阅读说明：本技术 单细胞文库制备系统及其控制方法、存储介质 (Single cell library preparation system, control method thereof and storage medium ) 是由 黄金城 索海军 焦少灼 李宗文 于 2021-08-24 设计创作，主要内容包括：本发明公开一种单细胞文库制备系统及其控制方法、存储介质,单细胞文库制备系统的控制方法包括：获取微流体芯片的第一特征信息及多岐板的第二特征信息；根据第一特征信息和第二特征信息,确定驱气装置的驱气方案；控制微流体芯片和多岐板活动至设定区域；在确定所各流道与各气道一一对应连通后,控制驱气装置按照驱气方案工作。本发明中,通过对第一特征信息和第二特征信息进行识别,可确定当前所需制备的单细胞的类型及制备过程,从而能够调整驱气装置的驱气方案,使得单细胞文库的制备系统能够灵活适用不同类型的单细胞的制备；通过验证第一特征信息和第二特征信息,有助于加强微流体芯片与多岐板的精准匹配,提高单细胞的制备质量。(The invention discloses a single cell library preparation system, a control method thereof and a storage medium, wherein the control method of the single cell library preparation system comprises the following steps: acquiring first characteristic information of the microfluidic chip and second characteristic information of the manifold plate; determining a purging scheme of the purging device according to the first characteristic information and the second characteristic information; controlling the microfluid chip and the manifold plate to move to a set area; and controlling the purging device to work according to the purging scheme after determining that the flow passages are communicated with the air passages in a one-to-one correspondence manner. According to the method, the type and the preparation process of the single cell required to be prepared at present can be determined by identifying the first characteristic information and the second characteristic information, so that the purging scheme of the purging device can be adjusted, and the preparation system of the single cell library can be flexibly suitable for preparing the single cells of different types; by verifying the first characteristic information and the second characteristic information, the accurate matching of the microfluidic chip and the manifold plate is facilitated to be enhanced, and the preparation quality of single cells is improved.)

1. The control method of the single cell library preparation system is characterized in that the single cell library preparation system comprises a microfluid chip, a manifold plate and an air driving device, wherein the microfluid chip and the manifold plate are respectively and movably arranged, the microfluid chip is provided with a plurality of flow channels, the plurality of flow channels comprise a main flow channel and a plurality of branch flow channels, the inlet ends of the plurality of branch flow channels are used for respectively storing a plurality of materials, the outlet ends of the plurality of branch flow channels are communicated with the main flow channel after being converged, so that the plurality of materials can enter the main flow channel after being prepared into formed single cells at the junctions, the manifold plate is provided with a plurality of air channels, and the air driving device is used for respectively driving the fluid of the plurality of air channels to flow;

the control method of the single cell library preparation system comprises the following steps:

respectively acquiring first characteristic information of the microfluidic chip and second characteristic information of the manifold plate;

determining a purging scheme of the purging device according to the first characteristic information and the second characteristic information;

respectively controlling the microfluid chip and the manifold plate to move to a set area;

and controlling the purging device to work according to the purging scheme after the flow passages are determined to be communicated with the air passages in a one-to-one correspondence manner.

2. The method of controlling the single cell library preparation system of claim 1, wherein the step of determining the purging protocol of the purging device based on the first characteristic information and the second characteristic information comprises:

according to the first feature information, inquiring preset second feature information related to the first feature information in a preset database;

and when the second characteristic information is matched with the preset second characteristic information, inquiring the purging scheme of the gas supply device associated with the preset second characteristic information in the database.

3. The method for controlling the single cell library preparation system of claim 2, wherein the step of determining the purging protocol of the purging device based on the first characteristic information and the second characteristic information further comprises:

and when the first characteristic information is strange characteristic information or the second characteristic information is not matched with the preset second characteristic information, sending a prompt, and recording the corresponding first characteristic information and the second characteristic information to an abnormal log.

4. The method for controlling the single cell library preparation system of claim 1, wherein the step of controlling the purging device to operate according to the purging protocol after determining that each of the flow channels is in one-to-one correspondence with each of the air passages comprises:

after the flow passages are determined to be communicated with the air passages in a one-to-one correspondence mode, the air purging device is controlled to perform pre-air supply on the flow passages through the air passages;

and when the difference value between the first air inlet pressure of each air passage and the second air inlet pressure of each corresponding flow passage is smaller than a preset air pressure difference threshold value, controlling the purging device to work according to the purging scheme.

5. The method for controlling a single-cell library preparation system according to claim 1, wherein the purging device comprises a first purging component corresponding to the main flow channel;

the purging protocol includes:

after the single cell preparation is completed, controlling the first purging component to evacuate so as to drive the fluid of the main flow channel to flow towards the outlet end of the main flow channel.

6. The method of controlling a single-cell library preparation system of claim 1, wherein the purging device comprises a plurality of second purging components corresponding to a plurality of the branch flow paths one-to-one;

the purging protocol includes:

and controlling the second purging assembly to purge so as to drive the fluid of the corresponding branch flow channel to flow towards the outlet end of the second purging assembly.

7. The method of controlling the single cell library preparation system of claim 6, wherein the purging protocol further comprises:

and in the air blowing process of the second purging assembly, controlling the second purging assembly to intermittently pump air so as to intermittently drive the fluid of the corresponding branch flow channel to flow towards the inlet end of the branch flow channel.

8. The method of controlling the single cell library preparation system of claim 1, wherein the single cell library preparation system further comprises an identification device comprising an imaging device or a scanning device;

the step of respectively acquiring first characteristic information of the microfluidic chip and second characteristic information of the manifold plate comprises:

controlling the identification device to identify the characteristic part of the microfluidic chip so as to acquire first characteristic information;

and controlling the identification device to identify the characteristic part of the multi-manifold plate so as to acquire second characteristic information.

9. A single cell library preparation system, comprising:

the main body comprises a base, a microfluid chip and a multi-manifold plate which are respectively movably arranged relative to the base, and an air driving device, wherein the microfluid chip is provided with a plurality of flow channels, the plurality of flow channels comprise a main flow channel and a plurality of branch flow channels, the inlet ends of the plurality of branch flow channels are used for respectively storing a plurality of materials, the outlet ends of the plurality of branch flow channels are communicated with the main flow channel after being converged, so that the plurality of materials can enter the main flow channel after being prepared into formed single cells at the intersection, the multi-manifold plate is provided with a plurality of air channels, and the air driving device is used for respectively driving the fluid of the plurality of air channels to flow; and the number of the first and second groups,

a control device to control the operation of the subject, the control device comprising a memory, a processor, and a control program of a single-cell library preparation system stored on the memory and executable on the processor, the control program of the single-cell library preparation system being configured to implement the steps of the control method of the single-cell library preparation system of any one of claims 1 to 8.

10. A storage medium, characterized in that a control program of a single-cell library preparation system is stored thereon, which when executed by a processor, implements the steps of the control method of the single-cell library preparation system according to any one of claims 1 to 8.

Technical Field

The invention relates to the technical field of single cell library preparation, in particular to a single cell library preparation system, a control method thereof and a storage medium.

Background

The existing single cell library preparation system generally needs manual operation, and the single cell library preparation system generally can only realize a single type of single cell preparation process, so that the application of the single cell library preparation system is limited.

Disclosure of Invention

The invention mainly aims to provide a single cell library preparation system, a control method and a storage medium thereof, and aims to solve the problem that the traditional single cell library preparation system is not applicable.

In order to achieve the above object, the present invention provides a method for controlling a single cell library preparation system, the single cell library preparation system includes a microfluidic chip, a manifold plate and an air-expelling device, the microfluidic chip is provided with a plurality of flow channels, the plurality of flow channels include a main flow channel and a plurality of branch flow channels, inlet ends of the plurality of branch flow channels are used for storing a plurality of materials, outlet ends of the plurality of branch flow channels are converged and communicated with the main flow channel, so that the plurality of materials are made into single cells at the junction and then enter the main flow channel, the manifold plate is provided with a plurality of air channels, and the air-expelling device is used for driving fluid of the plurality of air channels to flow;

the control method of the single cell library preparation system comprises the following steps:

respectively acquiring first characteristic information of the microfluidic chip and second characteristic information of the manifold plate;

determining a purging scheme of the purging device according to the first characteristic information and the second characteristic information;

respectively controlling the microfluid chip and the manifold plate to move to a set area;

and controlling the purging device to work according to the purging scheme after the flow passages are determined to be communicated with the air passages in a one-to-one correspondence manner.

Optionally, the step of determining the purging scheme of the purging device according to the first characteristic information and the second characteristic information includes:

according to the first feature information, inquiring preset second feature information related to the first feature information in a preset database;

and when the second characteristic information is matched with the preset second characteristic information, inquiring the purging scheme of the gas supply device associated with the preset second characteristic information in the database.

Optionally, the step of determining the purging scheme of the purging device according to the first characteristic information and the second characteristic information further includes:

and when the first characteristic information is strange characteristic information or the second characteristic information is not matched with the preset second characteristic information, sending a prompt, and recording the corresponding first characteristic information and the second characteristic information to an abnormal log.

Optionally, after it is determined that each of the flow passages is in one-to-one correspondence with each of the air passages, the step of controlling the purging device to operate according to the purging scheme includes:

after the flow passages are determined to be communicated with the air passages in a one-to-one correspondence mode, the air purging device is controlled to perform pre-air supply on the flow passages through the air passages;

and when the difference value between the first air inlet pressure of each air passage and the second air inlet pressure of each corresponding flow passage is smaller than a preset air pressure difference threshold value, controlling the purging device to work according to the purging scheme.

Optionally, the purging device comprises a first purging component corresponding to the main flow channel;

the purging protocol includes:

after the single cell preparation is completed, controlling the first purging component to evacuate so as to drive the fluid of the main flow channel to flow towards the outlet end of the main flow channel.

Optionally, the purging device includes a plurality of second purging components corresponding to the plurality of branch runners one to one;

the purging protocol includes:

and controlling the second purging assembly to purge so as to drive the fluid of the corresponding branch flow channel to flow towards the outlet end of the second purging assembly.

Optionally, the purging protocol further comprises:

and in the air blowing process of the second purging assembly, controlling the second purging assembly to intermittently pump air so as to intermittently drive the fluid of the corresponding branch flow channel to flow towards the inlet end of the branch flow channel.

Optionally, the single cell library preparation system further comprises an identification device comprising an imaging apparatus or a scanning apparatus;

the step of respectively acquiring first characteristic information of the microfluidic chip and second characteristic information of the manifold plate comprises:

controlling the identification device to identify the characteristic part of the microfluidic chip so as to acquire first characteristic information;

and controlling the identification device to identify the characteristic part of the multi-manifold plate so as to acquire second characteristic information.

In addition, to achieve the above object, the present invention also provides a single cell library preparation system comprising:

the main body comprises a base, a microfluid chip and a multi-manifold plate which are respectively movably arranged relative to the base, and an air driving device, wherein the microfluid chip is provided with a plurality of flow channels, the plurality of flow channels comprise a main flow channel and a plurality of branch flow channels, the inlet ends of the plurality of branch flow channels are used for respectively storing a plurality of materials, the outlet ends of the plurality of branch flow channels are communicated with the main flow channel after being converged, so that the plurality of materials can enter the main flow channel after being prepared into formed single cells at the intersection, the multi-manifold plate is provided with a plurality of air channels, and the air driving device is used for respectively driving the fluid of the plurality of air channels to flow; and the number of the first and second groups,

a control device for controlling the operation of the main body, the control device comprising a memory, a processor and a control program of the single cell library preparation system stored on the memory and operable on the processor, the control program of the single cell library preparation system being configured to implement the steps of the control method of the single cell library preparation system as described above.

In addition, in order to achieve the above object, the present invention also provides a storage medium having stored thereon a control program of a single-cell library preparation system, which when executed by a processor, implements the steps of the control method of the single-cell library preparation system as described above.

According to the technical scheme provided by the invention, the type and the preparation process of the single cell required to be prepared at present can be determined by identifying the first characteristic information and the second characteristic information, so that the purging scheme of the purging device can be adjusted, and the preparation system of the single cell library can be flexibly suitable for the preparation processes of the single cells of different types; in addition, the first characteristic information and the second characteristic information are verified, so that the accurate matching of the microfluidic chip and the manifold plate is facilitated, and the preparation quality of single cells is improved.

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 flow chart of a control method of a single-cell library preparation system according to a first embodiment of the present invention;

FIG. 2 is a schematic flow chart illustrating a control method of the single-cell library preparation system according to the second embodiment of the present invention;

FIG. 3 is a schematic flow chart of a control method of the single-cell library preparation system according to the third embodiment of the present invention;

FIG. 4 is a schematic flow chart illustrating a control method of the single-cell library preparation system according to the fourth embodiment of the present invention;

FIG. 5 is a schematic flow chart of a fifth embodiment of the control method of the single-cell library preparation system provided in the present invention;

FIG. 6 is a schematic flow chart illustrating a control method of the single-cell library preparation system according to the sixth embodiment of the present invention;

FIG. 7 is a schematic flow chart illustrating a control method of the single-cell library preparation system according to the seventh embodiment of the present invention;

FIG. 8 is a schematic flow chart illustrating a control method of the single-cell library preparation system according to the eighth embodiment of the present invention;

FIG. 9 is a schematic structural diagram of an embodiment of a system for preparing a single-cell library according to the present invention;

FIG. 10 is a schematic diagram showing a partial structure of the system for preparing a library of single cells in FIG. 9;

FIG. 11 is a schematic front view showing a partial structure of the system for preparing a single-cell library shown in FIG. 10;

FIG. 12 is a schematic side view showing a partial structure of the system for preparing a single-cell library of FIG. 10;

FIG. 13 is a schematic diagram of a view angle of the microfluidic chip of FIG. 10;

FIG. 14 is a schematic diagram of another view of the microfluidic chip of FIG. 10;

fig. 15 is a schematic structural diagram of a control device of a hardware operating environment according to an embodiment of the present invention.

The reference numbers illustrate:

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.

The existing single cell library preparation system generally needs manual operation, and the single cell library preparation system generally can only realize a single type of single cell preparation process, so that the application of the single cell library preparation system is limited.

In view of the above, the present invention provides a single cell library preparation system including a main body and a control device.

Referring to FIGS. 9-14, embodiments of the single cell library preparation system of the present invention are shown.

Referring to fig. 9, the main body of the single-cell library preparation system 1 of the present invention includes a housing 100, and a mounting cavity is formed inside the housing 100, and is used for accommodating at least part of the functional components of the single-cell library preparation system 1; the outer wall of the casing 100 is provided with an opening communicating with the installation cavity.

It is understood that the opening may be formed at any position of the casing 100, for example, at the top or any side of the casing 100, and for the convenience of understanding, in the following embodiments, the casing 100 is defined to have a front-rear direction and a left-right direction which are arranged to cross each other in a horizontal direction, wherein the opening is formed at the front side of the casing 100.

A set area is defined in the mounting cavity; the microfluidic chip 200 is located at a side of the setting region in the horizontal direction, for example, at the front side of the setting region, and the microfluidic chip 200 is movably mounted on the casing 100 in the front-back direction so as to be accommodated in the mounting cavity and be capable of translating from the opening to the outside of the casing 100 in the front-back direction. Specifically, the microfluidic chip 200 passes at least the set region during the movement in the front-back direction.

Further, in order to provide the smoothness and accuracy of the back-and-forth movement of the microfluidic chip 200, in an embodiment, the single-cell library preparation system 1 further comprises an access chamber 230, and the access chamber 230 is movably mounted on the housing 100 along the back-and-forth direction so as to be accommodated in the mounting cavity and can be horizontally moved from the opening to the outside of the housing 100 along the back-and-forth direction. The microfluidic chip 200 is mounted on the in-out bin 230 so as to be driven by the in-out bin 230 to enter the mounting cavity or move out of the casing 100.

The inlet and outlet bin 230 is formed with an installation position for positioning and installing the microfluidic chip 200, the specific expression form of the installation position is not limited, and the installation position may be an installation groove formed in the upper end surface of the inlet and outlet bin 230 or a positioning structure arranged on the upper end surface of the inlet and outlet bin 230, the positioning structure includes a positioning convex portion and a positioning concave portion, one of the positioning convex portion and the positioning concave portion is arranged on the inlet and outlet bin 230, and the other is arranged on the microfluidic chip 200, so that when the positioning convex portion is in concave-convex fit with the positioning concave portion, the microfluidic chip 200 is accurately positioned on the installation position of the inlet and outlet bin 230.

The forward and backward movement of the in-out bin 230 can be directly realized through manual operation of a user, based on this, a sliding rail mechanism can be arranged between the in-out bin 230 and the inner cavity wall of the installation cavity at the position where the in-out bin 230 is located, and the in-out bin 230 can be slidably installed on the machine shell 100 along a set path through sliding matching of a sliding groove and a sliding protrusion in the sliding rail mechanism.

Of course, the in-out bin 230 can also be automatically controlled to move back and forth by an electric control component, and based on this, there are various specific schemes of the electric control component, such as a screw nut mechanism, a directional rocker mechanism, and the like, please refer to fig. 10 to 14, in an embodiment, the electric control component includes a rack 231, a gear 232, and a first motor 233, wherein the rack 231 extends in the front-back direction and is fixedly installed on the inner cavity wall of the installation cavity, the gear 232 is installed on the in-out bin 230 in a manner of being capable of rotating back and forth along the left-right axis and is engaged with the rack 231, and the first motor 233 is connected with the gear 232 in a driving manner.

In addition, the specific expression form of the microfluidic chip 200 is not limited, please refer to fig. 10, fig. 13 and fig. 14, in an embodiment, the microfluidic chip 200 may include a plurality of chip units 200a, and the plurality of chip units 200a are sequentially arranged along a horizontal direction, it can be understood that the plurality of chip units 200a may be integrally arranged or separately arranged, wherein when the plurality of chip units 200a are separately arranged, every two adjacent chip units 200a are detachably connected, and a specific detachable connection manner may be one or more of screw fastening, buckling fastening, bonding fastening and adsorption fastening.

Each of the chip monomers 200a has a first side 210 and a second side 220 opposite to each other along the thickness direction thereof, and in general, in order to better perform a single cell preparation operation and to further facilitate the compact structural layout of the single cell library preparation system 1, the thickness direction of the chip monomer 200a is generally upward and downward, wherein the first side 210 may be, but is not limited to, an upper side of the chip monomer 200a, and the second side 220 corresponds to a lower side of the chip monomer 200 a.

It is understood that a plurality of flow channels are formed in each chip unit 200a, and the plurality of flow channels include a main flow channel 221 and a plurality of branch flow channels 222, wherein the main flow channel 221 may be one or more.

The flow channels have inlet ends and outlet ends which are arranged oppositely, the inlet ends of a plurality of flow channels can be formed on the first side 210, the inlet ends of a plurality of branch flow channels 222 are used for storing a plurality of raw materials, specifically, a plurality of grooves can be arranged on the first side 210, and the grooves are communicated with the inlet ends of the flow channels in a one-to-one correspondence manner; the slot is not limited, and when the thickness of the chip unit 200a is enough, the slot may be directly opened on the first side 210; when the plate thickness of the chip unit 200a is thin, a plurality of cylinders may be protruded on the first side 210 of the chip unit 200a, and the plurality of cylinders and the chip unit 200a may be integrally disposed or detachably disposed in a separate manner. The plurality of cylinders are in one-to-one correspondence to form a plurality of grooves. For the convenience of distinction, among the plurality of tanks, the stock tank 211 is disposed corresponding to the branch flow channel 222, and the finished product tank 212 is formed corresponding to the main flow channel 221.

The flow channel may be formed inside the chip unit 200a, or may be formed on the second side 220 of the chip unit 200 a; when the flow channel is formed on the second side 220 of the chip unit 200a, the microfluidic chip 200 further includes a cover film covering the second side 220 of the chip unit 200 a; the cover film may be made of a Cyclic Olefin Copolymer (COC) material or the like.

In the plurality of branched runners 222, the outlet ends of all branched runners 222 may be directly intersected, or at least two branched runners 222 are arranged to intersect with the rest branched runners 222 after intersecting first according to the single cell preparation requirement; or at least two branch runners 222 are arranged to be intersected to form a group, and a plurality of groups are sequentially intersected and then integrally intersected to one position.

In a plurality of the branch channels 222, an adjusting structure 223 may be disposed at least one of the branch channels 222 according to an actual preparation requirement, and the adjusting structure 223 may be disposed as an outlet end of the branch channel 222 to control a flow rate and a flow speed of the branch channel 222, for example, when the branch channel 222 circulates particulate materials, such as nuclei or magnetic beads, the adjusting structure 223 may adjust the nuclei or magnetic beads to be sequentially discharged according to a set number.

The manifold plate 300 is accommodated in the mounting cavity and located above the set region, and the manifold plate 300 is movably arranged in the up-down direction so as to be capable of moving down to the set region and stacking with the microfluidic chip 200; the manifold plate 300 is provided with a plurality of air passages, which are arranged corresponding to the plurality of flow passages, so that when the manifold plate 300 moves downward to be close to the microfluidic chip 200, the plurality of air passages communicate with the plurality of flow passages in a one-to-one correspondence.

Like the microfluidic chip 200, the up-and-down movement of the manifold 300 can be directly realized by manual operation of a user, and based on this, a slide rail mechanism can also be arranged between the manifold 300 and the inner cavity wall of the mounting cavity at the position of the manifold 300, and the manifold 300 can be slidably mounted on the housing case 100 along a set path by the sliding fit between the sliding groove and the sliding protrusion in the slide rail mechanism.

Of course, the up-and-down movement of the manifold plate 300 can also be automatically controlled by an electric control component, and based on this, there are various specific schemes of the electric control component, such as a screw nut mechanism, a directional rocker mechanism, and the like, please refer to fig. 10 to 14, in an embodiment, the electric control component includes a second motor 311, an eccentric rotating structure 313 and a propping protrusion 314, wherein the eccentric rotating structure 313 deflects up and down along the axis of the horizontal direction, the upper end of the propping protrusion 314 abuts against the outer peripheral edge of the eccentric rotating structure 313, and the lower end of the propping protrusion 314 abuts against the manifold plate 300, so that when the eccentric rotating structure 313 rotates, the propping protrusion 314 is intermittently driven to move up and down, and then the manifold plate 300 is driven to move up and down.

Further, when the control device 500 includes a circuit board, the circuit board is disposed between the abutting protrusion 314 and the manifold board 300, the electric control component of the manifold board 300 may further include a push plate 312, the push plate 312 is disposed between the circuit board and the abutting protrusion 314, and is movably disposed along the vertical direction, so that when the push plate is pushed by the abutting protrusion 314 to move up and down, the manifold board 300 can be driven to move, which is helpful to expand the stress area of the manifold board 300, and avoids the stress concentration from causing the motion unbalance or the structural damage of the manifold board 300.

Further, a guide hole and a guide shaft 315 which are used in cooperation can be arranged between the manifold plate 300 and the machine base, specifically, a plurality of guide shafts 315 can be arranged on the periphery of the manifold plate 300 or the push plate 312, a guide hole is arranged at a corresponding position of the machine base, and the manifold plate 300 and/or the push plate 312 can move up and down along an accurate path by mutual sliding between the guide hole and the guide shaft 315.

The purging device 400 includes, for example, a pump body 410, where the pump body 410 is configured to act on a plurality of air passages, so that an air flow can flow in the air passages and corresponding flow passages according to a set direction; the pump body 410 can be provided in one or more; the pump body 410 may be mounted to the housing by, for example, a mounting bracket 411.

Specifically, the mounting bracket 411 may be substantially longitudinally arranged, one end of the mounting bracket 411 is fixedly connected to the base, the other end of the mounting bracket 411 is connected to the pump body 410, and the pump body 410 is suspended on the base, so that the vibration generated by the pump body 410 during operation can be consumed by the semi-suspension damping of the mounting bracket 411.

Further, a shock absorbing member 412 may be disposed at a fixed connection between the mounting bracket 411 and the base, and the shock absorbing member 412 is abutted against the mounting bracket 411 and the base to reduce the shock between the mounting bracket 411 and the base.

In addition, the purging device 400 further includes a valve body assembly corresponding to each of the air passages, and the valve body assembly may be one or more of a switch valve, a flow valve and a pressure valve, so that the flow rate and the flow speed of the airflow flowing through the air passages and the corresponding flow passages can be adjusted.

For ease of understanding, the purging device 400 may include a first purging component and a second purging component, wherein the first purging component correspondingly regulates the fluid movement driving the branch flow passage 222; the second purging component drives the fluid of the primary channel 221 to move correspondingly.

Furthermore, based on the above-described embodiment, the body may further comprise identification means, for example comprising an imaging device or a scanning device, capable of identifying the microfluidic chip 200 and the manifold plate 300 in order to determine the type of the microfluidic chip 200 and the manifold plate 300.

It is understood that, in the above-described embodiment, the single-cell library preparation system 1 can be applied to the preparation of a variety of single cells. Referring to fig. 13 to 14, in an embodiment, the microfluidic chip 200 includes three material storage slots 211 and one product slot 212, and the three material storage slots 211 and the product slot 212 are sequentially arranged at intervals along a length direction of the microfluidic chip 200; in the direction close to the finished product tank 212, the three storage tanks 211 are used for storing oil phase, cell nuclei and magnetic beads respectively, wherein the branch flow channels 222 corresponding to the cell nuclei and the magnetic beads can be firstly converged, so that after the cell nuclei are combined with the magnetic beads, the branch flow channels 222 corresponding to the oil phase are converged with the flow channels of the combined cell nuclei and magnetic beads, so that the oil phase wraps the combination of the cell nuclei and the magnetic beads, single cells or microfluids are finally formed, the single cells enter the finished product tank 212 to be collected, and after a bar code is added, the oil phase is removed, so that a library for sequencing is obtained.

Referring to fig. 15, fig. 15 is a schematic structural diagram of a control device 500 of a hardware operating environment according to an embodiment of the present invention.

As shown in fig. 15, the control device 500 may include: a processor 501, e.g. a CPU, a communication bus 502, a user interface 503, a network interface 504, a memory 505. Wherein a communication bus 502 is used to enable connective communication between these components. The user interface 503 may comprise a Display screen (Display), an input unit such as a Keyboard (Keyboard), and the optional user interface 503 may also comprise a standard wired interface, a wireless interface. The network interface 504 may optionally include a standard wired interface, a wireless interface (e.g., WI-FI interface). The memory 505 may be a high-speed RAM memory or a non-volatile memory (e.g., a magnetic disk memory). The memory 505 may alternatively be a storage device separate from the processor 501 described above.

Those skilled in the art will appreciate that the configuration shown in fig. 15 does not constitute a limitation of the control device 500, and may include more or fewer components than those shown, or some components may be combined, or a different arrangement of components.

As shown in fig. 15, the memory 505, which is a kind of computer storage medium, may include therein an operating system, a network communication module, a user interface module, and a single cell library preparation system 1 control program.

The control device 500 shown in fig. 15 calls the single-cell library preparation system 1 control program stored in the memory 505 by the processor 501, and performs the following operations:

respectively acquiring first characteristic information of the microfluidic chip 200 and second characteristic information of the manifold plate 300;

determining a purging scheme of the purging device 400 according to the first characteristic information and the second characteristic information;

respectively controlling the microfluidic chip 200 and the manifold plate 300 to move to a set area;

and after the flow passages are determined to be communicated with the air passages in a one-to-one correspondence manner, controlling the purging device 400 to work according to the purging scheme.

Further, the processor 501 may call the single cell library preparation system 1 control program stored in the memory 505, and further perform the following operations:

the step of determining the purging scheme of the purging device 400 according to the first characteristic information and the second characteristic information comprises:

according to the first feature information, inquiring preset second feature information related to the first feature information in a preset database;

and when the second characteristic information is matched with the preset second characteristic information, inquiring the purging scheme of the gas supply device associated with the preset second characteristic information in the database.

Further, the processor 501 may call the single cell library preparation system 1 control program stored in the memory 505, and further perform the following operations:

the step of determining the purging scheme of the purging device 400 according to the first characteristic information and the second characteristic information further includes:

and when the first characteristic information is strange characteristic information or the second characteristic information is not matched with the preset second characteristic information, sending a prompt, and recording the corresponding first characteristic information and the second characteristic information to an abnormal log.

Further, the processor 501 may call the single cell library preparation system 1 control program stored in the memory 505, and further perform the following operations:

after determining that each flow passage is communicated with each air passage in a one-to-one correspondence manner, the step of controlling the purging device 400 to operate according to the purging scheme includes:

after determining that the flow passages are communicated with the air passages in a one-to-one correspondence manner, controlling the purging device 400 to perform pre-gas supply on the flow passages through the air passages;

and when the difference value between the first air inlet pressure of each air passage and the second air inlet pressure of each corresponding flow passage is smaller than a preset air pressure difference threshold value, controlling the purging device 400 to work according to the purging scheme.

Further, the processor 501 may call the single cell library preparation system 1 control program stored in the memory 505, and further perform the following operations:

the purging device 400 comprises a first purging component corresponding to the primary channel 221;

the purging protocol includes:

after the single cell preparation is completed, controlling the first purging component to evacuate so as to drive the fluid of the main channel 221 to flow toward the outlet end of the main channel 221.

Further, the processor 501 may call the single cell library preparation system 1 control program stored in the memory 505, and further perform the following operations:

the purging device 400 includes a plurality of second purging components corresponding to the plurality of branch runners 222 one to one;

the purging protocol includes:

controlling the second purging assembly to purge air to drive the fluid in the corresponding branch flow channel 222 toward the outlet end thereof.

Further, the processor 501 may call the single cell library preparation system 1 control program stored in the memory 505, and further perform the following operations:

the purging protocol further comprises:

and controlling the second purging assembly to intermittently pump air during the air blowing process of the second purging assembly so as to intermittently drive the fluid of the corresponding branch flow passage 222 to flow towards the air inlet end of the corresponding branch flow passage.

Further, the processor 501 may call the single cell library preparation system 1 control program stored in the memory 505, and further perform the following operations:

the single cell library preparation system 1 further comprises an identification device comprising an imaging device or a scanning device;

the step of acquiring first characteristic information of the microfluidic chip 200 and second characteristic information of the manifold plate 300, respectively, includes:

controlling the identification device to identify the characteristic part of the microfluidic chip 200 to acquire first characteristic information;

the identification device is controlled to identify the characteristic part of the manifold board 300 so as to acquire the second characteristic information.

In addition, based on the single cell library preparation system 1, the present invention further provides a control method of the single cell library preparation system 1, please refer to fig. 1 to 8, which show an embodiment of the control method of the single cell library preparation system 1 provided by the present invention.

Referring to fig. 1, in a first embodiment of the method for controlling the single cell library preparation system 1 according to the present invention, the method for controlling the single cell library preparation system 1 includes:

s10: respectively acquiring first characteristic information of the microfluidic chip 200 and second characteristic information of the manifold plate 300;

in this embodiment, the first characteristic information may be used to characterize the relevant characteristics of the microfluidic chip 200, and the relevant characteristics of the microfluidic chip 200 include, for example, the types of materials in the microfluidic chip 200, the position information of each storage tank 211 and the product tank 212, the arrangement and intersection of each branch channel 222 and the main channel 221, and the like, so as to uniquely and accurately determine the characteristics of the microfluidic chip 200 related to the single cell preparation process.

The second characteristic information can be used for characterizing relevant characteristics of the manifold plate 300, for example, the relevant characteristics of the manifold plate 300 include specifications and layout schemes of each airway, position information of each airway, specifications of valve body components corresponding to each airway, and the like in the manifold plate 300, and the characteristics of the manifold plate 300 related to the single cell preparation process can be uniquely and accurately determined.

It is understood that the determination of the specific manner of the first characteristic information and the second characteristic information may correspond to the improvement of the structure of the single cell library preparation system 1, for example, in an embodiment, if the second characteristic information includes the position information of each airway, each airway of the multi-manifold plate 300 may be movably configured, so that the position of each airway can be adjusted separately, which may be suitable for docking different specifications of the microfluidic chip 200; in an embodiment, if the second characteristic information includes specifications of valve body components corresponding to each air channel, etc., when the microfluidic chip 200 is dealing with different purging requirements, the valve body components may be adjusted to have different specifications or different operating states, so as to enhance the applicability of the single cell library preparation system 1.

S20: determining a purging scheme of the purging device 400 according to the first characteristic information and the second characteristic information;

it can be understood that when the first characteristic information and the second characteristic information are determined and matched, the type and the related preparation mode of the single cell to be prepared currently can be uniquely and accurately determined, the preparation mode includes the combination sequence, the flow demand and the like of each material, the purging device 400 corresponds to the above information and can match out a suitable purging scheme, the purging direction includes whether the purging device 400 is in an air pumping state or an air blowing state, the air pressure, the air supply frequency and the like, and the method is not limited in this respect and can be adjusted according to practical application.

S30: respectively controlling the microfluidic chip 200 and the manifold plate 300 to move to a set area;

it is understood that when the first characteristic information and the second characteristic information are determined, or the purging protocol is determined, the single cell preparation process may be started, the movement of the microfluidic chip 200 and the movement sequence of the manifold plate 300 are not limited, and the movement manner is also not limited, for example, in an embodiment, the microfluidic chip 200 may be first positioned and installed in the in-out bin 230 that is movably drawn out, and then the in-out bin 230 is operated to drive the microfluidic chip 200 to move to be in a set region; next, after the relative position between the manifold plate 300 and the microfluidic chip 200 in the horizontal direction is adjusted, the manifold plate moves downward until each air channel directly abuts against each flow channel, and it should be noted that the abutting of each air channel and each flow channel is generally configured as a sealed connection, and can be implemented by providing a sealing structure at the abutting position.

S40: and after the flow passages are determined to be communicated with the air passages in a one-to-one correspondence manner, controlling the purging device 400 to work according to the purging scheme.

It can be understood that, after it is determined that each flow channel is communicated with each air passage in a one-to-one correspondence manner and the communication position is sealed, the control device 500 may control the purging device 400 to operate, so that the purging device 400 performs purging according to the determined purging scheme, thereby completing the single cell preparation and collection process.

In the technical scheme provided by the invention, the type and the preparation process of the single cell required to be prepared at present can be determined by identifying the first characteristic information and the second characteristic information, so that the purging scheme of the purging device 400 can be adjusted, and the preparation system of the single cell library can be flexibly suitable for the preparation processes of the single cells of different types; in addition, by verifying the first characteristic information and the second characteristic information, the precise matching of the microfluidic chip 200 and the manifold plate 300 is facilitated to be enhanced, and the preparation quality of single cells is improved.

Referring to fig. 2, in the second embodiment of the control method of the single-cell library preparation system 1 according to the present invention, the step S20: according to the first characteristic information and the second characteristic information, determining the purging scheme of the purging device 400 comprises:

s21: according to the first feature information, inquiring preset second feature information related to the first feature information in a preset database;

s22: and when the second characteristic information is matched with the preset second characteristic information, inquiring the purging scheme of the gas supply device associated with the preset second characteristic information in the database.

It is understood that the control device 500 may pre-establish a database, thereby creating a one-to-one mapping relationship among the first characteristic information, the second characteristic information and the purging scheme. Specifically, the database establishment process may include: the method comprises the steps of collecting multiple kinds of first characteristic information required at present in advance, wherein the multiple kinds of first characteristic information can be classified according to actual needs and types, timestamps, preparation processes and the like of single cells, and are marked as preset first characteristic information; next, determining a suitable characteristic of the manifold board 300 for the preset first characteristic information, and defining the characteristic as preset second characteristic information; and then, determining a proper purging scheme aiming at the preset first characteristic information and the preset second characteristic information.

By pre-establishing one-to-one mapping correlation among the first characteristic information, the second characteristic information and the purging scheme, after at least one of the first characteristic information, the second characteristic information and the purging scheme is determined, the rest two characteristics can be determined uniquely or properly, and efficient and accurate preparation of the single cells required to be prepared currently is realized.

In this embodiment, the preset second characteristic information can be determined through the first characteristic information, whether the currently acquired second characteristic information is accurately matched with the currently acquired first characteristic information can be checked through identifying and comparing the second characteristic information with the preset second characteristic information, if not, the subsequent preparation operation can be directly terminated, and the loss can be stopped in time; if the first characteristic information is matched with the second characteristic information, the gas purging scheme corresponding to the preset second characteristic information is further identified and compared, and the gas purging scheme obtained through query is determined to be the finally executed gas purging scheme.

Further, in order to improve the accuracy of the preparation, in an embodiment, the control device 500 may record each preparation process, count the accuracy of the purging scheme determined by the first characteristic information and the second characteristic information, and send a prompt to alert the user that the purging scheme in the database is not the optimal purging scheme when the accuracy reaches a preset low value, so as to suggest the user to adjust and optimize.

Referring to fig. 3, in a third embodiment of the control method of the single-cell library preparation system 1 according to the present invention, the step S20: determining the purging scheme of the purging device 400 according to the first characteristic information and the second characteristic information further comprises:

s23: and when the first characteristic information is strange characteristic information or the second characteristic information is not matched with the preset second characteristic information, sending a prompt, and recording the corresponding first characteristic information and the second characteristic information to an abnormal log.

It can be understood that, since the first characteristic information, the second characteristic information and the purging scheme are in one-to-one mapping association, in principle, after one of the first characteristic information, the second characteristic information and the purging scheme is determined, the remaining two characteristics can be uniquely determined, so that in the process of querying the database, the first characteristic information, the second characteristic information or the purging scheme can be firstly compared and verified according to actual needs.

In this embodiment, the first characteristic information may be verified first, and when the first characteristic information is strange characteristic information, that is, the first characteristic information is not queried in the database, the current first characteristic information may be determined to be an error or a new type of microfluidic chip 200, and a prompt may be issued to remind the user to perform manual determination, and the process and related information thereof are recorded in an abnormal log.

In this embodiment, when the second characteristic information is not matched with the preset second characteristic information, a prompt may be sent to remind the user to perform manual determination, and the process and the related information thereof are recorded in the abnormal log.

The abnormal log can be used as the argument of the subsequent processes of analysis, summarization and the like of the user, and can also be set to be capable of further inquiring an abnormal record when the first characteristic information, the second characteristic information or the gas purging scheme is abnormal in the process of inquiring the first characteristic information and the second characteristic information in a database, and if the history condition occurs in the abnormal record, the abnormal record can be directly processed according to a history processing scheme or connected with the history processing scheme and sent to the user together; otherwise, if the history situation does not occur in the abnormal record, the prompt can be directly sent to the user.

Referring to fig. 4, in four embodiments of the control method of the single-cell library preparation system 1 of the present invention, the step S40: after determining that each flow passage is communicated with each air passage in a one-to-one correspondence manner, controlling the purging device 400 to operate according to the purging scheme includes:

s41: after determining that the flow passages are communicated with the air passages in a one-to-one correspondence manner, controlling the purging device 400 to perform pre-gas supply on the flow passages through the air passages;

s42: and when the difference value between the first air inlet pressure of each air passage and the second air inlet pressure of each corresponding flow passage is smaller than a preset air pressure difference threshold value, controlling the purging device 400 to work according to the purging scheme.

In this embodiment, after the manifold 300 is connected to the microfluidic chip 200, the purging device 400 may first pre-supply air to each air channel, so that the air flow with a set flow rate and flow velocity flows through each air channel and each corresponding flow channel; the user can record that the air pressure, the flow or the flow rate entering each air passage is the first air pressure, the first flow or the first flow rate in the circulation process of pre-air supply; the air pressure, the flow or the flow rate entering each flow channel is second air pressure, second flow or second flow rate, whether the sealing effect of the connection part between each air channel and each flow channel is up to the standard can be basically determined by comparing whether the air pressure difference value between the first air pressure and the second air pressure exceeds a preset air pressure difference threshold value, whether the flow difference value between the first flow and the second flow exceeds a preset flow difference threshold value and whether the flow rate difference value between the first flow and the second flow exceeds a preset flow difference threshold value, and if the sealing effect of the connection part between each air channel and each flow channel is up to the standard, a subsequent purging scheme can be carried out; and if the standard is not met, prompting the user to adjust.

Based on the above embodiments, referring to fig. 5, in a fifth embodiment of the control method of the single-cell library preparation system 1 provided by the present invention, the purging device 400 includes a plurality of second purging components corresponding to the plurality of branch flow channels 222 one by one; the purging protocol includes:

s421: controlling the second purging assembly to purge air to drive the fluid in the corresponding branch flow channel 222 toward the outlet end thereof.

It can be understood that, since the purging devices 400 are all applied to the air channel, when the second purging assembly is used for purging air, the fluid and the like can be driven to flow from the inlet end of the branch flow channel 222 to the outlet end of the branch flow channel 222, so as to drive the material at the branch flow channel 222 to sequentially flow according to a set speed or frequency.

When at least one branch flow channel 222 is provided with the adjusting structure 223, the adjusting structure 223 can be matched to work by adjusting the purging scheme of the second purging component, so as to achieve the purpose of controlling the flow rate and the flow velocity of the branch flow channel 222:

for example, in one embodiment, the adjusting structure 233 includes an elastic film layer covering the outlet end of the branch flow channel 222, and a through hole is formed through the elastic film layer along the feeding direction of the branch flow channel 222, so that when the elastic film layer is driven by an external force along the feeding direction to deform, the through hole is opened and exposed, and when the external force is removed, the elastic film layer is reset to close the through hole; based on this, when the second purging component purges the branch flow channel 222, the external force may be applied to the elastic film layer, and the deformation degree of the elastic film layer may be correspondingly driven by adjusting the purging parameters of the second purging component, so as to adjust the aperture of the via hole, where the via hole may be used for, for example, cell nuclei or magnetic beads to be sequentially and sequentially discharged according to a set number.

For example, in another embodiment, the branch flow channel 222 has a first side wall and a second side wall opposite to each other along the radial direction, and the adjusting structure 233 includes a rotating plate extending from the first side wall toward the second side wall, and one end of the rotating plate is rotatably mounted on the first side wall, so that the other end of the rotating plate can be driven by an external force to turn toward the feeding direction to open the branch flow channel 222 and turn away from the feeding direction to close the branch flow channel 222. Similarly, when the second purging component purges the branch flow channel 222, the external force may be applied to the rotating plate, and the purging parameters of the second purging component may be adjusted to correspondingly drive the turning angle of the rotating plate, so as to adjust the distance between the end edge of the rotating plate and the second side wall, and the interval between the end edge of the rotating plate and the second side wall may be used for passing through, for example, cell nuclei or magnetic beads flowing through the branch flow channel 222, so that the cell nuclei or the magnetic beads may be sequentially discharged according to the set number by adjusting the purging parameters of the second purging component according to actual needs.

Based on the above embodiments, referring to fig. 6, in a sixth embodiment of the control method of the single-cell library preparation system 1 provided by the present invention, the purging scheme further includes:

s422: and controlling the second purging assembly to intermittently pump air during the air blowing process of the second purging assembly so as to intermittently drive the fluid of the corresponding branch flow passage 222 to flow towards the air inlet end of the corresponding branch flow passage.

It can be understood that the second purging component mainly ensures that the materials are combined to prepare single cells through the air blowing operation, in the process, the second purging component can be set to intermittently pump air, for example, the second purging component can properly pump air in the middle stage of preparation or the later stage of preparation, the materials on each flow channel can be dredged to a certain extent, especially when the materials in the corresponding branch flow channel 222 are granular materials, the situation that the outlet end of the corresponding branch flow channel 222 is blocked due to accumulation due to unstable air pressure or other reasons can occur, through the air pumping process, the blocking situation can be dredged, the abnormality can be eliminated, and the high efficiency and high accuracy of the single cell preparation process can be realized.

Next, referring to fig. 7, in a seventh embodiment of the control method of the single-cell library preparation system 1 provided in the present invention, the purging device 400 includes a first purging component corresponding to the main channel 221; the purging protocol includes:

s423: after the single cell preparation is completed, controlling the first purging component to evacuate so as to drive the fluid of the main channel 221 to flow toward the outlet end of the main channel 221.

It can be understood that when the single cell preparation is completed, a part of the single cells or microfluids are accumulated in the finished product tank 212 or flow in the main flow channel 221, and the fluid in the main flow channel 221 can be driven to flow towards the outlet end of the main flow channel 221 by controlling the first purging assembly to evacuate air, so that the prepared single cells or microfluids can be rapidly and thoroughly collected.

In addition, referring to fig. 8, in the eighth embodiment of the control method of the single cell library preparation system 1 provided by the present invention, the single cell library preparation system 1 further includes a recognition device, and the recognition device includes an imaging device or a scanning device; the step S10: the acquiring the first characteristic information of the microfluidic chip 200 and the second characteristic information of the manifold plate 300, respectively, includes:

s11: controlling the identification device to identify the characteristic part of the microfluidic chip 200 to acquire first characteristic information;

s12: the identification device is controlled to identify the characteristic part of the manifold board 300 so as to acquire the second characteristic information.

It is understood that the first characteristic information and the second characteristic information may be obtained in various manners, specifically, the first characteristic information and the second characteristic information may be formed on the microfluidic chip 200 and the manifold 300 in any suitable manner, and the characteristic portions forming the microfluidic chip 200 and the manifold 300 may be presented in a manner of, for example, identifying images, descriptions, serial numbers, and the like, and according to the specific expression forms of the characteristic portions, the type of a suitable recognition device may be determined, for example, when the characteristic portions are images or characters, the recognition device may be set as an imaging device, and by capturing the images of the characteristic portions and recognizing the images, the corresponding first characteristic information or second characteristic information may be determined; when the feature part is a serial number, the identifying device may be set as a scanning device, and by scanning the serial number of the feature part and identifying the serial number, corresponding first feature information or second feature information and the like may be determined, which is not described in detail herein.

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.