Fluidic systems, biochemical analysis detection platforms, and methods of fluidic operation

Abstract

A fluid system, a biochemical analysis detection platform, and a fluid handling method are disclosed. The fluid system includes one or more first main flow paths (L6) configured to connect to a reagent storage chamber; a second main flow path (L1); a reaction flow path including 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; a first switching component (T1) connecting one or more first main flow paths (L6), the second main flow path (L1), and at least one branch flow path, such that any two different types of flow paths are connected while the remaining flow paths are disconnected; a second switching component (T2) connecting the second main flow path (L1), the reaction flow path, and the bypass flow path (L5), such that any two flow paths are connected while the remaining flow paths are disconnected; and a third switching component (T3) connecting the third main flow path (L4), the reaction flow path, and the bypass flow path (L5), such that any two flow paths are connected while the remaining flow paths are disconnected.

Description

Technical Field

[0001] This disclosure relates to the field of fluid system technology, and in particular to a fluid system, a biochemical analysis and detection platform, and a fluid handling method. Background Technology

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

[0003] Biochemical analysis and detection platforms typically involve one or more target chambers. Samples and various reactants are transported in solution form into these chambers 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 internal flow channels. The detection of the DNA sample is a periodic cyclic process, with each cycle detecting one base. Within a single cycle, multiple functional reagents or buffer solutions are sequentially transported from storage containers to the flow cell via a fluid system. Other biochemical analysis and detection platforms also have similar fluid systems and liquid transport processes.

[0004] The functional reagents consumed in the above processes are often very expensive, which is one of the main factors restricting 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 research and development of biochemical analysis and detection platforms. There are two main methods 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 is also constrained by market supply and demand. Therefore, reducing the volume of reagents used is a more effective way to reduce costs. While reducing the length of reagent transport tubing can directly reduce losses, it is often constrained by the overall structural layout of the machine and has a lower limit. In addition, reducing the diameter of the transport tubing will lead to excessive pressure drop in the entire fluid system. In short, although there is some room for optimization in the physical internal volume of the tubing, it is easy to encounter bottlenecks.

[0005] Another strategy to reduce reagent usage is reagent recycling and reuse. Taking a gene sequencer as an example again, suppose that without recycling, each cycle uses a volume V1 of reagent. After the cycle, this portion of reagent is no longer used and is discharged as waste. With recycling, each cycle removes a volume V1 of reagent from the storage container to the flow cell for reaction, and then recovers V2 of it. The net reagent usage is then V1 - V2, reducing reagent costs.

[0006] In related technologies, a common method for recovering and reusing reagents is to directly reverse the flow of a power source. During the discovery of this disclosure, the inventors found that in the above-mentioned related technologies:

[0007] In practical flow, especially in the field of microfluidics, the interface between the two reagents is crucial because the flow velocity is low near the wall and high far from the wall. Figure 1 The parabola P shown is an example. Therefore, the target reagent recovered each time is actually mixed with other reagents. Reagent reflux methods that use a power source to directly reverse-drive partial reagent reflux may lead to cross-contamination between reagents. In some scenarios, such cross-mixing can not only reduce the purity of the target reagent but also cause unfavorable reactions. With high recovery rates, other reagents may even enter the initial storage area of ​​the target reagent, leading to even more serious cross-contamination. Summary of the Invention

[0008] The purpose of this disclosure is to provide a fluid system, a biochemical analysis and detection platform, and a fluid handling method. The fluid system aims to reduce cross-contamination between different reagents during reagent recovery and to reduce the overall operating time of the system.

[0009] The first embodiment of this disclosure provides a fluid system, including:

[0010] One or more first main paths, the first main paths being configured to connect to at least one reagent storage chamber;

[0011] The second mainstream path;

[0012] The reaction flow path includes the flow cell;

[0013] A bypass flow path is connected in parallel with the reaction flow path;

[0014] The third mainstream path;

[0015] One or more branch paths; and

[0016] Multiple commutation components, the multiple commutation components including:

[0017] A first commutation component, connecting the one or more first main flow paths, the second main flow path, and at least one of the branch flow paths, is configured such that the second main flow path can selectively communicate with any one of the one or more first main flow paths and the at least one branch flow path, while disconnecting the remaining flow paths connected to the first commutation component;

[0018] A second commutation component, connecting the second main flow path, the reaction flow path, and the bypass flow path, is configured such that the second main flow path can selectively connect to either the reaction flow path or the bypass flow path, while disconnecting the remaining flow paths connected to the second commutation component; and

[0019] The third commutation component, which connects the third main flow path, the reaction flow path, and the bypass flow path, is configured such that the third main flow path can be selectively connected to either the reaction flow path or the bypass flow path, while the remaining flow paths connected to the third commutation component are disconnected.

[0020] In some embodiments of the fluid system, the reaction flow path further includes:

[0021] A first flow path connects the flow pool to the second reversing component; and / or

[0022] The second flow path connects the flow pool to the third reversing component.

[0023] In some embodiments of the fluid system, the reaction flow path includes two or more flow pools arranged in parallel.

[0024] In some embodiments of the fluid system, the one or more branch flow paths include a first waste liquid flow path connected to the first reversing component and configured to connect to a waste liquid storage chamber.

[0025] In some embodiments of the fluid system,

[0026] The fluid system further includes one or more fourth main channels, which are configured to connect at least one reagent storage chamber and / or at least one waste liquid storage chamber.

[0027] The plurality of commutation components further includes a fourth commutation component, which connects the third main flow path, the one or more fourth main flow paths, and at least one of the branch flow paths, and is configured such that the third main flow path can be selectively connected to any one of the one or more fourth main flow paths and the at least one branch flow path, while the remaining flow paths connected to the fourth commutation component are disconnected.

[0028] In some embodiments of the fluid system, the one or more branch flow paths include a second waste liquid flow path connected to the fourth reversing component and configured to connect to a waste liquid storage chamber.

[0029] In some embodiments of the fluid system, the one or more branch flow paths include a reservoir flow path, the reservoir flow path comprising:

[0030] Storage tank;

[0031] The first storage tank is connected to the flow path, connecting the first reversing component to the storage tank; and

[0032] The second storage tank is connected to the flow path, which connects the fourth reversing component to the storage tank.

[0033] In some embodiments of the fluid system, the storage flow path further includes a storage tank inlet flow path and / or a storage tank outlet flow path connected to the storage tank.

[0034] In some embodiments of the fluid system, the one or more branch flow paths include a plurality of reservoir flow paths arranged in parallel, which may be selectively connected to the first reversing component and / or the fourth reversing component.

[0035] In some embodiments of the fluid system, at least one of the plurality of reversing components is a rotary valve or a solenoid valve.

[0036] In some embodiments of the fluid system, the fluid system includes a drive mechanism that drives fluid flow within the fluid system, the drive mechanism driving the fluid flow using positive and / or negative pressure methods.

[0037] A second aspect of this disclosure provides a biochemical analysis and detection platform, including the fluid system described in the first aspect of this disclosure.

[0038] Some implemented biochemical analysis and detection platforms include molecular biology detection devices, which include the aforementioned fluid system.

[0039] In some embodiments of the biochemical analysis and detection platform, the molecular biology detection device includes a gene sequencer, and the gene sequencer includes the fluid system.

[0040] A third aspect of this disclosure provides a fluid operation method for the fluid system described in the first aspect of this disclosure, the fluid operation method comprising:

[0041] The reagent is allowed to enter the bypass flow path and at least one end near the second reversing component and the reaction flow path via the second main flow path;

[0042] The reaction flow path is disconnected from the second and third main flow paths, and the reagent undergoes a biochemical reaction within the flow cell of the reaction flow path; and

[0043] Recover the reagents within the bypass flow path and / or the reaction flow path.

[0044] In some embodiments of the fluid handling method, the reagent undergoes a biochemical reaction in the flow cell of the reaction flow path while the reagent in the bypass flow path is recovered.

[0045] In some embodiments of the fluid handling method, a portion of the reagent in the bypass flow path is diverted to the second main flow path to recover the reagent in the bypass flow path via the second main flow path.

[0046] In some embodiments of the fluid handling method, the reagent in the reaction flow path is directed to a second main flow path to recover the reagent in the reaction flow path via the second main flow path.

[0047] In some embodiments of the fluid handling method, the fluid handling method further includes causing the reagent recovered through the second main flow path to flow back to the first main flow path.

[0048] In some embodiments of the fluid handling method, the fluid handling method further includes causing the reagent in the bypass flow path and the reagent in the reaction flow path recovered through the second main flow path to flow to the third main flow path to recover the reagent through the third main flow path.

[0049] In some embodiments of the fluid handling method, the fluid system further includes a storage flow path connected to the first reversing component and the fourth reversing component, and the fluid handling method includes causing the reagent recovered through the third main flow path to flow to the storage flow path.

[0050] In some embodiments of the fluid handling method, the fluid handling method includes agitating the reagent within the fluid system via a buffer solution to recover the reagent.

[0051] In some embodiments of the fluid handling method, the fluid handling method includes discharging a mixture of the buffer solution and the reagent at a concentration less than a predetermined concentration into a waste liquid storage chamber.

[0052] In some embodiments of the fluid handling method,

[0053] The fluid handling method includes discharging a mixture of the buffer solution and the reagent at a concentration less than a predetermined concentration into the waste liquid storage chamber through at least one of the branch flow paths; and / or

[0054] The fluid system includes a fourth main flow path selectively connected to the third main flow path, the fourth main flow path being configured to connect to a waste liquid storage chamber, and the fluid handling method comprising discharging a mixture of the buffer solution or the reagent at a concentration less than a predetermined concentration into the waste liquid storage chamber through the fourth main flow path.

[0055] Based on the fluid system provided in this disclosure, by introducing a bypass flow path at the upstream end of the flow cell, each time a reagent enters the flow cell for reaction, the reagent with a lower concentration is diverted through the bypass flow path, thereby ensuring that the reagent entering the flow cell has a sufficiently high concentration. If different reagents are completely prevented from contacting each other, a buffer solution can be introduced with the participation of the bypass flow path and branch flow paths to isolate different reagents, thereby reducing cross-contamination between reagents. The fluid system provided in this disclosure also removes air bubbles that are not allowed to enter the flow cell through the bypass flow path before the reagents enter the flow cell for reaction. Furthermore, the fluid system provided in this disclosure can perform sample reaction and reagent recovery operations in parallel, which can shorten the waiting time for relevant steps and improve overall work efficiency.

[0056] The biochemical analysis and detection platform and fluid handling method provided in this disclosure have the advantages of the fluid system provided in this disclosure.

[0057] Other features and advantages of this disclosure will become clear from the following detailed description of exemplary embodiments with reference to the accompanying drawings. Attached Figure Description

[0058] The accompanying drawings, which are included to provide a further understanding of the embodiments of this disclosure and form part of this disclosure, illustrate exemplary embodiments of this disclosure and, together with their descriptions, serve to explain the embodiments of this disclosure and do not constitute an improper limitation of the embodiments of this disclosure. In the drawings:

[0059] Figure 1 This is a schematic diagram of the interface shape when the reagent flows in the flow channel.

[0060] Figure 2 This is a schematic diagram of a fluid system according to an embodiment of the present disclosure.

[0061] Figures 3 to 5 for Figure 2 A schematic diagram illustrating the principle of a fluid operation method for a fluid system in the embodiment shown.

[0062] Figure 6 This is a schematic diagram of a fluid system according to an embodiment of the present disclosure.

[0063] Figures 7 to 10 for Figure 6 A schematic diagram illustrating the principle of a fluid operation method for a fluid system in the embodiment shown.

[0064] Figure 11 This is a schematic diagram of a fluid system according to an embodiment of the present disclosure.

[0065] Figure 12 This is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure.

[0066] Figure 13 and Figure 14 for Figure 12 A schematic diagram illustrating the principle structure of the fluid operation method of the fluid system in the embodiment shown.

[0067] Figure 15 for Figure 12 The illustrated embodiment shows a reagent distribution diagram when recycled reagent, mixed reagent, and fresh reagent are simultaneously present in a pipeline.

[0068] Figure 16 This is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure.

[0069] Figure 17 and Figure 18 for Figure 16 A schematic diagram illustrating the principle structure of the fluid operation method of the fluid system in the embodiment shown.

[0070] Figure 19 This is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure.

[0071] Figure 20 for Figure 19 A schematic diagram of the basic structure of a fluid system. Detailed Implementation

[0072] The technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the embodiments of this disclosure, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the embodiments of this disclosure or its application or use. All other embodiments obtained by those skilled in the art based on the embodiments of this disclosure without creative effort are within the scope of protection of the embodiments of this disclosure.

[0073] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps set forth in these embodiments do not limit the scope of the embodiments of this disclosure. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters in the following drawings denote similar items; therefore, once an item is defined in one drawing, it need not be further discussed in subsequent drawings.

[0074] This disclosure provides a fluid system including one or more first main flow paths L6, second main flow paths L1, reaction flow paths, bypass flow paths L5, one or more branch flow paths, and multiple reversing components.

[0075] The first main path L6 is configured to connect to at least one reagent storage chamber.

[0076] The reaction flow path includes flow cell C1.

[0077] The bypass flow path L5 is connected in parallel with the reaction flow path.

[0078] The multiple commutation components include a first commutation component T1, a second commutation component T2, and a third commutation component T3.

[0079] The first reversing component T1 connects one or more first main flow paths L6, a second main flow path L1, and at least one branch flow path, and is configured such that the second main flow path L1 can be selectively connected to any one of the one or more first main flow paths L6 and at least one branch flow path, while the remaining flow paths connected to the first reversing component T1 are disconnected.

[0080] The second reversing component T2 is connected to the second main flow path L1, the reaction flow path, and the bypass flow path L5, and is configured such that the second main flow path L1 can be selectively connected to either the reaction flow path or the bypass flow path L5, while the remaining flow paths connected to the second reversing component T2 are disconnected.

[0081] The third commutation component T3 connects the third main flow path L4, the reaction flow path, and the bypass flow path L5, and is configured such that the third main flow path L4 can be selectively connected to either the reaction flow path or the bypass flow path L5, while the remaining flow paths connected to the third commutation component T3 are disconnected.

[0082] In the fluid system of this embodiment, by introducing a bypass flow path L5 at the upstream end of the flow cell C1, each time a reagent enters the flow cell C1 for reaction, a reagent with a lower concentration or air bubbles will be drawn away from the bypass flow path L5. This helps to ensure that the reagent entering the flow cell C1 has a sufficiently high concentration, such as preventing different reagents from coming into contact with each other. In addition, a buffer solution can be introduced with the participation of the bypass flow path and the branch flow path to isolate different reagents, thereby reducing cross-contamination between reagents. It can also drain air bubbles that are not allowed to enter the flow cell C1 from the bypass flow path L5.

[0083] The fluid system provided in this disclosure also removes air bubbles that are not allowed to enter the flow cell C1 through the bypass flow path L5 before the reagent enters the flow cell for reaction.

[0084] Furthermore, by introducing a bypass flow path L5 and adding branch flow paths, the reagent recovery process can be highly parallelized with the biochemical reaction process, which can shorten the waiting time of relevant steps and improve overall work efficiency.

[0085] 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 to the second reversing component T2. The second flow cell flow path L3 connects the flow cell C1 to the third reversing component T3.

[0086] In some embodiments of the fluid system, the reaction flow path includes two or more flow cells C1 arranged in parallel.

[0087] In some embodiments of the fluid system, one or more branch flow paths include a first waste liquid flow path L11, which is connected to a first reversing component T1 and configured to connect to a waste liquid storage chamber.

[0088] In some embodiments of the fluid system, the fluid system further includes one or more fourth main flow paths L7, which are configured to connect at least one reagent storage chamber and / or at least one waste liquid storage chamber; the plurality of switching components also include a fourth switching component T4, which 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 selectively communicate the third main flow path L4 with any one of the one or more fourth main flow paths L7 and at least one branch flow path, while disconnecting the remaining flow paths connected to the fourth switching component T4.

[0089] Regarding the flow path types, the first to fourth main flows belong to different types. For example, when there are multiple first main flows L6, all first main flows L6 belong to the same type of flow path; when there are multiple fourth main flows L7, all fourth main flows L7 belong to the same type of flow path; and when there are multiple branch flows, all branch flows belong to the same type of flow path. Furthermore, for example, any two of the first main flow L7, the second main flow L1, and the branch flows belong to different types of flow paths; similarly, any two of the fourth main flow L7, the second main flow, and the branch flows belong to different types of flow paths.

[0090] In some embodiments of the fluid system, one or more branch flow paths include a second waste liquid flow path L12, which is connected to a fourth reversing component T4 and is configured to connect to a waste liquid storage chamber.

[0091] In some embodiments of the fluid system, one or more branch flow paths include a storage flow path, which includes a storage tank C2, a first storage tank connecting flow path L8, and a second storage tank connecting flow path L9. The first storage tank connecting flow path L8 connects a first reversing component T1 to the storage tank C2. The second storage tank connecting flow path L9 connects a fourth reversing component T4 to the storage tank C2.

[0092] In some embodiments of the fluid system, the storage flow path also includes a storage tank inlet flow path L10 and / or a storage tank outlet flow path L13 connected to the storage tank C2.

[0093] In some embodiments of the fluid system, one or more branch flow paths include multiple storage flow paths arranged in parallel.

[0094] In some embodiments of the fluid system, at least one of the multiple reversing components is a rotary valve or a solenoid valve.

[0095] In some embodiments of the fluid system, the fluid system includes a drive mechanism for driving fluid flow within the fluid system, the drive mechanism driving fluid flow using positive and / or negative pressure methods.

[0096] This disclosure also provides a biochemical analysis and detection platform, including the fluid system of this disclosure. The biochemical analysis and detection platform of this disclosure has the same advantages as the fluid system of this disclosure.

[0097] Biochemical analysis and detection platforms may include, for example, molecular biology detection devices, which may include the fluid system of embodiments of this disclosure. Since the molecular biology detection devices include the fluid system of embodiments of this disclosure, the fluid manipulation methods of embodiments of this disclosure may also be used.

[0098] Molecular biology detection devices include, for example, gene sequencers, which include the fluid system of embodiments of this disclosure. Since the gene sequencer includes the fluid system of embodiments of this disclosure, the fluid manipulation method of embodiments of this disclosure can also be used.

[0099] This disclosure also provides a fluid operation method for a fluid system, the fluid operation method comprising: allowing a reagent to enter at least one end of a bypass flow path L5 near a second reversing component T2 and a reaction flow path via a 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 allowing the reagent to undergo a biochemical reaction in a flow cell C1 within the reaction flow path; and recovering the reagent within the bypass flow path L5 and / or the reaction flow path.

[0100] The fluid handling method of this disclosure has the same advantages as the fluid system of this disclosure.

[0101] In some embodiments of the fluid handling method, the reagent undergoes a biochemical reaction in the flow cell C1 of the reaction flow path while the reagent in the bypass flow path L5 is recovered.

[0102] In some embodiments of the fluid handling method, a portion of the reagent in the bypass flow path L5 is diverted to the second main flow path L1 to recover the reagent in the bypass flow path L5 through the second main flow path L1.

[0103] In some embodiments of the fluid handling method, the reagent in the reaction flow path is directed to a second main flow path L1 to recover the reagent in the reaction flow path through the second main flow path L1.

[0104] In some embodiments of the fluid handling method, the fluid handling method further includes causing the reagent recovered through the second main flow path L1 to flow to the first main flow path L6.

[0105] In some embodiments of the fluid handling method, the fluid handling method further includes causing the reagents in the bypass flow path L5 recovered through the second main flow path L1 and the reagents in the reaction flow path to flow to the third main flow path L4 to recover the reagents through the third main flow path L4.

[0106] In some embodiments of the fluid handling method, the fluid system further includes a storage flow path connected to a first reversing component T1 and a fourth reversing component T4, and the fluid handling method includes causing reagents recovered through a third main flow path L4 to flow into the storage flow path.

[0107] In some embodiments of the fluid handling method, the fluid handling method includes agitating a reagent within a fluid system via a buffer solution to recover the reagent.

[0108] In some embodiments of the fluid handling method, the fluid handling method includes discharging a mixture of buffer solution and reagent at a concentration less than a predetermined concentration into a waste liquid storage chamber.

[0109] In some embodiments of the fluid handling method, the fluid handling method includes discharging a mixture of buffer solution and reagent with a concentration of 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 selectively connected to a third main flow path L4, the fourth main flow path L7 being configured to connect to the waste liquid storage chamber, the fluid handling method including discharging a mixture of buffer solution and reagent with a concentration of less than a predetermined concentration into the waste liquid storage chamber through the fourth main flow path L7.

[0110] The following combination Figures 2 to 20 The fluid system and fluid operation method of the present disclosure will be described in more detail.

[0111] Figures 2 to 5 A schematic diagram of an embodiment of the present disclosure is shown. Figure 2This is a schematic diagram of the fluid system in this embodiment. Figures 3 to 5 for Figure 2 A schematic diagram illustrating the principle of a fluid operation method for a fluid system in the embodiment shown.

[0112] like Figures 2 to 5 As shown, the fluid system of this embodiment 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.

[0113] 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. A bypass flow path L5 is connected in parallel with the reaction flow path. A first waste liquid flow path L11 is configured to connect to a waste liquid storage chamber. A second waste liquid flow path L12 is configured to connect to a waste liquid storage chamber. A first reversing component T1 connects a first main flow path L6, a second main flow path L1, and a first waste liquid flow path L11, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths. A second reversing component T2 connects a second main flow path L1, a first flow cell flow path L2, and a bypass flow path L5, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths. The third reversing component T3 connects the third main flow path L4, the second flow tank flow path L3, and the bypass flow path L5, and is configured to selectively connect any two of these flow paths while disconnecting the remaining flow paths from the two connected flow paths. The fourth reversing component 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 these flow paths while disconnecting the remaining flow paths from the two connected flow paths.

[0114] The following combination Figures 2 to 5 This disclosure describes a logical timing scheme for an implementable fluid handling method including a reagent recovery process, according to embodiments of the present disclosure. In this logical timing scheme, reagent A is a reagent requiring partial recovery, reagent B is a reagent that cannot cross-contaminate with reagent A and does not require recovery, and buffer solution C serves as an intermediate medium separating reagents A and B. These three liquids, namely reagent A, reagent B, and buffer solution C, constitute the minimum component system of the reagent recovery scheme. In practical applications, the component system of the reagent recovery scheme can be expanded; for example, the reagents to be recovered may include multiple types, namely A1, A2, A3…An.

[0115] In the logical timing scheme of this 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 of reagent A; the downstream of the fourth main flow path L7 is in fluid communication with the storage chamber of other reagents (such as reagent B, buffer solution C, etc.); 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.

[0116] The steps of the logical timing scheme for this fluid manipulation method are as follows:

[0117] Step S1100: In the initial state, reagent A is contained in the first main flow path L6; buffer solution C is contained in the flow cell C1; buffer solution C is contained in the second main flow path L1, the first flow cell flow path L2, the second flow cell flow path L3, the third main flow path L4, the bypass flow path L5, and the fourth main flow path L7; reagent B has not yet entered the fluid system. The first switching component T1 connects the first main flow path L6 and the second main flow path L1; the second switching component T2 connects the second main flow path L1 and the bypass flow path L5; the third switching component T3 connects the bypass flow path L5 and the third main flow path L4; the fourth switching component T4 connects the third main flow path L4 and the second waste liquid flow path L12.

[0118] Step S1101: Reagent A enters the second main flow path L1 from the first main flow path L6 via the first switching component T1, and then enters the bypass flow path L5 via the second switching component T2, replacing the buffer solution C in the second main flow path L1 and the bypass flow path L5, until the first main flow path L6 and the second main flow path L1 are filled with reagent A at a concentration greater than 99%, and the bypass flow path L5 contains a mixture of reagent A and buffer solution C. Excess buffer solution C flows sequentially through the third switching component T3, the third main flow path L4, the fourth switching component T4, and the second waste flow path L12 before being discharged. This step S1101 is to ensure a high concentration of reagent A entering the flow cell C1.

[0119] Step S1102: The second reversing component T2 switches, making the second main flow path L1 fluidly connected to the first flow cell flow path L2; the third reversing component T3 switches, making the second flow cell flow path L3 fluidly connected to the third main flow path L4. At this time, both the upstream of the second reversing component T2 and the downstream of the third reversing component T3 are fluidly connected to the flow cell C1. High-concentration reagent A enters the flow cell C1 through the second reversing component T2 and the first flow cell flow path L2, replacing the buffer solution in the first flow cell flow path L2, the flow cell C1, and the second flow cell flow path L3, such as... Figure 3 As shown. The flow continues until the first flow cell path L2, flow cell C1, and the second flow cell path L3 are filled with reagent A with a concentration greater than 99%, and the third main flow path L4 is a mixture of reagent A and buffer C.

[0120] Step S1103: The DNA sample fixed inside the flow cell C1 then undergoes a biochemical reaction with reagent A; simultaneously, the second switching component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, and the upstream of the second switching component T2 is disconnected from the flow cell C1; the third switching component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, and the downstream of the third switching component T3 is disconnected from the flow cell C1; the fourth switching component T4 is switched to connect the third main flow path L4 with the fourth main flow path L7.

[0121] Step S1104: Buffer C flows from the fourth main flow path L7 through the fourth switching component T4 into the third main flow path L4, then through the third switching component T3 into the bypass flow path L5, replacing the high concentration of reagent A in the bypass flow path L5 near the second switching component T2, the second main flow path L1, and the first main flow path L6. Reagent A with a concentration greater than 95% is completely returned to the first main flow path L6 until the second main flow path L1 contains a mixture of reagent A and buffer C, and the bypass flow path L5 contains buffer C. Figure 4 As shown.

[0122] Step S1105: Switch the first reversing component T1 to connect the second main flow path L1 with the first waste flow path L11. Buffer C, after step S1104, continues to enter the fluid system, continuously filling the third main flow path L4 and bypass flow path L5 with buffer C until the fourth main flow path L7, the third main flow path L4, and the bypass flow path L5 are filled with buffer C at a concentration greater than 99%. Excess buffer C and low-concentration reagent A flow sequentially through the second reversing component T2, the second main flow path L1, the first reversing component T1, and the first waste flow path L11 before being discharged. Steps S1104 and S1105 can run in parallel with the biochemical reaction in flow cell C1, and the reaction time is shorter than that in flow cell C1.

[0123] Step S1106: After the biochemical reaction in flow cell C1 is completed, switch the third reversing component T3 to connect the second flow cell flow path L3 with the third main flow path L4, and connect flow cell C1 with the reagent storage chamber downstream of the fourth main flow path L7; switch the second reversing component T2 to connect the second main flow path L1 with the first flow cell flow path L2, and connect flow cell C1 with the waste liquid storage chamber through the first waste liquid flow path L11. High-concentration buffer solution C enters flow cell C1 through 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, the first flow cell flow path L2, and the mixture in the second main flow path L1. The mixture and the low-concentration reagent A are discharged through the first waste liquid flow path L11 until the second main flow path L1, the first flow cell flow path L2, and the side of flow cell C1 closest to the second reversing component T2 are filled with high-concentration reagent A.

[0124] Step S1107: Switch the first reversing component T1 to make the second main flow path L1 and the first main flow path L6 fluidly connected, and the buffer solution C continues to enter the flow cell C1. Reagent A with a concentration greater than 95% in the first flow cell flow path L2, flow cell C1, and second flow cell flow path L3 enters the first main flow path L6, such as... Figure 5 As shown. The recovery process for reagent A is now complete.

[0125] Step S1108: Switch the first reversing component T1 to make the second main flow path L1 and the first waste liquid flow path L11 in fluid communication. Subsequently, 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 cell flow path L2 and the flow cell C1 are discharged through the first waste liquid flow path L11 until the second main flow path L1, the first flow cell flow path L2, the second flow cell flow path L3, the third main flow path L4, the bypass flow path L5, the fourth main flow path L7 and the flow cell C1 are all filled with buffer solution C.

[0126] Step S1109: Switch the second reversing component T2 to connect the second main flow path L1 and the bypass flow path L5. Switch the third reversing component T3 to connect the third main flow path L4 and the bypass flow path L5. Disconnect the flow cell C1 from the upstream of the second reversing component T2 and the downstream of the third reversing component T3, thereby disconnecting it from the reagent storage chambers upstream of the first main flow path L6 and downstream of the fourth main flow path L7. Reagent B enters from the fourth main flow path L7, passes through the fourth reversing component T4 and the third main flow path L4, and enters the bypass flow path L5, replacing the buffer solution C in the third main flow path L4 and the bypass flow path L5 until the fourth main flow path L7 and the third main flow path L4 are filled with reagent B with a concentration greater than 99%. The bypass flow path L5 contains a mixture of reagent B and buffer solution C. Excess buffer solution C in the bypass flow path L5 flows sequentially through the second reversing component T2, the second main flow path L1, the first reversing component T1, and the first waste liquid flow path L11 before being discharged. Step S1109 is to ensure a high concentration of reagent B entering the flow cell.

[0127] Step S1110: The second reversing component T2 switches, making the second main flow path L1 fluidly connected to the first flow cell path L2; the third reversing component T3 switches, making the second flow cell path L3 fluidly connected to the third main flow path L4. At this time, the upstream of the second reversing component T2 and the downstream of the third reversing component T3 are both fluidly connected to the flow cell C1. High-concentration reagent B enters the flow cell C1 through the third reversing component T3 and the second flow cell path L3, replacing the buffer solution C in the second flow cell path L3, the flow cell C1, and the first flow cell path L2, until the second flow cell path L3, the flow cell C1, and the first flow cell path L2 are filled with reagent B with a concentration greater than 99%. The second main flow path L1 and the first waste liquid path L11 are a mixture of reagent B and buffer solution C.

[0128] Step S1111: The DNA sample fixed inside the flow cell C1 then undergoes a biochemical reaction with reagent B; simultaneously, the second switching component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, and the upstream of the second switching component T2 is disconnected from the flow cell C1; the third switching component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, and the downstream of the third switching component T3 is disconnected from the flow cell C1.

[0129] Step S1112: Buffer C flows from the fourth main flow path L7 through the fourth switching component T4 into the third main flow path L4, and then through the third switching component T3 into the bypass flow path L5, replacing reagent B in the bypass flow path L5 and the second main flow path L1. All reagent B is discharged from the first waste flow path L11 until the second main flow path L1, bypass flow path L5, third main flow path L4, and fourth main flow path L7 are filled with buffer C.

[0130] Step S1113: The biochemical reaction of reagent B is completed. The second reversing component T2 switches, connecting the second main flow path L1 with the first flow cell path L2. The third reversing component T3 switches, connecting the second flow cell path L3 with the third main flow path L4. At this time, the upstream of the second reversing component T2 and the downstream of the third reversing component T3 are both connected to the flow cell C1. Buffer C enters the 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, the flow cell C1, and the first flow cell path L2. At this point, all flow paths and the flow cell 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 flow path.

[0131] Repeating steps S1100 to S1113 can perform a new cycle. Throughout the fluid handling process, reagent A and reagent B are separated by buffer solution C and will not come into contact, thus avoiding cross-contamination of reagents.

[0132] In the above logical timing scheme of the fluid handling method, the operation performed on reagent A is to recover a portion of reagent A, while the operation performed on reagent B is not to recover reagent B. However, according to the above logical timing scheme, the recovery of reagent B can also be achieved by using the step of recovering a portion of reagent A. Furthermore, molecular biological detection involving more reagents can be achieved according to the aforementioned method steps, and the recovery of the corresponding reagents can be selected.

[0133] In the above logical timing scheme of the fluid operation method, taking a dual-reagent approach as an example, reagent B and buffer solution C both enter from the fourth main flow path L7, while reagent A enters from the first main flow path L6. In cases where more reagents are involved in molecular biology detection, multiple reagent storage chambers can be set upstream of the first switching component T1 and downstream of the fourth switching component T4 to store different reagents. These reagent storage chambers can be selectively connected to either the first main flow path L6 or the fourth main flow path L7. Alternatively, in embodiments not illustrated, multiple first main flow paths L6 connecting different reagent storage chambers can be directly connected to the first switching component T1, and / or multiple fourth main flow paths L7 connecting different reagent storage chambers can be directly connected to the fourth switching component T4. Different reagents can be introduced into the fluid system according to reaction requirements, and each reagent can be isolated with buffer solution C if necessary to avoid cross-contamination.

[0134] In this embodiment of the disclosure, when reagent A, reagent B, and buffer solution C enter the fluid system, they can be pushed in from the inlet side of the fluid flow direction using a positive pressure drive, for example, by using a diaphragm pump or syringe pump to push the liquid upstream of the first main flow path L6. Alternatively, they can be drawn in from the outlet side of the fluid flow direction using a negative pressure, for example, by using a syringe pump to draw liquid from the inlet end of the first main flow path L6 at the end of the fourth main flow path L7 / second waste liquid flow path L12.

[0135] In this embodiment of the disclosure, only one reaction flow path is shown. However, in embodiments not shown, multiple reaction flow paths may be connected in parallel to form a multi-inlet and multi-outlet reaction region.

[0136] In the above logical timing scheme of fluid operation method, reagent A will be recovered to the first main flow path L6 and its upstream. Each time, a portion of the reagent is consumed near the end of the flow cell C1. Considering the concentration dilution in the flow cell C1 and the 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 it is necessary to recover more than 95% of the concentration, the recovery ratio is generally below 25%.

[0137] Considering the short duration of each biochemical process, the reagent concentration in the first mainstream flow path L6 cannot be uniform solely due to diffusion. The reagent concentration near the second mainstream flow path L1 is relatively low, while the reagent further away from L1 is fresh. The portion entering the bypass flow path L5 and the initial small portion entering the flow cell C1 will contain relatively low-concentration reagent, followed by fresh reagent. During the pumping process, as the liquid passes through various switching components and flow paths, the two portions of reagent will mix to some extent. Therefore, the final reagent concentration in the flow cell C1 is relatively uniform, but slightly lower than that of the fresh reagent.

[0138] In the above logical timing scheme of fluid handling method, some steps of the reagent recovery process are carried out in parallel with the biochemical reaction in flow cell C1, which helps to save molecular biology detection time.

[0139] Figures 6 to 10 A schematic diagram of an embodiment of the present disclosure is shown. Figure 6 This is a schematic diagram of a fluid system according to an embodiment of the present disclosure. Figures 7 to 10 for Figure 6 A schematic diagram illustrating the principle of a fluid operation method for a fluid system in the embodiment shown.

[0140] like Figures 6 to 10 As shown, the fluid system of this embodiment 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, a fourth reversing component T4, and a storage flow path.

[0141] 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. 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 C2. A first reversing component T1 connects a first main flow path L6, a second main flow path L1, and a first storage cell connecting flow path L8, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths. The second reversing component T2 connects the second main flow path L1, the first flow tank flow path L2, and the bypass flow path L5, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths. The third reversing component T3 connects the third main flow path L4, the second flow tank flow path L3, and the bypass flow path L5, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths. The fourth reversing component T4 connects the third main flow path L4, the fourth main flow path L7, and the second storage tank connecting flow path L9, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths.

[0142] The following combination Figures 6 to 10This disclosure describes a logical timing scheme for an implementable fluid handling method including a reagent recovery process, according to embodiments of the present disclosure. In this logical timing scheme, reagent A is the reagent requiring partial recovery, reagent B is the reagent that cannot cross-contaminate with reagent A and does not require recovery, and buffer solution C serves as an intermediate medium separating reagents A and B. The three liquids, namely reagent A, reagent B, and buffer solution C, constitute the minimum component system of the reagent recovery scheme. In practical applications, the component system of the reagent recovery scheme can be expanded; for example, the reagents to be recovered may include multiple types, namely A1, A2, A3…An.

[0143] In the logical timing scheme of the fluid operation method in this embodiment of the disclosure, the first main flow path L6 is still used as the upstream of the fluid system. For example... Figures 6 to 10 As shown, this embodiment uses a storage flow path as a branch flow path instead of a storage flow path. Figures 2 to 5 The fluid system shown includes a first waste liquid flow path L11 and a second waste liquid flow path L12. The storage flow path includes a storage tank C2, a first storage tank connection flow path L8 and a second storage tank connection flow path L9 connected to storage tank C2, and a storage tank inlet flow path L10 and a storage tank outlet flow path L13 connected to the storage tank. Simultaneously, a unidirectional pumping method is used to allow reagents to enter flow tank C1 from the first flow tank flow path L2 and exit flow tank C1 from the second flow tank flow path L3; reagent A enters storage tank C2 temporarily from the storage tank inlet flow path L10; the upstream of the first main flow path L6 is in fluid communication with the reagent storage chambers of reagent B and buffer solution C; the downstream of the fourth main flow path L7 is in fluid communication with the waste liquid storage chamber.

[0144] The steps of the logical timing scheme for this fluid manipulation method are as follows:

[0145] Step S2100: In the initial state, flow cell C1 contains buffer solution C, and the second main flow path L1, first flow cell path L2, second flow cell path L3, third main flow path L4, bypass flow path L5, and first main flow path L6 all contain buffer solution C. The first storage tank connecting flow path L8 contains reagent A, and the second storage tank connecting flow path L9 contains air. Storage cell C2 contains a certain volume of reagent A. Because the amount of reagent A recovered in a single operation is less than the amount consumed, a certain volume of reagent A needs to be pre-filled in storage cell C2. The first switching component T1 connects the first main flow path L6 and the second main flow path L1; the second switching component T2 connects the second main flow path L1 and the bypass flow path L5; the third switching component T3 connects the bypass flow path L5 and the third main flow path L4; and the fourth switching component T4 connects the third main flow path L4 and the fourth main flow path L7.

[0146] Step S2101: The first switching component T1 switches, connecting the first storage tank connecting flow path L8 and the second main flow path L1. Reagent A flows from storage tank C2, through the first storage tank connecting flow path L8, through the first switching component T1 into the second main flow path L1, and then through the second switching component T2 into the bypass flow path L5, replacing the buffer solution C in the second main flow path L1 and the bypass flow path L5, until the first storage tank connecting flow path L8 and the second main flow path L1 are filled with reagent A at a concentration greater than 99%, and the bypass flow path L5 contains a mixture of reagent A and buffer solution C. Excess buffer solution C flows sequentially through the third switching component T3, the third main flow path L4, the fourth switching component T4, and the fourth main flow path L7 before being discharged. Step S2101 is to ensure a high concentration of reagent A entering the flow tank C1.

[0147] Step S2102: The second reversing component T2 switches, making the second main flow path L1 fluidly connected to the first flow cell flow path L2; the third reversing component T3 switches, making the second flow cell flow path L3 fluidly connected to the third main flow path L4. At this time, the upstream of the second reversing component T2 and the downstream of the third reversing component T3 are both fluidly connected to the flow cell C1. High-concentration reagent A enters the flow cell C1 through the second reversing component T2 and the first flow cell flow path L2, replacing the buffer solution C in the first flow cell flow path L2 and the flow cell C1, until the first flow cell flow path L2, the flow cell C1, and the second flow cell flow path L3 are filled with reagent A at a concentration greater than 99%. The third main flow path L4 is a mixture of reagent A and buffer solution C. Figure 7 As shown.

[0148] Step S2103: The DNA sample fixed inside the flow cell C1 then undergoes a biochemical reaction with reagent A; simultaneously, the second switching component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, while the upstream of the second switching component T2 is disconnected from the flow cell C1; the third switching component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, while the downstream of the third switching component T3, the third main flow path L4, is disconnected from the flow cell C1; the first switching 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 switching component T1 is disconnected from the storage cell C2.

[0149] Step S2104: Reagent A meeting the concentration requirements in the bypass flow path L5 near the second switching component T2 is returned to the second main flow path L1. Reagent A in the second main flow path L1 and the bypass flow path L5, which are downstream of the first switching component T1 and fluidly connected to the first main flow path L6, enters the first main flow path L6. Figure 8 As shown. In this step, part of reagent A is temporarily stored in the first main flow path L6, and will be recovered together with the reagents in the flow cell C1 later.

[0150] Step S2105: The biochemical reaction in flow cell C1 is completed. Switch the third reversing component T3 to connect the second flow cell path L3 with the third main flow path L4. Switch the fourth reversing component T4 to connect the third main flow path L4 with the fourth main flow path L7. At this time, flow cell C1 is connected to the waste liquid storage area downstream of the fourth main flow path L7. Switch the second reversing component T2 to connect the second main flow path L1 with the first flow cell path L2. Flow cell C1 is connected to the upstream of the second reversing component T2. High-concentration buffer solution C enters from the first main flow path L6, passes through the first reversing component T1, the second main flow path L1, the second reversing component T2, and the first flow cell path L2 to enter flow cell C1, replacing part of the reagent A recovered in step S2104 in the first main flow path L6, the reagent A in the first flow cell path L2, flow cell C1, the second flow cell path L3, and the mixture of reagent A and buffer solution C in the third main flow path L4. The mixture and low-concentration reagent A are discharged through the fourth main flow path L7 until the third main flow path L4, the second flow cell path L3, and the side of the flow cell C1 near the third reversing component T3 are filled with high-concentration reagent A.

[0151] Step S2106: Switch the fourth reversing component T4 to connect the third main flow path L4 with the second storage tank connecting flow path L9. At this time, flow cell C1 is connected to storage tank C2 via the second flow cell flow path L3, the third reversing component T3, the third main flow path L4, the fourth reversing component T4, and the second storage tank connecting flow path L9. The high-concentration buffer solution C continues to enter the fluid system from the first main flow path L6. As the buffer solution C flows, reagent A with a concentration greater than 95% in flow cell C1 enters the second storage tank connecting flow path L9 through the third main flow path L4, the second flow cell flow path L3, and then enters storage tank C2. Figure 9 As shown. The recovery process for reagent A is now complete.

[0152] Step S2107: Switch the fourth reversing component T4 to make the third main flow path L4 and the fourth main flow path L7 fluidly connected. At this time, the flow cell C1 is fluidly connected to the waste liquid storage area downstream of the fourth main flow path L7; subsequently, low-concentration reagent A and the mixture of reagent A and buffer solution C are discharged through the fourth main flow path L7. At this point, the first main flow path L6, the second main flow path L1, the first flow cell flow path L2, the bypass flow path L5, the second flow cell flow path L3, the third main flow path L4, the fourth main flow path L7, the ends near the fourth reversing component T4, and the flow cell C1 are filled with buffer solution C.

[0153] Step S2108: The first switching component T1 switches, connecting the first main flow path L6 and the second main flow path L1 in fluid communication, while disconnecting the upstream of the first switching component T1 from the storage tank C2. Reagent B flows from the first main flow path L6 through the first switching component T1 into the second main flow path L1, and then through the second switching component T2 into the bypass flow path L5, replacing the buffer solution C in the second main flow path L1 and the bypass flow path L5. At this time, the first main flow path L6 and the second main flow path L1 are filled with reagent B with a concentration greater than 99%, and the bypass flow path L5 contains a mixture of reagent B and buffer solution C. Excess buffer solution C flows sequentially through the third switching component T3, the third main flow path L4, the fourth switching component T4, and the fourth main flow path L7 before being discharged. Step S2108 is to ensure a high concentration of reagent B entering the flow cell.

[0154] Step S2109: Maintain the state of the first reversing component T1 unchanged, so that the first main flow path L6 is still in fluid communication with the second main flow path L1, while the upstream of the first reversing component T1 remains disconnected from the storage tank C2; maintain the state of the fourth reversing component T4 unchanged, so that the third main flow path L4 is still in fluid communication with the fourth main flow path L7, while the upstream of the fourth reversing component T4 remains disconnected from the storage tank C2. The second reversing component T2 switches, so that the second main flow path L1 is in fluid communication with the first flow tank flow path L2; the third reversing component T3 switches, so that the second flow tank flow path L3 is in fluid communication with the third main flow path L4. At this time, the upstream of the second reversing component T2 and the downstream of the third reversing component T3 are both in fluid communication with the flow tank C1. High-concentration reagent B enters flow cell C1 through the second reversing component T2 and the first flow cell flow path L2, replacing the buffer solution in the first flow cell flow path L2 and flow cell C1 until the first flow cell flow path L2, flow cell C1, and second flow cell flow path L3 are filled with reagent B with a concentration greater than 99%. The third main flow path L4 is a mixture of reagent B and buffer solution C.

[0155] Step S2110: The DNA sample fixed inside the flow cell C1 then undergoes a biochemical reaction with reagent B; simultaneously, the second switching component T2 is switched to connect the second main flow path L1 with the bypass flow path L5, while the upstream of the second switching component T2 is disconnected from the flow cell C1; the third switching component T3 is switched to connect the third main flow path L4 with the bypass flow path L5, while the downstream of the third switching component T3 is disconnected from the flow cell C1.

[0156] Step S2111: Buffer C flows from the first main flow path L6 through the first switching component T1 into the second main flow path L1, then through the second switching component T2 into the bypass flow path L5, replacing the high concentration of reagent B in the bypass flow path L5 near the second switching component T2, the second main flow path L1, and the first main flow path L6. The low concentration of reagent B or the mixture of reagent B and buffer C in the bypass flow path L5, away from the second switching component T2, flows sequentially through the third switching component T3, the third main flow path L4, the fourth switching 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 contain buffer C with a concentration greater than 99%, and the third main flow path L4 contains a mixture of reagent B and buffer C.

[0157] Step S2112: The biochemical reaction in flow cell C1 is completed; switch the third reversing component T3 to connect the second flow cell path L3 with the third main flow path L4, at which point flow cell C1 is connected to the waste liquid storage area downstream of the fourth main flow path L7; switch the second reversing component T2 to connect the second main flow path L1 with the first flow cell path L2, and flow cell C1 is connected to the reagent storage chamber upstream of the first main flow path L6. High-concentration buffer solution C enters the first main flow path L6, and then flows sequentially through the first reversing component T1, the second main flow path L1, the second reversing component T2, and the first flow cell path L2 into flow cell C1, replacing reagent B in the first flow cell path L2, flow cell C1, and the second flow cell path L3, as well as the mixture of reagent B and buffer solution C in the third main flow path L4. Reagent B and excess buffer solution C in the first flow cell path L2, flow cell C1, second flow cell path L3, and third main flow path L4 are discharged through the fourth main flow path L7. At this point, except for the first storage tank connecting flow path L8, the second storage tank connecting flow path L9, the storage tank inlet flow path L10, the storage tank outlet flow path L13, and the storage tank C2, all other flow paths and the flow cell C1 are filled with buffer solution C, and reagent B has been discharged from the fluid system.

[0158] Step S2113: Repeat steps S2101~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 storage tank C2 and the lower limit of the allowable concentration of reagent A when used in molecular biological detection. The larger the amount of reagent A in storage tank C2 and the lower the lower limit of the allowable concentration of reagent A when used in molecular biological detection, the larger the upper limit of n; conversely, the smaller the amount of reagent A in storage tank C2 and the higher the lower limit of the allowable concentration of reagent A when used in molecular biological detection, the smaller the upper limit of n.

[0159] Step S2114: Reagent A in storage tank C2 is discharged to the waste liquid storage area through storage tank drain flow path L13. Then, fresh reagent A enters the storage tank through storage tank inlet flow path L10 for use in the next n cycles.

[0160] In the above logical timing scheme of 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 storage tank C2.

[0161] In the logical timing scheme of the above fluid handling method, reagent A and reagent B are separated by buffer solution C and will not come into contact, thus preventing cross-contamination.

[0162] In the above logical timing scheme of the fluid handling method, the reagent recovery process is illustrated using a dual-reagent example including reagent A and reagent B. The operation performed on reagent A involves recovering a portion of reagent A, while the operation performed on reagent B involves not recovering reagent B. However, according to the above logical timing scheme, a corresponding storage flow path can also be set up for reagent B, and the recovery of reagent B can be achieved by using the step of recovering a portion of reagent A. Therefore, more reagents requiring partial recovery can be used in molecular biology detection according to the aforementioned method. Additionally, the first main flow path L6 can be selectively connected to different reagent storage chambers, or the first reversing component T1 can be selectively connected to multiple parallel first main flow paths, each connected to a different reagent storage chamber. This allows for the use of more reagents that do not require recovery in molecular biology detection according to the aforementioned method. Between any two reagents that need to enter the flow cell C1, buffer solution C can be used for isolation if necessary to prevent cross-contamination between the two reagents.

[0163] In the above logical timing scheme for fluid handling, reagents all enter flow cell C1 from the upstream side. Reagent A, reagent B, and buffer solution C enter flow cell C1 either by positive pressure from the inlet side of the corresponding flow path upstream of flow cell C1, or by negative pressure from the outlet side of the corresponding flow path downstream of flow cell C1. For example, if reagent A is introduced by positive pressure, it can first be drawn into the first main flow path L6 by negative pressure, and then pushed into flow cell C1 and the bypass flow path L5 upstream of the first main flow path L6 by positive pressure, as follows. Figure 10 As shown.

[0164] In the above logical timing scheme for fluid handling, reagent recovery within the bypass flow path L5 involves first returning the reagent upstream of L5, and then performing this portion of reagent recovery together with the subsequent reagent recovery in flow cell C1. This recovery method is suitable when the flow paths of bypass flow path L5 and the third main flow path L4 are relatively long, as it helps prevent the reagent concentration from being severely diluted when reaching the recovery position due to the long flow path, making it difficult to guarantee high-concentration reagent recovery. However, if the internal volumes of bypass flow path L5 and the third main flow path L4 are small, reagent recovery via bypass flow path L5 is feasible.

[0165] In the above logical timing scheme for fluid operation, the amount of reagent pre-stored in storage tank C2 plus the amount of recovered reagent is generally suitable for a cycle count of 20-30, i.e., n = 20-30. This is because: 1. A certain amount needs to be reserved each time fresh reagent A enters storage tank C2 to avoid the intake of air after reagent A is consumed; if the cycle count is small, the frequency of fresh reagent A entering storage tank C2 will be higher, and the cost of the reserve portion will be higher; 2. When the concentration of reagent A decreases to a certain level, it will affect the quality of the reaction in flow tank C1, while too many cycles will cause the reagent concentration in storage tank C2 to decrease, and the repeated use of some components of the reagent may adversely affect the quality of the reaction in flow tank C1.

[0166] In the above logical timing scheme for fluid handling, reagent A is recycled to storage tank C2. Assuming that the recycled reagent A and fresh reagent A can be thoroughly mixed in storage tank C2, and if the required reagent concentration entering flow tank C1 is greater than 95%, considering that the recycled reagent A can be mixed with the 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 recycled reagent A. Therefore, the concentration of the recycled reagent A can be less than 95%. Taking into account the pre-storage capacity of the storage tank and cost, the recycling ratio is... Figures 2 to 5 The illustrated embodiment shows an even higher rate, reaching 25-35%.

[0167] In the above logical timing scheme of fluid handling method, some steps of the reagent recovery process are carried out in parallel with the biochemical reaction in flow cell C1, which helps to save molecular biology detection time.

[0168] Figure 11 A schematic diagram of an embodiment of the present disclosure is shown.

[0169] like Figure 11As shown, the fluid system of this embodiment 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.

[0170] The reaction flow path includes a flow tank C1 and a first flow tank flow path L2 and a second flow tank flow path L3 connected to the flow tank C1. A bypass flow path L5 is connected in parallel with the reaction flow path. 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 outlet flow path L13 connected to the storage tank. A first waste liquid flow path L11 is configured to connect to a waste liquid storage chamber. A second waste liquid flow path L12 is configured to connect to a waste liquid storage chamber. A first reversing component T1 connects a first main flow path L6, a second main flow path L1, a first waste liquid flow path L11, and a first storage tank connecting flow path L8, and is configured to selectively connect any two of the following flow paths, while disconnecting the remaining flow paths from the two connected flow paths. The second reversing component T2 connects the second main flow path L1, the first flow tank flow path L2, and the bypass flow path L5, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths. The third reversing component T3 connects the third main flow path L4, the second flow tank flow path L3, and the bypass flow path L5, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths. The fourth reversing component T4 connects the third main flow path L4, the fourth main flow path L7, the second waste liquid flow path L12, and the second storage tank connecting flow path L9, and is configured to selectively connect any two of these flow paths, while disconnecting the remaining flow paths from the two connected flow paths.

[0171] like Figure 11 As shown, in this embodiment, the reaction flow path includes multiple flow cells C1 connected in parallel to allow for simultaneous biochemical reactions within the multiple flow cells C1. The multiple flow cells C1 can be connected to the first flow cell flow path L2 and the second flow cell flow path L3 via a first flow cell branch pipe L2_1 and a second flow cell branch pipe L3_1, respectively. The logical timing scheme of the implementable fluid manipulation method of this embodiment can be referred to... Figures 2 to 5 The illustrated embodiments and Figures 6 to 10The embodiments shown are illustrated. The fluid system of this disclosure has greater flexibility compared to the foregoing embodiments.

[0172] The following combination Figures 12 to 20 This describes an embodiment of a fluid system that applies the fluid system described in this disclosure.

[0173] Figures 12 to 15 The schematic structure of a fluid system according to an embodiment of the present disclosure is shown. Figure 12 This is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure. Figure 13 and Figure 14 for Figure 12 A schematic diagram illustrating the principle structure of the fluid operation method of the fluid system in the embodiment shown. Figure 15 for Figure 12 The illustrated embodiment shows a reagent distribution diagram when recycled reagent, mixed reagent, and fresh reagent are simultaneously present in a pipeline. The mixed reagent refers to a mixture of recycled and fresh reagent.

[0174] like Figures 12 to 14 As shown, the fluid system in this example is the one described above. Figures 2 to 5 A specific example of the fluid system is shown. 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 path L6 of the fluid system is implemented as a combination of pipes 101 and 108. Pipe 101 is connected to the reagent storage chamber R1, and pipe 101 is connected to pipe 108 in a switchable manner via rotary valve 1101. The second main flow path L1 of the fluid system is implemented as pipe 102; the third main flow path L4 of the fluid system is implemented as pipe 106; the fourth main flow path L7 of the fluid system is implemented as a combination of pipes 107 and 109. Pipe 107 is connected to the reagent storage chamber R2, and pipe 107 is connected to pipe 109 in a switchable manner via rotary valve 1102. The bypass flow path L5 of the fluid system is implemented as pipe 103. The first flow path L2 of the fluid system is implemented as pipe 104. The second flow path L3 of the fluid system is implemented as pipe 105. The first waste liquid flow path L11 of the fluid system is implemented as pipe 110. The second waste liquid flow path L12 of the fluid system is implemented as pipe 111. The flow cell C1 is implemented as chip 1201.

[0175] Figures 12 to 14 In the illustrated embodiment, rotary valve 1101 is connected to power source 1105 via pipe 108. Rotary valve 1102 is connected to power source 1106 via pipe 109. Pipe 101 is connected to reagent storage chamber R1, and pipe 107 is connected to reagent storage chamber R2. Pipes 110 and 111 are respectively connected to waste liquid storage chambers.

[0176] Figures 12 to 14 In the illustrated embodiment, rotary valves 1101 and 1102 are, for example, 25-hole rotary valves; solenoid valves 1103 and 1104 are, for example, two-position three-way solenoid valves; power sources 1105 and 1106 are, for example, injection pumps; and chip 1201 is, for example, a single-input single-output chip.

[0177] The following describes a feasible fluid operation method for the fluid system in this example. This fluid operation method provides four basic fluid flow modes: two normal flow modes without reagent recovery (bypass flow and chip flow), and two reagent recovery modes with reagent recovery processes (bypass reagent recovery and chip reagent recovery). In the feasible logical timing scheme for the reagent recovery process, the reagent to be recovered is reagent A, and buffer solution C is used to isolate reagent A. Before recovering reagent A, chip 1201 and tubing 102-106 are filled with buffer solution C.

[0178] 1. Bypass liquid transfer method

[0179] Step S3101: Rotary valve 1101 is activated, connecting tubing 101 and tubing 108. The reagent is drawn into tubing 108 by the injection pump through tubing 101 and rotary valve 1101 for temporary storage.

[0180] Step S3102: Solenoid valve 1103 is activated, connecting pipe 102 and pipe 103; solenoid valve 1104 is activated, connecting pipe 103 and pipe 106; rotary valve 1101 is activated, connecting pipe 108 and pipe 102; reagent enters pipe 102 through pipe 108 and rotary valve 1101.

[0181] Step S3103: The reagent enters the tubing 103 and then enters the tubing 106 through the solenoid valve 1104;

[0182] Step S3104: The reagent in pipeline 106 is discharged through pipeline 111 after passing through rotary valve 1102. During this process, no reagent passes through the reaction flow path including pipelines 104 and 105 and chip 1201.

[0183] 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 structurally symmetrical. Therefore, reverse pumping can also be performed using the same logic.

[0184] 2. Chip liquid transfer method

[0185] Step S3201: Rotary valve 1101 is activated, connecting tubing 101 and tubing 108. The reagent is drawn into tubing 108 by the syringe pump through tubing 101 and rotary valve 1101 for temporary storage.

[0186] Step S3202: Solenoid valve 1103 is activated, connecting pipes 102 and 103; solenoid valve 1104 is activated, connecting pipes 103 and 106; rotary valve 1101 is activated, connecting pipes 108 and 102. A certain volume of reagent enters pipe 102 through pipe 108 and rotary valve 1101 until the reagent concentration at pipe 102 reaches 99% or higher. The reagent with lower concentration enters pipe 103 so that a higher concentration of reagent can enter chip 1201 later.

[0187] Step S3203: Solenoid valve 1103 is activated, connecting pipe 102 and pipe 104; solenoid valve 1104 is activated, connecting pipe 105 and pipe 106; reagent enters pipe 104 and chip 1201.

[0188] Step S3204: After the reagent reacts in 1201, it enters 106 from pipeline 105 through solenoid valve 1104;

[0189] Step S3205: The reagent in the tubing 106 is finally discharged after passing through the rotary valve 1102 and the tubing 111.

[0190] 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 structurally symmetrical. Therefore, reverse pumping can also be performed using the same logic.

[0191] Both of the above normal liquid transfer methods include the step of temporarily storing the reagent in the tubing 108, namely steps S3101 and S3201. Subsequent steps beyond steps S3101 and S3201 can be performed alternately by the two normal liquid transfer methods to meet different detection requirements.

[0192] 3. Bypass reagent recovery method

[0193] Step S3301: Reagent A enters chip 1201 from one end of tube 101 to complete the corresponding biochemical reaction. Chip 1201, tube 102, tube 104, tube 105 and tube 103 near tube 102 contain a high concentration of reagent A. The middle of tube 103 contains a mixture of reagent A and buffer solution C. The side of tube 103 near tube 106 and inside tube 106 contain buffer solution C.

[0194] Step S3302: During the reaction of chip 1201, rotary valve 1101 is activated, disconnecting tubing 110 from tubing 102 and connecting tubing 101 to tubing 102. Buffer C enters the fluid system from tubing 107. Through the aforementioned bypass liquid flow method, a portion of reagent A in tubing 103 and tubing 102 is recovered. This portion of reagent A is recovered into tubing 101 through rotary valve 1101 for use in the next reaction.

[0195] If this step is immediately followed by the chip reagent recovery method, all reagent A meeting the concentration requirements can be transferred to line 102 and then the process can be stopped. It is not necessary to send all reagent A meeting the recovery conditions into line 101. Figure 13 As shown.

[0196] 4. Chip reagent recovery method

[0197] The chip reagent recovery method is generally carried out immediately after the bypass reagent recovery method. After the reaction of chip 1201 is completed, buffer solution C enters the fluid system from tube 101 through the chip liquid transfer method to recover part of reagent A in tube 104, tube 105 and chip 1201.

[0198] If other pumping processes have been performed in pipeline 102 during the biochemical reaction of chip 1201, then before executing the chip reagent recovery method, rotary valve 1101 must be activated to connect pipeline 102 and pipeline 110, allowing low-concentration reagents or other reagents in pipeline 102 to be discharged from pipeline 110. Then, rotary valve 1101 must be activated to connect pipeline 102 and pipeline 101, allowing reagent A with the required concentration to be returned to pipeline 101 through rotary valve 1101 for use in the next reaction. Figure 14 As shown.

[0199] In the two reagent recovery methods described above, if reagent A enters the fluid system from pipe 101, then buffer solution C can enter the fluid system from pipe 107. In pipe 101, the reagent near the rotary valve 1101 will be replaced, and a portion of the reagent near the reagent storage chamber R1 will be returned to the reagent storage chamber R1, ensuring that the volume of reagent in pipe 101 is greater than the volume of the recovered reagent. Figure 15 As shown, this ensures that the reagents returned to the reagent storage chamber R1 will not come into contact with the recovered reagents.

[0200] Figures 16 to 18 The schematic structure of a fluid system according to an embodiment of the present disclosure is shown. Figure 16 This is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure. Figure 17 and Figure 18 for Figure 16 A schematic diagram illustrating the principle structure of the fluid operation method of the fluid system in the embodiment shown.

[0201] like Figures 16 to 18 As shown, the fluid system in this example is as described above. Figures 6 to 10A specific example of the fluid system is shown. 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 a pipe 208. The second main flow path L1 of the fluid system is implemented as a pipe 202; the third main flow path L4 of the fluid system is implemented as a pipe 206; the fourth main flow path L7 of the fluid system is implemented as a pipe 210. The bypass flow path L5 of the fluid system is implemented as a pipe 203. The first flow pool flow path L2 of the fluid system is implemented as a pipe 204. The second flow pool flow path L3 of the fluid system is implemented as a pipe 205. The first reservoir connection flow path L8 of the fluid system is implemented as a pipe 209. The second reservoir connection flow path L9 of the fluid system is implemented as a pipe 207. The flow cell C1 is implemented as chip 2201. The storage cell C2 is implemented as storage cell 2202. The storage cell inlet flow path L10 is implemented as pipe 201. The storage cell outlet flow path L13 is implemented as pipe 211.

[0202] Figures 16 to 18 In the illustrated embodiment, pipe 208 is connected to power source 2105. Pipe 201 is connected to reagent storage chamber R3 via liquid pump 2106.

[0203] Figures 16 to 18 In the illustrated embodiment, rotary valve 2101 is, for example, a 25-hole rotary valve; solenoid valves 2102, 2103, and 2104 are, for example, two-position three-way solenoid valves; power source 1105 is, for example, an injection pump; liquid pump 2106 is, for example, a diaphragm liquid pump; chip 2201 is, for example, a single-inlet single-outlet chip; and storage tank 2202 is a measuring cup with an open top, the bottom of which has an opening for connection to pipeline 201.

[0204] The following describes a feasible fluid operation method for the fluid system in this example. This fluid operation method provides three basic fluid flow modes: two normal flow modes that do not recover reagents (bypass flow and chip flow), and a reagent recovery mode that includes a reagent recovery process (chip reagent recovery). In the feasible logical timing scheme for the reagent recovery process, the reagent to be recovered is reagent A, and buffer solution C is used to isolate reagent A. Before recovering reagent A, chip 2201 and tubing 202-206 are filled with buffer solution C.

[0205] The reagents in storage tank 2202 are updated as needed. For example, in this embodiment, every 20 cycles, the reagents in storage tank 2202 are drained from pipeline 211, and new reagents are pumped from reagent storage chamber R3 into storage tank 2202 by liquid pump 2106 to ensure the freshness of the reagents in storage tank 2202.

[0206] 1. Bypass liquid transfer method

[0207] Step S4101: Rotary valve 2101 is activated, connecting pipe 209 and pipe 208. The reagent is drawn into storage tank 2202 through liquid pump 2106 and pipe 201, and then temporarily stored in pipe 208 by power source 2105 through pipe 209 and rotary valve 2101.

[0208] Step S4102: Solenoid valve 2102 is activated, connecting pipes 202 and 203; solenoid valve 2103 is activated, connecting pipes 203 and 206; solenoid valve 2104 is activated, connecting pipes 206 and 210; rotary valve 2101 is activated, connecting pipes 202 and 208; reagent enters pipe 202 through pipe 208 and rotary valve 2101.

[0209] Step S4103: The reagent enters the tubing 203, and then enters the tubing 206 through the solenoid valve 2103;

[0210] Step S4104: The reagent in pipeline 206 passes through solenoid valve 2104 and is finally discharged from pipeline 210.

[0211] In the bypass liquid flow mode, no reagents will pass through the reaction flow path including pipes 204 and 205 and chip 2201.

[0212] 2. Chip liquid transfer method

[0213] Step S4201: Rotary valve 2101 is activated, connecting pipe 209 and pipe 208. The reagent is drawn into storage tank 2202 through liquid pump 2106 and pipe 201, and then drawn into 208 for temporary storage by power source 2105 through pipe 209 and rotary valve 2101.

[0214] Step S4202: Solenoid valve 2102 is activated, connecting pipes 202 and 203; solenoid valve 2103 is activated, connecting pipes 203 and 206; solenoid valve 2104 is activated, connecting pipes 206 and 210; rotary valve 2101 is activated, connecting pipes 202 and 208. The reagent enters pipe 202 through pipe 208 and rotary valve 2101, so that the reagent concentration at pipe 202 reaches more than 99%. The reagent with lower concentration enters pipe 203 so that the reagent with higher concentration can enter chip 2201 later.

[0215] Step S4203: Solenoid valve 2102 is activated, connecting pipe 202 and pipe 204; solenoid valve 2103 is activated, connecting pipe 205 and pipe 206; reagent enters pipe 204 and chip 2201.

[0216] Step S4204: After the reagent reacts in chip 2201, the reagent enters from tube 205 into tube 206;

[0217] Step S4205: The reagent in pipeline 206 is discharged after passing through solenoid valve 2104 and pipeline 210.

[0218] In the chip liquid transfer method, no reagent will pass through the tube 203, which serves as the bypass flow path L5.

[0219] Both of the above normal liquid transfer methods include the step of temporarily storing the reagent in tubing 208, namely steps S4101 and S4201. Subsequent steps beyond steps S4101 and S4201 can be performed alternately by the two normal liquid transfer methods to meet different detection requirements.

[0220] 3. Chip reagent recovery method

[0221] In this embodiment, the pipeline 203 serves as a bypass flow path L5 and has a certain length. The reagent recovery in the pipeline 203 relies on the chip 2201, so only the chip reagent recovery method is provided.

[0222] Step S4301: Reagent A enters chip 2201 via a chip-to-liquid transfer method to complete the biochemical reaction. At the start of the biochemical reaction, chip 2201, tubes 202, 204, 205, and the side of tube 203 closest to tube 202 contain a high concentration of reagent A. The middle of tube 203 contains a mixture of reagent A and buffer solution C, while the side of tube 203 closest to tube 206 and the inside of tube 206 contain buffer solution C. During the reaction in chip 2201, negative pressure is applied to the tubes to dissolve reagent A. 203. Reagents meeting the concentration requirements are recovered: Solenoid valve 2102 is activated, connecting pipelines 202 and 203; solenoid valve 2103 is activated, connecting pipelines 203 and 206; solenoid valve 2104 is activated, connecting pipelines 206 and 210; rotary valve 2101 is activated, connecting pipelines 202 and 208. Reagent A with the required concentration is drawn back to pipeline 202 by power source 2105. If the volume of reagent A is large enough, reagent A will also enter rotary valve 2101 and pipeline 208.

[0223] Step S4302: Wait for the reaction in chip 2201 to complete, solenoid valve 2102 is activated, connecting pipes 202 and 204, solenoid valve 2103 is activated, connecting pipes 205 and 206, power source 2105 pushes liquid, pushing the portion of reagent A recovered in the previous step back into pipe 202. Then, buffer C enters through another port of rotary valve 2101. Through the chip-based liquid transfer method, the reagent A and buffer C with lower concentrations in tubing 205 and 206 are first drained from tubing 210. Then, solenoid valve 2104 disconnects tubing 206 from tubing 210 and connects tubing 206 to tubing 207. Buffer C further enters chip 2201, and reagent A with the required concentration in tubing 202, tubing 204, chip 2201, tubing 205, and tubing 206 is sent through solenoid valve 2104 into tubing 207 and storage tank 2202 for the next reaction.

[0224] If other reagents besides buffer solution C pass through tube 203 during a biochemical reaction in chip 2201, step S4301 is skipped and step S4302 is performed directly. That is, the reagents in tube 203 and tube 202 are not recovered, only the reagents in the reaction flow path are recovered.

[0225] Figures 19 to 20 The schematic structure of a fluid system according to an embodiment of the present disclosure is shown. Figure 19 This is a schematic diagram of the principle structure of a fluid system according to an embodiment of the present disclosure. Figure 20 for Figure 19 A schematic diagram of the basic structure of a fluid system. Figure 20 It mainly shows the relationship with Figures 16 to 18 The differences between the fluid systems in the illustrated embodiments are as follows.

[0226] like Figures 19 to 20 As shown, the fluid system in this example is... Figures 16 to 18 Based on the fluid system of the illustrated embodiment, an additional flow path connecting to the storage channel is added. The following description only focuses on this embodiment and... Figures 16 to 18 For any differences not described in this embodiment, please refer to [the relevant documentation]. Figures 16 to 18 The illustrated embodiment.

[0227] like Figures 19 to 20 As shown, compared to Figures 16 to 18In the illustrated embodiment, the fluid system further includes a storage tank 2203 connected in parallel with the storage tank 2202. The storage tank 2203 is connected to a rotary valve 2101 via pipe 214, to a solenoid valve 2104 via pipe 213, and to a reagent storage chamber R4 via pipe 212. A liquid pump 2107, such as a diaphragm pump, is installed on pipe 212, which is connected to a waste liquid storage chamber W1 via pipe 215. Pipes 211 and 210 are also connected to the waste liquid storage chamber W1. Pipe 216 connects the solenoid valve 2104 and the waste liquid storage chamber W1. A solenoid valve 2108 is installed on pipe 207 to control the on / off state of pipe 207. A solenoid valve 2109 is installed on pipe 213 to control the on / off state of pipe 213. A solenoid valve 2110 is installed on pipe 216 to control the on / off state of pipe 216. Solenoid valves 2108, 2109, and 2110 are, for example, two-position two-way solenoid valves. Pipelines 207, 213, and 216 are all connected to solenoid valve 2104 via pipeline 217.

[0228] Storage tank 2203 is an open measuring cup with an opening at the bottom for connection to pipe 212. Similar to storage tank 2202, the reagents in storage tank 2203 are replenished as needed. For example, in this embodiment, after every 20 cycles, the reagents in storage tank 2203 are discharged from pipe 215 to waste liquid storage chamber W1, and new reagents are pumped from reagent storage chamber R4 into storage tank 2203 by liquid pump 2107 to ensure the freshness of the reagents in storage tank 2203.

[0229] The following describes a feasible fluid operation method for the fluid system in this example. This fluid operation method provides three basic fluid flow modes: two normal flow modes that do not recover reagents (bypass flow and chip flow), and a reagent recovery mode that includes a reagent recovery process (chip reagent recovery). In a feasible logical timing scheme for the reagent recovery process, the reagents to be recovered are reagent A and reagent B, and buffer solution C is used to isolate reagent A and reagent B. Before recovering reagent A and reagent B, chip 2201 and tubing 202-206 are filled with buffer solution C. Reagent A is stored in reagent storage chamber R3 and storage pool 2202, and reagent B is stored in reagent storage chamber R4 and storage pool 2203.

[0230] For bypass liquid flow method and chip liquid flow method, please refer to Figures 16 to 18 The following is a description of the embodiments shown.

[0231] The chip reagent recovery method is as follows:

[0232] S5301: The reagent to be recovered enters the corresponding storage tank via solenoid valve 2104. Assuming reagent A is recovered first, it can be processed according to... Figures 16 to 18In the illustrated embodiment, the chip reagent recovery method is used for recovery. During the recovery process, solenoid valve 2108 is opened, solenoid valve 2109 is closed, and solenoid valve 2110 is closed. Reagent A is recovered into storage tank 2202 through pipelines 217 and 207.

[0233] S5302: After reagent A is recovered, reagent A residue will remain in tubing 217. Therefore, if reagent B needs to be recovered, this portion of reagent A must first be carried away by buffer solution C. At this time, solenoid valves 2108 and 2109 are closed, and solenoid valve 2110 is opened. Buffer solution C flows through solenoid valve 2014 and tubing 217 to tubing 216. This step requires ensuring that tubing 217 is filled with buffer solution C.

[0234] S5303: Keep solenoid valve 2108 and solenoid valve 2019 closed. Reagent B enters pipeline 216 from solenoid valve 2104 through pipeline 217. This step requires ensuring that pipeline 217 is filled with reagent B at a concentration of 99% or higher.

[0235] S5304: Open solenoid valve 2109 and close solenoid valve 2110. Reagent B is recovered through pipelines 217 and 213 into storage tank 2203. The recovery of both reagents is now complete.

[0236] In this embodiment, tubing 217 should be made as short as possible to recover as much reagent as possible. Of course, assuming reagent A and reagent B are completely inaccessible, even if tubing 217 is very short, buffer solution C needs to be introduced for isolation during reagent recovery. If reagent A and reagent B can come into slight contact, buffer solution C is not required.

[0237] In this embodiment, each reagent has an independent storage tank. If more reagents are added for recovery, more branches can be added to pipeline 217 to connect to more storage flow paths, and valves can be used to ensure that the reagents can flow to the corresponding storage flow path individually. The valves for switching storage flow paths are not limited to the two-way two-position solenoid valves equipped on each branch in this embodiment. For example, multiple storage flow paths can also be switched by rotary valves.

[0238] In the embodiments of this disclosure, descriptions related to concentration, such as ensuring that reagent A has a 99% concentration in the second main flow path L1, are all calculations relative to the concentration of the reagent entering the system in the current round. For example, when reagent A first enters the entire fluid system, the initial concentration is 1, and the concentration requirement is greater than 99%. After recovery, the reagent A entering the flow cell C1 a second time has been premixed with the recovered portion, and the initial concentration is less than 1, for example, 0.98. The 99% at this time is 99% relative to 0.98, i.e., 0.97. The entire reagent recovery process ensures that the amount of reagent entering the flow cell in each round is fixed, although the concentration of the reagent entering the flow cell may vary slightly. The concentration of the reagent entering the flow cell has a reasonable range; for example, in the embodiments of this disclosure, it is required that the stable concentration after entering the flow cell C1 is greater than 95% of the initial concentration.

[0239] Provided that over 95% of the reagent concentration is recovered. Figures 2 to 5 In the illustrated embodiment, a maximum of approximately 25% of the reagent can be recovered in a single operation. Figures 6 to 10 In the illustrated embodiment, a maximum of about 35% of the reagent can be recovered in a single run. Since the required recovery concentration is very high, the recovery rate is already quite high.

[0240] Based on the above description, the embodiments of this disclosure have at least one of the following advantages:

[0241] Before the reagent enters the chip, a low-concentration portion is first sent to a bypass to ensure the concentration of the reagent entering the chip and to reduce cross-contamination.

[0242] Because the reagents are isolated using a buffer solution, the recovered reagents are slightly diluted with the buffer solution, but there is no mixing with other reagents, thus effectively avoiding cross-contamination.

[0243] The process of discharging low-concentration reagents and recovering some high-concentration reagents during reagent recovery can be carried out in parallel with the biochemical reaction in the flow cell or during the process of the next reagent entering the flow cell, reducing waiting time and not affecting the overall detection process time.

[0244] It can be used as a single reagent or multiple reagents simultaneously. When multiple reagents are used simultaneously, any one or more of the reagents can be selected for recovery.

[0245] Reagents that have been recovered and meet the required concentration can be placed in a section connected to the reagent storage room, ensuring that the recovered reagents do not enter the reagent storage room; alternatively, they can be placed in a relatively independent storage tank, rather than being returned to the flow tank after passing through it. Thus, the embodiments of this disclosure help to reduce cross-contamination.

[0246] During reagent recovery, some reagents are recovered in parallel with the biochemical reaction, while others are recovered when the buffer solution enters the flow cell C1 in the next step. Therefore, reagent recovery does not affect the working efficiency of the molecular biology detection equipment.

[0247] A multi-channel chip with multiple flow cells running in parallel and multiple inlets and outlets can be applied to the fluid system of this disclosure embodiment.

[0248] The driving mechanism for fluid flow can be flexibly selected. For example, it can drive fluid flow within the system using positive or negative pressure, allowing for unidirectional or multidirectional recovery of different reagents. The driving mechanism can employ mechanical pumps, such as diaphragm pumps or syringe pumps. In addition, other power systems such as pneumatic, electroosmotic microfluidics, and digital microfluidics can achieve the same effect.

[0249] When applying the fluid system of the embodiments of this disclosure, there are no limitations on the form of the flow pool, such as size and number of flow channels.

[0250] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the embodiments of this disclosure and not to limit them; although the embodiments of this disclosure have been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications can still be made to the specific implementation of the embodiments of this disclosure or equivalent substitutions can be made to some technical features without departing from the spirit of the technical solutions of the embodiments of this disclosure, and all of them should be covered within the scope of the technical solutions claimed in the embodiments of this disclosure.

Claims

1. A fluid system, characterized in that, include: One or more first mains paths (L6) are configured to connect to at least one reagent storage chamber; Second main road (L1); The reaction flow path includes the flow cell (C1); A bypass flow path (L5) is connected in parallel with the reaction flow path; Third main road (L4); One or more branch paths; One or more fourth main flow paths (L7) are configured to connect at least one reagent storage chamber and / or at least one waste liquid storage chamber; and Multiple commutation components, including a first commutation component (T1), a second commutation component (T2), a third commutation component (T3), and a fourth commutation component (T4), wherein the first commutation component (T1) connects the one or more first main flow paths (L6), the second main flow path (L1), and at least one of the branch flow paths, and is configured such that the second main flow path (L1) can selectively communicate with any one of the one or more first main flow paths (L6) and the at least one branch flow path, while the remaining flow paths connected to the first commutation component (T1) are disconnected; the second commutation component (T2) connects the second main flow path (L1), the reaction flow path, and the bypass flow path (L5), and is configured such that the second main flow path (L1) can selectively communicate with any one of the reaction flow path and the bypass flow path (L5). The third commutator (T3) is connected to the third main flow path (L4), the reaction flow path, and the bypass flow path (L5), and is configured such that the third main flow path (L4) can be selectively connected to either the reaction flow path or the bypass flow path (L5), while the remaining flow paths connected to the third commutator (T3) are disconnected. The fourth commutator (T4) is connected to the third main flow path (L4), one or more fourth main flow paths (L7), and at least one of the branch flow paths, and is configured such that the third main flow path (L4) can be selectively connected to either the one or more fourth main flow paths (L7) or the at least one branch flow path, while the remaining flow paths connected to the fourth commutator (T4) are disconnected. One or more branch flow paths include a storage flow path, the storage flow path including a storage tank (C2), a first storage tank connecting flow path (L8), and a second storage tank connecting flow path (L9). The first storage tank connecting flow path (L8) connects the first reversing component (T1) to the storage tank (C2), and the second storage tank connecting flow path (L9) connects the fourth reversing component (T4) to the storage tank (C2). The storage tank (C2) is configured to be pre-filled with a certain volume of reagent, the reagent being able to enter the second main flow path (L1) from the storage tank (C2) through the first storage tank connecting flow path (L8) and the first reversing component (T1), and to receive the reagent recovered through the third main flow path.

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

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

4. The fluid system according to claim 1, characterized in that, 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 is configured to connect to the waste liquid storage chamber.

5. The fluid system according to claim 1, characterized in that, 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 is configured to connect to the waste liquid storage chamber.

6. The fluid system according to claim 1, characterized in that, The storage flow path also includes a storage tank inlet flow path (L10) and / or a storage tank outlet flow path (L13) connected to the storage tank (C2).

7. The fluid system according to claim 6, characterized in that, The one or more branch flow paths include multiple storage flow paths arranged in parallel.

8. The fluid system according to any one of claims 1 to 7, characterized in that, At least one of the plurality of reversing components is a rotary valve or a solenoid valve.

9. The fluid system according to any one of claims 1 to 7, characterized in that, The fluid system includes a drive mechanism that drives the fluid flow within the fluid system, and the drive mechanism drives the fluid flow using positive pressure and / or negative pressure.

10. A biochemical analysis and detection platform, characterized in that, The fluid system includes any one of claims 1 to 9.

11. The biochemical analysis and detection platform according to claim 10, characterized in that, It includes molecular biology detection equipment, which includes the aforementioned fluid system.

12. The biochemical analysis and detection platform according to claim 11, characterized in that, The molecular biology detection device includes a gene sequencer, and the gene sequencer includes the fluid system.

13. A fluid manipulation method based on a fluid system, characterized in that, The fluid system includes: One or more first mains paths (L6) are configured to connect to at least one reagent storage chamber; Second main road (L1); The reaction flow path includes the flow cell (C1); A bypass flow path (L5) is connected in parallel with the reaction flow path; Third main road (L4); One or more branch paths; and Multiple commutation components, the multiple commutation components including: A first commutator (T1) is configured to connect the one or more first main flow paths (L6), the second main flow path (L1), and at least one of the branch flow paths, such that the second main flow path (L1) can be selectively connected to any one of the one or more first main flow paths (L6) and the at least one branch flow path, while the remaining flow paths connected to the first commutator (T1) are disconnected. The second commutator (T2), connecting the second main flow path (L1), the reaction flow path, and the bypass flow path (L5), is configured such that the second main flow path (L1) can be selectively connected to either the reaction flow path or the bypass flow path (L5), while the remaining flow paths connected to the second commutator (T2) are disconnected; and The third commutation component (T3), which connects the third main flow path (L4), the reaction flow path, and the bypass flow path (L5), is configured such that the third main flow path (L4) can be selectively connected to either the reaction flow path or the bypass flow path (L5), while the remaining flow paths connected to the third commutation component (T3) are disconnected. The fluid manipulation method includes: The reagent is allowed to enter the bypass flow path (L5) through the second main flow path (L1) at least near the end of the second reversing component (T2), and then the reagent is allowed to enter the reaction flow path through the second main flow path (L1), so that the reagent or bubbles with lower concentrations are diverted away from the bypass flow path (L5) before entering the flow cell (C1); Then, the reaction flow path is disconnected from the second main flow path (L1) and the third main flow path (L4). The reagent undergoes a biochemical reaction in the flow cell (C1) of the reaction flow path. While the reagent undergoes a biochemical reaction in the flow cell (C1) of the reaction flow path, a portion of the reagent in the bypass flow path (L5) is allowed to flow to the second main flow path (L1) to recover the reagent in the bypass flow path (L5) through the second main flow path (L1); and Then, the reagents in the reaction flow path are recovered.

14. The fluid manipulation method according to claim 13, characterized in that, The reagent in the reaction flow path is directed to the second main flow path (L1) to recover the reagent in the reaction flow path through the second main flow path (L1).

15. The fluid manipulation method according to claim 14, characterized in that, The fluid handling method further includes causing the reagent recovered through the second main flow path (L1) to flow to the first main flow path (L6).

16. The fluid manipulation method according to claim 14, characterized in that, The fluid handling method further includes causing the reagents in the bypass flow path (L5) recovered through the second main flow path (L1) and the reagents in the reaction flow path to flow to the third main flow path (L4) to recover the reagents through the third main flow path (L4).

17. The fluid manipulation method according to claim 16, characterized in that, The fluid system includes one or more fourth main flow paths (L7), which are configured to connect at least one reagent storage chamber and / or at least one waste liquid storage chamber; The plurality of commutation components include a fourth commutation component (T4), which connects the third main flow path (L4), the one or more fourth main flow paths (L7), and at least one of the branch flow paths. The fourth commutation component (T4) is configured 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 from the remaining flow paths connected to the fourth commutation component (T4). The one or more branch flow paths include storage flow paths connected to the first reversing component (T1) and the fourth reversing component (T4); The fluid handling method includes directing the reagent recovered through the third main flow path (L4) to the storage flow path.

18. The fluid manipulation method according to claim 13, characterized in that, The fluid handling method includes agitating the reagent within the fluid system using a buffer solution to recover the reagent.

19. The fluid manipulation method according to claim 18, characterized in that, The fluid handling method includes discharging a mixture of the buffer solution and the reagent at a concentration less than a predetermined concentration into a waste liquid storage chamber.

20. The fluid manipulation method according to claim 19, characterized in that, The fluid handling method includes discharging a mixture of the buffer solution and the reagent at a concentration less than a predetermined concentration into the waste liquid storage chamber through at least one of the branch flow paths; and / or The fluid system includes a fourth main flow path (L7) selectively connected to the third main flow path (L4), the fourth main flow path (L7) being configured to connect to a waste liquid storage chamber, and the fluid handling method including discharging a mixture of the buffer solution or the reagent at a concentration less than a predetermined concentration into the waste liquid storage chamber through the fourth main flow path (L7).

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