Liquid path and method of using same, liquid path system and method of using same, and sequencer

Abstract

A liquid path and its usage method, a liquid path system and its usage method, and a sequencer are provided. The liquid path includes a first surface and a second surface. The first surface includes at least an exposed chip surface, and the first surface and the second surface are separated by a preset distance. A reagent liquid is present at a preset position on the second surface, and the second surface can move in a preset direction, causing the reagent liquid at the preset position to be injected into the gap between the chip surface and the second surface. The reagent liquid is moved by the movement of the second surface, avoiding the use of pressure to drive the reagent liquid. Since the chip surface is stationary, the average flow rate of the liquid path is half the movement speed of the second surface, and the thickness of the liquid entering the gap will be at least twice the original thickness, thereby reducing the thickness of the injected reagent. Furthermore, the liquid path is an open liquid path, and the first surface and the second surface do not require adhesive bonding for fixation, thus overcoming the technological barrier of sealing the liquid path in small gaps.

Description

Liquid circuit and its use method, liquid circuit system and its use method and sequencer Technical Field

[0001] The present application relates to the field of gene sequencing technology, and in particular to a liquid circuit and a method for using the same, a liquid circuit system and a method for using the same, and a sequencer. Background Art

[0002] With the development of gene sequencing technology, gene sequencers have made great progress in system integration and sequencing time.

[0003] The widely used flow cell technology for second-generation gene sequencing involves introducing reagents into a flow cell composed of two planar substrates with biological information attached, mounted one above the other. The flow cell then undergoes multiple rounds of imaging to identify base sequences. During the sequencing process, sample loading and the biochemical reactions of fluorescent markers are both performed within the gene sequencing chip.

[0004] Currently, the surface and bottom surfaces of the fluidic circuits in flow cell technology are typically secured by gluing. This method suffers from poor reproducibility, high reagent costs, and prolonged sequencing times. Furthermore, flow cell technology increases costs, as the sequencing process requires up to 200 "reaction-photograph" cycles using multiple reagents. During each cycle, the thickness of the liquid on the chip surface is the thickness of the gap between the two planar substrates, a minimum of 50 microns with existing technology. However, the reagent layer that reacts only occurs within the 1 micron closest to the chip, leaving over 95% of the reagents wasted.

[0005] Summary of the Invention

[0006] In order to solve the above technical problems, the present application provides a liquid circuit and a method of using the same, a liquid circuit system and a method of using the same, and a sequencer.

[0007] In order to achieve the above objectives, the technical solutions provided in the embodiments of the present application are as follows:

[0008] The present application provides a fluid circuit, comprising a first surface and a second surface;

[0009] The first surface at least includes an exposed chip surface, and the first surface and the second surface are arranged at a preset distance;

[0010] A reagent liquid is present at a preset position of the second surface, and the second surface is capable of moving in a preset direction and driving the reagent liquid at the preset position to at least be injected into the gap between the chip surface and the second surface.

[0011] In some possible embodiments, the preset distance is less than or equal to twice the thickness of the reagent liquid at the preset position.

[0012] In some possible embodiments, the first surface and the second surface are both planes and arranged in parallel, and the preset direction is parallel to the first surface.

[0013] In some possible embodiments, both the first surface and the second surface are curved surfaces, and the preset direction is clockwise or counterclockwise.

[0014] In some possible embodiments, a cosine value of a contact angle between the first surface and the reagent liquid is greater than 0, and a cosine value of a contact angle between the second surface and the reagent liquid is greater than 0.

[0015] In some possible embodiments, at least the surface of the second surface that contacts the reagent solution is a surface of a soft film.

[0016] According to the above-mentioned liquid circuit, the present application also provides a method for using the liquid circuit, the method comprising:

[0017] applying a reagent solution to a preset position on the second surface of the liquid path;

[0018] The second surface is controlled to move in a preset direction, and the reagent solution at the preset position is driven to at least be injected into the gap between the chip surface and the second surface.

[0019] The present application also provides a fluid circuit system, comprising:

[0020] A stationary module, the stationary module at least comprising a chip in a naked state, the stationary module having a first surface, and the first surface at least comprising a chip surface of the chip;

[0021] A reagent transfer module is arranged opposite to the chip, and the surface of the reagent transfer module is arranged opposite to the first surface and at a preset distance as a second surface. The second surface and the first surface are surrounded by a liquid path as described in any one of the above items. There is a reagent liquid at a preset position on the second surface of the reagent transfer module. The reagent transfer module can drive the second surface to move relative to the first surface, and drive the reagent liquid at the preset position to at least be injected into the gap between the chip surface and the second surface.

[0022] In some possible embodiments, the reagent transfer module includes:

[0023] a strip, wherein a surface of the strip opposite to the first surface is the second surface; and

[0024] A reeling and unreeling device, wherein the number of the reeling and unreeling devices is at least 2, and at least one of the reeling and unreeling devices is used for unreeling the strip, and at least one of the reeling and unreeling devices is used for reeling the strip.

[0025] In some possible embodiments, the fluid system further includes a positioning device;

[0026] The positioning device is used to position the chip and the reagent transfer module respectively.

[0027] In some possible embodiments, the positioning device includes:

[0028] A first suction cup for adsorbing the chip; and

[0029] A second suction cup is arranged opposite to the first suction cup and is used to absorb the reagent transfer module.

[0030] In some possible embodiments, the positioning device further includes a lifting drive mechanism;

[0031] The driving end of the lifting drive mechanism is connected to the first suction cup or the second suction cup to drive either the first suction cup or the second suction cup to move away from or towards the other to adjust the distance between the first surface and the second surface.

[0032] In some possible embodiments, the liquid circuit system further includes a liquid supply module;

[0033] The liquid application module is used to apply the reagent solution to a preset position on the second surface.

[0034] In some possible embodiments, the liquid applying module includes at least one of a scraper-type liquid applying device, a die-type liquid applying device, a spray-type liquid applying device, a spin-coating liquid applying device, a screen-type liquid applying device, a needle-type liquid applying device, a drip-type liquid applying device, and a pipette-type liquid applying device;

[0035] and / or

[0036] The upper liquid module applies at least one type of the reagent liquid to a preset position on the second surface, and when the types of the reagent liquid are greater than or equal to two, the reagent transfer module can drive the latter reagent liquid to replace the former reagent liquid, clean and fill the liquid path.

[0037] In some possible embodiments, the fluid circuit system further includes a temperature control device;

[0038] The temperature control device is used to control the temperature of the chip to adjust the temperature of the fluid flowing through the surface of the chip.

[0039] In some possible embodiments, the fluid circuit system further includes a control unit;

[0040] The control unit is respectively connected to each electrical component in the fluid system via signals to control each electrical component.

[0041] According to the above-mentioned fluid circuit system, the present application also provides a method for using the fluid circuit system, the method comprising:

[0042] Applying the reagent solution to a preset position of the reagent transfer module;

[0043] The reagent transfer module is controlled to move along a preset direction relative to the first surface, and drives the reagent liquid at the preset position to at least be injected into the gap between the chip and the reagent transfer module.

[0044] In some possible embodiments, the reagent liquid is applied to the preset position of the reagent transfer module by at least one of a scraper-type liquid application device, a die-type liquid application device, a spray-type liquid application device, a spin-coating liquid application device, a screen-type liquid application device, a needle-type liquid application device, a drip-type liquid application device, and a pipette-type liquid application device.

[0045] and / or

[0046] Before applying the reagent liquid to the preset position of the reagent transfer module, the method further includes: sucking the chip by the first suction cup of the liquid path system, sucking the reagent transfer module by the second suction cup, so that the second surface of the reagent transfer module is at a preset distance from the surface of the chip;

[0047] and / or

[0048] During the process of the reagent transfer module driving the reagent solution to move, the temperature of the chip is also controlled by the temperature control unit of the liquid path system.

[0049] The present application also provides a sequencer, comprising the liquid circuit as described in any one of the above items or the liquid circuit system as described in any one of the above items.

[0050] Through the above technical solution, it can be seen that this application has the following beneficial effects:

[0051] The liquid path provided by the present application is to apply the reagent liquid to a preset position on the second surface, and then move the second surface so that the reagent liquid at the preset position is injected into the gap between the first surface and the second surface, covering and contacting the chip surface to react. In the present application, since the reagent liquid is driven to move by the movement of the second surface, the use of pressure drive is avoided. Therefore, on the one hand, a lower reagent usage can be achieved than the flow cell, and on the other hand, there is no problem of exceeding the system pressure limit after the flow cell speed increases; In addition, the reagent liquid is driven by the movement of the second surface, and the chip surface is in a stationary state, so the average flow rate of the liquid path is half the movement speed of the second surface. Because the speed of the liquid inlet is equal to the speed of the second surface, the thickness of the liquid entering the gap between the first surface and the second surface will be at least twice the original, thereby reducing the thickness of the reagent inlet; and the liquid path is an open liquid path, and the first surface and the second surface do not need to be fixed by gluing. Therefore, there is no need to apply glue on either the first surface or the second surface. There is no glue layer between the first surface and the second surface, that is, the present application abandons the glue layer that occupies a certain height of the gap. Therefore, the present application overcomes the process barriers of sealing the liquid path under a small gap. In addition, compared with the prior art in which the liquid path uses a solid wall, which causes the reagent liquid components to stay on the solid wall, resulting in a longer residence time for each reagent liquid component, and sequencing requires more of the next reagent liquid for flushing before the reaction can begin, in this application, the second surface and the first surface are used to form a liquid path, and the reagent liquid moves with the movement of the second surface, so that the reagent liquid can move out of the first surface along with the second surface after the reaction with the chip is completed, avoiding the problem of the reagent liquid staying on the solid wall and requiring more of the next reagent liquid for cleaning. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0053] FIG1 is a schematic diagram of a fluid circuit system provided in an embodiment of the present application;

[0054] FIG2 is a schematic diagram of a planar fluid path system provided in an embodiment of the present application;

[0055] FIG3 is a schematic diagram of a hyperbolic fluid path system provided in an embodiment of the present application;

[0056] FIG4 is a schematic diagram of a pipette-type fluid circuit system provided in an embodiment of the present application;

[0057] FIG5 is a schematic diagram of a scraper-type fluid path system provided in an embodiment of the present application;

[0058] FIG6 is a schematic diagram of a needle-type fluid path system provided in an embodiment of the present application;

[0059] FIG7 is a schematic diagram of a spraying liquid circuit system provided in an embodiment of the present application.

[0060] In Figures 1 to 7: first surface 01, second surface 02, chip 03, chip positioning reference 04, reagent liquid 05, first reagent liquid 05a, second reagent liquid 05b, moving surface positioning reference 06, liquid loading module 08, reagent transfer module 07. DETAILED DESCRIPTION

[0061] In order to help better understand the solution provided by the embodiment of the present application, before introducing the method provided by the embodiment of the present application, the application scenario of the solution of the embodiment of the present application is first introduced.

[0062] The widely used second-generation gene sequencing method, flow cell technology, introduces reagent solution into a flow cell composed of two planar substrates with biological information attached, assembled one above the other. The flow cell is then photographed multiple times to identify base sequences. Current second-generation sequencing technologies primarily include fluorescent labeling based on optical detection and chemical sequencing methods that identify bases based on changes in hydrogen ion concentration. Chemical sequencing methods that identify bases based on changes in hydrogen ion concentration offer advantages in instrument size and speed, but suffer from homopolymer errors and low throughput. Second-generation sequencing technologies based on optical detection and recognition offer the highest base recognition accuracy and currently the highest throughput. In the sequencing field, flow cells are often referred to as flow cells, reaction cells, chips, sequencing chips, gene sequencing chips, or colloidal gold. Common English names include FlowCell, Flowcell, Chip, Chip Kit, and Cartridge. During the sequencing process, sample loading and the biochemical reactions of fluorescent labeling are both performed within the gene sequencing chip. The surface and bottom surfaces of the fluidic system in current flow cell technology are typically fixed by gluing. This leads to poor reproducibility, high reagent costs, and long sequencing times.

[0063] In order to solve the above technical problems, the present application provides a liquid circuit. Specifically, the liquid circuit includes a first surface 01 and a second surface 02 .

[0064] The first surface 01 at least includes the exposed surface of the chip 03 . Specifically, the exposed surface of the chip 03 refers to the surface of the chip to be sequenced 03 loaded with the DNB (DNA nanoball) library and used for reaction.

[0065] It should be noted that the exposed surface of the chip 03 may also be the surface of the chip 03 to be sequenced that is loaded with other substances.

[0066] It should also be noted that the first surface 01 may be a completely exposed chip 03 surface, or may include, in addition to the exposed chip 03 surface, a circumferential protective surface for protecting the chip 03 surface provided at a position not participating in the reaction.

[0067] A reagent liquid 05 is provided at a preset position on the second surface 02 , and the reagent liquid 05 can move along with the movement of the second surface 02 .

[0068] The second surface 02 can move in a preset direction and drive the reagent solution 05 at a preset position to at least be injected into the gap between the surface of the chip 03 and the second surface 02. In the present application, by injecting the reagent solution 05 at least into the gap between the surface of the chip 03 and the second surface 02, the reagent solution 05 can at least flow through the surface of the chip 03 to complete the sequencing.

[0069] It should be noted that the reagent liquid 05 at the preset position of the second surface 02 can be applied by a liquid application device. The types of the applied reagent liquid 05 are sequentially loaded to the preset position according to the reaction sequence. As the second surface 02 moves, each type of reagent liquid 05 can be cleaned and replaced by the next reagent liquid 05 entering the liquid path.

[0070] Referring to Figure 1 , first surface 01 can be located above or below second surface 02. Figure 1 provided in this embodiment of the present application is provided for illustrative purposes only and is not intended to be limiting. Reagent solution 05 in the gap between first surface 01 and second surface 02 is used to detect gene sequences. Specifically, reagent solution 05 reacts with the exposed surface of chip 03 to identify the base sequence in the gene.

[0071] During gene sequencing, the reagent solution 05 flows through different positions on the surface of the chip 03 as the second surface 02 moves to react. As an example, the sequencing process may require replacing multiple reagent solutions 05 in the gap to achieve up to 200 "reaction-photographing" cycles. In the embodiment of the present application, a reagent solution 05 is applied to a preset position on the second surface 02, and then the second surface 02 moves in a preset direction V, so that the reagent solution 05 at the preset position is injected into the gap between the first surface 01 and the second surface 02, i.e., the gap gap. At the same time, the second surface 02 originally located above the first surface 01 moves out of the top of the first surface 01, so that the reagent solution 05 in the gap attached to the second surface 02 is extracted from the gap as the second surface 02 moves. As the new reagent solution 05 at the preset position is continuously injected and the original reagent solution 05 in the gap is continuously extracted, the reagent solution 05 in the gap is gradually replaced by the new reagent solution 05 to complete the cleaning and filling of the liquid path, thereby achieving the displacement of the reagent solution 05 in contact with the sequencing chip 03. For ease of description, the original reagent solution 05 is named as the first reagent solution 05a, and the new reagent solution 05 is named as the second reagent solution 05b.

[0072] In this embodiment, when the first reagent liquid 05a in the gap between the first surface 01 and the second surface 02 is completely displaced by the second reagent liquid 05b, the first reagent liquid 05a has reacted and the reaction results have been photographed and recorded. At this point, other reagent liquids 05 can be provided, and the second surface 02 continues to move. The second reagent liquid 05b will replace the first reagent liquid 05a in the gap between the first surface 01 and the second surface 02, thus achieving multiple "reaction-photographing" cycles and obtaining multiple gene sequencing results.

[0073] In order to ensure that the gap between the first surface 01 and the second surface 02 is filled with the reagent liquid 05, the gap height between the first surface 01 and the second surface 02 is less than or equal to twice the thickness of the reagent liquid 05 at the preset position. It should be noted that during the movement of the second surface 02, the flow rate entering the gap is the moving speed of the second surface 02 multiplied by the liquid thickness and liquid width at the preset position on the first surface 01. Since the first surface 01 is stationary, the average flow rate of the reagent liquid 05 in the gap is half the moving speed of the second surface 02. Therefore, the flow rate of the reagent liquid 05 in the gap is the moving speed of the second surface 02 multiplied by the gap height and the reagent liquid 05 width. Therefore, in order to make the flow rate of the reagent liquid 05 in the gap less than or equal to the liquid inlet flow rate, that is, the gap between the first surface 01 and the second surface 02 is filled with the reagent liquid 05, the gap height between the first surface 01 and the second surface 02 is less than or equal to twice the thickness of the reagent liquid 05 at the preset position.

[0074] In the embodiment of the present application, the hydrophilicity of the first surface 01 and the second surface 02 meets the requirements of the reagent liquid 05 entering the gap, the cosine value of the contact angle between the first surface 01 and the reagent liquid 05 is greater than 0, and the cosine value of the contact angle between the second surface 02 and the reagent liquid 05 is greater than 0.

[0075] The second surface 02 is at least the surface in contact with the reagent solution 05 and is a rollable soft film. In practical applications, the second surface 02 needs to be moved in a preset direction multiple times. In this embodiment of the application, the second surface 02 moved out of the gap can be rolled up for storage.

[0076] Referring to Figure 2, as a possible embodiment, the first surface 01 and the second surface 02 can both be planes, and the first surface 01 is parallel to the second surface 02, and the spacing between the first surface 01 and the second surface 02, that is, the gap height gap between the first surface 01 and the second surface 02 is less than or equal to twice the thickness a of the reagent solution 05 at the preset position. The preset direction V is parallel to the first surface 01. The first surface 01 is connected to the chip positioning reference 04, and the second surface 02 is connected to the moving surface positioning reference 06. In actual applications, the first surface 01 and the chip positioning reference 04 can be connected by a first suction cup, and the second surface 02 and the moving surface positioning reference 06 can also be connected by a second suction cup. It should be noted that the chip positioning reference 04 can be the adsorption surface of the first suction cup for adsorbing the first surface 01, or it can be a separately provided positioning block with a surface having the chip positioning reference 04, one end of the first suction cup is fixed to the positioning block, and the other end is used to adsorb with the first surface 01. Similarly, the moving surface positioning reference 06 can be the adsorption surface of the second suction cup for adsorbing the second surface 02, or it can be a separately set positioning block with a surface having the moving surface positioning reference 06, one end of the second suction cup is fixed on the positioning block, and the other end is used to adsorb with the second surface 02.

[0077] Referring to Figure 3, as another possible embodiment, the first surface 01 and the second surface 02 are both curved surfaces, and the preset direction V is clockwise or counterclockwise. The gap height gap between the first surface 01 and the second surface 02 is less than or equal to twice the thickness of the reagent liquid 05 at the preset position. The reagent liquid 05 at the preset position in the first surface 01 is consistent with the reagent liquid 05 in the gap between the first surface 01 and the second surface 02. When the second surface 02 moves in the preset direction, the reagent liquid 05 at the preset position displaces the reagent liquid 05 in the gap between the first surface 01 and the second surface 02. The first surface 01 is connected to the chip positioning reference 04, and the second surface 02 is connected to the moving surface positioning reference 06. In actual applications, the first surface 01 and the chip positioning reference 04 can be connected by a first suction cup, and the second surface 02 and the moving surface positioning reference 06 can also be connected by a second suction cup.

[0078] The present application also provides a method for using a liquid circuit, wherein the liquid circuit is such as the liquid circuit in any of the above embodiments, and the method for using the liquid circuit includes:

[0079] Step S1: applying the reagent solution 05 to a predetermined position on the second surface 02 of the liquid channel.

[0080] Step S2 : controlling the second surface 02 to move in a preset direction, and driving the reagent solution 05 at a preset position to be injected into at least the gap between the surface of the chip 03 and the second surface 02 .

[0081] The present application also provides a fluid circuit system. Specifically, the fluid circuit system includes a static module and a reagent transfer module 07 .

[0082] The static module at least includes the chip 03 in a naked state, that is, the static module may only include the chip 03 in a naked state, or may include, in addition to the chip 03 in a naked state, also protective parts distributed around the chip 03.

[0083] The stationary module has a first surface 01 , and the first surface 01 includes at least a chip 03 surface of the chip 03 .

[0084] The reagent transfer module 07 is arranged opposite to the chip 03, and the surface of the reagent transfer module 07 opposite to the first surface 01 and at a preset distance is the second surface 02. The second surface 02 and the first surface 01 are surrounded by a liquid path as in any of the above embodiments.

[0085] The reagent transfer module 07 has a reagent liquid 05 at a preset position on the second surface 02. The reagent transfer module 07 can drive the second surface 02 to move relative to the first surface 01 and drive the reagent liquid 05 at the preset position to at least inject into the gap between the chip 03 surface and the second surface 02.

[0086] In the present application, since the movement of the reagent transfer module 07 is used to drive the movement of the reagent liquid 05, the use of pressure drive is avoided. Therefore, on the one hand, a lower reagent usage amount can be achieved than that of the flow pool, and on the other hand, there is no problem of exceeding the system pressure limit after the flow pool speed increases; in addition, the movement of the reagent transfer module 07 is used to drive the reagent liquid 05, and the surface of the chip 03 is in a static state, so the average flow rate of the liquid path is half of the movement speed of the reagent transfer module 07. Because the speed of the liquid inlet is equal to the movement speed of the reagent transfer module 07, the thickness of the liquid entering the gap between the first surface 01 and the second surface 02 will be at least twice the original thickness, thereby reducing the thickness of the reagent inlet; since the reagent transfer module 07 and the stationary module do not need to be glued for fixation, there is no need to glue the reagent transfer module 07 and the stationary module on the first surface 01 and the second surface 02. Glue is applied on any one of the surfaces 02, and there is no glue layer between the first surface 01 and the second surface 02, that is, the present application abandons the glue layer that occupies a certain height of the gap. Therefore, the present application overcomes the process barrier of sealing the liquid path under a small gap; in addition, compared with the prior art in which the liquid path adopts a solid wall, which causes the reagent liquid 05 components to stay on the solid wall, resulting in a longer residence time of each reagent liquid 05 component, and sequencing requires more of the next reagent liquid 05 to be flushed before the reaction can start, in the present application, the second surface 02 and the first surface 01 are enclosed to form a liquid path, and the reagent liquid 05 moves with the movement of the second surface 02, so that the reagent liquid 05 can move out of the first surface 01 along with the second surface 02 after the reaction with the chip 03 is completed, avoiding the problem that the reagent liquid 05 stays on the solid wall and requires more of the next reagent liquid 05 to be cleaned.

[0087] In some embodiments, the reagent transfer module 07 includes a strip and a reeling and unreeling device, wherein the surface of the strip opposite to the first surface 01 is the second surface 02 .

[0088] The number of the reeling and unreeling devices is at least 2, and at least one reeling and unreeling device is used for unreeling the strip, and at least one reeling and unreeling device is used for reeling the strip. The arrangement of the reeling and unreeling devices facilitates the reeling and unreeling of the strip, and is convenient and quick.

[0089] In some embodiments, the fluid system further includes a positioning device, which is used to position the chip 03 and the reagent transfer module 07 respectively.

[0090] Specifically, the positioning device includes a first suction cup and a second suction cup, wherein the first suction cup is used to adsorb the chip 03 , and the second suction cup is arranged opposite to the first suction cup and is used to adsorb the reagent transfer module 07 .

[0091] It should be noted that the specific structure of the positioning device is not limited to the above structure, and can also be set to other structures.

[0092] Furthermore, the positioning device also includes a lifting drive mechanism, the driving end of the lifting drive mechanism is connected to the first suction cup or the second suction cup to drive either the first suction cup or the second suction cup to move away from or closer to the other to adjust the distance between the first surface 01 and the second surface 02.

[0093] Specifically, the lifting drive mechanism can be a screw nut, or an electric push rod, etc.

[0094] In some embodiments, the liquid system further includes a liquid application module 08 , which is used to apply the reagent liquid 05 to a preset position on the second surface 02 .

[0095] Furthermore, the liquid applying module 08 includes at least one of a scraper-type liquid applying device, a die-type liquid applying device, a spray-type liquid applying device, a spin-coating liquid applying device, a screen-type liquid applying device, a needle-type liquid applying device, a drip-type liquid applying device and a pipette-type liquid applying device.

[0096] As shown in Figure 4, the upper liquid module 08 in the liquid circuit system provided in the embodiment of the present application is a pipette-type upper liquid module 08. As shown in Figure 5, the upper liquid module 08 in the liquid circuit system provided in the embodiment of the present application is a scraper-type upper liquid module 08. As shown in Figure 6, the upper liquid module 08 in the liquid circuit system provided in the embodiment of the present application is a needle-type upper liquid module 08. As shown in Figure 7, the upper liquid module 08 in the liquid circuit system provided in the embodiment of the present application is a spray-type upper liquid module 08. The above-mentioned upper liquid module 08 in the embodiment of the present application is only an example and does not limit the upper liquid module 08 in the embodiment of the present application. In fact, as long as the industrial device can apply the reagent liquid 05 to a preset position, it can be applied to the technical solution of the present application. The coating method in the present application is not limited to scraper, die, spraying, spin coating, screen, dripping and other methods.

[0097] In some embodiments, the upper liquid module 08 applies at least one type of reagent liquid 05 to a preset position on the second surface 02, and when the number of types of reagent liquid 05 is greater than or equal to two, the reagent transfer module 07 can drive the latter reagent liquid 05 to replace the former reagent liquid 05, clean and fill the liquid path.

[0098] In the fluid path system provided in the embodiment of the present application, the fluid path system further includes a temperature control device, which is used to control the temperature of the chip 03 to adjust the temperature of the fluid flowing through the surface of the chip 03 .

[0099] It should be noted that, during the actual reaction process, the temperature of the chip 03 to be sequenced may need to be limited. After the gap between the first surface 01 and the second surface 02 is filled with the reagent liquid 05, the embodiment of the present application can adjust the temperature of the chip 03 to be sequenced through a temperature control device, thereby realizing the sequencing reaction and obtaining the reaction results.

[0100] Furthermore, the fluid circuit system also includes a control unit that is connected to each electrical component in the fluid circuit system via signals to control each electrical component. Specifically, the electrical components include but are not limited to a temperature control device, a liquid loading module 08, a reagent transfer module 07, and a positioning device.

[0101] The present application also provides a method for using a fluid circuit system, such as the fluid circuit system in any of the above embodiments, and the method for using the fluid circuit system includes:

[0102] Step S10: Apply the reagent solution 05 to the preset position of the reagent transfer module 07.

[0103] Specifically, the reagent liquid 05 is coated to the preset position through the liquid applying module 08. More specifically, the liquid applying module 08 includes at least one of a scraper-type liquid applying device, a die-type liquid applying device, a spray-type liquid applying device, a spin-coating liquid applying device, a screen-type liquid applying device, a needle-type liquid applying device, a drip-type liquid applying device and a pipette-type liquid applying device.

[0104] Step S20: Control the reagent transfer module 07 to move along a preset direction relative to the first surface 01 , and drive the reagent solution 05 at the preset position to at least be injected into the gap between the chip 03 and the reagent transfer module 07 .

[0105] Specifically, while the reagent transfer module 07 drives the reagent solution 05 to move, the temperature of the chip 03 is also controlled by the temperature control unit of the liquid path system.

[0106] It should be noted that controlling the reagent transfer module 07 to drive the reagent liquid 05 at the preset position to at least be injected into the gap between the chip 03 and the reagent transfer module 07 includes: when there is only one reagent liquid 05, the reagent liquid 05 is filled into the gap; when at least two reagent liquids 05 are included (the at least two reagent liquids 05 include at least two reagent liquids 05 in one sequencing cycle and at least two reagent liquids 05 that circulate alternately in two adjacent test cycles), the reagent transfer module 07 can drive the latter reagent liquid 05 to replace the former reagent liquid 05, clean and fill the liquid path.

[0107] Furthermore, the present application discloses that before step S10, step S30 is also included: the chip 03 is adsorbed by the first suction cup of the liquid system, and the reagent transfer module 07 is adsorbed by the second suction cup, so that the second surface 02 of the reagent transfer module 07 is at a preset distance from the surface of the chip 03.

[0108] Specifically, the preset distance is less than or equal to twice the thickness of the reagent solution 05 at the preset position.

[0109] The present application also provides a sequencer, comprising a liquid path as in any one of the above embodiments or a liquid path system as in any one of the above embodiments.

[0110] Through the description of the above embodiments, it can be seen that those skilled in the art can clearly understand that all or part of the steps in the above-mentioned embodiment methods can be implemented by means of software plus the necessary general hardware platform. Based on this understanding, the technical solution of the present application, or the part that contributes to the prior art, can be embodied in the form of a software product, which can be stored in a storage medium such as ROM / RAM, a magnetic disk, an optical disk, etc., and includes a number of instructions for enabling a computer device (which can be a personal computer, a server, or a network communication device such as a media gateway, etc.) to execute the methods described in each embodiment of the present application or certain parts of the embodiments.

[0111] It should be noted that the various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. Reference can be made to the common and similar parts between the various embodiments. The methods disclosed in the embodiments are described briefly because they correspond to the systems disclosed in the embodiments. For relevant details, refer to the description of the systems.

[0112] It should also be noted that, in this document, the terms "comprises," "includes," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, article, or apparatus comprising a series of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus. In the absence of further limitations, an element defined by the phrase "comprising a ..." does not exclude the presence of other identical elements in the process, method, article, or apparatus comprising the element.

[0113] The above description of the disclosed embodiments will enable those skilled in the art to implement or use various modifications of these embodiments, and it will be apparent to those skilled in the art that the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to the embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A liquid path, characterized in that, It includes a first surface and a second surface; The first surface at least includes an exposed chip surface, and the first surface and the second surface are arranged at a preset distance from each other; At a preset position on the second surface, there is reagent liquid. The second surface can move in a preset direction and drive the reagent liquid at the preset position to be injected at least into the gap between the chip surface and the second surface.

2. The liquid path according to claim 1, characterized in that, The preset distance is less than or equal to twice the thickness of the reagent liquid at the preset position.

3. The liquid path according to claim 1, characterized in that, Both the first surface and the second surface are planes and are arranged in parallel, and the preset direction is parallel to the first surface.

4. The liquid path according to claim 1, characterized in that, Both the first surface and the second surface are curved surfaces, and the preset direction is clockwise or counterclockwise.

5. The liquid path according to claim 1, characterized in that, The cosine value of the contact angle between the first surface and the reagent liquid is greater than 0, and the cosine value of the contact angle between the second surface and the reagent liquid is greater than 0.

6. The liquid path according to any one of claims 1 - 5, characterized in that, At least the surface of the second surface in contact with the reagent liquid is the surface of a soft film.

7. A method for using a liquid path, characterized in that, The liquid path is the liquid path according to any one of claims 1-6. The using method includes: Coating reagent liquid at a preset position on the second surface of the liquid path; Controlling the second surface to move in a preset direction and driving the reagent liquid at the preset position to be injected at least into the gap between the chip surface and the second surface.

8. A liquid path system, characterized in that, It includes: A stationary module, the stationary module at least includes a chip in an exposed state. The stationary module has a first surface, and the first surface at least includes the chip surface of the chip; A reagent transfer module arranged opposite to the chip. The surface of the reagent transfer module opposite to the first surface and at a preset distance from it is the second surface. The second surface and the first surface enclose a liquid path according to any one of claims 1-6. At a preset position on the second surface of the reagent transfer module, there is reagent liquid. The reagent transfer module can drive the second surface to move relative to the first surface and drive the reagent liquid at the preset position to be injected at least into the gap between the chip surface and the second surface.

9. The liquid path system according to claim 8, characterized in that, The reagent transfer module includes: A strip. The surface of the strip opposite to the first surface is the second surface; and A winding and unwinding device. The number of winding and unwinding devices is at least 2, and at least 1 winding and unwinding device is used for unwinding the strip, and at least 1 winding and unwinding device is used for winding the strip.

10. The liquid path system according to claim 8, characterized in that, It further includes a positioning device; The positioning device is used to position the chip and the reagent transfer module respectively.

11. The liquid path system according to claim 10, characterized in that, The positioning device includes: A first suction cup for adsorbing the chip; and A second suction cup arranged opposite to the first suction cup and used for adsorbing the reagent transfer module.

12. The liquid path system according to claim 11, characterized in that, The positioning device further includes a lifting drive mechanism; The drive end of the lifting drive mechanism is connected to the first suction cup or the second suction cup to drive either the first suction cup or the second suction cup to move away from or close to the other, so as to adjust the distance between the first surface and the second surface.

13. The liquid path system according to claim 8, characterized in that, It further includes a liquid supply module; The liquid supply module is used to coat the reagent liquid at a preset position on the second surface.

14. The liquid path system according to claim 13, wherein The liquid application module includes at least one of a blade-type liquid application device, a die head-type liquid application device, a spraying-type liquid application device, a spin coating-type liquid application device, a screen printing-type liquid application device, a needle-type liquid application device, a dropping-type liquid application device, and a pipette-type liquid application device; and / or The type of the reagent liquid coated by the liquid application module at a preset position on the second surface is at least one kind, and when the type of the reagent liquid is greater than or equal to two kinds, the reagent transfer module can drive the latter reagent liquid to displace the former reagent liquid, clean and fill the liquid path.

15. The liquid path system according to claim 8, wherein It further includes a temperature control device; The temperature control device is used to control the temperature of the chip to adjust the temperature flowing through the surface of the chip.

16. The liquid path system according to any one of claims 8-15, wherein It further includes a control unit; The control unit is respectively signal-connected to each electrical component in the liquid path system to control each electrical component.

17. A method for using a liquid path system, wherein The liquid path system is the liquid path system in any one of claims 8-16, and the usage method includes: Coating a reagent liquid at a preset position of the reagent transfer module; Controlling the reagent transfer module to move relative to the first surface along a preset direction, and driving the reagent liquid at the preset position to be injected into at least the gap between the chip and the reagent transfer module.

18. The method for using according to claim 17, wherein Coating a reagent liquid at a preset position of the reagent transfer module is specifically realized by at least one of a blade-type liquid application device, a die head-type liquid application device, a spraying-type liquid application device, a spin coating-type liquid application device, a screen printing-type liquid application device, a needle-type liquid application device, a dropping-type liquid application device, and a pipette-type liquid application device; and / or Before coating the reagent liquid at a preset position of the reagent transfer module, it further includes: adsorbing the chip by the first suction cup of the liquid path system, and adsorbing the reagent transfer module by the second suction cup, so that the second surface of the reagent transfer module is at a preset distance from the surface of the chip; and / or During the process of the reagent transfer module driving the reagent liquid to move, the temperature of the chip is further controlled by the temperature control unit of the liquid path system.

19. A sequencer, wherein It includes the liquid path according to any one of claims 1-6 or the liquid path system according to any one of claims 8-16.

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