CN114166719B - Method and device for screening nucleic acid synthetic vector - Google Patents

Method and device for screening nucleic acid synthetic vector Download PDF

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Publication number
CN114166719B
CN114166719B CN202111438898.7A CN202111438898A CN114166719B CN 114166719 B CN114166719 B CN 114166719B CN 202111438898 A CN202111438898 A CN 202111438898A CN 114166719 B CN114166719 B CN 114166719B
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nucleic acid
acid synthesis
flow parameter
synthesis
detected
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CN114166719A (en
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马石金
朱强
陈园园
周建国
尤俊龙
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Tsingke Biotechnology Co Ltd
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Tsingke Biotechnology Co Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/08Investigating permeability, pore-volume, or surface area of porous materials
    • G01N15/088Investigating volume, surface area, size or distribution of pores; Porosimetry
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/08Investigating permeability, pore-volume, or surface area of porous materials
    • G01N15/0806Details, e.g. sample holders, mounting samples for testing
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/08Investigating permeability, pore-volume, or surface area of porous materials
    • G01N15/082Investigating permeability by forcing a fluid through a sample
    • G01N15/0826Investigating permeability by forcing a fluid through a sample and measuring fluid flow rate, i.e. permeation rate or pressure change

Abstract

The invention relates to a method and a device for screening nucleic acid synthetic vectors. The screening method of the nucleic acid synthetic vector comprises the following steps: s100, mounting a nucleic acid synthesis carrier to be detected in an accommodating through hole of a synthesis assembly; s200, enabling a detection fluid to flow through the nucleic acid synthesis carrier to be detected; s300, acquiring a starting-end flow parameter a1 of the detection fluid; s400, acquiring a terminal flow parameter a2 of the detection fluid at the inlet close to the accommodating through hole; s500, obtaining a flow parameter difference value a3 between the flow parameter a1 at the starting end and the flow parameter a2 at the tail end, comparing the flow parameter difference value a3 with a preset error range, and if the flow parameter difference value a3 is outside the preset error range, determining that the nucleic acid synthesis carrier to be detected is unqualified. The screening method of the nucleic acid synthetic vector can screen unqualified nucleic acid synthetic vectors, and the operation of the screening process is simpler.

Description

Method and device for screening nucleic acid synthetic vector
Technical Field
The invention relates to the technical field of DNA synthesis, in particular to a method and a device for screening nucleic acid synthetic vectors.
Background
The artificial synthesis of DNA is the only way for the directional modification of gene sequences known at present, and is widely applied to various fields such as protein modification and life science. When synthesis is performed, a common method is to place the nucleic acid synthesis vector in a synthesis column or a synthesis purification plate, sequentially introduce different reagents into the synthesis column or the synthesis purification plate, and sequentially react the nucleic acid synthesis vector with the various reagents to obtain a final product. In general, since nucleic acid synthesis carriers are made of nanoporous glass, the uniformity of pore diameters of nucleic acid synthesis carriers is difficult to control during the production process, and thus, the air resistance values of a plurality of nucleic acid synthesis carriers produced are greatly different from each other, and the discharge rate of reagents flowing through nucleic acid synthesis carriers is also greatly different from each other, resulting in high and low synthesis quality and poor uniformity. Therefore, it is important to screen nucleic acid synthesis vectors before synthesis to eliminate unsatisfactory nucleic acid synthesis vectors. However, some screening methods in the related art are complicated to operate.
Disclosure of Invention
Based on the method, the invention provides the method for screening the nucleic acid synthetic carriers, which can screen unqualified nucleic acid synthetic carriers and has simpler operation in the screening process.
The screening method of the nucleic acid synthetic vector comprises the following steps:
s100, mounting a nucleic acid synthesis carrier to be detected in an accommodating through hole of a synthesis assembly;
s200, flowing detection fluid through the nucleic acid synthesis carrier to be detected;
s300, acquiring a flow parameter a1 at the initial end of the detection fluid;
s400, acquiring a terminal flow parameter a2 of the detection fluid at the inlet close to the accommodating through hole;
s500, obtaining a flow parameter difference a3 between the initial end flow parameter a1 and the tail end flow parameter a2, comparing the flow parameter difference a3 with a preset error range, and if the flow parameter difference a3 is outside the preset error range, determining that the nucleic acid synthesis carrier to be detected is unqualified.
In one embodiment, in S100, a plurality of nucleic acid synthesis vectors to be tested are mounted in a one-to-one correspondence manner in a plurality of the accommodating through holes;
in S200, the detection fluid is shunted and then flows through a plurality of nucleic acid synthesis carriers to be detected respectively;
in S400, acquiring the terminal flow parameter a2 corresponding to each nucleic acid synthesis vector to be detected;
in S500, the flow parameter difference a3 corresponding to each of the multiple nucleic acid synthesis vectors to be tested is respectively obtained according to the start-end flow parameter a1 and the end-end flow parameter a2 corresponding to each nucleic acid synthesis vector to be tested, and is respectively compared with the preset error range.
In one embodiment, the initial end flow parameter and the final end flow parameter are the flow rate or the pressure of the detection fluid; and/or the presence of a gas in the gas,
the detection fluid is a gas or a liquid.
The screening method of the nucleic acid synthesis carrier enables the detection fluid to pass through the nucleic acid synthesis carrier to be detected, obtains the initial end flow parameter a1 of the detection fluid and the tail end flow parameter a2 of the detection fluid at the inlet close to the accommodating through hole, obtains the flow parameter difference a3 by calculating the difference between the initial end flow parameter a1 and the tail end flow parameter a2, and compares the flow parameter difference a3 with the preset error range. The flow resistance of the nucleic acid synthesis carrier to be detected can influence the acquired terminal flow parameter a2, so that the obtained difference flow parameter difference value a3 is influenced, if the flow parameter difference value a3 is too large or too small, the flow parameter difference value a3 is compared with a preset error range, and then the difference value a3 cannot fall into the preset error range, so that the flow resistance of the nucleic acid synthesis carrier to be detected deviates from the standard flow resistance more, and the nucleic acid synthesis carrier to be detected belongs to defective products, and the defective products are screened and removed. In the method, the defective products can be screened out only by detecting two flow parameters and comparing the difference value with a preset error range, and the whole screening process is simple to operate.
The invention also provides a nucleic acid synthetic vector screening device, and when the nucleic acid synthetic vector screening device is used for screening, the operation of the screening process is simpler.
The nucleic acid synthesis vector screening apparatus based on the above nucleic acid synthesis vector screening method includes:
a storage for storing the test fluid;
the synthesis assembly is provided with the accommodating through hole for accommodating the nucleic acid synthesis carrier to be detected;
a delivery module connected between the storage member and the synthesis assembly, the delivery module for delivering the detection fluid to the accommodation through hole;
a first detecting member for detecting a starting end flow parameter a1 of the detection fluid;
and the second detection piece is arranged on the conveying module and close to the inlet of the accommodating through hole, and is used for detecting the terminal flow parameter a2 of the detection fluid.
In one of them embodiment, still include the reposition of redundant personnel subassembly, it is provided with a plurality of to hold the through-hole on the synthetic subassembly, the reposition of redundant personnel subassembly includes inflow entrance and a plurality of egress opening, the delivery module includes first conveyer pipe and a plurality of second conveyer pipe, first conveyer pipe connect in the inflow entrance with between the storage piece, second conveyer pipe connect in corresponding the outflow with hold between the through-hole, every be provided with on the second conveyer pipe the second detects the piece, first detect with the storage piece is connected.
In one embodiment, the conveying module comprises a mounting assembly, the mounting assembly comprises a plurality of mounting parts, a plurality of accommodating parts are arranged on the combining assembly, the accommodating parts define the accommodating through holes inside, and the corresponding second conveying pipes are detachably connected with the accommodating parts through the mounting parts.
In one embodiment, the corresponding mounting member is plugged with the accommodating member; and/or the presence of a gas in the atmosphere,
the corresponding second conveying pipe is inserted into the mounting piece; and/or the presence of a gas in the gas,
the mounting assembly includes a mounting base from which a plurality of the mounting members extend toward the composite assembly, and to which the plurality of mounting members are removably attachable.
In one embodiment, the device further comprises a moving assembly, at least one of the synthesis assembly and the conveying module is connected with the moving assembly, and the moving assembly is used for driving the synthesis assembly and the conveying module to move relatively.
In one embodiment, the synthesis assembly comprises a synthesis purification plate and a support base, the accommodating through hole is arranged on the synthesis purification plate, and the synthesis purification plate is detachably connected with the support base.
In one embodiment, the device further comprises a processor and a display screen, wherein the display screen, the first detection element and the second detection element are all in communication connection with the processor, the processor is used for calculating a difference value between the initial end flow parameter a1 and the terminal end flow parameter a2 and comparing the difference value with the preset error range, and the display screen is used for displaying a comparison result.
According to the screening device for the nucleic acid synthetic vector, by applying the screening method for the nucleic acid synthetic vector, only two flow parameters need to be detected, and the difference value is calculated and compared with a preset error range, so that defective products can be screened out, and the whole screening process is simple to operate.
Drawings
FIG. 1 is a schematic view of a nucleic acid synthesis vector screening apparatus according to an embodiment of the present invention;
FIG. 2 is a schematic diagram showing the overall configuration of a nucleic acid synthesis vector screening apparatus according to an embodiment of the present invention;
FIG. 3 is a schematic diagram showing the overall configuration of a nucleic acid synthesis vector screening apparatus according to another embodiment of the present invention;
FIG. 4 is an enlarged view of a portion of FIG. 3 at A;
FIG. 5 is a schematic diagram showing the construction of a synthesis module in the nucleic acid synthesis vector screening apparatus according to one embodiment of the present invention;
fig. 6 is an exploded view of the composite assembly of fig. 5.
Reference numerals:
the synthetic component 100, the supporting seat 110, the supporting portion 111, the fixing portion 112, the sliding slot 1121, the synthetic purification plate 120, the accommodating member 121, the accommodating through hole 1211, the protruding portion 1212, and the fastening member 130;
a storage member 200;
a first delivery pipe 310, a first valve 311, a second valve 312, a second delivery pipe 320;
a first detecting member 410, a second detecting member 420;
a flow splitting assembly 500, an inflow port 510, an outflow port 520, a flow splitting flow passage 530;
mounting member 600, annular groove 610;
a first moving module 710 and a second moving module 720;
detecting system inflow module 800;
test nucleic acid synthesis vector 900.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, embodiments accompanying figures are described in detail below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.
In the description of the present invention, it is to be understood that the terms "central," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," "circumferential," and the like are used in the orientations and positional relationships indicated in the drawings for convenience in describing the invention and to simplify the description, and are not intended to indicate or imply that the referenced device or element must have a particular orientation, be constructed and operated in a particular orientation, and are not to be considered limiting of the invention.
Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless specifically limited otherwise.
In the present invention, unless otherwise expressly stated or limited, the terms "mounted," "connected," "secured," and the like are to be construed broadly and can, for example, be fixedly connected, 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 meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
In the present invention, unless otherwise expressly stated or limited, the first feature "on" or "under" the second feature may be directly contacting the first and second features or indirectly contacting the first and second features through an intermediate. Also, a first feature "on," "over," and "above" a second feature may be directly or diagonally above the second feature, or may simply indicate that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature may be directly under or obliquely under the first feature, or may simply mean that the first feature is at a lesser elevation than the second feature.
It will be understood that when an element is referred to as being "secured to" or "disposed on" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and the like as used herein are for illustrative purposes only and do not denote a unique embodiment.
Referring to FIG. 2, when the nucleic acid synthesis vector screening apparatus shown in FIG. 2 is used for screening a nucleic acid synthesis vector, the following steps are included:
s100, installing the nucleic acid synthesis carrier 900 to be detected in the containing through hole 1211 of the synthesis assembly 100;
s200, enabling the detection fluid to flow through the nucleic acid synthesis carrier 900 to be detected;
s300, acquiring a starting-end flow parameter a1 of the detection fluid;
s400 acquiring a terminal flow parameter a2 of the detection fluid near the inlet of the receiving through-hole 1211;
s500, obtaining a flow parameter difference a3 of the flow parameter a1 at the beginning and the flow parameter a2 at the tail end, comparing the flow parameter difference a3 with a preset error range, and if the flow parameter difference a3 is outside the preset error range, determining that the nucleic acid synthesis carrier 900 to be detected is unqualified.
Specifically, in the view shown in the figure, in S100, the synthesis assembly 100 is provided with an accommodating through hole 1211 extending in the vertical direction, and the nucleic acid synthesis carrier 900 to be tested is installed in the accommodating through hole 1211 to seal the accommodating through hole 1211. In S200, the detection fluid is introduced into the containing hole 1211 to flow through the test nucleic acid synthesis carrier 900 in a porous state. In S300, the start-end flow parameter a1 is a flow parameter acquired at a position near the start end on the flow path of the detection fluid. In S400, the tip flow parameter a2 refers to a flow parameter acquired at a position on the flow path of the detection fluid near the tip near the entrance of the accommodation through-hole 1211. In S500, the flow resistance of the nucleic acid synthesis vector 900 to be detected may affect the obtained terminal flow parameter a2, so as to affect the obtained difference flow parameter difference a3, and if the flow parameter difference a3 is too large or too small, the flow parameter difference a3 is compared with a preset error range, and then does not fall within the preset error range, which indicates that the flow resistance of the nucleic acid synthesis vector 900 to be detected deviates from the standard flow resistance more, and belongs to a non-defective product, and needs to be screened and removed. In the method, the defective products can be screened out only by detecting two flow parameters and comparing the difference value with a preset error range, and the whole screening process is simple to operate.
Referring to fig. 3 and 4, preferably, in some embodiments, in S100, a plurality of nucleic acid synthesis vectors 900 to be tested are installed in the plurality of receiving through holes 1211 in a one-to-one correspondence manner; in S200, the detection fluid is shunted and then flows through a plurality of nucleic acid synthesis carriers 900 to be detected respectively; in S400, acquiring terminal flow parameters a2 corresponding to each nucleic acid synthesis vector 900 to be detected; in S500, flow parameter differences a3 corresponding to the multiple nucleic acid synthesis vectors 900 to be tested are respectively obtained according to the flow parameter a1 at the beginning end and the flow parameter a2 at the end corresponding to each nucleic acid synthesis vector 900 to be tested, and are respectively compared with a preset error range. Specifically, in S100, a plurality of receiving through holes 1211 extending in the vertical direction are provided in the synthesizing assembly 100, and one nucleic acid synthesis carrier 900 to be tested is loaded into each receiving through hole 1211 to block the corresponding receiving through hole 1211. In S200, the detection fluid is branched into a plurality of channels, and the plurality of detection fluids flow into the plurality of receiving through-holes 1211 in a one-to-one correspondence, thereby flowing through the corresponding nucleic acid synthesis vectors 900 to be detected. In S400, the end flow parameter a2 corresponding to each nucleic acid synthesis vector 900 to be tested is obtained. In S500, the tail end flow parameter a2 obtained from the branch corresponding to each nucleic acid synthesis vector 900 to be tested is compared with the start end flow parameter a1 obtained in S300 respectively to find the difference, so as to screen out the unqualified product with the difference value outside the preset error range. In this embodiment, the detection fluid is shunted and then flows through the plurality of nucleic acid synthesis vectors 900 to be detected, so that the terminal flow parameter a2 corresponding to each of the plurality of nucleic acid synthesis vectors 900 to be detected can be obtained simultaneously in a single screening, that is, the plurality of nucleic acid synthesis vectors 900 to be detected can be screened simultaneously, and the screening efficiency is high. For example, in the screening, a plurality of test nucleic acid synthesis vectors 900 of the same lot may be screened simultaneously to screen out a defective product in the lot.
In some embodiments, the detection fluid may be a liquid. Specifically, a liquid with stable properties and no corrosiveness can be selected so as to avoid influencing the subsequent synthesis after the residue is caused. Preferably, in some embodiments, the detection fluid is a gas. For example, a gas having stable properties such as an inert gas or nitrogen gas can be used. When gas is selected as the detection fluid, it is not easy to cause residue in the receiving through hole 1211 and the nucleic acid synthesis carrier 900 to be detected, so that the quality of DNA synthesis is high.
In some embodiments, the start-end flow parameter a1 and the end-end flow parameter a2 are flow rates of the test fluid. The preset error range is a range formed by up-down floating of a certain error of the difference value of the flow rate at the starting end and the standard flow rate at the tail end. The standard flow rate at the end was measured with a standard flow resistance. If the flow resistance of the nucleic acid synthesis vector 900 to be detected is too large, the measured end flow rate will be small, and the obtained flow rate difference will be large; on the contrary, if the flow resistance of the nucleic acid synthesis vector 900 to be detected is too small, the measured flow rate at the end will be too large, and the flow rate difference obtained will be too small. If the flow rate difference obtained is not within the preset error range, it indicates that the flow resistance of the nucleic acid synthesis vector 900 to be detected is too large or too small, and the nucleic acid synthesis vector belongs to a defective product, and needs to be removed. In other embodiments, the start flow parameter a1 and the end flow parameter a2 are pressures of the test fluid. The preset error range is a range formed by up-down floating of a certain error of the difference value between the pressure at the starting end and the standard pressure at the tail end. The standard pressure at the end is measured with a standard flow resistance. If the flow resistance of the nucleic acid synthesis vector 900 to be detected is too large, the fluid is difficult to flow out when flowing through the nucleic acid synthesis vector 900 to be detected, the measured end pressure is too large, and the obtained pressure difference is too small; on the contrary, if the flow resistance of the nucleic acid synthesis vector 900 to be detected is too small, the measured end pressure will be too small, and the calculated pressure difference will be too large. If the obtained pressure difference is not within the preset error range, it indicates that the flow resistance of the nucleic acid synthesis vector 900 to be detected is too large or too small, and the nucleic acid synthesis vector belongs to a defective product, and needs to be removed. In the following examples, the pressure of the detection fluid will be described by taking the detection fluid as a gas and the start-end flow parameter a1 and the end-end flow parameter a2 as examples.
Referring to fig. 2, in some embodiments, the nucleic acid synthesis vector screening apparatus includes a synthesis element 100, a storage element 200, a first detection element 410, a second detection element 420, and a delivery module. The storage member 200 is used to store the test fluid. The synthesis unit 100 is provided with an accommodating through-hole 1211 for accommodating the nucleic acid synthesis carrier 900 to be tested. A transport module for transporting the detection fluid to the containing through-hole 1211 to flow through the nucleic acid synthesis carrier 900 to be detected installed in the containing through-hole 1211 is connected between the storage member 200 and the synthesis unit 100. The first detecting member 410 is used for detecting a beginning flow parameter a1 of the detection fluid, the second detecting member 420 is disposed on the delivery module near the entrance of the receiving through-hole 1211, and the second detecting member 420 is used for detecting an end flow parameter a2 of the detection fluid. When the nucleic acid synthesis vector screening device in the embodiment is used, the nucleic acid synthesis vector screening method is applied, only two flow parameters need to be detected, and the difference value is obtained and compared with a preset error range, so that the defective products can be screened out, and the whole screening process is simple to operate.
Specifically, the storage member 200 may be a high-pressure gas tank in which the detection gas is stored. Alternatively, the storage member 200 may be an air pump, a plunger pump, or the like. The synthesis unit 100 is disposed below the storage unit 200 with the transport module disposed therebetween, and the high-pressure gas tank provides positive pressure driving force for the detection gas to flow downward through the nucleic acid synthesis carrier 900 to be detected, which is installed in the accommodation through-hole 1211. The conveying module comprises a first conveying pipe 310 and a second conveying pipe 320, wherein a first valve 311 is arranged on the first conveying pipe 310, and a second valve 312 is arranged at the joint of the first conveying pipe 310 and the second conveying pipe 320. Specifically, the first valve 311 and the second valve 312 may be solenoid valves, but other types of valves are also possible. The first detecting member 410 and the second detecting member 420 are both pressure sensors. The first detecting member 410 is disposed on the first conveying pipe 310, and the second detecting member 420 is disposed on the second conveying pipe 320. Of course, the first sensing member 410 may be mounted on the storage member 200 to directly sense the gas pressure at the outlet of the storage member 200. When the first valve 311 is opened and the second valve 312 is closed after the high pressure gas tank is opened, the sensing gas flows in the first delivery pipe 310, and the first sensing member 410 can sense the initial pressure. Then, the second valve 312 is opened to allow the gas to flow into the second transport pipe 320 and further through the nucleic acid synthesizing carrier 900 to be detected, and the second detecting member 420 can detect the end pressure. In the above-described embodiment, the high-pressure gas tank provides a driving force of positive pressure to the detection gas, causing the detection gas to flow upward and downward through the nucleic acid synthesis carrier 900 to be tested, which is mounted in the accommodation through-hole 1211. In other embodiments, the detection gas may be introduced into the receiving through-hole 1211 by a negative pressure adsorption method on the outlet side, i.e., below, of the receiving through-hole 1211. In this case, the first detector 410 may be directly mounted on the storage device 200.
Referring to fig. 3 and 4, in some embodiments, it is preferable that the composite member 100 further includes a flow dividing assembly 500, the composite member 100 is provided with a plurality of receiving through holes 1211, the flow dividing assembly 500 includes an inflow port 510 and a plurality of outflow ports 520, the delivery module includes a first delivery pipe 310 and a plurality of second delivery pipes 320, the first delivery pipe 310 is connected between the inflow port 510 and the storage element 200, the second delivery pipes 320 are connected between the corresponding outflow ports 520 and the receiving through holes 1211, each of the second delivery pipes 320 is provided with a second detection element 420, and the first detection element 410 is connected to the storage element 200.
Specifically, the flow dividing assembly 500 is provided therein with flow dividing channels 530, the flow dividing channels 530 are branched in a tree shape, and the detection gas flows in from the inlet 510 of the flow dividing assembly 500, is divided by the flow dividing channels 530, finally flows out from the plurality of outlets 520, flows into the corresponding second conveying pipes 320, and is conveyed to the corresponding accommodating through holes 1211 through the second conveying pipes 320. The flow splitting channel 530 in the flow splitting assembly 500 may be a single flow splitting or a plurality of flow splitting. In the embodiment shown in the drawings, the flow dividing passage 530 may perform the flow dividing multiple times. Specifically, the detection gas flowing from the inflow port 510 is branched into two branches, the two branches are each branched into two branches, and each of the four branches is branched into two branches … …, and the number of times the detection gas is branched can be determined according to the number of the receiving through holes 1211 in design and manufacture. The first sensing member 410 is disposed on the first delivery pipe 310 and indirectly connected to the storage member 200 through the first delivery pipe 310. When the first valve 311 is opened and the second valve 312 is closed after the high pressure gas tank is opened, the sensing gas flows in the first delivery pipe 310, and the first sensing member 410 may sense the gas pressure in the first delivery pipe 310. Then, the second valve 312 is opened to allow the gas to flow through the flow dividing assembly 500 into the plurality of second delivery pipes 320 and further flow through the corresponding nucleic acid synthesizing carriers 900 to be detected, and the second detecting member 420 can detect the gas pressure in the second delivery pipes 320. In this embodiment, shunt assembly 500 is used for shunting, so that the detection gas can flow through a plurality of nucleic acid synthesis carriers 900 to be detected simultaneously, and the plurality of nucleic acid synthesis carriers 900 to be detected are detected and screened simultaneously, so that the screening efficiency is high.
Referring to fig. 2 to 4, in some embodiments, the conveying module includes a mounting assembly including a plurality of mounting members 600, the combining assembly 100 is provided with a plurality of receiving members 121, receiving through holes 1211 are defined inside the receiving members 121, and the corresponding second conveying pipes 320 are detachably connected to the receiving members 121 through the mounting members 600. Specifically, the upper half portions of the receiving members 121 are integrally connected, the lower half portions of the receiving members 121 respectively extend downward to form extending portions 1212, the outer shapes of which are tapered with a large upper portion and a small lower portion and have a gap therebetween, and the receiving members 121 have receiving through holes 1211 formed therein and penetrating in the vertical direction. The two ends of the mounting member 600 are respectively connected between the corresponding second conveying pipe 320 and the accommodating member 121, and the mounting member 600 is used for realizing detachable connection between the corresponding second conveying pipe 320 and the accommodating member 121. Because the detachable connection structure is adopted, if parts are worn or aged, the parts can be detached and replaced, the whole screening device does not need to be replaced, and the use cost can be reduced. And the screening device can be disassembled and stored in an idle state, so that the storage space is fully utilized.
Specifically, in some embodiments, a corresponding mounting member 600 is plugged into the receiving member 121. Specifically, the mounting member 600 is inserted into the receiving through-hole 1211 from above the receiving member 121, and is interference-fitted with a hole wall of the receiving through-hole 1211. When the mounting member 600 is mounted or dismounted, the mounting member is directly inserted into or pulled out of the receiving through-hole 1211, which is very convenient and time-saving. The mounting member 600 can be made of rubber or silica gel and other elastic materials, so that the risk that the accommodating member 121 is excessively propped open and is broken in the dismounting process is reduced. Preferably, the mounting member 600 is provided with an annular groove 610 on the outer peripheral surface thereof, and the annular groove 610 may be provided with a sealing ring to enhance the sealing property between the mounting member 600 and the wall of the hole of the receiving through hole 1211 so as to prevent the gas leakage from affecting the accuracy of the value measured by the pressure sensor. In other embodiments, the corresponding mounting member 600 and the receiving member 121 can be connected by other conventional detachable connection methods such as snap connection or threaded fastener connection. In other embodiments, the composite member 100 may be inverted, i.e., the protrusion 1212 of the composite member 100 protrudes upward, the inner cavity of the mounting member 600 may be tapered to match the shape of the protrusion 1212, and the mounting member 600 may be sleeved outside the protrusion 1212, i.e., the protrusion 1212 is inserted into the inner cavity of the mounting member 600. Of course, the extension 1212 may have a shape other than a taper, and the shape of the inner cavity of the mounting member 600 may be matched thereto.
In some embodiments, a corresponding second delivery tube 320 is docked with the mount 600. Specifically, the bottom end of the second delivery tube 320 is inserted into the inner cavity of the mounting member 600 and is in interference fit with the cavity wall of the inner cavity of the mounting member 600. Alternatively, the mounting member 600 is inserted into the lumen of the second delivery tube 320 and interference-fitted with the lumen wall of the lumen. During the assembly and disassembly, the second conveying pipe 320 and the mounting part 600 can be directly plugged and pulled, which is very convenient and time-saving.
In some embodiments, the mounting assembly includes a mount from which the plurality of mounts 600 extend toward the composite assembly 100, and each of the plurality of mounts 600 is removably coupled to the mount. Specifically, be provided with a plurality of through-holes that link up along vertical direction on the mount pad, every installed part 600 from down in stretching into corresponding through-hole up to with pore wall threaded connection. If only one of the mounting members 600 of the mounting assembly is damaged, the mounting member 600 may be removed from the bottom end of the second transfer pipe 320, the mounting member 600 may be removed from the top end of the receiving member 121, and the mounting member 600 may be removed from the mounting seat for replacement. The installation component does not need to be integrally replaced by the arrangement, and the use cost can be reduced. In other embodiments, the mounting member 600 and the mounting seat may be fixed by plugging or clipping.
Referring to fig. 1, in some embodiments, the screening apparatus further includes a moving assembly, at least one of the synthesizing assembly 100 and the conveying module is connected to the moving assembly, and the moving assembly is used for driving the synthesizing assembly 100 and the conveying module to move relatively. Specifically, the moving elements include a first moving module 710 and a second moving module 720, the detection system inflow module 800 is installed at the first moving module 710, and the combining element 100 is installed at the second moving module 720. The detection system inflow module 800 can move up and down to approach or move away from the synthesis assembly 100 driven by the first movement module 710. The combining member 100 can be horizontally moved by the second moving module 720, so that the plurality of rows of receiving through holes 1211 participate in the screening in sequence. The detection system inflow module 800 includes the aforementioned storage member 200, a delivery module, a first detection member 410, and a second detection member 420. The first moving module 710 and the second moving module 720 can be mobile modules commonly used in the prior art. In other embodiments, the synthesis assembly 100 may be fixed in position, and the detection system inflow module 800 may be driven by the moving assembly to perform horizontal and vertical movements. Alternatively, the detection system inflow module 800 may be fixed in position, and the synthesis assembly 100 may be driven by the moving assembly to perform horizontal and vertical movements.
Referring to fig. 5 and 6, in some embodiments, the synthesis assembly 100 includes a synthesis purification plate 120 and a support base 110, the receiving through hole 1211 is disposed on the synthesis purification plate 120, and the synthesis purification plate 120 is detachably connected to the support base 110. Specifically, the accommodating element 121 is disposed on the synthetic purification plate 120, an upper half portion of the accommodating element 121 is connected to form a main structure of the synthetic purification plate 120, and a lower half portion of the accommodating element 121 extends downward from the main structure to form an extending portion 1212. The supporting base 110 is installed on the second moving module 720, and if the synthesis and purification plate 120 is damaged, it can be detached from the supporting base 110 for replacement. In the screening process, the entire synthesis and purification plate 120 can be detached from the support base 110, and other synthesis and purification plates 120 not being screened can be replaced, so as to improve the screening efficiency. Specifically, the synthetic purification plate 120 is clamped to the support base 110, or connected by a screw fastener, or inserted. In the embodiment shown in the drawings, the supporting base 110 includes a supporting portion 111 and a fixing portion 112 fixedly connected to each other, a sliding slot 1121 extending horizontally is formed in the fixing portion 112, the synthetic purification plate 120 is clamped in the sliding slot 1121, and meanwhile, the synthetic purification plate 120 and the fixing portion 112 are fixed by a fastening member 130 so as to prevent the synthetic purification plate 120 from reversely sliding out of the sliding slot 1121. The fastener 130 may be a screw or a pin, among other components.
In some embodiments, the device further comprises a processor and a display screen, the first detecting element 410 and the second detecting element 420 are all communicatively connected to the processor, the processor is configured to calculate a difference value between the initial flow parameter a1 and the final flow parameter a2 and compare the difference value with a preset error range, and the display screen is configured to display a comparison result. Specifically, when performing the inspection and screening, the processor may automatically find the difference between the start-end flow parameter a1 and the end-end flow parameter a2 after obtaining the difference, compare the difference with a preset error range, and display the result on the display screen, where the result may be pass or fail, or may include detailed information, such as the specific values of the start-end flow parameter a1 and the end-end flow parameter a2 and the difference between the two. The operator only needs to read the screening result on the display screen, manual calculation is not needed, the labor intensity is reduced, and the efficiency is improved.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (10)

1. The method for screening a nucleic acid synthesis vector is characterized by comprising the following steps:
s100, mounting a nucleic acid synthesis carrier to be detected in an accommodating through hole of a synthesis assembly;
s200, enabling a detection fluid to flow through the nucleic acid synthesis carrier to be detected;
s300, acquiring a starting-end flow parameter a1 of the detection fluid;
s400, acquiring a terminal flow parameter a2 of the detection fluid at the inlet close to the accommodating through hole;
s500, obtaining a flow parameter difference value a3 between the flow parameter a1 at the starting end and the flow parameter a2 at the tail end, comparing the flow parameter difference value a3 with a preset error range, and if the flow parameter difference value a3 is outside the preset error range, determining that the nucleic acid synthesis carrier to be detected is unqualified;
wherein the initial end flow parameter a1 and the final end flow parameter a2 are the flow rate or the pressure of the detection fluid.
2. The method for screening a nucleic acid synthesis vector according to claim 1,
s100, correspondingly mounting a plurality of nucleic acid synthesis carriers to be detected in a plurality of accommodating through holes one by one;
in S200, the detection fluid is shunted and then flows through a plurality of nucleic acid synthesis carriers to be detected respectively;
in S400, acquiring the terminal flow parameter a2 corresponding to each nucleic acid synthesis vector to be detected;
in S500, the flow parameter difference a3 corresponding to each of the multiple nucleic acid synthesis vectors to be tested is respectively obtained according to the start-end flow parameter a1 and the end-end flow parameter a2 corresponding to each nucleic acid synthesis vector to be tested, and is respectively compared with the preset error range.
3. The method for screening a nucleic acid synthesis vector according to claim 1, wherein the detection fluid is a gas or a liquid.
4. The nucleic acid synthesis vector screening apparatus according to the nucleic acid synthesis vector screening method of claim 1, comprising:
a storage for storing the test fluid;
the synthesis assembly is provided with the accommodating through hole for accommodating the nucleic acid synthesis carrier to be detected;
a delivery module connected between the storage member and the synthesis assembly, the delivery module for delivering the detection fluid to the accommodation through hole;
a first detecting member for detecting a starting end flow parameter a1 of the detection fluid;
and the second detection piece is arranged on the conveying module and close to the inlet of the accommodating through hole, and is used for detecting the terminal flow parameter a2 of the detection fluid.
5. The nucleic acid synthesis vector screening apparatus according to claim 4, further comprising a flow distribution module, wherein the synthesis module is provided with a plurality of the receiving through-holes, the flow distribution module includes an inflow port and a plurality of outflow ports, the delivery module includes a first delivery pipe and a plurality of second delivery pipes, the first delivery pipe is connected between the inflow port and the storage member, the second delivery pipes are connected between the corresponding outflow ports and the receiving through-holes, each of the second delivery pipes is provided with the second detection member, and the first detection member is connected to the storage member.
6. The nucleic acid synthesis vector screening apparatus according to claim 5, wherein the transport module includes a mounting assembly including a plurality of mounting members, the synthesis assembly is provided with a plurality of receiving members, the receiving members define the receiving through-holes therein, and the corresponding second transport tubes are detachably connected to the receiving members through the mounting members.
7. The nucleic acid synthesis vector screening apparatus according to claim 6,
the corresponding mounting piece is plugged with the accommodating piece; and/or the presence of a gas in the gas,
the corresponding second conveying pipe is inserted into the mounting piece; and/or the presence of a gas in the gas,
the mounting assembly includes a mounting base from which a plurality of the mounting members extend toward the composite assembly, and to which the plurality of mounting members are removably attachable.
8. The nucleic acid synthesis vector screening apparatus according to claim 6, further comprising a moving member to which at least one of the synthesis member and the transport module is connected, the moving member being configured to drive the synthesis member and the transport module to move relatively.
9. The apparatus for screening nucleic acid synthesis vector according to claim 4, wherein the synthesis module comprises a synthesis purification plate and a support base, the receiving through hole is provided in the synthesis purification plate, and the synthesis purification plate is detachably connected to the support base.
10. The nucleic acid synthesis vector screening apparatus according to claim 4, further comprising a processor and a display screen, wherein the display screen, the first detecting element and the second detecting element are all communicatively connected to the processor, the processor is configured to calculate a difference between the initial flow parameter a1 and the final flow parameter a2 and compare the difference with the predetermined error range, and the display screen is configured to display a comparison result.
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