Biological sample analysis device and system

Abstract

The application provides a biological sample analysis device and system, relates to the technical field of gene sequencing, wherein the biological sample analysis device comprises a base, a first substrate, a second substrate, a sealing gasket, a chip and a rotary valve, the base is provided with a first flow channel, a second flow channel and a third flow channel; the first substrate is provided with a liquid inlet and a liquid outlet, the liquid outlet is communicated with the third flow channel; the chip, the sealing gasket and the second substrate are fixedly connected and define a flow cavity, one end of the flow cavity is communicated with the first flow channel, and the other end of the flow cavity is communicated with the second flow channel; the rotary valve is rotated relative to the base to an open position and a closed position, when the rotary valve is rotated to the open position, liquid can be injected into the first flow channel; the second flow channel is communicated with the third flow channel, when the rotary valve is rotated to the closed position, liquid cannot be injected into the first flow channel, the second flow channel and the third flow channel are cut off in communication, and / or a vertical channel is arranged between the flow cavity and the first flow channel and / or the second flow channel. The application controls flow through the rotary valve, improves the sealing property and the storage period.

Description

Cross-references to related applications

[0001] This application claims priority to Chinese Patent Application No. 2026200592731, filed on January 16, 2026, entitled "Biosample Analysis Device and System", the contents of which are incorporated herein by reference in whole or in part. Technical Field

[0002] This application relates to the field of gene sequencing technology, and more specifically, to a biological sample analysis device and system. Background Technology

[0003] Biological sample analysis technology plays a vital role in medical diagnostics, gene sequencing, and scientific research. With the development of precision medicine and personalized treatment, the requirements for the accuracy and reliability of biological sample analysis devices are becoming increasingly stringent. Currently, mainstream biological sample analysis devices typically consist of a sample loading module, a reaction module, a detection module, and a data processing module.

[0004] In existing technologies, the manufacturing process of biological sample analysis devices mostly employs traditional mechanical sealing methods, using rubber gaskets or silicone sealing strips to achieve sealing between modules. During sequencing, the device needs to operate for extended periods at temperatures above room temperature, which places high demands on the device's sealing performance. However, due to factors such as differences in material expansion coefficients and mechanical wear, existing sealing structures are prone to developing micro-gaps after prolonged use. These micro-gaps become a major source of air bubbles during sequencing, severely limiting the lifespan of biological sample analysis devices.

[0005] For the storage of biological samples, current technologies mainly rely on low-temperature environments or chemical preservatives to extend preservation time. Bioanalytical devices typically have internal temporary storage compartments made of ordinary plastic or glass, which have limited barrier properties and leak-proof capabilities. Especially during transportation or movement, vibration and temperature changes can easily cause the storage compartment's seal to fail, affecting the integrity of the sample.

[0006] It should be noted that the methods described in this section are not necessarily methods that had been previously conceived or adopted. Unless otherwise specified, no method described in this section should be assumed to be prior art simply because it is included in this section. Similarly, unless otherwise specified, the issues mentioned in this section should not be considered to be accepted in any prior art. Summary of the Invention

[0007] The purpose of this application is to provide a biological sample analysis device and system that can improve the high airtightness during production and sequencing, and extend the shelf life during storage.

[0008] In a first aspect, this application provides a biological sample analysis device, which includes: The base is provided with a first flow channel, a second flow channel, and a third flow channel; A first substrate is disposed on one side of the base and fixedly connected to the base. The first substrate is provided with a liquid inlet and a liquid outlet, and the liquid outlet is connected to the third flow channel. A chip is disposed on the side of the base away from the second substrate, and the chip and the base are connected and define a flow cavity. One end of the flow cavity is connected to the first flow channel, and the other end of the flow cavity is connected to the second flow channel. A rotary valve rotates relative to the base to an open position and a closed position. When the rotary valve is rotated to the open position, liquid can be injected into the first flow channel through the inlet, and the second flow channel is connected to the third flow channel. When the rotary valve is rotated to the closed position, liquid cannot be injected into the first flow channel through the inlet, and the second flow channel is disconnected from the third flow channel; and / or, A vertical channel is provided between the flow cavity and the first flow channel and / or the second flow channel.

[0009] In an optional embodiment, the device further includes: a second substrate disposed on the side of the base away from the first substrate; A sealing gasket is disposed on the side of the second substrate away from the base; The chip is disposed on the side of the sealing gasket away from the second substrate, and the chip, the sealing gasket, and the second substrate are fixedly connected and define the flow cavity. In an optional embodiment, the width of one end of the vertical channel matches the width of the first flow channel and / or the second flow channel, and the width of the other end of the vertical channel matches the width of the flow cavity, so that the vertical channel forms a variable diameter channel.

[0010] In an optional embodiment, the first flow channel and / or the second flow channel are provided with a variable diameter region at one end near the flow cavity, so that the width of the end of the first flow channel and / or the second flow channel matches the width of the flow cavity, and the vertical channel forms a constant diameter channel.

[0011] In an optional embodiment, the vertical channel (180) has a rectangular cross-sectional shape perpendicular to the vertical direction and a uniform thickness.

[0012] In an optional embodiment, the rotary valve has a liquid injection state and a storage state. The rotary valve includes a valve body and an operating element. At least a portion of the operating element is located on the side of the first substrate opposite to the base. The valve body is mounted on the base and is fixedly connected to the operating element.

[0013] In an optional embodiment, the valve body is provided with a first connecting groove and a second connecting groove, and the liquid inlet is disconnected from the first flow channel. When the rotary valve is in the liquid injection state, the rotary valve is rotated to the open position, the first connecting groove connects the liquid inlet and the first flow channel respectively, and the second connecting groove connects the second flow channel and the third flow channel respectively.

[0014] In an optional embodiment, the valve body is further provided with a limiting part that protrudes radially from the valve body. When the rotary valve is rotated to the open position, the limiting part abuts against the second base plate.

[0015] In an optional embodiment, both the first flow channel and the second flow channel are located on the side of the base facing the first substrate.

[0016] In an optional embodiment, the third flow channel includes a first flow segment, a second flow segment, and a third flow segment that are connected to each other. The first flow segment and the third flow segment are located on the side of the base facing the first substrate, and the second flow segment is located on the side of the base away from the first substrate.

[0017] In an optional embodiment, the rotary valve has a liquid filling state and a storage state, and the rotary valve includes a valve body and a rod; the valve body is mounted on the side of the first substrate away from the base, and the rod extends from the edge of the valve body in a direction away from the valve body.

[0018] In an optional embodiment, the valve body is provided with a sample inlet and a third connecting groove, and the liquid inlet is kept in communication with one end of the first flow channel. When the rotary valve is in the liquid injection state, the rotary valve is rotated to the open position, the sample inlet is connected to the liquid inlet, and the third connecting groove is connected to the second flow channel and the third flow channel respectively.

[0019] In an optional embodiment, a stop portion is provided on the valve body facing the first substrate, and a limiting groove is formed on the first substrate. The stop portion is slidably inserted into the limiting groove. When the stop portion abuts against one end of the limiting groove, the rotary valve is in the liquid injection state; when the stop portion abuts against the other end of the limiting groove, the rotary valve is in the storage state.

[0020] In an optional embodiment, a proton exchange membrane is also included. The base is further provided with an interaction hole and a salt bridge channel. The salt bridge channel is located on the side of the base away from the first substrate. The two ends of the interaction hole extend to the second channel and the salt bridge channel, respectively. The proton exchange membrane is attached to the base, and the proton exchange membrane covers the interaction hole to separate the second channel and the salt bridge channel.

[0021] In an optional embodiment, the biological sample analysis device further includes a platinum electrode plate mounted on a second substrate and in contact with the liquid in the salt bridge channel, wherein the probe end of the chip is connected to the platinum electrode plate.

[0022] In an optional embodiment, the biological sample analysis device further includes a sealing element. The first substrate is provided with an injection hole and an outlet hole. The base is provided with a first through hole and a second through hole. The injection hole, the first through hole, and the inlet end of the salt bridge channel are connected. The outlet end of the salt bridge channel is connected to the second through hole and the outlet hole. The sealing element is fixedly connected to the first substrate and seals the injection hole and the outlet hole.

[0023] In an optional embodiment, the inner edge of the sealing gasket is located outside the biochemical reaction area of ​​the chip, so that the top of the flow cavity where the biochemical reaction area of ​​the chip, such as the nanopore sequencing area, is located, and / or the adjacent periphery does not contain areas that cannot be wetted by a preset fluid, thereby reducing the amount of air bubbles. In the fluid design of the sequencing region, dead zones exist in the sequencing chip fixture that are difficult to wet sufficiently. These dead zones can generate bubbles during storage and sequencing, which may migrate into the sequencing region (containing the amphiphilic molecular layer and embedded nanopore structures), leading to widespread membrane rupture and nanopore detachment. Notably, these bubbles can continue to expand due to factors such as prolonged sequencing time, increased temperature, or fluid movement (similar to bubble nucleation). When their size reaches a critical value, they may displace, highly probably invading the sequencing region and causing pore failure and membrane structure damage.

[0024] Furthermore, even after the sequenced chips are recycled and cleaned (to remove library residues and preserve pores and membrane structures for reuse), the regeneration of air bubbles cannot be completely eliminated. During subsequent sequencing, residual air bubbles continue to accumulate and gradually expand, ultimately having a systemic impact on chip performance, including but not limited to: reduced sequencing throughput, fewer reusable cycles, and increased overall sequencing costs, among other key technical indicators.

[0025] In an optional embodiment, the second substrate is made of a transparent material to facilitate observation of the biochemical reaction region of the chip and / or the salt bridge channel.

[0026] Secondly, this application provides a biological sample analysis system, which includes a sequencer and the biological sample analysis device described in the foregoing embodiments, wherein the biological sample analysis device is installed on the sequencer.

[0027] Compared to existing technologies, the beneficial effects of this application are: This application uses a base as a flow carrier for biological samples. After the biological sample is injected through the inlet of the first substrate, it flows through the first flow channel, the vertical channel, the flow chamber, the vertical channel, the second flow channel, and the third flow channel, and finally flows out from the outlet of the first substrate. This application utilizes a rotary valve to achieve two different functions: opening and closing, thereby improving the high airtightness during production and sequencing, and extending the shelf life during storage.

[0028] Other features and advantages of this application will be described in detail in the following detailed description section. Attached Figure Description

[0029] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0030] Figure 1 A three-dimensional structural schematic diagram of the biological sample analysis device in some embodiments is shown; Figure 2 An exploded schematic diagram of the biological sample analysis apparatus in some embodiments is shown; Figure 3 A schematic diagram of the combination of the base and the rotary valve in some embodiments is shown (the rotary valve is in the open position). Figure 4 A plan view of the base (the side of the base away from the first substrate) is shown in some embodiments. Figure 5 A planar schematic diagram of the first substrate is shown in some embodiments; Figure 6 It shows Figure 1 Schematic diagram of the AA section; Figure 7 A schematic diagram of the combination of the base and the rotary valve in some embodiments is shown (the rotary valve is in the closed position). Figure 8 A three-dimensional structural schematic diagram of the valve body is shown in some embodiments; Figure 9 Schematic diagrams of the base and rotary valve in other embodiments are shown; Figure 10 Schematic diagrams of the rotary valve in other embodiments are shown; Figure 11 A schematic diagram of the structure of the first substrate is shown in some other embodiments; Figure 12 Schematic diagrams of the base structure are shown in some other embodiments; Figure 13 A structural schematic diagram of a vertical channel in some embodiments is shown; Figure 14 Another structural schematic diagram of the vertical channel in some embodiments is shown; Figure 15 Schematic diagrams of the vertical channel in other embodiments are shown.

[0031] icon: 100 - Base; 110 - First flow channel; 120 - Second flow channel; 130 - Third flow channel; 131 - First flow section; 132 - Second flow section; 133 - Third flow section; 140 - Interchange hole; 150 - Salt bridge flow channel; 160 - First through hole; 170 - Second through hole; 180 - Vertical channel; 190 - Variable diameter area; 200 - First substrate; 210 - Liquid inlet; 220 - Liquid outlet; 230 - Injection hole; 240 - Outlet hole; 250 - Limiting groove; 300 - Second substrate; 400 - Sealing gasket; 500 - Chip; 600 - Rotary valve; 601 - First connecting groove; 602 - Second connecting groove; 603 - Sample inlet; 604 - Third connecting groove; 610 - Valve body; 611 - Soft adhesive layer; 612 - Valve seat; 613 - Limiting part; 614 - Stopping part; 620 - Operating component; 630 - Rod body; 700 - Proton exchange membrane; 800 - Platinum electrode sheet; 900 - Sealing component; a - Flow chamber. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. The components of the embodiments of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0033] In the description of this application, it should be noted that the terms "inner" and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product is in use. They are used only for the convenience of describing this application and for 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 application. Furthermore, the terms "first," "second," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0034] In the description of this application, it should also be noted that, unless otherwise expressly specified and limited, the terms "setup" and "connection" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0035] This embodiment is applicable to the detection of 500 pairs of biological samples using a nanopore sequencing chip. After sequencing is completed, a cleaning solution needs to be injected to clean the waste liquid in the flow channel.

[0036] Please see Figure 1 and Figure 2 This embodiment provides a biological sample analysis device, which includes a base 100, a first substrate 200, a second substrate 300, a sealing gasket 400, a chip 500, and a rotary valve 600.

[0037] Please see Figures 2 to 4 The base 100 is made of polymer injection molding and is made of polycarbonate (PC). Polycarbonate is a thermoplastic resin with high transparency and impact resistance. The base 100 is provided with a first flow channel 110, a second flow channel 120 and a third flow channel 130; in this embodiment, the first flow channel 110 and the second flow channel 120 are the main flow channels, and the third flow channel 130 is the waste liquid flow channel.

[0038] In this embodiment, the first flow channel 110 and the second flow channel 120 are both located on the side of the base 100 facing the first substrate 200. The third flow channel 130 includes a first flow segment 131, a second flow segment 132, and a third flow segment 133 that are connected to each other. The first flow segment 131 and the third flow segment 133 are located on the side of the base 100 facing the first substrate 200, and the second flow segment 132 is located on the side of the base 100 away from the first substrate 200.

[0039] The first flow section 131 and the third flow section 133 are collectively referred to as the upper waste liquid flow channel, and the second flow section 132 is referred to as the lower waste liquid flow channel. The lower waste liquid flow channel is connected to the upper waste liquid flow channel and is located in the middle section of the upper waste liquid flow channel. In this embodiment, the design of the flow channel height gradient reduces the residue of waste liquid during suction.

[0040] In some other embodiments, the location and composition of the first flow channel 110, the second flow channel 120 and the third flow channel 130 can be in other ways, for example: the third flow channel 130 is all located on the side of the base 100 facing the first substrate 200.

[0041] In this embodiment, the first flow channel 110, the second flow channel 120, and the third flow channel 130 can all be configured as groove structures.

[0042] Please see Figure 7 ,as well as Figures 12 to 14 A vertical channel 180 is provided between the flow chamber a and the first flow channel 110 and / or the second flow channel 120. In actual use, the liquid injected from the inlet 210 flows into the first flow channel 110, flows through the first flow channel 110 to the vertical channel 180, and then flows from the vertical channel 180 into the flow chamber a. After filling the flow chamber a, it flows out from the vertical channel 180 at the other end of the flow chamber a and flows into the second flow channel 120 to continue subsequent operations.

[0043] The vertical channel 180 can serve as a fluid guiding structure, allowing liquid to enter the flow chamber a from the bottom center or a specific location, avoiding direct impact on the sensitive area of ​​the chip 500. This makes the filling process more controllable, reduces turbulence or localized drying, ensures that the entire biochemical reaction area is uniformly wetted, and improves sequencing signal consistency.

[0044] Furthermore, planar area is precious in the microfluidic chip 500. By connecting the upper and lower layers through the vertical channel 180, fluid can be introduced into or extracted from functional chambers located in different layers without increasing the planar size of the chip 500, thus saving planar layout space.

[0045] Please see Figure 2 The first substrate 200 is disposed on one side of the base 100 and fixedly connected to the base 100. The fixed connection method includes, but is not limited to, laser bonding, UV adhesive bonding, solvent bonding, etc. It is understood that compared with UV adhesive bonding, laser bonding can significantly reduce the amount of UV adhesive used and eliminate the risk of biochemical incompatibility between UV adhesive and the biochemical system inside the chip 500.

[0046] Please see Figures 3 to 5 The first substrate 200 is provided with a liquid inlet 210 and a liquid outlet 220. The liquid outlet 220 is connected to the third flow channel 130. The liquid inlet 210 can be filled with liquids such as biological samples or cleaning solutions. After the liquid passes through the biological sample analysis device, it flows out from the liquid outlet 220.

[0047] Please see Figures 2 to 4 The second substrate 300 is disposed on the side of the base 100 away from the first substrate 200, that is, the second substrate 300 and the first substrate 200 are respectively disposed on both sides of the base 100.

[0048] In this embodiment, when the first substrate 200 is attached to the base 100, the first flow channel 110, the second flow channel 120, the first flow section 131 and the third flow section 133 respectively form a closed flow space with the first substrate 200. Then, when the second substrate 300 is attached to the base 100, the second flow section 132 forms a closed flow space with the second substrate 300.

[0049] A sealing gasket 400 is disposed on the side of the second substrate 300 away from the base 100.

[0050] Please see Figure 2 , Figure 3 and Figure 6 The chip 500 is disposed on the side of the sealing gasket 400 away from the second substrate 300, and the chip 500, the sealing gasket 400 and the second substrate 300 are fixedly connected and define a flow cavity a. One end of the flow cavity a is connected to the first flow channel 110, and the other end of the flow cavity a is connected to the second flow channel 120.

[0051] As described above, the chip 500 and the second substrate 300 are fixed by bolts, and the sealing gasket 400 is sandwiched between the chip 500 and the second substrate 300 to achieve relative fixation of the three. Under the sealing effect of the sealing gasket 400, the flow cavity a will not leak.

[0052] As mentioned above, the inner edge of the sealing gasket 400 is located outside the biochemical reaction area of ​​the chip 500, so that the top and / or adjacent periphery of the biochemical reaction area of ​​the chip 500, such as the nanopore sequencing area, does not contain areas that cannot be wetted by the preset fluid, thereby reducing the amount of air bubbles. The second substrate 300 may be made of a transparent material, either entirely or partially, to facilitate observation of the biochemical reaction area and / or the salt bridge channel 150 of the chip 500.

[0053] In one embodiment, exemplarily, such as Figure 3 , Figure 15As shown, the width of one end of the vertical channel 180 matches the width of the first flow channel 110 and / or the second flow channel 120, and the width of the other end of the vertical channel 180 matches the width of the flow cavity a, so that the vertical channel 180 forms a variable-diameter channel. The vertical channel 180 forms a variable-diameter channel when the widths of the first flow channel 110 and the second flow channel 120 are significantly different from the width of the flow cavity a. Generally, the widths of the first flow channel 110 and the second flow channel 120 are the same. Depending on whether their widths are less than or greater than the width of the flow cavity a, the vertical channel 180 is set as a variable-diameter channel that transitions from narrow to wide or from wide to narrow. This creates a localized low-velocity region within the vertical channel 180. If a user accidentally introduces microbubbles during sample loading, the bubbles tend to remain in the widened portion of the channel due to buoyancy and velocity changes as they flow through the variable-diameter channel. Since this location is far from the biochemical reaction area of ​​the chip 500, the presence of bubbles will not interfere with the sequencing signal. Of course, the width of the first flow channel 110 and the width of the second flow channel 120 may not be the same. In this case, it is only necessary to match the width of the end of the vertical channel 180 away from the flow cavity a with the width of the first flow channel 110 or the second flow channel 120.

[0054] However, in actual production, if the venting is insufficient or the wetting is incomplete during the injection molding and multilayer bonding process of the base 100, microbubbles are very likely to remain at the corners of the diameter change before leaving the factory. These bubbles remain in the fluid dead zone for a long time and may be slowly released during sequencing, contaminating the flow cavity a or changing the local flow resistance and affecting the consistency of flow rate.

[0055] Based on the above problems, in one embodiment, exemplarily, such as Figures 12 to 14 As shown, the first flow channel 110 and / or the second flow channel 120 have a variable diameter region 190 near the flow cavity a, so that the width of the end of the first flow channel 110 and / or the second flow channel 120 matches the width of the flow cavity a, and the vertical channel 180 forms a constant diameter channel. The vertical channel 180 has a rectangular cross-sectional shape perpendicular to the vertical direction and a uniform thickness. This simplifies the process preparation and avoids bubbles generated by fluid flow due to thickness variations. The width and thickness dimensions of the rectangle and their ratio can be adjusted according to actual use, generally the width is significantly larger than the thickness. The constant diameter of the vertical channel 180 means that the flow channel cross-section remains constant along the flow direction, avoiding sudden drops or increases in flow velocity caused by abrupt changes in cross-section, and thus eliminating local low-velocity regions. The liquid smoothly transitions when entering or leaving the flow cavity a, resulting in a more uniform flow velocity distribution, allowing the biological sample to pass through the flow cavity a stably and laminarly.

[0056] Of course, importantly, in injection molding and multilayer bonding processes, equal-diameter channels are easier to fully wet and degas than variable-diameter channels. Equal-diameter channels have no geometric abrupt change points, which means there are no places where air bubbles are easily generated. The capillary action is more consistent, and the liquid can spontaneously fill the entire channel, ensuring that the finished product is free of native air bubbles.

[0057] It should also be noted that the diameter-changing function is transferred from the vertical channel 180 to the diameter-changing region 190 at the end of the horizontal channel. This has two advantages: firstly, the horizontal channel is integrally molded on the base 100 via injection molding, making the diameter-changing region 190 easy to process; secondly, almost no air bubbles are generated when the liquid flows within the horizontal channel, further preventing air bubbles from forming within the channel in this embodiment and affecting normal sequencing. Furthermore, placing the diameter-changing region 180 at the end of the horizontal channel ensures that the diameter-changing region 190 can match the width of both the first channel 110 and the second channel 120, thus forming a channel of equal diameter in the vertical channel 180.

[0058] Please see Figure 1 , Figure 3 and Figure 5 The rotary valve 600 rotates relative to the base 100 to an open position and a closed position, and the rotary valve 600 has a liquid injection state and a storage state. In the normal state, the liquid inlet 210 is disconnected from the first flow channel 110. In the liquid injection state, the rotary valve 600 rotates to the open position, the liquid inlet 210 is connected to the first flow channel 110, and the second flow channel 120 is connected to the third flow channel 130. Specifically, a biological sample or cleaning solution or other liquid is injected through the liquid inlet 210. The liquid inlet 210, the first flow channel 110, the flow chamber a, the second flow channel 120, the third flow channel 130, and the liquid outlet 220 are all connected.

[0059] Please see Figure 1 , Figure 5 and Figure 7 In the storage state, the rotary valve 600 is rotated to the closed position, the liquid inlet 210 is disconnected from the first flow channel 110, and the second flow channel 120 is disconnected from the third flow channel 130. Specifically, the first flow channel 110, the flow chamber a and the second flow channel 120 are connected, while the third flow channel 130 and the liquid outlet 220 are still connected.

[0060] Please see Figure 2 The rotary valve 600 includes a valve body 610 and an operating member 620. At least a portion of the operating member 620 is located on the side of the first base plate 200 away from the base 100. The valve body 610 is mounted on the base 100 and is fixedly connected to the operating member 620.

[0061] Specifically, the valve body 610 is injection molded from polymer overmolded material, which is polycarbonate (PC) and thermoplastic elastomer (TPE) or thermoplastic polyurethane (TPU). In this embodiment, the soft rubber layer 611 can be made of a harder thermoplastic elastomer (TPE).

[0062] The operating component 620 is injection molded from a polymer and is made of polycarbonate (PC).

[0063] Please see Figure 2 and Figure 8 The valve body 610 is composed of a soft rubber layer 611 and a valve seat 612. The valve seat 612 has a cylindrical structure, and the soft rubber layer 611 is laid on the valve seat 612. The outer contour of the soft rubber layer 611 is adapted to the valve seat 612.

[0064] The valve body 610 is provided with a first connecting groove 601 and a second connecting groove 602. The first connecting groove 601 and the second connecting groove 602 are located on the soft rubber layer 611, and both the first connecting groove 601 and the second connecting groove 602 are arc-shaped grooves.

[0065] Please see Figure 2 , Figure 3 and Figure 8 When the rotary valve 600 is in the liquid injection state, the rotary valve 600 is rotated to the open position, the first connecting groove 601 is connected to the liquid inlet 210 and the first flow channel 110 respectively, and the second connecting groove 602 is connected to the second flow channel 120 and the third flow channel 130 respectively.

[0066] The valve body 610 is also provided with a limiting part 613, which protrudes from the valve body 610 radially. When the rotary valve 600 is rotated to the open position, the limiting part 613 abuts against the second base plate 300.

[0067] In this embodiment, the setting of the limiting part 613 realizes the positioning prompt of the state switching, ensuring that the two ends of the first connecting groove 601 are located at the liquid inlet 210 and the liquid inlet end of the first flow channel 110, and ensuring that the two ends of the second connecting groove 602 are located at the liquid outlet end of the second flow channel 120 and the liquid inlet end of the third flow channel 130.

[0068] Of course, the limiting part 613 may not be provided in this embodiment.

[0069] In some other embodiments, the indication of the state switch can also be indicated by indicator lines, for example: an indicator line for the open position and an indicator line for the closed position are provided on the first substrate 200, and when the rotary valve 600 rotates to the corresponding indicator line, it indicates that the state switch is in place.

[0070] Please see Figure 3 and Figure 5 In this embodiment, a rotary valve 600 is used to simultaneously seal the liquid inlet 210 and the liquid outlet of the third flow channel 130, which greatly improves the storage life of the chip 500.

[0071] Please see Figures 9 to 11 In other embodiments, the rotary valve 600 has a liquid filling state and a storage state. The rotary valve 600 includes a valve body 610 and a rod 630. The valve body 610 is mounted on the side of the first base plate 200 away from the base 100, and the rod 630 extends from the edge of the valve body 610 in a direction away from the valve body 610. The rod 630 extends radially from the edge of the valve body 610, forming a clear operating handle. When the user operates the rotary valve 600, the valve body 610 can be rotated by directly moving the rod 630, thereby allowing the rotary valve 600 to switch between the liquid filling state and the storage state without the need for additional tools, thus improving the ease of use of this embodiment.

[0072] The valve body 610 and the rod 630 are integrally formed, eliminating the need for additional connecting parts and avoiding the risk of loosening or breakage that may occur due to the assembly of multiple parts, thus improving the overall reliability of the rotary valve 600. At the same time, both the valve body 610 and the rod 630 are located on the outside of the first base plate 200, meaning that the valve body 610 has no impact on the internal flow channel, ensuring a clean and compact internal fluid path.

[0073] In one embodiment, exemplarily, such as Figures 9 to 11 As shown, the valve body 610 has a sample inlet 603 and a third connecting groove 604, and the liquid inlet 210 is connected to one end of the first flow channel 110. When the rotary valve 600 is in the liquid injection state, the rotary valve 600 is rotated to the open position, the sample inlet 603 is connected to the liquid inlet 210, and the third connecting groove 604 is connected to the second flow channel 120 and the third flow channel 130 respectively.

[0074] In detail, when the rotary valve 600 is rotated to the liquid injection state, the valve body 610 rotates to the preset position, and the sample inlet 603 coincides with the liquid inlet 210. The user can directly inject liquid into the sample inlet 603 on the valve body 610. The injected liquid will flow into the first flow channel 110 through the sample inlet 603 and the liquid inlet 210. Then, the liquid flows into the flow chamber a through the vertical channel 180, enters the second flow channel 120 through another vertical channel 180, and then flows into the third flow channel 130 through the third connecting groove 604 on the valve body 610, and continues to flow normally.

[0075] The sample dispensing port 603 is positioned on the valve body 610, making it easily visible and locating, and ensuring that its location is not obstructed by other structures or components. During liquid injection, there is no need to align the pipette tip with the tiny inlet 210; simply align the pipette tip with the sample dispensing port 603 on the valve body 610. This reduces operational difficulty, simplifies the sample dispensing process, and improves the ease of use of this embodiment.

[0076] When the rotary valve 600 is in the storage state, the valve body 610 rotates to another preset position, causing the sample inlet 603 on the valve body 610 to be misaligned with the liquid inlet 210 on the first substrate 200, thus sealing the liquid inlet 210 itself. At the same time, the third connecting groove 604 is no longer connected to the second flow channel 120 and the third flow channel 130, thereby storing the liquid in its current flow channel.

[0077] In one embodiment, exemplarily, such as Figures 9 to 11 As shown, a stop portion 614 is provided on the valve body 610 facing the first substrate 200. A limiting groove 250 is formed on the first substrate 200, and the stop portion 614 is slidably inserted into the limiting groove 250. When the stop portion 614 abuts against one end of the limiting groove 250, the rotary valve 600 is in the liquid injection state; when the stop portion 614 abuts against the other end of the limiting groove 250, the rotary valve 600 is in the storage state.

[0078] When it is necessary to switch the rotary valve 600 to the liquid injection state, the user holds the rod 630 and rotates the valve body 610 in a certain direction. The stop part 614 slides synchronously within the limiting groove 250. When the stop part 614 abuts against the first end face of the limiting groove 250, the rotation is physically blocked, and the valve body 610 stops rotating. At this time, the sample inlet 603 and the liquid inlet 210 are completely aligned, and the third connecting groove 604 is aligned with the interface between the second flow channel 120 and the third flow channel 130. In this embodiment, the liquid injection or cleaning state is entered, and the flow path is open.

[0079] When it is necessary to switch the rotary valve 600 to the storage state, the user rotates the lever 630 in the reverse direction. The stop part 614 slides in the reverse direction along the limiting groove 250. When it abuts against the second end face of the limiting groove 250, the rotation is blocked again, and the valve body 610 stops at another preset angle. At this time, the sample inlet 603 is deviated from the liquid inlet 210, the solid material of the valve body 610 covers and seals the liquid inlet 210, the third connecting groove 604 is offset from the flow channel interface, and the connection between the second flow channel 120 and the third flow channel 130 is cut off. In this embodiment, the system enters a sealed storage state, and the internal fluid is completely sealed.

[0080] The two ends of the limiting groove 250 serve as mechanical hard stops, ensuring that the valve body 610 is always in the preset position when rotated to its final position, and improving the consistency of each rotation. This avoids situations such as partial overlap between the sample inlet 603 and the liquid inlet 210, incomplete alignment of the third connecting groove 604, or poor sealing caused by manual operation deviations. Of course, when the stop part 614 impacts the end face of the limiting groove 250, the user will feel a significant change in resistance or a "click" sensation. Even without directly visually inspecting this embodiment, the user can judge by touch whether the valve has switched to the correct position.

[0081] It is also worth mentioning that the limiting groove 250 only provides stable stopping points at both ends, with no positioning structure in the middle area. If the user does not rotate it to the correct position, there will be no clear tactile feedback, thus reminding the user to avoid the dangerous state of being half-open or half-closed, and to prevent air bubble retention, slow leakage, or signal drift caused by partial blockage of the flow path.

[0082] Please see Figure 4 , Figure 6 and Figure 7 In some embodiments, the biological sample analysis device further includes a proton exchange membrane 700. The base 100 is also provided with an interaction hole 140 and a salt bridge channel 150. The salt bridge channel 150 is located on the side of the base 100 facing away from the first substrate 200. The two ends of the interaction hole 140 extend to the second channel 120 and the salt bridge channel 150, respectively. The proton exchange membrane 700 is attached to the base 100, and the proton exchange membrane 700 covers the interaction hole 140 to separate the second channel 120 and the salt bridge channel 150.

[0083] In this embodiment, the side of the base 100 facing away from the substrate has a large usable space. Designing the salt bridge channel 150 to this side can increase the volume of the salt bridge channel 150, which greatly reduces the rate of change of the concentration of related ions caused by electrochemical reactions in the salt bridge (and can maintain a stable concentration for a long time), thus improving the stability of sequencing performance; that is, the salt bridge volume needs to be set according to actual needs.

[0084] Please see Figure 2 , Figure 4 and Figure 6 In some embodiments, the biological sample analysis device further includes a platinum electrode 800, which is mounted on the second substrate 300 and is in contact with the liquid in the salt bridge channel 150. The detection end of the chip 500 is connected to the platinum electrode 800.

[0085] It is worth noting that the salt bridge achieves ion interaction through the proton exchange membrane 700 and the flow chamber a, while the salt bridge achieves electrical connection and communication through the platinum electrode plate 800 and the chip 500.

[0086] Please see Figure 1 , Figure 4 and Figure 5 In some embodiments, the biological sample analysis device further includes a sealing element 900. The first substrate 200 is provided with an injection hole 230 and an outlet hole 240. The base 100 is provided with a first through hole 160 and a second through hole 170. The injection hole 230, the first through hole 160 and the inlet end of the salt bridge channel 150 are connected. The outlet end of the salt bridge channel 150 is connected to the second through hole 170 and the outlet hole 240. The sealing element 900 is fixedly connected to the first substrate 200 and seals the injection hole 230 and the outlet hole 240.

[0087] The sealing element 900 is configured as a salt bridge sealing plate or a rubber stopper. Taking the salt bridge sealing plate as an example, the salt bridge sealing plate is attached to the first substrate 200, thereby blocking the injection hole 230 and the outlet hole 240.

[0088] In this embodiment, the base 100 serves as a flow carrier for biological samples. After the biological sample is injected through the inlet 210 of the first substrate 200, it flows through the first flow channel 110, the second flow channel 120, the flow chamber a, and the third flow channel 130, and finally flows out through the outlet 220 of the first substrate 200. This embodiment utilizes the rotary valve 600 to achieve two different positions: open and closed, thereby improving the high airtightness during production and sequencing, and extending the long shelf life during storage.

[0089] Based on the above, this embodiment also provides a biological sample analysis system, which includes a sequencer and the aforementioned biological sample analysis device, wherein the biological sample analysis device is installed on the sequencer.

[0090] Based on the above, this embodiment further explains the operating principle of the biological sample analysis system as follows: S100. Sample loading before sequencing.

[0091] Please see Figure 3 , Figure 4 , Figure 5 and Figure 6 Rotate the rotary valve 600 to the open position, inject the biological sample into the inlet 210 through a pipette, and with the continuous injection of the biological sample, the biological sample moves along the first flow channel 110 and the flow chamber a to the second flow channel 120, and then close the rotary valve 600.

[0092] S200. Sequencing.

[0093] Please see Figure 4 and Figure 6The biological sample analysis device is loaded onto the sequencer, and sequencing is performed by ion interaction between the sequencer and the salt bridge in the salt bridge channel 150 through the interaction hole 140. During the sequencing process, there is only electrical signal exchange between the sequencer and the chip 500, and no fluid flow.

[0094] S300. Cleaning after sequencing.

[0095] Please continue reading. Figure 3 , Figure 4 , Figure 5 and Figure 6 After sequencing is complete, open the rotary valve 600 again and inject cleaning solution into the inlet 210. The cleaning solution will push the biological sample into the outlet 220 channel. After cleaning, turn the rotary valve 600 to the closed position and use a pipette to remove the waste liquid from the outlet 220.

[0096] If the filter cleaning solution is injected before closing the rotary valve 600, the biological sample will flow out from the outlet 220.

[0097] S400. Storage when not in use.

[0098] After cleaning, turn the rotary valve 600 to the closed position for effective storage until the next use.

[0099] Since the biological sample analysis system provided in this embodiment includes a biological sample analysis device, this embodiment has all the advantages of a biological sample analysis device.

[0100] It should be noted that, where there is no conflict, the features in the embodiments of this application can be combined with each other.

[0101] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A biological sample analysis device, characterized in that, include: The base (100) is provided with a first flow channel (110), a second flow channel (120) and a third flow channel (130); A first substrate (200) is disposed on one side of the base (100) and fixedly connected to the base (100). The first substrate (200) is provided with a liquid inlet (210) and a liquid outlet (220). The liquid outlet (220) is connected to the third flow channel (130). A chip (500) is disposed on the side of the base (100) away from the first substrate (200), and the chip (500) is connected to the base (100) and defines a flow cavity (a). One end of the flow cavity (a) communicates with the first flow channel (110), and the other end of the flow cavity (a) communicates with the second flow channel (120); and A rotary valve (600) rotates relative to the base (100) to an open position and a closed position. When the rotary valve (600) is rotated to the open position, liquid can be injected into the first flow channel (110) through the inlet (210), and the second flow channel (120) is connected to the third flow channel (130). When the rotary valve (600) is rotated to the closed position, liquid cannot be injected into the first flow channel (110) through the inlet (210), and the second flow channel (120) is disconnected from the third flow channel (130); and / or, A vertical channel (180) is provided between the flow cavity (a) and the first flow channel (110) and / or the second flow channel (120).

2. The biological sample analysis device as described in claim 1, characterized in that, The device further includes: a second substrate (300) disposed on the side of the base (100) away from the first substrate (200); A sealing gasket (400) is disposed on the side of the second substrate (300) away from the base (100); The chip (500) is disposed on the side of the sealing gasket (400) away from the second substrate (300), and the chip (500), the sealing gasket (400) and the second substrate (300) are fixedly connected and define the flow cavity (a).

3. The biological sample analysis device as described in claim 1 or 2, characterized in that, The width of one end of the vertical channel (180) matches the width of the first flow channel (110) and / or the second flow channel (120), and the width of the other end of the vertical channel (180) matches the width of the flow cavity (a), so that the vertical channel (180) forms a variable diameter channel.

4. The biological sample analysis device as described in claim 1 or 2, characterized in that, The first flow channel (110) and / or the second flow channel (120) are provided with a variable diameter region (190) at one end near the flow cavity (a) so that the width of the end of the first flow channel (110) and / or the second flow channel (120) matches the width of the flow cavity (a), and the vertical channel (180) forms a constant diameter channel.

5. The biological sample analysis device as described in claim 4, characterized in that, The vertical channel (180) has a rectangular cross-sectional shape perpendicular to the vertical direction and a uniform thickness.

6. The biological sample analysis device as described in claim 1 or 2, characterized in that, The rotary valve (600) has a liquid injection state and a storage state. The rotary valve (600) includes a valve body (610) and an operating member (620). At least a portion of the operating member (620) is located on the side of the first base plate (200) away from the base (100). The valve body (610) is mounted on the base (100) and the valve body (610) is fixedly connected to the operating member (620).

7. The biological sample analysis device as described in claim 6, characterized in that, The valve body (610) is provided with a first connecting groove (601) and a second connecting groove (602), and the liquid inlet (210) is disconnected from the first flow channel (110); When the rotary valve (600) is in the liquid injection state, the rotary valve (600) is rotated to the open position, the first connecting groove (601) is connected to the liquid inlet (210) and the first flow channel (110) respectively, and the second connecting groove (602) is connected to the second flow channel (120) and the third flow channel (130) respectively.

8. The biological sample analysis device as described in claim 6, characterized in that, The valve body (610) is also provided with a limiting part (613), which protrudes from the valve body (610) radially. When the rotary valve (600) is rotated to the open position, the limiting part (613) abuts against the second base plate (300).

9. The biological sample analysis device as described in claim 8, characterized in that, The first flow channel (110) and the second flow channel (120) are both located on the side of the base (100) facing the first substrate (200); The third flow channel (130) includes a first flow section (131), a second flow section (132), and a third flow section (133) that are connected to each other. The first flow section (131) and the third flow section (133) are located on the side of the base (100) facing the first substrate (200), and the second flow section (132) is located on the side of the base (100) away from the first substrate (200).

10. The biological sample analysis device as described in claim 1 or 2, characterized in that, The rotary valve (600) has a liquid injection state and a storage state. The rotary valve (600) includes a valve body (610) and a rod (630). The valve body (610) is mounted on the side of the first base plate (200) away from the base (100). The rod (630) is formed at the edge of the valve body (610) extending away from the valve body (610).

11. The biological sample analysis device as described in claim 10, characterized in that, The valve body (610) is provided with a sample inlet (603) and a third connecting groove (604), and the liquid inlet (210) is connected to one end of the first flow channel (110); When the rotary valve (600) is in the liquid injection state, the rotary valve (600) is rotated to the open position, the sample inlet (603) is connected to the liquid inlet (210), and the third connecting groove (604) is connected to the second flow channel (120) and the third flow channel (130) respectively.

12. The biological sample analysis device as described in claim 10, characterized in that, A stop portion (614) is provided on the valve body (610) facing the first substrate (200), and a limiting groove (250) is formed on the first substrate (200). The stop portion (614) is slidably inserted into the limiting groove (250). When the stop part (614) abuts against one end of the limiting groove (250), the rotary valve (600) is in the liquid injection state; when the stop part (614) abuts against the other end of the limiting groove (250), the rotary valve (600) is in the storage state.

13. The biological sample analysis device as described in claim 1 or 2, characterized in that, It also includes a proton exchange membrane (700), the base (100) is further provided with an interactive hole (140) and a salt bridge channel (150), the salt bridge channel (150) is located on the side of the base (100) away from the first substrate (200), the two ends of the interactive hole (140) extend to the second channel (120) and the salt bridge channel (150) respectively, the proton exchange membrane (700) is attached to the base (100), and the proton exchange membrane (700) covers the interactive hole (140) to separate the second channel (120) and the salt bridge channel (150); it also includes a platinum electrode sheet (800), the platinum electrode sheet (800) is mounted on the second substrate (300), and the platinum electrode sheet (800) is in contact with the liquid in the salt bridge channel (150), and the detection end of the chip (500) is connected to the platinum electrode sheet (800).

14. The biological sample analysis device as described in claim 13, characterized in that, It also includes a sealing element (900). The first substrate (200) is provided with an injection hole (230) and an outlet hole (240). The base (100) is provided with a first through hole (160) and a second through hole (170). The injection hole (230), the first through hole (160) and the inlet end of the salt bridge channel (150) are connected. The outlet end of the salt bridge channel (150) is connected to the second through hole (170) and the outlet hole (240). The sealing element (900) is fixedly connected to the first substrate (200) and seals the injection hole (230) and the outlet hole (240).

15. The biological sample analysis device as described in claim 2, characterized in that, The inner edge of the sealing gasket (400) is located outside the biochemical reaction area of ​​the chip (500); The second substrate (300) is made of transparent material.

16. A biological sample analysis system, characterized in that, It includes a sequencer and a biological sample analysis device as described in any one of claims 1 to 15, wherein the biological sample analysis device is mounted on the sequencer.

Images