CN110252592A - A nanoliter droplet distribution device and method based on wettability partition structure - Google Patents

Abstract

The invention discloses a nano-upgrade liquid drop distribution device based on wettability partition structure, which comprises a shock absorbing table, a second connecting plate is fixed on the shock absorbing table, an X-axis electric displacement platform is fixed on the second connecting plate, and the X The first connecting plate is fixed on the axis electric displacement stage, the Y-axis electric displacement stage is fixed on the first connecting plate, the third connecting plate is fixed on the Y-axis electric displacement stage, and the Z-axis electric displacement stage is fixed on the third connecting plate. The Z-axis electric translation stage is fixed with a stage, the shock absorber is fixed with a Y-axis manual translation platform, an X-axis manual translation platform and a Z-axis manual translation platform, and a fourth connecting plate is fixed on the Z-axis manual translation platform. A needle holder is fixed on the four connecting plates, and a high-precision syringe pump and a liquid storage bottle are also arranged on the shock-absorbing table. Also disclosed is a method for automatically dispensing nanoliter droplets. The method can realize high-efficiency automatic distribution of nanoliter liquid droplets; in addition, the method has simple structure and convenient operation, and can realize industrial production.

Description

A nanoliter droplet distribution device and method based on wettability partition structure

technical field

The invention belongs to the technical field of liquid automatic processing equipment, and in particular relates to a nanoliter liquid drop distribution device based on a wettability partition structure, and also relates to the nanoliter liquid drop automatic distribution method.

Background technique

Nanoliter-volume droplet dispensing is playing an increasingly important role in biomedical, chemical, materials synthesis, and microfluidics applications. At present, the most common droplet dispensing technologies mainly include contact dispensing technology and non-contact dispensing technology. For the distribution of nanoliter droplets, the contact dispensing technology is fast, but the precision is low; the non-contact dispensing technology can meet the requirements of high precision and high efficiency at the same time, but it is expensive. Therefore, it is necessary to develop a low-cost nano-liter droplet distribution technology that can meet the requirements in both accuracy and efficiency.

Contents of the invention

The purpose of the present invention is to provide a nano-liter liquid drop distribution device based on wettability partition structure, which can realize high-precision and high-efficiency automatic distribution of nano-liter liquid droplets.

Another object of the present invention is to provide the above nanoliter droplet distribution method.

The technical solution adopted in the present invention is a nanoliter droplet distribution device based on wettability partition structure, including a shock absorbing table, a second connecting plate is fixed on the shock absorbing table, and an X-axis is fixed on the second connecting plate Electric displacement stage, the first connecting plate is fixed on the loading block of the X-axis electric displacement stage, and the Y-axis electric displacement stage is fixed on the first connecting plate through the inner hexagonal bolt, and the loading block of the Y-axis electric displacement stage is passed through the inner hexagon The bolt is fixed with the third connecting plate, and the third connecting plate is fixed with the Z-axis electric displacement stage through the inner hexagonal bolt. The Y-axis manual translation stage is fixed by the hexagonal bolt, the X-axis manual translation platform is fixed on the loading block of the Y-axis manual translation platform through the inner hexagonal bolt, and the L-shaped connecting plate is fixed on the X-axis manual translation platform through the inner hexagonal bolt. The Z-axis manual translation stage is fixed on the type connecting plate through the inner hexagonal bolt, and the fourth connecting plate is vertically fixed on the loading block of the Z-axis manual moving stage through the inner hexagonal bolt, and the needle holder is fixed on the fourth connecting plate. The needle holder is equipped with a dispensing needle, and the shock absorber is also equipped with a high-precision syringe pump and a liquid storage bottle. The high-precision syringe pump is respectively connected to the dispensing needle and the liquid storage bottle through a plastic hose. The X-axis electric displacement stage , Y-axis electric displacement stage and Z-axis electric displacement stage are connected to the controller through cables, and the controller is connected to the COM port of the computer through the RS232 direct serial port line.

The present invention is also characterized in that,

A supporting platform is also fixed on the shock-absorbing platform, an industrial camera is fixed on the supporting platform through a camera bracket, and the industrial camera is connected with the microscope lens through threads.

The shock-absorbing table and the support table are fixed by bolts.

The industrial camera is connected to the USB port of the computer through a cable.

The high-precision syringe pump is connected to the COM port of the computer through the RS-232 direct serial line.

The second connecting plate is fixed on the vibration damping table by four hexagon socket bolts, and the X-axis electric translation stage is fixed on the second connecting plate by hexagon socket bolts.

Another technical solution adopted by the present invention is a nanoliter droplet distribution method based on wettability partition structure, which is specifically implemented according to the following steps:

Step 1, according to the preparation process to manufacture a sample with a wettability partition structure, and divide the sample surface into a hydrophilic area and a super-hydrophobic area; install the prepared sample on the stage;

Step 2. Control the X-axis electric translation stage, Y-axis electric translation stage and Z-axis electric translation stage through the controller, so that the sample on the moving stage is located directly under the distribution needle, and a 0.5mm interval is left, using high-precision injection The pump delivers the liquid in the reservoir bottle to the dispensing needle, where a mother droplet is formed; the stage is moved so that the mother droplet contacts the sample;

Step 3. Control the movement of the stage so that the dispensing needle drags the mother liquid droplet to move on the sample surface; when the mother liquid droplet passes through the hydrophilic area on the surface, a sub-droplet of a certain volume will be distributed in the hydrophilic area;

Step 4. Control the movement of the stage so that the mother droplet quickly passes through all the hydrophilic positions on the sample in sequence, and then a sub-droplet of a certain volume will be allocated to all the hydrophilic areas, and the automatic distribution of nanoliter droplets will be completed. .

The beneficial effect of the present invention is,

This method combines the wettability partition structure with robotic technology, which can realize high-efficiency automatic distribution of nanoliter droplets with high precision, and can also achieve more efficient droplet distribution by increasing the number of distribution needles; in addition, its structure The method is simple, low in cost and convenient in operation, and can realize industrialized production.

Description of drawings

Fig. 1 is a schematic structural diagram of a nanoliter droplet distribution device based on a wettability partition structure in the present invention;

Fig. 2 is the sample schematic diagram used in the embodiment of the present invention;

Fig. 3 is a schematic diagram (1) of the distributing process of nanoliter droplets in the embodiment of the present invention;

Fig. 4 is a schematic diagram (2) of the distributing process of nanoliter droplets in the embodiment of the present invention;

Fig. 5 is a schematic diagram (3) of the distributing process of nanoliter droplets in the embodiment of the present invention;

Fig. 6 is a schematic diagram (4) of the distributing process of nanoliter droplets in the embodiment of the present invention;

In the figure, 1. High-precision syringe pump, 2. Liquid storage bottle, 3. Plastic hose, 4. Fourth connecting plate, 5. Needle holder, 6. Dispensing needle, 7. Microscope lens, 8. Camera bracket , 9. Industrial camera, 10. Support table, 11. Sample, 12. Stage, 13. Z-axis electric translation stage, 14. The third connecting plate, 15. Y-axis electric moving stage, 16. The first connecting plate , 17. Shock absorber, 18. X-axis electric translation stage, 19. Second connecting plate, 20. Z-axis manual translation stage, 21. L-type connecting plate, 22. X-axis manual translation stage, 23. Y-axis manual Translation stage, 24. Hydrophilic region, 25. Superhydrophobic region, 26. Sub-droplet, 27. Mother droplet, 28. Hydrophilic region, 29. Superhydrophobic region.

Detailed ways

The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments.

A nanoliter liquid drop distribution device based on wettability partition structure of the present invention, as shown in Figure 1, includes a shock absorber 17, on which a second connecting plate 19 is fixed, and the second connecting plate 19 passes through four An inner hexagonal bolt is fixed on the damping table 17, an X-axis electric translation stage 18 is fixed on the second connecting plate 19, and a threaded hole is provided on the second connecting plate 19, and the X-axis electric translation stage 18 is fixed on the On the second connecting plate 19, the axial direction of the X-axis electric displacement table 18 is parallel to the length direction of the shock absorber 17, and the first connecting plate 16 is fixed on the loading block of the X-axis electric moving table 18, and the first connecting plate 16 The Y-axis electric translation stage 15 is fixed on the top by the inner hexagonal bolt, the axial direction of the Y-axis electric translation stage 15 is perpendicular to the axial direction of the X-axis electric translation stage 18, and the loading block of the Y-axis electric translation stage 15 is fixed by the inner hexagonal bolt. A third connecting plate 14 is fixed, and the third connecting plate 14 is fixed with a Z-axis electric displacement platform 13 through an inner hexagonal bolt. The axial direction of the Z-axis electric displacement platform 13 is perpendicular to the shock absorber 17. An L-shaped object stage 12 is fixed on the block by bolts, and grooves are arranged on the object stage 12;

The loading block of the X-axis electric translation table 18 can move along the X-axis direction, the loading block of the Y-axis electric translation table 15 can move along the Y-axis direction, and the loading block of the Z-axis electric translation table 15 can move along the Z-axis direction ; The X-axis electric translation platform 18, the Y-axis electric translation platform 15 and the Z-axis electric translation platform 13 are combined into a three-dimensional electric translation platform;

The shock absorber 17 is fixed with a Y-axis manual displacement platform 23 by an inner hexagonal bolt, and an X-axis manual displacement platform 22 is fixed on the loading block of the Y-axis manual displacement platform 23 by an inner hexagonal bolt, and the X-axis manual displacement platform 22 is axially aligned with the The Y-axis manual displacement table 23 is axially vertical, and the X-axis manual displacement table 22 is fixed with an L-shaped connecting plate 21 through an inner hexagonal bolt. The L-shaped connecting plate 21 is fixed with a Z-axis manual displacement table 20 through an inner hexagonal bolt. The loading block of the displacement table 20 is vertically fixed with a fourth connection plate 4 by a hexagon socket head bolt, and a needle holder 5 is horizontally fixed on the fourth connection plate 4, and a distribution needle 6 is arranged on the needle holder 5; Multiple needles 6 can be set;

The X-axis manual displacement table 22, the Y-axis manual displacement table 23 and the Z-axis manual displacement table 20 are combined into a three-dimensional manual displacement platform, all of which can move along the X-axis, Y-axis, and Z-axis directions;

Also be fixed with supporting platform 10 on the shock-absorbing platform 17, on supporting platform 10, be fixed with industrial camera 9 by camera support 8, industrial camera 9 is connected with microscope lens 7 by self-contained screw thread; bolted;

The shock absorber 17 is also provided with a high-precision injection pump 1 and a liquid storage bottle 2, and the high-precision syringe pump 1 is respectively connected to the distribution needle 6 and the liquid storage bottle 2 through a plastic hose 3 in a sealed manner;

The X-axis electric displacement stage 18, the Y-axis electric displacement stage 15 and the Z-axis electric displacement stage 13 are all connected to the controller through cables;

The high-precision syringe pump 1 is connected to the COM port of the computer through the RS-232 direct serial line;

The controller is a four-channel servo controller provided by the manufacturer of the electric displacement platform. The controller is connected to the COM port of the computer through the RS232 direct serial cable. The industrial camera 9 is connected to the computer (USB port) with its own cable.

The X-axis electric translation stage 18, the Y-axis electric translation stage 15 and the Z-axis electric translation stage 13 all drive the ball screw through a DC motor to drive the loading block to achieve reciprocating linear motion. The main parameters: stroke 25mm, maximum speed 20mm/s, The minimum displacement is 0.2μm;

The manufacturers of X-axis electric translation stage 18, Y-axis electric translation stage 15 and Z-axis electric translation stage 13 are German Physik Instrumente GmbH&Co.KG, the model is M-122.2DD;

The manufacturer of the controller is Physik Instrumente GmbH&Co.KG in Germany, the model is C-884.4DB;

X-axis manual translation stage 22, Y-axis manual translation stage 23 and Z-axis manual translation stage 20 are manufactured by Beijing Zhuoli Hangong Instrument Co., Ltd., the model is PSM25-65SR;

The manufacturer of the high-precision syringe pump 1 is Tecan Group in Switzerland, and the model is XCalibur;

The manufacturer of industrial camera 9 is Point Gray GmbH&Co.KG, Canada, and the model is GS3-U3-23S6M;

The manufacturer of the microscope lens 7 is Edmund Optics GmbH&Co.KG in the United States, and the model is VZM1000i;

The present invention is a nanoliter droplet distribution device based on wettability partition structure, and its specific working principle is:

After installing the drivers of the X-axis electric translation stage 18, the Y-axis electric translation stage 15, the Z-axis electric translation stage 13, and the high-precision injection pump 1 on the computer, the phases can be controlled by operating under the respective control software panels. Corresponding hardware, and the above drivers can be integrated through secondary development to achieve unified control of the hardware. The controller controls the motorized stage X-axis motorized stage 18, Y-axis motorized stage 15 and Z-axis motorized stage 13, so that the stage 12 moves in the three dimensions of X, Y and Z, and high-precision injection Pump 1 delivers the liquid in the reservoir bottle to the dispensing needle and forms mother drops. The three manual translation stages are all manually controlled. The overall position of the three-dimensional manual translation platform can be adjusted by changing the placement position of the Y-axis manual translation platform 23 on the shock absorber 17, and then manually adjusting the positions of each axis to adjust the distribution. The needle head 6 is fixed, and it is ensured that the distribution needle head 6 remains still during the droplet distribution process, so that the three-dimensional electric displacement platform can perform relative motion to complete the liquid droplet distribution. By controlling the movement of each axis of the three-dimensional electric displacement platform, the load 12 can be driven. Relative movement is made to make the mother liquid droplet across the sample surface, and then complete the distribution of nanoliter droplets. The industrial camera 9 and the microscope lens 7 are mainly responsible for real-time monitoring to observe the distribution result (taking pictures of the distributed liquid droplets, and then calculating the volume of the liquid droplets in matlab to verify the distribution results).

A method for automatically distributing nanoliter liquid droplets in the present invention is specifically implemented according to the following steps:

Step 1, manufacturing a sample with a wettability partition structure according to the preparation process, and dividing the sample surface into a hydrophilic area and a super-hydrophobic area; installing the prepared sample 11 on the stage 12;

Step 2, control the X-axis electric displacement stage 18, the Y-axis electric displacement stage 15 and the Z-axis electric displacement stage 13 through the controller, so that the sample on the moving stage 12 is located directly under the distribution needle 6, and a 0.5mm interval is left , that is, the distance between the sample and the dispensing needle 6 is 0.5mm, which can prevent the needle from colliding with the sample, and can also leave space for the distribution of the mother liquid droplet. Use the high-precision syringe pump 1 to deliver the liquid in the liquid storage bottle 2 To the dispensing needle 6, and form a drop of mother liquid at the needle; move the stage 12, so that the drop of mother liquid is in contact with the sample;

Step 3, control the stage 12 to move in the X/Y direction at an appropriate speed, so that the distribution needle 6 drags the mother liquid drop to move on the sample surface; when the mother liquid drop passes through the hydrophilic area on the surface, it will be in the hydrophilic area Distribute a sub-droplet of a certain volume; for other regions, there will be no droplet distribution due to its superhydrophobic properties;

Step 4, control the movement of the stage 12, so that the mother droplet quickly passes through all the hydrophilic positions on the sample in sequence, and then a sub-droplet of a certain volume will be allocated to all the hydrophilic areas, and the high-level droplet of the nanoliter droplet will be completed. Accurate, high-efficiency automatic distribution.

Example

A method for automatically distributing nanoliter liquid droplets in the present invention is specifically implemented according to the following steps:

Step 1, according to the preparation process to manufacture a sample with a wettability partition structure, and divide the sample surface into a hydrophilic region and a super-hydrophobic region; as shown in Figure 2, the black part is the hydrophilic region 24 on the sample surface, and the blank part Be the superhydrophobic region 25; The prepared sample is mounted on the stage 12;

Step 2, control the X-axis electric displacement stage 18, the Y-axis electric displacement stage 15 and the Z-axis electric displacement stage 13 through the controller, so that the sample on the moving stage 12 is located directly under the distribution needle 6, and a 0.5mm interval is left , that is, the distance between the sample and the dispensing needle 6 is 0.5mm, which can prevent the needle from colliding with the sample, and can also leave space for the distribution of the mother liquid droplet. Use the high-precision syringe pump 1 to deliver the liquid in the liquid storage bottle 2 To the dispensing needle 6, and form a mother liquid drop 27 at the needle, as shown in Figure 3; move the stage 12 to make the mother liquid drop contact with the sample;

Step 3, control the stage 12 to move in the X/Y direction at an appropriate speed, after the mother liquid droplet 27 crosses the surface of the sample piece 11, it will leave the child as shown in Figure 6 on the hydrophilic region 28 shown in Figure 4 . Droplets 26, and the superhydrophobic region 29 shown in Figure 5 will not have droplet residues;

Step 4: Control the movement of the stage 12 so that the mother liquid droplet 27 quickly passes through all the hydrophilic positions on the sample in turn, and a sub-droplet 26 of a certain volume will be allocated to all the hydrophilic areas 28 to complete the nanoliter liquid High-precision, high-efficiency automated dispensing of drops.

Claims (7)

1. a kind of nanoliter level liquid droplet distribution device based on wetability partitioned organization, which is characterized in that including vibration-damped table (17), institute It states and is fixed on vibration-damped table (17) the second connecting plate (19), be fixed with X-axis electricity driving displacement platform on second connecting plate (19) (18), it is fixed with the first connecting plate (16) on the loading block of the X-axis electricity driving displacement platform (18), first connecting plate (16) is logical It crosses hexagon socket head cap screw and is fixed with Y-axis electricity driving displacement platform (15), pass through interior hexagonal on the loading block of the Y-axis electricity driving displacement platform (15) Bolt is fixed with third connecting plate (14), and the third connecting plate (14) is fixed with Z axis electricity driving displacement platform by hexagon socket head cap screw (13), the objective table (12) of L-type, the vibration-damped table are bolted on the loading block of the Z axis electricity driving displacement platform (13) (17) Y-axis manual displacement platform (23) is fixed with by hexagon socket head cap screw, passed through on the loading block of the Y-axis manual displacement platform (23) Hexagon socket head cap screw is fixed with X-axis manual displacement platform (22), is fixed on the X-axis manual displacement platform (22) by hexagon socket head cap screw L-type connecting plate (21), the L-type connecting plate (21) are fixed with Z axis manual displacement platform (20), the Z axis by hexagon socket head cap screw The 4th connecting plate (4), the 4th connecting plate are vertically fixed by hexagon socket head cap screw on the loading block of manual displacement platform (20) (4) it is fixed on Needle Holder (5), distribution syringe needle (6), the vibration-damped table (17) is provided on the Needle Holder (5) On be additionally provided with high-accuracy syringe pump (1) and liquid storage bottle (2), the high-accuracy syringe pump (1) respectively with distribution syringe needle (6), storage Liquid bottle (2) is tightly connected by plastic flexible pipe (3), the X-axis electricity driving displacement platform (18), Y-axis electricity driving displacement platform (15) and Z axis electricity Dynamic displacement platform (13) have controller by cable connection, and the controller passes through the direct Serial Port Line of RS232 and computer com port Connection.

2. a kind of nanoliter level liquid droplet distribution device based on wetability partitioned organization according to claim 1, feature exist In being further fixed on supporting table (10) on the vibration-damped table (17), the supporting table (10) is fixed with industry by camera support (8) Camera (9), the industrial camera (9) are connected with microlens (7) by screw thread.

3. a kind of nanoliter level liquid droplet distribution device based on wetability partitioned organization according to claim 2, feature exist In being bolted between the vibration-damped table (17) and supporting table (10).

4. a kind of nanoliter level liquid droplet distribution device based on wetability partitioned organization according to claim 2, feature exist In the industrial camera (9) is connected by cable with computer USB port.

5. a kind of nanoliter level liquid droplet distribution device based on wetability partitioned organization according to claim 1, feature exist In the high-accuracy syringe pump (1) is connect by the direct Serial Port Line of RS-232 with computer com port.

6. a kind of nanoliter level liquid droplet distribution device based on wetability partitioned organization according to claim 1, feature exist In second connecting plate (19) is fixed on vibration-free tables (17) by four hexagon socket head cap screws, the X-axis electricity driving displacement platform (18) it is fixed on the second connecting plate (19) by hexagon socket head cap screw.

7. a kind of nanoliter level liquid droplet distribution method based on wetability partitioned organization, which is characterized in that specifically according to the following steps Implement:

Step 1, according to preparation process manufacture have wetability partitioned organization sample, and by sample surfaces be divided into hydrophilic region and Super-hydrophobic region；The sample prepared is installed on objective table (12)；

Step 2, pass through controller control X-axis electricity driving displacement platform (18), Y-axis electricity driving displacement platform (15) and Z axis electricity driving displacement platform (13), so that the sample on moving stage (12) is located at the underface of distribution syringe needle (6), and the interval 0.5mm is stayed, use is high-precision Liquid in liquid storage bottle (2) is delivered to distribution syringe needle (6) by close syringe pump (1), and mother liquor drop is formed at syringe needle；Mobile loading Platform (12) makes mother liquor drop be in contact with sample；

Step 3, control objective table (12) movement keeps distribution syringe needle (6) dragging mother liquor drop mobile in sample surfaces；When mother liquor drop is logical It, will be in the sub- drop of hydrophilic region one determining volume of distribution after crossing the hydrophilic region on surface；

Step 4, control objective table (12) movement makes mother liquor drop successively quickly through all hydrophilic positions on sample, Bian Hui The sub- drop of a determining volume is distributed on all hydrophilic regions respectively, completes the automation distribution of nanoliter level drop.