A biological sample analysis apparatus

Abstract

The application provides a biological sample analysis device, and relates to the technical field of gene sequencing. The biological sample analysis device comprises a base, a carrier plate, a rotary valve and a liquid suction and discharge device. The base is provided with a first flow channel. The carrier plate is arranged on the base, and a biochip is arranged on the carrier plate. The biochip cooperates with the base to form a flow chamber. One end of the flow chamber is in communication with the first flow channel. The rotary valve is rotatably arranged on the base. A sample adding groove and a first through hole are arranged in the rotary valve in communication. The first through hole is used for being in communication with the first flow channel. The liquid suction and discharge device is arranged on the base and is in communication with the flow chamber, so as to suck the liquid sample in the sample adding groove, the first through hole and / or the first flow channel into the flow chamber. The biological sample analysis device can effectively reduce the difficulty of sample adding.

Description

Technical Field

[0001] This application relates to the field of gene sequencing technology, and more specifically, to a biological sample analysis device. Background Technology

[0002] With the rapid development of gene sequencing technology, sequencing chips, as a core component of high-throughput sequencing, directly affect the accuracy and efficiency of sequencing results. In existing sequencing workflows, precise sample and reagent loading is one of the key steps to ensure sequencing quality. Currently, mainstream sequencing platforms generally achieve precise dispensing of trace amounts of liquid through the design of sample loading wells.

[0003] Automating the entire library preparation and sequencing process is an industry trend. Currently, the most popular method is to use a pipetting workstation. However, using a pipette in a pipetting workstation to complete the sample addition process requires ensuring a seal between the pipette tip and the chip sample addition port. This places very high demands on the spatial positioning accuracy of the pipette tip and the fixed position of the chip within the pipetting workstation, making it extremely difficult to achieve. Utility Model Content

[0004] The purpose of this application includes, for example, providing a biological sample analysis device that can effectively reduce the difficulty of sample addition.

[0005] The embodiments of this application can be implemented as follows:

[0006] Embodiments of this application provide a biological sample analysis device, which includes:

[0007] A base, wherein a first flow channel is provided on the base;

[0008] A carrier plate is disposed on the base, and a biochip is disposed on the carrier plate. The biochip and the base cooperate to form a flow chamber, and one end of the flow chamber is connected to the first flow channel.

[0009] A rotary valve is rotatably mounted on the base. The rotary valve has a connected sample loading groove and a first through hole, which is used to connect with the first flow channel.

[0010] A liquid aspiration and drainage device is disposed on the base and communicates with the flow chamber to aspirate liquid samples from the sample loading tank, the first through hole and / or the first flow channel into the flow chamber.

[0011] Optionally, the base is further provided with a second flow channel, the other end of the flow chamber is connected to the second flow channel, and the liquid suction and discharge device is connected to the second flow channel.

[0012] Optionally, the rotary valve includes an upper rotary valve part and a lower rotary valve part connected to each other, the sample loading groove and the first through hole are both opened in the upper rotary valve part, and the lower rotary valve part is provided with a drive groove;

[0013] The opening of the sample loading groove faces upward, and the inner bottom surface of the sample loading groove is an inclined surface. The first through hole is located at the lowest point of the inclined surface.

[0014] Optionally, the upper part of the rotary valve includes a first valve body and a second valve body connected to each other. The first valve body is connected to the lower part of the rotary valve. The sample loading groove is opened in the first valve body. The first through hole passes through the first valve body and the second valve body. The second valve body is made of a flexible sealing material and fits against the base to achieve a seal.

[0015] Optionally, the liquid suction and discharge device includes a housing, a piston, and a drive screw. The housing is disposed on the base, the piston is movably disposed within the housing, and the drive screw is disposed on the housing and connected to the piston to drive the piston to move within the housing.

[0016] The housing has a second through hole, which is connected to the second flow channel.

[0017] Optionally, the housing is detachably connected to the base, and the housing is provided with a sealing ring at the point of communication with the second through hole.

[0018] Optionally, the base includes a substrate and a cover plate connected together, the carrier plate is disposed on the side of the substrate away from the cover plate, the first flow channel and the second flow channel are formed between the substrate and the cover plate, the flow chamber is formed between the biochip and the substrate, and the cover plate is provided with a third through hole communicating with the first flow channel.

[0019] When the rotary valve is in the sample feeding state, the first through hole is connected to the third through hole;

[0020] When the rotary valve is in a stored state, the first through hole and the third through hole are not connected.

[0021] Optionally, the rotary valve is provided with a first connecting groove and a second connecting groove, and the base plate is provided with a first production flow channel and a second production flow channel;

[0022] When the rotary valve is in production mode, both the first production flow channel and the second flow channel are connected to the first connecting groove, and both the second production flow channel and the first flow channel are connected to the second connecting groove.

[0023] Optionally, the cover plate is provided with a fourth through hole communicating with the second flow channel, a fifth through hole communicating with the first production flow channel, and a sixth through hole communicating with the second production flow channel.

[0024] When the rotary valve is in production, the fourth and fifth through holes are both connected to the first connecting groove, and the third and sixth through holes are both connected to the second connecting groove.

[0025] Optionally, both the first connecting groove and the second connecting groove are arc-shaped grooves.

[0026] Optionally, the first flow channel includes a first horizontal flow channel and a first vertical flow channel that are connected to each other, the third through hole is connected to the first horizontal flow channel, and the first vertical flow channel is connected to the flow chamber.

[0027] Optionally, the second flow channel includes a second horizontal flow channel and a second vertical flow channel that are connected to each other, the second vertical flow channel being connected to the flow chamber; the liquid suction and discharge device is connected to the second horizontal flow channel to draw liquid from the first flow channel into the flow chamber.

[0028] Optionally, the carrier plate is disposed on the side of the substrate away from the cover plate, and at least the portion of the substrate corresponding to the biochip is made of transparent material, and the cover plate has an observation window that matches the position of the biochip.

[0029] Optionally, a sealing gasket is provided between the biochip and the substrate.

[0030] Optionally, the substrate and the cover plate are laser welded, thermo-press bonded, or bonded.

[0031] The beneficial effects of the biological sample analysis device provided in this application include, for example, that by cooperating with the rotary valve and the aspiration / discharge device, it is not necessary to insert the pipette tip into the sample loading port. Instead, the liquid sample is simply added to the sample loading slot on the rotary valve using the pipette. Then, a certain volume of liquid sample is first discharged through the aspiration / discharge device, thereby purging air bubbles from the sample loading slot, the first through-hole, and the first flow channel. Finally, the liquid sample is actively aspirated and introduced from the sample loading slot through the first through-hole and the first flow channel into the flow chamber. This design eliminates stringent requirements on details such as pipette tip insertion depth and sealing, significantly reducing the need for precise positioning of the pipetting workstation, and making the sample loading process more convenient and reliable. Attached Figure Description

[0032] 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.

[0033] Figure 1 This is a schematic diagram of the overall structure of the biological sample analysis device in the embodiments of this application;

[0034] Figure 2 This is an exploded view of the biological sample analysis device in the embodiments of this application;

[0035] Figure 3 This is a cross-sectional view of the biological sample analysis device in an embodiment of this application;

[0036] Figure 4 This is an exploded view of the rotary valve in an embodiment of this application;

[0037] Figure 5 This is a cross-sectional view of the upper part of the rotary valve in an embodiment of this application;

[0038] Figure 6 This is a schematic diagram of the liquid suction and discharge device in the embodiments of this application;

[0039] Figure 7 This is a partial cross-sectional view of a biological sample analysis device illustrating the communication relationship between the liquid aspiration and drainage device and the second flow channel in an embodiment of this application.

[0040] Figure 8 This is a schematic diagram of the cover plate in an embodiment of this application;

[0041] Figure 9 This is a schematic diagram of the rotary valve in the sample feeding state in an embodiment of this application;

[0042] Figure 10 This is a schematic diagram of the rotary valve in its stored state in an embodiment of this application;

[0043] Figure 11 This is a schematic diagram of the substrate in an embodiment of this application;

[0044] Figure 12 This is a schematic diagram of the rotary valve in its production state in an embodiment of this application;

[0045] Figure 13 This is a schematic diagram of the carrier board in an embodiment of this application.

[0046] Icons: 100 - Base; 110 - First flow channel; 111 - First horizontal flow channel; 112 - First vertical flow channel; 120 - Second flow channel; 121 - Second horizontal flow channel; 1211 - Main flow section; 1212 - Bypass flow section; 122 - Second vertical flow channel; 130 - Substrate; 131 - First production flow channel; 132 - Second production flow channel; 140 - Cover plate; 141 - Third through hole; 142 - Fourth through hole; 143 - Fifth through hole; 144 - Sixth through hole; 145 - Observation window;

[0047] 200 - Carrier plate; 210 - Biochip; 220 - Flow chamber; 230 - Sealing gasket; 240 - Second screw;

[0048] 300 - Rotary valve; 310 - Sample loading groove; 320 - First through hole; 330 - Upper part of rotary valve; 331 - First valve body; 332 - Second valve body; 3321 - First connecting groove; 3322 - Second connecting groove; 340 - Lower part of rotary valve; 341 - Drive groove; 350 - First screw;

[0049] 400-Liquid suction and discharge device; 410-Housing shell; 411-Second through hole; 412-Sealing ring; 413-Limiting block; 420-Piston; 430-Drive screw. Detailed Implementation

[0050] 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.

[0051] Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of the application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0052] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0053] In the description of this application, it should be noted that if terms such as "upper," "lower," "inner," or "outer" are used to indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the product of the invention is usually placed during use, they are only for the convenience of describing this application 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, and therefore should not be construed as a limitation of this application.

[0054] Furthermore, the terms "first" and "second" are used only to distinguish descriptions and should not be interpreted as indicating or implying relative importance.

[0055] It should be noted that, where there is no conflict, the features in the embodiments of this application can be combined with each other.

[0056] Traditional sequencing chips typically rely on pipettes to inject samples or reagents into the wells via the pipette tip during sample loading. This method demands high alignment accuracy between the pipette tip and the well, especially in automated systems (such as pipetting workstations). The equipment must possess extremely high positioning control capabilities to ensure accurate tip insertion and effective seal; otherwise, leakage or air bubbles will be introduced, affecting the reliability of experimental results. Therefore, this loading method is not only complex but also highly dependent on the mechanical precision of the equipment, increasing the difficulty of practical use.

[0057] Please refer to Figures 1-3 This application provides a biological sample analysis device, including a base 100, a carrier plate 200, a rotary valve 300, and a liquid aspiration / discharge device 400. The base 100 is provided with a first flow channel 110. The carrier plate 200 is disposed on the base 100 and a biochip 210 is disposed on the carrier plate 200. The biochip 210 and the base 100 cooperate to form a flow chamber 220, and one end of the flow chamber 220 is connected to the first flow channel 110. The rotary valve 300 is rotatably disposed on the base 100 and has a connected sample loading groove 310 and a first through hole 320. The first through hole 320 is used to connect with the first flow channel 110. The liquid aspiration / discharge device 400 is disposed on the base 100 and communicates with the flow chamber 220 to draw liquid samples from the sample loading groove 310, the first through hole 320, and / or the first flow channel 110 into the flow chamber 220.

[0058] The first flow channel 110 guides the liquid sample into the flow chamber 220. A biochip 210 is mounted on the carrier plate 200. The biochip 210, together with the base 100, forms the flow chamber 220, which serves as the main area for the liquid sample to undergo biological reactions. One end of the flow chamber 220 is introduced into the liquid sample through the first flow channel 110. In this embodiment, the biochip 210 is a sequencing chip, such as a nanopore sequencing chip; the carrier plate 200 is mainly a PCB board, on which some electronic components are mounted, and adhesive layers for encapsulation are also provided on both sides of the biochip 210.

[0059] The rotary valve 300 is equipped with a connected sample loading groove 310 and a first through hole 320. The sample loading groove 310 serves as a sample storage area, with its opening facing upwards for easy addition of liquid samples. The first through hole 320 is used to guide the liquid sample in the sample loading groove 310 into the first flow channel 110, thereby establishing a liquid pathway from the sample loading groove 310 to the flow chamber 220. The suction and discharge device 400 is mounted on the base 100. Its function is to use suction to draw the liquid sample present in the sample loading groove 310, the first through hole 320, and the first flow channel 110 into the flow chamber 220, allowing the sample to complete subsequent reactions with the biochip 210 within the flow chamber 220.

[0060] The opening diameter of the sample loading groove 310 is 1.5 to 3 times or more the diameter of the pipette tip. The first through hole 320 is located at the edge of the rotary valve 300 away from its rotation center to allow for adjustment of the position of the first through hole 320. In this embodiment, the first through hole 320 is a through hole extending axially along the rotary valve 300 to shorten the flow path. Of course, in other embodiments, the first through hole 320 can also be a curved through hole, depending on the actual needs.

[0061] By cooperating with the rotary valve 300 and the aspiration / discharge device 400, it is unnecessary to insert the pipette tip into the sample application port. Instead, the liquid sample is simply added to the sample application slot 310 on the rotary valve 300 using the pipette. Then, the aspiration / discharge device 400 pushes back to expel air bubbles from the sample application slot 310, the first through-hole 320, and the first flow channel 110. The aspiration / discharge device 400 then draws in the liquid sample and introduces it from the sample application slot 310 through the first through-hole 320 and the first flow channel 110 into the flow chamber 220. This design eliminates stringent requirements on details such as pipette tip insertion depth and sealing, significantly reducing the need for precise positioning on the pipetting workstation and making the sample application process more convenient.

[0062] In some embodiments, the base 100 is further provided with a second flow channel 120, the other end of the flow chamber 220 is connected to the second flow channel 120, and the liquid suction and discharge device 400 is connected to the second flow channel 120.

[0063] In addition to a first flow channel 110 for introducing liquid samples into the flow chamber 220, the base 100 also has a second flow channel 120. This second flow channel 120 serves as an outlet channel for the liquid sample after it completes its flow path within the flow chamber 220, and it is simultaneously connected to both the flow chamber 220 and the liquid suction / discharge device 400. This arrangement allows the liquid suction / discharge device 400 to discharge the liquid sample from the flow chamber 220 through the second flow channel 120, thereby forming a complete liquid flow path within the flow chamber 220 and improving the flow efficiency and uniformity of the liquid sample within the flow chamber 220.

[0064] When the aspiration and dissipation device 400 is working, the negative pressure it generates not only causes the liquid sample in the sample loading tank 310 to sequentially enter the flow chamber 220 through the first through-hole 320 and the first flow channel 110, but also draws out the liquid sample from the flow chamber 220 through the second flow channel 120. This guides the liquid sample to flow within the flow chamber 220, avoiding problems such as stagnation or uneven distribution of the liquid sample. This ensures that the liquid sample can fully contact the surface of the biochip 210 within the flow chamber 220, providing more stable reaction conditions for subsequent biological reactions. For example, when the biochip 210 is a nanopore sequencing chip, the liquid sample can fully react with the nanopore sequencing chip within the flow chamber 220 to undergo predetermined reactions such as the formation of amphiphilic layers, bio-pore embedding, and through-pore sequencing.

[0065] Please refer to Figure 4 , Figure 5 In some embodiments, the rotary valve 300 includes an upper rotary valve 330 and a lower rotary valve 340 connected to each other. The sample loading groove 310 and the first through hole 320 are both opened in the upper rotary valve 330, and the lower rotary valve 340 is provided with a drive groove 341. The opening of the sample loading groove 310 faces upward, the inner bottom surface of the sample loading groove 310 is a slope, and the first through hole 320 is located at the lowest inclined end of the slope.

[0066] The sample loading groove 310 and the first through hole 320 are both located on the upper part 330 of the rotary valve, while the lower part 340 of the rotary valve is provided with a drive groove 341. The function of the drive groove 341 is to cooperate with the external drive mechanism. The external drive mechanism drives the entire rotary valve 300 to rotate on the base 100 by inserting into the drive groove 341 and applying rotational force, thereby realizing the switching of the flow path state.

[0067] The opening of the sample loading tank 310 faces upward, making it easy for the pipette to add liquid samples into it. The inner bottom surface of the sample loading tank 310 has a sloping structure, and its sloping direction makes the lowest point of the tank bottom correspond to the inlet position of the first through hole 320. This sloping design helps the liquid sample to flow automatically to the first through hole 320 under the action of gravity, reducing the possibility of liquid sample residue in the sample loading tank 310, thereby improving the sample loading efficiency and sample utilization rate.

[0068] Optionally, the upper part 330 and the lower part 340 of the rotary valve can be connected by a first screw 350, which passes through the lower part 340 and the upper part 330 of the rotary valve from bottom to top, so that the upper part 330 and the lower part 340 of the rotary valve are connected as one unit.

[0069] In this embodiment, the upper part 330 of the rotary valve includes a first valve body part 331 and a second valve body part 332 connected to each other. The first valve body part 331 is connected to the lower part 340 of the rotary valve. The sample loading groove 310 is opened in the first valve body part 331. The first through hole 320 passes through the first valve body part 331 and the second valve body part 332. The second valve body part 332 is made of flexible sealing material and fits against the base 100 to achieve sealing.

[0070] The sample loading slot 310 is formed on the first valve body 331 and serves as a temporary storage area for liquid samples. The first through hole 320 penetrates the first valve body 331 and the second valve body 332, serving as a communication path between the sample loading slot 310 and the first flow channel 110, allowing the liquid sample to enter the first flow channel 110 through the first through hole 320 and finally flow into the flow chamber 220.

[0071] The second valve body 332 is fixedly connected to the first valve body 331. The second valve body 332 is made of a flexible sealing material, such as an elastic polymer material or other flexible material suitable for achieving a sealing function. The second valve body 332 is fitted to the surface of the base 100, and through its material properties, it maintains close contact with the base 100 during the rotation of the rotary valve 300, thereby effectively preventing liquid samples from leaking from the gap between the rotary valve 300 and the base 100 when the rotary valve 300 is in different states.

[0072] Please refer to Figure 6 , Figure 7 In some embodiments, the liquid suction and discharge device 400 includes a housing 410, a piston 420, and a drive screw 430. The housing 410 is disposed on the base 100, the piston 420 is movably disposed inside the housing 410, and the drive screw 430 is disposed on the housing 410 and connected to the piston 420 to drive the piston 420 to move inside the housing 410. A second through hole 411 is provided on the housing 410, and the second through hole 411 is connected to the second flow channel 120.

[0073] The aspiration and dissipation device 400 is a key component for actively drawing liquid samples from the sample loading tank 310 into the flow chamber 220 and discharging air bubbles from the liquid sample's flow path. Its core function is achieved through the cooperation of the housing 410 and the piston 420. The housing 410 is a closed cavity with a certain volume, its internal space accommodating the piston 420 and allowing it to move within it. A second through-hole 411 is provided on the housing 410, the position of which corresponds to the second flow channel 120 on the base 100, thus establishing communication between the two when the aspiration and dissipation device 400 is installed on the base 100. This design allows the aspiration and dissipation device 400 to control the suction and dissipation of liquid through the movement of the piston 420. After purging air bubbles from the sample loading tank 310, the first through-hole 320, and the first flow channel 110, it guides the liquid sample from the flow chamber 220 into the second flow channel 120.

[0074] The piston 420 is movably disposed within the housing 410. When the drive screw 430 rotates and applies a pushing or pulling action to the piston 420, the piston 420 will move axially within the housing 410, thereby changing the internal volume of the housing 410. When the piston 420 is pushed inward, air bubbles in the sample loading groove 310, the first through hole 320, and the first flow channel 110 are emptied. When the piston 420 is pulled outward, a negative pressure is formed inside the housing 410, causing the liquid sample to flow from the flow chamber 220 into the second flow channel 120.

[0075] To achieve precise adjustment of the piston 420's displacement, the piston 420 is provided with a threaded hole. When the drive screw 430 is inserted into and engaged with the threaded hole, the piston 420 can be moved axially within the housing 410 by rotating the drive screw 430. A limiting block 413 can be provided on the base 100 to restrict the movement of the drive screw 430. The limiting block 413 and the base 100 can be optionally engaged in a snap-fit ​​manner. The limiting block 413 enables the drive screw 430 to rotate only, thereby causing the piston 420 to move linearly. This threaded transmission method is not only compact and stable in transmission, but also enables precise control of the piston 420's displacement, thereby improving the controllability of the liquid sample aspiration of the liquid suction and discharge device 400.

[0076] When the external drive device starts and drives the drive screw 430 to rotate, due to the threaded engagement between the piston 420 and the drive screw 430, the piston 420 will move linearly in a predetermined direction within the housing 410. For example, if the drive screw 430 rotates in the forward direction, the piston 420 will move inward into the housing 410, compressing the internal space of the housing 410, creating positive pressure, and expelling air bubbles; if the drive screw 430 rotates in the reverse direction, the piston 420 will move outward, increasing the internal volume of the housing 410, creating negative pressure, thereby causing the liquid sample to flow from the flow chamber 220 into the second flow channel 120.

[0077] In some embodiments, the housing 410 is detachably connected to the base 100, and the housing 410 is provided with a sealing ring 412 at the point of communication with the second through hole 411.

[0078] The housing 410 and the base 100 are detachably connected, for example by snap-fit, screw, plug-in, or magnetic attraction, allowing the liquid aspiration / discharge device 400 to be installed or removed from the base 100 as an independent module. This detachable design not only facilitates equipment maintenance and replacement but also improves the adaptability of the equipment in different application scenarios. For example, during the use of different batches of the biochip 210, the liquid aspiration / discharge device 400 can be replaced according to actual needs.

[0079] The housing 410 is provided with a sealing ring 412 at a position communicating with the second through hole 411. The sealing ring 412 is typically made of a flexible elastic material, such as silicone, rubber, or other polymeric materials suitable for achieving fluid sealing. When the housing 410 is mounted on the base 100, the sealing ring 412 is compressed to form a tightly fitting sealing interface, thereby preventing leakage of liquid samples between the housing 410 and the base 100.

[0080] In some embodiments, the base 100 includes a substrate 130 and a cover plate 140 connected together, a first flow channel 110 and a second flow channel 120 are formed between the substrate 130 and the cover plate 140, and a flow chamber 220 is formed between the biochip 210 and the substrate 130. Figure 8 As shown, the cover plate 140 is provided with a third through hole 141 that communicates with the first flow channel 110; as Figure 9 As shown, when the rotary valve 300 is in the sample feeding state, the first through hole 320 is connected to the third through hole 141; Figure 10 As shown, the rotary valve 300 is in a stored state, and the first through hole 320 and the third through hole 141 are not connected.

[0081] The base 100 is composed of a substrate 130 and a cover plate 140. The substrate 130 and the cover plate 140 are connected by a sealing method such as laser welding, hot pressing bonding or adhesive bonding, thereby forming a first flow channel 110 and a second flow channel 120 between the substrate 130 and the cover plate 140. The adhesive bonding method can be glue bonding or double-sided adhesive bonding.

[0082] A carrier plate 200 is disposed on the side of the substrate 130 opposite to the cover plate 140, i.e., in the area below the substrate 130. A biochip 210 is mounted on the carrier plate 200. The carrier plate 200 and the substrate 130 are fixed together by second screws 240. For example, second screws 240 are provided at each of the four corners of the carrier plate 200 to ensure a stable connection between the carrier plate 200 and the bottom of the substrate 130. A flow chamber 220 is formed between the biochip 210 and the substrate 130, serving as the main area for biological reactions of the liquid sample. One end of the flow chamber 220 is connected to the first flow channel 110, and the other end is connected to the second flow channel 120, thereby forming a complete liquid flow path under the action of the liquid aspiration and dissipation device 400.

[0083] The cover plate 140 is provided with a third through hole 141, which is connected to the first flow channel 110 and serves as an interface for establishing a fluid connection between the rotary valve 300 and the base 100. When the rotary valve 300 is in the sample feeding state, the first through hole 320 on the rotary valve 300 is aligned with the third through hole 141 on the cover plate 140, forming a continuous passage from the sample feeding tank 310 through the first through hole 320 and the third through hole 141 to the first flow channel 110, allowing the liquid sample to smoothly enter the flow chamber 220. When the rotary valve 300 is in the storage state, the rotary valve 300 rotates until the first through hole 320 is offset from the third through hole 141, and the first through hole 320 and the third through hole 141 are no longer connected, thereby cutting off the liquid sample transmission path and keeping the flow chamber 220 in a closed state to prevent liquid leakage or external contamination.

[0084] In this embodiment, the rotary valve 300 is provided with a first connecting groove 3321 and a second connecting groove 3322, combined with Figure 11 As shown, a first production flow channel 131 and a second production flow channel 132 are formed on the substrate 130; as Figure 12 As shown, when the rotary valve 300 is in production, the first production flow channel 131 and the second flow channel 120 are both connected to the first connecting groove 3321, and the second production flow channel 132 and the first flow channel 110 are both connected to the second connecting groove 3322.

[0085] The second valve body 332 is attached to the cover plate 140. A first connecting groove 3321 and a second connecting groove 3322 are formed on the surface of the second valve body 332 that is attached to the cover plate 140. These two connecting grooves serve as fluid interfaces for the rotary valve 300 in the production state, establishing different liquid communication paths. Specifically, the base plate 130 is provided with a first production flow channel 131 and a second production flow channel 132, used to introduce the liquid sample required for production and to discharge the liquid sample after the reaction, respectively. When the rotary valve 300 is in the production state, the rotary valve 300 rotates until the first connecting groove 3321 is simultaneously connected to the first production flow channel 131 and the second flow channel 120, and simultaneously the second connecting groove 3322 is simultaneously connected to the first flow channel 110 and the second production channel 132.

[0086] In the specific operation, the liquid sample enters the device through the first production channel 131, flows into the second channel 120 via the first connecting groove 3321, and then enters the flow chamber 220 to react with the surface of the biochip 210. If there is excess liquid after the reaction, the reacted liquid and the excess liquid flow together from the other end of the flow chamber 220 through the first channel 110 into the second connecting groove 3322, and finally exit the device through the second production channel 132. This design allows the device to form a complete flow path from the first production channel 131 to the second production channel 132 in production mode, facilitating the continuous supply of reagents in automated production or testing processes.

[0087] It is understood that the liquid sample can also enter the equipment through the second production channel 132, and flow into the first channel 110 through the second connecting groove 3322, and then enter the flow chamber 220 to react with the surface of the biochip 210; if there is excess liquid after the reaction, the liquid after the reaction and the excess liquid together enter the first connecting groove 3321 through the second channel 120 from the other end of the flow chamber 220, and finally exit the equipment through the first production channel 131.

[0088] In this embodiment, the cover plate 140 is provided with a fourth through hole 142 connected to the second flow channel 120, a fifth through hole 143 connected to the first production flow channel 131, and a sixth through hole 144 connected to the second production flow channel 132; when the rotary valve 300 is in the production state, the fourth through hole 142 and the fifth through hole 143 are both connected to the first connecting groove 3321, and the third through hole 141 and the sixth through hole 144 are both connected to the second connecting groove 3322.

[0089] The cover plate 140 not only encapsulates the first flow channel 110 and the second flow channel 120, but also provides interfaces for establishing fluid connections between the rotary valve 300 and different flow channels through multiple through holes. Specifically, the cover plate 140 has a fourth through hole 142, a fifth through hole 143, and a sixth through hole 144. The fourth through hole 142 is connected to the second flow channel 120, the fifth through hole 143 is connected to the first production flow channel 131, and the sixth through hole 144 is connected to the second production flow channel 132. The positions of these through holes correspond to the first connecting groove 3321 and the second connecting groove 3322 on the rotary valve 300. When the rotary valve 300 is in production, the rotary valve 300 rotates until the first connecting groove 3321 is simultaneously connected to the fourth through hole 142 and the fifth through hole 143, and the second connecting groove 3322 is simultaneously connected to the third through hole 141 and the sixth through hole 144.

[0090] When the equipment enters production mode, the external liquid supply system introduces the liquid sample required for production into the fifth through-hole 143 through the first production flow channel 131, and then flows into the second flow channel 120 through the first connecting groove 3321 and the fourth through-hole 142. Subsequently, the liquid enters the flow chamber 220 and reacts with the surface of the biochip 210. The reacted liquid sample then enters the third through-hole 141 through the first flow channel 110 from the other end of the flow chamber 220, and enters the sixth through-hole 144 through the second connecting groove 3322, and finally exits the equipment through the second production flow channel 132.

[0091] Both the first connecting groove 3321 and the second connecting groove 3322 are arc-shaped grooves, and the rotary valve 300 is circular. The center of the first connecting groove 3321 and the second connecting groove 3322 is the center of the rotary valve 300. In other embodiments, the first connecting groove 3321 and the second connecting groove 3322 may also be straight or irregular in shape, and there is no limitation thereto.

[0092] In this embodiment, the first flow channel 110 includes a first horizontal flow channel 111 and a first vertical flow channel 112 that are connected to each other. The third through hole 141 is connected to the first horizontal flow channel 111, and the first vertical flow channel 112 is connected to the flow chamber 220.

[0093] The first vertical flow channel 112, as an extension of the first horizontal flow channel 111, runs perpendicular to the first horizontal flow channel 111 and penetrates the substrate 130 to connect with the flow chamber 220. This design allows the liquid sample to smoothly change direction after flowing through the first horizontal flow channel 111 and enter the flow chamber 220 along the first vertical flow channel 112, thereby realizing the transfer of the liquid sample from the rotary valve 300 to the surface of the biochip 210. This flow channel structure formed by the horizontal and vertical flow channels helps to rationally arrange the flow path within a limited space.

[0094] In this embodiment, the second flow channel 120 includes a second horizontal flow channel 121 and a second vertical flow channel 122 that are connected to each other. The second vertical flow channel 122 is connected to the flow chamber 220. The liquid suction and discharge device 400 is connected to the second horizontal flow channel 121 to draw the liquid in the first flow channel 110 into the flow chamber 220.

[0095] The second horizontal flow channel 121 is an extension of the second vertical flow channel 122. The second horizontal flow channel 121 and the first horizontal flow channel 111 are located on the same horizontal plane. The second horizontal flow channel 121 includes a main flow section 1211 and a bypass section 1212. One end of the main flow section 1211 is connected to the second vertical flow channel 122. The main flow section 1211 is L-shaped. The end of the main flow section 1211 away from the second vertical flow channel 122 is connected to the non-end position of the bypass section 1212. One end of the bypass section 1212 is close to the rotary valve 300. The other end of the bypass section 1212 is connected to the second through hole 411 on the housing 410. The liquid suction and discharge device 400 is connected to one end of the bypass section 1212 through the second through hole 411 on the housing 410, and the bypass section 1212 is connected to the main section 1211. Thus, when the liquid suction and discharge device 400 is working, it can apply negative pressure to the inside of the main section 1211 to suck up the sample or apply positive pressure to discharge the air bubbles in the flow channel.

[0096] When the biological sample analysis equipment is in production, liquid samples can enter the equipment through the first production channel 131, flow into the bypass section 1212 through the first connecting channel 3321, then flow into the main channel 1211 from the bypass section 1212, and then enter the flow chamber 220 to react with the biochip 210.

[0097] In some embodiments, at least the portion of the substrate 130 corresponding to the biochip 210 is made of transparent material, and the cover plate 140 has an observation window 145 that matches the position of the biochip 210.

[0098] The biochip 210 mounted on the carrier plate 200 serves as the core area for sample reaction. It forms a flow chamber 220 with the substrate 130. The liquid sample enters the flow chamber 220 through the first flow channel 110 and completes the flow and reaction process under the drive of the liquid aspiration and dissipation device 400.

[0099] Specifically, the substrate 130 is made of a transparent material, such as transparent glass, quartz, or transparent polymer material, in the area corresponding to the biochip 210, to allow light to pass through and enable observation of the biological reaction process within the flow chamber 220. Simultaneously, the cover plate 140 has an observation window 145 that matches the position of the biochip 210. When the device is assembled, the observation window 145 faces the area where the biochip 210 is located, and together with the transparent portion of the substrate 130, forms an observation path from the outside of the device to the surface of the biochip 210. This design allows users or detection systems (such as microscopic imaging systems, fluorescence detection modules, etc.) to observe and acquire images of the biological reaction process within the flow chamber 220 in real time through the observation window 145 and the transparent area of ​​the substrate 130.

[0100] Please combine Figure 13 In this embodiment, a sealing gasket 230 is provided between the biochip 210 and the substrate 130.

[0101] To ensure good sealing of the flow chamber 220 during liquid sample flow, a sealing gasket 230 is provided between the biochip 210 and the substrate 130. This sealing gasket 230 can be made of a flexible material, such as silicone, rubber, or other elastic and chemically stable polymers. The sealing gasket 230 is annular in shape, matching the boundary contour of the biochip 210, and is positioned around the periphery of the flow chamber 220 to form a closed sealing interface between the biochip 210 and the substrate 130.

[0102] After the equipment is assembled, the sealing gasket 230 is compressed between the biochip 210 and the substrate 130 to form a seal, thereby effectively preventing liquid samples from leaking from the flow chamber 220 to the outside. The sealing gasket 230 is not only suitable for the liquid introduction process in the sample loading state, but also for liquid sealing in the storage state and continuous liquid flow in the production state, providing effective sealing when the equipment is in the sample loading state, storage state, and production state.

[0103] In summary, this application provides a biological sample analysis device, which includes a base 100, a carrier plate 200, a rotary valve 300, and a liquid aspiration / discharge device 400. Through the cooperation of the rotary valve 300 and the liquid aspiration / discharge device 400, it is not necessary to insert the pipette tip into the sample application port. Instead, the liquid sample is simply added to the sample application slot 310 on the rotary valve 300 using a pipette. Then, the liquid aspiration / discharge device 400 pushes back to expel air bubbles from the sample application slot 310, the first through hole 320, and the first flow channel 110. The liquid sample is then actively aspirated and introduced from the sample application slot 310 through the first through hole 320 and the first flow channel 110 into the flow chamber 220. This eliminates the stringent requirements for details such as the insertion depth of the pipette tip and the sealing performance, significantly reducing the need for positioning accuracy of the pipetting workstation and making the sample application process more convenient.

[0104] The above description is merely a specific embodiment of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. A biological sample analysis device, characterized in that, include: A base (100) is provided with a first flow channel (110); A carrier plate (200) is disposed on the base (100), and a biochip (210) is disposed on the carrier plate (200). The biochip (210) and the base (100) cooperate to form a flow chamber (220), and one end of the flow chamber (220) is connected to the first flow channel (110). A rotary valve (300) is rotatably mounted on the base (100). The rotary valve (300) has a connected sample loading groove (310) and a first through hole (320), which is used to communicate with the first flow channel (110). A liquid suction and discharge device (400) is disposed on the base (100) and communicates with the flow chamber (220) to draw liquid samples from the sample loading tank (310), the first through hole (320) and / or the first flow channel (110) into the flow chamber (220).

2. The biological sample analysis device according to claim 1, characterized in that, The base (100) is also provided with a second flow channel (120), the other end of the flow chamber (220) is connected to the second flow channel (120), and the liquid suction and discharge device (400) is connected to the second flow channel (120).

3. The biological sample analysis device according to claim 1, characterized in that, The rotary valve (300) includes an upper rotary valve part (330) and a lower rotary valve part (340) connected to each other. The sample loading groove (310) and the first through hole (320) are both opened in the upper rotary valve part (330), and the lower rotary valve part (340) is provided with a drive groove (341). The opening of the sample loading groove (310) faces upward, the inner bottom surface of the sample loading groove (310) is inclined, and the first through hole (320) is located at the lowest inclined end of the inclined surface.

4. The biological sample analysis device according to claim 3, characterized in that, The upper part (330) of the rotary valve includes a first valve body part (331) and a second valve body part (332) connected to each other. The first valve body part (331) is connected to the lower part (340) of the rotary valve. The sample loading groove (310) is opened in the first valve body part (331). The first through hole (320) passes through the first valve body part (331) and the second valve body part (332). The second valve body part (332) is made of flexible sealing material. The second valve body part (332) fits against the base (100) to achieve sealing.

5. The biological sample analysis device according to claim 2, characterized in that, The liquid suction and discharge device (400) includes a housing (410), a piston (420), and a drive screw (430). The housing (410) is disposed on the base (100). The piston (420) is movably disposed within the housing (410). The drive screw (430) is disposed on the housing (410) and connected to the piston (420) to drive the piston (420) to move within the housing (410). The housing (410) has a second through hole (411) which is connected to the second flow channel (120).

6. The biological sample analysis device according to claim 5, characterized in that, The housing (410) is detachably connected to the base (100), and the housing (410) is provided with a sealing ring (412) at the point where it communicates with the second through hole (411).

7. The biological sample analysis device according to claim 2, characterized in that, The base (100) includes a substrate (130) and a cover plate (140) connected to each other. The carrier plate (200) is disposed on the side of the substrate (130) away from the cover plate (140). The first flow channel (110) and the second flow channel (120) are formed between the substrate (130) and the cover plate (140). The flow chamber (220) is formed between the biochip (210) and the substrate (130). The cover plate (140) is provided with a third through hole (141) communicating with the first flow channel (110). When the rotary valve (300) is in the sample feeding state, the first through hole (320) is connected to the third through hole (141); When the rotary valve (300) is in a stored state, the first through hole (320) and the third through hole (141) are not connected.

8. The biological sample analysis device according to claim 7, characterized in that, The rotary valve (300) has a first connecting groove (3321) and a second connecting groove (3322), and the substrate (130) has a first production flow channel (131) and a second production flow channel (132). When the rotary valve (300) is in production, the first production flow channel (131) and the second flow channel (120) are both connected to the first connecting groove (3321), and the second production flow channel (132) and the first flow channel (110) are both connected to the second connecting groove (3322).

9. The biological sample analysis device according to claim 8, characterized in that, The cover plate (140) is provided with a fourth through hole (142) communicating with the second flow channel (120), a fifth through hole (143) communicating with the first production flow channel (131), and a sixth through hole (144) communicating with the second production flow channel (132). When the rotary valve (300) is in production, the fourth through hole (142) and the fifth through hole (143) are both connected to the first connecting groove (3321), and the third through hole (141) and the sixth through hole (144) are both connected to the second connecting groove (3322).

10. The biological sample analysis device according to claim 8, characterized in that, Both the first connecting groove (3321) and the second connecting groove (3322) are arc-shaped grooves.

11. The biological sample analysis device according to claim 7, characterized in that, The first flow channel (110) includes a first horizontal flow channel (111) and a first vertical flow channel (112) that are connected to each other. The third through hole (141) is connected to the first horizontal flow channel (111), and the first vertical flow channel (112) is connected to the flow chamber (220).

12. The biological sample analysis device according to claim 7, characterized in that, The second flow channel (120) includes a second horizontal flow channel (121) and a second vertical flow channel (122) that are connected to each other. The second vertical flow channel (122) is connected to the flow chamber (220). The liquid suction and discharge device (400) is connected to the second horizontal flow channel (121) to draw the liquid in the first flow channel (110) into the flow chamber (220).

13. The biological sample analysis device according to claim 7, characterized in that, The carrier plate (200) is disposed on the side of the substrate (130) away from the cover plate (140). At least the portion of the substrate (130) corresponding to the biochip (210) is made of transparent material. The cover plate (140) has an observation window (145) that matches the position of the biochip (210).

14. The biological sample analysis device according to claim 13, characterized in that, A sealing gasket (230) is provided between the biochip (210) and the substrate (130).

15. The biological sample analysis device according to claim 7, characterized in that, The substrate (130) and the cover plate (140) are laser welded, thermo-press bonded or bonded.

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