CN110760438A

CN110760438A - Droplet generating device

Info

Publication number: CN110760438A
Application number: CN201911072338.7A
Authority: CN
Inventors: 刘聪; 周武平; 蒋克明; 张涛; 张志强; 黎海文
Original assignee: Suzhou Institute of Biomedical Engineering and Technology of CAS
Current assignee: Suzhou Zhongke Medical Device Industry Development Co ltd
Priority date: 2019-11-05
Filing date: 2019-11-05
Publication date: 2020-02-07
Anticipated expiration: 2039-11-05

Abstract

The invention discloses a droplet generating device, comprising: the gas circuit pressure supply system, the pressing mechanism, the chip holder and the chip arranged in the chip holder; a second pressure head of the pressing mechanism is provided with an air outlet channel communicated with the output end of the air path pressure supply system; the chip seat is arranged below a second pressure head of the pressing mechanism, and positive/negative air pressure output by the air path pressure supply system is led into the chip through the pressing mechanism so as to generate micro-droplets. By adopting the gas tank, the invention can ensure that corresponding pressure supply can be provided instantly when the gas pressure supply is needed, greatly shorten the working time of the whole system and ensure that the pressure in the whole gas pressure supply process is more gentle; according to the pressing mechanism, the horizontal movement of the push rod assembly is converted into the vertical movement of the pressure head assembly through the movement conversion assembly so as to extrude a sample, and no shielding exists above a pressed object before and after pressing, so that the pressing mechanism is convenient to operate and wide in visual field.

Description

Droplet generating device

Technical Field

The invention relates to the technical field of droplet generation, in particular to a droplet generation device.

Background

The high-sensitivity and rapid nucleic acid detection technology has strong advantages in the fields of low-abundance nucleic acid detection such as cancer molecular marker discovery, infectious diseases, genetic disease research and the like, and has great significance for the extreme research on disease onset, early diagnosis and personalized treatment! Typical nucleic acid detection techniques include fluorescence quantitative PCR, molecular hybridization, and gene sequencing, which have limited detection accuracy, high cost, and long time consumption. The Digital PCR (Digital PCR-dPCR) technology is a novel nucleic acid detection and quantification method, and the copy number of a target sequence is directly detected in an absolute quantification mode without depending on a standard curve and a reference sample. Principle of digital PCR: a standard PCR reaction is distributed into a large number of tiny reactors, each reactor contains or does not contain one or more copies of a target molecule (DNA template), so that single-molecule template PCR amplification is realized, and after the amplification is finished, the copy number of a target sequence is counted through the number of positive reactors. The digital PCR process comprises: droplet generation → overlay → amplification → droplet readout. Wherein droplet generation is used to generate thousands of droplets, using droplet generation apparatus. Current droplet generation devices suffer from drawbacks such as inadequate pressure control, inadequate space above the droplet generation chip, and inconvenient operation.

Disclosure of Invention

The present invention is directed to a droplet generating apparatus, which overcomes the above-mentioned shortcomings of the prior art.

In order to solve the technical problems, the invention adopts the technical scheme that: a droplet generation apparatus comprising: the gas circuit pressure supply system, the pressing mechanism, the chip holder and the chip arranged in the chip holder;

a second pressure head of the pressing mechanism is provided with an air outlet channel communicated with the output end of the air path pressure supply system; the chip seat is arranged below a second pressure head of the pressing mechanism, and positive/negative air pressure output by the air path pressure supply system is introduced into the chip through the pressing mechanism so as to generate micro-droplets;

the gas path pressure supply system comprises a positive pressure gas supply unit and a negative pressure gas supply unit which are communicated with the gas outlet channel;

the positive pressure gas supply unit comprises a positive pressure main pipeline communicated with the gas outlet channel, and a positive pressure tank, a first positive pressure branch pipe and a positive pressure gas outlet valve which are arranged on the positive pressure main pipeline, wherein a positive pressure pump and a positive pressure gas inlet valve are arranged on the first positive pressure branch pipe;

an air filter is also arranged at the air inlet end of the positive pressure pump;

the negative pressure gas supply unit comprises a negative pressure main pipeline communicated with the gas outlet channel and a negative pressure tank, a first negative pressure branch pipe and a negative pressure gas outlet valve, wherein the negative pressure tank, the first negative pressure branch pipe and the negative pressure gas outlet valve are arranged on the negative pressure main pipeline, and a negative pressure pump and a negative pressure gas inlet valve are arranged on the first negative pressure branch pipe.

Preferably, the pneumatic device further comprises a shell, and the pneumatic circuit pressure supply system and the pressing mechanism are both arranged on a bottom plate of the shell; still be provided with chip seat installation piece on the bottom plate, offer on the chip seat installation piece and be used for holding the holding tank of chip seat.

Preferably, the chip is provided with a generated oil pool, a sample pool and a droplet collecting pool, the generated oil pool leads out a first generated oil channel and a second generated oil channel, the sample pool leads out a sample channel, and the first generated oil channel and the second generated oil channel converge from two sides of the sample channel in a cross structure to form a droplet channel which is communicated to the droplet collecting pool.

Preferably, the chip holder comprises a left cover plate, a right cover plate, a chip base and a sealing gasket, wherein the left cover plate and the right cover plate are detachably connected, and a cavity for accommodating the chip base is formed in the middle of the left cover plate and the right cover plate; the chip base is provided with a chip groove for accommodating the chip, the chip is arranged in the chip groove, and the sealing gasket is arranged on the upper surface of the chip.

Preferably, sliding grooves are formed in the front side and the rear side of the chip base, and sliding strips used for being arranged in the sliding grooves in a matched mode are arranged on the left cover plate and the right cover plate; one of the left cover plate and the right cover plate is provided with a buckle, and the other cover plate is provided with a clamping hole which is matched and connected with the buckle;

a limiting hole is formed from the sliding groove to the interior of the chip base, a pin is inserted into the limiting hole, and the outer end of the pin extends out of the limiting hole; the front side and the rear side of the left cover plate and the right cover plate are both provided with grooves;

the chip comprises a chip base and is characterized in that a column hole is formed in the side portion of the chip base, a spring rod is inserted into the column hole and comprises a thin rod portion and a thick rod portion which are connected with each other, the diameter of the thick rod portion is larger than that of the thin rod portion, the thick rod portion is hollow inside, the thin rod portion is slidably inserted into the thick rod portion, an uncovering spring is sleeved on the thin rod portion, a limiting cap with the diameter larger than that of the column hole is arranged at the outer end of the thick rod portion, and the limiting cap is used for jacking and opening the left cover plate or the right cover plate through the elastic action of the uncovering spring.

Preferably, the pressing mechanism comprises a slide rail, a first slide block and a second slide block which are arranged on the slide rail in a sliding manner along the horizontal direction, a first adapter plate fixedly connected to the first slide block, a pressure head assembly arranged on the first adapter plate in a sliding manner along the vertical direction, a second adapter plate fixedly connected to the second slide block, a push rod assembly connected to the second adapter plate, a power assembly arranged on the second adapter plate, and a motion conversion assembly connected between the push rod assembly and the first adapter plate.

Preferably, the power assembly is used for driving the second slider, the push rod assembly and the first slider to move along the horizontal direction, and the motion conversion assembly is used for converting the horizontal motion of the push rod assembly into the vertical motion of the pressure head assembly;

the push rod assembly comprises a first connecting rod and a connecting rod sleeve, the first end of the first connecting rod is connected with the second adapter plate, the second end of the first connecting rod is connected with the first end of the connecting rod sleeve, and the second end of the connecting rod sleeve is connected with the motion conversion assembly;

the first end of the connecting rod sleeve is axially provided with a connecting rod hole for the first connecting rod to be slidably inserted, a first spring is arranged in the connecting rod hole, and a limiting groove which penetrates through the connecting rod sleeve and is communicated with the connecting rod hole is formed in the side portion of the first end of the connecting rod sleeve.

Preferably, the second end of the first connecting rod is provided with a pin hole, a limit pin is inserted into the pin hole, and two ends of the limit pin are slidably arranged in the limit groove.

Preferably, the motion conversion assembly comprises an L-shaped conversion block, a first rotating shaft and a second rotating shaft, the conversion block comprises a vertical part and a horizontal part, the upper end of the vertical part is rotatably connected with the second end of the second connecting rod through the first rotating shaft, and the joint of the vertical part and the horizontal part is rotatably connected with the first conversion plate through the second rotating shaft;

the bottom surface of the vertical part is provided with a spherical jacking part.

Preferably, the pressure head assembly comprises a guide post fixedly connected to the base of the first adapter plate, a limit top plate fixedly connected to the top of the first adapter plate and located above the guide post, a first pressure head sleeved on the guide post and capable of sliding between the base of the first adapter plate and the limit top plate along the guide post, a second spring sleeved on the guide post and located between the bottom surface of the first pressure head and the base of the first adapter plate, a pressure plate fixedly connected with the pressure cylinder, and a second pressure head connected to the other end of the pressure plate;

the first pressure head is provided with a guide hole which is penetrated along the vertical direction and is used for inserting the guide post;

the middle part of spacing roof has seted up the mounting groove, be provided with the pin in the mounting groove, the horizontal part setting of conversion piece is in between the upper surface of pin and first pressure head.

The invention has the beneficial effects that:

by adopting the gas tank, the invention can ensure that corresponding pressure supply can be provided instantly when the gas pressure supply is needed, greatly shorten the working time of the whole system and ensure that the pressure in the whole gas pressure supply process is more gentle;

according to the pressing mechanism, the horizontal movement of the push rod assembly is converted into the vertical movement of the pressure head assembly through the movement conversion assembly so as to extrude a sample, and no shielding exists above a pressed object before and after pressing, so that the pressing mechanism is convenient to operate and wide in visual field; the transmission of force and movement between the first connecting rod and the connecting rod sleeve is carried out by arranging the first spring, the compression displacement is amplified by the small spring, and the pressure control is stable; the motion conversion assembly is in contact with the upper surface of the first pressure head through the spherical jacking portion, and in the process of pressing down the motion conversion assembly, the motion conversion assembly is in point-surface contact with the first pressure head all the time, and the first pressure head can be guaranteed to be vertically pressed downwards by adopting a point driving surface in cooperation with the guide post, so that the pressing force is guaranteed to be stable.

Drawings

FIG. 1 is a schematic diagram of the internal structure of a droplet generation apparatus of the present invention;

FIG. 2 is a schematic view of the droplet generator of the present invention with the chip carrier mounting block removed from the interior thereof;

FIG. 3 is a schematic diagram of the external configuration of a droplet generation apparatus of the present invention;

FIG. 4 is a schematic structural diagram of the gas circuit pressure supply system of the present invention;

FIG. 5 is a schematic diagram of the structure of the bottom of the chip of the present invention;

FIG. 6 is a schematic diagram of a chip carrier according to the present invention;

FIG. 7 is an exploded view of the chip carrier of the present invention;

FIG. 8 is a schematic view of the chip carrier with the right cover plate removed;

FIG. 9 is a schematic view of the construction of the spring beam of the present invention;

FIG. 10 is a schematic view of the pressing mechanism of the present invention;

FIG. 11 is a schematic view of another embodiment of the hold-down mechanism of the present invention;

FIG. 12 is a schematic cross-sectional view of the hold-down mechanism of the present invention;

FIG. 13 is a schematic structural view of a ram assembly of the present invention;

FIG. 14 is a schematic structural diagram of a conversion block of the present invention;

figure 15 is a schematic view of the structure of the outlet channels in the second head of the present invention.

Description of reference numerals:

1-a housing; 10-a base plate; 11-chip carrier mounting block; 12-a hold-down mechanism mounting plate; 13-a sensor; 110-mounting groove;

2, a pressing mechanism; 20-a slide rail; 21 — a first slider; 22 — a second slide; 23-a first transfer plate; 24-a second adapter plate; 25-a ram assembly; 26-a pushrod assembly; 27-a power assembly; 28-a motion conversion assembly; 29-a scaffold;

250-a guide post; 251-a limit top plate; 252 — a first ram; 253-a second spring; 254-pressing plate; 255-a second ram; 256-guide holes; 257 — mounting groove 110; 258-stop lever; 2550-air outlet channel;

260-a first link; 261-a connecting rod sleeve; 262-connecting rod hole; 263 — first spring; 264-limiting groove; 265-pin hole; 266-a spacing pin;

270-a motor; 271-a screw rod; 272-a threaded hole;

280-a conversion block; 281-a first rotating shaft; 282-second rotation axis; 2800-vertical part; 2801 — horizontal section; 2802-spherical top press;

290 — an upper top plate; 291-first optical coupler; 292-a second optocoupler; 293-optical coupling baffle plate; 294-a limiting block;

3-gas circuit pressure supply system;

30-positive pressure gas supply unit; 300-positive pressure main pipeline; 301-positive pressure tank; 302-first positive pressure manifold; 304-positive pressure outlet valve; 305-a positive pressure pump; 306-positive pressure inlet valve; 307 — air filter; 309-positive pressure sensor;

31-a negative pressure gas supply unit; 310-negative pressure tank; 311-first negative pressure branch pipe; 313-negative pressure air outlet valve; 314 — a negative pressure pump; 315-negative pressure inlet valve; 317-negative pressure sensor;

4-chip holder; 40-left cover plate; 41-right cover plate; 42-chip mount; 43-a gasket; 44-a cavity; 45-a sliding bar; 46-slotting; 47-a support sheet; 48-a carrier plate; 400-buckling; 401-hole locking; 420-chip slot; 421-a positioning block; 422-chute; 423-pin; 424-spring rod; 425-slender rod part; 426-thick rod part; 427-a limit cap; 428-cover opening spring;

5-chip; 50-generating an oil pool; 51-a sample cell; 52-droplet collection tank; 53 — first production oil channel; 54 — second generation oil passage; 55-sample channel; 56-droplet channel; 57-positioning groove.

Detailed Description

The present invention is further described in detail below with reference to examples so that those skilled in the art can practice the invention with reference to the description.

It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.

As shown in fig. 1-15, a droplet generating apparatus of the present embodiment includes: the gas circuit pressure supply system 3, the pressing mechanism 2, the chip seat 4 and the chip 5 arranged in the chip seat 4;

an air outlet channel 2550 communicated with the output end of the air path pressure supply system 3 is arranged on the second pressure head 255 of the pressing mechanism 2; the chip holder 4 is disposed below the second ram 255 of the pressing mechanism 2, and the positive/negative air pressure output from the air pressure supply system 3 is introduced into the chip by the pressing mechanism 2 to generate droplets.

In the invention, positive/negative air pressure is provided by the air path pressure supply system 3, the chip is pressed by the pressing mechanism 2, and then the positive/negative air pressure gas provided by the air path pressure supply system 3 is introduced into the chip, so that micro-droplets are formed inside the chip 5.

The droplet generating apparatus in this embodiment further includes a housing 1, and the gas path pressure supply system 3 and the pressing mechanism 2 are disposed on a bottom plate 10 inside the housing 1.

In one embodiment, referring to fig. 4, the gas path pressure supply system 3 includes a positive pressure gas supply unit 30 and a negative pressure gas supply unit 31 both communicating with the gas outlet passage 2550;

the positive pressure gas supply unit 30 comprises a positive pressure main pipe 300 communicated with the gas outlet channel 2550, a positive pressure tank 301 arranged on the positive pressure main pipe 300, a first positive pressure branch pipe 302 and a positive pressure gas outlet valve 304, wherein the first positive pressure branch pipe 302 is provided with a positive pressure pump 305 and a positive pressure gas inlet valve 306;

the air inlet end of the positive pressure pump 305 is also provided with an air filter 307;

the negative pressure gas supply unit 31 includes a negative pressure main pipe communicated with the gas outlet passage 2550, a negative pressure tank 310, a first negative pressure branch pipe 311, and a negative pressure gas outlet valve 313, which are disposed on the negative pressure main pipe, and the first negative pressure branch pipe 311 is provided with a negative pressure pump 314 and a negative pressure gas inlet valve 315. Furthermore, the positive pressure main pipe 300 and the negative pressure main pipe are respectively provided with a positive pressure sensor 309 and a negative pressure sensor 317 for respectively measuring the gas pressure in the positive pressure main pipe 300 and the negative pressure main pipe; a conventional gas pressure sensor 13 may be employed. The respective components of the positive pressure gas supply unit 30 and the negative pressure gas supply unit 31 are mounted on the base plate 10, which is not specifically shown in fig. 1.

Referring to fig. 4, the operation of the positive pressure gas supply unit 30 is as follows: the positive pressure pump 305 works, the positive pressure air inlet valve 306 is opened, the positive pressure air outlet valve 304 is opened, and outside air is filtered by the air filter 307 and then enters the positive pressure tank 301 through the first positive pressure branch pipe 302 to store the positive pressure air; when the positive pressure is used, the positive pressure outlet valve 304 is opened, and the positive pressure gas stored in the positive pressure tank 301 enters the gas outlet passage 2550 through the pipe to supply the positive pressure to the chip 5.

The working process of the negative pressure gas supply unit 31 is as follows: the negative pressure pump 314 works, the negative pressure air inlet valve 315 is opened, the negative pressure air outlet valve 313 is opened, and the gas in the negative pressure tank 310 is discharged outwards to form negative pressure in the negative pressure tank 310; when the negative pressure is used, the negative pressure gas outlet valve 313 is opened, and gas is sucked through the gas outlet passage 2550 by the negative pressure stored in the negative pressure tank 310 to supply the negative pressure to the chip 5.

In the preferred embodiment, a positive pressure tank 301 and a negative pressure tank 310 having a volume in excess of 300mL are used, and the pressures in these two tanks can be maintained substantially constant at the corresponding operating pressures after the instrument is turned on. The volume of the pipeline between the pipeline behind the positive pressure gas outlet valve 304 and the negative pressure gas outlet valve 313 and the chip 5 is about 3mL, and according to an ideal gas state equation, in the process from the beginning to the end of gas pressure work, the pressure change does not exceed 1%, and the requirement of droplet generation can be met.

By adopting the gas tank, corresponding pressure supply can be provided instantly when gas pressure supply is needed, and the working time of the whole system is greatly shortened. In addition, the positive pressure pump 305 and the negative pressure pump 314 in the system can adopt stepless speed regulating pumps, and due to the adoption of the air tank mode, the pressure fluctuation in the working process of the stepless speed regulating pump is further relieved, so that the pressure in the whole gas pressure supply process is more gentle.

In one embodiment, referring to fig. 5 and 7, a production oil pool 50, a sample pool 51 and a droplet collecting pool 52 are arranged on the chip 5, the production oil pool 50 leads out a first production oil channel 53 and a second production oil channel 54, the sample pool 51 leads out a sample channel 55, and the first production oil channel 53 and the second production oil channel 54 are merged into a formed droplet channel 56 in a crisscross structure from two sides of the sample channel 55 and are communicated with the droplet collecting pool 52.

In this example, droplets are generated by a conventional liquid-in-oil method, specifically: under the action of air pressure, a sample in the sample pool 51 flows to the droplet collecting pool 52 through the sample channel 55, oil liquid in the generating oil pool 50 is divided into two parts and flows to the droplet collecting pool 52 through the first generating oil channel 53 and the second generating oil channel 54, the first generating oil channel 53 and the second generating oil channel 54 are converged from two sides of the sample channel 55 at the inlet of the droplet channel 56 and form a cross structure, the oil liquid divides the sample liquid to form sample droplets, the sample droplets are wrapped to separate the sample droplets, and then the sample droplets flow into the droplet collecting pool 52 through the droplet channel 56 to be stored.

In this embodiment, the droplets may be formed by either positive pressure or negative pressure. When droplets are generated by negative pressure, the negative pressure generated by the negative pressure gas supply unit 31 is communicated with the droplet collecting tank 52 by the second pressure head 255, and the oil and the sample are caused to flow toward the droplet collecting tank 52 by the action of the negative pressure. When droplets are generated by positive pressure, the positive pressure generated by the positive pressure gas supply means 30 is communicated with the generation oil pool 50 and the sample pool 51 through the head, and the oil and the sample are caused to flow into the droplet collection pool 52 by the positive pressure action. The number and location of the gas outlet channels 2550 on the second ram 255 correspond to the number and location of the oil wells, sample wells 51 and droplet collection wells 52 on the chip 5.

In one embodiment, referring to fig. 5-9, the bottom plate 10 is further provided with a chip carrier mounting block 11, and the chip carrier mounting block 11 is provided with a receiving groove 110 for receiving the chip carrier 4. The chip holder 4 comprises a left cover plate 40, a right cover plate 41, a chip base 42 and a sealing gasket 43, wherein the left cover plate 40 and the right cover plate 41 are detachably connected, and a cavity 44 for accommodating the chip base 42 is formed in the middle; the chip base 42 is provided with a chip slot 420 for accommodating a chip, and the sealing gasket 43 is arranged on the upper surface of the chip after the chip is arranged in the chip slot 420. The chip is provided with a positioning slot 57, and a positioning block 421 is arranged in the chip slot 420 for being inserted into the chip slot in a matching manner, so as to realize quick installation and positioning. In a further embodiment, a sensor 13 for detecting whether the chip holder 4 is present in the receiving groove 110 of the chip-holder mounting block 11 is further provided on the bottom plate 10 at the side of the chip-holder mounting block 11. The sensor 13 can adopt a conventional reflective photoelectric sensor 13, the side of the chip seat mounting block 11 is provided with a detection hole communicated with the receiving groove 110, a signal emitted by the sensor 13 reaches the receiving groove 110 through the detection hole, and when the chip seat 4 is mounted in the receiving groove 110, the signal emitted by the sensor 13 can be returned by the chip seat 4, so that the chip seat 4 is detected to be mounted.

In this embodiment, the front and rear sides of the chip base 42 are both provided with sliding grooves 422, and the left cover plate 40 and the right cover plate 41 are both provided with sliding strips 45 which are arranged in the sliding grooves 422 in a matching manner; the left cover plate 40 is provided with a buckle 400, the right cover plate 41 is provided with a clamping hole 401 which is matched and connected with the buckle 400, the buckle 400 is provided with a clamping hook structure, and the clamping hook structure is hooked into the clamping hole 401 to realize buckling connection; the clip 400 has elasticity, and the clip hole 401 can be moved back and forth by a small distance by pressing to hook into the clip hole 401 or disengage from the clip hole 401. The left cover plate 40 is fixedly connected with the chip base 42 through screws, and the right cover plate 41 can slide left and right on the chip base 42.

A limiting hole is formed from the sliding groove 422 to the interior of the chip base 42, a pin 423 is inserted into the limiting hole, the outer end of the pin 423 extends out of the limiting hole, and the front side and the rear side of the right cover plate 41 are provided with open grooves 46; the pin 423 is used to prevent the right cover plate 41 from sliding excessively rightward and separating from the chip base 42. When the right cover plate 41 is installed on the chip base 42, the right cover plate 41 can slide left and right, the pin 423 is located in the slot 46, and when the right cover plate 41 slides to the extreme position rightwards, the pin 423 abuts against the inner wall of the left side of the slot 46 to prevent the right cover plate 41 from continuously sliding rightwards, so that the limiting is realized. The bottom of the chip base 42 is also provided with a carrier plate 48.

The right side of chip base 42 has been seted up the column hole (not shown in the figure), the interpolation of column hole is equipped with spring-loaded mast 424, spring-loaded mast 424 includes thin pole portion 425 and thick pole portion 426 that interconnect's diameter all is less than the column hole, thick pole portion 426's diameter is greater than thin pole portion 425, thick pole portion 426 is inside hollow, thin pole portion 425 slidable inserts and establishes in thick pole portion 426, and the cover is equipped with uncapping spring 428 on thin pole portion 425, thick pole portion 426's outer end is provided with the diameter and is greater than the spacing cap 427 of column hole. The limiting cap 427 is used for pressing and opening the right cover plate 41 through the elastic force of the cover opening spring 428, the left end of the cover opening spring 428 is in contact with the inner wall of the left end of the column hole, the right end of the cover opening spring 428 is pressed and pressed against the left end surface of the thick rod part 426, the thick rod part 426 can be pressed and opened by the cover opening spring 428 when sliding relative to the thin rod part 425 leftwards, and therefore the thick rod part 426 can be oriented to the rightmost side under the elastic force of the cover opening spring 428 to press and open the right cover plate 41.

The left cover plate 40 and the right cover plate 41 are both provided with a support sheet 47 for supporting the gasket 43.

When the chip opening device is used, the hook is pressed to be separated from the clamping hole 401, the right cover plate 41 is extruded to slide backwards and open under the action of the elastic force of the cover opening spring 428, then the chip 5 is placed in the chip groove 420 of the chip base 42, and the cover plate is pushed leftwards to be buckled and connected with the left cover plate 40. Then, the chip 5 is fitted with the sealing pad 43, and the chip holder 4 with the chip mounted thereon is mounted in the mounting groove 110 of the chip holder mounting block 11.

In one embodiment, referring to fig. 10-15, the pressing mechanism 2 includes a slide rail 20, a first slide block 21 and a second slide block 22 slidably disposed on the slide rail 20 along a horizontal direction, a first adapter plate 23 fixedly connected to the first slide block 21, a pressing head assembly 25 slidably disposed on the first adapter plate 23 along a vertical direction, a second adapter plate 24 fixedly connected to the second slide block 22, a pushing rod assembly 26 connected to the second adapter plate 24, a power assembly 27 disposed on the second adapter plate 24, and a motion conversion assembly 28 connected between the pushing rod assembly 26 and the first adapter plate 23.

The power assembly 27 is used for driving the second slider 22, the push rod assembly 26 and the first slider 21 to move in the horizontal direction, and the motion conversion assembly 28 is used for converting the horizontal motion of the push rod assembly 26 into the vertical motion of the pressure head assembly 25.

Further, the push rod assembly 26 includes a first link 260 and a link sleeve 261, a first end of the first link 260 is connected to the second adaptor plate 24, a second end of the first link 260 is connected to a first end of the link sleeve 261, and a second end of the link sleeve 261 is connected to the motion conversion assembly 28; a first end of the connecting rod sleeve 261 is axially provided with a connecting rod hole 262 for the first connecting rod 260 to be slidably inserted, a first spring 263 is arranged in the connecting rod hole 262, and a side part of the first end of the connecting rod sleeve 261 is provided with a limit groove 264 which penetrates through the connecting rod sleeve 261 and is communicated with the connecting rod hole 262. The second end of the first link 260 is provided with a pin hole 265, a limit pin 266 is inserted into the pin hole 265, and two ends of the limit pin 266 are slidably disposed in the limit groove 264.

Under the action of the power assembly 27, the first link 260 moves leftwards, but after the pressure head assembly 25 reaches the bottom and is above the sample to be pressed, the first link 260 continues to move leftwards to press the first spring 263, and the pressure head assembly 25 is further driven to move downwards to press the sample through the first spring 263. The purpose of the first spring 263 is to amplify the pressing process, since the pressing head is a solid, the pressed sample is a chip and a sealing pad 43 arranged on the chip, the deformation distance of the sealing pad 43 in the pressing process is small, the first spring 263 functions to slowly apply the pushing force of the push rod assembly 26 to the pressed object through the spring deformation force, the distance of the whole pressing process is amplified, and the precise control of the clamping process is realized. The limiting pin 266 can only move within the length range of the limiting groove 264, so that the movement range of the first connecting rod 260 is limited, namely when the first connecting rod 260 moves to the condition that the limiting pin 266 reaches the leftmost end of the limiting groove 264, the pressure head assembly 25 reaches the lowest end, the limit position of the downward movement of the pressure head assembly 25 can be limited, and the sample is prevented from being damaged due to excessive extrusion. On the other hand, when the first link 260 returns to the right, the first link 260 can drive the link cover 261 to return to the right by the stopper pin 266.

Further, the motion converting assembly 28 includes a converting block 280 having an L shape, a first rotating shaft 281 and a second rotating shaft 282, the converting block 280 includes a vertical portion 2800 and a horizontal portion 2801, an upper end of the vertical portion 2800 is rotatably connected to a second end of the second link by the first rotating shaft 281, and a joint of the vertical portion 2800 and the horizontal portion 2801 is rotatably connected to the first converting plate 23 by the second rotating shaft 282; the bottom surface of the vertical portion 2800 is provided with a spherical pressing portion 2802, and the motion conversion member 28 is in point-surface contact with the pressing head member 25 through the spherical pressing portion 2802 to transmit the pressure.

Further, the pressing head assembly 25 includes a guiding post 250 fixedly connected to the base of the first adapter plate 23, a limit top plate 251 fixedly connected to the top of the first adapter plate 23 and located above the guiding post 250, a first pressing head 252 sleeved on the guiding post 250 and capable of sliding along the guiding post 250 between the base of the first adapter plate 23 and the limit top plate 251, a second spring 253 sleeved on the guiding post 250 and located between the bottom surface of the first pressing head 252 and the base of the first adapter plate 23, a pressing plate 254 fixedly connected to the pressing cylinder, and a second pressing head 255 connected to the other end of the pressing plate 254;

the first pressure head 252 is provided with a guide hole 256 which is penetrated along the vertical direction and is used for inserting the guide post 250; in this embodiment, 2

guide posts

250 and 2 guide holes 256 are included. The motion conversion assembly 28 is in contact with the upper surface of the first pressing head 252 through the spherical pressing part 2802, and in the process of pressing down the motion conversion assembly 28, the motion conversion assembly is in point-surface contact with the first pressing head 252 all the time, and the guide columns 250 are matched, so that the first pressing head 252 can be vertically pressed downwards in height, and the pressing force is stable.

The material of the second pressing head 255 may be metal or plastic, and may be selected according to the actual application. The number and location of gas outlet channels 2550 on second ram 255 correspond to the number and location of oil wells, sample wells 51, and droplet collection wells 52 on the chip to ensure that positive and negative gas pressures can be provided to each of the oil wells, sample wells 51, and droplet collection wells 52. Referring to fig. 15, an outlet passage 2550 forms an inlet at a side of the second ram 255 to communicate with an output end of the gas path pressure supply system 3 through a pipe; the gas outlet passage 2550 forms an outlet at the bottom of the second ram 255 to introduce the gas pressure supplied from the gas path pressure supply system 3 into the chip.

The middle of the limit top plate 251 is provided with a mounting groove 257, a stop lever 258 is arranged in the mounting groove 257, and the horizontal part 2801 of the conversion block 280 is arranged between the stop lever 258 and the upper surface of the first pressing head 252. When the link sleeve 261 is reset to the right, the motion conversion assembly 28 is driven to rotate clockwise, and the horizontal portion 2801 is caught by the blocking rod 258, so that the motion conversion assembly 28, the pressure head assembly 25 and the first slide block 21 are driven to move and reset to the right together.

Further, a pressing mechanism 2 mounting plate 12 is further arranged on the bottom plate 10, and the sliding rail 20 is fixedly connected to the pressing mechanism 2 mounting plate 12; the support 29 is arranged on the mounting plate 12 of the pressing mechanism 2, the upper portion of the support 29 is provided with an upper top plate 290, the bottom surface of the upper top plate 290 is provided with a first optical coupler 291 and a second optical coupler 292, and the second adapter plate 24 is provided with an optical coupler blocking piece 293 used for being matched with the first optical coupler 291 and the second optical coupler 292. The base plate 10 is further provided with a stopper 294 for limiting the movement of the first slider 21 to the end position. After the power assembly 27 drives the first slide block 21 to move to the end position, the first slide block 21 stops moving, and the pressure head assembly 25 reaches the position above the sample to be pressed; the power assembly 27 drives the second slide block 22 and the push rod assembly 26 to move continuously, and the movement conversion assembly 28 drives the pressure head assembly 25 to vertically press the sample to be pressed downwards.

In a further preferred embodiment, the power assembly 27 includes a motor 270 fixedly connected to the second adapter plate 24 and a screw rod 271 drivingly connected to an output shaft of the motor 270, and the second adapter plate 24 is provided with a threaded hole 272 threadedly engaged with the screw rod 271; the screw 271 passes through the screw hole 272, and both ends thereof are rotatably connected to the bracket 29.

Referring to fig. 1 and 2, the operation of the power assembly 27 in this embodiment is: when the motor 270 works, the screw rod 271 rotates, so that the second adapter plate 24 and the second slider 22 fixedly connected with the second adapter plate are driven to move leftwards, force is transferred through the push rod assembly 26 and the motion conversion assembly 28, the first slider 21, the first adapter plate 23 fixedly connected with the first slider 21 and the pressure head assembly 25 are driven to slide leftwards, when the optical coupler blocking piece 293 reaches and blocks the first optical coupler 291, the second pressure head 255 of the pressure head assembly 25 just reaches the position right above a sample to be pressed, the first slider 21 reaches the leftmost end and contacts with the limiting block 294, and the left movement cannot be performed any more; the first connecting rod 260 of the push rod assembly 26 continues to move leftwards and presses the first spring 263, the first spring 263 continues to drive the connecting rod sleeve 261 to move leftwards, the motion conversion assembly 28 drives the second pressure head 255 of the pressure head assembly 25 to move downwards to press a sample, when the optical coupler blocking piece 293 reaches the second optical coupler 292 and is blocked, the second pressure head 255 of the pressure head assembly 25 moves to the lowest part to realize pressing, at the moment, the limiting pin 266 at the left end of the first connecting rod 260 also moves to the leftmost end of the limiting groove 264, and the second pressure head 255 cannot move downwards; when resetting, the motor 270 rotates reversely to drive the second slider 22, the push rod assembly 26, the motion conversion assembly 28, the first slider 21, the pressure head assembly 25 and the like to reset rightwards, the second pressure head 255 moves upwards to reset quickly under the action of the elastic force of the second spring 253, and the second pressure head 255 takes off the sample and returns to the initial position rightwards. Through the mode that adopts two sliders, can guarantee to compress tightly the front and back, by compressing tightly the spacious in the top field of vision (pressure head subassembly 25 is in the side top of sample, can not shelter from the sample), guarantee to get and put the convenience, especially to having the object that compresses tightly of getting the put requirement, can facilitate.

In one embodiment, the droplet generation apparatus of the present invention operates as a whole by: firstly, a chip 5 is arranged in a chip seat 4, and the chip seat 4 is arranged in a chip seat mounting block 11; then, the second pressure head 255 is driven by the pressing mechanism 2 to press the chip 5 tightly, so that the air outlet channel 2550 on the second pressure head 255 is communicated with the corresponding pool body on the chip 5; then, positive or negative pressure is supplied through the channel pressure supply system 3, thereby generating droplets in the chip 5.

While embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields of application of the invention, and further modifications may readily be effected by those skilled in the art, so that the invention is not limited to the specific details without departing from the general concept defined by the claims and the scope of equivalents.

Claims

1. A droplet generation apparatus, comprising: the gas circuit pressure supply system, the pressing mechanism, the chip holder and the chip arranged in the chip holder;

2. The droplet generating apparatus of claim 1 further comprising a housing, the pneumatic pressure supply system and the hold-down mechanism each being disposed on a floor of the housing; still be provided with chip seat installation piece on the bottom plate, offer on the chip seat installation piece and be used for holding the holding tank of chip seat.

3. The droplet generating apparatus according to claim 2, wherein a generating oil pool, a sample pool and a droplet collecting pool are arranged on the chip, the generating oil pool leads out a first generating oil channel and a second generating oil channel, the sample pool leads out a sample channel, and the first generating oil channel and the second generating oil channel are communicated to the droplet collecting pool from droplet channels formed by merging in a crisscross structure from two sides of the sample channel.

4. The droplet generating device of claim 2, wherein the chip holder comprises a left cover plate, a right cover plate, a chip base, and a gasket, wherein the left and right cover plates are detachably connected to form a cavity therebetween for receiving the chip base; the chip base is provided with a chip groove for accommodating the chip, the chip is arranged in the chip groove, and the sealing gasket is arranged on the upper surface of the chip.

5. The droplet generating apparatus according to claim 4, wherein the chip base has sliding grooves formed on both the front and rear sides thereof, and the left and right cover plates have sliding bars disposed thereon for engaging with the sliding grooves; one of the left cover plate and the right cover plate is provided with a buckle, and the other cover plate is provided with a clamping hole which is matched and connected with the buckle;

6. The droplet generating apparatus of claim 1 wherein the hold down mechanism includes a slide rail, a first slide and a second slide slidably disposed on the slide rail in a horizontal direction, a first adapter plate secured to the first slide, a pressure head assembly slidably disposed on the first adapter plate in a vertical direction, a second adapter plate secured to the second slide, a push rod assembly coupled to the second adapter plate, a power assembly disposed on the second adapter plate, and a motion conversion assembly coupled between the push rod assembly and the first adapter plate.

7. A droplet generation apparatus according to claim 6, wherein the power assembly is configured to drive the second slider, the push rod assembly, and the first slider in a horizontal direction, and the motion conversion assembly is configured to convert horizontal motion of the push rod assembly into vertical motion of the head assembly;

8. The droplet generating apparatus according to claim 7, wherein the second end of the first link has a pin hole, a stopper pin is inserted into the pin hole, and both ends of the stopper pin are slidably disposed in the stopper groove.

9. The droplet generating apparatus of claim 8, wherein the motion conversion assembly comprises a conversion block having an L-shape, a first rotation shaft and a second rotation shaft, the conversion block comprises a vertical portion and a horizontal portion, an upper end of the vertical portion is rotatably connected to the second end of the second link via the first rotation shaft, and a connection point of the vertical portion and the horizontal portion is rotatably connected to the first connection plate via the second rotation shaft;

10. The droplet generating apparatus of claim 9 wherein the pressure head assembly comprises a guide post secured to the base of the first adapter plate, a stop plate secured to the top of the first adapter plate and above the guide post, a first pressure head disposed over the guide post and slidable along the guide post between the base of the first adapter plate and the stop plate, a second spring disposed over the guide post and between a bottom surface of the first pressure head and the base of the first adapter plate, a pressure plate secured to the pressure tube, and the second pressure head attached to the other end of the pressure plate;