CN212396766U - Droplet micro-fluidic chip - Google Patents
Droplet micro-fluidic chip Download PDFInfo
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- CN212396766U CN212396766U CN202020327598.6U CN202020327598U CN212396766U CN 212396766 U CN212396766 U CN 212396766U CN 202020327598 U CN202020327598 U CN 202020327598U CN 212396766 U CN212396766 U CN 212396766U
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Abstract
The invention provides a liquid drop microfluidic chip which comprises a PMMA plate, a first micro-injection pump, a first micro-injector, an adjusting cylinder, a second micro-injection pump and a second micro-injector, wherein a main channel penetrating through the PMMA plate is arranged in the PMMA plate, two sides of the main channel are respectively provided with symmetrically communicated side channels, the side channels extend to the side edge of the PMMA plate, the first micro-injection pump is connected with the first micro-injector, a hose is arranged on the first micro-injector, a micro-needle is arranged on the adjusting cylinder, the hose is used for communicating the first micro-injector with the micro-needle, the micro-needle extends into the main channel, the side channels are respectively connected with the second micro-injector, and the second micro-injector is respectively provided with the second micro-injection pump. The channel structure of the invention is simple and easy to design, the manufacturing cost is low, the applicability is wide, the generation frequency, the size and the fracture position of the liquid drop in the main channel can be quickly and flexibly regulated, the generation of the periodic monodispersity liquid drop in a jet flow mode can be realized, and the generation range of the size of the liquid drop is further enlarged.
Description
Technical Field
The invention relates to the technical field of tiny droplet flow control, in particular to a droplet micro-fluidic chip.
Background
The droplet microfluidics is a new technology for manipulating tiny droplets, and mainly utilizes the interaction between flow shear force and surface tension to divide and separate continuous fluid into discrete nano-liter or even smaller-volume droplets. Compared to continuous flow technology, droplet microfluidics has many advantages, such as: the liquid drop has small volume, reduced reagent consumption, no diffusion among liquid drop samples, stable reaction environment, and can avoid cross contamination among samples, etc. The micro-droplets can be used as an ideal micro-reactor and are widely applied to various fields such as biology, chemistry, medicine, food industry and the like at present. The generation of liquid drops is an important prerequisite of the liquid drop microfluidic technology, and the generation of micro liquid drops mainly adopts an active mode and a passive mode at present. The active mode mainly utilizes external field driving forces such as mechanical disturbance, sound, light, electricity, temperature, magnetic field and the like to change the natural flow characteristics of the liquid, thereby effectively controlling the generation of micro liquid drops and realizing the accurate control of the liquid drops. The passive mode does not need to apply any external force, and generates micro-droplets depending on the channel configuration and the fluid flow characteristics of the chip. Compared with an active mode, the passive mode for preparing the liquid drops has the advantages of simplicity in manufacturing, high speed, high flux, simplicity in operation and the like, and can provide a reliable and controllable environment for generating the monodisperse liquid drops.
The active mode drives microfluid in a non-contact way, so that the liquid drop control is more flexible, but the problems of complex manufacture, high requirement on external equipment, high manufacturing cost, limitation of the control range by the conditions of a sample or the equipment and the like exist. For example, although the generation of micro droplets can be flexibly controlled by adding an electric field or a thermal field, the molecular structure of substances contained in the droplets can be influenced or even destroyed by a high-voltage electric field or a high temperature; in the electrowetting method, a microelectrode needs to be integrated on a chip, and a programmable microelectrode switch control system is configured, so that the requirement on a chip system is high. In addition, the microelectrodes may interfere with or contaminate the contents of the droplet, for example, the contents of the droplet may be deposited on the microelectrodes, and the electrical signal may affect the biocompatibility of the biomolecule (DNA or protein). The three most common channels in the passive mode are the T-type, coaxial flow and focused flow channels. Wherein T-channel is the simplest and earlier proposed microfluidic device for controllable generation of droplets; the liquid drops generated in the coaxial flow channel are stable and uniform in size, and contact pollution between the dispersed phase in the liquid drops and the channel wall can be avoided; the liquid drops generated in the focusing flow channel are more stable, easy to operate and wide in application range, and micro liquid drops which are uniformly distributed and have the same shape can be prepared in one step. However, T-channels suffer from contamination of the droplets from contact with the channel walls, and the droplet size generation range based on a single type of channel is still relatively limited. For example, in a coaxial flow channel, when the capillary number of a continuous phase or the weber number of a dispersed phase is higher than a certain critical value, the flow of the dispersed phase can present a jet flow mode, and at the moment, a jet liquid column has the problem that the jet liquid column is thick or thin and cannot be broken to generate liquid drops.
Disclosure of Invention
The invention aims to overcome the defect of limited production range of the size of liquid drops in the conventional passive mode and provides a liquid drop microfluidic chip. The channel structure is simple and easy to design, the manufacturing cost is low, the applicability is wide, the generation frequency, the size and the fracture position of the liquid drop can be quickly and flexibly regulated, the generation of the periodic monodispersity liquid drop in a jet flow mode can be realized, and the generation range of the size of the liquid drop is further enlarged.
In order to solve the technical problems, the invention adopts the technical scheme that: the utility model provides a liquid droplet micro-fluidic chip, wherein, includes PMMA board, first micro-injection pump, first micro-syringe, regulation section of thick bamboo, be equipped with in the PMMA board and run through the main entrance of PMMA board, the both sides of main entrance respectively are equipped with the side passageway of symmetry intercommunication, the side passageway extends to the side of PMMA board, first micro-injection pump with first micro-syringe is connected, be equipped with the hose on the first micro-syringe, be equipped with the micropin on the regulation section of thick bamboo, the hose will first micro-syringe with the micropin intercommunication, adjust the section of thick bamboo with main entrance sealing connection, the micropin gos deep into the main entrance, all be connected with the second micro-syringe on the side passageway, the second micro-syringe all is equipped with the second micro-injection pump, the side passageway with be equipped with the valve between the second micro-syringe.
In the technical scheme, PMMA is polymethyl methacrylate. The continuous phase is firstly injected into the main channel and all side channels in the PMMA plate by using the second micro-injection pump and the second micro-injector, then the dispersed phase is injected into the main channel in the PMMA plate by using the first micro-injection pump and the first micro-injector, the dispersed phase is broken in the continuous phase to form liquid drops, and the frequency and the size of the formed liquid drops can be controlled by regulating and controlling the two-phase flow of the first micro-injection pump and the second micro-injection pump.
Further, adjust a section of thick bamboo and include barrel, piston handle, piston shaft and piston, the barrel with the sealed butt joint of main entrance, the piston is located in the barrel, piston shaft one end is connected the piston, and the other end is connected the piston handle, the hose passes piston handle and piston shaft, the hose is in the piston with the micropin is connected. In the technical scheme, the position of the piston communicated with the piston handle in the cylinder body is controlled by moving the piston handle, so that the position of a microneedle outlet connected with the piston in the main channel is changed, and the generation control of continuous relative liquid drops in the side channel is realized.
Furthermore, the edge of the PMMA plate is provided with a PMMA cover plate, and channel openings of the main channel and the side channels are reserved on the PMMA cover plate. The PMMA cover plate seals the edges of the PMMA plate except the channel openings of the main channel and the side channels.
Further, the microneedle is located on a center line of the main channel. The micro-needle is positioned on the central line of the main channel, so that the main channel and the micro-needle form a coaxial flow channel, liquid drops generated in the coaxial flow channel are stable and uniform in size, and contact pollution between a dispersed phase in the liquid drops and the inner wall of the main channel can be avoided.
Furthermore, two sides of the main channel are respectively provided with a side channel which is symmetrically communicated, namely a first side channel, a second side channel, a third side channel and a fourth side channel, wherein the first side channel and the third side channel are symmetrically arranged around the main channel, and the second side channel and the fourth side channel are symmetrically arranged around the main channel. The first side channel, the second side channel, the third side channel and the fourth side channel are respectively provided with a second micro injector communicated with the first side channel, the second side channel, the third side channel and the fourth side channel, each second micro injector is provided with a second micro injection pump, and valves are arranged among the first side channel, the second side channel, the third side channel and the fourth side channel and the second micro injectors communicated with the first side channel, the second side channel, the third side channel and the fourth side channel.
According to the technical scheme, valves of the second side channel and the fourth side channel are closed, the continuous phase is injected into the main channel and all the side channels of the PMMA plate by using the second micro-injection pump and the second micro-injector, the disperse phase is injected into the main channel of the PMMA plate by using the first micro-injection pump and the first micro-injector, the disperse phase is broken in the continuous phase to form liquid drops, and the frequency and the size of the formed liquid drops can be controlled by regulating and controlling the two-phase flow of the first micro-injection pump and the second micro-injection pump. When the liquid drops generated by the micro-needle of the main channel are in a dripping mode, the micro-needle is moved to the position where the main channel is communicated with the second and the four-side channels through the adjusting cylinder, the valves of the second and the four-side channels are opened, and the continuous phase loaded in the micro-syringe flows into the main channel from the second and the four-side channels through the second micro-injection pump, so that the shearing action of the continuous phase relative to the dispersed phase is enhanced, and the liquid drops are rapidly generated. Closing the valves of the second and the four-side channels, and when the liquid drop generated by the microneedle of the main channel is generated in a jet flow mode, the liquid drop is generated by breaking at the downstream of the elongated liquid column, and the position of the breaking point gradually moves downstream along with time, so that the generated liquid drop has polydispersity; when the jet liquid column flows through the communication position between the second and the four side channels and the main channel, the valves of the second and the four side channels are opened, and the continuous phase flows into the main channel from the second and the four side channels, so that the shearing action of the continuous phase on the liquid column is strengthened, the convection instability in the jet mode can be effectively inhibited, the change of the droplet flow pattern from the jet mode to the trickle mode can be controlled, and the droplets can be continuously generated by breaking at the downstream position of the communication position between the second and the four side channels and the main channel. The device can effectively control the generation frequency, size and breaking position of the liquid drop by controlling the position of the micro-needle in the main channel and the switch of the valve, and increase the generation range of the size of the liquid drop. In addition, the technical scheme can also achieve the purpose of controlling the generation frequency and the size of the liquid drops by changing the included angle between the side channel and the main channel.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the invention, the position of the microneedle in the main channel is changed through the adjusting cylinder, so that the generation frequency, the size and the fracture position of the liquid drop can be rapidly and flexibly regulated and controlled;
2. according to the invention, the symmetrical side channels are arranged on the two sides of the main channel, so that the generation of the periodic monodispersed liquid drops in a jet flow mode is realized, and the generation range of the size of the liquid drops is enlarged;
3. the invention is composed of PMMA board, micro-injection pump, micro-injector and adjusting cylinder, the structure is simple and easy to design, the manufacturing cost is low, and the applicability is wide.
Drawings
Fig. 1 is a schematic structural diagram of a droplet microfluidic chip according to a first embodiment.
Fig. 2 is a schematic diagram of a process of droplet formation in a droplet microfluidic chip according to a second embodiment.
Fig. 3 is a schematic diagram of a process of forming droplets in a droplet microfluidic chip according to a third embodiment.
The graphic symbols are illustrated as follows:
1-a first micro-injection pump, 2-a first micro-injector, 3-a hose, 4-a piston handle, 5-a piston, 6-a piston shaft, 7-a cylinder, 8-a micro-needle, 9-a PMMA plate, 10-a main channel, 11-a PMMA cover plate, 12-a first side channel, 13-a second side channel, 14-a third side channel, 15-a fourth side channel, 16 a first micro-valve, 17-a second micro-valve, 18-a third micro-valve and 19-a fourth micro-valve.
Detailed Description
The present invention will be further described with reference to the following embodiments. Wherein the showings are for the purpose of illustration only and are shown by way of illustration only and not in actual form, and are not to be construed as limiting the present patent; to better illustrate the embodiments of the present invention, some parts of the drawings may be omitted, enlarged or reduced, and do not represent the size of an actual product; it will be understood by those skilled in the art that certain well-known structures in the drawings and descriptions thereof may be omitted.
The same or similar reference numerals in the drawings of the embodiments of the present invention correspond to the same or similar components; in the description of the present invention, it should be understood that if there is an orientation or positional relationship indicated by the terms "upper", "lower", "left", "right", etc. based on the orientation or positional relationship shown in the drawings, it is only for convenience of describing the present invention and simplifying the description, but it is not intended to indicate or imply that the referred device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and therefore, the terms describing the positional relationship in the drawings are only used for illustrative purposes and are not to be construed as limiting the present patent, and the specific meaning of the terms may be understood by those skilled in the art according to specific circumstances.
First embodiment
Fig. 1 shows a first embodiment of a microfluidic chip according to the present invention. The utility model provides a droplet micro-fluidic chip, wherein, including PMMA board 9, first micro-injection pump 1, first micro-injector 2, adjust a section of thick bamboo, PMMA board 9's inside is equipped with a main entrance 10, inside main entrance 10 runs through PMMA board 9, the one end of main entrance 10 and the sealed butt joint of regulation section of thick bamboo, it is equipped with micropin 8 to adjust a section of thick bamboo inside, micropin 9 gos deep into in the main entrance 10, be located the central line of main entrance 10, the micropin 8 of adjusting a section of thick bamboo passes through hose 3 with first micro-injector 2 and communicates, first micro-injection pump 1 is connected with first micro-injector 2, the injection volume and the injection flow volume of fluid in first micro-injector 2 of first micro-injection pump 1 control. The edge of the PMMA plate 9 is provided with a PMMA cover plate 11.
In this embodiment, symmetrical side channels are respectively arranged in front of and behind two sides of the main channel 10, which are a first side channel 12, a second side channel 13, a third side channel 14 and a fourth side channel 15, the first side channel 12 and the third side channel 14 are symmetrically arranged with respect to the main channel 10, the second side channel 13 and the fourth side channel 15 are symmetrically arranged with respect to the main channel 10, the four side channels all extend to the edge of the PMMA plate 9, second micro-syringes are correspondingly arranged on the first side channel 12, the second side channel 13, the third side channel 14 and the fourth side channel 15, each second micro-syringe is correspondingly connected with one second micro-syringe pump, and a channel port of the main channel 10 and each side channel is reserved on the PMMA cover plate 11. In this embodiment, the main channel 10, the first side channel 12, the second side channel 13, the third side channel 14 and the fourth side channel 15 are all formed by capillary tubes embedded in a PMMA plate.
Because the PMMA plate 9 of this embodiment has a small size, the valve is a micro valve, a first micro valve 16 is disposed between the first side channel 12 and the second micro injector connected thereto, a second micro valve 17 is disposed between the second side channel 13 and the second micro injector connected thereto, a third micro valve 18 is disposed between the third side channel 14 and the second micro injector connected thereto, and a fourth micro valve 19 is disposed between the fourth side channel 15 and the second micro injector connected thereto.
In this embodiment, the adjusting cylinder includes a cylinder 7, a piston handle 4, a piston shaft 6 and a piston 5, the cylinder 7 is in sealed butt joint with the main channel 10, the piston 5 is located in the cylinder 7, one end of the piston shaft 6 is connected with the piston 5 in the cylinder 7, the other end of the piston shaft is connected with the piston handle 4 outside the cylinder 7, and the hose 3 passes through the piston handle 4 and the piston shaft 6 and is connected with the microneedle 8 in the piston 5. The position of the piston 5 connected with the piston handle 4 through the piston shaft 6 in the cylinder 7 is controlled by moving the piston handle 4, so that the position of the outlet of the microneedle 8 connected with the piston 5 in the main channel 10 is changed.
The working principle of the embodiment is as follows: firstly, the second micro valve 17 and the fourth micro valve 19 are closed, the continuous phase is injected into the main channel 10 and all side channels of the PMMA plate 9 by using the second micro injection pump and the second micro injector, the disperse phase is injected into the main channel 10 of the PMMA plate 9 by using the first micro injection pump 1 and the first micro injector 2, the disperse phase is broken in the continuous phase to form liquid drops, and the generation frequency and the size of the liquid drops can be controlled by regulating and controlling the flow rate of the first micro injection pump or the second micro injection pump.
When the droplets generated by the microneedles 8 in the main channel 10 are in a dripping mode, the microneedles 8 are moved to the position where the main channel is communicated with the second side channel 13 and the fourth side channel 15 through the adjusting cylinder, the second micro valve 17 and the fourth micro valve 19 are opened, and the continuous phases in the two second micro injectors enter the main channel 10 from the second side channel 13 and the fourth side channel 15, so that the shearing action of the continuous phase relative to the dispersed phase is strengthened, and the dispersed phase droplets are rapidly generated.
Closing the second and fourth microvalves 17 and 19, when the droplet generation by the microneedles 8 of the main channel 10 is in a fluidic mode, the droplet is generated by breaking downstream of the elongated liquid column, and the breaking point position gradually moves downstream with time, so that the generated droplet has polydispersity; when the jet liquid column flows through the communication position between the second micro valve 17 and the fourth micro valve 19 and the main channel 10, the second micro valve 17 and the fourth micro valve 19 are opened, and the continuous phase flows into the main channel 10 from the second side channel 13 and the fourth side channel 15, so that the continuous phase shearing action borne by the liquid column is strengthened, the convection instability in the jet mode can be effectively inhibited, the change of the droplet flow pattern from the jet mode to the trickle mode can be controlled, and the droplets can be continuously generated by breaking at the downstream position of the communication position between the second side channel 13 and the main channel 10 and the fourth side channel 15. The present embodiment can control the generation frequency, size, and breaking position of droplets and increase the generation range of droplet size by controlling the position of the microneedles 8 in the main channel 10 and the microvalve switches.
Second embodiment
This embodiment is similar to the first embodiment except that the dispersed phase uses water and the continuous phase uses silicone oil, the microneedle 8 has an inner diameter of 32.5 μm, the main channel 10 has an inner diameter of 115 μm, the main channel 10 has an inner diameter of 50 μm, and the first side channel 12, the second side channel 13, the third side channel 14, and the fourth side channel 15 each have an inner diameter of 50 μm.
In the present embodiment, fluent numerical simulation is employed. In this numerical simulation, the flow rates of the dispersed phase and the continuous phase were set to 0.05m/s and 0.2m/s, the densities were set to 965kg/m3 and 998kg/m3, the viscosity coefficients were set to 0.01pa.s and 0.001pa.s, the surface tension coefficients of the two phases were set to 0.015N/m, and the wall contact angle was set to 135 °.
In this embodiment, the first and third microvalves 16 and 18 are opened, the second and fourth microvalves 17 and 19 are closed, the calculation model adopts a VOF/CSF model, the simulation result is shown in fig. 2, the dispersed phase flows out from the microneedles 8, and a narrow jet mode is formed under the shearing action of the continuous phase, as shown in fig. 2 (a). And other conditions are unchanged, the second micro valve 17 and the fourth micro valve 19 are opened, the distance from the microneedle 10 to the second side channel 13 and the fourth side channel 15 is adjusted, when the distance from the tip of the microneedle 8 to the second side channel 13 and the fourth side channel 15 is smaller, the jet liquid column is subjected to continuous phase strong shearing action, and breaks at the position downstream of the communication between the second side channel 13 and the fourth side channel 15 to generate liquid drops, and the liquid drop flow pattern is changed from a jet flow pattern to a dripping flow pattern, as shown in fig. 2 (a-b). The distance from the tip of the microneedle 8 to the second side channel 13 and the fourth side channel 15 is different, the shearing action of the continuous phase on the jet liquid column is also different, and further, the generation frequency, the size and the fracture position of the liquid drop can be controlled by the distance from the tip of the microneedle 8 to the second side channel 13 and the fourth side channel 15, so that the liquid drops with different sizes are generated, as shown in fig. 2 (b-e). When the distance from the microneedle 8 to the second side channel 13 and the fourth side channel 15 is large, the convection instability of the jet liquid column in the main channel 10 is enhanced, and polydisperse droplets begin to be formed periodically, as shown in fig. 2(c-e), which also provides important preconditions for subsequent droplet fusion, splitting, sorting and the like.
Third embodiment
This embodiment is similar to the second embodiment except that the present embodiment increases the two-phase flow rate compared to the second embodiment, wherein the dispersed phase flow rate is increased to 0.1m/s and the continuous phase flow rate is increased to 0.6m/s, otherwise the conditions are unchanged. Under this parameter, the jet liquid column in the main channel 10 can be more slender, as shown in fig. 3 (f). By adjusting the distance from the microneedle 8 to the second side channel 13 and the fourth side channel 15, when the distance from the microneedle 8 to the second side channel 13 and the fourth side channel 15 is small, under the continuous phase strong shearing action, a droplet with a smaller size can be generated stably and controllably at a high frequency, as shown in fig. 3 (g). Continuing to increase the distance from the microneedle 10 to the second side channel 13 and the fourth side channel 15, the droplet generation changes from monodisperse droplets to polydisperse droplets, as shown in fig. 3 (h-j).
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.
Claims (6)
1. A droplet microfluidic chip, comprising: including PMMA board, first micro syringe, regulation section of thick bamboo, be equipped with in the PMMA board and run through the main entrance of PMMA board, the both sides of main entrance respectively are equipped with the side passageway of symmetry intercommunication, the side passageway extends to the side of PMMA board, first micro syringe with first micro syringe is connected, be equipped with the hose on the first micro syringe, be equipped with the micropin on the regulation section of thick bamboo, the hose will first micro syringe with the micropin intercommunication, adjust the section of thick bamboo with main entrance sealing connection, the micropin gos deep into the main entrance, all be connected with the second micro syringe on the side passageway, the second micro syringe all is equipped with the second micro syringe pump, the side passageway with be equipped with the valve between the second micro syringe.
2. A droplet microfluidic chip according to claim 1, wherein: the adjusting cylinder comprises a cylinder body, a piston handle, a piston shaft and a piston, the cylinder body is in sealed butt joint with the main channel, the piston is located in the cylinder body, one end of the piston shaft is connected with the piston, the other end of the piston shaft is connected with the piston handle, the hose penetrates through the piston handle and the piston shaft, and the hose is connected with the microneedle in the piston.
3. A droplet microfluidic chip according to claim 2, wherein: the edge of the PMMA plate is provided with a PMMA cover plate, and channel openings of the main channel and the side channels are reserved in the PMMA cover plate.
4. A droplet microfluidic chip according to claim 2, wherein: the microneedle is located on a centerline of the main channel.
5. A droplet microfluidic chip according to claim 4, wherein: two sides of the main channel are respectively provided with a first side channel, a second side channel, a third side channel and a fourth side channel which are symmetrically communicated, the first side channel and the third side channel are symmetrically arranged around the main channel, and the second side channel and the fourth side channel are symmetrically arranged around the main channel.
6. A droplet microfluidic chip according to claim 5, wherein: the first side channel, the second side channel, the third side channel and the fourth side channel are respectively provided with a second micro injector communicated with the first side channel, the second side channel, the third side channel and the fourth side channel, each second micro injector is provided with a second micro injection pump, and valves are arranged among the first side channel, the second side channel, the third side channel and the fourth side channel and the second micro injectors communicated with the first side channel, the second side channel, the third side channel and the fourth side channel.
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| CN114210378A (en) * | 2021-11-22 | 2022-03-22 | 广东省科学院健康医学研究所 | Liquid drop generating device based on microporous capillary and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114210378A (en) * | 2021-11-22 | 2022-03-22 | 广东省科学院健康医学研究所 | Liquid drop generating device based on microporous capillary and preparation method thereof |
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