Fluid system, biochemical analysis and detection platform and fluid operation method

CN119630973AActive Publication Date: 2025-03-14MGI TECH CO LTD
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Patent Information

Application Number
CN202280098822.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2022-11-29
Publication Date
2025-03-14
Estimated Expiration
2042-11-29

AI Technical Summary

Technical Problem

Existing fluid systems have problems with cross-contamination between reagents during the reagent recovery process, resulting in reduced purity of target reagents and more serious interactions, affecting detection efficiency and cost control.

Method used

A fluid system is designed. By introducing bypass flow paths and branch flow paths, and using the configuration of reversing components, the concentration of reagents can be adjusted and isolated before entering the flow cell to ensure that there is no contact between reagents, and through parallel sample reactions and reagents Recycling operations shorten working times.

Benefits of technology

It effectively reduces cross-contamination between reagents, improves reagent purity and recovery efficiency, shortens the waiting time for detection steps, and reduces overall work costs.

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Abstract

The invention discloses a fluid system, a biochemical analysis detection platform and a fluid operation method. The fluidic system comprises one or more first main flow paths (L6) configured to connect the reagent storage chambers; a second main flow path (L1); a reaction flow path comprising a flow cell (C1); a bypass flow path (L5) connected in parallel with the reaction flow path; a third main flow path (L4); one or more branch flow paths; the first reversing component (T1) is connected with one or more first main flow paths (L6), the second main flow path (L1) and at least one branch flow path, so that any two different types of flow paths in the connected flow paths are communicated, and the other flow paths are disconnected; the second reversing part (T2) is connected with the second main flow path (L1), the reaction flow path and the bypass flow path (L5), so that any two flow paths in the connected flow paths are communicated and the other flow paths are disconnected; and a third reversing member (T3) which connects the third main flow path (L4), the reaction flow path, and the bypass flow path (L5) so that any two of the connected flow paths communicate with each other and the remaining flow paths are disconnected.
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Description

Fluid system, biochemical analysis detection platform and fluid operation method Technical Field

[0001] The embodiments of the present disclosure relate to the technical field of fluid systems, and in particular to a fluid system, a biochemical analysis and detection platform, and a fluid operation method. Background Art

[0002] Molecular biological detection technologies such as gene sequencing, polymerase chain reaction (PCR), and biochips are being increasingly widely used in many scenarios such as non-invasive prenatal testing and detection of infectious pathogens such as the new coronavirus. These application scenarios are usually carried out in complex biochemical analysis and detection platforms.

[0003] Biochemical analysis and testing platforms generally involve one or more target cavities, into which samples and various reactants are transported in solution for reaction or detection. Taking a gene sequencer as an example, the DNA sample to be tested is generally fixed on the surface of a flow cell with an internal flow channel. The detection of the DNA sample is a periodic cycle, with each cycle detecting one base. Within a single cycle, multiple functional reagents or buffer solutions are sequentially transported from a storage container to the flow cell through a fluid system. Other biochemical analysis and testing platforms also have similar fluid systems and liquid transport processes.

[0004] The functional reagents consumed in the above process are often very expensive, which is one of the main factors that currently restrict the further popularization and large-scale routine application of molecular biology detection technologies such as gene sequencing. Therefore, reducing reagent costs has always been a key task in the development of biochemical analysis and detection platforms. There are two main ways to reduce costs: one is to reduce the unit volume price of reagents, and the other is to reduce the amount of reagents used. Among them, the unit volume cost of reagents is not only strongly related to factors such as formulation and process, but also subject to market supply and demand. Therefore, reducing the volume of reagents used is a more effective way to reduce costs. Among them, although reducing the length of the reagent transport pipeline can intuitively reduce losses, it is often restricted by the overall structural layout and has a lower length limit; in addition, reducing the diameter of the transport pipeline will lead to excessive pressure drop in the entire fluid system. In short, although there is room for optimization of the physical internal volume of the pipeline, it is easy to encounter bottlenecks.

[0005] Another strategy for reducing reagent usage is to recycle and reuse reagents. Still using a gene sequencer as an example, assume that without recycling, a volume of V1 of reagent is used in each cycle. After the cycle is complete, this volume of reagent is no longer used and is discharged as waste. With recycling, each cycle removes a volume of V1 of reagent from the storage container to the flow cell for reaction. After the reaction, V2 is recovered. The net amount of reagent used is V1-V2, reducing reagent costs.

[0006] In the related art, a power source is generally used to directly reversely drive the reagent backflow to recover and reuse part of the reagent. In the process of discovering the present disclosure, the inventors found that in the above related art:

[0007] In actual flow, especially in the field of microfluidics, since the flow velocity is low near the wall and high away from the wall, the interface between the two reagents is the parabola P shown in Figure 1. Therefore, the target reagent recovered each time is actually mixed with other reagents. The reagent reflux method that uses a power source to directly reversely drive the reflux of part of the reagent may cause cross-contamination between reagents. In some scenarios, such cross-mixing will not only reduce the purity of the target reagent, but also lead to adverse reactions. When the recovery rate is high, other reagents may even enter the initial storage area of ​​the target reagent, resulting in more serious cross-contamination.

[0008] Summary of the Invention

[0009] The present disclosure aims to provide a fluid system, a biochemical analysis and detection platform, and a fluid operation method. The fluid system aims to reduce cross-contamination between different reagents when recovering reagents and reduce the overall working time of the system.

[0010] A first embodiment of the present disclosure provides a fluid system, comprising:

[0011] one or more first main flow paths configured to connect to at least one reagent storage chamber;

[0012] Second main road;

[0013] reaction flow path, including flow cell;

[0014] a bypass flow path, connected in parallel with the reaction flow path;

[0015] the third mainstream road;

[0016] one or more branch flow paths; and

[0017] A plurality of switching components, the plurality of switching components comprising:

[0018] a first reversing component, connecting the one or more first main channels, the second main channel, and the at least one branch channel, and configured to enable the second main channel to selectively communicate with any one of the one or more first main channels and the at least one branch channel, while disconnecting the remaining channels connected to the first reversing component;

[0019] a second reversing component, connecting the second main flow path, the reaction flow path, and the bypass flow path, and configured to selectively connect the second main flow path to any one of the reaction flow path and the bypass flow path, while disconnecting the remaining flow paths connected to the second reversing component; and

[0020] The third reversing component connects the third main flow path, the reaction flow path and the bypass flow path, and is configured to enable the third main flow path to selectively communicate with any one of the reaction flow path and the bypass flow path, while disconnecting the remaining flow paths connected to the third reversing component.

[0021] In the fluid system of some embodiments, the reaction flow path further comprises:

[0022] A first flow cell flow path connecting the flow cell and the second reversing component; and / or

[0023] The second flow cell flow path connects the flow cell and the third reversing component.

[0024] In the fluid system of some embodiments, the reaction flow path includes two or more flow cells arranged in parallel.

[0025] In the fluid system of some embodiments, the one or more branch flow paths include a first waste liquid flow path, wherein the first waste liquid flow path is connected to the first reversing component and is configured to be connected to a waste liquid storage chamber.

[0026] In some embodiments of the fluid system,

[0027] The fluid system further comprises one or more fourth main flow paths, wherein the fourth main flow paths are configured to connect at least one reagent storage chamber and / or at least one waste liquid storage chamber;

[0028] The multiple switching components also include a fourth switching component, which connects the third main flow path, the one or more fourth main flow paths and at least one branch flow path, and is configured to enable the third main flow path to be selectively connected to any one of the one or more fourth main flow paths and the at least one branch flow path, while disconnecting the remaining flow paths connected to the fourth switching component.

[0029] In the fluid system of some embodiments, the one or more branch flow paths include a second waste liquid flow path, and the second waste liquid flow path is connected to the fourth reversing component and is configured to be connected to a waste liquid storage chamber.

[0030] In the fluid system of some embodiments, the one or more branch flow paths include a storage flow path, and the storage flow path includes:

[0031] storage tanks;

[0032] a first reservoir connecting flow path connecting the first reversing member and the reservoir; and

[0033] The second tank connecting flow path connects the fourth switching member and the tank.

[0034] In the fluid system of some embodiments, the storage flow path further includes a storage tank inlet flow path and / or a storage tank drain flow path connected to the storage tank.

[0035] In the fluid system of some embodiments, the one or more branch flow paths include the plurality of storage flow paths arranged in parallel, and the plurality of storage flow paths are selectively connected to the first reversing component and / or the fourth reversing component.

[0036] In the fluid system of some embodiments, at least one of the plurality of switching components is a rotary valve or a solenoid valve.

[0037] In the fluid system of some embodiments, the fluid system includes a driving mechanism for driving the flow of fluid in the fluid system, and the driving mechanism drives the flow of the fluid by positive pressure and / or negative pressure.

[0038] A second aspect of the present disclosure provides a biochemical analysis and detection platform, comprising the fluid system described in the first aspect of the present disclosure.

[0039] In some implementations of the biochemical analysis detection platform, a molecular biology detection device is included, and the molecular biology detection device includes the fluid system described above.

[0040] In the biochemical analysis detection platform of some embodiments, the molecular biology detection equipment includes a gene sequencer, and the gene sequencer includes the fluid system.

[0041] A third aspect of the present disclosure provides a fluid operation method of the fluid system according to the first aspect of the present disclosure, the fluid operation method comprising:

[0042] allowing the reagent to enter at least one end of the bypass flow path close to the second conversion component and the reaction flow path through the second main flow path;

[0043] Disconnecting the reaction channel from the second main channel and the third main channel, and allowing the reagent to undergo a biochemical reaction in the flow cell of the reaction channel; and

[0044] The reagent in the bypass flow channel and / or the reaction flow channel is recovered.

[0045] In the fluid manipulation method of some embodiments, the reagent in the bypass flow path is recovered while the reagent undergoes a biochemical reaction in the flow cell of the reaction flow path.

[0046] In the fluid operation method of some embodiments, part of the reagent in the bypass flow path is caused to flow to the second main flow path so as to recover the reagent in the bypass flow path through the second main flow path.

[0047] In the fluid operation method of some embodiments, the reagent in the reaction flow path is caused to flow to the second main flow path so as to recover the reagent in the reaction flow path through the second main flow path.

[0048] In some embodiments of the fluid operation method, the fluid operation method further includes allowing the reagent recovered through the second main flow path to flow to the first main flow path.

[0049] In some embodiments of the fluid operation method, the fluid operation method further includes flowing the reagent in the bypass loop and the reagent in the reaction flow path recovered through the second main flow path to the third main flow path to recover the reagent through the third main flow path.

[0050] In the fluid operation method of some embodiments, the fluid system further includes a storage flow path connected to the first conversion component and the fourth conversion component, and the fluid operation method includes allowing the reagent recovered through the third main flow path to flow to the storage flow path.

[0051] In some embodiments of the fluid manipulation method, the fluid manipulation method includes driving the reagent to flow within the fluid system through a buffer to recover the reagent.

[0052] In some embodiments of the fluid manipulation method, the fluid manipulation method includes discharging a mixed solution of the buffer solution and the reagent in which the concentration of the buffer solution or the reagent is less than a predetermined concentration into a waste liquid storage chamber.

[0053] In some embodiments of the fluid manipulation method,

[0054] The fluid operation method includes discharging the mixed solution of the buffer solution and the reagent, wherein the concentration of the buffer solution or the reagent is less than a predetermined concentration, into the waste liquid storage chamber through at least one branch flow path; and / or

[0055] The fluid system includes a fourth main flow path that is selectively connected to the third main flow path, and the fourth main flow path is configured to be connected to a waste liquid storage chamber. The fluid operation method includes discharging a mixed solution of the buffer solution and the reagent in which the concentration of the buffer solution or the reagent is less than a predetermined concentration into the waste liquid storage chamber through the fourth main flow path.

[0056] Based on the fluid system provided by the present disclosure, by introducing a bypass flow path at the upstream end of the flow cell, each time before the reagent enters the flow cell for reaction, the reagent with lower concentration will be led away from the bypass flow path, so as to ensure that the reagent entering the flow cell has a sufficiently high concentration. For example, different reagents are completely incontactable, and a buffer solution can be introduced with the participation of the bypass flow path and the branch flow path to isolate different reagents, so as to help reduce cross contamination between reagents. The fluid system provided by the present disclosure will also discharge bubbles that are not allowed to enter the flow cell from the bypass flow path before the reagent enters the flow cell for reaction. In addition, the fluid system provided by the present disclosure can perform sample reaction and reagent recovery operations in parallel, which can shorten the waiting time of the relevant steps and help improve overall work efficiency.

[0057] The biochemical analysis detection platform and fluid operation method provided by the present disclosure have the advantages of the fluid system provided by the present disclosure.

[0058] Other features and advantages of the present disclosure will become apparent from the following detailed description of exemplary embodiments of the present disclosure with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] The drawings described herein are used to provide a further understanding of the embodiments of the present disclosure and constitute a part of the present disclosure. The illustrative embodiments of the embodiments of the present disclosure and their descriptions are used to explain the embodiments of the present disclosure and do not constitute an improper limitation of the embodiments of the present disclosure. In the drawings:

[0060] FIG1 is a schematic diagram of the interface shape when the reagent flows in the flow channel.

[0061] FIG2 is a schematic diagram showing the principle of a fluid system according to an embodiment of the present disclosure.

[0062] 3 to 5 are schematic diagrams showing the principles of the fluid operation method of the fluid system of the embodiment shown in FIG. 2 .

[0063] FIG6 is a schematic diagram showing the principle of a fluid system according to an embodiment of the present disclosure.

[0064] 7 to 10 are schematic diagrams showing the principles of the fluid operation method of the fluid system of the embodiment shown in FIG. 6 .

[0065] FIG11 is a schematic diagram showing the principle of a fluid system according to an embodiment of the present disclosure.

[0066] FIG12 is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure.

[0067] 13 and 14 are schematic diagrams of the principle structure of the fluid operation method of the fluid system of the embodiment shown in FIG. 12 .

[0068] FIG15 is a schematic diagram of reagent distribution when a recovered reagent, a mixed reagent, and a fresh reagent coexist in a pipeline in the embodiment shown in FIG12 .

[0069] FIG16 is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure.

[0070] 17 and 18 are schematic diagrams of the principle structure of the fluid operation method of the fluid system of the embodiment shown in FIG. 16 .

[0071] FIG19 is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure.

[0072] FIG20 is a schematic diagram of a partial principle structure of the fluid system of FIG19. DETAILED DESCRIPTION

[0073] The following will be combined with the drawings in the embodiments of the present disclosure to clearly and completely describe the technical solutions in the embodiments of the present disclosure. Obviously, the described embodiments are only part of the embodiments of the present disclosure, rather than all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the embodiments of the present disclosure and its application or use. Based on the embodiments of the present disclosure, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the embodiments of the present disclosure.

[0074] Unless otherwise specifically stated, the relative arrangement of the parts and steps, numerical expressions and numerical values ​​set forth in these embodiments do not limit the scope of the embodiments of the present disclosure. At the same time, it should be understood that, for ease of description, the sizes of the various parts shown in the drawings are not drawn according to actual proportional relationships. The techniques, methods and equipment known to those of ordinary skill in the relevant art may not be discussed in detail, but in appropriate cases, the techniques, methods and equipment should be considered as part of the specification. In all examples shown and discussed here, any specific values ​​should be interpreted as being merely exemplary, rather than as limitations. Therefore, other examples of the exemplary embodiments may have different values. It should be noted that similar numbers and letters represent similar items in the following figures, and therefore, once an item is defined in one figure, it does not need to be further discussed in subsequent figures.

[0075] An embodiment of the present disclosure provides a fluid system, including one or more first main flow paths L6 , a second main flow path L1 , a reaction flow path, a bypass flow path L5 , one or more branch flow paths, and a plurality of switching components.

[0076] The first main flow channel L6 is configured to connect to at least one reagent storage chamber.

[0077] The reaction flow path includes a flow cell C1.

[0078] The bypass flow path L5 is connected in parallel with the reaction flow path.

[0079] The plurality of switching elements include a first switching element T1 , a second switching element T2 , and a third switching element T3 .

[0080] The first switching component T1 connects one or more first main flow paths L6, the second main flow path L1 and at least one branch flow path, and is configured to enable the second main flow path L1 to be selectively connected to any one of the one or more first main flow paths L6 and at least one branch flow path, while disconnecting the remaining flow paths connected to the first switching component T1.

[0081] The second switching element T2 connects the second main flow path L1, the reaction flow path and the bypass flow path L5, and is configured to selectively connect the second main flow path L1 to any one of the reaction flow path and the bypass flow path L5, while disconnecting the remaining flow paths connected to the second switching element T2.

[0082] The third switching element T3 connects the third main flow path L4, the reaction flow path and the bypass flow path L5, and is configured to selectively connect the third main flow path L4 to any one of the reaction flow path and the bypass flow path L5, while disconnecting the remaining flow paths connected to the third switching element T3.

[0083] In the fluid system of the embodiment of the present disclosure, by introducing the bypass flow path L5 at the upstream end of the flow pool C1, each time before the reagent enters the flow pool C1 for reaction, the reagent with lower concentration or the bubble will be drawn away from the bypass flow path L5, thereby ensuring that the reagent entering the flow pool C1 has a sufficiently high concentration. For example, if different reagents are completely incontactable, a buffer solution can be introduced with the participation of the bypass flow path and the branch flow path to isolate the different reagents, thereby reducing cross-contamination between reagents; and bubbles that are not allowed to enter the flow pool C1 can also be discharged from the bypass flow path L5.

[0084] The fluid system provided by the present disclosure will also discharge bubbles that are not allowed to enter the flow cell C1 from the bypass flow path L5 before the reagents enter the flow cell for reaction.

[0085] Furthermore, by introducing the bypass flow path L5 and adding a branch flow path, the reagent recovery process and the biochemical reaction process can be highly parallelized, which can shorten the waiting time of the relevant steps and help improve the overall work efficiency.

[0086] In some embodiments of the fluid system, the reaction flow path further includes a first flow cell flow path L2 and / or a second flow cell flow path L3. The first flow cell flow path L2 connects the flow cell C1 and the second switching component T2. The second flow cell flow path L3 connects the flow cell C1 and the third switching component T3.

[0087] In the fluid system of some embodiments, the reaction flow path includes two or more flow cells C1 arranged in parallel.

[0088] In the fluid system of some embodiments, the one or more branch flow paths include a first waste liquid flow path L11 , which is connected to the first reversing component T1 and configured to be connected to the waste liquid storage chamber.

[0089] In the fluid system of some embodiments, the fluid system also includes one or more fourth main flow paths L7, and the fourth main flow path 7 is configured to connect at least one reagent storage chamber and / or at least one waste liquid storage chamber; the multiple switching components also include a fourth switching component T4, and the fourth switching component T4 connects the third main flow path L4, one or more fourth main flow paths L7 and at least one branch flow path, and is configured to enable the third main flow path L4 to be selectively connected to any one of the one or more fourth main flow paths L7 and at least one branch flow path, while the remaining flow paths connected to the fourth switching component T4 are disconnected.

[0090] Regarding flow path types, the first to fourth main flow paths belong to different types. For example, when multiple first main flow paths L6 are included, all first main flow paths L6 are of the same type. When multiple fourth main flow paths L7 are included, all fourth main flow paths L7 are of the same type. When multiple branch flow paths are included, all branch flow paths are of the same type. For another example, any two of the first main flow path L7, the second main flow path L1, and the branch flow paths belong to different types. And any two of the fourth main flow path L7, the second main flow path, and the branch flow paths belong to different types.

[0091] In the fluid system of some embodiments, the one or more branch flow paths include a second waste liquid flow path L12 , which is connected to the fourth reversing component T4 and configured to be connected to the waste liquid storage chamber.

[0092] In some embodiments of the fluid system, one or more branch flow paths include a reservoir flow path, which includes a reservoir C2, a first reservoir connecting flow path L8, and a second reservoir connecting flow path L9. The first reservoir connecting flow path L8 connects the first reversing component T1 and the reservoir C2. The second reservoir connecting flow path L9 connects the fourth reversing component T4 and the reservoir C2.

[0093] In the fluid system of some embodiments, the storage flow path further includes a storage tank inlet flow path L10 and / or a storage tank drain flow path L13 connected to the storage tank C2.

[0094] In the fluid system of some embodiments, the one or more branch flow paths include a plurality of storage flow paths arranged in parallel.

[0095] In the fluid system of some embodiments, at least one of the plurality of switching components is a rotary valve or a solenoid valve.

[0096] In the fluid system of some embodiments, the fluid system includes a driving mechanism for driving the flow of fluid in the fluid system, and the driving mechanism drives the flow of fluid by positive pressure and / or negative pressure.

[0097] The present disclosure also provides a biochemical analysis and detection platform, including the fluid system of the present disclosure. The biochemical analysis and detection platform of the present disclosure has the same advantages as the fluid system of the present disclosure.

[0098] The biochemical analysis detection platform includes, for example, a molecular biology detection device, which includes the fluid system of the embodiment of the present disclosure. Since the molecular biology detection device includes the fluid system of the embodiment of the present disclosure, the fluid operation method of the embodiment of the present disclosure can also be used.

[0099] The molecular biology detection equipment includes, for example, a gene sequencer, which includes the fluid system of the embodiment of the present disclosure. Since the gene sequencer includes the fluid system of the embodiment of the present disclosure, the fluid operation method of the embodiment of the present disclosure can also be adopted.

[0100] The embodiment of the present disclosure also provides a fluid operation method of the fluid system of the embodiment of the present disclosure, and the fluid operation method includes: allowing the reagent to enter the bypass flow path L5 at least at one end close to the second conversion component T2 and the reaction flow path through the second main flow path L1; disconnecting the reaction flow path from the second main flow path L1 and the third main flow path L4, and the reagent undergoing a biochemical reaction in the flow pool C1 of the reaction flow path; and recovering the reagent in the bypass flow path L5 and / or the reaction flow path.

[0101] The fluid operation method according to the embodiment of the present disclosure has the same advantages as the fluid system according to the embodiment of the present disclosure.

[0102] In the fluid manipulation method of some embodiments, while the reagent undergoes a biochemical reaction in the flow cell C1 of the reaction flow path, the reagent in the bypass flow path L5 is recovered.

[0103] In the fluid operation method of some embodiments, part of the reagent in the bypass flow path L5 is made to flow to the second main flow path L1 so as to recover the reagent in the bypass flow path L5 through the second main flow path L1 .

[0104] In the fluid operation method of some embodiments, the reagent in the reaction flow path is made to flow to the second main flow path L1 so as to recover the reagent in the reaction flow path through the second main flow path L1.

[0105] In some embodiments of the fluid operation method, the fluid operation method further includes allowing the reagent recovered through the second main flow path L1 to flow to the first main flow path L6.

[0106] In some embodiments of the fluid operation method, the fluid operation method further includes flowing the reagent in the bypass loop L5 and the reagent in the reaction flow path recovered through the second main flow path L1 to the third main flow path L4 to recover the reagent through the third main flow path L4.

[0107] In some embodiments of the fluid operation method, the fluid system further includes a storage flow path connected to the first conversion component T1 and the fourth conversion component T4 , and the fluid operation method includes allowing the reagent recovered through the third main flow path L4 to flow to the storage flow path.

[0108] In some embodiments of the fluid manipulation method, the fluid manipulation method includes driving a reagent through a buffer solution within a fluid system to recover the reagent.

[0109] In some embodiments of the fluid manipulation method, the fluid manipulation method includes discharging a mixed solution of a buffer and a reagent in which the concentration of the buffer or the reagent is less than a predetermined concentration into a waste liquid storage chamber.

[0110] In some embodiments of the fluid operation method, the fluid operation method includes discharging a mixture of a buffer solution and a reagent in which the concentration of the buffer solution or the reagent is less than a predetermined concentration into a waste liquid storage chamber through at least one branch flow path; and / or the fluid system includes a fourth main flow path L7 that is selectively connected to the third main flow path L4, and the fourth main flow path L7 is configured to be connected to the waste liquid storage chamber, and the fluid operation method includes discharging a mixture of a buffer solution and a reagent in which the concentration of the buffer solution or the reagent is less than a predetermined concentration into the waste liquid storage chamber through the fourth main flow path L7.

[0111] The fluid system and fluid operation method of the embodiment of the present disclosure are described in more detail below with reference to FIG. 2 to FIG. 20 .

[0112] Figures 2 to 5 illustrate schematic diagrams of the principles of an embodiment of the present disclosure. Figure 2 is a schematic diagram of the principles of the fluid system of this embodiment. Figures 3 to 5 are schematic diagrams of the principles of the fluid operation method of the fluid system of the embodiment shown in Figure 2.

[0113] As shown in Figures 2 to 5, the fluid system of the embodiment of the present disclosure includes a first main flow path L6, a second main flow path L1, a reaction flow path, a bypass flow path L5, a third main flow path L4, a fourth main flow path L7, a first waste liquid flow path L11 as a branch flow path, a second waste liquid flow path L12 as a branch flow path, a first reversing component T1, a second reversing component T2, a third reversing component T3 and a fourth reversing component T4.

[0114] The reaction flow path includes a flow cell C1 and a first flow cell flow path L2 and a second flow cell flow path L3 respectively connected to the flow cell C1. A bypass flow path L5 is connected in parallel with the reaction flow path. The first waste liquid flow path L11 is configured to connect to a waste liquid storage chamber. The second waste liquid flow path L12 is configured to connect to a waste liquid storage chamber. The first reversing component T1 connects the first main flow path L6, the second main flow path L1, and the first waste liquid flow path L11, and is configured to selectively connect any two of the first main flow path L6, the second main flow path L1, and the first waste liquid flow path L11, while the remaining flow paths are disconnected from the two connected flow paths. The second reversing component T2 connects the second main flow path L1, the first flow cell flow path L2, and the bypass flow path L5, and is configured to selectively connect any two of the second main flow path L1, the first flow cell flow path L2, and the bypass flow path L5, while the remaining flow paths are disconnected from the two connected flow paths. The third reversing element T3 connects the third main flow path L4, the second flow cell flow path L3, and the bypass flow path L5, and is configured to selectively connect any two of the third main flow path L4, the second flow cell flow path L3, and the bypass flow path L5, while disconnecting the remaining flow path from the two connected flow paths. The fourth reversing element T4 connects the third main flow path L4, the fourth main flow path L7, and the second waste liquid flow path L12, and is configured to selectively connect any two of the third main flow path L4, the fourth main flow path L7, and the second waste liquid flow path L12, while disconnecting the remaining flow path from the two connected flow paths.

[0115] The following describes a logic sequence scheme of a fluid operation method including a reagent recovery process that can be implemented in accordance with an embodiment of the present disclosure, in conjunction with Figures 2 to 5. In this logic sequence scheme, reagent A is a reagent that needs to be partially recovered, reagent B is a reagent that cannot be cross-contaminated with reagent A and does not need to be recovered, and buffer C serves as an intermediate medium separating reagents A and B. Three liquids, namely reagent A, reagent B and buffer C, constitute the minimum component system of the reagent recovery scheme. In actual applications, the component system of the reagent recovery scheme can be expanded. For example, the reagents to be recovered can include multiple types, namely A1, A2, A3...An.

[0116] In the logic sequence scheme of the disclosed embodiment, the first main flow path L6 is described as the upstream of the fluid system. The upstream of the first main flow path L6 is in fluid communication with the storage chamber for reagent A; the downstream of the fourth main flow path L7 is in fluid communication with the storage chambers for other reagents (such as reagent B and buffer C); and the downstream of the first waste liquid flow path L11 and the second waste liquid flow path L12 are in fluid communication with the waste liquid storage chamber.

[0117] The steps of the logical timing scheme of the fluid operation method are as follows:

[0118] Step S1100: In the initial state, reagent A is contained in the first main channel L6; buffer C is contained in the flow cell C1; buffer C is contained in the second main channel L1, the first flow cell channel L2, the second flow cell channel L3, the third main channel L4, the bypass channel L5, and the fourth main channel L7; reagent B has not yet entered the fluid system. The first reversing component T1 connects the first main channel L6 with the second main channel L1; the second reversing component T2 connects the second main channel L1 with the bypass channel L5; the third reversing component T3 connects the bypass channel L5 with the third main channel L4; and the fourth reversing component T4 connects the third main channel L4 with the second waste channel L12.

[0119] Step S1101: Reagent A flows from the first main flow channel L6 through the first reversing component T1 into the second main flow channel L1, and then through the second reversing component T2 into the bypass flow channel L5, replacing the buffer C in the second main flow channel L1 and the bypass flow channel L5. This process continues until the first main flow channel L6 and the second main flow channel L1 are filled with reagent A to a concentration greater than 99%, and the bypass flow channel L5 contains a mixture of reagent A and buffer C. Excess buffer C flows sequentially through the third reversing component T3, the third main flow channel L4, the fourth reversing component T4, and the second waste flow channel L12 before being discharged. This step S1101 ensures a high concentration of reagent A entering the flow cell C1.

[0120] Step S1102: The second reversing component T2 switches, placing the second main flow path L1 in fluid communication with the first flow cell path L2. The third reversing component T3 switches, placing the second flow cell path L3 in fluid communication with the third main flow path L4. At this point, both the upstream side of the second reversing component T2 and the downstream side of the third reversing component T3 are in fluid communication with the flow cell C1. High-concentration reagent A enters flow cell C1 through the second reversing component T2 and the first flow cell path L2, replacing the buffer in the first flow cell path L2, flow cell C1, and second flow cell path L3, as shown in Figure 3. This continues until the first flow cell path L2, flow cell C1, and second flow cell path L3 are filled with reagent A at a concentration greater than 99%, leaving the third main flow path L4 with a mixture of reagent A and buffer C.

[0121] Step S1103: The DNA sample fixed inside the flow cell C1 immediately undergoes a biochemical reaction with the reagent A. Simultaneously, the second reversing component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, and the upstream portion of the second reversing component T2 is disconnected from the flow cell C1. The third reversing component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, and the downstream portion of the third reversing component T3 is disconnected from the flow cell C1. The fourth reversing component T4 is switched to connect the third main flow path L4 with the fourth main flow path L7.

[0122] Step S1104: Buffer C flows from the fourth main flow path L7 through the fourth reversing element T4 into the third main flow path L4, then through the third reversing element T3 into the bypass flow path L5, replacing the high-concentration reagent A in the bypass flow path L5 near the second reversing element T2, the second main flow path L1, and the first main flow path L6. Reagent A with a concentration greater than 95% is completely transferred back to the first main flow path L6, until a mixture of reagent A and buffer C is present in the second main flow path L1 and buffer C is present in the bypass flow path L5, as shown in Figure 4.

[0123] Step S1105: Switch the first reversing component T1 to establish fluid communication between the second main channel L1 and the first waste channel L11. Buffer C continues to enter the fluid system after step S1104, and continues to be added to the third main channel L4 and bypass channel L5 until the fourth main channel L7, the third main channel L4, and the bypass channel L5 are filled with buffer C to a concentration greater than 99%. Excess buffer C and low-concentration reagent A flow sequentially through the second reversing component T2, the second main channel L1, the first reversing component T1, and the first waste channel L11 before being discharged. Steps S1104 and S1105 can be performed in parallel with the biochemical reaction in flow cell C1 and can be performed in a shorter time than the biochemical reaction in flow cell C1.

[0124] Step S1106: After the biochemical reaction in flow cell C1 is completed, the third reversing component T3 is switched to connect the second flow cell flow path L3 with the third main flow path L4, connecting flow cell C1 to the reagent storage chamber downstream of the fourth main flow path L7. The second reversing component T2 is switched to connect the second main flow path L1 with the first flow cell flow path L2, connecting flow cell C1 to the waste liquid storage chamber via the first waste liquid path L11. High-concentration buffer C enters flow cell C1 via the third reversing component T3 and the second flow cell flow path L3, replacing reagent A in the second flow cell flow path L3, flow cell C1, and the first flow cell flow path L2, as well as the mixed solution in the second main flow path L1. The mixed solution and the low-concentration reagent A are then discharged via the first waste liquid path L11 until the second main flow path L1, the first flow cell flow path L2, and the side of flow cell C1 near the second reversing component T2 are filled with high-concentration reagent A.

[0125] Step S1107: Switching the first reversing element T1 establishes fluid communication between the second main flow path L1 and the first main flow path L6, allowing buffer C to continue entering flow cell C1. Reagent A, with a concentration greater than 95% in flow cell path L2, flow cell C1, and second flow cell path L3, enters the first main flow path L6, as shown in Figure 5. This completes the recovery process for reagent A.

[0126] Step S1108: Switch the first reversing component T1 to connect the second main flow path L1 with the first waste liquid flow path L11 fluid, and then the low concentration of reagent A and the mixture of reagent A and buffer solution C in the second main flow path L1, the first flow pool flow path L2 and the flow pool C1 are discharged through the first waste liquid flow path L11 until the second main flow path L1, the first flow pool flow path L2, the second flow pool flow path L3, the third main flow path L4, the bypass flow path L5, the fourth main flow path L7 and the flow pool C1 are all filled with buffer solution C.

[0127] Step S1109: Switching the second reversing element T2 establishes fluid communication between the second main channel L1 and the bypass channel L5. Switching the third reversing element T3 establishes fluid communication between the third main channel L4 and the bypass channel L5. The flow cell C1 is disconnected from both upstream of the second reversing element T2 and downstream of the third reversing element T3, thereby disconnecting it from all reagent storage chambers upstream of the first main channel L6 and downstream of the fourth main channel L7. Reagent B enters the fourth main channel L7, passes through the fourth reversing element T4 and the third main channel L4, and enters the bypass channel L5, replacing the buffer C in the third main channel L4 and the bypass channel L5. This process continues until the fourth main channel L7 and the third main channel L4 are filled with reagent B at a concentration greater than 99%, leaving the bypass channel L5 with a mixture of reagent B and buffer C. Excess buffer C in the bypass channel L5 flows sequentially through the second reversing element T2, the second main channel L1, the first reversing element T1, and the first waste channel L11 before being discharged. Step S1109 is to ensure a high concentration of reagent B entering the flow cell.

[0128] Step S1110: The second reversing component T2 switches, placing the second main flow path L1 in fluid communication with the first flow cell path L2. The third reversing component T3 switches, placing the second flow cell path L3 in fluid communication with the third main flow path L4. At this point, both the upstream portion of the second reversing component T2 and the downstream portion of the third reversing component T3 are in fluid communication with the flow cell C1. High-concentration reagent B enters flow cell C1 through the third reversing component T3 and the second flow cell path L3, replacing buffer C in the second flow cell path L3, flow cell C1, and first flow cell path L2, until the second flow cell path L3, flow cell C1, and first flow cell path L2 are filled with reagent B at a concentration greater than 99%. The second main flow path L1 and first waste liquid path L11 contain a mixture of reagent B and buffer C.

[0129] Step S1111: The DNA sample immobilized inside the flow cell C1 undergoes a biochemical reaction with the reagent B. Simultaneously, the second reversing component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, and the upstream portion of the second reversing component T2 is disconnected from the flow cell C1. The third reversing component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, and the downstream portion of the third reversing component T3 is disconnected from the flow cell C1.

[0130] Step S1112: Buffer C flows from the fourth main channel L7 through the fourth reversing component T4 into the third main channel L4, then through the third reversing component T3 into the bypass channel L5, replacing the reagent B in the bypass channel L5 and the second main channel L1. All reagent B is discharged from the first waste liquid channel L11 until the second main channel L1, bypass channel L5, third main channel L4, and fourth main channel L7 are filled with buffer C.

[0131] Step S1113: After the biochemical reaction of reagent B is complete, the second reversing component T2 switches, placing the second main flow path L1 in fluid communication with the first flow cell path L2. The third reversing component T3 switches, placing the second flow cell path L3 in fluid communication with the third main flow path L4. At this point, both the upstream portion of the second reversing component T2 and the downstream portion of the third reversing component T3 are in fluid communication with flow cell C1. Buffer C enters flow cell C1 through the third reversing component T3 and the second flow cell path L3, replacing reagent B in the second flow cell path L3, flow cell C1, and the first flow cell path L2. At this point, all flow paths and flow cells, except the first main flow path L6, the first waste liquid path L11, and the second waste liquid path L12, are filled with buffer C, and reagent B has been discharged from the recovery path.

[0132] A new cycle can be performed by re-executing steps S1100 to S1113. In the entire fluid operation method, reagent A and reagent B are separated by buffer solution C and will not come into contact with each other, thereby avoiding cross contamination of the reagents.

[0133] In the logical sequence of the fluid manipulation method described above, the operation performed on reagent A is to partially recover reagent A, while the operation performed on reagent B is not to recover reagent B. However, according to the logical sequence, the step of partially recovering reagent A can also be used to recover reagent B. Furthermore, the aforementioned method steps can be used to implement molecular biology assays involving a wider range of reagents, and whether or not to recover the corresponding reagents can be selected.

[0134] In the logic sequence scheme of the above fluid operation method, taking double reagents as an example, reagent B and buffer C both enter from the fourth main flow path L7, and reagent A enters from the first main flow path L6. In the case where more reagents are involved in molecular biology detection, multiple reagent storage chambers can be set up upstream of the first reversing component T1 and downstream of the fourth reversing component T4 to store different reagents, and the reagent storage chambers storing different reagents can be selectively connected to the first main flow path L6 or the fourth main flow path L7. Alternatively, in an embodiment not shown in the figure, multiple first main flows L6 connected to different reagent storage chambers can be directly connected to the first reversing component T1 and / or multiple fourth main flows L7 connected to different reagent storage chambers can be directly connected to the fourth reversing component T4. Different reagents are connected to the fluid system according to the reaction requirements. If necessary, each reagent can also be isolated with buffer C to avoid cross contamination caused by contact between different reagents.

[0135] In the disclosed embodiment, when reagent A, reagent B, and buffer C enter the fluid system, they can be pushed in from the inlet side of the fluid flow direction by using positive pressure drive, for example, a diaphragm liquid pump or an injection pump can be used to push the liquid upstream of the first main flow path L6, or they can be sucked in from the outlet side of the fluid flow direction by using negative pressure, for example, the reagent at the inlet end of the first main flow path L6 can be used to aspirate the liquid at the end of the fourth main flow path L7 / the second waste liquid flow path L12 by using an injection pump.

[0136] In the embodiment of the present disclosure, only one reaction flow path is shown. However, in an embodiment not shown, multiple reaction flow paths may be arranged in parallel to form a multi-input and multi-output reaction area.

[0137] In the logical timing scheme of the above fluid operation method, reagent A will be recovered to the first main flow path L6 and its upstream, and part of the reagent near one end of the flow cell C1 will be consumed each time. Considering the concentration dilution in the flow cell C1 and the various flow paths connected to the flow cell C1, the recovery amount is limited. Under the premise that the cross-section of the flow cell C1 is a wide and shallow rectangle, if a concentration of more than 95% needs to be recovered, the recovery ratio is generally less than 25%.

[0138] Given the short duration of each biochemical process, diffusion alone cannot achieve uniform reagent concentration within the first main flow path L6. The concentration of reagent near the second main flow path L1 is relatively low, while fresh reagent is present further away. The portion of reagent entering the bypass flow path L5 and the small portion that initially enters the flow cell C1 contain reagents of relatively low concentration. Fresh reagent then enters. As the liquid is pumped through the various reversing components and flow paths, the two reagents mix to some extent. As a result, the reagent concentration within the flow cell C1 is relatively uniform, but slightly lower than that of fresh reagent.

[0139] In the logical timing scheme of the above fluid operation method, some steps of the reagent recovery process are carried out in parallel with the biochemical reaction in the flow cell C1, which is beneficial to saving molecular biology detection time.

[0140] Figures 6 to 10 are schematic diagrams showing the principles of an embodiment of the present disclosure. Figure 6 is a schematic diagram showing the principles of a fluid system according to an embodiment of the present disclosure. Figures 7 to 10 are schematic diagrams showing the principles of a fluid operation method of the fluid system according to the embodiment of Figure 6.

[0141] As shown in Figures 6 to 10, the fluid system of the embodiment of the present disclosure includes a first main flow path L6, a second main flow path L1, a reaction flow path, a bypass flow path L5, a third main flow path L4, a fourth main flow path L7, a storage flow path as a branch flow path, a first reversing component T1, a second reversing component T2, a third reversing component T3 and a fourth reversing component T4 and a storage flow path.

[0142] The reaction flow path includes a flow cell C1 and a first flow cell flow path L2 and a second flow cell flow path L3, respectively connected to the flow cell C1. A bypass flow path L5 is connected in parallel with the reaction flow path. The reservoir flow path includes a reservoir C2, a first reservoir connecting flow path L8 and a second reservoir connecting flow path L9 connected to the reservoir C2, and a reservoir inlet flow path L10 and a reservoir discharge flow path L13 connected to the reservoir C2. A first reversing component T1 connects the first main flow path L6, the second main flow path L1, and the first reservoir connecting flow path L8, and is configured to selectively connect any two of the first main flow path L6, the second main flow path L1, and the first reservoir connecting flow path L8, while disconnecting the remaining flow paths from the two connected flow paths. The second reversing element T2 connects the second main flow path L1, the first flow pool flow path L2, and the bypass flow path L5, and is configured to selectively connect any two of the second main flow path L1, the first flow pool flow path L2, and the bypass flow path L5, while disconnecting the remaining flow path from the two connected flow paths. The third reversing element T3 connects the third main flow path L4, the second flow pool flow path L3, and the bypass flow path L5, and is configured to selectively connect any two of the third main flow path L4, the second flow pool flow path L3, and the bypass flow path L5, while disconnecting the remaining flow path from the two connected flow paths. The fourth reversing element T4 connects the third main flow path L4, the fourth main flow path L7, and the second reservoir connection flow path L9, and is configured to selectively connect any two of the third main flow path L4, the fourth main flow path L7, and the second reservoir connection flow path L9, while disconnecting the remaining flow path from the two connected flow paths.

[0143] The following describes a logic sequence scheme of a fluid operation method including a reagent recovery process that can be implemented in accordance with an embodiment of the present disclosure, in conjunction with Figures 6 to 10. In this logic sequence scheme, reagent A is a reagent that needs to be partially recovered, reagent B is a reagent that cannot be cross-contaminated with reagent A and does not need to be recovered, and buffer C serves as an intermediate medium separating reagents A and B. Three liquids, namely reagent A, reagent B and buffer C, constitute the minimum component system of the reagent recovery scheme. In actual applications, the component system of the reagent recovery scheme can be expanded. For example, the reagents to be recovered can include multiple types, namely A1, A2, A3...An.

[0144] In the logic sequence scheme of the fluid operation method of the embodiment of the present disclosure, the first main flow path L6 is still used as the upstream of the fluid system. As shown in Figures 6 to 10, this embodiment uses a storage flow path as a branch flow path to replace the first waste liquid flow path L11 and the second waste liquid flow path L12 in the fluid system shown in Figures 2 to 5. The storage flow path includes a storage tank C2, a first storage tank connecting flow path L8 and a second storage tank connecting flow path L9 connected to the storage tank C2, and a storage tank inlet flow path L10 and a storage tank discharge flow path L13 connected to the storage tank. At the same time, a one-way pumping liquid method is adopted to allow the reagent to enter the flow tank C1 from the first flow tank flow path L2 and flow out of the flow tank C1 from the second flow tank flow path L3; reagent A enters the storage tank C2 from the storage tank inlet flow path L10 for temporary storage; the upstream of the first main flow path L6 is connected to the reagent storage chamber fluid of reagent B and buffer C; the downstream of the fourth main flow path L7 is connected to the waste liquid storage chamber fluid.

[0145] The steps of the logical timing scheme of the fluid operation method are as follows:

[0146] Step S2100: In the initial state, flow cell C1 contains buffer C, while the second main channel L1, first flow cell channel L2, second flow cell channel L3, third main channel L4, bypass channel L5, and first main channel L6 all contain buffer C. The first reservoir connecting channel L8 contains reagent A, and the second reservoir connecting channel L9 contains air. Reservoir C2 contains a certain volume of reagent A. Because the amount of reagent A recovered in a single run is less than the amount consumed, a certain volume of reagent A must be pre-loaded in reservoir C2. The first reversing element T1 connects the first main channel L6 with the second main channel L1; the second reversing element T2 connects the second main channel L1 with the bypass channel L5; the third reversing element T3 connects the bypass channel L5 with the third main channel L4; and the fourth reversing element T4 connects the third main channel L4 with the fourth main channel L7.

[0147] Step S2101: The first reversing component T1 switches, placing the first reservoir connecting flow path L8 in fluid communication with the second main flow path L1. Reagent A flows from reservoir C2 and the first reservoir connecting flow path L8 through the first reversing component T1 into the second main flow path L1. Then, it flows through the second reversing component T2 into the bypass flow path L5, replacing the buffer C in the second main flow path L1 and the bypass flow path L5. This process continues until the first reservoir connecting flow path L8 and the second main flow path L1 are filled with reagent A to a concentration greater than 99%, leaving the bypass flow path L5 with a mixture of reagent A and buffer C. Excess buffer C flows sequentially through the third reversing component T3, the third main flow path L4, the fourth reversing component T4, and finally the fourth main flow path L7 for discharge. Step S2101 ensures a high concentration of reagent A entering flow cell C1.

[0148] Step S2102: The second reversing component T2 switches, placing the second main flow path L1 in fluid communication with the first flow cell path L2. The third reversing component T3 switches, placing the second flow cell path L3 in fluid communication with the third main flow path L4. At this point, both the upstream portion of the second reversing component T2 and the downstream portion of the third reversing component T3 are in fluid communication with the flow cell C1. High-concentration reagent A enters flow cell C1 through the second reversing component T2 and the first flow cell path L2, displacing buffer C in the first flow cell path L2 and flow cell C1. This continues until the first flow cell path L2, flow cell C1, and second flow cell path L3 are filled with reagent A at a concentration greater than 99%. The third main flow path L4 then contains a mixture of reagent A and buffer C, as shown in Figure 7.

[0149] Step S2103: The DNA sample fixed inside the flow cell C1 immediately undergoes a biochemical reaction with the reagent A. Simultaneously, the second reversing component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, while the upstream of the second reversing component T2 is disconnected from the flow cell C1. The third reversing component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, while the third main flow path L4 downstream of the third reversing component T3 is disconnected from the flow cell C1. The first reversing component T1 is switched to connect the first main flow path L6 with the second main flow path L1, while the upstream of the first reversing component T1 is disconnected from the storage cell C2.

[0150] Step S2104: Reagent A that meets the required concentration in bypass flow path L5 near the end of the second reversing element T2 is returned to the second main flow path L1. Reagent A in the second main flow path L1 and bypass flow path L5, which are fluidically connected to the first main flow path L6 downstream of the first reversing element T1, enters the first main flow path L6, as shown in Figure 8. In this step, some reagent A is temporarily stored in the first main flow path L6 and will be recovered later along with the reagent in the flow cell C1.

[0151] Step S2105: After the biochemical reaction in flow cell C1 is complete, the third reversing element T3 is switched to connect the second flow cell channel L3 with the third main channel L4. The fourth reversing element T4 is switched to connect the third main channel L4 with the fourth main channel L7. At this point, flow cell C1 is connected to the waste liquid storage area downstream of fourth main channel L7. The second reversing element T2 is switched to connect the second main channel L1 with the first flow cell channel L2, connecting flow cell C1 upstream of the second reversing element T2. High-concentration buffer C enters first main channel L6, passes through the first reversing element T1, the second main channel L1, the second reversing element T2, and the first flow cell channel L2, and enters flow cell C1. This replaces the mixture of reagent A recovered in step S2104 in first main channel L6, reagent A in the first flow cell channel L2, flow cell C1, second flow cell channel L3, and reagent A and buffer C in the third main channel L4. The mixed solution and the low-concentration reagent A are discharged through the fourth main channel L7 until the third main channel L4, the second flow cell channel L3, and the side of the flow cell C1 near the third reversing component T3 are filled with the high-concentration reagent A.

[0152] Step S2106: Switching the fourth reversing element T4 places the third main flow path L4 in fluid communication with the second reservoir connecting flow path L9. Flow cell C1 is now in fluid communication with reservoir C2 via the second flow cell flow path L3, the third reversing element T3, the third main flow path L4, the fourth reversing element T4, and the second reservoir connecting flow path L9. High-concentration buffer C continues to enter the fluid system via the first main flow path L6. As buffer C flows, reagent A, with a concentration greater than 95%, in the third main flow path L4, the second flow cell flow path L3, and flow cell C1 enters the second reservoir connecting flow path L9 and then enters reservoir C2, as shown in Figure 9. This completes the reagent A recovery process.

[0153] Step S2107: Switching the fourth reversing element T4 establishes fluid communication between the third main channel L4 and the fourth main channel L7. The flow cell C1 is now in fluid communication with the waste liquid storage area downstream of the fourth main channel L7. Subsequently, low-concentration reagent A and a mixture of reagent A and buffer C are discharged through the fourth main channel L7. At this point, the first main channel L6, the second main channel L1, the first flow cell channel L2, the bypass channel L5, the second flow cell channel L3, the third main channel L4, the fourth main channel L7 near the fourth reversing element T4, and the flow cell C1 are filled with buffer C.

[0154] Step S2108: The first reversing component T1 switches, placing the first main channel L6 in fluid communication with the second main channel L1. The upstream portion of the first reversing component T1 is disconnected from the reservoir C2. Reagent B flows from the first main channel L6 through the first reversing component T1 into the second main channel L1, then through the second reversing component T2 into the bypass channel L5, replacing the buffer C in the second main channel L1 and the bypass channel L5. At this point, the first and second main channels L6 and L1 are filled with reagent B at a concentration greater than 99%, while the bypass channel L5 contains a mixture of reagent B and buffer C. Excess buffer C flows sequentially through the third reversing component T3, the third main channel L4, the fourth reversing component T4, and finally the fourth main channel L7 for discharge. Step S2108 ensures a high concentration of reagent B entering the flow cell.

[0155] Step S2109: Maintaining the state of the first reversing element T1, the first main flow path L6 remains in fluid communication with the second main flow path L1, while the upstream portion of the first reversing element T1 remains disconnected from the reservoir C2. Maintaining the state of the fourth reversing element T4, the third main flow path L4 remains in fluid communication with the fourth main flow path L7, while the upstream portion of the fourth reversing element T4 remains disconnected from the reservoir C2. The second reversing element T2 is switched to fluid communication with the second main flow path L1 and the first flow pool path L2. The third reversing element T3 is switched to fluid communication with the second flow pool path L3 and the third main flow path L4. At this point, both the upstream portion of the second reversing element T2 and the downstream portion of the third reversing element T3 are in fluid communication with the flow pool C1. The high-concentration reagent B enters the flow pool C1 through the second reversing component T2 and the first flow pool flow path L2, replacing the buffer solution in the first flow pool flow path L2 and the flow pool C1, until the first flow pool flow path L2, the flow pool C1, and the second flow pool flow path L3 are filled with reagent B with a concentration greater than 99%, and the third main flow path L4 is a mixture of reagent B and buffer solution C.

[0156] Step S2110: The immobilized DNA sample inside the flow cell C1 undergoes a biochemical reaction with reagent B. Simultaneously, the second reversing component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, while the upstream portion of the second reversing component T2 is disconnected from the flow cell C1. The third reversing component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, while the downstream portion of the third reversing component T3 is disconnected from the flow cell C1.

[0157] Step S2111: Buffer C flows from the first main flow path L6 through the first reversing component T1 into the second main flow path L1, then through the second reversing component T2 into the connected bypass flow path L5, replacing the high-concentration reagent B in the bypass flow path L5 near the second reversing component T2, the second main flow path L1, and the first main flow path L6. The low-concentration reagent B or a mixture of reagent B and buffer C in the bypass flow path L5 away from the second reversing component T2 flows sequentially through the third reversing component T3, the third main flow path L4, the fourth reversing component T4, and the fourth main flow path L7, until the first main flow path L6, the second main flow path L1, and the bypass flow path L5 are filled with buffer C with a concentration greater than 99%, and the third main flow path L4 is filled with a mixture of reagent B and buffer C.

[0158] Step S2112: The biochemical reaction in flow cell C1 is completed. The third reversing element T3 is switched to connect the second flow cell channel L3 with the third main channel L4. At this point, flow cell C1 is connected to the waste liquid storage area downstream of the fourth main channel L7. The second reversing element T2 is switched to connect the second main channel L1 with the first flow cell channel L2. This connects flow cell C1 to the reagent storage chamber upstream of the first main channel L6. High-concentration buffer C enters the first main channel L6 and then flows sequentially through the first reversing element T1, the second main channel L1, the second reversing element T2, the first flow cell channel L2, and into flow cell C1, replacing reagent B in the first flow cell channel L2, flow cell C1, and the second flow cell channel L3, as well as the mixture of reagent B and buffer C in the third main channel L4. Reagent B in the first flow cell channel L2, flow cell C1, the second flow cell channel L3, and the third main channel L4, as well as excess buffer C, is then discharged through the fourth main channel L7. At this point, except for the first reservoir connecting flow path L8, the second reservoir connecting flow path L9, the reservoir inlet flow path L10, the reservoir discharge flow path L13 and the reservoir C2, all other flow paths and the flow pool C1 are filled with buffer C, and reagent B has been discharged from the fluid system.

[0159] Step S2113: Loop through steps S2101 to S2112 n times, where n is a natural number greater than or equal to 1, such as 5, 10, 20, or 30. The upper limit of n can be determined based on the amount of reagent A in reservoir C2 and the lower limit of the concentration allowed for use in molecular biology assays. The greater the amount of reagent A in reservoir C2 and the lower limit of the concentration allowed for use in molecular biology assays, the greater the upper limit of n. Conversely, the smaller the amount of reagent A in reservoir C2 and the higher the lower limit of the concentration allowed for use in molecular biology assays, the lower the upper limit of n.

[0160] Step S2114: Reagent A in the storage tank C2 is discharged to the waste liquid storage area through the storage tank discharge flow path L13, and then fresh reagent A enters the storage tank from the storage tank inlet flow path L10 for the next round of n cycles.

[0161] In the logic sequence scheme of the above fluid operation method, after each execution of steps S2101 - S2108 , a portion of reagent A with a concentration greater than or equal to 95% can be recovered to the storage tank C2 .

[0162] In the logical timing scheme of the above fluid operation method, reagent A and reagent B are separated by buffer C and will not come into contact with each other, thereby preventing cross contamination.

[0163] In the logic sequence scheme of above fluid operation method, only the double reagent comprising reagent A and reagent B is taken as example to illustrate the reagent recovery process, wherein the operation performed on the test A is to recycle part reagent A, and the operation performed on reagent B is not to recycle reagent B. However, according to the above logic sequence scheme, corresponding storage flow path can also be set for reagent B, and the step of adopting the recovery part reagent A is realized to recycle reagent B. Therefore, it is possible to realize that more reagents that need part recovery participate in molecular biology detection according to the aforementioned method steps. In addition, it is also possible to make the first main flow path L6 selectively communicate with different reagent storage chambers, or make the first reversing component T1 selectively connect a plurality of parallel first main flow paths, each first main flow path is connected to different reagent storage chambers respectively, thereby it is possible to realize that more reagents that do not need recovery participate in molecular biology detection according to the aforementioned method steps. Between the two reagents that need to enter the flow cell C1 before and after arbitrarily, if necessary, equally isolate with buffer C, avoid that two kinds of reagents contact each other and cross contamination occurs.

[0164] In the logical timing scheme of the above fluid manipulation method, all reagents enter flow cell C1 from the upstream side of flow cell C1. Reagents A, B, and buffer C can enter flow cell C1 by pushing them from the inlet side of the corresponding flow path upstream of flow cell C1 using positive pressure, or by drawing them from the outlet side of the corresponding flow path downstream of flow cell C1 using negative pressure. For example, if reagent A is pushed in using positive pressure, reagent A can first be pumped into the first main flow path L6 using negative pressure, and then pushed into flow cell C1 and bypass flow path L5 using positive pressure upstream of first main flow path L6, as shown in Figure 10.

[0165] In the logical sequence scheme of above fluid operation method, the reagent recovery in the bypass flow path L5 is to send reagent back to the bypass flow path L5 upstream first, and then this part of reagent is carried out together with the reagent recovery in the subsequent flow cell C1. This recovery mode is suitable for the long flow channel of bypass flow path L5 and the 3rd main flow path L4. When being conducive to preventing reagent from being recovered by the bypass flow path L5, when arriving at the recovery position through the long flow channel, the reagent concentration is diluted more seriously, and it is difficult to ensure the situation of high concentration recovery reagent. However, if the inner volume of bypass flow path L5 and the 3rd main flow path L4 is less, it is feasible for reagent to be recovered by the bypass flow path L5.

[0166] In the logical timing scheme of the fluid manipulation method described above, the combined amount of reagents stored in reservoir C2 and recovered is typically cycled 20 to 30 times, meaning n is 20 to 30. This is because: 1. A certain amount of excess reagent A must be left each time fresh reagent A enters reservoir C2 to prevent air from being drawn in after reagent A is consumed. If the number of cycles is low, fresh reagent A enters reservoir C2 more frequently, increasing the cost of the excess. 2. Reagent A concentration, once reduced to a certain level, can affect the quality of the reaction in flow cell C1. Excessive cycles can also lower the reagent concentration in reservoir C2, and repeated use of some reagent components can adversely affect the quality of the reaction in flow cell C1.

[0167] In the logical sequence scheme of the above fluid operation method, reagent A is recovered to storage tank C2. Assuming that the recovered reagent A and fresh reagent A can be fully mixed in storage tank C2, if the concentration of the reagent entering flow cell C1 is required to be greater than 95%, considering that the recovered reagent A can be mixed with fresh reagent A in storage tank C2, the concentration of reagent A in storage tank C2 after mixing will be greater than the concentration of the recovered reagent A. Therefore, the concentration of the recovered reagent A can be less than 95%. Taking into account the pre-stocked storage tank and cost, the recovery rate is higher than that of the embodiments shown in Figures 2 to 5, reaching 25-35%.

[0168] In the logical timing scheme of the above fluid operation method, some steps of the reagent recovery process are carried out in parallel with the biochemical reaction in the flow cell C1, which is beneficial to saving molecular biology detection time.

[0169] FIG11 is a schematic diagram showing the principles of an embodiment of the present disclosure.

[0170] As shown in Figure 11, the fluid system of the embodiment of the present disclosure includes a first main flow path L6, a second main flow path L1, a reaction flow path, a bypass flow path L5, a third main flow path L4, a fourth main flow path L7, a first waste liquid flow path L11 as a branch flow path, a second waste liquid flow path L12 as a branch flow path, a storage flow path as a branch flow path, a first reversing component T1, a second reversing component T2, a third reversing component T3 and a fourth reversing component T4.

[0171] The reaction flow path includes a flow cell C1 and a first flow cell flow path L2 and a second flow cell flow path L3 connected to the flow cell C1, respectively. A bypass flow path L5 is connected in parallel with the reaction flow path. The storage flow path includes a storage cell C2, a first storage cell connecting flow path L8 and a second storage cell connecting flow path L9 connected to the storage cell C2, and a storage cell inlet flow path L10 and a storage cell outlet flow path L13 connected to the storage cell. The first waste liquid flow path L11 is configured to connect to a waste liquid storage chamber. The second waste liquid flow path L12 is configured to connect to the waste liquid storage chamber. The first reversing element T1 connects the first main flow path L6, the second main flow path L1, the first waste liquid flow path L11, and the first storage cell connecting flow path L8, and is configured to selectively connect any two of the first main flow path L6, the second main flow path L1, the first waste liquid flow path L11, and the first storage cell connecting flow path L8, while disconnecting the remaining flow paths from the two connected flow paths. The second reversing element T2 connects the second main flow path L1, the first flow pool flow path L2, and the bypass flow path L5, and is configured to selectively connect any two of the second main flow path L1, the first flow pool flow path L2, and the bypass flow path L5, while disconnecting the remaining flow path from the two connected flow paths. The third reversing element T3 connects the third main flow path L4, the second flow pool flow path L3, and the bypass flow path L5, and is configured to selectively connect any two of the third main flow path L4, the second flow pool flow path L3, and the bypass flow path L5, while disconnecting the remaining flow path from the two connected flow paths. The fourth reversing element T4 connects the third main flow path L4, the fourth main flow path L7, the second waste liquid flow path L12, and the second reservoir connection flow path L9, and is configured to selectively connect any two of the third main flow path L4, the fourth main flow path L7, the second waste liquid flow path L12, and the second reservoir connection flow path L9, while disconnecting the remaining flow path from the two connected flow paths.

[0172] As shown in Figure 11, in the present embodiment, the reaction flow path includes multiple flow cells C1 in parallel to carry out biochemical reactions simultaneously in multiple flow cells C1. Wherein, multiple flow cells C1 both sides can be connected to the first flow cell flow path L2 and the second flow cell flow path L3 by the first flow cell branch L2_1 and the second flow cell branch L3_1 respectively. The logic timing scheme of the implementable fluid operation method of the disclosed embodiment can refer to the embodiment shown in Figures 2 to 5 and the embodiment shown in Figures 6 to 10. The fluid system of the disclosed embodiment has higher flexibility than the aforementioned embodiment.

[0173] An embodiment of a fluid system to which the fluid system of the present disclosure is applied is described below with reference to FIG. 12 to FIG. 20 .

[0174] Figures 12 to 15 illustrate the principle structure of a fluid system according to an embodiment of the present disclosure. Figure 12 is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure. Figures 13 and 14 are schematic diagrams of the principle structure of the fluid operation method of the fluid system according to the embodiment shown in Figure 12. Figure 15 is a schematic diagram of the reagent distribution when a recovered reagent, a mixed reagent, and a fresh reagent are simultaneously present in a pipeline according to the embodiment shown in Figure 12. The mixed reagent refers to a mixture of a recovered reagent and a fresh reagent.

[0175] As shown in Figures 12 to 14, the fluid system of this embodiment is a specific example of the fluid system shown in Figures 2 to 5. The first reversing component T1 of the fluid system is implemented as a rotary valve 1101. The second reversing component T2 of the fluid system is implemented as a solenoid valve 1103. The third reversing component T3 of the fluid system is implemented as a solenoid valve 1104. The fourth reversing component T4 of the fluid system is implemented as a rotary valve 1102. The first main flow L6 of the fluid system is implemented as a combination of pipeline 101 and pipeline 108. Pipeline 101 is connected to the reagent storage chamber R1, and pipeline 101 is connected to pipeline 108 via rotary valve 1101 in a switchable manner. The second main flow path L1 of the fluid system is implemented as pipeline 102; the third main flow path L4 of the fluid system is implemented as pipeline 106; the fourth main flow path L7 of the fluid system is implemented as a combination of pipeline 107 and pipeline 109, pipeline 107 is connected to the reagent storage chamber R2, and pipeline 107 is connected to pipeline 109 via a rotary valve 1102. The bypass flow path L5 of the fluid system is implemented as pipeline 103. The first flow cell flow path L2 of the fluid system is implemented as pipeline 104. The second flow cell flow path L3 of the fluid system is implemented as pipeline 105. The first waste liquid flow path L11 of the fluid system is implemented as pipeline 110. The second waste liquid flow path L12 of the fluid system is implemented as pipeline 111. The flow cell C1 is implemented as chip 1201.

[0176] In the embodiment shown in Figures 12 to 14, rotary valve 1101 is connected to power source 1105 via pipeline 108. Rotary valve 1102 is connected to power source 1106 via pipeline 109. Pipeline 101 is connected to reagent storage chamber R1, and pipeline 107 is connected to reagent storage chamber R2. Pipelines 110 and 111 are respectively connected to the waste liquid storage chamber.

[0177] In the embodiments shown in Figures 12 to 14, the rotary valve 1101 and the rotary valve 1102 are, for example, 25-hole rotary valves; the solenoid valve 1103 and the solenoid valve 1104 are, for example, two-position three-way solenoid valves; the power source 1105 and the power source 1106 are, for example, injection pumps; and the chip 1201 is, for example, a single-input single-output chip.

[0178] The following describes a feasible fluid operation method for the fluid system of this example. This fluid operation method provides four basic fluid flow modes, including two normal flow modes that do not recover reagents: a bypass flow mode and a chip flow mode, and two reagent recovery modes that have a reagent recovery process: a bypass reagent recovery mode and a chip reagent recovery mode. In the feasible logical timing scheme of the reagent recovery process, the reagent to be recovered is reagent A, and buffer C is used to isolate reagent A. Before recovering reagent A, the chip 1201 and pipelines 102-106 are filled with buffer C.

[0179] 1. Bypass liquid flow method

[0180] Step S3101: Rotary valve 1101 is actuated to connect pipeline 101 and pipeline 108. The reagent is pumped into pipeline 108 through pipeline 101 and rotary valve 1101 by syringe pump 1105 for temporary storage.

[0181] Step S3102: Solenoid valve 1103 is actuated to connect pipeline 102 and pipeline 103. Solenoid valve 1104 is actuated to connect pipeline 103 and pipeline 106. Rotary valve 1101 is actuated to connect pipeline 108 and pipeline 102. The reagent enters pipeline 102 through pipeline 108 and rotary valve 1101.

[0182] Step S3103: The reagent enters pipeline 103 and then enters pipeline 106 through solenoid valve 1104;

[0183] Step S3104: The reagent in pipeline 106 passes through rotary valve 1102 and is finally discharged through pipeline 111. During this process, no reagent passes through the reaction flow path including pipeline 104, pipeline 105 and chip 1201.

[0184] In this embodiment, the fluid system itself and the power source, reagent storage chamber, and waste liquid storage chamber connected to the fluid system are symmetrical in structure. Therefore, reverse pumping can also be performed using the same logic.

[0185] 2. Chip liquid flow method

[0186] Step S3201: The rotary valve 1101 is actuated to connect the pipeline 101 and the pipeline 108. The reagent is pumped into the pipeline 108 by the syringe pump 1105 through the pipeline 101 and the rotary valve 1101 for temporary storage.

[0187] Step S3202: Solenoid valve 1103 is actuated to connect pipeline 102 and pipeline 103. Solenoid valve 1104 is actuated to connect pipeline 103 and pipeline 106. Rotary valve 1101 is actuated to connect pipeline 108 and pipeline 102. A certain volume of reagent enters pipeline 102 through pipeline 108 and rotary valve 1101 until the reagent concentration in pipeline 102 reaches above 99%. Reagent with lower concentration enters bypass 103, allowing higher concentration reagent to enter chip 1201 later.

[0188] Step S3203: Solenoid valve 1103 is actuated to connect pipeline 102 and pipeline 104. Solenoid valve 1104 is actuated to connect pipeline 105 and pipeline 106. The reagent enters pipeline 104 and chip 1201.

[0189] Step S3204: After the reagent reacts in 1201, it enters pipeline 106 from pipeline 105 through solenoid valve 1104;

[0190] Step S3205: The reagent in pipeline 106 finally passes through rotary valve 1102 and pipeline 111 and is finally discharged.

[0191] In this embodiment, the fluid system itself and the power source, reagent storage chamber, and waste liquid storage chamber connected to the fluid system are symmetrical in structure. Therefore, reverse pumping can also be performed using the same logic.

[0192] The above two normal flow-through methods both include the step of pumping the reagent into the pipeline 108 for temporary storage, namely step S3101 and step S3201. The subsequent steps other than step S3101 and step S3201 can be performed alternately between the two normal flow-through methods to meet different detection requirements.

[0193] 3. Bypass reagent recovery method

[0194] Step S3301: Reagent A enters chip 1201 from one end of pipeline 101 to complete the corresponding biochemical reaction. Chip 1201, pipeline 102, pipeline 104, pipeline 105, and pipeline 103 on the side close to pipeline 102 have a higher concentration of reagent A. The middle part of pipeline 103 is a mixture of reagent A and buffer C; pipeline 103 on the side close to pipeline 106 and in pipeline 106 contain buffer C.

[0195] Step S3302: During the reaction of chip 1201, rotary valve 1101 is actuated to disconnect pipeline 110 from pipeline 102, while pipeline 101 is connected to pipeline 102. Buffer C enters the fluid system from pipeline 107, and part of reagent A in pipeline 103 and pipeline 102 is recovered through the aforementioned bypass liquid method. This part of reagent A is recovered into pipeline 101 through rotary valve 1101 for the next reaction.

[0196] If the chip reagent recovery method is followed immediately after this step, all the reagent A that meets the concentration requirements can be transported to 102 and then stopped, without having to send all the reagent A that meets the recovery conditions into pipeline 101, as shown in Figure 13.

[0197] 4. Chip reagent recovery method

[0198] The chip reagent recovery method is generally performed immediately after the bypass reagent recovery method. After the reaction of chip 1201 is completed, buffer C enters the fluid system from pipeline 101 through the chip flow method to recover part of the reagent A in pipeline 104, pipeline 105 and chip 1201.

[0199] If pipeline 102 has undergone other pumping processes during the biochemical reaction process of chip 1201, before executing the chip reagent recovery method, it is necessary to operate the rotary valve 1101 to connect pipeline 102 and pipeline 110, and discharge the low-concentration reagent or other reagent in pipeline 102 from pipeline 110, and then operate the rotary valve 1101 to connect pipeline 102 with pipeline 101, and recycle the reagent A with the required concentration into pipeline 101 through the rotary valve 1101 for the next reaction, as shown in Figure 14.

[0200] In the two reagent recovery methods described above, if reagent A enters the fluid system through pipeline 101, buffer C can enter the fluid system through pipeline 107. In pipeline 101, the reagent near the rotary valve 1101 end will be refreshed, and the portion of reagent near the reagent storage chamber R1 end will be returned to the reagent storage chamber R1, ensuring that the volume of reagent in pipeline 101 is greater than the volume of the recovered reagent, as shown in Figure 15. This ensures that the reagent returned to the reagent storage chamber R1 does not come into contact with the recovered reagent.

[0201] Figures 16 to 18 illustrate the principle structure of a fluid system according to an embodiment of the present disclosure. Figure 16 is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure. Figures 17 and 18 are schematic diagrams of the principle structure of the fluid system according to the embodiment of Figure 16 related to the fluid operation method.

[0202] As shown in Figures 16 to 18 , the fluid system of this embodiment is a specific example of the fluid system shown in Figures 6 to 10 . The first reversing component T1 of the fluid system is implemented as a rotary valve 2101. The second reversing component T2 of the fluid system is implemented as a solenoid valve 2102. The third reversing component T3 of the fluid system is implemented as a solenoid valve 2103. The fourth reversing component T4 of the fluid system is implemented as a solenoid valve 2104. The first main flow path L6 of the fluid system is implemented as pipeline 208. The second main flow path L1 of the fluid system is implemented as pipeline 202; the third main flow path L4 of the fluid system is implemented as pipeline 206; and the fourth main flow path L7 of the fluid system is implemented as pipeline 210. The bypass flow path L5 of the fluid system is implemented as pipeline 203. The first flow cell flow path L2 of the fluid system is implemented as pipeline 204. The second flow cell flow path L3 of the fluid system is implemented as pipeline 205. The first reservoir connection flow path L8 of the fluid system is implemented as pipeline 209. The second reservoir connecting flow path L9 of the fluid system is implemented as a pipe 207. The flow cell C1 is implemented as a chip 2201. The reservoir C2 is implemented as a reservoir 2202. The reservoir inlet flow path L10 is implemented as a pipe 201. The reservoir outlet flow path L13 is implemented as a pipe 211.

[0203] 16 to 18 , the pipeline 208 is connected to the power source 2105 , and the pipeline 201 is connected to the reagent storage chamber R3 via the liquid pump 2106 .

[0204] In the embodiments shown in Figures 16 to 18, the rotary valve 2101 is, for example, a 25-hole rotary valve; the solenoid valve 2102, the solenoid valve 2103 and the solenoid valve 2104 are, for example, two-position three-way solenoid valves; the power source 1105 is, for example, an injection pump; the liquid pump 2106 is, for example, a diaphragm liquid pump; the chip 2201 is, for example, a single-inlet and single-outlet chip; the storage tank 2202 is a measuring cup with an open top, and the bottom of the measuring cup is provided with an opening connected to the pipeline 201.

[0205] The following describes a feasible fluid operation method for the fluid system of this example. This fluid operation method provides three basic fluid flow modes, including a bypass flow mode and a chip flow mode, two normal flow modes that do not recycle reagents, and a chip reagent recovery mode, a reagent recovery mode that includes a reagent recovery process. In a feasible logical timing scheme for the reagent recovery process, the reagent to be recovered is reagent A, and buffer C is used to isolate reagent A. Before recovering reagent A, the chip 2201 and pipelines 202-206 are filled with buffer C.

[0206] The reagents in the storage tank 2202 are updated as needed. For example, in this embodiment, after every 20 cycles, the reagents in the storage tank 2202 are drained from the pipeline 211 and new reagents are pumped from the reagent storage chamber R3 into the storage tank 2202 by the liquid pump 2106 to ensure the freshness of the reagents in the storage tank 2202.

[0207] 1. Bypass liquid flow method

[0208] Step S4101: Rotary valve 2101 is actuated to connect pipeline 209 and pipeline 208. The reagent is pumped into storage tank 2202 via liquid pump 2106 and pipeline 201. The reagent is then pumped into pipeline 208 for temporary storage via pipeline 209 and rotary valve 2101 by power source 2105.

[0209] Step S4102: Solenoid valve 2102 is actuated to connect pipeline 202 and pipeline 203. Solenoid valve 2103 is actuated to connect pipeline 203 and pipeline 206. Solenoid valve 2104 is actuated to connect pipeline 206 and pipeline 210. Rotary valve 2101 is actuated to connect pipeline 202 and pipeline 208. The reagent enters pipeline 202 through pipeline 208 and rotary valve 2101.

[0210] Step S4103: The reagent enters the pipeline 203 and then enters the pipeline 206 through the solenoid valve 2103;

[0211] Step S4104 : The reagent in pipeline 206 passes through solenoid valve 2104 and is finally discharged from pipeline 210 .

[0212] In the bypass flow mode, no reagent will pass through the reaction flow path including the pipeline 204, the pipeline 205 and the chip 2201.

[0213] 2. Chip liquid flow method

[0214] Step S4201: Rotary valve 2101 is actuated to connect pipeline 209 and pipeline 208. The reagent is pumped into storage tank 2202 through liquid pump 2106 and pipeline 201. The reagent is then pumped into 208 for temporary storage through pipeline 209 and rotary valve 2101 by power source 2105.

[0215] Step S4202: Solenoid valve 2102 is actuated to connect pipeline 202 and pipeline 203. Solenoid valve 2103 is actuated to connect pipeline 203 and pipeline 206. Solenoid valve 2104 is actuated to connect pipeline 206 and pipeline 210. Rotary valve 2101 is actuated to connect pipeline 202 and pipeline 208. Reagent enters pipeline 202 through pipeline 208 and rotary valve 2101, raising the reagent concentration in pipeline 202 to above 99%. Reagent with a lower concentration enters pipeline 203, allowing subsequent reagent with a higher concentration to enter chip 2201.

[0216] Step S4203: Solenoid valve 2102 is actuated to connect pipeline 202 and pipeline 204. Solenoid valve 2103 is actuated to connect pipeline 205 and pipeline 206. The reagent enters pipeline 204 and chip 2201.

[0217] Step S4204: After the reagent reacts in the chip 2201, the reagent enters the pipeline 206 from the pipeline 205;

[0218] Step S4205 : The reagent in the pipeline 206 is discharged after passing through the solenoid valve 2104 and the pipeline 210 .

[0219] In the chip flow mode, no reagent will pass through the pipe 203 serving as the bypass flow path L5.

[0220] The above two normal flow-through methods both include the steps of pumping the reagent into the pipeline 208 for temporary storage, namely step S4101 and step S4201. The subsequent steps other than step S4101 and step S4201 can be performed alternately between the two normal flow-through methods to meet different detection requirements.

[0221] 3. Chip reagent recovery method

[0222] In this embodiment, the pipeline 203 serves as the bypass flow path L5 and has a certain length. The reagent recovery in the pipeline 203 is performed by relying on the chip 2201, and thus only one reagent recovery method, namely, chip reagent recovery, is provided.

[0223] Step S4301: Reagent A enters chip 2201 in a chip-through-liquid manner to complete the biochemical reaction. When the biochemical reaction starts, a high concentration of reagent A is present in chip 2201, pipeline 202, pipeline 204, pipeline 205, and the side of pipeline 203 close to pipeline 202. The middle of pipeline 203 is a mixture of reagent A and buffer C. The side of pipeline 203 close to pipeline 206 and the inside of pipeline 206 are buffer C. During the reaction of chip 2201, negative pressure is applied to reagent A in the pipeline. 203 The reagent that meets the concentration requirement is recovered: the solenoid valve 2102 is actuated to connect pipeline 202 and pipeline 203, the solenoid valve 2103 is actuated to connect pipeline 203 and pipeline 206, the solenoid valve 2104 is actuated to connect pipeline 206 and pipeline 210, the rotary valve 2101 is actuated to connect pipeline 202 and pipeline 208, and the reagent A with the concentration meeting the standard is drawn back to pipeline 202 by the power source 2105. If the volume of reagent A is large enough, reagent A will also enter the rotary valve 2101 and pipeline 208.

[0224] Step S4302: Wait for the reaction in chip 2201 to be completed, solenoid valve 2102 is actuated to connect pipeline 202 and pipeline 204, solenoid valve 2103 is actuated to connect pipeline 205 and pipeline 206, and power source 2105 pushes the liquid to push part of reagent A recovered in the previous step into pipeline 202 again. Then, buffer C enters from another hole of the rotary valve 2101, and passes through the chip. First, the reagent A and buffer C with lower concentrations in pipeline 205 and pipeline 206 are discharged from pipeline 210; then the solenoid valve 2104 disconnects pipeline 206 and pipeline 210, and instead connects pipeline 206 and pipeline 207, and buffer C further enters the chip 2201, and the reagent A that meets the concentration requirements in pipeline 202, pipeline 204, chip 2201, pipeline 205, and pipeline 206 is sent into pipeline 207 and storage tank 2202 through the solenoid valve 2104 for the next reaction.

[0225] If other reagents besides buffer C pass through pipeline 203 when a biochemical reaction occurs in chip 2201, step S4301 is not performed and step S4302 is performed directly, i.e., the reagents in pipelines 203 and 202 are not recovered, and only the reagents in the reaction flow path are recovered.

[0226] Figures 19 and 20 illustrate the principle structure of a fluid system according to an embodiment of the present disclosure. Figure 19 is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure. Figure 20 is a schematic diagram of a portion of the principle structure of the fluid system of Figure 19. Figure 20 primarily illustrates the differences from the fluid system of the embodiment shown in Figures 16 to 18.

[0227] As shown in Figures 19 and 20, the fluid system of this embodiment adds a storage flow path to the fluid system of the embodiment shown in Figures 16 to 18. The following only describes the differences between this embodiment and Figures 16 to 18. Any unexplained parts of this embodiment refer to the embodiment shown in Figures 16 to 18.

[0228] As shown in Figures 19 to 20, compared to the embodiment shown in Figures 16 to 18, the fluid system further includes a storage tank 2203 connected in parallel with the storage tank 2202. Storage tank 2203 is connected to rotary valve 2101 via pipeline 214, to solenoid valve 2104 via pipeline 213, and to reagent storage chamber R4 via pipeline 212. A liquid pump 2107, such as a diaphragm liquid pump, is provided on pipeline 212 and is connected to waste liquid storage chamber W1 via pipeline 215. Pipelines 211 and 210 are also connected to waste liquid storage chamber W1. Pipeline 216 connects solenoid valve 2104 and waste liquid storage chamber W1. A solenoid valve 2108 is provided on pipeline 207 to control the on / off of pipeline 207. A solenoid valve 2109 is provided on pipeline 213 to control the on / off of pipeline 213. A solenoid valve 2110 is provided on the pipeline 216 to control the on / off of the pipeline 216. The solenoid valves 2108, 2109 and 2110 are, for example, two-position, two-way solenoid valves. The pipelines 207, 213 and 216 are all connected to the solenoid valve 2104 via the pipeline 217.

[0229] Reservoir 2203 is a measuring cup with an open top and an opening at the bottom for connection to pipe 212. Similar to reservoir 2202, the reagents in reservoir 2203 are refreshed as needed. For example, in this embodiment, after every 20 cycles, the reagents in reservoir 2203 are discharged from pipe 215 to waste liquid storage chamber W1. Fresh reagents are then pumped into reservoir 2203 from reagent storage chamber R4 by liquid pump 2107 to ensure the freshness of the reagents in reservoir 2203.

[0230] The following is an explanation of the feasible fluid operation method of the fluid system of this example. In this fluid operation method, three basic fluid flow modes are provided, including two normal flow modes that do not recycle reagents, namely the bypass flow mode and the chip flow mode, and a reagent recovery mode with a reagent recovery process, namely the chip reagent recovery mode. In the feasible logical timing scheme of the reagent recovery process, the reagents that need to be recovered are reagent A and reagent B, and buffer C is used to isolate reagent A and reagent B. Before reagent A and reagent B are recovered, the chip 2201 and the pipelines 202-206 are filled with buffer C. Reagent A is stored in the reagent storage area R3 and the reservoir 2202, and reagent B is stored in the reagent storage area R4 and the reservoir 2203.

[0231] For the bypass liquid flow method and the chip liquid flow method, please refer to the relevant descriptions of the embodiments shown in Figures 16 to 18.

[0232] The chip reagent recovery method is as follows:

[0233] S5301: The reagent to be recovered enters the corresponding storage tank through solenoid valve 2104. Assuming that reagent A is recovered first, it can be recovered according to the chip reagent recovery method in the embodiments shown in Figures 16 to 18. During the recovery process, solenoid valve 2108 is opened, solenoid valve 2109 is closed, and solenoid valve 2110 is closed. Reagent A is recovered through pipes 217 and 207 and enters storage tank 2202;

[0234] S5302: After reagent A is recovered, some reagent A will remain in pipeline 217. Therefore, if reagent B needs to be recovered, this portion of reagent A must first be removed through buffer C. At this point, solenoid valves 2108 and 2109 are closed, and solenoid valve 2110 is opened. Buffer C flows through solenoid valve 2014 and pipeline 217 to pipeline 216. Ensure that pipeline 217 is fully filled with buffer C during this step.

[0235] S5303: Keeping the electromagnetic valve 2108 and the electromagnetic valve 2019 closed, reagent B enters the pipeline 216 from the electromagnetic valve 2104 through the pipeline 217. This step requires ensuring that the pipeline 217 is filled with reagent B with a concentration of more than 99%.

[0236] S5304: Open the electromagnetic valve 2109 and close the electromagnetic valve 2110. Reagent B is recovered through the pipeline 217 and the pipeline 213 and enters the storage tank 2203. At this point, the recovery of the two reagents is completed.

[0237] In this embodiment, the pipe 217 should be made as short as possible to recover as much reagent as possible. Of course, assuming that reagent A and reagent B are completely incontactable, even if the pipe 217 is very short, it is necessary to introduce buffer C for isolation during the reagent recovery process. If reagent A and reagent B can be slightly in contact, buffer C isolation is not required.

[0238] In this embodiment, each reagent has an independent storage tank. If more recovery reagents are added, more branches can be added to pipeline 217 to connect more storage channels, and valves can be used to ensure that the reagents can flow to the corresponding storage channels. The valves for switching storage channels are not limited to the two-way two-way solenoid valves on each branch as in this embodiment. For example, rotary valves can also be used to achieve switching of multiple storage channels.

[0239] In each embodiment of the present disclosure, the descriptions related to concentration, such as ensuring that there is 99% concentration of reagent A in the second main flow path L1, are all converted relative to the concentration of the reagent entering the system in the current round. For example, the first time reagent A enters the entire fluid system, the initial concentration is 1, and the concentration is required to be greater than 99%. After recovery, the reagent A entering the flow pool C1 for the second time has been premixed with the recovered part, and the initial concentration is already less than 1, such as 0.98. At this time, 99% is 99% relative to 0.98, that is, 0.97. The entire reagent recovery process ensures that the amount of reagent entering the flow pool in each round is fixed, and the concentration of the reagent entering the flow pool will vary slightly. The concentration of the reagent entering the flow pool has a reasonable range. As in each embodiment of the present disclosure, it is required that the stable concentration after entering the flow pool C1 is greater than 95% of the initial concentration.

[0240] Under the premise of recovering reagents with a concentration of more than 95%, in the embodiments shown in Figures 2 to 5, a maximum of about 25% of the reagents can be recovered in a single time. In the embodiments shown in Figures 6 to 10, a maximum of about 35% of the reagents can be recovered in a single time. Since the recovery concentration requirement is very high, the recovery ratio is already very high.

[0241] Based on the above description, the embodiments of the present disclosure have at least one of the following advantages:

[0242] Before the reagent enters the chip, the low-concentration portion will be sent into the bypass first to ensure the concentration of the reagent entering the chip and also help reduce cross contamination.

[0243] Since the buffer solution is used to isolate the reagent, the recovered reagent is slightly diluted by the buffer solution, but there is no mixing with other reagents, thereby effectively avoiding cross contamination of the reagents.

[0244] During the reagent recovery process, the process of discharging low-concentration reagents and the recovery process of some high-concentration reagents can be completed in parallel with the biochemical reaction in the flow cell or while the next reagent enters the flow cell, reducing waiting time and not affecting the total detection process time.

[0245] It can be used as a single reagent or with multiple reagents at the same time. When multiple reagents are used at the same time, any one or several reagents can be selected for recovery.

[0246] Recovered reagents that meet the required concentration can enter the portion connected to the reagent storage chamber, preventing them from entering the reagent storage chamber; they can also enter a relatively independent storage tank, rather than being sent back to the flow cell after passing through the flow cell. Thus, the disclosed embodiments are beneficial in reducing cross contamination.

[0247] During the reagent recovery process, part of the reagent is recovered in parallel with the biochemical reaction, and the other part of the reagent is recovered when the buffer solution enters the flow cell C1 in the next step. Therefore, the reagent recovery does not affect the working efficiency of the molecular biology detection equipment.

[0248] A multi-channel chip with multiple flow cells in parallel and multiple inputs and outputs can be applied to the fluid system of the embodiment of the present disclosure.

[0249] The drive mechanism for fluid flow can be flexibly selected. For example, positive or negative pressure can be used to drive fluid flow within the fluid system, allowing for unidirectional or multidirectional recovery of different reagents. Mechanical pumps, such as diaphragm pumps or syringe pumps, can be used. Other power systems, such as pneumatic, electroosmotic, and digital microfluidics, can also achieve equivalent results.

[0250] When applying the fluid system of the embodiment of the present disclosure, there is no limitation on the form of the flow cell, such as size and number of flow channels.

[0251] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the embodiments of the present disclosure and are not intended to limit them. Although the embodiments of the present disclosure have been described in detail with reference to preferred embodiments, ordinary technicians in the relevant field should understand that the specific implementation methods of the embodiments of the present disclosure can still be modified or some technical features can be replaced by equivalents without departing from the spirit of the technical solutions of the embodiments of the present disclosure, and they should all be included in the scope of the technical solutions requested for protection in the embodiments of the present disclosure.

Claims

1. A fluid system, characterized in that: include: one or more first main flow paths (L6), the first main flow path (L6) being configured to connect to at least one reagent storage chamber; Second main flow (L1); a reaction flow path, including a flow cell (C1); a bypass flow path (L5), connected in parallel with the reaction flow path; the third main road (L4); one or more branch flow paths; and A plurality of switching components, the plurality of switching components comprising: a first reversing component (T1) connecting the one or more first main flow paths (L6), the second main flow path (L1) and at least one branch flow path, and configured to enable the second main flow path (L1) to selectively communicate with any one of the one or more first main flow paths (L6) and the at least one branch flow path, while disconnecting the remaining flow paths connected to the first reversing component (T1); a second reversing component (T2) connecting the second main flow path (L1), the reaction flow path, and the bypass flow path (L5), and configured to selectively connect the second main flow path (L1) to any one of the reaction flow path and the bypass flow path (L5), while disconnecting the remaining flow paths connected to the second reversing component (T2); and A third reversing component (T3) connects the third main flow path (L4), the reaction flow path and the bypass flow path (L5), and is configured to enable the third main flow path (L4) to selectively communicate with any one of the reaction flow path and the bypass flow path (L5), while disconnecting the remaining flow paths connected to the third reversing component (T3).

2. The fluid system according to claim 1, characterized in that The reaction flow path further comprises: a first flow cell flow path (L2), connecting the flow cell (C1) and the second reversing component (T2); and / or The second flow cell flow path (L3) connects the flow cell (C1) and the third reversing component (T3).

3. The fluid system according to claim 1, wherein: The reaction flow path includes two or more flow cells (C1) arranged in parallel.

4. The fluid system according to claim 1, wherein: The one or more branch flow paths include a first waste liquid flow path (L11), which is connected to the first switching component (T1) and is configured to be connected to a waste liquid storage chamber.

5. The fluid system according to claim 1, wherein: The fluid system further comprises one or more fourth main flow paths (L7), wherein the fourth main flow paths (7) are configured to connect at least one reagent storage chamber and / or at least one waste liquid storage chamber; The plurality of reversing components further include a fourth reversing component (T4), the fourth reversing component (T4) connecting the third main flow path (L4), the one or more fourth main flow paths (L7) and at least one branch flow path, and being configured to enable the third main flow path (L4) to selectively communicate with any one of the one or more fourth main flow paths (L7) and the at least one branch flow path, while disconnecting the remaining flow paths connected to the fourth reversing component (T4).

6. The fluid system according to claim 5, characterized in that The one or more branch flow paths include a second waste liquid flow path (L12), which is connected to the fourth switching component (T4) and is configured to be connected to a waste liquid storage chamber.

7. The fluid system according to claim 5 or 6, characterized in that The one or more branch flow paths include a storage flow path, and the storage flow path includes: Storage tank (C2); a first storage tank connecting flow path (L8) connecting the first reversing member (T1) and the storage tank (C2); and The second storage tank connecting flow path (L9) connects the fourth reversing member (T4) and the storage tank (C2).

8. The fluid system according to claim 7, characterized in that The storage flow path further includes a storage tank liquid inlet flow path (L10) and / or a storage tank liquid discharge flow path (L13) connected to the storage tank (C2).

9. The fluid system according to claim 7, wherein: The one or more branch flow paths include a plurality of the storage flow paths arranged in parallel.

10. The fluid system according to any one of claims 1 to 6, characterized in that At least one of the multiple switching components is a rotary valve or a solenoid valve.

11. The fluid system according to any one of claims 1 to 6, characterized in that The fluid system includes a driving mechanism for driving the flow of fluid in the fluid system, and the driving mechanism drives the flow of the fluid by positive pressure and / or negative pressure.

12. A biochemical analysis and detection platform, characterized in that: Comprising a fluid system according to any one of claims 1 to 11.

13. The biochemical analysis detection platform according to claim 12, characterized in that: It comprises a molecular biology detection device, and the molecular biology detection device comprises the fluid system.

14. The biochemical analysis and detection platform according to claim 13, characterized in that: The molecular biology detection equipment includes a gene sequencer, and the gene sequencer includes the fluid system.

15. A fluid operation method for a fluid system according to any one of claims 1 to 11, characterized in that: The fluid operation method comprises: allowing the reagent to enter at least one end of the bypass flow path (L5) close to the second conversion component (T2) and the reaction flow path through the second main flow path (L1); Disconnecting the reaction channel from the second main channel (L1) and the third main channel (L4), and allowing the reagent to undergo a biochemical reaction in the flow cell (C1) of the reaction channel; and The reagent in the bypass channel (L5) and / or the reaction channel is recovered.

16. The fluid operation method according to claim 15, characterized in that: The reagent undergoes a biochemical reaction in the flow cell (C1) of the reaction channel while the reagent in the bypass channel (L5) is recovered.

17. The fluid operation method according to claim 16, characterized in that: A portion of the reagent in the bypass flow path (L5) is caused to flow into the second main flow path (L1) so as to recover the reagent in the bypass flow path (L5) through the second main flow path (L1).

18. The fluid operation method according to any one of claims 15 to 17, characterized in that: The reagent in the reaction channel is caused to flow to the second main channel (L1) so as to recover the reagent A in the reaction channel through the second main channel (L1).

19. The fluid operation method according to claim 18, characterized in that: The fluid operation method further includes allowing the reagent A recovered through the second main channel (L1) to flow to the first main channel (L6).

20. The fluid operation method according to claim 18, characterized in that: The fluid operation method further includes causing the reagent in the bypass loop (L5) recovered through the second main flow path (L1) and the reagent in the reaction flow path to flow to the third main flow path (L4) to recover the reagent A through the third main flow path (L4).

21. The fluid operation method according to claim 20, characterized in that: The fluid system further includes a storage flow path connected to the first conversion component (T1) and the fourth conversion component (T4), and the fluid operation method includes causing the reagent recovered through the third main flow path (L4) to flow to the storage flow path.

22. The fluid operation method according to any one of claims 15 to 17, characterized in that: The fluid manipulation method includes driving the reagent through the fluid system through a buffer to recover the reagent.

23. The fluid operation method according to claim 22, characterized in that: The fluid operation method includes discharging a mixed solution of the buffer solution and the reagent in which the concentration of the buffer solution or the reagent is less than a predetermined concentration into a waste liquid storage chamber.

24. The fluid operation method according to claim 23, characterized in that: The fluid operation method includes discharging a mixed solution of the buffer solution and the reagent, wherein the concentration of the buffer solution or the reagent is less than a predetermined concentration, into the waste liquid storage chamber through at least one branch flow path; and / or The fluid system includes a fourth main flow path (L7) that is selectively connected to the third main flow path (L4), and the fourth main flow path (L7) is configured to be connected to a waste liquid storage chamber. The fluid operation method includes discharging a mixed solution of the buffer solution and the reagent in which the concentration of the buffer solution or the reagent is less than a predetermined concentration into the waste liquid storage chamber through the fourth main flow path (L7).

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