CN108393103A - A kind of achievable drop size does not depend on the micro-fluidic chip of flow - Google Patents

Abstract

The invention discloses a microfluidic chip capable of realizing that the droplet size does not depend on flow rate, and belongs to the technical field of microfluidic chips. The microfluidic chip highlights the influence of interfacial tension and geometric configuration on droplet generation, and reduces the dependence of droplet size on velocity. The microfluidic chip includes an upper layer channel structure, a middle layer and a lower layer channel structure. The upper channel is composed of the discrete phase channel, the continuous phase channel, the droplet generation chamber and the droplet observation chamber; at the same time, the Taguchi method is used to reduce the number of experiments and determine the optimal geometric parameter structure of the droplet generation chamber. This chip enables the uniform and stable generation of droplets without depending on the change of the two-phase flow rate, which helps to break through the driving limit of droplet generation, expands the speed range in which the chip performance is stable, and makes the two-phase flow of micro-droplets suitable for different applications. driving conditions.

Description

A microfluidic chip that realizes droplet size independent of flow rate

technical field

The invention designs a microfluidic chip capable of satisfying that the size of the droplet is not dependent on the flow rate based on the channel structure for generating microdroplets induced by interfacial tension, and belongs to the technical field of microfluidic chips.

Background technique

Microfluidic chip refers to the science and technology involved in using micropipes (tens to hundreds of microns in size) to process or manipulate tiny fluid systems. It is a subject involving chemistry, fluid physics, microelectronics, new materials, biology and the emerging interdiscipline of biomedical engineering. Compared with the traditional analysis platform, the micro-droplets prepared by the microfluidic chip can effectively reduce the cost of the experiment. Only a small amount is used in the experiment, which can greatly save the use of expensive biochemical reagents, and has good monodispersity ; Accurate and controllable, uniform size; fast generation frequency (tens of thousands of hertz, hundreds of droplets can be generated per second); full mixing, fast reaction time; high throughput, no cross-contamination and other advantages. It has a wide range of applications in DNA and polymerase chain reaction analysis, blood testing, protein crystallization, single cell culture, particle synthesis, etc.

At present, the droplet microfluidic technology in the experiment relies on the precise liquid flow rate provided by the supporting driving equipment, which makes the speed dependence of the generation of microdroplets particularly prominent. This not only makes it difficult for microfluidic technology to be suitable for quick and easy manual operation, and limits its application in detection and reaction, but also, the flow velocity provided by commonly used driving devices is fluctuating, which easily leads to poor performance of microfluidic chips. Stablize. Therefore, it is necessary to weaken the requirements of droplet microfluidic technology on flow rate accuracy, and convert unstable driving input conditions into stable output results, so as to expand the applicable flow rate range of microfluidic chips. Taguchi method is a low-cost, high-efficiency quality engineering method, which emphasizes that the improvement of product quality is not through inspection, but through design. The Taguchi method can analyze the sensitivity of each geometric parameter and determine the optimal parameter combination. It is based on the L9 orthogonal array (Orthogonal Array) experiment to achieve parameter optimization. Using the L9 orthogonal array reduces the number required in the analysis from 34581 to 9, can greatly reduce the number of experiments.

The flow velocity of the liquid affects the function of the droplet microfluidic chip by changing the force on the two-phase interface. In the process of multiphase flow, weakening the force related to the flow velocity and highlighting the interfacial tension determined by the geometric structure and physical parameters of the flow medium can reduce the influence of the two-phase flow velocity on the droplet formation and flow behavior. Therefore, the present invention realizes a microfluidic chip based on the induction of interfacial tension, which can make the droplet size less dependent on the velocity, and uses the Taguchi method to improve the channel geometry to obtain the optimal chip structure. The chip helps to break through the driving limitation of droplet generation, expands the speed range in which the chip performance maintains stability, and makes the micro-droplet two-phase flow applicable to different driving conditions.

Contents of the invention

The present invention is based on the microchannel structure induced by interfacial tension, by changing the geometric size of the channel structure, and using the Taguchi method to experiment and obtain the sensitivity of various geometric parameters, and aims to obtain a microfluidic chip that can realize the droplet size independent of the flow rate.

The technical solution adopted in the present invention is a microfluidic chip induced by interfacial tension. The microfluidic chip obtains an optimal parameter structure by changing geometric parameters based on the microchannel structure induced by interfacial tension.

The microfluidic chip includes an upper microchannel 1, an intermediate film 2, and a lower microchannel 3; the upper microchannel 1 includes a discrete phase channel 4, a discrete phase inlet 5, a continuous phase channel 6, a continuous phase inlet 7, and a driving phase channel 8 , driving phase inlet 9, droplet generation chamber 10, main channel 11, droplet observation chamber 12, outlet 13;

The lower microchannel 3 includes grooves 14 . One end of the discrete phase channel 4 and the continuous phase channel 6 are respectively connected to the discrete phase inlet 5 and the continuous phase inlet 7; the other ends of the discrete phase channel 4 and the continuous phase channel 6 are jointly connected to the droplet generation chamber 10; the other end of the droplet generation chamber 10 Connected to the main channel 11; the driving phase inlet 9 is connected to the driving phase channel 8 and then connected to the main channel 11 at one end of the droplet observation chamber 12; the other end of the droplet observation chamber 12 is connected to the outlet 13. The upper microchannel 1 and the middle layer film 2 are bonded and connected by an ultraviolet plasma bonding machine, and then the groove 14 in the lower microchannel 3 is aligned with the droplet generation cavity 10 of the upper microchannel 1, and the lower microchannel 3 and the The interlayer film 2 is bonded.

The PDMS prefabricated reagent is passed into the lower microchannel 3 , pressure is applied to the upper microchannel 1 , the PDMS prefabricated reagent is fixed by thermosetting method, and an arc-shaped wall surface is formed at the bottom of the droplet generation chamber 10 . When the two-phase fluid flows, the arc-shaped wall of the channel makes the curvature of the discrete phase at the front and rear ends different. When the Laplace pressure difference cannot be balanced by the interface deformation, the discrete phase forms droplets. During the formation of droplets from the discrete phase, due to the relatively small flow resistance, the interfacial tension plays a dominant role and determines the critical condition for droplet breakage.

Considering that the two-phase flow has little influence on the droplet in this structure, in order to ensure that the droplet can pass through smoothly and not stay in the droplet observation chamber 12, the driving phase channel 8 is connected to the droplet observation chamber 12. At the same time, the droplet observation chamber 12 is not set in the conventional micro-scale channel, but the bottom of the droplet generation chamber 10 forms an arc-shaped wall surface, which makes it difficult to measure the droplet size and motion shape, so the main channel is connected behind the droplet generation chamber 10 11. After the main channel 11, the liquid drop observation chamber 12 is connected to facilitate data measurement.

The upper microchannel 1, the middle film 2 and the lower microchannel 3 are all made of PDMS material.

The fabrication process of the microfluidic chip is as follows:

1) The upper layer microchannel 1, the lower layer microchannel 3 and the middle layer film 2 with the channel structure are fabricated respectively by PDMS pouring, which are PDMS films cast on silicon wafers by centrifugal force.

2) Bond the molded upper layer microchannel 1 and the middle layer film 2 using an ultraviolet light plasma bonding machine, and then align the groove 14 in the lower layer microchannel 3 with the droplet generation cavity 10 of the upper layer microchannel 1, and the lower layer The microchannel 3 is bonded to the upper microchannel 1 .

3) Pass the PDMS prefabricated reagent into the groove 14, apply pressure to the upper microchannel 1, fix the PDMS prefabricated reagent by thermosetting method, form an arc-shaped wall surface, and obtain a microchannel structure induced by interfacial tension.

The specific working process of the microfluidic chip is as follows: the discrete phase liquid flows in from the discrete phase inlet 5, and the continuous phase liquid flows in from the continuous phase inlet 7; the discrete phase liquid and the continuous phase liquid meet at the droplet generation chamber 10, and the discrete phase liquid The liquid droplets generated by rupture flow downstream together with the continuous phase liquid, enter the droplet observation chamber 12 through the main channel, and finally flow out of the chip through the outlet 13 .

Description of drawings

Fig. 1 is a schematic diagram of a three-dimensional general outline of a microfluidic chip capable of realizing droplet size independent of flow rate according to the present invention.

Fig. 2 is a schematic cross-sectional view of a microfluidic chip capable of realizing droplet size independent of flow rate according to the present invention.

Fig. 3 is a schematic diagram of the working process of the upper microchannel of a microfluidic chip capable of realizing droplet size independent of flow rate according to the present invention.

Fig. 4 is a schematic diagram of the lower microchannel structure of a microfluidic chip capable of realizing droplet size independent of flow rate according to the present invention.

The data provided in Fig. 5 are measured under the condition that the flow rate of the continuous phase is 50 μL/min.

Figure 6 shows the influence of the three factors on the signal-to-noise ratio.

In the figure: 1. Upper microchannel; 2. Middle film; 3. Lower channel; 4. Discrete phase channel; 5. Discrete phase inlet; 6. Continuous phase channel; 7. Continuous phase inlet; 8. Driving phase channel; 9. Drive phase inlet; 10. Droplet generation cavity; 11. Main channel; 12. Droplet observation cavity; 13. Outlet; the lower channel structure includes: 14. Groove.

Detailed ways

The working process and effect of inventing a microfluidic chip capable of realizing droplet size independent of flow will be described in detail below in conjunction with the structural drawings.

The specific working process of this chip is as follows: the discrete phase liquid flows in from the discrete phase inlet 5, the continuous phase liquid flows in from the continuous phase inlet 7, and the two meet in the droplet generation chamber 10, and the discrete phase liquid breaks to generate droplets and together with the continuous phase It flows downstream, enters the droplet observation cavity 12 through the main channel, and finally flows out of the chip through the outlet 13 .

Fig. 1 is a schematic diagram of a three-dimensional general outline of a microfluidic chip capable of realizing droplet size independent of flow rate according to the present invention. Figure 2 and Figure 3 are schematic diagrams of the working process. There are nine microchannel structures of different sizes. The two fluids flow into the microfluidic chip through two inlets driven by external forces, and the flow speed of the two liquids is adjusted to generate microfluidics. Droplets, and maintain the flow rate for a period of time to stabilize the flow state, the continuous phase is introduced into the inlet of the driving phase, and when the droplets enter the droplet observation chamber, the droplet generation recording experiment is performed. The droplet size uniformity of the nine groups of experiments is shown in Figure 4, and the droplet size of the sixth group structure has little dependence on the two-phase flow rate, which shows that the present invention can significantly affect the droplet generation.

The optimal parameters of the cavity length l, cavity width w, and cavity expansion angle θ of the droplet generating cavity 10 are obtained by Taguchi method (as shown in FIG. 3 ). Three parameter tables are designed as shown in Table 1. The experimental scheme of Taguchi method orthogonal matrix is shown in Table 2. The influence of the three factors on the signal-to-noise ratio obtained from the 9 groups of experiments is shown in Figure 6. The optimal parameters were determined to be a cavity expansion angle of 30°, a cavity width of 0.5 mm, and a cavity length of 2.6 mm.

Table 1. Parameter factor table

Table 2. Orthogonal matrix experimental scheme

Claims (5)

1. a kind of achievable drop size does not depend on the micro-fluidic chip of flow, which is a kind of based on interfacial tension Micro-fluidic chip under induction, it is characterised in that：Microchannel structure under the micro-fluidic chip is induced based on interfacial tension passes through Change geometric parameter, obtains optimal argument structure；

The micro-fluidic chip includes upper layer microchannel (1), intermediate layer film (2), lower layer microchannel (3)；It wraps upper layer microchannel (1) Include discrete phase channel (4), discrete phase entrance (5), continuous phase channel (6), continuous phase entrance (7), driving phase channel (8), driving Phase entrance (9), drop formation chamber (10), main channel (11), drop observation chamber (12), outlet (13)；

Lower layer microchannel (3) includes groove (14)；Discrete phase channel (4) and continuous phase channel (6) one end are separately connected discrete phase Entrance (5) and continuous phase entrance (7)；Discrete phase channel (4) and continuous phase channel (6) other end are commonly connected to drop formation chamber (10) on；Drop formation chamber (10) other end connects main channel (11)；Drive phase entrance (9) connect driving phase channel (8) afterwards with Main channel (11) is commonly connected to one end of drop observation chamber (12)；Drop observes chamber (12) other end connection outlet (13)；On Layer microchannel (1) carries out bonding by ultraviolet light plasma bonder with intermediate layer film (2) and connects, then by lower layer microchannel (3) the drop formation chamber (10) of groove (14) alignment upper layer microchannel (1) in, by lower layer microchannel (3) and intermediate layer film (2) bonding connection is carried out；

PDMS prefabricated reagents are passed through in lower layer microchannel (3), are pressed to upper layer microchannel (1), it will using thermosetting method PDMS prefabricated reagents are fixed, and curved wall is formed in the bottom of drop formation chamber (10)；When two-phase fluid flows, gate arc Shape wall surface keeps discrete phase different in the curvature of rear and front end, when laplace pressure difference can not continue to be balanced by interface deformation, Discrete phase forms drop；Discrete phase is formed during drop, and since flow resistance is relatively small, interfacial tension plays a leading role, certainly Determine the critical condition of drop fracture.

2. a kind of achievable drop size according to claim 1 does not depend on the micro-fluidic chip of flow, it is characterised in that： In view of two phase flow is to drips very little in the structure, to ensure that drop can pass through, not in drop observation chamber (12) Middle stop, therefore access driving phase channel (8) at drop observation chamber (12)；Drop observation is not arranged for conventional microscale channel simultaneously Chamber (12), but curved wall is formed on the bottom of drop formation chamber (10), is caused centainly to the measurement of drop size and motion morphology Difficulty, therefore main channel (11) is connected afterwards in drop formation chamber (10), drop observation chamber (12), side are connected afterwards in main channel (11) Just DATA REASONING.

3. a kind of achievable drop size according to claim 1 does not depend on the micro-fluidic chip of flow, it is characterised in that： Upper layer microchannel (1), intermediate layer film (2) and lower layer microchannel (3) are made of PDMS material.

4. a kind of achievable drop size according to claim 1 does not depend on the micro-fluidic chip of flow, it is characterised in that： The production process of the micro-fluidic chip is as follows：

1) upper layer microchannel (1), lower layer microchannel (3) and centre containing channel design are made respectively in such a way that PDMS is poured Layer film (2) is the PDMS film for getting rid of system using centrifugal force on silicon chip；

2) ultraviolet plasma bonder is used to be bonded the upper layer microchannel (1) of cast molding and intermediate layer film (2), then By in lower layer microchannel (3) groove (14) be aligned upper layer microchannel (1) drop formation chamber (10), lower layer microchannel (3) with Upper layer microchannel (1) is bonded；

3) PDMS prefabricated reagents are passed through in groove (14), pressed to upper layer microchannel (1), it is using thermosetting method that PDMS is pre- Reagent processed is fixed, and curved wall is formed, and obtains the microchannel structure under interfacial tension induction.

5. a kind of achievable drop size according to claim 1 does not depend on the micro-fluidic chip of flow, it is characterised in that： The specific work process of the micro-fluidic chip is as follows：Discrete phase liquid is flowed into from discrete phase entrance (5), and continuous phase liquid is from continuous Phase entrance (7) flows into；Discrete phase liquid and continuous phase liquid cross at drop formation chamber (10), and discrete phase liquid ruptures generate Drop and with continuous phase liquid toward downstream flow, drop is entered by main channel and observes chamber (12), eventually by outlet (13) chip is flowed out.