US-20260124617-A1 - FLUID SYSTEM, FLUID TRANSPORT METHOD, GENE SEQUENCER, AND BIOCHEMICAL ASSAY METHOD

US20260124617A1US 20260124617 A1US20260124617 A1US 20260124617A1US-20260124617-A1

Abstract

Provided are a fluid system, a fluid transport method, a gene sequencer, and a biochemical assay method. The fluid transport method includes the following steps: step a) of aspirating a first fluid from a fluid cartridge by using a pump valve assembly, so that the first fluid is input from an outlet of a flow cell into a lane of the flow cell, and the first fluid output from an inlet of the flow cell is returned to the fluid cartridge; and/or step b) of aspirating a second fluid from a fluid cartridge by using a pump valve assembly, so that the second fluid is input from the inlet of the flow cell into the lane of the flow cell, and the second fluid output from the outlet of the flow cell is returned to the fluid cartridge.

Inventors

Zihua Niu
HAO LU
CHUTIAN XING
XINGYE CUI

Assignees

MGI TECH CO., LTD.

Dates

Publication Date: 20260507
Application Date: 20221008

Claims (20)

1 . A fluid transport method, comprising: step a) of aspirating a first fluid from a fluid cartridge by using a pump valve assembly, so that the first fluid is input from an outlet of a flow cell into a lane of the flow cell, and the first fluid output from an inlet of the flow cell is returned to the fluid cartridge; and/or step b) of aspirating a second fluid from a fluid cartridge by using a pump valve assembly, so that the second fluid is input from the inlet of the flow cell into the lane of the flow cell, and the second fluid output from the outlet of the flow cell is returned to the fluid cartridge.
2 . The fluid transport method according to claim 1 , wherein the pump valve assembly comprises a fluid driving assembly configured to provide a positive pressure driving force or a negative pressure driving force in the step a) and the step b); and wherein the step a) comprises: a positive pressure driving step of generating the positive pressure driving force on an outlet side of the flow cell so that the first fluid is input into the lane from the outlet; or a negative pressure driving step of generating the negative pressure driving force on an inlet side of the flow cell so that the first fluid is input into the lane from the outlet.
3 . The fluid transport method according to claim 2 , wherein the pump valve assembly further comprises a first fluid loading module configured to be switchable at least between a first position for fluidly connecting the fluid driving assembly to the fluid cartridge and a second position for fluidly connecting the fluid driving assembly to the outlet of the flow cell; and wherein the step a) comprises: firstly switching the first fluid loading module to the first position so that the negative pressure driving force is generated to aspirate the first fluid from the fluid cartridge, and then switching the first fluid loading module to the second position so that the positive pressure driving step is performed on the outlet side of the flow cell.
4 . The fluid transport method according to claim 3 , wherein the pump valve assembly further comprises a second fluid loading module configured to be switchable at least between a first position for fluidly connecting the inlet of the flow cell to the fluid cartridge and a second position for fluidly connecting the inlet of the flow cell to the fluid driving assembly; wherein the first fluid loading module is further configured to be switchable between the first position, the second position, and a third position for fluidly connecting the fluid cartridge to the outlet of the flow cell; and wherein the step a) comprises: firstly switching the first fluid loading module to the first position so that the negative pressure driving force is generated to aspirate the first fluid from the fluid cartridge, and then switching the first fluid loading module to the second position and switching the second fluid loading module to the first position so that the positive pressure driving step is performed on the outlet side of the flow cell; or switching the first fluid loading module to the third position and switching the second fluid loading module to the second position so that the negative pressure driving step is performed on the inlet side of the flow cell.
5 . The fluid transport method according to claim 4 , wherein the fluid cartridge comprises a sample cartridge and a first reagent kit arranged in parallel, and the fluid transport method further comprises: selectively performing a fluid transport of a sample in the sample cartridge or a fluid transport of a reagent in the first reagent kit.
6 . The fluid transport method according to claim 5 , wherein a second reagent kit in fluid communication with the second fluid loading module is provided, and the second fluid loading module is further configured to be switchable between the first position, the second position, and a third position for fluidly connecting the second reagent kit to the inlet of the flow cell; and wherein the step b) comprises: switching the first fluid loading module to the second position and switching the second fluid loading module to the third position, so that the negative pressure driving force is generated on the outlet side of the flow cell to input a reagent in the second reagent kit into the lane of the flow cell from the inlet.
7 . The fluid transport method according to claim 6 , wherein a fluid drive control assembly is provided, and the fluid transport method further comprises: controlling at least one of the fluid driving assembly, the first fluid loading module or the second fluid loading module through the fluid drive control assembly, wherein a sample cartridge/reagent kit recovery module is provided, and the fluid transport method further comprises: recovering the sample cartridge and/or the first reagent kit through the sample cartridge/reagent kit recovery module.
8 . (canceled)
9 . The fluid transport method according to claim 6 , wherein the fluid cartridge further comprises a cleaning module a cleaning liquid/pure water storage module in fluid communication with the cleaning module, and a waste liquid storage module in fluid communication with the cleaning module, and the fluid transport method further comprises: performing cleaning of the lane of the flow cell by using the cleaning module, the cleaning liquid/pure water storage module and the waste liquid storage module, wherein the cleaning module is arranged in parallel with the sample cartridge and the first reagent kit, and the fluid transport method further comprises: selectively performing the fluid transport of the sample in the sample cartridge, the fluid transport of the reagent in the first reagent kit, or the cleaning of the lane of the flow cell; and performing the cleaning of the lane of the flow cell through the positive pressure driving step or the negative pressure driving step in the step a) or through the step b) when the cleaning of the lane of the flow cell is selectively performed.
10 - 12 . (canceled)
13 . A fluid system, comprising: a flow cell comprising a plurality of lanes, inlets and outlets; a sample cartridge and a first reagent kit, wherein the sample cartridge is configured to store a sample, and the first reagent kit is configured to store a reagent for sequencing; a fluid driving assembly configured to generate a driving force to transport the sample or the reagent in the fluid system; and a first fluid loading module on an outlet side of the flow cell, wherein the first fluid loading module is configured to be switchable at least between a first position for fluidly connecting the fluid driving assembly to a fluid cartridge, a second position for fluidly connecting the fluid driving assembly to the outlet of the flow cell, and a third position for fluidly connecting the fluid cartridge to the outlet of the flow cell.
14 . The fluid system according to claim 13 , wherein the first fluid loading module comprises: a first valve group consisting of a plurality of first valves, a second valve group consisting of a plurality of second valves, and a first pipette assembly consisting of a plurality of first pipettes, wherein the plurality of first valves, the plurality of second valves and the plurality of first pipettes correspond to the plurality of lanes of the flow cell respectively; wherein each first valve is connected to the fluid driving assembly, a corresponding first pipette and a corresponding lane of the flow cell, and each first valve is configured to be switchable at least between a first position for fluidly connecting the fluid driving assembly to the first pipette and a second position for fluidly connecting the fluid driving assembly to an outlet of the corresponding lane of the flow cell; and wherein each second valve is connected to the fluid driving assembly, a corresponding first valve and a corresponding lane of the flow cell, and each second valve is configured to be switchable at least between a first position for connecting the fluid driving assembly to the corresponding first valve and a second position for directly fluidly connecting the fluid driving assembly to an outlet of the corresponding lane of the flow cell.
15 . The fluid system according to claim 13 , wherein the first fluid loading module further comprises: a plurality of groups of sensing assemblies, wherein each group of sensing assemblies is connected between the fluid driving assembly and an outlet of a corresponding lane of the flow cell, and each group of sensing assemblies is configured to monitor fluid characteristics.
16 . The fluid system according to claim 14 , further comprising: a second fluid loading module on an inlet side of the flow cell, wherein the second fluid loading module is configured to be switchable at least between a first position for fluidly connecting the inlet of the flow cell to the fluid cartridge and a second position for fluidly connecting the inlet of the flow cell to the fluid driving assembly, and at least one second reagent kit on an inlet side of the plurality of lanes of the flow cell, wherein the second fluid loading module is arranged between the inlets of the plurality of lanes of the flow cell and the at least one second reagent kit.
17 . (canceled)
18 . The fluid system according to claim 16 , wherein the second fluid loading module further comprises: a solenoid valve, a third valve group consisting of a plurality of third valves, a second pipette assembly consisting of a plurality of second pipettes, and a manifold assembly, wherein the plurality of third valves and the plurality of second pipettes correspond to the plurality of lanes of the flow cell respectively, and the plurality of second pipettes are connected to the at least one second reagent kit and are in fluid communication with the plurality of lanes of the flow cell via the manifold assembly; wherein each third valve has a first port connected to the manifold assembly and a second port connected to a corresponding second pipette, and each third valve is configured to be switchable between a first position for closing fluid communication between the manifold assembly and the corresponding second pipette and a second position for opening the fluid communication between the manifold assembly and the corresponding second pipette; and wherein the plurality of lanes of the flow cell are connected to the sample cartridge or the first reagent kit via the solenoid valve
19 . The fluid system according to claim 18 , further comprising: a fluid drive control assembly configured to control at least one of the fluid driving assembly, the first fluid loading module or the second fluid loading module, a sample cartridge/reagent kit recovery module configured to recover the sample cartridge and/or the first reagent kit; a cleaning module between the fluid driving assembly and the first fluid loading module, wherein the cleaning module is configured to perform cleaning of the plurality of lanes of the flow cell; a cleaning liquid/pure water storage module in fluid communication with the cleaning module and the second fluid loading module, wherein the cleaning liquid/pure water storage module is configured to provide cleaning liquid and/or pure water when the cleaning of the plurality of lanes of the flow cell is performed; and a waste liquid storage module in fluid communication with the cleaning module and the fluid driving assembly, wherein the waste liquid storage module is configured to recover and/or discharge waste liquid, wherein the fluid driving assembly comprises: a syringe having a plurality of independent channels, and a plurality of reversing valves; wherein the plurality of independent channels and the plurality of reversing valves correspond to the plurality of lanes of the flow cell respectively; and wherein the plurality of reversing valves are controllable individually or simultaneously.
20 - 28 . (canceled)
29 . The fluid system according to claim 16 , further comprising: a sequencing platform between the first fluid loading module and the second fluid loading module; a loading platform between the sample cartridge and the fluid driving assembly and between the first reagent kit and the fluid driving assembly; and an automatic transfer device configured to automatically transfer the flow cell between the sequencing platform and the loading platform.
30 . A gene sequencer, comprising: the fluid system according to claim 13 .

Description

CROSS REFERENCE TO RELATED APPLICATION(S) This application is a National Stage Application of International Application No. PCT/CN2022/123789, filed on Oct. 8, 2022, entitled “FLUID SYSTEM, FLUID TRANSPORT METHOD, GENE SEQUENCER, AND BIOCHEMICAL ASSAY METHOD”, the entire contents of which are incorporated herein in their entireties by reference. TECHNICAL FIELD The present disclosure relates to a fluid system, a fluid transport method, a gene sequencer, and a biochemical assay method. BACKGROUND After decades of development, gene sequencing technology has been widely used in the field of medical health, such as infectious disease tracing, targeted tumor treatment, and whole genome testing. These diverse applications require gene sequencers to have increasing flexibility, especially in terms of types and quantities of samples supported in each sequencing run. To meet this demand, a gene sequencing chip is generally designed to have a plurality of lanes each loaded with different DNA samples. On the other hand, reagents used in a gene sequencing process are expensive, and an amount of reagents needs to be minimized. Therefore, there is typically only one pipeline connecting the sequencing chip and the reagent kit to reduce a pipeline volume and a loss of reagents in the pipeline. The pipeline may be divided into a plurality of branches at a front end of the sequencing chip, to connect to the plurality of lanes of the chip respectively. This leads to a contradiction that different samples are inevitably mixed in the pipeline before reaching different lanes of the chip, thus failing to meet the requirement that each lane corresponds to one sample. To achieve loading of multiple samples, three methods are generally adopted in the related art. A first method is to pre-treat different DNA samples by attaching a known base sequence as a “barcode” to distinguish samples. The samples are then mixed together and uniformly loaded into the lanes of the chip. After sequencing is completed, the mixed samples may be split and identified using the barcode. A second method is to load samples outside the sequencer (off-sequencer), which requires a specially designed automated instrument or is implemented manually. The samples are firstly loaded into the chip, and then the chip is transferred to the sequencer for subsequent sequencing steps. A third method is to load samples in reverse through a fluid system on the sequencer so that different samples are loaded into different chip lanes. These three related methods described above have the following disadvantages. In the first method, the samples are mixed by means of barcode, and the mixed samples need to be split and identified using the barcode at the end of sequencing, which greatly increases sequencing cost and sequencing time. In the second method, loading samples outside the sequencer involves many steps and is inefficient, which also increases sequencing time and sequencing cost. In the third method, designs of the fluid system and the reverse loading of samples need to be further optimized. SUMMARY According to an aspect of the embodiments of the present disclosure, a fluid transport method is provided, including: step a) of aspirating a first fluid from a fluid cartridge by using a pump valve assembly, so that the first fluid is input from an outlet of a flow cell into a lane of the flow cell, and the first fluid output from an inlet of the flow cell is returned to the fluid cartridge; and/orstep b) of aspirating a second fluid from a fluid cartridge by using a pump valve assembly, so that the second fluid is input from the inlet of the flow cell into the lane of the flow cell, and the second fluid output from the outlet of the flow cell is returned to the fluid cartridge. In some exemplary embodiments, the pump valve assembly includes a fluid driving assembly configured to provide a positive pressure driving force or a negative pressure driving force in the step a) and the step b); and the step a) includes: a positive pressure driving step of generating the positive pressure driving force on an outlet side of the flow cell so that the first fluid is input into the lane from the outlet; or a negative pressure driving step of generating the negative pressure driving force on an inlet side of the flow cell so that the first fluid is input into the lane from the outlet. In some exemplary embodiments, the pump valve assembly further includes a first fluid loading module configured to be switchable at least between a first position for fluidly connecting the fluid driving assembly to the fluid cartridge and a second position for fluidly connecting the fluid driving assembly to the outlet of the flow cell; and the step a) includes: firstly switching the first fluid loading module to the first position so that the negative pressure driving force is generated to aspirate the first fluid from the fluid cartridge, and then switching the first fluid loading module to the second