CN114570449B

CN114570449B - Liquid transfer device and multi-path parallel liquid transfer device

Info

Publication number: CN114570449B
Application number: CN202210446146.3A
Authority: CN
Inventors: 蒋太交; 梁松松; 耿鹏; 李胜光; 张辉; 马然
Original assignee: Guangzhou National Laboratory
Current assignee: Guangzhou National Laboratory
Priority date: 2022-04-26
Filing date: 2022-04-26
Publication date: 2022-08-16
Anticipated expiration: 2042-04-26
Also published as: CN114570449A

Abstract

The embodiment of the disclosure discloses a liquid transfer device and a multi-path parallel liquid transfer device, the liquid transfer device comprises: the bottom of the liquid path valve plate is provided with a valve film covered area, and the valve film covered area is provided with at least one pipetting channel and a plurality of valve holes; a first preset distance is reserved between the valve hole and the pipetting channel; the card box body is fixed at the top of the liquid path valve plate and comprises a plurality of reagent pipes, and each reagent pipe is communicated with one valve hole; the elastic valve film covers the valve film covering area; the elastic valve membrane is provided with a plurality of first preset areas, and a plurality of membrane valves are formed between the first preset areas and the liquid path valve plate; a driving assembly for opening or closing the membrane valve. By the scheme, the sample transfer process is carried out in a fully closed state, the liquid reagent can be transferred and detected in a non-negative pressure biological experiment environment, and the risk of cross infection caused by aerosol is avoided.

Description

Liquid transfer device and multi-path parallel liquid transfer device

Technical Field

The disclosure relates to the technical field of biomedical instruments, in particular to a liquid transfer device and a multi-path parallel liquid transfer device.

Background

In the production, test or detection process in the fields of biology, chemistry, food, medicine, epidemic prevention or environmental monitoring and the like, the transfer of gas or liquid reagents is usually involved, and some liquid chemical reagents, such as diethyl ether, phenol and other volatile and toxic medicines; or, some microbial pathogens which easily cause diseases such as infection, allergy, tumor and the like, such as virus, bacteria, rickettsia, mycoplasma, chlamydia, spirochaete, fungi, actinomycetes and the like, during the transfer process, most of the methods adopt an open type suction and transfer device or a pouring mode between reagent bottles and the like, so that the sealing operation cannot be performed during the transfer process of the reagent, and therefore volatile toxic reagents are easily volatilized and diffused to the outside of the container, the external environment is polluted, and the personal safety of operators is endangered.

The diseases such as SARS, highly pathogenic avian influenza, novel coronavirus and the like which appear in recent years have strong infectivity, so that the transfer and detection of pathogens must be safe, rapid and accurate. For example, nucleic acid detection has the characteristics of high sensitivity and good specificity, and has important application in the fields of disease diagnosis, epidemic prevention and control, health monitoring and the like. In the current nucleic acid detection technology, the following two detection forms are mainly included:

the first is the traditional manual detection, which is to repeatedly add various biochemical reaction reagents into a PCR reaction tube by manually operating a pipette, and transfer the sample. The method needs to be completed under the condition of negative pressure, depends on the manual operation of professional detection personnel, generally uses a rigid reagent tube made of glass and the like in the sample storage, extraction or transfer process, is inconvenient for sample extraction or transfer, has complex operation process and low automation degree, and easily causes cross contamination during sample detection or transfer, thereby causing a series of problems of false positive and the like; and it is easy for a tester to increase the probability of infection with viruses in an open environment.

The second is an automatic detection device, most of the nucleic acid automatic detection devices on the market adopt an independent mode in the steps of nucleic acid extraction, amplification and detection, namely, each step needs to be completed by independent equipment, and a plurality of equipment are needed to operate in one nucleic acid detection process. On the one hand, many equipment occupation space is great, on the other hand, the sample after the preorder step is accomplished need be shifted to in subsequent equipment, complex operation, it is consuming time longer, and current nucleic acid testing equipment controls liquid through the form of solenoid valve and shifts mostly, adopt the form of solenoid valve, the case has the contact with reagent, and the case needs the motion, must produce certain clearance, therefore reagent has the risk of revealing, also receive external environment's pollution or pollution detection environment easily in sample transfer process.

In addition, the current commercialized nucleic acid detection equipment also has fully automatic nucleic acid detection equipment integrating extraction, amplification and detection, but most of the equipment adopts a single-channel or single-liquid transfer and detection mode, namely, the detection equipment can only extract one sample at a time to detect a single pathogen, such as GeneXpert of Cepheid company, FilmArray of biological Merrieay company and the like, and the detection flux and efficiency of the products are low.

Disclosure of Invention

In order to solve the problems in the related art, embodiments of the present disclosure provide a liquid transfer device and a multi-path parallel liquid transfer device.

In a first aspect, embodiments of the present disclosure provide a liquid transfer device.

Specifically, the liquid transfer device includes:

the bottom of the liquid path valve plate is provided with a valve film covering area, and the valve film covering area is provided with at least one pipetting channel and a plurality of valve holes; a first preset distance is reserved between the valve hole and the pipetting channel;

the card box body is fixed at the top of the liquid path valve plate and comprises a plurality of reagent pipes, and each reagent pipe is communicated with one valve hole;

the elastic valve film covers the valve film covering area; the elastic valve membrane is provided with a plurality of first preset areas, and a plurality of membrane valves are formed between the first preset areas and the liquid path valve plate and are used for conducting or blocking the valve hole and the liquid transfer channel;

and the driving assembly is used for opening or closing the membrane valve.

Optionally, a plurality of notches are arranged on the liquid path valve plate, and the notches cover the elastic valve plate to form the pipetting channel.

Optionally, the pipetting channel has a branch portion extending towards the valve bore.

Optionally, the elastic valve membrane further has a plurality of second preset areas; a plurality of membrane valves are formed between the second preset area and the liquid path valve plate and are used for conducting or blocking two adjacent liquid transfer channels; wherein, a second preset distance is arranged between the two adjacent pipetting channels.

Optionally, the drive assembly comprises: a plurality of driving members;

each driving member includes: the film-sticking device comprises a shell body, a push-pull rod and a film, wherein the push-pull rod and the film are positioned in the shell body; the rubber sheet is fixed at the opening of the shell body, one side of the rubber sheet is connected with the push-pull rod, and the other side of the rubber sheet is connected with the elastic valve membrane.

Optionally, the elastic valve membrane is laid on the liquid path valve plate in an integrated or separated manner.

Optionally, the liquid path valve plate is further provided with a liquid outlet and a liquid outlet channel;

one end of the liquid outlet channel is communicated with the liquid outlet, the other end of the liquid outlet channel is communicated with one valve hole, and the liquid outlet channel is controlled by the membrane valve to be communicated with or blocked from the liquid transfer channel.

Optionally, the top of the liquid path valve plate is provided with a first coating area; the first film covering area is provided with the liquid outlet channel.

Optionally, the liquid path valve plate is further provided with at least one liquid receiving pipe; the liquid receiving pipe is communicated with the liquid outlet.

Optionally, the liquid path valve plate is further provided with a gas path joint; the air path joint is communicated with one valve hole and is controlled by the membrane valve to realize the communication or the blockage with the pipetting channel.

Optionally, the liquid path valve plate is further provided with a quantitative pool, which is arranged between two adjacent reagent tubes and is positioned in the pipetting channel.

Optionally, a piston push rod is arranged in part of the reagent tube.

Optionally, the reagent tube is a sealed chamber, and includes a waste liquid chamber, a sample chamber, a lysis chamber, an empty chamber, a washing liquid chamber, an elution liquid chamber, a magnetic adsorption and elution chamber, a mixing tube, a mineral oil chamber, an excess chamber, and a secondary sample addition chamber, which are sequentially arranged.

Optionally, the sealed chamber is sealed by a seal selected from a film or a piston.

Optionally, the pipetting channels are four, the first pipetting channel is used for liquid transfer of the waste liquid chamber, the sample chamber, the lysis chamber, the empty chamber, the washing liquid chamber and the elution liquid chamber, the second pipetting channel is used for liquid transfer of the magnetic adsorption and elution chamber and the mixing tube, the third pipetting channel is used for liquid transfer of the mineral oil chamber and the excess chamber, and the fourth pipetting channel is used for liquid transfer of the secondary sample adding chamber.

Optionally, the liquid path valve plate is further provided with a quantitative pool positioned in the pipetting channel between the mineral oil chamber and the excess chamber.

Optionally, the elastic valve membrane further has three second preset areas; the second preset area and the liquid path valve plate form three membrane valves which are respectively used for conducting or blocking the first liquid transferring channel and the second liquid transferring channel which are adjacent, the second liquid transferring channel and the third liquid transferring channel which are adjacent, and the third liquid transferring channel and the fourth liquid transferring channel which are adjacent.

In a second aspect, embodiments of the present disclosure provide a multiple parallel liquid transfer device.

In particular, each of the multiple parallel liquid transfer devices comprises a liquid transfer device according to any one of the first aspect.

The technical scheme provided by the embodiment of the disclosure can have the following beneficial effects:

the present disclosure provides a liquid transfer device comprising: the bottom of the liquid path valve plate is provided with a valve film covering area, and the valve film covering area is provided with at least one pipetting channel and a plurality of valve holes; a first preset distance is reserved between the valve hole and the pipetting channel; the card box body is fixed at the top of the liquid path valve plate and comprises a plurality of reagent pipes, and each reagent pipe is communicated with one valve hole; the elastic valve film covers the valve film covering area; the elastic valve membrane is provided with a plurality of first preset areas, and a plurality of membrane valves are formed between the first preset areas and the liquid path valve plate and are used for conducting or blocking the valve hole and the liquid transfer channel; a driving assembly for opening or closing the membrane valve. The sample transfer process is carried out in a fully closed state, and the transfer and detection of the liquid reagent can be carried out in a non-negative pressure biological experiment environment, so that the risk of cross infection caused by aerosol is avoided; the reagent is pre-filled in the reagent tube, the elastic membrane valve is controlled to move towards the direction of the reagent tube by the driving assembly, the membrane valve is closed, the elastic membrane valve is enabled to be tightly attached to a fluid outlet of the reagent tube, and the reagent in the reagent tube is packaged in the reagent tube; when the device is used, the driving assembly controls the elastic membrane valve to move towards the opposite direction of the reagent tube, the membrane valve is opened, a gap is generated between the elastic membrane valve and the outlet of the reagent tube, and the reagent in the reagent tube is released into the liquid transfer channel of the liquid path valve plate. Under the state that the membrane valve is opened, the membrane valve is matched with a push rod preset in the reagent tube, so that the fluid can be quickly transferred and uniformly mixed between the reagent tubes. And through parallelly connected a plurality of liquid transfer device, both can carry out the transfer and the detection of liquid sample in each way alone, also can realize the simultaneous transfer and the detection of the different individual sample of multichannel, degree of automation is high to transfer and detection flux and transfer and detection efficiency have been promoted.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure.

Drawings

Other features, objects, and advantages of the present disclosure will become more apparent from the following detailed description of non-limiting embodiments when taken in conjunction with the accompanying drawings. The following is a description of the drawings.

Fig. 1 illustrates a perspective view of a liquid transfer device according to an embodiment of the present disclosure.

Fig. 2 shows an exploded view of a liquid transfer device according to an embodiment of the present disclosure.

Fig. 3 shows a schematic view of a positional relationship between a cartridge body and a liquid path valve plate according to an embodiment of the present disclosure.

Fig. 4 shows a schematic diagram of a positional relationship between an elastic valve membrane and a liquid passage valve plate according to an embodiment of the present disclosure.

FIG. 5 is a schematic diagram illustrating the positional relationship of a drive assembly and a fluid circuit valve plate according to an embodiment of the disclosure.

Fig. 6 shows a schematic structural diagram of a drive assembly according to an embodiment of the present disclosure.

It should be understood that the dimensions of the various elements shown in the figures are not drawn to scale. Further, the same or similar reference numerals denote the same or similar components.

Detailed Description

Hereinafter, exemplary embodiments of the present disclosure will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily implement them. Also, for the sake of clarity, parts not relevant to the description of the exemplary embodiments are omitted in the drawings.

Further, those of ordinary skill in the art will appreciate that the drawings provided herein are for illustrative purposes and are not necessarily drawn to scale.

Unless the context clearly requires otherwise, throughout the description, the words "comprise", "comprising", and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is, what is meant is "including, but not limited to".

In the description of the present disclosure, it is to be understood that the terms "first," "second," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance. Further, in the description of the present disclosure, "a plurality" means two or more unless otherwise specified.

Unless expressly stated or limited otherwise, the terms "mounted," "connected," "secured," and the like are intended to be inclusive and mean that, for example, they may be fixedly connected or detachably connected or integrally formed; can be mechanically or electrically connected; they may be directly connected or indirectly connected through intervening media, or they may be connected internally or in any other suitable relationship, unless expressly stated otherwise. The specific meaning of the above terms in the present disclosure can be understood by those of ordinary skill in the art as appropriate.

It should be further noted that the embodiments and features of the embodiments in the present disclosure may be combined with each other without conflict. The present disclosure will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.

The present disclosure is made to solve, at least in part, the problems in the prior art that the inventors have discovered.

As shown in fig. 1 to 6, the liquid transfer device 100 includes: cartridge body 110, liquid path valve plate 120, elastic valve membrane 130, drive assembly 140. The cartridge body 110 is located on the top of the liquid path valve plate 120, the cartridge body 110 and the liquid path valve plate 120 can be integrally formed or assembled for use, the bottom of the liquid path valve plate 120 has a valve film covering region P, the elastic valve film 130 is covered on the valve film covering region P by bonding, for example, and the driving assembly 140 is located below the elastic valve film 130 and is connected with the elastic valve film 130 by ultrasonic welding, for example.

The cartridge body 110 includes a plurality of reagent tubes 111, the plurality of reagent tubes 111 being fixed to the top of the liquid passage valve plate 120, and two types of reagent tubes 111, namely,

reagent tubes

01, 02, 03, 04, 05, 06, 07, 08, 012 and

reagent tubes

09, 010, 011, 013 are shown in the drawing, wherein the

reagent tubes

09, 10, 011, 013 incorporate a piston pusher rod 112 (see fig. 2), and the reagent tubes 01-08, 012 are configured to seal a chamber. In the following examples, applicants will further describe the application scenario of extracting nucleic acid by combining the magnetic bead method, and will not be described herein.

The liquid passage valve plate 120 is provided with valve holes b corresponding to the number of the reagent tubes 111, that is, valve holes b1, b2, b3, … …, and b13, and each valve hole b communicates with one reagent tube 111. For example, the valve hole b1 communicates with the reagent tube 01, the valve hole b2 communicates with the reagent tube 02, and so on.

At least one liquid transfer channel 121 is disposed in a valve membrane covering region P of the liquid path valve plate 120, the liquid transfer channel 121 and the valve hole b have a first preset distance, the elastic valve membrane 130 has a plurality of first preset regions P1, when the elastic valve membrane 130 covers the valve membrane covering region P, a plurality of membrane valves are formed between the plurality of first preset regions P1 and the liquid path valve plate 120, when the membrane valves are closed, a gap between the liquid transfer channel 121 and the valve hole b is blocked by the elastic valve membrane 130, so that the liquid transfer channel and the valve hole b cannot be conducted, the liquid reagent pre-disposed in the reagent tube 111 cannot flow into the liquid transfer channel 121 through the valve hole b, when the membrane valves are opened, a gap between the first preset region P1 and the liquid path valve plate 120 is formed, and the liquid reagent pre-disposed in the reagent tube 111 flows into the liquid transfer channel 121 through the gap through the valve hole b. The driving assembly 140 provides a force to open or close the membrane valves, and the plurality of reagent vessels 111 can achieve liquid transfer via the pipetting channel 121 by opening the membrane valves corresponding to two or more reagent vessels 111.

In the embodiment of the present disclosure, as shown in fig. 4, the first predetermined region p1 covers the valve hole b and part of the pipetting channel 121 at the same time, and the part outside the first predetermined region p1, such as the hatched part in the figure, is welded on the valve film covering region p, so as to ensure that a gap is formed between only the first predetermined region p1 and the liquid path valve plate 120 under the action of external force, and the liquid in the reagent tube 111 does not leak from the edge of the elastic valve film 130.

In the embodiment of the present disclosure, the elastic valve film 130 further has a second preset area p2, and a plurality of film valves are formed between the second preset area p2 and the liquid path valve plate 120 for conducting or blocking two adjacent liquid transfer channels; wherein, a second preset distance is arranged between two adjacent pipetting channels.

Specifically, the area where the second preset area P2 is covered on the liquid path valve plate 120 is the P3 area, when the elastic valve film 130 is covered on the P3 area, a plurality of film valves are formed between a plurality of second preset areas P2 and the liquid path valve plate 120, the end portions of two adjacent pipetting channels 121 are located in the P3 area, the two pipetting channels 121 are not conducted, when the film valves are closed, the gap between the two adjacent pipetting channels 121 is blocked by the elastic valve film 130, that is, the liquid in the reagent tube 111 cannot be transferred through the two pipetting channels 121, for example, the liquid cannot be transferred between the reagent tubes 07, 08, when the film valves are opened, the gap between the second preset area P2 and the liquid path valve plate 120 is formed, which conducts the two adjacent pipetting channels 121, for example, the gap of the pipetting channel which conducts the reagent tubes 07, 08, the liquid in the reagent tube 07 can flow to the reagent tube 08 through the gap, so that the reagent tube 111 is divided into different pipetting function areas according to the corresponding pipetting channels 121, liquid transfer can be performed in the same functional area through a common pipetting channel 121, and liquid transfer between different functional areas is realized through control of a membrane valve formed between the second preset area p2 and the liquid path valve plate 120.

Further, for example, as shown in fig. 4, when the elastic valve film 130 has a plurality of second preset regions p2, and liquid transfer is performed between two adjacent functional regions, and the reagent tubes 111 of other functional regions do not need to participate in liquid transfer, the membrane valves of the second preset regions of the corresponding functional regions may be closed to cut off the passage with the other functional regions, so as to avoid the influence on the other functional regions caused by liquid transfer. For example, when transferring liquid between the

reagent vessels

07 and 08, the membrane valve for opening the second predetermined area of the pipette channel in which the

reagent vessels

07 and 08 are located may be opened, and the membrane valve for closing the second predetermined area of the pipette channel in which the reagent vessels b10 and b11 are located may be closed, in other words, the liquid transfer between the reagent vessels b11 and b12 may be performed independently without being affected by the liquid transfer between the

reagent vessels

07 and 08.

In the embodiment of the present disclosure, the elastic valve membrane 130 is integrally or separately laid on the liquid path valve plate 120 to form several membrane valves.

In an embodiment of the present disclosure, as shown in fig. 5, for example, the driving assembly 140 includes a plurality of driving members 141, such as driving members c1, c2 … … c13, and driving members c1, c2 … … c13 are in a one-to-one correspondence with the valve holes b1, b2 … … b 13.

For example, as shown in fig. 6, each driving member 141 includes a housing 1411 made of PP, a push-pull rod 1412 located inside the housing 1411, and a film 1413 made of soft rubber; the film 1413 is fixed to the opening of the case body 1411 by, for example, a double-sided tape, and has one surface connected to the push-pull rod 1412 and the other surface connected to the elastic valve film 130. The housing bodies 1411 of the driving members 141 may be integrally formed or separately formed, so that the number of the driving members 141 is increased or decreased as required, which is not limited in the present disclosure.

Each driving member 141 is used for controlling the opening or closing of one membrane valve, specifically, the elastic valve membrane 130 is attached to the liquid path valve plate 120 by the internal stress of the film 1413, so that the membrane valve is in a normally closed state, the push-pull rod 1412 is attached to one side of the film 1413, and by pulling the push-pull rod 1412 outwards, the film 1413 is separated from the liquid path valve plate 120 along with the elastic valve membrane 130 attached thereto, so that a gap for liquid to pass through is formed between the liquid path valve plate 120 and the elastic valve membrane 130, thereby realizing the opening of the membrane valve and further conducting the corresponding reagent tube 111 and the liquid transfer channel 121.

It should be noted that the driving members 141 in fig. 5, such as the driving members d1, d2, d3, are driving members for adapting the membrane valve formed by the second predetermined area p2 and the liquid passage valve plate 120, and correspond to the position of the second predetermined area p2 one by one. The driving elements d1, d2 and d3 refer to the driving elements c1 and c2 … … c13, and the action principle is the same, which is not described in detail.

It is understood that the number of reagent tubes, valve openings, and drive members shown in fig. 1-6 are merely illustrative and can be flexibly adjusted by one skilled in the art as desired and are not to be construed as limiting the present disclosure.

In the embodiment of the present disclosure, the pipetting channel 121 may be a tube through which the liquid passes, only the end of the tube being a covered area of the first preset area p1, e.g. the end being provided in an open configuration, while the complete tube is formed by the cover film. Alternatively, the entire pipetting channel 121 may be formed of a scored film. Specifically, the liquid passage valve plate 120 is provided with a plurality of notches, and the notches cover the elastic valve membrane 130 to form the pipetting channel 121. Wherein the first preset area p1 covers a part of the notch so that the reagent in the reagent tube 111 can be led out to the pipetting channel 121 when the membrane valve is opened.

In the embodiment of the present disclosure, for example, as shown in fig. 4, the pipetting channel 121 has a branch portion 1211 extending toward the valve hole b, the branch portion 1211 is closer to the valve hole b, and when the first predetermined area p1 covers the valve hole b, only the branch portion 1211 needs to be covered to discharge the reagent to the pipetting channel 121.

In the embodiment of the present disclosure, as shown in fig. 2 and fig. 3, for example, the liquid path valve plate 120 is further provided with a liquid outlet 123, such as a valve hole b16 and a liquid outlet channel 124, one end of the liquid outlet channel 124 is communicated with the liquid outlet 123, the other end of the liquid outlet channel 124 is communicated with one valve hole, and the liquid outlet channel is controlled by a membrane valve to be communicated with or blocked from the liquid transfer channel 121, so that the liquid in the reagent tube 111 can be further led out from the liquid outlet 123 through the liquid outlet channel 124 on the basis of liquid transfer between the reagent tubes.

Specifically, one of the membrane valves as a liquid outlet membrane valve, for example, the membrane valve formed by the first predetermined area p1 covering the valve hole b15 and the portion of the pipetting channel 121 as shown in fig. 3, is located between one of the pipetting channel 121 and the liquid outlet channel 124, and is used for controlling the passage of the liquid outlet channel 124, and the liquid outlet membrane valve is opened, so that the liquid in the reagent tube 111 can flow from the liquid outlet channel 124 to the liquid outlet 123.

In the embodiment of the present disclosure, the liquid outlet channel 124 may be a pipe provided on the liquid path valve plate 120 for liquid to pass through, or may be a complete pipe formed by cutting and coating a film, for example, as shown in fig. 3, the liquid outlet channel 124 is provided on the top of the liquid path valve plate 120, that is, on the opposite side of the valve film covering region p, the liquid path valve plate 120 has a first film covering region p4, and the complete liquid outlet channel 124 is formed after the first film covering region p4 is coated with a film. When the film is coated, one side of the valve holes b15 and b16 is covered, the other side of the valve hole b15 is covered by the elastic valve film 130, and the other side of the liquid outlet b16 can be connected with a liquid receiving tube 150 (see fig. 2). By disposing the first coating region p4 and the valve film covering region p on both sides of the liquid path valve plate 120, respectively, and disposing the liquid outlet passage 124 on the top of the liquid path valve plate 120, the liquid can flow from the top to the bottom toward the liquid outlet 123, facilitating the liquid transfer.

In the embodiment of the present disclosure, for example, as shown in fig. 2, the liquid path valve plate 120 is further provided with at least one liquid receiving tube 150 communicating with the liquid outlet 123.

In the embodiment of the present disclosure, for example, as shown in fig. 2 and fig. 3, the liquid path valve plate 120 further includes a gas path connector 125, one end of the gas path connector 125 is connected to an external gas source, and the other end is connected to a valve hole, and is controlled by a membrane valve to realize connection or disconnection with the pipetting channel 121, so as to clean the residual liquid in the pipetting channel 121.

Specifically, one of the membrane valves is used as a pipeline cleaning membrane valve, for example, the membrane valve shown in fig. 3, which is formed by the first preset area p1 covering the valve hole b14 and the pipetting channel 121, and is used for controlling the on-off of the external air source, the pipeline cleaning membrane valve is opened, and the air enters the pipetting channel 121, at this time, one of the reagent tubes 111 can be used as a waste liquid chamber, the residual liquid in the pipetting channel 121 can be blown into the waste liquid chamber only by opening the membrane valve of the waste liquid chamber at the same time, and after the residual liquid in the pipetting channel 121 is cleaned, the liquid transfer in the next reagent tube 111 is performed, so that the cross contamination of the liquid is avoided.

It should be noted that the gas circuit connector 125 is a one-way valve, and is only used as a gas inlet of an external gas source, when the pipeline cleaning membrane valve is opened to transfer the liquid to the liquid receiving tube 150, the gas channel in the gas circuit connector 125 is closed, and the liquid is not in contact with the external environment, so that cross infection of aerosol is not caused, and the liquid transfer device 100 is still maintained in a fully closed environment.

In an embodiment of the present disclosure, such as shown in fig. 4, the liquid path valve plate 120 is further provided with a quantitative reservoir 126 for quantitatively transferring liquid. Specifically, the quantification pool 126 may be disposed between two adjacent reagent tubes 111, and within the pipetting channel 121.

In the embodiment of the present disclosure, the reagent tube 111, for example, the reagent tubes 01-08, 012 in fig. 3, may be composed of a rigid plastic and a film, specifically, a tube body of the rigid plastic may be axially cut and coated with a film, for example, a PE, PVC, TPU film, so that after the film valve is opened by an external force, the reagent in the reagent tubes 01-08, 012 is extruded outwards by the action of the retraction of the film by operating the piston push rod 112 in the

reagent tubes

09, 010 to provide a negative pressure, thereby better discharging the reagent. It will be appreciated that the rigid plastic may have at least one axial cross-section, for example two, and be separately coated to ensure hermeticity, and the present disclosure is not limited thereto.

In the embodiment of the present disclosure, the reagent tube 01-08, 012 has an inlet end and an outlet end, the outlet end is communicated with the valve hole b, and after the reagent is put into the inlet end, the inlet end is configured as a closed end to ensure that the reagent is in a sealed environment. Specifically, the liquid inlet end may be sealed by a film or by a sealing plug, which is not limited by the present disclosure.

As mentioned above, the traditional artificial nucleic acid detection method has complex operation process and low automation degree, and the sample is easy to have cross contamination during detection or transfer; the prior automatic detection equipment needs a plurality of pieces of equipment to operate cooperatively, the sample after the preorder step is completed needs to be transferred to subsequent equipment, the operation is complicated, the time consumption is long, the sample is also easily polluted by the external environment or pollutes the detection environment in the sample transfer process, and the transfer and detection flux and the detection efficiency are low.

This disclosed liquid transfer device realizes the transfer of liquid between a plurality of reagent pipes through opening of control membrane valve, can put into the sample in advance in the reagent pipe, draw reagent etc. and seal the reagent pipe, forms sealed environment to guaranteed that liquid transfer can accomplish in the environment of not contacting with the external world, avoided the pollution that the sample probably received, improved the sample detection precision.

The following examples are illustrative of the extraction of nucleic acids by the magnetic bead method.

Firstly, explaining the principle of extracting nucleic acid by a magnetic bead method, after a sample is added into a lysis solution, releasing the nucleic acid, then performing specific binding on the treated magnetic bead (for example, silicon-based or amino coating treatment) and the nucleic acid to form a nucleic acid-magnetic bead compound, separating the compound under the action of an external magnetic field, and finally washing off impurities which are not specifically adsorbed by eluent, desalting and purifying to obtain a nucleic acid substance to be extracted.

In the liquid transfer device of the present disclosure, for example, as shown in fig. 3 to 5, reagent tubes 01 to 013 are: the device comprises a waste liquid chamber 01, a sample chamber 02, a cracking chamber 03, an empty chamber 04, a washing liquid chamber 05, a washing liquid chamber II 06, an elution liquid chamber 07, a magnetic adsorption elution chamber 08, a mixing tube I09, a mixing tube II 010, a mineral oil chamber 011, an excess chamber 012 and a secondary sample adding chamber 013; the waste liquid chamber 01, the sample chamber 02, the cracking chamber 03, the empty chamber 04, the washing liquid chamber 05, the washing liquid chamber 06 and the elution liquid chamber 07 are respectively communicated with the valve holes b1 and b2 … … b7, and liquid transfer is realized in one pipetting channel 121 under the control of the driving parts c1 and c2 … … c 7; the magnetic adsorption elution chamber 08, the first mixing tube 09 and the second mixing tube 010 are respectively communicated with the valve holes b8, b9 and b10, and liquid transfer is realized in one pipetting channel 121 under the control of driving pieces c8, c8 and c 9; the mineral oil chamber 011 and the excess chamber 012 are respectively communicated with the valve holes b11 and b12, and liquid transfer is realized in one pipetting channel 121 under the control of driving pieces c11 and c 12; the secondary sample adding chamber 013 is communicated with the valve hole b13 and is directly communicated with the liquid outlet channel 124 by the control of the driving piece c 13. The two pipetting channels 121 are respectively communicated by the control of the driving pieces d1, d2 and d 3. The liquid passage valve plate 120 is further provided with a fixed-amount reservoir 126 which is located in the liquid transfer passage 121 between the mineral oil chamber 011 and the excess chamber 012.

The pipetting channels 121 are four, the first pipetting channel is used for liquid transfer of the waste liquid chamber 01, the sample chamber 02, the lysis chamber 03, the empty chamber 04, the washing liquid chamber 05, the washing liquid chamber 06 and the elution liquid chamber 07, the second pipetting channel is used for liquid transfer of the magnetic adsorption elution chamber 08, the mixing tube 09 and the mixing tube 010, the third pipetting channel is used for liquid transfer of the mineral oil chamber 011 and the excess chamber 012, and the fourth pipetting channel is used for liquid transfer of the secondary sample adding chamber 013.

The elastic valve membrane 130 has three second predetermined areas P2, three membrane valves are formed between the three second predetermined areas P2 and the liquid path valve plate 120 for respectively conducting or blocking the adjacent first pipetting channel and the second pipetting channel, the adjacent second pipetting channel and the third pipetting channel, and the adjacent third pipetting channel and the fourth pipetting channel.

The liquid transfer device provided by the embodiment of the disclosure is used for PCR nucleic acid extraction, and comprises the following steps:

and (3) reagent packaging: respectively placing a sample (such as a nucleic acid sample) and lysis solution, magnetic bead preservation solution, washing solution, eluent and mineral oil into corresponding reagent tubes, for example, placing the sample into a sample chamber 02, placing the lysis solution into a lysis chamber 03, placing the washing solution into a washing solution chamber I05, a washing solution chamber II 06, placing the eluent into an eluent chamber 07, placing the magnetic bead preservation solution into a magnetic absorption elution chamber 08, placing the mineral oil into a mineral oil chamber 011, sealing the reagent tubes, and placing a piston push rod 112 in the mixing tube I09, the mixing tube II 010, the mineral oil chamber 011 and the secondary sample adding chamber 013;

magnetic bead activation: opening membrane valves corresponding to the magnetic adsorption and elution chamber 08 and the mixing tube I09, operating a piston push rod 112 arranged in the mixing tube I to move in a reciprocating mode to activate magnetic beads, applying a permanent magnet outside the magnetic adsorption and elution chamber 08 to magnetically adsorb the magnetic beads, and pumping magnetic bead activation liquid into the mixing tube I09; then, the membrane valves of the empty chamber 04 and the first pipetting channel and the second pipetting channel are opened, the membrane valve corresponding to the magnetic adsorption and elution chamber 08 is closed, the piston push rod 112 is operated, the waste liquid is transferred into the empty chamber 04, and then the membrane valve corresponding to the empty chamber 04 is closed;

cleaning a pipeline: opening the waste liquid chamber 01, a membrane valve corresponding to the first pipetting channel and the second pipetting channel, a membrane valve corresponding to the second pipetting channel and the third pipetting channel, a membrane valve corresponding to the third pipetting channel and the fourth pipetting channel, and a pipeline cleaning membrane valve corresponding to the gas circuit joint 125, and allowing external gas source to intake gas to blow residual liquid in the liquid circuit into the waste liquid chamber 01;

sample lysis releases nucleic acids: opening the membrane valves corresponding to the sample chamber 02 and the first mixing tube 09, operating a piston push rod 112 arranged in the first mixing tube 09 to transfer the sample into the first mixing tube 09, similarly, transferring the lysate into the second mixing tube 010, and closing the membrane valves corresponding to the first pipetting channel and the second pipetting channel; then, the magnetic beads are separated from the magnetic field, the sample is pushed to the magnetic adsorption and elution chamber 08 through a piston rod arranged in the first mixing tube 09, the piston push rod 112 arranged in the first mixing tube 09 is operated to reciprocate, and the sample carrying the magnetic beads is transferred into the first mixing tube 09; then operating piston push rods 112 arranged in the first mixing tube and the second mixing tube to mix the sample and the lysis solution, and lysing the sample to release nucleic acid;

nucleic acid extraction and transfer: transferring the mixed solution after sample cracking to a magnetic adsorption elution chamber 08, operating a piston push rod 112 arranged in a first mixing tube 09 and a second mixing tube 010, repeatedly transferring a washing liquid, an eluent and the mixed solution after sample cracking to the magnetic adsorption elution chamber 08, the first mixing tube 09 and the second mixing tube 010 for nucleic acid extraction, wherein the steps of cleaning the pipelines can be repeated in the extraction process to avoid cross contamination of reagents, discharging waste liquid into the corresponding reagent tubes, then pushing the excessive part of the extracted nucleic acid solution into an excessive chamber 012 through a quantitative pool 126, and then moving the quantitative nucleic acid solution out to a liquid receiving tube 150 through the piston push rod 112 arranged in an operating mineral oil chamber 011;

and (3) secondary sample adding: by operating the plunger 112 provided in the secondary sample addition chamber 013, a secondary reagent (usually, a reagent that is not easily put into the reagent tube 111 at a low temperature) can be added to the liquid junction tube 150, and then a subsequent PCR amplification process can be prepared.

There is also provided, in accordance with an embodiment of the present disclosure, a multiple parallel liquid transfer device, each path including a liquid transfer device as in the embodiment shown in fig. 1-6. Specific technical details may be found in the above description and are not described herein.

The multi-path parallel liquid transfer device provided by the embodiment of the disclosure can be always ensured to be in a fully closed state during liquid transfer, the reaction process does not need to be in contact with atmospheric air, transfer and detection in non-negative pressure biological experiment environments such as families, communities, outdoors and the like can be realized, and cross infection caused by aerosol can not be caused; and through multichannel integral type structure, both can carry out the transfer and the detection of liquid sample alone in each way, also can realize the simultaneous transfer and the detection of the different individual sample of multichannel, degree of automation is high to transfer and detection flux and transfer and detection efficiency have been promoted.

The foregoing description is only exemplary of the preferred embodiments of the disclosure and is illustrative of the principles of the technology employed. It will be appreciated by those skilled in the art that the scope of the invention in the present disclosure is not limited to the specific combination of the above-mentioned features, but also encompasses other embodiments in which any combination of the above-mentioned features or their equivalents is made without departing from the inventive concept. For example, the above features and (but not limited to) the features disclosed in this disclosure having similar functions are replaced with each other to form the technical solution.

Claims

1. A liquid transfer device, comprising:

the card box body is fixed at the top of the liquid path valve plate and comprises a plurality of reagent pipes, and each reagent pipe is communicated with one valve hole; a piston push rod is arranged in part of the reagent tube;

the elastic valve film covers the valve film covering area; the elastic valve membrane is provided with a plurality of first preset areas, and a plurality of membrane valves are formed between the first preset areas and the liquid path valve plate and are used for conducting or blocking the valve hole and the liquid transfer channel; the liquid path valve plate is provided with a plurality of notches, and the notches cover the elastic valve membrane to form the liquid transfer channel;

a driving assembly for opening or closing the membrane valve; when the membrane valve is opened, the membrane valve is matched with the piston push rod to realize rapid transfer and uniform mixing of fluid between the reagent pipes;

wherein the drive assembly comprises: a plurality of driving members;

2. The liquid transfer device of claim 1,

the pipetting channel has a branch portion extending toward the valve hole.

3. The liquid transfer device of claim 1,

the elastic valve film is also provided with a plurality of second preset areas; a plurality of membrane valves are formed between the second preset area and the liquid path valve plate and are used for conducting or blocking two adjacent liquid transfer channels; wherein, a second preset distance is arranged between the two adjacent pipetting channels.

4. Liquid transfer device according to any of claims 1-3,

the elastic valve membrane is laid on the liquid path valve plate in an integrated or split mode.

5. The liquid transfer device of claim 1,

the liquid path valve plate is also provided with a liquid outlet and a liquid outlet channel;

6. The liquid transfer device of claim 5, wherein the top of the fluidic valve plate has a first coated area; the first film covering area is provided with the liquid outlet channel.

7. The liquid transfer device of claim 5, wherein the liquid circuit valve plate is further provided with at least one liquid receiving tube; the liquid receiving pipe is communicated with the liquid outlet.

8. The liquid transfer device of claim 1,

the liquid path valve plate is also provided with a gas path joint; the air path joint is communicated with one valve hole and is controlled by the membrane valve to realize the communication or the blockage with the liquid transfer channel.

9. The liquid transfer device of claim 1,

the liquid way valve plate is also provided with a quantitative pool which is arranged between the two adjacent reagent tubes and is positioned in the liquid transfer channel.

10. The liquid transfer device of claim 1,

the reagent tube is a sealed chamber and comprises a waste liquid chamber, a sample chamber, a cracking chamber, an empty chamber, a washing liquid chamber, an elution liquid chamber, a magnetic absorption elution chamber, a mixing tube, a mineral oil chamber, an excess chamber and a secondary sample adding chamber which are sequentially arranged.

11. The liquid transfer device of claim 10,

the sealed chamber is sealed by a seal selected from a film or a piston.

12. The liquid transfer device of claim 10, wherein the pipetting channels are four, the first pipetting channel is used for liquid transfer of the waste chamber, the sample chamber, the lysis chamber, the empty chamber, the wash chamber and the elution chamber, the second pipetting channel is used for liquid transfer of the magnetic absorption elution chamber and the mixing tube, the third pipetting channel is used for liquid transfer of the mineral oil chamber and the excess chamber, and the fourth pipetting channel is used for liquid transfer of the secondary sample addition chamber.

13. The liquid transfer device of claim 12,

the liquid path valve plate is also provided with a quantitative pool which is positioned in the liquid transfer channel between the mineral oil chamber and the excess chamber.

14. The liquid transfer device of claim 12,

the elastic valve membrane also has three second preset areas; the second preset area and the liquid path valve plate form three membrane valves which are respectively used for conducting or blocking the first liquid transferring channel and the second liquid transferring channel which are adjacent, the second liquid transferring channel and the third liquid transferring channel which are adjacent, and the third liquid transferring channel and the fourth liquid transferring channel which are adjacent.

15. A multi-path parallel liquid transfer device, wherein each path comprises a liquid transfer device according to any of claims 1-14.