Gene sequencing fluid system and gene sequencer

Abstract

The utility model provides a gene sequencing fluid system and a gene sequencer, and the gene sequencing fluid system comprises a reaction reagent storage device, a biochip, a first waste liquid storage device, a first selection valve assembly and a pump assembly; through the selection effect of the first selection valve assembly, the pump assembly can be controlled to be communicated with the reaction reagent storage device firstly and suck a reagent to a pipeline between the pump assembly and the first selection valve assembly in a negative pressure mode for temporary storage, then the pump assembly is switched to be communicated with the flowing channel of the biological chip, and then the reagent is pumped into the flowing channel of the biological chip in a positive pressure mode. By means of the mode that the reagent is pumped into the flowing channel under positive pressure, gas dissolved in the reagent is limited from escaping when the reagent enters the flowing channel from the pipeline, and therefore the number of bubbles in the reagent in the flowing channel is reduced, and the size of the bubbles in the reagent in the flowing channel is reduced.

Description

Technical Field

[0001] The present application relates to the field of gene sequencing technology, and in particular to a gene sequencing fluid system and a gene sequencer. Background Art

[0002] When a gene sequencer extracts reagents, some dissolved gases escape, forming bubbles within the reagents. These bubbles can affect the uniformity of sample mixing within the biochip's flow channels and the stability of the sequencing reaction. When sequencing using optical detection methods, larger bubbles can scatter light, affecting the accuracy of biochip imaging.

[0003] In the existing technology, the escape of gas dissolved in the reagent is usually limited by controlling the reagent temperature and the ambient temperature during gene sequencing, reducing the vibration of the gene sequencer, etc. However, these methods are limited in their effectiveness in limiting gas escape, and more and larger bubbles will still be generated in the reagent. Utility Model Content

[0004] The present application provides a gene sequencing fluid system and a gene sequencer to reduce gas escape from reagents, thereby reducing the number and size of bubbles in the reagents.

[0005] In a first aspect, the present application provides a gene sequencing fluid system, comprising: a reaction reagent storage, a biochip, a first waste liquid storage, a first selection valve assembly, and a pump assembly; wherein,

[0006] The first selection valve assembly has at least a reagent port, a pump port and at least one chip port;

[0007] The biochip includes at least one flow channel, which is used to provide a reaction area for gene sequencing; one end of each flow channel is connected to one of the chip ports, and the other end of each flow channel is connected to the first waste liquid storage; the first waste liquid storage is used to store waste liquid generated during the gene sequencing process;

[0008] The reaction reagent storage is in communication with the reagent port of the first selection valve assembly, and the reaction reagent storage is used to store the reaction reagents required for gene sequencing;

[0009] The pump assembly is in communication with the pump port of the first selection valve assembly, and the pump assembly is used to drive the fluid flow in the gene sequencing fluid system;

[0010] The first selection valve assembly can selectively connect the reaction reagent reservoir to the pump assembly or connect the flow channel to the pump assembly.

[0011] In the above technical solution, during the gene sequencing process, the first selector valve assembly is selectively activated to control the pump assembly to first connect to the reaction reagent reservoir and draw the reagent into the pipeline between the pump assembly and the first selector valve assembly for temporary storage. The pump assembly is then switched to connect to the flow channel of the biochip, and the reagent is then pumped into the flow channel of the biochip under positive pressure. By pumping the reagent into the flow channel under positive pressure, the escape of gas dissolved in the reagent during the process of entering the flow channel from the pipeline is limited, thereby reducing the number and size of bubbles in the reagent within the flow channel.

[0012] In one possible embodiment, the gene sequencing fluid system further includes a second waste liquid storage, and the pump assembly includes a second selection valve and at least one pump;

[0013] The second selection valve has a plurality of ports, and the plurality of ports are respectively in communication with at least the pump port of the first selection valve assembly, the second waste liquid reservoir, and the pump;

[0014] The second selector valve is used to selectively connect the pump to the pump port of the first selector valve assembly or to connect the pump to the second waste liquid storage;

[0015] The second waste liquid storage is used to store the fluid discharged from the pump.

[0016] In a possible implementation, the number of the pumps is equal to the number of the flow channels, and the pumps correspond to the flow channels one-to-one.

[0017] In one possible embodiment, the gene sequencing fluid system further includes a buffer storage device, wherein the buffer storage device is used to store a buffer solution required for cleaning the flow channel;

[0018] The buffer reservoir is connected to one of the plurality of ports of the second selector valve, and the second selector valve can further selectively connect the pump to the buffer reservoir.

[0019] In one possible embodiment, the gene sequencing fluid system further includes an inert gas source, which is used to provide the inert gas required to dry the flow channel;

[0020] The first selector valve assembly further has an inert gas port to which the inert gas source is connected, and the first selector valve assembly can also selectively connect the flow channel to the inert gas source.

[0021] In one possible embodiment, the gene sequencing fluid system further includes a pressure valve;

[0022] The pressure valve is disposed between the inert gas source and the first selection valve assembly, and is used to adjust and control the pressure of the inert gas injected into the flow channel.

[0023] In one possible embodiment, the gene sequencing fluid system further includes a flow meter;

[0024] The flow meter is connected between the inert gas source and the first selection valve assembly and is used to monitor the working flow rate of the inert gas injected into the flow channel.

[0025] In a possible implementation, the first selection valve assembly includes a first solenoid valve and a second solenoid valve;

[0026] The first solenoid valve has a first port, a second port and a third port; the second solenoid valve has a fourth port, a fifth port and a sixth port;

[0027] The first port is in communication with the reaction reagent storage, the second port is in communication with the flow channel, the fifth port is in communication with the pump assembly, and the sixth port is in communication with the inert gas source;

[0028] The third port is communicated with the fourth port. Meanwhile, the third port can be selectively communicated with the first port or the second port, and the fourth port can be selectively communicated with the fifth port or the sixth port.

[0029] In a second aspect, the present application provides a gene sequencing fluid system, which includes: a reaction reagent storage, a biochip, a first waste liquid storage, a first selection valve assembly, and a pump assembly; wherein,

[0030] The first selection valve assembly has at least a reagent port, a pump port and at least one chip port;

[0031] The biochip includes at least one flow channel, which is used to provide a reaction area for gene sequencing; one end of each flow channel is connected to one of the chip ports, and the other end of each flow channel is connected to the first waste liquid storage; the first waste liquid storage is used to store waste liquid generated during the gene sequencing process;

[0032] The reaction reagent storage is in communication with the reagent port of the first selection valve assembly, and the reaction reagent storage is used to store the reaction reagents required for gene sequencing;

[0033] The pump assembly is in communication with the pump port of the first selection valve assembly, and the pump assembly is used to drive the fluid flow in the gene sequencing fluid system;

[0034] The first selection valve assembly can selectively connect the reaction reagent reservoir to the pump assembly or connect the flow channel to the pump assembly.

[0035] The gene sequencing fluid system also includes a controller configured to control the first selection valve assembly to be in a first position so that the pump assembly is connected to the reaction reagent storage, and control the pump assembly to transport the reagent in the reaction reagent storage to the pipeline between the pump assembly and the first selection valve assembly by generating negative pressure; and control the first selector valve to be in a second position so that the pump assembly is connected to the flow channel in the biochip, and control the pump assembly to transport the reagent in the pipeline between the pump assembly and the first selection valve assembly to the flow channel in the biochip by generating positive pressure.

[0036] In the above technical solution, the controller can selectively control the first selector valve assembly to be in different working positions, and can control the pump assembly to first connect with the reaction reagent storage device and negatively draw the reagent into the pipeline between the pump assembly and the first selector valve assembly for temporary storage. Then, the pump assembly is switched to connect with the flow channel of the biochip, and the reagent is then positively pumped into the flow channel of the biochip. By pumping the reagent into the flow channel with positive pressure, the escape of gas dissolved in the reagent during the process of the reagent entering the flow channel from the pipeline is limited, thereby reducing the number of bubbles in the reagent in the flow channel and reducing the size of bubbles in the reagent in the flow channel.

[0037] In a third aspect, the present application provides a gene sequencer, comprising an optical detection system and a computer system, and further comprising any gene sequencing fluid system as described above;

[0038] The flow channel in the biochip receives a sequencing object, and the sequencing object contacts the reagent and undergoes a chemical reaction so as to carry a fluorescent label;

[0039] The optical detection system is configured to excite the fluorescent marker carried by the sequencing object and detect the fluorescent signal generated by the excited fluorescent marker;

[0040] The computer system is configured to obtain a fluorescent image from the optical detection system and identify the gene sequence of the sequencing object based on the fluorescent image.

[0041] During the gene sequencing process, the gene sequencing fluid system of the aforementioned gene sequencer, through the selection of the first selector valve assembly, can control the pump assembly to first connect with the reaction reagent storage device and draw the reagent into the pipeline between the pump assembly and the first selector valve assembly for temporary storage under negative pressure. The pump assembly then switches to connect with the flow channel of the biochip, and then positively pumps the reagent into the flow channel of the biochip. By pumping the reagent into the flow channel under positive pressure, the escape of gas dissolved in the reagent during the process of entering the flow channel from the pipeline is limited, thereby reducing the number and size of bubbles in the reagent in the flow channel. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 This is a schematic diagram of negative pressure sampling in a biochip in the prior art;

[0043] Figure 2 Schematic diagram of the gene sequencing fluid system provided for this application;

[0044] Figure 3 This is a schematic diagram of positive pressure injection of a biochip in an embodiment of the present application;

[0045] Figure 4 A schematic diagram of a specific embodiment of the gene sequencing fluid system provided in an embodiment of the present application;

[0046] Figure 5 This is a schematic diagram of the first selection valve assembly composed of the solenoid valve in the embodiment of the present application. DETAILED DESCRIPTION

[0047] In order to make the purpose, technical solutions and advantages of this application clearer, this application will be further described in detail below with reference to the accompanying drawings.

[0048] It should be noted that, unless otherwise defined, the technical terms or scientific terms used in one or more embodiments of this specification should have the usual meanings understood by people with ordinary skills in the field to which this disclosure belongs. The "first", "second" and similar words used in one or more embodiments of this specification do not indicate any order, quantity or importance, but are only used to distinguish different components. "Include" or "comprise" and similar words mean that the elements or objects appearing before the word include the elements or objects listed after the word and their equivalents, without excluding other elements or objects. "Connect" or "connected" and similar words are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Up", "down", "left", "right" and the like are only used to indicate relative position relationships. When the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0049] To facilitate understanding of the gene sequencing fluid system provided in the embodiment of the present application, its application scenario is first described. The gene sequencing fluid system provided in the embodiment of the present application can be applied to a gene sequencer. When the gene sequencing fluid system extracts the reagent into the flow channel of the biochip, due to the flow of the reagent, the pressure change of the reagent itself, etc., a portion of the gas dissolved in the reagent will escape, and the escaped gas can easily form bubbles in the reagent. In the prior art, the generation of gas dissolved in the reagent that escapes is usually limited by controlling the reagent temperature and the ambient temperature during gene sequencing, reducing the vibration of the gene sequencer, etc., but these methods are limited in effect in limiting gas escape, and more and larger bubbles will still be produced in the reagent.

[0050] refer to Figure 1 , Figure 1 This is a schematic diagram of negative pressure injection in a biochip in the prior art. In the prior art, the method of delivering reagents is mostly to connect the pump component, the flow channel of the biochip and the reaction reagent storage in series, and the reagent stored in the reaction reagent storage is sucked into the flow channel by the suction action of the pump component for reaction. Figure 1 The dashed line cluster with arrows in the middle illustrates the reagent flow path. The reagent is drawn from the thicker pipe into the thinner flow channel through the negative pressure of the pump assembly, enabling the biochip to be sampled. In the negative pressure suction sampling method, due to the relatively low reagent pressure itself, and the liquid being sucked from the thicker pipe into the thinner flow channel, the reagent pressure flow rate in the flow channel accelerates, further reducing the reagent pressure, which in turn causes a large amount of gas dissolved in the reagent to escape, forming bubbles in the reagent. These bubbles often accumulate in the flow channel, affecting the uniformity of sample mixing in the biochip, the stability of the sequencing reaction within the biochip, and the accuracy of the biochip photo detection.

[0051] Based on this, a first aspect of an embodiment of the present application provides a gene sequencing fluid system to reduce gas escape from reagents, thereby reducing the number and size of bubbles in the reagents. The gene sequencing fluid system provided by an embodiment of the present application is described in detail below with reference to the accompanying drawings.

[0052] refer to Figure 2 , Figure 2 Schematic diagram of the gene sequencing fluid system provided in this application. The gene sequencing fluid system provided in this embodiment includes a reaction reagent reservoir 01, a biochip 02, a pump assembly 03, a first selector valve assembly 04, and a first waste liquid reservoir 05. The reaction reagent reservoir 01, pump assembly 03, and biochip 02 are each connected to the first selector valve assembly 04 via a pipeline.

[0053] The first selection valve assembly 04 has multiple selection ports, for example, at least a reagent selection port, a pump selection port and a chip selection port. These selection ports are used to maintain communication with the reaction reagent storage 01, the biochip 02 and the pump assembly 03 respectively.

[0054] Specifically, the biochip 02 has one or more flow channels 021, such as Figure 4 As shown, flow channel 021 is used to provide a reaction area for gene sequencing. One end of each flow channel 021 is connected to a liquid inlet / outlet of biochip 2, and each liquid inlet / outlet is further connected to a chip selection port, thereby connecting biochip 2 to first selection valve assembly 04. Reagent reservoir 01 is connected to the reagent selection port of first selection valve assembly 04 and is used to store various reaction reagents required for gene sequencing. Pump assembly 03 is connected to the pump selection port of first selection valve assembly 04 and is used to drive fluid flow within the gene sequencing fluid system.

[0055] The first selector valve assembly 04 can selectively maintain communication between the reaction reagent reservoir 01 and the pump assembly 03, or selectively maintain communication between the flow channel 021 and the pump assembly 03. That is, when the gene sequencing fluid system is in operation, the pump assembly 03 can selectively communicate with either the biochip 02 or the reaction reagent reservoir 01 through the first selector valve assembly 04.

[0056] In the specific implementation of the selective communication process, the first selector valve assembly 04 may have multiple positions to control the communication relationship between the various components connected to the first selector valve assembly 04. When the first selector valve assembly 04 is in the first position, the pump assembly 03 maintains communication with the reaction reagent reservoir 01; when the first selector valve assembly 04 is in the second position, the pump assembly 03 maintains communication with the biochip 02.

[0057] During sequencing operations, pump assembly 03 is used to drive fluid flow within the gene sequencing fluid system. Specifically, pump assembly 03 can be in either a suction or discharge state, and in conjunction with first selector valve assembly 04, can switch between the first and second stations to deliver reagents from reaction reagent reservoir 01 to biochip 02. Specifically, first, first selector valve assembly 04 is switched to the first station, connecting pump assembly 03 to reaction reagent reservoir 01. Pump assembly 03 is kept in the suction state to extract reagents from reaction reagent reservoir 01 and temporarily store them in the pipeline between first selector valve assembly 04 and pump assembly 03, or in the pipeline and pump assembly 03. Then, first selector valve assembly 04 is switched to the second station, connecting pump assembly 03 to flow channel 021 of biochip 02. Pump assembly 03 is then kept in the discharge state to pump reagents temporarily stored in the pipeline between first selector valve assembly 04 and pump assembly 03, or in the pipeline and pump assembly 03, into flow channel 021.

[0058] After the biochemical reaction in the biochip 02 is completed, the first selection valve assembly 04 can be kept in the second position and the pump assembly 03 can be kept in the discharge state to discharge the waste liquid in the biochip 02 into the first waste liquid storage 05 for storage.

[0059] For reference Figure 2 and Figure 3 , Figure 3 This is a schematic diagram of positive pressure injection of the biochip 02 in the embodiment of this application. Figure 3 The cluster of dashed lines with arrows illustrates the flow of reagents temporarily stored in the pipeline between first selector valve assembly 04 and pump assembly 03 when first selector valve assembly 04 is in the second position and pump assembly 03 is in the discharge state. When pump assembly 03 pumps reagents into flow channel 021 of biochip 02 using positive pressure, it must apply pressure to the reagents, resulting in a high pressure, which is detrimental to the escape of gases dissolved in the reagents. Furthermore, when pump assembly 03 extracts reagents from reaction reagent reservoir 01, it does not need to pass through narrow flow channel 021 within biochip 02, resulting in relatively little gas escape during the extraction process.

[0060] In summary, the gene sequencing fluid system provided in the embodiment of the present application does not pass through the narrow flow channel 021 when the reagent is attracted by negative pressure, and adopts positive pressure pumping when the reagent enters the flow channel 021. This can effectively limit the precipitation of gas dissolved in the reagent during the sampling process of the biochip 02, thereby reducing the number of bubbles in the reagent in the biochip 02 and reducing the size of the bubbles in the reagent in the biochip 02.

[0061] For reference Figure 4 , Figure 4A schematic diagram of a specific embodiment of the gene sequencing fluid system provided in an embodiment of the present application. As an optional embodiment, the gene sequencing fluid system provided in an embodiment of the present application also includes a second waste liquid reservoir 08, which is connected to the pump assembly 03 and can be used to store fluid discharged from the pump assembly 03.

[0062] Specifically, pump assembly 03 includes a second selector valve 031 and at least one pump 032. Second selector valve 031 has multiple selector ports and a common port, the common port being connected to pump 032. The multiple selector ports are connected to at least the pump selector port of first selector valve assembly 04 and second waste liquid reservoir 08, respectively. Second selector valve 031 is configured to selectively connect pump 032 to the pump selector port of first selector valve assembly 04 or to the second waste liquid reservoir 08. In other words, pump 032 can selectively connect to either the first selector valve assembly 04 or the second waste liquid reservoir 08 through second selector valve 031.

[0063] Specifically, the second selector valve 031 may have a third position and a fourth position. When the second selector valve 031 is in the third position, the pump 032 is connected to the second waste liquid reservoir 08. When the second selector valve 031 is in the fourth position, the pump 032 is connected to the first selector valve assembly 04. When the second selector valve 031 is in the fourth position, the first selector valve assembly 04 may be in the first position, allowing the pump 032 to be connected to the reagent storage 01. When the second selector valve 031 is in the fourth position, the first selector valve assembly 04 may be in the second position, allowing the pump 032 to be connected to the flow channel 021. In specific implementations, the second selector valve and the pump 032 may be integrated into one component or may be provided separately, which is not a restriction here.

[0064] When the gene sequencing fluid system performs a sequencing operation, the second selector valve 031 can be kept in the fourth position to ensure that the pump 032 can be connected to the biochip 02 or the reagent storage 01. After the sequencing operation is completed, the second selector valve 031 can be switched to the third position so that the pump 032 is connected to the second waste liquid storage 08. At this time, the pump 032 can be in a discharge state and can discharge the remaining fluid in the pump 032 into the second waste liquid storage 08. It is worth noting that the fluid directly discharged from the pump 032 to the second waste liquid storage 08 can be the residual reaction reagent in the pump 032 or the cleaning fluid used to clean the pipeline. By providing the second waste liquid storage 08, the remaining fluid in the pump 032 is discharged without being discharged through the flow channel 021, which can reduce the risk of contamination of the biochip 02 and the pipeline from the pump 032 to the flow channel 021.

[0065] After the sequencing operation of the gene sequencing fluid system is completed, residual reagents or waste liquid may have an adverse effect on the gene sequencing fluid system. The gene sequencing fluid system can also have a self-cleaning function to clean the pipeline after the sequencing operation is completed.

[0066] As an optional embodiment, the gene sequencing fluid system also includes a buffer storage 07, which is used to store the buffer required for cleaning the flow channel. The buffer storage 07 is connected to one of the multiple selection ports of the second selection valve 031, and the second selection valve 031 can also selectively keep the pump 032 connected to the buffer storage 07.

[0067] Specifically, the second selector valve 031 may also have a fifth position. When the second selector valve is in the fifth position, the pump 032 remains in communication with the buffer reservoir 07. During sequencing operations in the gene sequencing fluidic system, the second selector valve 06 may be maintained in the fourth position to ensure that the pump 032 remains in communication with the flow channel 021 or the reagent reservoir 01. After the sequencing operation is completed, the second selector valve 06 may be switched to the fifth position, maintaining communication between the pump 032 and the buffer reservoir 07. At this point, with the pump 032 in the suction state, cleaning fluid may be drawn into the pump 032 for temporary storage. Once a certain amount of cleaning fluid is stored in the pump 032, the second selector valve 031 may be switched to the fourth position, while the first selector valve assembly 04 is maintained in the second position and the pump 032 in the discharge state. The cleaning fluid may then flow along the route of the pump 032, the second selector valve 031, the first selector valve assembly 04, and the flow channel 021, thereby cleaning the pipelines and components along this route, particularly the flow channel 021. After flowing through flow channel 021, the cleaning fluid can be directly stored in the second waste liquid reservoir 05 for further processing. By connecting the cleaning device with the second selector valve 031, the gene sequencing fluid system can be self-cleaned. The cleaning process can be completed by switching the valve group position and pump 032 state, which is very convenient.

[0068] After the gene sequencing fluid system completes the cleaning process, flow channel 021 remains wet, and residual cleaning fluid may be present inside flow channel 021. This residual cleaning fluid may accelerate corrosion or rusting of components within flow channel 021. The gene sequencing fluid system may also be equipped with a drying device to dry flow channel 021 after cleaning.

[0069] Continue to refer Figure 4As an optional embodiment, the gene sequencing fluid system further includes an inert gas source 09. The inert gas source 09 is used to provide the inert gas required to dry the flow channel. Specifically, the first selector valve assembly 04 further includes an inert gas selection port, to which the inert gas source 09 is connected, and the first selector valve assembly 04 can selectively maintain communication between the flow channel 021 and the inert gas source 09. That is, the first selector valve assembly 04 can also include a sixth position. When the first selector valve assembly 04 is in the sixth position, the first selector valve assembly 04 can control only the inert gas source 09 to maintain communication with the flow channel 021.

[0070] After the gene sequencing fluid cleaning operation is completed, the first selection valve assembly 04 can be switched to the sixth position. At this time, the inert gas source 09 is connected to the biochip 02, and the drying gas can enter the biochip 02 through the first selection valve assembly 04 to dry the biochip 02.

[0071] Using inert gas to dry the biochip 02 can extend the lifespan of the biochip 02. Furthermore, the inert gas source 09 and the biochip 02 can be connected via the first selector valve assembly 04. This means that the biochip 02 can be dried simply by switching the positions of the first selector valve assembly 04, making the operation more convenient.

[0072] Optionally, when using an inert gas source 09 to dry the biochip 02, a pressure valve 10 can be placed between the inert gas source 09 and the biochip 02. As the drying gas passes through the pressure valve 10, it can regulate and control the pressure of the inert gas injected into the flow channel 021. On the one hand, an appropriate pressure ensures a good drying effect as the drying gas passes through the flow channel 021, improving the efficiency of the drying process. On the other hand, this ensures a good drying effect without damaging components due to excessive pressure, thereby extending the life of the flow channel 021.

[0073] Optionally, when using inert gas source 09 to dry biochip 02, a flow meter 11 can be placed between inert gas source 09 and biochip 02. As the drying gas passes through flow meter 11, flow meter 11 can be used to monitor the operating flow rate of the inert gas injected into flow channel 021. By monitoring the flow rate of the drying gas and whether it is normal, operators can easily observe the drying process and reduce the risk of oxidation or chemical changes in components within flow channel 021 caused by abnormal drying gas flow.

[0074] When the first selection valve assembly 04 is specifically configured, the first selection valve assembly 04 can be in the form of a multi-way selection valve or a plurality of three-way valves connected in coordination.

[0075] For reference Figure 4 and Figure 5 , Figure 5 This is a schematic diagram of the first selector valve assembly composed of solenoid valves in an embodiment of the present application. As an optional embodiment, the first selector valve assembly 04 includes a first solenoid valve 041 and a second solenoid valve 042. The first solenoid valve 041 and the second solenoid valve 042 cooperate to enable the first selector valve assembly 04 to switch between the first station, the second station, and the sixth station. Specifically, the first solenoid valve 041 has a first port 0411 and a second port 0412; the first port 0411 is connected to the reagent storage 01, and the second port 0412 is connected to the flow channel 021. The second solenoid valve 042 has a fifth port 0422 and a sixth port 0423; the fifth port 0422 is connected to the pump group 03, and the sixth port 0423 is connected to the inert gas source 09. When the pump group 03 includes the second selector valve 031, the fifth port 0422 can be connected to the second selector valve 06. The first solenoid valve 041 further has a third port 0413 , and the second solenoid valve 042 further has a fourth port 0421 . The third port 0413 is in communication with the fourth port 0421 , connecting the first solenoid valve 041 and the second solenoid valve 042 to form a solenoid valve group.

[0076] The first solenoid valve 041 can realize that either the first port 0411 or the second port 0412 is connected to the third port 0413 by controlling the on / off power of the valve core. The second solenoid valve 042 can realize that either the third port 0413 or the fourth port 0421 is connected to the sixth port 0423 by controlling the on / off power of the valve core.

[0077] When the first selector valve assembly 04 is in the first position, the first solenoid valve 041 controls the communication between the first port 0411 and the third port 0413, the second solenoid valve 042 controls the communication between the fourth port 0421 and the fifth port 0422, and the third port 0413 and the fourth port 0421 are connected, thereby achieving communication between the pump group 03 and the reagent reservoir 01. At this time, the pump group 03 can extract reagent from the reagent reservoir 01.

[0078] When the second selector valve 06 is in the second position, the first solenoid valve 041 controls the second port 0412 to communicate with the third port 0413, the second solenoid valve 042 controls the fourth port 0421 to communicate with the fifth port 0422, and the third port 0413 is connected to the fourth port 0421, thereby achieving communication between the pump group 03 and the flow channel 021. At this time, the pump group 03 can pump the reagent into the flow channel 021.

[0079] When the first selector valve assembly 04 is in the sixth position, the first solenoid valve 041 controls the second port 0412 to communicate with the third port 0413, the second solenoid valve 042 controls the fourth port 0421 to communicate with the sixth port 0423, and the third port 0413 is connected to the fourth port 0421, thereby achieving communication between the inert gas source 09 and the biochip 02. At this point, the biochip 02 can be dried.

[0080] The first solenoid valve 041 and the second solenoid valve 042 work together to switch the working positions of the first selector valve assembly 04. This simple, stable structure is less prone to failure. Furthermore, the solenoid valve components themselves are relatively low in cost, reducing the production cost of the gene sequencing fluid system and the operating and maintenance costs of the first selector valve assembly 04 during use.

[0081] When implementing the gene sequencing fluid system in the embodiment of the present application, the number of pumps 032 and the number of flow channels 021 are both at least one, that is, on the same biochip 02, only one flow channel can be set, or two, four, or six flow channels can be set at the same time; similarly, the fluid flow in the gene sequencing fluid system can be driven by only one pump 032, or by two, four, or six pumps 032 at the same time.

[0082] As an optional embodiment, when specifically setting the pumps 032 and the flow channels 021, the number of pumps 032 can be set to be the same as the number of flow channels 021, and the pumps 032 and the flow channels 021 correspond one to one. As an example, continue to refer to Figure 4 ,like Figure 4 Four flow channels 021 are provided in the biochip 02, and the pump 031 includes four injection pumps (0311, 0312, 0313, 0314), wherein the four flow channels 021 correspond one to one with the four injection pumps 031, that is, each injection pump is only responsible for pumping reaction reagents and buffer solutions into its corresponding flow channel 021.

[0083] When the first selector valve assembly consists of a first solenoid valve 041 and a second solenoid valve 042, the first selector valve assembly 04 includes four first solenoid valves 041 and four second solenoid valves 042. Each first solenoid valve 041 is connected to a second solenoid valve 042 to form a solenoid valve group. That is, the first selector valve assembly 04 includes four solenoid valve groups. The fifth port 0422 of each second solenoid valve 042 is connected to a syringe pump, and the second port 0412 of each first solenoid valve 041 is connected to a flow channel 021. The sixth port 0423 of all second solenoid valves 042 is connected to an inert gas source 09, and the first port 0411 of all first solenoid valves 041 is connected to the reagent reservoir 01. During sequencing operations, the four solenoid valve groups can maintain the same working position to perform functions of the gene sequencing fluid system, such as extracting reagents, delivering reagents to the biochip 02, draining waste liquids, cleaning, and drying.

[0084] By setting the same number of flow channels 021 and pumps 032 and corresponding them one to one, each pump 032 can be controlled individually to accurately control the amount of reagent injected into each flow channel 021, thereby improving the operating accuracy of the gene sequencing fluid system.

[0085] A second aspect of an embodiment of the present application also provides a gene sequencing fluid system, which includes a reaction reagent storage, a biochip, a first waste liquid storage, a first selection valve assembly and a pump assembly; wherein the first selection valve assembly has at least a reagent port, a pump port and at least one chip port.

[0086] The biochip includes at least one flow channel, which is used to provide a reaction area for gene sequencing; one end of each flow channel is connected to a chip port, and the other end of each flow channel is connected to a first waste liquid storage; the first waste liquid storage is used to store waste liquid generated during the gene sequencing process.

[0087] The reaction reagent reservoir is connected to the reagent port of the first selector valve assembly and is used to store the reaction reagents required for gene sequencing. The pump assembly is connected to the pump port of the first selector valve assembly and is used to drive the fluid flow in the gene sequencing fluid system.

[0088] The first selector valve assembly can selectively connect the reagent reservoir to the pump assembly or connect the flow channel to the pump assembly.

[0089] For the specific implementation and some possible methods of the gene sequencing fluid system, reference can be made to the relevant description of the gene sequencing fluid system provided in the first aspect of this embodiment.

[0090] The gene sequencing fluid system provided in the second aspect of this embodiment also includes a controller, which is configured to control the first selection valve assembly to be in a first position, so that the pump assembly is connected to the reaction reagent storage, and control the pump assembly to transport the reagent in the reaction reagent storage to the pipeline between the pump assembly and the first selection valve assembly by generating negative pressure; and control the first selector valve to be in a second position, so that the pump assembly is connected to the flow channel in the biochip, and control the pump assembly to transport the reagent in the pipeline between the pump assembly and the first selection valve assembly to the flow channel in the biochip by generating positive pressure.

[0091] The controller of this biochip fluid system can selectively control the first selector valve assembly to be in different working positions, and can control the pump assembly to first connect with the reaction reagent storage device and draw the reagent into the pipeline between the pump assembly and the first selector valve assembly for temporary storage under negative pressure. Then, the pump assembly is switched to connect with the flow channel of the biochip, and the reagent is pumped into the flow channel of the biochip under positive pressure. By pumping the reagent into the flow channel under positive pressure, the escape of gas dissolved in the reagent during the process of the reagent entering the flow channel from the pipeline is limited, thereby reducing the number of bubbles in the reagent in the flow channel and reducing the size of bubbles in the reagent in the flow channel.

[0092] A third aspect of an embodiment of the present application provides a gene sequencer, which includes any one of the gene sequencing fluid systems described in the first or second aspect above.

[0093] The gene sequencing fluid system of the gene sequencer receives a sequencing object in its flow channel. Specifically, the sequencing object can be a nucleotide sequence at one end, etc. The sequencing object contacts a reagent and undergoes a chemical reaction so as to carry a fluorescent marker. The optical detection system is configured to excite the fluorescent marker carried by the sequencing object and detect the fluorescent signal generated by the excited fluorescent marker. As for the computer system, it is configured to obtain a fluorescent image from the optical detection system and identify the gene sequence of the sequencing object based on the fluorescent image.

[0094] It should be noted that in a gene sequencer system, the sequencing sample can be, for example, blood, cell tissue, etc., from which a single-stranded DNA (deoxyribonucleotide) or single-stranded RNA (ribonucleotide) can be extracted and separated. In some implementations of the present application, the sequencing object can be, for example, a single-stranded DNA or RNA chain cut into multiple fragments, which are then chemically modified and linkers are added to the DNA or RNA fragments. That is, the sequencing object can be a library obtained through a library preparation process, or the sequencing object can be an entire single-stranded DNA or RNA chain, where the RNA can be obtained by DNA transcription.

[0095] During the gene sequencing process, the gene sequencing fluid system of the aforementioned gene sequencer, through the selection of the first selector valve assembly, can control the pump assembly to first connect with the reaction reagent storage device and draw the reagent into the pipeline between the pump assembly and the first selector valve assembly for temporary storage under negative pressure. The pump assembly then switches to connect with the flow channel of the biochip, and then positively pumps the reagent into the flow channel of the biochip. By pumping the reagent into the flow channel under positive pressure, the escape of gas dissolved in the reagent during the process of entering the flow channel from the pipeline is limited, thereby reducing the number and size of bubbles in the reagent in the flow channel.

[0096] The one or more embodiments of this specification are intended to cover all such substitutions, modifications, and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of one or more embodiments of this specification shall be included within the scope of protection of this disclosure.

[0097] The above are only specific embodiments of the present application, but the scope of protection of this application is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in this application should be included in the scope of protection of this application. Therefore, the scope of protection of this application should be based on the scope of protection of the claims.

Claims

1. A gene sequencing fluid system, characterized in that: include: Reaction reagent storage, biochip, first waste liquid storage, first selection valve assembly and pump assembly; wherein, The first selection valve assembly has at least a reagent port, a pump port and at least one chip port; The biochip includes at least one flow channel, which is used to provide a reaction area for gene sequencing; one end of each flow channel is connected to one of the chip ports, and the other end of each flow channel is connected to the first waste liquid storage; the first waste liquid storage is used to store waste liquid generated during the gene sequencing process; The reaction reagent storage is in communication with the reagent port of the first selection valve assembly, and the reaction reagent storage is used to store the reaction reagents required for gene sequencing; The pump assembly is in communication with the pump port of the first selection valve assembly, and the pump assembly is used to drive the fluid flow in the gene sequencing fluid system; The first selection valve assembly can selectively connect the reaction reagent reservoir to the pump assembly or connect the flow channel to the pump assembly.

2. The gene sequencing fluid system according to claim 1, characterized in that The gene sequencing fluid system further includes a second waste liquid storage, and the pump assembly includes a second selection valve and at least one pump; The second selection valve has a plurality of ports, and the plurality of ports are respectively in communication with at least the pump port of the first selection valve assembly, the second waste liquid reservoir, and the pump; The second selector valve is used to selectively connect the pump to the pump port of the first selector valve assembly or to connect the pump to the second waste liquid storage; The second waste liquid storage is used to store the fluid discharged from the pump.

3. The gene sequencing fluid system according to claim 2, characterized in that: The number of the pumps is equal to the number of the flow channels, and the pumps correspond to the flow channels one by one.

4. The gene sequencing fluid system according to claim 2, characterized in that: The gene sequencing fluid system further includes a buffer storage device, wherein the buffer storage device is used to store a buffer solution required for cleaning the flow channel; The buffer reservoir is connected to one of the plurality of ports of the second selector valve, and the second selector valve can further selectively connect the pump to the buffer reservoir.

5. The gene sequencing fluid system according to any one of claims 1 to 4, characterized in that: The gene sequencing fluid system further includes an inert gas source, which is used to provide the inert gas required to dry the flow channel; The first selector valve assembly further has an inert gas port to which the inert gas source is connected, and the first selector valve assembly can also selectively connect the flow channel to the inert gas source.

6. The gene sequencing fluid system according to claim 5, characterized in that: The gene sequencing fluid system further includes a pressure valve; The pressure valve is disposed between the inert gas source and the first selection valve assembly, and is used to adjust and control the pressure of the inert gas injected into the flow channel.

7. The gene sequencing fluid system according to claim 6, characterized in that: The gene sequencing fluid system further includes a flow meter; The flow meter is connected between the inert gas source and the first selector valve assembly and is used to monitor the working flow rate of the inert gas injected into the flow channel.

8. The gene sequencing fluid system according to claim 5, characterized in that: The first selector valve assembly includes a first solenoid valve and a second solenoid valve; The first solenoid valve has a first port, a second port and a third port; the second solenoid valve has a fourth port, a fifth port and a sixth port; The first port is in communication with the reaction reagent storage, the second port is in communication with the flow channel, the fifth port is in communication with the pump assembly, and the sixth port is in communication with the inert gas source; The third port is communicated with the fourth port. Meanwhile, the third port can be selectively communicated with the first port or the second port, and the fourth port can be selectively communicated with the fifth port or the sixth port.

9. A gene sequencing fluid system, characterized in that: include: Reaction reagent storage, biochip, first waste liquid storage, first selection valve assembly and pump assembly; wherein, The first selection valve assembly has at least a reagent port, a pump port and at least one chip port; The biochip includes at least one flow channel, which is used to provide a reaction area for gene sequencing; one end of each flow channel is connected to one of the chip ports, and the other end of each flow channel is connected to the first waste liquid storage; the first waste liquid storage is used to store waste liquid generated during the gene sequencing process; The reaction reagent storage is in communication with the reagent port of the first selection valve assembly, and the reaction reagent storage is used to store the reaction reagents required for gene sequencing; The pump assembly is in communication with the pump port of the first selection valve assembly, and the pump assembly is used to drive the fluid flow in the gene sequencing fluid system; The first selector valve assembly can selectively connect the reaction reagent reservoir to the pump assembly or connect the flow channel to the pump assembly; The gene sequencing fluid system also includes a controller, configured to control the first selection valve assembly to be in a first position, so that the pump assembly is connected to the reaction reagent storage, and control the pump assembly to transport the reagent in the reaction reagent storage to the pipeline between the pump assembly and the first selection valve assembly by generating negative pressure; and control the first selection valve to be in a second position, so that the pump assembly is connected to the flow channel in the biochip, and control the pump assembly to transport the reagent in the pipeline between the pump assembly and the first selection valve assembly to the flow channel in the biochip by generating positive pressure.

10. A gene sequencer, characterized in that: comprising an optical detection system and a computer system, and further comprising the gene sequencing fluid system according to any one of claims 1 to 8 or the gene sequencing fluid system according to claim 9; The flow channel in the biochip receives a sequencing object, and the sequencing object contacts the reagent and undergoes a chemical reaction so as to carry a fluorescent label; The optical detection system is configured to excite the fluorescent marker carried by the sequencing object and detect the fluorescent signal generated by the excited fluorescent marker; The computer system is configured to obtain a fluorescent image from the optical detection system and identify the gene sequence of the sequencing object based on the fluorescent image.

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