CN210683796U

CN210683796U - Enrichment and separation system

Info

Publication number: CN210683796U
Application number: CN201921702861.9U
Authority: CN
Inventors: B·瓦希迪; 王涛; 李东文; 祝晨; 林顺迎
Original assignee: Zhuhai Livzon Cynvenio Diagnostics Ltd
Current assignee: Zhuhai Livzon Cynvenio Diagnostics Ltd
Priority date: 2019-10-11
Filing date: 2019-10-11
Publication date: 2020-06-05
Anticipated expiration: 2029-10-11

Abstract

An enrichment and separation system relates to the technical field of medical instruments. The enrichment and separation system comprises a supporting device, an operation and control switch device, a multi-coupler device and a sample adding arm device; the control switch device, the multi-coupler device and the sample adding arm device are respectively connected with the supporting device; the chip is arranged in the multi-coupler device and can move up and down along the multi-coupler device; the control switch device is connected with the chip; when the control switch device is turned on or off, the control switch device can push the chip upwards or downwards; the sample adding arm device can move and reciprocate among the liquid suction gun head frame, the reagent pipe frame, the sample frame, the multi-connector device and the waste device. An object of the utility model is to provide an enrichment piece-rate system to the experiment precision that exists is lower among the certain extent solved prior art, the reliability is relatively poor, and occupy the technical problem that the manpower time is long, inefficiency.

Description

Enrichment and separation system

Technical Field

The utility model relates to the technical field of medical equipment, particularly, relate to an enrichment piece-rate system.

Background

Circulating tumor cells, abbreviated as CTCs, are a collective term for the various types of tumor cells present in peripheral blood. In 1869, the concept of circulating tumor cells was first proposed by Ashworth, an australian medical doctor. Tumor cells invade peripheral tissues of primary tumor cells, enter blood and lymphatic systems to form circulating tumor cells CTC, are transported to a far-end tissue, exude, adapt to a new microenvironment, and finally are sown, proliferated and colonized to form a metastasis, so that the tumor cells are spread and transferred to other organs of a body. Therefore, the early detection of CTC in blood plays an important guiding role in patient prognosis judgment, curative effect evaluation and individualized treatment.

In the prior art, a biological magnetic bead which is combined with target CTC cells in a reaction way is artificially added into a target sample, and after a series of mixing treatment is carried out in an external test tube, the CTC cells are labeled by a reagent reaction and the attached magnetic bead can be adsorbed. And adding the sample into the chip by a sample injector at a certain flow rate and volume, adsorbing the target cells combined with the biological magnetic beads by a magnet, and removing redundant cells to achieve the effect of enriching or separating the target cells. Finally, residual cells in the chip are used for analyzing the state of the patient, so that powerful data support is provided for clinic.

However, the prior art has the following problems:

1. the process of injecting the sample into the chip after mixing is manual operation, the flow rate and the capacity are difficult to guarantee, and the experimental precision is influenced.

2. The steps of the preparation and use processes in the early stage of the experiment are multiple, errors are easy to miss, and the reliability of the experiment is influenced; in addition, the problems of long time of occupying manpower, low efficiency and the like exist.

SUMMERY OF THE UTILITY MODEL

An object of the utility model is to provide an enrichment piece-rate system to the experiment precision that exists is lower among the certain extent solved prior art, the reliability is relatively poor, and occupy the technical problem that the manpower time is long, inefficiency.

The embodiment of the utility model is realized like this:

an enrichment and separation system comprises a supporting device, an operation and control switch device, a multi-coupler device and a sample adding arm device; the control switch device, the multi-coupler device and the sample adding arm device are respectively connected with the supporting device;

a chip is arranged in the multi-coupler device and can move up and down along the multi-coupler device; the control switch device is connected with the chip; when the control switch device is turned on or off, the control switch device can push the chip upwards or downwards;

the supporting device is sequentially provided with a sample rack for storing samples, a reagent pipe rack for storing reagent pipes, a liquid suction gun head rack for storing liquid suction gun heads and a waste device for scraping the liquid suction gun heads;

the sample adding arm device can move and reciprocate among the liquid suction gun head frame, the reagent pipe frame, the sample frame, the multi-connector device and the waste device.

Optionally, the enrichment and separation system further comprises a multi-way valve micro-flow pump control device and a liquid storage device; when the control switch device pushes the chip upwards to load, the chip is communicated with the liquid storage device through the multi-way valve microflow pump control device;

the liquid storage device comprises a bottom buffer liquid bottle, a top buffer liquid bottle and a waste liquid bottle;

the multi-way valve microfluidic control device comprises a first shunt, a second shunt, a first confluence device, a second confluence device and a plurality of microfluidic control components;

the microfluidic control assembly comprises a first microfluidic pump, a second microfluidic pump, a third microfluidic pump and a fourth microfluidic pump; the first micro-flow pump, the second micro-flow pump, the third micro-flow pump and the fourth micro-flow pump respectively comprise a first interface, a second interface and a third interface;

an inlet of the first shunt is communicated with the bottom buffer liquid bottle, and an outlet of the first shunt is communicated with a first interface of each first micro-flow pump; the second interface of each first micro-flow pump is communicated with the inner cavity of a corresponding chip, so that each first micro-flow pump can drive liquid in the bottom buffer liquid bottle to flow into the corresponding chip; a third interface of each first micro-flow pump is communicated with an inlet of the first junction station, so that each first micro-flow pump can drive the liquid in the bottom buffer liquid bottle to flow into the first junction station;

an inlet of the second flow divider is communicated with the top buffer liquid bottle, and an outlet of the second flow divider is communicated with a first interface of each second micro-flow pump; a second interface of each second micro-flow pump is communicated with the inner cavity of a corresponding chip, so that each second micro-flow pump can drive liquid in the top buffer liquid bottle to flow into the corresponding chip; a third interface of each second micro-flow pump is communicated with an inlet of the first junction station, so that each second micro-flow pump can drive the liquid in the top buffer liquid bottle to flow into the first junction station;

the first interface of each third micro-flow pump and the first interface of each fourth micro-flow pump are respectively communicated with the inner cavity of the corresponding chip, and the second interface of each third micro-flow pump and the second interface of each fourth micro-flow pump are respectively communicated with the inlet of the second junction station, so that each third micro-flow pump and each fourth micro-flow pump can respectively drive the liquid in the corresponding chip to flow into the second junction station;

and the outlet of the first confluence device and the outlet of the second confluence device are respectively communicated with the waste liquid bottle.

Optionally, the liquid storage device further comprises a detergent bottle;

the multi-way valve microfluidic control device also comprises a third flow divider;

and the inlet of the third flow divider is communicated with the detergent bottle, and the third interface of each third micro-flow pump and the third interface of each fourth micro-flow pump are respectively communicated with the outlet of the third flow divider, so that each third micro-flow pump and each fourth micro-flow pump can respectively drive the liquid in the detergent bottle to flow into the second flow combiner.

Optionally, the multi-coupler device includes a multi-coupler upper cover, a multi-coupler base, a multi-coupler chip tray, and a multi-coupler movable tray; the upper cover of the multi-coupler is detachably covered on the base of the multi-coupler; the multi-connector base is fixedly connected with the supporting device;

the multi-connected device chip tray is detachably arranged on the multi-connected device movable tray, and a plurality of chip grooves for containing the chips are formed in the upper surface of the multi-connected device chip tray;

the multi-coupler movable tray is movably arranged in the multi-coupler base; the control switch device penetrates through the multi-coupler base to be connected with the bottom of the multi-coupler movable tray, so that the control switch device can push the multi-coupler movable tray upwards;

the multi-coupler upper cover is provided with a plurality of multi-coupler magnet boxes matched with the chip slots in number;

a top buffer hole, a bottom buffer hole and a waste liquid hole are formed in the position, corresponding to each chip groove, of the upper cover of the multi-connector; the bottom buffer liquid hole is communicated with a second interface of a first micro-flow pump of the multi-way valve micro-flow pump control device through a micro-flow pipe, and the top buffer liquid hole is communicated with a second interface of a second micro-flow pump of the multi-way valve micro-flow pump control device through the micro-flow pipe; the waste liquid hole is communicated with a first interface of a third micro-flow pump and a first interface of a fourth micro-flow pump of the multi-way valve micro-flow pump control device through a micro-flow pipe; the bottoms of the top buffer hole, the bottom buffer hole and the waste liquid hole are all connected with sealing rings, and the sealing rings protrude out of the lower surface of the upper cover of the multi-coupler;

a reagent storage pool placing hole is formed in the position, corresponding to each chip slot, of the upper cover of the multi-connector;

the reagent storage pool placing hole is provided with a reagent storage pool, and the upper surface of the upper cover of the multi-coupler is provided with a reagent storage pool positioning seat for fixing the reagent storage pool.

Optionally, when the chip is unloaded, the distance from the upper surface of the chip to the bottom of the sealing ring is a, the distance from the upper surface of the chip to the lower surface of the upper cover of the multi-coupler is B, and the distance from the upper surface of the chip to the bottom of the magnet box of the multi-coupler is C, wherein A, B and C are in a relationship: b is more than A and more than C;

when the control switch device pushes the chip upwards for loading, the distance of the chip moving upwards is D, and B is more than D and more than A; the bottom of the multi-coupler magnet box is attached to the upper surface of the chip; the sealing ring is in fit sealing with the upper surface of the chip.

Optionally, the enrichment separation system further comprises a chassis and a control device; the control device and the supporting device are fixedly arranged in the case;

a man-machine control screen electrically connected with the control device is arranged on the case; the man-machine control screen is used for sending instructions to the control device and receiving information sent by the control device;

the control switch device is electrically connected with the control device;

the supporting device is connected with a sample adding arm driving motor electrically connected with the control device, and the sample adding arm driving motor drives the sample adding arm device to move.

Optionally, the operating switch device comprises an operating switch button pressing shaft, an operating switch operating lever, an operating switch push rod locking plate and an operating switch positioning seat fixedly connected with the supporting device;

the operating switch positioning seat is provided with a positioning seat swinging sliding chute; the operating lever of the operating switch can reciprocate along the positioning seat swinging sliding chute; the operating switch positioning seat is provided with an operating switch positioning groove, and the operating switch button pressing shaft is provided with an operating switch locking key clamped with the operating switch positioning groove; the operating switch button pressing shaft is in sliding insertion connection with the operating switch operating lever; pressing the operating switch button pressing shaft to enable the operating switch locking key to leave the operating switch positioning groove, so that the operating switch operating rod can move along the positioning groove swinging sliding groove;

the operating switch push rod locking plate is arranged on the operating switch operating rod, and an operating switch locking groove is formed in the side wall of the operating switch button pressing shaft and used for enabling the operating switch push rod locking plate to be arranged in the operating switch locking groove after the operating switch is closed so as to clamp the operating switch button pressing shaft;

the control switch device also comprises a control switch driving rocker, a control switch driven rocker, a control switch reciprocating push rod and a control switch base; the operating switch base is fixedly connected with the supporting device; the bottom of the operating lever of the operating switch and one end of the driven rocker of the operating switch are both hinged with the operating switch base; one end of the operating switch driving rocker is connected with the operating switch operating lever, the other end of the operating switch driving rocker, the other end of the operating switch driven rocker and one end of the operating switch reciprocating push rod are connected together, and the operating switch driving rocker, the operating switch driven rocker and the operating switch reciprocating push rod rotate mutually; the other end of the reciprocating push rod of the operating switch is rotatably connected with a chip moving bracket which can be abutted against the chip;

the operating switch operating lever is provided with an operating switch electromagnet electrically connected with the control device, and the operating switch electromagnet is connected with the operating switch push rod lock plate and used for controlling the sliding state of the operating switch push rod lock plate on the operating switch operating lever according to the power-on and power-off state of the operating switch electromagnet;

the control switch device further comprises a control switch distance sensor electrically connected with the control device, and the control switch distance sensor is used for monitoring the distance of the control switch control lever moving along the positioning seat swinging sliding groove to enable the chip to move upwards.

Optionally, a clamping assembly for fixing the liquid suction gun head frame is arranged on the supporting device;

the clamping assembly comprises a cam base and a cam pressing block; the bottom of the cam base is fixedly connected with the supporting device; part of the cam pressing block protrudes out of the cam base;

the cam pressing block is connected with the cam base through a rotating shaft, and the cam pressing block can swing around the rotating shaft relative to the cam base so as to enable the cam pressing block to be in pressure connection with the liquid suction gun rack on the supporting device;

the rotating shaft is a damping hinge.

Optionally, the liquid storage device, the pipette tip rack, the reagent tube rack, the sample rack, the waste device and the multi-connector device are sequentially arranged at intervals along a direction;

the waste device is characterized in that a waste device bottom through hole capable of leaking the liquid suction gun head downwards is formed in the bottom of the waste device, and a waste collecting box corresponding to the waste device bottom through hole is arranged below the waste device.

The embodiment of the utility model provides a beneficial effect is:

when the enrichment and separation system provided by the utility model is turned on or turned off by operating the switch device, the operating the switch device can push the chip upwards or downwards, so that the chip moves upwards or downwards along the multi-coupler device, and the chip is changed from the no-load state to the loading state or from the loading state to the no-load state; the sample adding arm device can move and reciprocate among the liquid suction gun head frame, the reagent pipe frame, the sample frame, the multi-coupler device and the waste device, so that the sample adding arm device can take out the liquid suction gun head from the liquid suction gun head frame, move the liquid suction gun head to the reagent pipe frame to suck the experimental reagent and move the liquid suction gun head to the sample frame to inject the experimental reagent to form a mixed sample; and then, the liquid suction gun head sucks the mixed sample, moves the mixed sample to the multi-coupler device, and injects the mixed sample to the chip. This enrichment piece-rate system has integrated consumptive materials such as reagent, chip and imbibition rifle head, has still integrated the sample, has removed the mixed liquid as an organic whole, can release personnel's labour, raises the efficiency, avoids manual misoperation, has guaranteed to a certain extent that the mixed sample pours into the velocity of flow and the capacity of chip into, has improved experiment precision and reliability.

In order to make the aforementioned and other objects, features and advantages of the present application more comprehensible, preferred embodiments accompanied with figures are described in detail below.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are required to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention, and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.

Fig. 1 is a perspective view of an enrichment and separation system provided in an embodiment of the present invention (a front door of a chassis is not shown in the figure);

fig. 2 is a top view of an enrichment and separation system provided in an embodiment of the present invention (structures such as a sample application arm device and a top plate of a chassis are not shown in the figure);

fig. 3 is a perspective view of a multi-coupler apparatus according to an embodiment of the present invention;

fig. 4 is a schematic structural view of the multi-coupler device according to the embodiment of the present invention for opening the upper cover of the multi-coupler device;

FIG. 5 is a cross-sectional view of the upper cover of the multiconnector shown in FIG. 4;

fig. 6 is a schematic view of an upper surface structure of a multi-connected chip tray of a multi-connected device according to an embodiment of the present invention;

fig. 7 is a schematic view of a lower surface structure of a multi-connected chip tray of a multi-connected device according to an embodiment of the present invention;

fig. 8 is a schematic structural view of a magnet positioning plate and a multi-coupler magnet box of a multi-coupler device according to an embodiment of the present invention;

fig. 9 is a schematic partial structure diagram of a multi-connected device according to an embodiment of the present invention after a reagent storage pool is placed;

fig. 10 is a schematic structural view of an upper cover spring plug of a multi-coupler device according to an embodiment of the present invention;

fig. 11 is a schematic diagram illustrating an unloaded state of chips of a multi-coupler device according to an embodiment of the present invention;

fig. 12 is a schematic diagram illustrating a state of chip loading of a multi-coupler device according to an embodiment of the present invention;

fig. 13 is a schematic structural diagram of an operating switch device according to an embodiment of the present invention;

fig. 14 is a flow chart of an operation method of the enrichment separation system according to an embodiment of the present invention;

fig. 15 and fig. 16 are two schematic structural diagrams of liquid transfer of the pipette tip according to the embodiment of the present invention.

In the figure: 1-a support device; 2-operating the switching device; 3-chip; 4-a multi-coupler device; 5-a waste collection tank; 6-a waste device; 8-a sample rack; 9-reagent tube rack; 10-a clamping assembly; 11-liquid suction gun head frame; 1101-a pipette tip; 1102-liquid level; 12-a multi-way valve micro-flow pump control device; 13-a man-machine control screen; 14-a sample application arm device; 15-a sample adding arm driving motor; 16-a cleanser bottle; 17-bottom buffer solution bottle; 18-top buffer solution bottle; 19-waste liquid bottle;

20-an upper cover of the multi-connector; 2001-waste well; 2002-top buffer well; 2003-bottom buffer well; 2004-reagent storage pool placement holes; 21-a multiconnector base; 22-a multiple connector latch switch; 23-a multi-connected chip tray; 2301-chip locating pins; 2302-triangular boss; 24-a multi-connected movable tray; 25-a multi-linkage magnet box; 2501-magnet positioning compression spring; 26-reagent storage pool positioning seat; 2601-reagent reservoir; 27-magnet locating plate; 28-a multi-link inductor support; 29-a multi-coupler pin shaft; 30-multiple connector pin combination; 31-upper cover spring plug; 3101-spring plug innerspring; 3102-spring plug piston; 32-a multi-coupler pipe rack base; 33-a multi-link pipe frame cover; 34-a sealing ring;

201-operating a switch button pressing shaft; 203-operating switch positioning seat; 204-operating switch lever; 205-operating the switch push rod locking plate; 206-operation switch electromagnet; 207-operating switch active rocker; 208-a steering switch distance sensor; 209-operating switch base; 2010-operating the switch driven rocker; 2011-operate switch reciprocating push rod; 2012-chip moving rack; 2016-manipulating a switch positioning slot; 2018-a positioning seat swing chute.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. The components of embodiments of the present invention, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.

Thus, the following detailed description of the embodiments of the present invention, presented in the accompanying drawings, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative efforts belong to the protection scope of the present invention.

It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, it need not be further defined and explained in subsequent figures.

In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", and the like indicate the position or positional relationship based on the position or positional relationship shown in the drawings, or the position or positional relationship which is usually placed when the product of the present invention is used, and are only for convenience of description and simplification of the description, but do not indicate or imply that the device or element referred to must have a specific position, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," "third," and the like are used solely to distinguish one from another and are not to be construed as indicating or implying relative importance.

Furthermore, the terms "horizontal", "vertical", "overhang" and the like do not imply that the components are required to be absolutely horizontal or overhang, but may be slightly inclined. For example, "horizontal" merely means that the direction is more horizontal than "vertical" and does not mean that the structure must be perfectly horizontal, but may be slightly inclined.

In the description of the present invention, it should also be noted that, unless otherwise explicitly specified or limited, the terms "disposed," "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meaning of the above terms in the present invention can be understood in specific cases to those skilled in the art.

Some embodiments of the present invention will be described in detail below with reference to the accompanying drawings. The embodiments described below and the features of the embodiments can be combined with each other without conflict.

Examples

Referring to fig. 1 to 13, an enrichment and separation system is provided in the present embodiment, and fig. 1 is a perspective view of the enrichment and separation system provided in the present embodiment, in which a front door of a chassis is not shown, a Z axis indicates a vertical direction, an X axis indicates a horizontal (horizontal) direction, and a Y axis indicates a front-rear direction; fig. 2 is a top view of the enrichment and separation system provided in this embodiment, in which structures such as the sample loading arm device and the top plate of the housing are not shown, and arrows shown in the figure indicate arrangement directions. Fig. 3 is a perspective view of a multiple coupling device according to the present embodiment; fig. 4 is a schematic structural view of the multi-coupler apparatus of the present embodiment for opening the upper cover of the multi-coupler apparatus, and fig. 5 is a cross-sectional view of the upper cover of the multi-coupler apparatus for more clearly showing the structure, in which only the bottom buffer hole shows a sealing ring, and neither the top buffer hole nor the waste liquid hole shows a sealing ring; fig. 6 to 10 are views of parts of a multi-coupler device, respectively, fig. 11 is a schematic diagram illustrating a state in which chips of the multi-coupler device according to the present embodiment are unloaded, and fig. 12 is a schematic diagram illustrating a state in which chips of the multi-coupler device according to the present embodiment are loaded. Fig. 13 is a schematic structural diagram of the operation switch device provided in this embodiment.

In an alternative of this embodiment, the enrichment and separation system includes a chassis, and the supporting device 1 is fixedly disposed in the chassis.

In this embodiment, the loading state of the chip 3 is that the control switch device 2 pushes the chip 3 upwards to load the chip 3, and at this time, the chip 3 and the liquid storage device are hermetically communicated through the multi-way valve microflow pump control device 12;

the no-load state of the chip 3 is that the control switch device 2 drives the chip 3 downwards to enable the chip 3 to have no load, and at the moment, the chip 3 is not connected with or disconnected from the multi-way valve microflow pump control device 12.

Referring to fig. 1 and fig. 2, the enrichment and separation system of the present embodiment includes a supporting device 1, a control switch device 2, a multi-coupler device 4, and a sample-loading arm device 14; the control switch device 2, the multi-coupler device 4 and the sample adding arm device 14 are respectively connected with the supporting device 1. Alternatively, the sample application arm arrangement 14 is directly or indirectly connected to the support arrangement 1. For example, the sample application arm device 14 is mounted on a horizontal power device X-axis electric cylinder, which is connected to the support device 1 directly or through other structural members.

The chip 3 is arranged in the multi-coupler device 4, and the chip 3 can move up and down along the multi-coupler device 4; the control switch device 2 is connected with the chip 3; alternatively, the pilot switching device 2 is directly or indirectly connected to the chip 3, for example, the pilot switching device 2 is connected to a component of the multiple connection device 4 in which the chip 3 is disposed.

When the control switch device 2 is turned on or off, the control switch device 2 can push the chip 3 upwards or downwards to enable the chip 3 to move upwards or downwards along the multi-coupler device 4; optionally, when the chip 3 is in a loaded state from an unloaded state, the switch device 2 is operated to push the chip 3 upwards; when the chip 3 is in a loaded state to an unloaded state, the switch device 2 is operated to push the chip 3 downwards. The chip 3 moves up or down along the multi-coupler device 4, and may move up and down in a direction perpendicular to the ground, or in a direction in which the chip 3 and the ground form an included angle.

The supporting device 1 is sequentially provided with a sample rack 8 for storing samples, a reagent pipe rack 9 for storing reagent pipes, a pipette tip rack 11 for storing pipette tips and a waste device 6 for scraping the pipette tips;

the sample application arm device 14 can move and reciprocate among the pipette tip rack 11, the reagent tube rack 9, the sample rack 8, the multi-connector device 4, and the waste device 6. The sample application arm device 14 described in this embodiment can move and reciprocate between the pipette tip holder 11, the reagent tube holder 9, the sample holder 8, the multi-coupler device 4, and the waste device 6, and the movement range of the sample application arm device 14 is not limited to only this region, and the sample application arm device 14 may also move to other positions. Referring to fig. 1, the sample arm device 14 of the present embodiment can optionally move in multiple dimensions, such as moving along three orthogonal axes x, y, and z and moving around one or more degrees of freedom of the three axes.

In the enrichment and separation system of the embodiment, when the switching device 2 is operated to be turned on or turned off, the switching device 2 can be operated to push the chip 3 upwards or downwards, so that the chip 3 moves upwards or downwards along the multi-coupler device 4, and further the chip 3 is changed from an idle state to a loaded state or from the loaded state to the idle state; the sample adding arm device 14 can move and reciprocate among the pipette tip rack 11, the reagent tube rack 9, the sample rack 8, the multi-coupler device 4 and the waste device 6, so that the sample adding arm device 14 can take out pipette tips from the pipette tip rack 11, move the pipette tips to the reagent tube rack 9 to absorb the experimental reagent and move the pipette tips to the sample rack 8 to inject the experimental reagent to form a mixed sample; then, the pipette tip sucks the mixed sample and moves to the multiplexer device 4, and injects the mixed sample to the chip 3. This enrichment piece-rate system has integrated consumptive materials such as reagent, chip 3 and imbibition rifle head, has still integrated the sample, has removed the mixed liquid as an organic whole, can release personnel's labour, raises the efficiency, avoids artificial misoperation, has guaranteed to a certain extent that the mixed sample pours into the velocity of flow and the capacity of chip 3 into, has improved experiment precision and reliability.

Referring to fig. 1 and 2, in an alternative embodiment, the enrichment and separation system includes a multi-way valve microfluidic control device 12 and a liquid storage device; the chip 3 and the liquid storage device can be communicated through a multi-way valve micro-flow pump control device 12; optionally, when the chip 3 is loaded, that is, when the switching device 2 is operated to push the chip 3 upward for loading, the chip 3 is communicated with the liquid storage device through the multi-way valve micro-flow pump control device 12; when the chip 3 is in no-load, that is, when the control switch device 2 drives the chip 3 downwards to be in no-load, the chip 3 is not communicated with the multi-way valve microflow pump control device 12.

The liquid storage device comprises a bottom buffer liquid bottle 17, a top buffer liquid bottle 18 and a waste liquid bottle 19; alternatively, the bottom buffer bottle 17 is used for storing the bottom buffer or for storing the cleaning solution, the top buffer bottle 18 is used for storing the top buffer or for storing the cleaning solution, and the waste liquid bottle 19 is used for collecting waste liquid.

The multi-way valve microfluidic control device 12 comprises a first shunt, a second shunt, a first flow combiner, a second flow combiner and a plurality of microfluidic control components; optionally, the first flow divider, the second flow divider, the first flow combiner and the second flow combiner adopt a multi-way valve, so that liquid can be collected and distributed in a centralized manner, and occupied space is saved.

The microfluidic control assembly comprises a first microfluidic pump, a second microfluidic pump, a third microfluidic pump and a fourth microfluidic pump; the first micro-flow pump, the second micro-flow pump, the third micro-flow pump and the fourth micro-flow pump respectively comprise a first interface, a second interface and a third interface. Alternatively, the first, second, third and fourth micro-flow pumps in this embodiment may be commercially available standard components, for example, a four-way valve, a piston injector and two stepping motors are disposed inside the micro-flow pump, and the rotational movement of the four-way valve and the up-and-down movement of the piston injector are respectively controlled by the two stepping motors. The four-way valve is used for enabling the movable end to form a passage with one end connected with the bottom piston injector when the valve is rotated to the positions of 0 degrees, 90 degrees and 270 degrees, and enabling liquid to pass through without obstruction. The piston injector is used for generating a closed space, converting the rotary motion of the motor into the up-and-down motion of the piston, and indirectly controlling the pumping speed and the force of the injector by controlling the speed and the current of the motor. One of the four ports of the four-way valve is connected with the piston injector, and the other three ports are respectively a first port, a second port and a third port.

An inlet of the first splitter is communicated with the bottom buffer liquid bottle, and an outlet of the first splitter is communicated with the first interface of each first micro-flow pump; the second interface of each first micro-flow pump is communicated with the inner cavity of the corresponding chip, so that each first micro-flow pump can drive liquid in the bottom buffer liquid bottle to flow through the first shunt and then flow into the corresponding chip; the third interface of each first micro-flow pump is communicated with the inlet of the first confluence device, so that each first micro-flow pump can drive liquid in the bottom buffer liquid bottle to flow through the first shunt, then flow into the first confluence device and further flow into the waste liquid bottle; that is, the bottom buffer solution in the bottom buffer solution bottle is driven by the first shunt through the first micro-fluid pump and injected into the chip. Or when the first micro-flow pump is cleaned, the cleaning liquid in the bottom buffer liquid bottle is driven by the first flow divider through the first micro-flow pump and then is injected into the waste liquid bottle through the first confluence device.

The outlet of the first confluence device and the outlet of the second confluence device are respectively communicated with a waste liquid bottle.

An inlet of the second flow divider is communicated with the top buffer liquid bottle, and an outlet of the second flow divider is communicated with the first interface of each second micro-flow pump; the second interface of each second micro-flow pump is communicated with the inner cavity of the corresponding chip, so that each second micro-flow pump can drive liquid in the top buffer liquid bottle to flow through the second flow divider and then flow into the corresponding chip; the third interface of each second micro-flow pump is communicated with the inlet of the first confluence device, so that each second micro-flow pump can drive liquid in the top buffer liquid bottle to flow through the second shunt, then flow into the first confluence device and further flow into the waste liquid bottle; that is, the top buffer solution in the top buffer solution bottle is driven by the second shunt through the second micro-fluid pump to be injected into the chip. Or when the second micro-flow pump is cleaned, cleaning liquid in the top buffer liquid bottle is driven by the second flow divider through the second micro-flow pump and then is injected into the waste liquid bottle through the first confluence device.

The first interface of each third micro-flow pump and the first interface of each fourth micro-flow pump are respectively communicated with the inner cavity of the corresponding chip, and the second interface of each third micro-flow pump and the second interface of each fourth micro-flow pump are respectively communicated with the inlet of the second junction station, so that each third micro-flow pump and each fourth micro-flow pump can respectively drive the liquid in the corresponding chip to flow into the second junction station and further flow into the waste liquid bottle; through third miniflow pump, fourth miniflow pump and second ware that converges, be convenient for arrange the waste liquid of chip to the waste liquid bottle.

In this embodiment, the multi-way valve microfluidic control device may clean the first microfluidic pump with a bottom buffer solution injected by the first splitter, clean the second microfluidic pump with a top buffer solution injected by the second splitter, and discharge the waste liquid to the waste liquid bottle through the first confluence device; then the bottom buffer solution in the bottom buffer solution bottle is driven by the first shunt through the first micro-fluid pump to be injected into the chip, and the top buffer solution in the top buffer solution bottle is driven by the second shunt through the second micro-fluid pump to be injected into the chip.

Optionally, the liquid storage device further comprises a detergent bottle 16; the multi-way valve microfluidic control device also comprises a third shunt; optionally, a detergent bottle 16 is used to store cleaning solution.

And the inlet of the third flow divider is communicated with the detergent bottle, and the third interface of each third micro-flow pump and the third interface of each fourth micro-flow pump are respectively communicated with the outlet of the third flow divider, so that the third micro-flow pumps and the fourth micro-flow pumps can respectively drive the liquid in the detergent bottle to flow into the second confluence device and further flow into the waste liquid bottle. In this embodiment, multiple unit valve miniflow pump control unit can introduce the cleaning solution in the cleaning agent bottle through the third current divider, washs third miniflow pump and fourth miniflow pump to discharge the waste liquid to the waste liquid bottle through the second confluence ware.

The enrichment and separation system in the embodiment can simplify the connection structure and reduce the installation space through the control device of the multi-way valve micro-flow pump, is convenient to connect a plurality of chips 3 through one structure, and has high control efficiency. The multi-way valve micro-flow pump control device can obtain the effects of pumping and injecting liquid to the chip 3, pumping and injecting liquid from the bottom buffer liquid bottle 17, the top buffer liquid bottle 18 and the cleaning agent bottle 16 and discharging waste liquid to the waste liquid bottle 19 through a plurality of groups of micro-flow pump control components and the chip 3, the bottom buffer liquid bottle 17, the top buffer liquid bottle 18, the cleaning agent bottle 16 and the waste liquid bottle 19 which are matched, and greatly improves the application range and the automation degree of the multi-way valve micro-flow pump control device 12.

Referring to fig. 3 to 5, in an alternative embodiment, the multiple coupling device 4 includes a multiple coupling device upper cover 20, a multiple coupling device base 21, a multiple coupling device chip tray 23, and a multiple coupling device movable tray 24; the upper cover 20 of the multi-connector is detachably covered on the base 21 of the multi-connector; the multi-coupler base 21 is fixedly connected with the support device 1.

The multiple chip tray 23 is detachably disposed on the multiple movable tray 24, and a plurality of chip grooves for accommodating the chips 3 are disposed on an upper surface of the multiple chip tray 23.

The multi-coupler movable tray 24 is movably arranged in the multi-coupler base 21; the operation switch device 2 passes through the multi-coupler base 21 to be connected with the bottom of the multi-coupler movable tray 24, so that the operation switch device 2 can push the multi-coupler movable tray 24 upwards, further push the multi-coupler chip tray 23 to move upwards along with the multi-coupler movable tray 24, and further push the chip 3 to move upwards. Alternatively, the operation switch device 2 passes through the copper sleeve on the supporting device for lubrication and guidance, then passes through the multi-coupler base 21, and then is connected with the bottom of the multi-coupler movable tray 24.

Optionally, a number of multi-coupler magnet boxes 25 matching the chip slots are provided on the multi-coupler upper cover 20. Alternatively, the multi-coupler magnet box 25 positions correspond to grid positions on the chip.

A buffer hole and a waste liquid hole 2001 are formed in the position of the upper cover 20 of the multi-coupler corresponding to each chip groove; optionally, the buffer wells include a bottom buffer well 2003 and a top buffer well 2002; optionally, the bottom buffer hole is communicated with a second interface of a first micro-flow pump of the multi-way valve micro-flow pump control device through a micro-flow pipe, so that a bottom buffer in the bottom buffer bottle is injected into the bottom buffer hole under the driving of the first micro-flow pump, and then the bottom buffer is injected into the chip 3.

Optionally, the top buffer hole is communicated with a second interface of a second microfluidic pump of the multi-way valve microfluidic pump control device through a microfluidic pipe, so that a top buffer in the top buffer bottle is injected into the top buffer hole under the driving of the second microfluidic pump, and then injected into the chip 3.

Optionally, the waste liquid hole is communicated with a first interface of a third micro-flow pump and a first interface of a fourth micro-flow pump of the multi-way valve micro-flow pump control device through a micro-flow pipe; so that the waste liquid in the chip is discharged to a waste liquid bottle through the waste liquid hole.

The bottoms of the buffer liquid hole and the waste liquid hole 2001 are both connected with a sealing ring 34, and the sealing ring 34 protrudes out of the lower surface of the upper cover 20 of the multi-connector so as to be convenient for sealing; optionally, a seal ring 34 is attached to the bottom of both the bottom buffer well 2003 and the top buffer well 2002.

Optionally, the bottom buffer well 2003, the top buffer well 2002 and the waste well 2001 each comprise an upper portion and a lower portion in sequential communication; the upper portions of the bottom buffer well 2003, top buffer well 2002 and waste well 2001 are all threaded holes for locking the ends of the micro flow tubes, and the lower portions of the bottom buffer well 2003, top buffer well 2002 and waste well 2001 are all unthreaded holes for seating a sealing ring 34, as shown in fig. 5. Optionally, a multi-coupler pipe rack base 32 is fixedly connected to the upper surface of the multi-coupler upper cover 20; the top of many antithetical couplet pipe support bases 32 is connected with many antithetical couplet pipe support lid 33, and many antithetical couplet pipe support bases 32 all are provided with the recess that is used for holding the miniflow pipe with many antithetical couplet pipe support lid 33, and just the recess of many antithetical couplet pipe support bases 32 and the recess position of many antithetical couplet pipe support lid 33 correspond to the trend of fixed miniflow pipe, reduce the miniflow pipe and receive the extruded probability of external force, prevent the unexpected rupture of miniflow pipe.

Optionally, a reagent storage pool placement hole 2004 is provided on the multi-coupler cover 20 at a location corresponding to each chip slot.

Referring to fig. 9, optionally, reagent reservoir placement hole 2004 is fitted with reagent reservoir 2601; optionally, the top of the reagent reservoir 2601 is funnel shaped to facilitate injection of the liquid.

Optionally, a reagent storage pool positioning seat 26 for fixing the reagent storage pool 2601 is disposed on the upper surface of the upper cover 20 of the multi-coupler at a position corresponding to the reagent storage pool placing hole 2004, so that the pipette tip moves to the reagent storage pool 2601 and injects the mixed sample, and the mixed sample flows through the reagent storage pool placing hole 2004 into the chip. The reagent storage pool locator stand 26 is provided to facilitate location of the reagent storage pool. The direction of the arrow shown in fig. 9 is a direction in which the reagent storage pool 2601 is pulled out by a force, and the reagent storage pool 2601 is restricted by the reagent storage pool placement hole 2004 so that the reagent storage pool positioning seat 26 restricts the reagent storage pool 2601 from being pulled out.

Referring to fig. 11 and 12, in the alternative embodiment, when the chip 3 is unloaded, the distance from the upper surface of the chip 3 to the bottom of the packing 34 is a, the distance from the upper surface of the chip 3 to the lower surface of the multi-coupler upper cover 20 is B, and the distances from the upper surface of the chip 3 to the bottom of the multi-coupler magnet case 25 are C, A, B and C in the following relationship: b is more than A and more than C;

when the control switch device 2 pushes the chip 3 upwards for loading, the distance that the chip 3 moves upwards is D, and B is more than D and more than A; the bottom of the multi-coupler magnet box 25 is attached to the upper surface of the chip 3; the sealing ring is sealed with the upper surface of the chip 3 in a fitting manner. Wherein, the hole of sealing washer can not be because of warping the jam, does not influence the miniflow pipe and passes through buffer solution hole or waste liquid hole 2001 and pour into buffer solution or waste liquid into the chip groove, can also form effective return circuit. Alternatively, when the bottom of the multi-coupling magnet case 25 is attached to the upper surface of the chip 3, a magnet positioning compression spring described below is compressed to protect the chip 3 from being rigidly crushed by the multi-coupling magnet case 25. Alternatively, when the chip 3 is loaded by pushing the chip 3 upward by operating the switch device 2, the distance from the upper surface of the chip 3 to the lower surface of the upper cover 20 of the multi-coupler is B ', and B > B'.

Alternatively, as shown in fig. 4 and 10, an upper cover spring plug 31 is provided on the lower surface of the upper cover 20 of the multi-coupler at a position corresponding to each chip slot; the upper cover spring plug 31 is used for pressing and positioning the chip 3;

a spring plug built-in spring 3101 and a spring plug piston 3102 are detachably arranged in the shell of the upper cover spring plug 31; the spring plug innerspring 3101 has a tendency to extend the spring plug piston 3102 out of the housing of the upper cover spring plug such that the spring plug piston 3102 presses against the positioning chip 3.

Referring to fig. 3 and 4, alternatively, one end of the multi-coupler base 21 is hinged to one end of the multi-coupler upper cover 20, for example, one end of the multi-coupler base 21 is hinged to one end of the multi-coupler upper cover 20 by a multi-coupler pin 29.

The other end of the multi-coupler base 21 is provided with a mounting seat which is detachably connected with the multi-coupler upper cover 20; the other end of the multi-coupler upper cover 20 is detachably connected with the mounting seat of the multi-coupler base 21 through a multi-coupler latch switch 22. The multiple connector latch switch 22, which is similar to a latch structure, is inserted into the holes of the multiple connector upper cover 20 and the multiple connector base 21, so that the multiple connector upper cover 20 is fixed and does not move any more. Optionally, the multi-coupler base 21 and the multi-coupler upper cover 20 are in clearance fit with the same size of the multi-coupler latch switch, respectively.

Referring to fig. 3 and 4, optionally, a multiple connector sensor for detecting whether the multiple connector latch switch 22 is inserted is arranged on a position, close to the multiple connector latch switch 22, of the mounting seat of the multiple connector base 21, and the multiple connector sensor detects whether the multiple connector upper cover 20 is locked in place, and a next step of instruction can be operated only after the multiple connector upper cover is locked in place, so that subsequent detection work can be better performed. Optionally, the mounting seat of the multi-coupler base 21 is fixedly connected with a multi-coupler inductor bracket 28; the multiple inductor support 28 is fixedly connected to the multiple inductor.

Optionally, the multi-coupler base 21 is provided with a multi-coupler engagement pin 30 for defining an open position of the multi-coupler upper cover 20; the multi-coupler upper cover 20 is designed to be opened at an angle that does not break the micro fluid channel due to an excessive angle, without falling freely or interfering with other components, by the multi-coupler pin 30.

Optionally, the multiple chip tray 23 is disposed on the multiple movable tray 24, and is used for placing a tooling fixture for the chip 3, allowing repeated assembly and disassembly. Referring to fig. 6, alternatively, the multi-gang chip tray 23 may simultaneously place a plurality of chips 3, for example, the multi-gang chip tray 23 may simultaneously place 4, 5, 8, etc. chips 3. The upper surface of multi-connector chip tray 23 is provided with chip locating pin 2301 and triangle boss 2302, and the hole cooperation on chip locating pin 2301 and the chip 3 is placed, and triangle boss 2302 is used for preventing that the chip 3 of placing from adorning conversely, plays and prevents down the effect.

Referring to fig. 7, optionally, the lower surface of the multiple unit chip tray 23 has a tray positioning pin, and correspondingly, the upper surface of the multiple unit movable tray 24 is provided with a pin hole to be matched with the tray positioning pin of the lower surface of the multiple unit chip tray 23. Optionally, the lower surface of the multiple unit chip tray 23 has three tray positioning pins, and correspondingly, the upper surface of the multiple unit movable tray 24 is provided with three pin holes matched with the tray positioning pins of the multiple unit chip tray 23. Optionally, the multiple unit chip tray 23 and the multiple unit movable tray 24 are close to zero clearance fit, and three tray positioning pins are arranged in a triangular mode, so that the aim of preventing falling is fulfilled. The positioning pins and the triangular bosses on the upper surface and the lower surface jointly determine the placing position of the chip 3 without error.

Alternatively, the multiple unit movable tray 24 is mounted on a manipulation switch lever in the manipulation switch device for placing the multiple unit chip tray 23.

Referring to fig. 3 and 8, optionally, a magnet positioning piece 27 is fixedly connected to the upper surface of the upper cover 20 of the multi-coupler; the magnet positioning piece 27 is arranged above the multi-coupling magnet box 25, and a magnet positioning compression spring 2501 is arranged between the magnet positioning piece 27 and the multi-coupling magnet box 25; the magnet positioning compression spring 2501 has a tendency to move the multiple magnet box 25 away from the magnet positioning piece 27. Magnets are arranged in the multi-coupler magnet box 25 and are used for adsorbing biological magnetic beads in the chip 3. The compression spring is positioned by the magnet, so that the multi-coupler magnet box 25 can automatically contract when contacting with the chip 3, and the chip 3 is protected from being rigidly crushed by the multi-coupler magnet box 25.

Referring to fig. 1 and 2, in an alternative of this embodiment, the enrichment and separation system further includes a cabinet (not shown) and a control device (not shown); the control device and the supporting device 1 are fixedly arranged in the case.

A man-machine control screen 13 electrically connected with the control device is arranged on the case; the man-machine control screen 13 is used for sending instructions to the control device and receiving information sent by the control device;

the control switch device 2 is electrically connected with the control device;

the supporting device 1 is connected with a sample adding arm driving motor 15 electrically connected with the control device, and the sample adding arm driving motor 15 drives the sample adding arm device 14 to move.

Referring to fig. 13, in an alternative embodiment, the operating switch device 2 includes an operating switch button pressing shaft 201, an operating switch operating lever 204, an operating switch push rod locking plate 205 and an operating switch positioning seat 203 fixedly connected to the supporting device 1;

the operating switch positioning seat 203 is provided with a positioning seat swinging chute 2018; the operating switch operating rod 204 can reciprocate along the positioning seat swinging chute 2018; the operating switch positioning seat 203 is provided with an operating switch positioning groove 2016, and the operating switch button pressing shaft 201 is provided with an operating switch locking key clamped with the operating switch positioning groove 2016; the operating switch button pressing shaft 201 is inserted with the operating switch operating lever 204 in a sliding way; pressing the manipulation switch button pressing shaft 201 to move the manipulation switch locking key away from the manipulation switch positioning groove 2016, thereby allowing the manipulation switch manipulation lever 204 to move along the positioning groove swing chute 2018;

the operating switch push rod locking plate 205 is disposed on the operating switch operating rod 204, and an operating switch locking groove is disposed on a side wall of the operating switch button pressing shaft 201, so that the operating switch push rod locking plate 205 can be disposed in the operating switch locking groove to lock the operating switch button pressing shaft 201 after the operating switch is turned off. For example, a spring is further provided in the manipulation switch manipulation lever 204 for pre-tightening the manipulation switch push-rod locking piece so as to be disposed in the manipulation switch locking groove. The operation switch push rod locking groove is formed in the operation switch push rod 201, the operation switch push rod locking plate 205 is arranged on the operation switch operation rod 204, after the operation switch device 2 is closed, the operation switch push rod locking plate 205 is inserted into the operation switch locking groove, the operation switch push rod 201 is axially locked, the operation switch push rod 201 cannot axially move, the operation switch operation rod 204 is further locked on the operation switch positioning seat 203, namely, the operation switch device 2 cannot be opened, self-locking of the operation switch device 2 is achieved, and the risk that the operation switch device 2 fails is reduced.

The operation switch device 2 further comprises an operation switch driving rocker 207, an operation switch driven rocker 2010, an operation switch reciprocating push rod 2011 and an operation switch base 209; the operating switch base 209 is fixedly connected with the supporting device 1; the bottom of the operating switch operating rod 204 and one end of the operating switch driven rocker 2010 are hinged with the operating switch base 209; one end of the operating switch driving rocker 207 is connected with the operating switch operating lever 204, the other end of the operating switch driving rocker 207, the other end of the operating switch driven rocker 2010 and one end of the operating switch reciprocating push rod 2011 are connected together, and the operating switch driving rocker 207, the operating switch driven rocker 2010 and the operating switch reciprocating push rod 2011 rotate mutually; the other end of the manipulation switch reciprocating push rod 2011 is rotatably connected with a chip moving support 2012 capable of abutting against the chip 3. In this embodiment, one end and the other end are relative to the two ends of the rod-like structure.

The operating switch operating lever 204 is provided with an operating switch electromagnet 206 electrically connected with the control device, the operating switch electromagnet 206 is connected with an operating switch push rod lock plate 205 and is used for controlling the sliding state of the operating switch push rod lock plate 205 on the operating switch operating lever 204 according to the power-on and power-off state of the operating switch electromagnet 206;

the operating switch device 2 further comprises an operating switch distance sensor 208 electrically connected with the control device, and the operating switch distance sensor 208 is used for monitoring the distance that the operating switch operating rod moves along the positioning seat swinging sliding groove to enable the chip to move upwards. When the joystick is in position as monitored by the joystick distance sensor 208, the next command can be optionally sent.

Referring to fig. 1 and 2, in an alternative embodiment, a clamping assembly 10 for fixing a pipette head holder 11 is provided on the supporting device 1;

the clamping assembly 10 comprises a cam base and a cam pressing block; the bottom of the cam base is fixedly connected with the supporting device 1; part of the cam pressing block protrudes out of the cam base;

the cam pressing block is connected with the cam base through a rotating shaft, and the cam pressing block can swing around the rotating shaft relative to the cam base, so that the cam pressing block can be in pressure joint with the liquid suction gun head frame 11 on the supporting device 1, namely the liquid suction gun head frame 11 is fixed on the supporting device 1.

Optionally, the rotation axis is a damped hinge.

Referring to fig. 1 and 2, in an alternative of the present embodiment, a liquid storage device, a pipette head rack 11, a reagent tube rack 9, a sample rack 8, a waste device 6, and a multi-connector device 4 are sequentially provided at intervals in one direction; so as to optimize the structure of the enrichment and separation system.

Optionally, the bottom of the waste device 6 is provided with a through hole at the bottom of the waste device 6, which can leak the pipette head down, and a waste collection tank 5 is arranged below the waste device 6, which corresponds to the through hole at the bottom of the waste device 6. The scraped-off pipette tips are collected and stored by a waste collection tank 5.

The enrichment and separation system in the embodiment has the advantages that the structure is adopted: as long as consumable materials such as samples and reagents are quantitatively loaded on the equipment, the operations such as subsequent mixing, adsorption, filtration and the like can be automatically completed, the labor force of people is released to the maximum extent, and no careless mistakes are caused in the process. The multi-connector device and the operation switch device are used in a linkage mode, so that the connection between the multi-way valve micro-flow pump control device and the chip is effectively and reliably achieved. The specific arrangement of consumable loading parts prevents cross-contamination to some extent. The specific liquid injection mode also prevents the liquid from being easily splashed out by manual operation to a certain extent.

The present embodiment also provides an operation method applicable to the enrichment separation system described above, and a reagent storage pool placing hole 2004 is provided in a position of the multi-coupler upper cover 20 corresponding to each chip 3.

Fig. 14 is a flow chart of an operation method suitable for the enrichment separation system, which includes:

preparation before operation: the pipette tip is arranged on a pipette tip rack 11, a sample is loaded by a reagent tube and is placed on a sample rack 8, and an experimental reagent is loaded by the reagent tube and is placed on a reagent tube rack 9; cleaning solution is injected into the cleaning agent bottle 16, different buffer solutions are respectively injected into the bottom buffer solution bottle and the top buffer solution bottle, and the waste solution bottle 19 is emptied; the centrifugally degassed chip 3 is placed on a multiplex device 4. Optionally, 4 reagent storage pools, 12 reagent tubes of 5mL, 16 reagent tubes of 1mL, 12 pipette tips of sterile low-adsorption transparent filter elements of 1000uL, 16 sealing rings and 4 centrifugally degassed chips are prepared before operation; the materials are all disposable consumables and cannot be reused. Alternatively, the top buffer solution bottle 18, the bottom buffer solution bottle 17 and the cleanser bottle 16 are filled with enough reagents, respectively. Optionally, 12 sterile low adsorption transparent filter element pipette tips of 1000uL are fully placed on the pipette tip rack 11. Alternatively, the sample is loaded with a 5mL reagent tube and placed on the sample holder 8; the sample is, for example, blood. Alternatively, the experimental reagent is loaded into a 5mL reagent tube or a 1mL reagent tube as needed, and placed on the reagent tube holder 9. Optionally, opening the upper cover 20 of the multi-coupler, and installing 12 seal rings into the unthreaded holes in the lower surface of the upper cover of the multi-coupler using a seal ring insertion tool; the 4 seal rings are mounted to the bottom of the reagent storage pool placement hole 2004, and then the seal rings are placed from the reagent storage pool positioning seats and rotated clockwise to the bottom.

The centrifugally degassed chip is placed on a multi-connector chip tray 23, the multi-connector chip tray 23 is placed on a multi-connector movable tray 24, the multi-connector upper cover 20 is closed, and a multi-connector latch switch is inserted, so that gaps between the chip and each component on the multi-connector device are shown in fig. 11.

Loading: and pushing the control switch device 2 to enable the chip 3 to move upwards along the multi-coupler device 4 so as to load the chip 3, so that the chip is communicated with the multi-way valve micro-flow pump control device in a sealing way. Alternatively, the joystick 204 is pushed to make the chip moving holder 2012 push the chip 3 to move upward along the multi-coupler device 4 to load the chip 3.

Experiment: the sample adding arm device 14 moves to the sample adding gun head frame 11 to take out the sample adding gun head, the sample adding gun head moves to the reagent tube of the reagent tube frame 9 along with the sample adding arm device 14 and sucks the experiment reagent, then the sample adding gun head moves to the reagent tube of the sample frame 8 along with the sample adding arm device 14 and inserts the experiment reagent into the sample, and a mixed sample in the reagent tube of the sample frame is formed. The liquid is repeatedly sucked and taken in the reagent tube of the sample rack 8 by moving to achieve the effect of full mixing. Optionally, the moving liquid is repeatedly sucked, taken and mixed in the reagent tube of the sample rack 8, and is matched with the set low sucking speed of the micro-flow pump module, so that the sample is not splashed out of the reagent tube, the target cells in the sample and the reagent are combined in a reaction manner as much as possible, and the combined target cells have the capacity of being adsorbed by the magnet. Optionally, after the pipette head moves into the reagent tube of the sample holder and injects the experiment reagent, the pipette head repeatedly sucks and releases the liquid in the reagent tube of the sample holder to mix the sample, so that the mixed sample in the reagent tube of the sample holder is mixed more uniformly.

The pipette tip moves into a reagent tube of the sample rack 8 along with the sample adding arm device 14 and sucks a mixed sample, and then the pipette tip moves into a reagent storage pool and injects the mixed sample; optionally, repeating the steps of sucking the mixed sample by the pipette head and injecting the mixed sample into the reagent storage pool;

the multi-way valve micro-flow pump control device 12 respectively injects the mixed sample, the buffer solution in the bottom buffer solution bottle and the buffer solution in the top buffer solution bottle into the chip 3 to form sheath flow, and discharges the waste liquid in the chip 3 to the waste solution bottle 19; the waste liquid is, for example, a liquid such as an unnecessary cell or a reagent. Alternatively, the formation of the sheath flow within the chip 3 can be performed using the prior art, see in particular patent CN102713640A, entitled sheath flow device and method. The multi-way valve micro-flow pump control device 12 controls the buffer solution in the bottom buffer solution bottle to be injected into the chip 3, and specifically drives the buffer solution in the bottom buffer solution bottle to be injected into the chip through each first micro-flow pump, namely the bottom buffer solution in the bottom buffer solution bottle is driven by the first shunt through the first micro-flow pump to be injected into the chip; the multi-way valve micro-flow pump control device 12 controls the buffer solution in the top buffer solution bottle to be injected into the chip 3, specifically, each second micro-flow pump drives the buffer solution in the top buffer solution bottle to be injected into the chip, that is, the top buffer solution in the top buffer solution bottle is driven by the second shunt through the second micro-flow pump to be injected into the chip. Optionally, the step of discharging the waste liquid in the chip 3 to the waste liquid bottle 19 specifically includes that each third micro-flow pump and each fourth micro-flow pump respectively drive the liquid in the corresponding chip to flow through the second flow combiner and flow into the waste liquid bottle.

The sample adding arm device 14 moves to the waste device 6 to scrape the liquid suction gun head, and then freely falls into the waste collection box 5, and then is uniformly processed after the experiment is finished.

Optionally, the method further comprises:

cleaning: cleaning liquid is respectively injected into the bottom buffer liquid bottle, the top buffer liquid bottle and the cleaning agent bottle;

the multi-way valve micro-flow pump control device respectively injects the cleaning solution in the bottom buffer solution bottle, the cleaning solution in the top buffer solution bottle and the cleaning solution in the cleaning agent bottle into the waste solution bottle to respectively clean the first micro-flow pump, the second micro-flow pump, the third micro-flow pump and the fourth micro-flow pump. Namely, the cleaning liquid in the bottom buffer liquid bottle is driven by the first shunt through the first micro-flow pump and then injected into the waste liquid bottle through the first confluence device; cleaning liquid in the top buffer liquid bottle is driven by a second shunt through a second micro-flow pump and then is injected into the waste liquid bottle through a first confluence device; and the cleaning liquid in the cleaning agent bottle is driven by the third flow divider through the third micro-flow pump and the fourth micro-flow pump and then is injected into the waste liquid bottle through the second confluence device.

In the alternative of this embodiment, the pipette tip is moved into the reagent tube of the reagent tube rack 9, and the test reagent is aspirated at a distance of about 1mm to 3mm from the bottom of the reagent tube; for example, the distance from the bottom of the reagent vessel is 1mm, 2mm, 2.5mm, 3mm, or the like.

In the alternative of this embodiment, the pipette tip is moved into the reagent tube of the sample holder 8, and the test reagent is injected into the sample at a distance of about 1mm to 3mm from the bottom of the reagent tube; for example, the distance from the bottom of the reagent vessel is 1mm, 2mm, 2.5mm, 3mm, or the like. Alternatively, the pipette tip is stopped at the bottom of the reagent tube of the sample rack 8, and repeatedly sucks and releases the liquid in the reagent tube of the sample rack to mix the sample.

Fig. 15 and 16 are schematic diagrams of two structures of pipetting by using the pipette tip provided in this embodiment.

Referring to fig. 15, in an alternative of this embodiment, moving the pipette tip 1101 to the reagent storage pool 2601 to inject the mixed sample specifically includes centering on the reagent storage pool 2601, and injecting the mixed sample at a low speed above and close to the liquid level 1102 of the remaining liquid in the reagent storage pool 2601 to prevent the liquid from splashing out; optionally, aligning the pipette tip 1101 with the center of the reagent storage pool 2601, and making the height of the pipette tip as close as possible to the liquid level 1102 of the remaining liquid in the reagent storage pool 2601, so as to inject the mixed sample at a low speed and prevent the liquid from splashing; the method requires the same injection amount every time, so that partial cells with a large injection amount at a certain time are prevented from remaining at the high position of the reagent storage pool 2601, and the subsequent injection cannot be cleaned.

Referring to fig. 16, in an alternative embodiment, the pipette tip 1101 moves to the reagent storage pool 2601 to inject the mixed sample, and specifically includes a pipette tip that is close to the inner side wall of the upper end of the reagent storage pool 2601 and injects the mixed sample at a position with a gap of 0.01mm to 0.3 mm. That is, the pipette tip injects the mixed sample proximate to the inner sidewall of the funnel end of the reagent storage reservoir 2601. Optionally, the pipette tip 1101 is above the level 1102 of the liquid remaining in the reagent reservoir 2601. Optionally, the direction of the slope in the side wall of the reagent reservoir 2601 is the same as the direction of the mixed sample injection, so the inner wall acts as a buffer and does not splash liquid out; optionally, the reagent reservoir is circular in cross-section, and when injected, the liquid will flow down the entire circular inner wall, and may also act as a flush to flush cells from the inner wall of the residual reagent reservoir 2601 into the chip.

FIGS. 15 and 16 show two ways of pipetting into the reagent reservoir, both to prevent spillage of the liquid and to ensure that no excess cells remain on the inner walls of the reagent reservoir into the chip.

The operation method in this embodiment has the advantages of the enrichment and separation system, and the advantages of the enrichment and separation system disclosed in this embodiment will not be described repeatedly.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. An enrichment and separation system is characterized by comprising a supporting device, an operation and control switch device, a multi-coupler device and a sample adding arm device; the control switch device, the multi-coupler device and the sample adding arm device are respectively connected with the supporting device;

2. The enrichment separation system of claim 1, further comprising a multiplex valve micro-fluidic pump control device and a liquid storage device; when the control switch device pushes the chip upwards to load, the chip is communicated with the liquid storage device through the multi-way valve microflow pump control device;

3. The enrichment separation system of claim 2, wherein the liquid storage device further comprises a detergent bottle;

4. The enrichment separation system of claim 2, wherein the multi-coupler apparatus comprises a multi-coupler upper cover, a multi-coupler base, a multi-coupler chip tray, and a multi-coupler movable tray; the upper cover of the multi-coupler is detachably covered on the base of the multi-coupler; the multi-connector base is fixedly connected with the supporting device;

5. The enrichment separation system of claim 4, wherein the distance from the top surface of the chip to the bottom of the gasket is A, the distance from the top surface of the chip to the bottom surface of the upper cover of the multi-coupler is B, and the distance from the top surface of the chip to the bottom of the multi-coupler magnet cassette is C, A, B and C, when the chip is unloaded, the relationship between: b is more than A and more than C;

6. The enrichment separation system of claim 1, further comprising a cabinet and a control device; the control device and the supporting device are fixedly arranged in the case;

the control switch device is electrically connected with the control device;

7. The enrichment separation system of claim 6, wherein the operating switch device comprises an operating switch button pressing shaft, an operating switch operating lever, an operating switch push rod locking plate and an operating switch positioning seat fixedly connected with the supporting device;

8. The enrichment separation system of claim 1, wherein the support device is provided with a clamping assembly for fixing the pipette tip rack;

the rotating shaft is a damping hinge.

9. The enrichment separation system of claim 1, wherein the pipette gun head rack, the reagent tube rack, the sample rack, the waste device, and the multi-connector device are sequentially spaced in one direction.

10. The enrichment separation system of claim 1, wherein the bottom of the waste device is provided with a waste device bottom through hole capable of leaking a pipette tip downwards, and a waste collection tank is provided below the waste device corresponding to the waste device bottom through hole.