manner on both sides of the detection area, and connecting the first waste liquid channel and the second waste liquid channel through a third waste liquid channel, the path of waste liquid flow is greatly lengthened, so that more waste liquid can be stored, thus eliminating the need to handle waste liquid at all times and simplifying the operation steps of the operator. On the other hand, the waste liquid flow path is lengthened, thereby preventing the waste liquid from flowing back into the detection channel. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. The elements or parts in the drawings are not necessarily drawn to scale. Obviously, the drawings described below are some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without any creative effort.

[0032] Figure 1 This is a schematic diagram of the assembly between the detection chip, PCB board and card holder in a drug concentration detection component of this utility model;

[0033] Figure 2 To reflect Figure 1 Assembly diagram of the PCB board and card slot with the bottom of the detection chip;

[0034] Figure 3 This is a schematic diagram illustrating the detection channel and the inlet and outlet channels on both sides of the drug concentration detection component.

[0035] Figure 4 This is a cross-sectional view of the flow channel cover;

[0036] Figure 5 This is a cross-sectional view of the lower cover of the flow channel;

[0037] Figure 6 This is a schematic diagram of the upper and lower cover of the flow channel in the drug concentration detection chip of this utility model;

[0038] Figure 7 This is a schematic diagram of the top structure of the flow channel cover of this utility model;

[0039] Figure 8 This is a schematic diagram of the back of the flow channel cover;

[0040] Figure 9 This is a schematic diagram of the flow channel cover structure of this utility model;

[0041] Figure 10 A schematic diagram illustrating the liquid flow path of this utility model.

[0042] Figure 11 This is a cross-sectional view (EE) of the structure of a drug concentration detection component according to the present invention;

[0043] Figure 12 This is a schematic diagram of the flow channel switch pressure plate at the bottom of the knob device in this utility model;

[0044] Figure 13 This is a side view of the knob device of this utility model;

[0045] Figure 14 This is a schematic diagram of the knob device of this utility model;

[0046] Figure 15 This is a schematic diagram of the top surface of the flow channel cover of this utility model;

[0047] Figure 16 This is a schematic diagram illustrating the connection between the waste liquid inlet and outlet when the knob is in the first position.

[0048] Figure 17 for Figure 16 Enlarged view of section A;

[0049] Figure 18 This is a schematic diagram illustrating that the waste liquid inlet and outlet are not connected when the knob is in the second position.

[0050] Figure 19 for Figure 18 Enlarged view of section B;

[0051] Figure 20 This is an exploded view of the detection component of this utility model;

[0052] Figure 21 A schematic diagram illustrating the nanopore array on a PCB board;

[0053] Figure 22a This is a schematic diagram illustrating the dual-sided detection contacts on the PCB board;

[0054] Figure 22b This is a schematic diagram illustrating a single-sided detection contact on a PCB board;

[0055] Figure 23 This is a schematic diagram showing the detection component of this utility model installed inside the detection box.

[0056] Among them, 1-upper cover of the flow channel, 2-lower cover of the flow channel, 3-liquid inlet, 4-first liquid inlet flow channel, 5-first buffer flow channel, 6-second buffer flow channel, 7-third buffer flow channel, 8-detection flow channel, 9-protective component, 10-fourth buffer flow channel, 11-first liquid outlet flow channel, 12-liquid outlet, 13-sixth buffer flow channel, 14-fifth buffer flow channel, 15-first protrusion, 16-second protrusion. 17-Waste liquid outlet; 18-Card slot; 19-Flow channel switch pressure plate; 20-Knob device; 21-Knob handle; 22-Indicator mark; 23-Limiting strip; 24-Flow channel connecting groove; 25-PCB board; 26-Card holder; 27-Sealing gasket; 28-Knob body; 29-Waste liquid inlet; 30-Observation window; 31-Support ear; 32-First groove; 33-Second groove; 34-Third groove; 36-Electrode; 37-Fourth groove; 38-Fifth groove; 39-Detection box; 40-First waste liquid tank; 41-Second waste liquid tank; 44-Nanopore array; 45-Footproof notch; 46-Detection contact; 47-Card slot; 48-Embedded nut; 49-Reinforcing rib; 50-Pre-compression contact area; 51-Ventilation hole; 52-Positioning pin; 53-First positioning hole; 54-Second positioning hole. Detailed Implementation

[0057] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this utility model. All other embodiments obtained by those skilled in the art based on the embodiments of this utility model without creative effort are within the scope of protection of this utility model.

[0058] In this document, the terms "upper," "lower," "inner," "outer," "front," "rear," "one end," and "the other end," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this utility model. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0059] In this document, unless otherwise explicitly specified and limited, the terms "installed," "equipped with," and "connected," etc., should be interpreted broadly. For example, "connected" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, a direct connection, or an indirect connection through an intermediate medium; it can be a connection within two components. Those skilled in the art can understand the specific meaning of the above terms in this utility model based on the specific circumstances.

[0060] In this document, "and / or" includes any and all combinations of one or more of the listed related items.

[0061] In this article, "multiple" means two or more, that is, it includes two, three, four, five, etc.

[0062] In existing technologies using microfluidic chips for drug concentration detection, a single sample addition is typically performed for detection, followed by drug concentration analysis based on the results. This method has limited accuracy. Performing multiple detections using the chip and then analyzing the results from these multiple tests would make the entire process cumbersome and time-consuming. In recent years, nanopore sequencers have developed rapidly and are increasingly being used in commercial DNA sequencing. Some nanopores with unique naturally confined structures have improved the sensitivity of bio-nanopores for detecting peptide molecules, effectively extending the residence time of amino acids in the nanopores. This allows for the differentiation of individual charged amino acids within a single peptide molecule, and can initially distinguish several simple amino acids. Known arrayed nanopore sensor devices include the MinION manufactured and sold by Oxford Nanopore Technologies Ltd., and the Obrit16 manufactured and sold by Nanion. The Obrit16 and MinION have similar arrayed nanopore sensor circuit structures and measure the ion current signal of the analyte molecule passing through the bio-nanopore based on the sensing principle of nanopores. Similarly, drug molecules of different concentrations produce different ion current signals when passing through nanopores. Therefore, the drug concentration can be calculated from the current signals generated by drug molecules of different concentrations passing through nanopores. Thus, the liquid to be detected can be added to the nanopore array at one time, and then multiple current signals can be obtained for analysis to obtain a more reliable drug concentration (e.g., the average value can be calculated based on the detection results of each pore) (i.e., high-throughput detection). This is a subsequent application of this invention and is not the core point of this invention, so it will not be elaborated here.

[0063] However, the nanopores on the PCB board (or microcontroller) appear in an array. Therefore, how to add liquid to the nanopore array and ensure the uniformity of liquid addition among the channels (or most channels, for example, more than 80%) is a problem that urgently needs to be solved. To solve this problem, this invention proposes a chip that can add drugs to a PCB board (or microcontroller) with multiple detection holes (i.e., nanopore array) for high-throughput drug concentration detection. Specifically, the chip adds liquid uniformly to the nanopore array on the PCB board through its liquid inlet, specially designed detection channels, buffer channels, etc.

[0064] For example, a detection area is provided on the chip body, and a detection channel is provided within the detection area; the two ends of the detection channel are connected to an inlet channel and an outlet channel, and a first waste liquid channel and a second waste liquid channel are respectively arranged in a meandering pattern on both sides of the detection channel, as well as a third waste liquid channel connecting the first waste liquid channel and the second waste liquid channel; a knob device is also rotatably provided on the chip body, the knob device including a channel switch pressure plate provided at the bottom, and a channel communication groove provided at the bottom of the channel switch pressure plate; wherein, the inlet channel includes: an inlet, the inlet being provided at the top of the chip body, the inlet being connected to a first inlet channel, the other end of the first inlet channel being connected to a first buffer channel, the other end of the first buffer channel being connected to a second buffer channel, and a confluence cavity is provided between the first buffer channel and the second buffer channel, the first buffer channel and the second buffer channel being respectively provided on both sides of the confluence cavity, such that the first buffer channel, the confluence cavity and the second buffer channel form A buffer zone with a V-shaped cross-section is provided. The other end of the second buffer channel is connected to the detection channel via an inclined third buffer channel. The liquid outlet channel includes: a liquid outlet, which is connected to a first liquid outlet channel. The other end of the first liquid outlet channel is connected to an inclined fourth buffer channel, the other end of which is connected to the detection channel. A waste liquid inlet is provided at the end of the first waste liquid channel near the liquid outlet. A waste liquid outlet is provided at the end of the second waste liquid channel near the liquid outlet. One end of the third waste liquid channel is connected to the end of the first waste liquid channel away from the liquid outlet, and the other end extends along the edge of the chip body and is connected to the end of the second waste liquid channel away from the liquid outlet. When the knob is rotated to the first position, the liquid outlet is connected to the waste liquid inlet through the channel connecting groove. When the knob is rotated to the second position, the channel connecting groove shifts, causing the channel switch plate to close the liquid outlet and the waste liquid inlet. A detailed description is provided below with reference to specific embodiments.

[0065] Example 1: As Figure 1 and Figure 2As shown, this utility model includes a chip body, and a detection channel 8 is provided in the detection area (preferably, the detection area is located in the middle position inside the chip body) on the chip body, through which the detection liquid flows. The two ends of the detection channel 8 are connected to an inlet channel and an outlet channel. When the chip body is placed horizontally, the horizontal position of the detection channel 8 is lower than the inlet and outlet channels at both ends, making the cross-section of the entire channel bowl-shaped. (See [reference]). Figure 3 That is, the inlet and outlet channels at both ends of the detection channel 8 are partially inclined, and the bottom middle section is the detection reaction area of ​​the corresponding PCB board.

[0066] In some embodiments, the liquid inlet channel includes: a liquid inlet 3 located at the top of the chip body for detecting the addition of liquid; the lower end of the liquid inlet 3 is connected to a first liquid inlet channel 4 (preferably, the first liquid inlet channel 4 extends along the height direction of the chip body); the bottom of the first liquid inlet channel 4 is connected to one end of an inclined first buffer channel 5; the other end of the first buffer channel 5 is connected to one end of an inclined second buffer channel 6; specifically, both the first buffer channel 5 and the second buffer channel 6 are at a certain inclination angle; a manifold is provided between the first buffer channel 5 and the second buffer channel 6 (preferably, an electrode 36 is connected to the bottom of the manifold); the manifold and the first buffer channels on both sides... 5. The second buffer channel 6 forms a V-shaped buffer zone. The detection liquid flows into the buffer zone from the first inlet channel 4. The structure of the buffer zone reduces or slows down the flow rate of the incoming liquid. The other end of the second buffer channel 6 is connected to one end of the inclined third buffer channel 7. The other end of the third buffer channel 7 is connected to the detection channel 8. The detection liquid flows into the detection channel 8 through the third buffer channel 7. After being slowed down by the buffer zone, the detection liquid is appropriately accelerated through the third buffer channel 7. This avoids the second buffer channel 6 in the buffer zone being set too steep, which would cause the flow rate to be greatly resisted, thus making the already slow flow rate of the detection liquid even smaller and affecting the detection efficiency.

[0067] In this embodiment, the V-shape includes the standard English letter V, as well as structures similar to the English letter V. For example, a groove structure with inclined walls, that is, a groove whose two side walls have a certain inclination angle and the middle part is horizontal. The middle is set as a horizontal structure, which facilitates the installation of the electrode 36 on the card holder 26 and ensures that the detection liquid fully submerges the top of the electrode 36.

[0068] In some embodiments, the liquid outlet flow channel includes: a liquid outlet 12, which is disposed at a position away from the liquid inlet 3. The liquid outlet 12 is connected to a first liquid outlet flow channel 11 (preferably, the first liquid inlet flow channel 4 extends along the height direction of the chip body). The bottom of the first liquid outlet flow channel 11 is connected to one end of a fourth buffer flow channel 10 with a cross-section in a 乁 shape. The other end of the fourth buffer flow channel 10 is connected to a detection flow channel 8. The detection liquid flows from the detection flow channel 8 to the fourth buffer flow channel 10 and finally flows out of the liquid outlet 12 through the first liquid outlet flow channel 11. By providing the fourth buffer flow channel 10 with a cross-section in a 乁 shape and the third buffer flow channel 7 disposed obliquely, a bowl-shaped or trumpet-shaped structure is formed. Among them, the third buffer flow channel 7 plays an accelerating role, while the fourth buffer flow channel 10 plays a decelerating role. Under the combined action of the three, a depression is formed to ensure that the nanopore array 44 on the PCB board 25 can be fully filled, avoiding the problem of uneven liquid in multiple nanopore arrays 44 on the PCB board 25 due to the fluid flowing too fast or too slow.

[0069] In some embodiments, such as Figure 6 and Figure 11 shown, the chip body of the present invention is composed of a flow channel upper cover 1 and a flow channel lower cover 2, and the two are detachably connected. The flow channel upper cover 1 and the flow channel lower cover 2 are integrated by dispensing or ultrasonic welding. The liquid inlet 3, the first liquid inlet flow channel 4, the liquid outlet 12, and the first liquid outlet flow channel 11 are all disposed on the flow channel upper cover 1 part.

[0070] See Figure 5 , the flow channel upper cover 1 includes a first groove 32 and a third groove 34. The flow channel lower cover 2 is provided with a second groove 33 with a cross-section in a v shape and an obliquely disposed fifth buffer flow channel 14 (preferably, the fifth buffer flow channel 14 is symmetrically disposed with the third buffer flow channel 7). When the flow channel upper cover 1 and the flow channel lower cover 2 are installed together such that the first groove 32 covers the second groove 33, the first groove 32 and the second groove 33 form the buffer area, that is, the first buffer flow channel 5, the confluence chamber, and the second buffer flow channel 6 are formed; at the same time, the third groove 34 and the upper surface of the flow channel lower cover 2 form a sixth buffer flow channel 13, so that the fifth buffer flow channel 14 passing through the protective member 9 and the sixth buffer flow channel 13 form a fourth buffer flow channel 10 in a 乁 shape. When the liquid is added from the liquid inlet 3 and flows to the buffer area, due to the existence of the confluence chamber, even if the flow rate of the added liquid is large, it will be buffered in the confluence chamber, and under the action of the resistance of the obliquely upwardly disposed second buffer flow channel 6, the liquid flow rate is reduced, and under the action of the third buffer flow channel 7, the decelerated liquid is appropriately accelerated, so as to ensure that the liquid enters the detection flow channel 8.

[0071] Preferably, see Figure 4The lower cover 2 of the flow channel is provided with a fourth groove 37 for mounting the PCB board 25 on the side away from the upper cover 1 of the flow channel. A fifth groove 38 is provided on the bottom of the fourth groove 37. When the PCB board 25 is installed in the fourth groove 37, a detection flow channel 8 is formed between the fifth groove 38 and the upper surface of the PCB board 25. The bottom of the fifth groove 38 is formed as a protective member 9 located on the detection flow channel 8. The fifth buffer flow channel 14 and the third buffer flow channel 7 are symmetrically arranged on the protective member 9 and the bottom of the fifth groove 38.

[0072] See Figure 9 , Figures 14-15 In some embodiments, the flow channel cover 1 is provided with a knob device 20, which includes a knob body 28 and a flow channel switch pressure plate 19 disposed at the bottom of the knob body 28. Preferably, the knob body 28 and the flow channel switch pressure plate 19 are injection molded. The bottom of the flow channel switch pressure plate 19 is provided with a flow channel communication groove 24, and the bottom of the knob device 20 is also provided with a limiting strip 23. Correspondingly, the flow channel cover 1 is provided with two slots 18 formed by two lugs 31. When the limiting strip 23 rotates to one of the slots 18, the knob body 28 rotates to a first position; when the limiting strip 23 rotates to the other slot 18, the knob body 28 rotates to a second position. When the knob body 28 rotates to the first position, the liquid outlet 12 is connected to the waste liquid inlet 29 through the flow channel communication groove 24. See [reference needed]. Figure 16 and Figure 17 When the knob body 28 is rotated to the second position, the flow channel connecting groove 24 shifts, and the flow channel switch plate 19 closes the outlet 12, thus disconnecting the passage between the outlet 12 and the waste liquid inlet 29. (See [link]) Figure 18 and Figure 19 .

[0073] Furthermore, the knob body 28 is provided with a knob handle 21 and an indicator mark 22 with a rotation direction arrow on its surface. The knob handle 21 can be rotated to a first position or a second position according to the rotation direction arrow. See [reference needed]. Figure 16 and Figure 18 A knob device 20 is provided to connect and disconnect the detection channel and the waste liquid channel.

[0074] See Figure 6 , Figure 7In some embodiments, the lower cover 2 of the flow channel further includes: first protrusions 15 symmetrically arranged on both sides of the protective member 9, and second protrusions 16 connected to the two first protrusions 15. The two first protrusions 15 are arranged in a meandering (or serpentine) manner on both sides of the protective member 9; the second protrusion 16 extends from one end of one of the first protrusions 15 away from the outlet 12 along the edge of the lower cover 2 of the flow channel to the other end of the first protrusion 15 away from the outlet 12, and the upper cover 1 of the flow channel is provided with a first waste liquid tank 40 and a second waste liquid tank 41 corresponding to the positions of the first protrusions 15 and the second protrusion 16, respectively. When the upper cover 1 of the flow channel and the lower cover 2 of the flow channel are closed, see Figure 10 The two first protrusions 15 and their corresponding first waste liquid tanks 40 form two first waste liquid channels, and the second protrusion 16 and the second waste liquid tank 41 form a second waste liquid channel that connects the two first waste liquid channels.

[0075] In this embodiment, the two symmetrically arranged first protrusions 15 refer to those whose shapes and arrangements are almost identical, or mostly identical, such as... Figure 7 As shown, the two first protrusions 15 differ only in the arrangement of a small portion of the flow channel near the outlet 12; the rest are arranged in the same serpentine pattern. Similarly, the two symmetrically arranged first waste liquid tanks 40 refer to those whose shapes and arrangements are almost identical, or mostly identical. Figure 10 As shown, the first waste liquid tanks 40 on both sides of the protective component 9 have the same serpentine arrangement, except for a small part of the flow channel arrangement at the end near the liquid outlet 12.

[0076] In practice, since both the upper cover 1 and the lower cover 2 of the flow channel are processed by molds, and they are usually sheet-like structures with small volume and thin thickness, the upper cover 1 and the lower cover 2 of the flow channel are very prone to deformation after processing. Therefore, in order to prevent deformation, the first protrusion 15 on the lower cover 2 is arranged in a meandering manner (or a serpentine arrangement) and a second protrusion 16 is provided to connect the two first protrusions 15 to support the overall structure of the lower cover 2. At the same time, the first waste liquid tank 40 on the upper cover 1 corresponding to the first protrusion 15 is arranged in a meandering manner, and a corresponding second waste liquid tank 41 is provided corresponding to the second protrusion 16 to connect the two first waste liquid tanks 40. This supports the overall structure of the upper cover 2 and ensures that the upper cover 1 and the lower cover 2 of the flow channel form a connected, complete and stable waste liquid channel when they are combined.

[0077] Preferably, see Figure 8The back of the flow channel cover 2 is provided with reinforcing ribs 49 in a mesh structure. As mentioned above, the flow channel cover 2 is processed by a mold and is very easy to deform. Therefore, the first protrusion 15 on the flow channel cover 2 is arranged in a meandering manner (or a serpentine arrangement), and a second protrusion 16 is provided to connect the two first protrusions 15 to support the overall structure of the flow channel cover 2. Furthermore, the reinforcing ribs 49 on the back of the flow channel cover 2 work together with the three protrusions to further enhance the stability of the flow channel cover 2 and prevent the flow channel cover 2 from deforming, which would prevent it from being able to fit tightly with the flow channel cover 1.

[0078] Preferably, see Figure 10 The back side of the upper cover 1, which is the side that fits with the lower cover 2, has an embedded nut 48 for easy locking with the lower cover 2. As mentioned earlier, since the upper cover 1 and the lower cover 2 are relatively small and have limited thickness, using self-tapping screws to connect them in the traditional way can easily cause deformation or even damage to the upper cover 1 and the lower cover 2 during installation. To avoid this problem, in this embodiment, an embedded nut 48 is provided around the protective member 9 or the detection area on the upper cover 1, so that drilling is not required for the upper cover 2 during installation, thus ensuring the integrity of the structure.

[0079] like Figure 15 As shown, the upper cover 1 of the flow channel is provided with a liquid outlet 12 and a waste liquid inlet 29 (preferably, the waste liquid inlet 29 is located at one end of the first waste liquid tank 40 near the liquid outlet 12, see [reference]). Figure 9 The waste liquid flows out from the outlet 12 connected to the fifth buffer channel 14. Under the control of the knob device 20, the channel connecting groove 24 connects the outlet 12 and the waste liquid inlet 29. Therefore, the liquid flowing out from the outlet 12 will enter the first waste liquid channel formed by the first protrusion 15 and the first waste liquid tank 40 of the channel lower cover 2 through the waste liquid inlet 29, and enter the second waste liquid channel formed by the second protrusion 16 and the second waste liquid tank 41 through the second waste liquid channel into another first waste liquid channel formed by the first protrusion 15 and the first waste liquid tank 40.

[0080] Preferably, adhesive dots or solder joints are provided around the first protrusion 15 and the second protrusion 16, so as to bond or weld with the corresponding first waste liquid tank 40 and the tank wall of the second waste liquid tank 41 to form a waste liquid flow channel.

[0081] Furthermore, the upper cover 1 of the flow channel is provided with a waste liquid outlet 17 on one side of the rotating device 20. The waste liquid outlet 17 is located at the end of the second waste liquid flow channel (i.e., the end of the second waste liquid tank 41 near the outlet 12, see...). Figure 10This ensures that the waste liquid has a sufficiently long flow path in the waste liquid channel formed by the entire protrusion and the waste liquid tank, that is, it is possible to set up a longer waste liquid channel in a relatively limited space, so that more waste liquid can be stored, while increasing the resistance to liquid flow.

[0082] Furthermore, an observation window 30 is provided on the upper cover 1 of the flow channel, which corresponds to the position and shape of the protective member 9 in the lower cover 2 of the flow channel. A fourth groove 37 for mounting the PCB board 25 is provided at the bottom of the chip body corresponding to the position of the protective member 9. When the PCB board 25, the chip body, and the card holder 26 are installed together by a fixing device, the gap between the fourth groove 37 and the PCB board 25 forms the detection flow channel 8. The detection liquid flows through the detection flow channel 8 into each nanopore array 44 of the PCB board 25. Due to the design of the buffer flow channel in the chip body, the problem of uneven filling of liquid in each nanopore array 44 of the PCB board 25 due to the excessively fast flow rate of the added liquid is avoided.

[0083] See Figure 20 Based on the detection chip described above, this utility model also provides a drug concentration detection component, which includes the detection chip, PCB board 25 and card holder 26 described in Embodiment 1 above.

[0084] See Figure 21 The reaction area on the PCB board 25 is provided with a nanopore array 44 for detection. When the PCB board 25 is installed in the fourth groove 37 at the bottom of the flow channel cover 2 of the detection chip, a detection flow channel 8 is formed between the upper surface of the nanopore array 44 on the PCB board 25 and the fifth groove 38.

[0085] Furthermore, on the other side of the PCB board 25, where the nanopore array 44 is provided, there are detection contacts 46 that can cooperate with the contacts inside the detection box 39. See specifically... Figure 22a The detection contact 46 can be symmetrically configured as a double-sided contact. Alternatively, it can be configured as a single-sided contact, with the other side designated as a pre-compression contact area 50 (during installation, the pre-compression contact area 50 can be pre-pressed against one side of the detection box 39, and then the position of the detection contact 46 on the other side can be adjusted). See [link / reference needed]. Figure 22b .

[0086] Furthermore, for sealing purposes, a sealing gasket 27 is provided between the PCB board 25 and the fourth groove 37, and the sealing gasket 27 has an observation opening corresponding to the area of ​​the nanopore array 44.

[0087] In some embodiments, the card holder 26 is U-shaped, and one of its side walls has a mounting hole for mounting the detection electrode 36. The PCB board 25 has slots 47 on both sides that mate with the side walls of the card holder 26. Furthermore, the PCB board 25 also has a foolproof notch 45 for indicating the mounting direction.

[0088] In some embodiments, participate Figure 20 and Figure 8 The card holder 26 is equipped with three positioning pins 52. Correspondingly, the PCB board 25 is equipped with three second positioning holes 54 at the positions of the positioning pins 52. These holes, together with the three positioning pins 52 on the card holder 26, form a foolproof and positioning function, ensuring that only one correct assembly action is performed during assembly; otherwise, assembly will fail. When the PCB board 25 is assembled with the flow channel lower cover 2, the positioning pins 52 on the card holder 26 cooperate with the first positioning holes 53 at the bottom of the flow channel lower cover 2 to form foolproof positioning. The foolproof design ensures the correct assembly of the detection chip, PCB board 25, and card holder 26 during the assembly process. Without the foolproof design, repeated checks and quality inspections are required during assembly, and even with checks, errors may still occur, leading to the inability to form detection channels and waste liquid channels, thus preventing detection. In this embodiment, the foolproof positioning design completely avoids such situations.

[0089] Working principle: such as Figures 20-23 As shown, the chip body, PCB board 25, and card holder 26 of this utility model are assembled into a whole (i.e., the PCB board 25 is first installed on the card holder 26, and then the card holder 26 is fixed to the bottom of the chip body by fasteners such as screws, so that the upper surface of the nanopore array 44 on the PCB board 25 forms a detection channel 8 between it and the fifth groove 38 at the bottom of the drug concentration detection chip, and the top of the detection electrode 36 on the card holder 26 is located at the bottom of the manifold in the drug concentration detection chip, see [reference]). Figure 3First, cleaning fluid is added to the chip body through the inlet 3 to clean the flow channels inside the chip body and the detection flow channels between the chip body and the PCB board 25, and to filter out the air inside the chip body. Then, liquid is added multiple times, and the flow of detection liquid is observed through the observation window 30 to confirm the yield of the nanopore array in the PCB board 25. If the yield reaches a preset threshold (for example, above 80%), detection liquid is added, and the detection liquid is observed to fill the detection area in the PCB board 25 through the observation window 30. Then, the inlet 3 is sealed with adhesive, and the entire detection assembly is installed in the existing detection box 39, so that the detection contact 46 on the PCB board 25 corresponds to the contact in the detection box 39. Then, detection is started to obtain microcurrent (different concentrations of drug molecules will generate different microcurrents when passing through the protein nanopores in the nanopore array 44 in the PCB board 25). The drug concentration is obtained by data processing based on the obtained microcurrent.

[0090] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0091] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A drug concentration detection chip, characterized by, Comprising: A chip body, a detection area is provided on the chip body, and a detection flow channel is provided in the detection area; both ends of the detection flow channel are connected to a liquid inlet flow channel and a liquid outlet flow channel. The liquid inlet flow channel includes: A liquid inlet, the liquid inlet is provided on the top of the chip body, the liquid inlet is connected to a first liquid inlet flow channel, the other end of the first liquid inlet flow channel is connected to a first buffer flow channel, the other end of the first buffer flow channel is connected to a second buffer flow channel, and a confluence cavity is provided between the first buffer flow channel and the second buffer flow channel. The first buffer flow channel and the second buffer flow channel are respectively arranged on both sides of the confluence cavity, so that the first buffer flow channel, the confluence cavity and the second buffer flow channel form a buffer area with a V-shaped cross section. The other end of the second buffer flow channel is connected to the detection flow channel through an inclined third buffer flow channel; The liquid outlet flow channel includes: a liquid outlet, the liquid outlet is connected to a first liquid outlet flow channel, the other end of the first liquid outlet flow channel is connected to an inclined fourth buffer flow channel, and the other end of the fourth buffer flow channel is connected to the detection flow channel.

2. The drug concentration detection chip according to claim 1, wherein, The chip body includes a flow channel upper cover and a flow channel lower cover detachably connected to the flow channel upper cover. The liquid inlet, the first liquid inlet flow channel, the liquid outlet and the first liquid outlet flow channel are all provided on the flow channel upper cover; Among them, the flow channel upper cover includes a first groove and a third groove, and the flow channel lower cover includes a second groove with a V-shaped cross section and a fifth buffer flow channel. When the flow channel upper cover and the flow channel lower cover are installed together and the first groove covers the second groove, the first groove and the second groove form the buffer area connected to the third buffer flow channel; The third groove and the upper surface of the flow channel lower cover form a sixth buffer flow channel, so that the fifth buffer flow channel and the sixth buffer flow channel form the fourth buffer flow channel with a ∟-shaped cross section.

3. The drug concentration detection chip according to claim 1, wherein, A fourth groove is provided at the bottom of the chip body corresponding to the position of the detection area, and when the PCB board is installed with the chip body, the gap between the fourth groove and the PCB board forms the detection flow channel.

4. The drug concentration detection chip according to claim 2, wherein, The flow channel lower cover further includes: first protrusions symmetrically arranged on both sides of the detection area, and a second protrusion connected to the two first protrusions. The first protrusions are arranged in a meandering manner, and the second protrusion is arranged along the edge of the flow channel lower cover; On the flow channel upper cover, a first waste liquid groove arranged in a meandering manner is provided corresponding to the position of the first protrusion, and a second waste liquid groove arranged along the edge of the flow channel upper cover is provided corresponding to the position of the second protrusion; When the flow channel lower cover and the flow channel upper cover are combined together, the first protrusion matches the first waste liquid groove, the second protrusion matches the second waste liquid groove, and a gap between the first protrusion and the groove bottom of the first waste liquid groove forms a first waste liquid passage; a gap between the second protrusion and the groove bottom of the second waste liquid groove forms a second waste liquid passage, and the first waste liquid passage and the second waste liquid passage are communicated, wherein one of the first waste liquid grooves is provided with a waste liquid inlet at one end close to the liquid outlet, and the other of the first waste liquid grooves is provided with a waste liquid outlet at one end close to the liquid outlet.

5. The drug concentration detection chip according to claim 2, wherein The flow channel upper cover comprises an observation window provided through the flow channel upper cover, and the observation window corresponds to the position and shape of the detection area in the flow channel lower cover.

6. The drug concentration detection chip according to claim 4, wherein The flow channel upper cover is rotationally provided with a knob device, the knob device comprises a knob body and a flow channel switch pressing piece provided at the bottom of the knob body, and the flow channel switch pressing piece is provided with a flow channel communication groove at the bottom. When the knob body is rotated to a first position, the liquid outlet is communicated with the waste liquid inlet through the flow channel communication groove, and when the knob body is rotated to a second position, the flow channel communication groove is offset, and the flow channel switch pressing piece closes the liquid outlet.

7. The drug concentration detection chip according to claim 6, wherein The bottom of the knob device is further provided with a limiting clamping strip, and correspondingly, the flow channel upper cover is provided with two clamping grooves. When the limiting clamping strip is rotated to one of the clamping grooves, the knob body is rotated to the first position. When the limiting clamping strip is rotated to the other clamping groove, the knob body is rotated to the second position.

8. The drug concentration detection chip according to claim 6, wherein, The knob body is provided with a flow channel switch knob and a rotation direction arrow on the surface.

9. The drug concentration detection chip according to claim 8, wherein, The flow channel switch knob is provided with a vent hole.

10. A drug concentration detection assembly, comprising: Comprise: The drug concentration detection chip according to any one of claims 1 to 9; The PCB board and the clamping seat, wherein The reaction area on the PCB board is provided with an array of nano channels for detection; the clamping seat is provided with a detection electrode; when the PCB board is installed on the clamping seat, and the clamping seat is installed on the drug concentration detection chip, the upper surface of the PCB board provided with the array of nano channels and the fifth groove at the bottom of the drug concentration detection chip form a detection flow channel, and the top of the detection electrode on the clamping seat is located at the bottom of the confluence cavity in the drug concentration detection chip.

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