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CN113845995A - Single cell library preparation system - Google Patents

Single cell library preparation system Download PDF

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Publication number
CN113845995A
CN113845995A CN202110977986.8A CN202110977986A CN113845995A CN 113845995 A CN113845995 A CN 113845995A CN 202110977986 A CN202110977986 A CN 202110977986A CN 113845995 A CN113845995 A CN 113845995A
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library preparation
cell library
preparation system
single cell
output shaft
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CN113845995B (en
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黄金城
索海军
焦少灼
李宗文
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Beijing Xunyin Biological Technology Co ltd
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Beijing Xunyin Biological Technology Co ltd
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/02Form or structure of the vessel
    • C12M23/16Microfluidic devices; Capillary tubes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

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Abstract

本发明公开一种单细胞文库制备系统,包括机座、移送机构以及挤压机构,机座上形成有工作区域;移送机构包括沿水平方向可活动地安装于机座的进出仓,进出仓用于供微流体芯片安装;挤压机构包括设于工作区域的上方且沿上下向可活动设置的多岐板,用于在多岐板向下活动至工作区域时,与工作区域处的微流体芯片组接,以驱动所述微流体芯片的各原材料自各原料槽依次流经各流道后成型并流入成型槽中。在本发明的技术方案中,通过移送机构移送微流体,挤压机构驱动微流体芯片的多个原料槽内的各原材料进入所述微流体芯片的流道内成型并流入所述微流体芯片的成型槽中,实现单个单细胞样本成型和单细胞文库制备。

Figure 202110977986

The invention discloses a single-cell library preparation system, comprising a machine base, a transfer mechanism and an extrusion mechanism, and a work area is formed on the machine base; For the installation of microfluidic chips; the extrusion mechanism includes a polybasic plate arranged above the working area and movably arranged in the up and down direction, and is used for connecting with the microfluidic chip set at the working area when the polybasic plate moves downward to the working area. Then, to drive the raw materials of the microfluidic chip to flow through the flow channels in sequence from the raw material grooves, and then form and flow into the forming grooves. In the technical solution of the present invention, the microfluidic is transferred by the transfer mechanism, and the extrusion mechanism drives the raw materials in the multiple raw material grooves of the microfluidic chip to enter the flow channels of the microfluidic chip for molding and flow into the molding of the microfluidic chip. tank, enabling single-cell sample formation and single-cell library preparation.

Figure 202110977986

Description

Single cell library preparation system
Technical Field
The invention relates to the field of single cell library preparation, in particular to a single cell library preparation system.
Background
In recent years, with the continuous progress of sequencing technology, the high-depth single-cell sequencing is developed towards higher-throughput application. In addition to the base reads themselves, sample cDNA synthesis and library preparation are another important cost component of the overall single cell sequencing process. The labeling and library building of the cDNA of each cell is usually completed by using a single cell library preparation system through independent encapsulation, reverse transcription, tag sequence addition, library building and other processes of thousands of cells, that is, a single cell library preparation system is required to realize single cell sample molding and single cell library preparation.
Disclosure of Invention
The invention mainly aims to provide a single cell library preparation system, and aims to provide a system for realizing single cell sample molding and single cell library preparation.
In order to achieve the above object, the present invention provides a single cell library preparation system, comprising:
the engine base is provided with a working area and has a front direction and a rear direction in the horizontal direction;
the transfer mechanism comprises an inlet and outlet bin which is movably arranged on the base along the front and back directions, is used for installing the microfluidic chip and can move to the working area along the front and back directions under the driving of external force; and the number of the first and second groups,
the extruding mechanism comprises a manifold plate which is arranged above the working area and can be movably arranged along the vertical direction, and the manifold plate is used for being assembled with the microfluidic chip at the working area when moving downwards to the working area so as to drive the raw materials of the microfluidic chip to flow through the flow channels in sequence from the raw material grooves for molding and flow into the molding grooves.
Optionally, the transfer mechanism further comprises:
a first motor having a first output shaft; and the number of the first and second groups,
the transfer transmission assembly is used for being in transmission connection with the first output shaft and the in-out bin.
Optionally, the machine base further has a left direction and a right direction in the horizontal direction;
the first output shaft extends along the left-right direction;
the transfer transmission assembly comprises a gear and a rack which are meshed with each other, the gear is installed on the first output shaft, the rack is arranged at the bottom of the in-out bin, and the rack extends forwards and backwards.
Optionally, the transfer mechanism further includes a sliding groove disposed in one of the base and the in-and-out bin, and a sliding bar correspondingly disposed in the other, and the sliding bar extends in the front-back direction and is slidably mounted in the sliding groove.
Optionally, the pressing mechanism further comprises an air pump mounted on the base;
a gas passing channel is formed in the manifold plate, and a gas inlet and a plurality of gas outlets are respectively arranged on two opposite sides of the manifold plate from top to bottom;
the air inlet is communicated with the air passing channel and the outlet of the air pump;
the plurality of air outlets are used for respectively communicating the air passing channel with the plurality of raw material grooves of the microfluidic chip in the working area when the manifold plate moves downwards to the working area.
Optionally, the pressing mechanism further comprises:
a second motor having a second output shaft; and the number of the first and second groups,
and the extrusion transmission assembly is in transmission connection with the second output shaft and the multi-manifold plate.
Optionally, the second output shaft extends in the front-back direction;
the extrusion drive assembly includes a cam mechanism, the cam mechanism including:
a cam mounted to the second output shaft; and the number of the first and second groups,
the ejector rod extends up and down and is provided with a first end and a second end which are opposite to each other, the first end is abutted to the periphery of the cam, the ejector rod can move up and down, and in the downward movement stroke of the ejector rod, the second end is abutted to the top of the multi-manifold plate so as to push the multi-manifold plate to move down.
Optionally, the transfer mechanism comprises a first motor which is in driving connection with the in-out bin;
the extrusion mechanism comprises an air pump;
the single cell library preparation system further comprises:
the integrated circuit board is arranged on the top of the multi-manifold board and used for electrically connecting the first motor, the second motor and the air pump; and the number of the first and second groups,
the connecting plate is arranged at the top of the multi-manifold plate and is positioned above the integrated circuit board;
and in the downward movable stroke of the ejector rod, the second end is used for abutting against the top of the connecting plate.
Optionally, the single-cell library preparation system further comprises a noise reduction structure disposed on the base, and the noise reduction structure is disposed corresponding to the extrusion mechanism.
Optionally, the pressing mechanism comprises an air pump mounted on the base;
the noise reduction structure comprises a vibration reduction piece, the vibration reduction piece is provided with a fixed section and an installation section which are oppositely arranged in the front-back direction, the fixed section is arranged on the machine base, and the installation section is arranged outside the machine base in a suspended mode;
wherein the air pump is mounted to the mounting section.
In the technical scheme of the invention, the single cell library preparation system mainly comprises a transfer mechanism and an extrusion mechanism, wherein the transfer mechanism and the extrusion mechanism jointly act on a microfluidic chip, the microfluidic chip comprises a carrier plate, a first side surface and a second side surface which are opposite to each other are formed on the carrier plate, a plurality of raw material grooves and a forming groove are sequentially formed on the first side surface, a flow channel is formed on the second side surface, the flow channel is communicated with the raw material grooves and the forming groove, different raw materials are respectively placed in the raw material grooves, after the single cell library preparation system is started, the microfluidic chip is placed in a feeding bin of the transfer mechanism, the microfluidic chip is transferred to a working area by the feeding bin, a plurality of manifold plates of the extrusion mechanism move downwards to be connected with the microfluidic chip at the working area, and the raw materials in the raw material grooves are driven to enter the flow channel to be formed into a single cell sample, and the single cell sample flows into the forming groove, an operator counts and builds a library for the single cell sample in the forming groove, and the single cell sample forming and the single cell library preparation are realized through the single cell library preparation system.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the structures shown in the drawings without creative efforts.
FIG. 1 is a schematic perspective view of a single-cell library preparation system according to an embodiment of the present invention;
FIG. 2 is a schematic perspective view of the single cell library preparation system of FIG. 1 from another perspective;
FIG. 3 is an enlarged schematic view of detail A of FIG. 2;
FIG. 4 is a schematic front view of the single cell library preparation system of FIG. 1.
The embodiment of the invention is illustrated by reference numerals:
reference numerals Name (R) Reference numerals Name (R)
100 Cell library preparation system 31 Manifold board
1 Engine base 32 Air pump
2 Transfer mechanism 33 Second electric machine
21 In-out bin 34 Extrusion drive assembly
22 First motor 341 Cam wheel
23 Transfer drive assembly 342 Top rod
231 Gear wheel 4 Integrated circuit board
232 Rack bar 5 Connecting plate
24 Sliding chute 6 Noise reduction structure
25 Slide bar 61 Vibration damping member
3 Extrusion mechanism
The implementation, functional features and advantages of the objects of the present invention will be further explained with reference to the accompanying drawings.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that, if directional indications (such as up, down, left, right, front, and back … …) are involved in the embodiment of the present invention, the directional indications are only used to explain the relative positional relationship between the components, the movement situation, and the like in a specific posture (as shown in the drawing), and if the specific posture is changed, the directional indications are changed accordingly.
In addition, if there is a description of "first", "second", etc. in an embodiment of the present invention, the description of "first", "second", etc. is for descriptive purposes only and is 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 addition, the meaning of "and/or" appearing throughout includes three juxtapositions, exemplified by "A and/or B" including either A or B or both A and B. In addition, technical solutions between various embodiments may be combined with each other, but must be realized by a person skilled in the art, and when the technical solutions are contradictory or cannot be realized, such a combination should not be considered to exist, and is not within the protection scope of the present invention.
In recent years, with the continuous progress of sequencing technology, the high-depth single-cell sequencing is developed towards higher-throughput application. In addition to the base reads themselves, sample cDNA synthesis and library preparation are another important cost component of the overall single cell sequencing process. The labeling and library building of the cDNA of each cell is usually completed by using a single cell library preparation system through the processes of independent encapsulation, reverse transcription, tag sequence addition, library building and the like of thousands of cells, that is, a single cell library preparation system is needed to realize the single cell sample molding and the single cell library preparation.
In view of the above, the present invention provides a single cell library preparation system. Fig. 1 to 4 are diagrams illustrating an embodiment of a single-cell library preparation system according to the present invention.
Referring to fig. 1, the cell library preparation system 100 includes a base 1, a transfer mechanism 2, and a pressing mechanism 3, wherein a working area is formed on the base 1, and the base 1 has a front and a rear direction in a horizontal direction; the transfer mechanism 2 comprises an in-out bin 21 movably arranged on the base 1 along the front-back direction, the in-out bin 21 is used for installing a microfluidic chip and can move to the working area along the front-back direction under the driving of external force; the extruding mechanism 3 comprises a manifold plate 31 which is arranged above the working area and can be movably arranged along the vertical direction, and is used for being assembled with the microfluidic chip at the working area when the manifold plate 31 moves downwards to the working area, so as to drive the raw materials of the microfluidic chip to flow through the flow channels in sequence from the raw material grooves, then be molded and flow into the molding grooves.
In the technical scheme of the present invention, a single cell library preparation system 100 mainly comprises a transfer mechanism 2 and an extrusion mechanism 3, wherein the transfer mechanism 2 and the extrusion mechanism 3 jointly act on a microfluidic chip, it should be noted that the microfluidic chip comprises a carrier plate, a first side surface and a second side surface opposite to each other are formed on the carrier plate, a plurality of raw material grooves and a molding groove are sequentially formed on the first side surface, a flow channel is formed on the second side surface, the flow channel is communicated with the plurality of raw material grooves and the molding groove, different raw materials are respectively placed in the plurality of raw material grooves, after the single cell library preparation system 100 is opened, the microfluidic chip is placed in an in-out bin 21 of the transfer mechanism 2, the in-out bin 21 transfers the microfluidic chip to a working area, and the manifold plate 31 of the extrusion mechanism 3 moves down, and the microfluidic chip group at the working area drives the raw materials in the raw material grooves to enter the flow channel to be molded into a single cell sample and flow into the molding groove, an operator counts and builds a library for the single cell sample in the molding groove, and the single cell sample molding and the single cell library preparation are realized through the single cell library preparation system 100.
It should be noted that the single cell library preparation system 100 is further provided with a plurality of enclosing plates, the enclosing plates and the base 1 enclose together to form a sealed cavity, and the moving mechanism 2 and the squeezing mechanism 3 are arranged in the sealed cavity, so that the preparation environment is better, and the accuracy of the single cell library preparation is improved.
Specifically, the transfer mechanism 2 further comprises a first motor 22 and a transfer transmission assembly 23, wherein the first motor 22 is provided with a first output shaft; the transfer transmission assembly 23 is used for driving and connecting the first output shaft and the in-out bin 21, and the in-out bin 21 conveys the microfluidic chip through the combined action of the transfer transmission assembly 23 and the first motor 22.
The present invention is not limited to the specific mounting manner of the first output shaft and the specific form of the transfer transmission assembly 23, and the first output shaft may be extended in the front-rear direction; the transfer transmission assembly 23 comprises a ball screw, the ball screw comprises a screw rod and a nut which are in threaded fit, the screw rod is fixedly connected with the first output shaft and can rotate coaxially with the first output shaft, and the peripheral side surface of the nut is fixedly connected with the bottom surface of the in-out bin 21; when the first motor 22 is started, the first output shaft rotates around the front-back axis and drives the screw rod to rotate around the front-back axis, and the nut can make linear motion on the screw rod along the front-back direction, so that the in-out bin 21 is driven to move along the front-back direction, and the micro-fluid chip is transferred; specifically, in the present embodiment (please refer to fig. 2 and fig. 3), the base 1 further has a left-right direction in the horizontal direction, and the first output shaft extends along the left-right direction; the transfer transmission assembly 23 comprises a gear 231 and a rack 232 which are engaged with each other, the gear 231 is sleeved outside the first output shaft and can rotate coaxially with the first output shaft, the rack 232 is arranged at the bottom of the in-out bin 21, and the rack 232 extends in the front-back direction; when the first motor 22 is started, the first output shaft rotates around the left-right axis, and simultaneously drives the gear 231 to rotate around the left-right axis, and the rack 232 engaged with the gear 231 can make linear motion in the front-back direction, so as to drive the in-out bin 21 to move in the front-back direction, thereby transferring the microfluidic chip.
In order to facilitate the activity of the in-and-out bin 21, further refer to fig. 3, the transfer mechanism 2 further comprises a sliding groove 24 arranged on the base 1 and one of the in-and-out bin 21 and a sliding strip 25 correspondingly arranged on the other side, the sliding strip 25 is arranged in the sliding groove 24 in a forward and backward extending manner, and is slidably mounted in the sliding groove 24, through the sliding groove 24 and the sliding strip 25 in a sliding fit manner, so that the activity of the in-and-out bin 21 is smoother, and further the in-and-out bin 21 is prevented from generating unnecessary vibration during the transfer of the microfluidic chip, and the risk of raw material overflow in the raw material tank caused by vibration is eliminated.
The concrete arrangement positions of the sliding groove 24 and the sliding strip 25 are not limited, the sliding groove 24 can be arranged on the in-out bin 21, and correspondingly, the sliding strip 25 can be arranged on the machine base 1, specifically, in this embodiment, the sliding groove 24 is arranged on the machine base 1, and the sliding strip 25 is correspondingly arranged on the in-out bin 21.
It should be noted that, in order to further stabilize the installation of the microfluidic chip, the microfluidic chip is provided with an installation structure, the installation structure includes a base and a fixing structure, an installation groove is formed on the upper end surface of the base, and the installation groove is used for placing the microfluidic chip; fixed knot construct be used for with microfluid chip press hold in on the diapire of mounting groove, the bottom of base is provided with spacing portion, and is corresponding, also be provided with the installation department on the business turn over storehouse 21, spacing portion with the spacing cooperation of installation department, in order to incite somebody to action the base is fixed in business turn over storehouse 21, thereby improves microfluid chip's steadiness, and then avoid business turn over storehouse 21 is transferring produce unnecessary vibration during the microfluid chip, has just also eliminated because of the vibration and has made the risk that raw and other materials in the raw materials groove spill over.
Specifically, the specific forms of the limiting part and the mounting part are not limited, the limiting part can be a pin, correspondingly, the mounting part can be a pin hole, and the pin is in limit fit with the pin hole to fix the base to the in-out bin 21; spacing portion with the installation department corresponds respectively and sets up two magnetism and inhale the portion, two magnetism is inhaled the mutual actuation of portion, in order will the base is fixed in business turn over storehouse 21, in this embodiment, spacing portion sets up to the elasticity card post, and is corresponding, the installation department is for offering in the card hole on the bottom plate of business turn over storehouse 21, the elasticity card post with card hole is held each other to block, in order to incite somebody to action the base is fixed in business turn over storehouse 21, thereby makes the installation of microfluid chip is more firm.
In the present invention, in order to ensure the stability of the transfer of the in-out bin 21, the in-out bin 21 has a deceleration position and a stop position in the moving stroke of the in-out bin 21, and before the deceleration position is located at the stop position, when the in-out bin 21 transfers the microfluidic chip to enter the working area, the front end of the in-out bin 21 moves to the deceleration position, the movement of the in-out bin 21 starts to decelerate, the in-out bin 21 continues to move, when the rear end of the in-out bin 21 reaches the stop position, the in-out bin 21 transfers the microfluidic chip to completely enter the working area, and the in-out bin 21 stops moving; in the process that the in-out bin 21 exits from the working area, when the front section of the in-out bin 21 moves to the deceleration position, the movement of the in-out bin 21 starts to decelerate, the in-out bin 21 continues to move, when the front end of the in-out bin 21 reaches the stop position, the in-out bin 21 completely exits from the working area, and the in-out bin 21 stops moving; correspondingly, in order to guarantee that the shift position of business turn over storehouse 21 is more accurate, transfer mechanism 2 still includes first detector, first detector includes first position sensor and second position sensor, first position sensor with second position sensor corresponds respectively the deceleration position with operating position sets up, is used for business turn over storehouse 21 activity extremely the deceleration position with during the operating position, trigger respectively, in order to detect the shift position of business turn over storehouse 21.
The conveying mechanism 2 is further provided with a limiting structure, the limiting structure comprises two limiting plates arranged on the base 1, the two limiting plates respectively correspond to the deceleration position and the stop position, so that when the detector fails, the movement of the inlet and outlet bin 21 is limited.
Referring to fig. 1 and 4, in the present invention, the pressing mechanism 3 includes an air pump 32 mounted on the base 1; a gas passing channel is formed in the manifold plate 31, and a gas inlet and a plurality of gas outlets are respectively arranged on two opposite sides of the manifold plate 31 from top to bottom; wherein the air inlet is communicated with the air passage and the outlet of the air pump 32; the plurality of air outlets are used for respectively communicating the air passing channel with a plurality of raw material grooves of the microfluidic chip in the working area when the manifold plate 31 moves downwards to the working area, the air pump 32 inflates air into the plurality of raw material grooves and the forming groove through the manifold plate 31, and the air pump drives a plurality of raw materials in the raw material grooves to enter the flow channel to be formed into a single-cell sample by air pressure and flow into the forming groove, so that the single-cell sample is formed.
Specifically, the squeezing mechanism 3 further comprises a second motor 33 and a squeezing transmission assembly 34, wherein the second motor 33 is provided with a second output shaft; the extrusion transmission assembly 34 is in transmission connection with the second output shaft and the manifold plate 31, and the manifold plate 31 moves up and down under the combined action of the extrusion transmission assembly 34 and the second motor 33, so that the extrusion mechanism 3 completes the driving operation.
It should be noted that, the present invention does not limit the specific installation manner of the second output shaft and the specific form of the extrusion transmission assembly 34, and may include that an installation groove is formed at the top of the manifold plate 31, the second output shaft extends in the up-down direction, the extrusion transmission assembly 34 may include a ball screw, the ball screw includes a screw rod and a nut that are in threaded fit, one end of the screw rod, which is up-down and up-down, is fixedly connected to the second output shaft and can rotate coaxially with the second output shaft, the other end of the screw rod, which is opposite to the screw rod, is movably disposed in the installation groove, and the lower end surface of the nut is fixedly connected to the top of the manifold plate 31; when the second motor 33 is started, the second output shaft rotates around the vertical axis and drives the screw to rotate around the vertical axis, and the nut can do linear motion on the screw up and down, so that the manifold plate 31 is driven to move up and down, the manifold plate 31 can move up and down, and the extrusion mechanism 3 can complete the driving operation; the extrusion transmission assembly 34 may also be a rack-and-pinion transmission assembly, the rack-and-pinion transmission assembly includes a gear and a rack that are engaged with each other, the gear is sleeved outside the second output shaft and can rotate coaxially with the second output shaft, the rack is disposed on one side of the gear on the manifold plate 31, and the rack extends up and down, when the second motor 33 is started, the second output shaft rotates around the up-and-down axis and simultaneously drives the gear to rotate around the up-and-down axis, and the rack engaged with the gear can move linearly up and down, so as to drive the manifold plate 31 to move up and down, thereby enabling the extrusion mechanism 3 to complete the driving operation.
Specifically, in the present embodiment (please refer to fig. 4 further), the second output shaft extends along the front-back direction; the extrusion transmission assembly 34 comprises a cam mechanism, the cam mechanism comprises a cam 341 and a push rod 342, and the cam 341 is mounted on the second output shaft; the top rod 342 extends vertically and has a first end and a second end opposite to each other, the first end abuts against the periphery of the cam 341, the top rod 342 is movable vertically and has a second end in the downward movement stroke, the second end abuts against the top of the manifold plate 31 to push the manifold plate 31 to move downward, when the second motor 33 is started, the second output shaft rotates around the forward and backward axis and drives the cam 341 to rotate around the forward and backward axis, because the periphery of the cam 341 is provided with a convex portion, when the cam 341 rotates until the periphery of the convex portion abuts against the first end, the convex portion pushes the top rod 342 to move downward, so that the manifold plate 31 is pushed downward, and the pressing mechanism 3 completes the driving operation.
More specifically, in order to cooperate with the cam 341 for operation, the extrusion transmission assembly 34 is further provided with an elastic resetting piece, the elastic resetting piece is arranged between the manifold plate 31 and the machine base 1, and the expansion direction of the elastic resetting piece is arranged along the up-down direction; because the cam 341 is provided with a convex part on its periphery, when the cam 341 rotates until the periphery of the convex part abuts against the first end, the convex part pushes the ejector rod 342 to move downwards, and thus pushes the manifold plate 31 to move downwards, and when the cam 341 rotates until the edge of the convex part leaves the first end, the elastic resetting piece drives the manifold plate 31 to move upwards, so that the periphery of the cam 341 always abuts against the first end, and the manifold plate 31 also moves upwards and downwards.
In this embodiment, the elastic restoring member is provided as a spring, and the spring is provided on the manifold plate 31 and the housing 1, so that when the cam 341 rotates until the edge of the convex portion leaves the first end, the elastic restoring member drives the manifold plate 31 to move upwards.
In the present invention, the pressing mechanism 3 is further provided with a second detector for detecting the displacement of the manifold plate 31 in the up-down direction to ensure the accuracy of the displacement of the manifold plate 31.
Specifically, the present invention does not limit the specific form of the second detector, the second detector may be a distance measuring sensor, the distance measuring sensor is disposed corresponding to the convex portion of the cam 341 and above the cam 341, and during the rotation of the cam 341, the detection of the displacement of the multi-manifold plate 31 is realized by measuring the position of the convex portion, in this embodiment, the second detector is a code wheel, and the code wheel is disposed on the second output shaft to detect the displacement of the multi-manifold plate 31, it should be noted that the code wheel (encoding disk) is a digital encoder for measuring the angular displacement, and it has the advantages of strong resolving capability, high measuring accuracy, reliable operation, and the like, and is a displacement sensor most commonly used for measuring the rotational angle position of the shaft. The displacement of the manifold plate 31 is measured by detecting the rotation angle of the second output shaft by placing the code wheel on the second output shaft, so that the detection is more convenient.
In the present invention, the single cell library preparation system 100 further comprises an integrated circuit board 4 and a connection board 5, wherein the integrated circuit board 4 is mounted on the top of the multi-manifold board 31 for electrically connecting the first motor 22, the second motor 33 and the air pump 32; the connecting plate 5 is arranged on the top of the multi-manifold plate 31 and is positioned above the integrated circuit board 4; in the downward moving stroke of the ejector rod 342, the second end is used for abutting against the top of the connecting plate 5, and the integrated circuit board 4 is arranged on the top of the manifold plate 31, so that the structure is more reasonable, and the installation space is saved.
In order to avoid the extrusion drive assembly 34 with integrated circuit board 4 direct contact causes integrated circuit board 4's damage integrated circuit board 4's top still erect connecting plate 5, ejector pin 342 is connected connecting plate 5 can not only realize the activity of manifold board 31 from top to bottom, still avoid because of ejector pin 342 with integrated circuit board 4 direct contact causes integrated circuit board 4's damage.
It should be noted that, because machining dimension errors and assembly errors exist among the components, in order to ensure the sealing performance of the manifold plate 31, a support plate is further arranged on the machine base 1, the support plate is located above the connecting plate 5, the ejector rod 342 penetrates through the connecting plate 5 and can move up and down relative to the connecting plate 5, the extrusion mechanism 3 is further provided with a gap adjusting gasket, the gap adjusting gasket is arranged at the upper end of the support plate and correspondingly sleeved outside the ejector rod 342, the ejector rod 342 moves down, and the moving stroke of the manifold plate 31 in the up and down direction is adjusted by abutting against the gap adjusting gasket, so that the sealing performance of the manifold plate is improved.
It should be noted that, in the present invention, please refer to fig. 1 and fig. 2, the single cell library preparation system 100 further includes a noise reduction structure 6 disposed on the base 1, the noise reduction structure 6 is disposed corresponding to the squeezing mechanism 3 for eliminating noise generated when the squeezing mechanism 3 operates, since the squeezing mechanism 3 provides driving force when the single cell library preparation system 100 is started, vibration and noise are inevitably generated, so as to affect normal operation of the single cell library preparation system 100, the noise reduction structure 6 is disposed corresponding to the squeezing mechanism 3 for eliminating noise generated when the squeezing mechanism 3 operates, which not only improves the operating environment of the single cell library preparation system 100, but also eliminates influence of vibration and noise on preparation of the single cell library.
Specifically, the noise reduction structure 6 includes a vibration reduction piece 61, the vibration reduction piece 61 has a fixing section and an installation section which are oppositely arranged along the front-back direction, the fixing section is arranged on the machine base 1, and the installation section is arranged outside the machine base 1 in a suspended manner; the air pump 32 is mounted on the mounting section, and the mounting section is suspended on the base 1, so that the mounting section can swing up and down when the extrusion mechanism 3 works, thereby absorbing the up-and-down vibration of the extrusion mechanism 3 and further eliminating the noise generated by the vibration.
More specifically, damping piece 61 is the platelike setting, damping piece 61 is being close to mounting segment department extends towards a lateral buckling and is formed with the ladder face, the ladder face with mounting segment prescribes a limit to the mounting groove jointly, air pump 32 holds and establishes in the mounting groove, just air pump 32's lateral wall supports on the ladder face, so, air pump 32's lateral wall just by the ladder face supports, makes air pump 32 is more stable when the operation.
Furthermore, the fixed section extends along the surface of the base 1 at the position to form a fixed plate, the fixed section is installed on the base 1 through the fixed plate, the fixed plate is in surface contact with the surface of the base 1, and the situation that the surface of the base 1 is damaged due to overlarge pressure generated by the damping piece 61 on the surface of the base 1 when the installation section swings up and down is avoided.
In this embodiment, the fixed section with be equipped with the strengthening rib between the fixed plate, so, the fixed section with be connected between the fixed plate is more firm to improve the stability of fixed section when installing on frame 1.
And, the up end of frame 1 is equipped with the fixed orifices, the fixed plate corresponds fixed orifices department is equipped with the through-hole, it still includes the screw joint spare (not shown in the figure) to fall structure 6 of making an uproar, screw joint spare threaded connection the through-hole with the fixed orifices, so that the fixed plate with frame 1 reciprocal anchorage, the fixed plate passes through the screw joint spare with frame 1 is connected, connects reliably and convenient to detach.
In this embodiment, the noise reduction structure 6 further includes a damping sleeve, the damping sleeve is at least partially disposed in the through hole and sleeved on the periphery of the screw, so as to facilitate eliminating the vibration of the fixing plate in the horizontal direction, and further eliminate the vibration of the air pump 32 in the horizontal direction.
Specifically, the telescopic lateral wall of damping is inwards sunken to be formed with annular joint groove, the both sides wall in annular joint groove respectively with the cooperation of week side joint of the both ends mouth of through-hole helps eliminating the upper and lower vibration of fixed plate to further eliminate the upper and lower vibration of air pump 32.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention, and all modifications and equivalents of the present invention, which are made by the contents of the present specification and the accompanying drawings, or directly/indirectly applied to other related technical fields, are included in the scope of the present invention.

Claims (10)

1. A single cell library preparation system, comprising:
the engine base is provided with a working area and has a front direction and a rear direction in the horizontal direction;
the transfer mechanism comprises an inlet and outlet bin which is movably arranged on the base along the front and back directions, is used for installing the microfluidic chip and can move to the working area along the front and back directions under the driving of external force; and the number of the first and second groups,
the extruding mechanism comprises a manifold plate which is arranged above the working area and can be movably arranged along the vertical direction, and the manifold plate is used for being assembled with the microfluidic chip at the working area when moving downwards to the working area so as to drive the raw materials of the microfluidic chip to flow through the flow channels in sequence from the raw material grooves for molding and flow into the molding grooves.
2. The single cell library preparation system of claim 1, wherein the transfer mechanism further comprises:
a first motor having a first output shaft; and the number of the first and second groups,
the transfer transmission assembly is used for being in transmission connection with the first output shaft and the in-out bin.
3. The single cell library preparation system of claim 2, wherein the housing further has a left-right direction in the horizontal direction;
the first output shaft extends along the left-right direction;
the transfer transmission assembly comprises a gear and a rack which are meshed with each other, the gear is installed on the first output shaft, the rack is arranged at the bottom of the in-out bin, and the rack extends forwards and backwards.
4. The single-cell library preparation system of claim 1, wherein the transfer mechanism further comprises a slide groove provided in one of the base and the in-out chamber, and a slide bar provided in the other, the slide bar extending in the front-back direction and being slidably mounted in the slide groove.
5. The single cell library preparation system of claim 1, wherein the pressing mechanism further comprises an air pump mounted to the housing;
a gas passing channel is formed in the manifold plate, and a gas inlet and a plurality of gas outlets are respectively arranged on two opposite sides of the manifold plate from top to bottom;
the air inlet is communicated with the air passing channel and the outlet of the air pump;
the plurality of air outlets are used for respectively communicating the air passing channel with the plurality of raw material grooves of the microfluidic chip in the working area when the manifold plate moves downwards to the working area.
6. The single cell library preparation system of claim 1, wherein the expression mechanism further comprises:
a second motor having a second output shaft; and the number of the first and second groups,
and the extrusion transmission assembly is in transmission connection with the second output shaft and the multi-manifold plate.
7. The single-cell library preparation system of claim 6, wherein the second output shaft extends in a front-back direction;
the extrusion drive assembly includes a cam mechanism, the cam mechanism including:
a cam mounted to the second output shaft; and the number of the first and second groups,
the ejector rod extends up and down and is provided with a first end and a second end which are opposite to each other, the first end is abutted to the periphery of the cam, the ejector rod can move up and down, and in the downward movement stroke of the ejector rod, the second end is abutted to the top of the multi-manifold plate so as to push the multi-manifold plate to move down.
8. The single cell library preparation system of claim 7, wherein the transfer mechanism comprises a first motor drivingly connected to the access compartment;
the extrusion mechanism comprises an air pump;
the single cell library preparation system further comprises:
the integrated circuit board is arranged on the top of the multi-manifold board and used for electrically connecting the first motor, the second motor and the air pump; and the number of the first and second groups,
the connecting plate is arranged at the top of the multi-manifold plate and is positioned above the integrated circuit board;
and in the downward movable stroke of the ejector rod, the second end is used for abutting against the top of the connecting plate.
9. The single-cell library preparation system of claim 1, further comprising a noise reduction structure disposed on the base, wherein the noise reduction structure is disposed corresponding to the pressing mechanism.
10. The single cell library preparation system of claim 9, wherein the pressing mechanism comprises an air pump mounted to the housing;
the noise reduction structure comprises a vibration reduction piece, the vibration reduction piece is provided with a fixed section and an installation section which are oppositely arranged in the front-back direction, the fixed section is arranged on the machine base, and the installation section is arranged outside the machine base in a suspended mode;
wherein the air pump is mounted to the mounting section.
CN202110977986.8A 2021-08-24 A single cell library preparation system Active CN113845995B (en)

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Application Number Priority Date Filing Date Title
CN202110977986.8A CN113845995B (en) 2021-08-24 A single cell library preparation system

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110977986.8A CN113845995B (en) 2021-08-24 A single cell library preparation system

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CN113845995A true CN113845995A (en) 2021-12-28
CN113845995B CN113845995B (en) 2025-04-18

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103894248A (en) * 2014-04-09 2014-07-02 国家纳米科学中心 Micro-fluidic chip and micro-fluidic chip system for single cell analysis and single cell analyzing method
US20190212233A1 (en) * 2016-11-29 2019-07-11 Stevan Jovanovich Method and apparatus for processing tissue samples
CN110538680A (en) * 2019-08-19 2019-12-06 昆山汇先医药技术有限公司 Micro-fluidic sample processing equipment
US20210214673A1 (en) * 2018-06-01 2021-07-15 S2 Genomics, Inc. Method and apparatus for processing tissue samples
CN216236946U (en) * 2021-08-24 2022-04-08 北京寻因生物科技有限公司 A single cell library preparation system

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103894248A (en) * 2014-04-09 2014-07-02 国家纳米科学中心 Micro-fluidic chip and micro-fluidic chip system for single cell analysis and single cell analyzing method
US20190212233A1 (en) * 2016-11-29 2019-07-11 Stevan Jovanovich Method and apparatus for processing tissue samples
US20210214673A1 (en) * 2018-06-01 2021-07-15 S2 Genomics, Inc. Method and apparatus for processing tissue samples
CN110538680A (en) * 2019-08-19 2019-12-06 昆山汇先医药技术有限公司 Micro-fluidic sample processing equipment
CN216236946U (en) * 2021-08-24 2022-04-08 北京寻因生物科技有限公司 A single cell library preparation system

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