WO2021168768A1

WO2021168768A1 - Microfluidic chip, and microfluidic system

Info

Publication number: WO2021168768A1
Application number: PCT/CN2020/077080
Authority: WO
Inventors: 樊博麟; 赵莹莹; 姚文亮; 古乐; 廖辉; 赵楠; 高涌佳; 李月
Original assignee: 京东方科技集团股份有限公司; 北京京东方传感技术有限公司
Priority date: 2020-02-28
Filing date: 2020-02-28
Publication date: 2021-09-02
Also published as: CN113811389A; CN113811389B

Abstract

A microfluidic chip and a microfluidic system. The microfluidic chip comprises: a first substrate (1) and a second substrate (2) disposed oppositely, and a droplet accommodation space (3) located between the first substrate (1) and the second substrate (2), wherein the droplet accommodation space (3) comprises an operation region (S1) used to generate a sub-droplet. The first substrate (1) comprises a first base (11), and multiple drive units (12) spaced apart and disposed on a side of the first base (11) close to the second substrate (2) and in a region of the first base (11) corresponding to the operation region (S1). The second substrate (2) comprises a second base (21) capable of deforming along with a temperature increase, and multiple temperature control units (22) having a one-to-one correspondence with the drive units (12) and used to enable a temperature of the second substrate (21) to increase at a location corresponding to the temperature control units (22) and create deformation accordingly, such that a deformation location of the second substrate (21) squeezes a droplet in the droplet accommodation space (3) and divides the droplet into at least two sub-droplets. The microfluidic system comprises the microfluidic chip.

Description

Microfluidic chip and microfluidic system

Technical field

The invention belongs to the technical field of micro-droplets, and specifically relates to a microfluidic chip and a microfluidic system.

Background technique

Microfluidics is a technology for precisely controlling micro-scale fluids. Through this technology, microfluidics technology is applied to various fields, such as microfluidic chips. The microfluidic chip can divide the droplet into multiple sub-droplets for analysis and detection. A typical microfluidic chip usually adopts a three-layer structure, that is, controlled droplets are sandwiched between the upper substrate and the lower substrate. The lower substrate is composed of a base, a microelectrode array, a dielectric layer and a lyophobic layer from bottom to top. By pressing the electrodes in the microelectrode array, based on the principle of dielectric wetting, the controlled droplets can be controlled to move on the microelectrode array, and the controlled droplets can be divided into multiple sub-droplets.

In the existing microfluidic technology, the generation of sub-droplets is generally achieved by making electrodes of different sizes, and only using the dielectric wetting effect to achieve the generation of sub-droplets. If you want to improve the drive for dividing the controlled droplet into sub-droplets The force is usually used to increase the voltage of the electrode and increase the dielectric constant of the dielectric layer. When the voltage of the electrode is too large, it is easy to cause irreversible thermal breakdown of the dielectric layer. Moreover, if the dielectric constant of the dielectric layer is too large, the controlled droplets will be easily polarized during the movement process, thereby affecting the generation of sub-droplets. Therefore, the technical solutions in the microfluidic chip to increase the driving force of dividing the controlled droplet into sub-droplets all face technical bottlenecks.

Summary of the invention

The present invention aims to solve at least one of the technical problems existing in the prior art and provide a microfluidic chip and a microfluidic system.

In the first aspect, an embodiment of the present invention provides a microfluidic chip, including:

A first substrate and a second substrate are opposed to each other. The microfluidic chip includes a droplet splitting area for splitting droplets. In the droplet splitting area, the first substrate and the second substrate There is a droplet accommodating space in between; wherein, the droplet accommodating space includes a working area for generating sub-droplets;

The first substrate includes:

First substrate

A plurality of driving units are arranged at intervals on the side of the first substrate close to the second substrate, and are arranged in an area of the first substrate corresponding to the working area;

The second substrate includes:

The second substrate can deform as the temperature rises;

A plurality of temperature control units corresponding to the driving unit one-to-one, and the temperature control unit is used to cause the second substrate to deform in response to an increase in temperature where the temperature unit is located, so that the second substrate The bottom deformation squeezes the droplet in the droplet accommodating space to split it into at least two sub-droplets.

In the microfluidic chip provided by the embodiment of the present invention, since the second substrate can be deformed as the temperature rises, and a plurality of temperature control units are provided in the second substrate, so that the droplet flows through the droplet accommodating space. In the working area of the second substrate, the temperature control unit heats the second substrate corresponding to the temperature control unit to increase its temperature and produce deformation, so that the deformation of the second substrate will squeeze the droplets in the droplet accommodating space to make The droplet splits into at least two sub-droplets.

Optionally, the orthographic projection of the temperature control unit on the first substrate is limited to the corresponding orthographic projection of the driving unit on the first substrate.

Optionally, the central area of the orthographic projection of the temperature control unit on the first substrate overlaps the central area of the orthographic projection of the driving unit on the first substrate.

Optionally, the shape of the temperature control unit is a square with a side length of 0.12 mm; the shape of the driving unit is a square with a side length of 0.4 mm.

Optionally, the first substrate further includes:

The dielectric layer is arranged on the side of the driving unit close to the second substrate;

The first liquid repellent layer is arranged on the side of the dielectric layer close to the second substrate;

The second substrate further includes:

The second lyophobic layer is arranged on the outermost side of the second substrate close to the droplet accommodating space.

Optionally, the temperature control unit includes: a temperature rise device and a temperature measurement device;

The heating device is arranged on a side of the second substrate close to the first substrate, and is used to heat the position of the second substrate corresponding to the heating device;

The temperature measuring device is arranged on the side of the second substrate away from the first substrate, and is used to detect the temperature of the position of the second substrate corresponding to the heating device, so that the second substrate corresponds to The position of the heating device reaches a preset temperature.

Optionally, the temperature increasing device includes a thermal resistance; the temperature measuring device includes a thermocouple.

Optionally, the central area of the orthographic projection of the heating device on the second substrate overlaps with the central area of the orthographic projection of the temperature measuring device on the second substrate.

Optionally, the area of the orthographic projection of the heating device on the second substrate is the same as the area of the orthographic projection of the temperature measuring device on the second substrate.

Optionally, the driving unit includes a first electrode, which drives the droplet in the working area to move or split by a voltage.

Optionally, the droplet accommodating space further includes a liquid storage area for storing the droplets;

The first substrate further includes a plurality of second electrodes, which are provided on the same layer as the first electrode on the side of the first substrate close to the second substrate, and are provided on the first substrate corresponding to the liquid storage The area of the area, which drives the droplets in the liquid storage area to move to the working area by voltage.

Optionally, the area of the orthographic projection of the second electrode on the first substrate is larger than the area of the orthographic projection of the first electrode on the first substrate.

Optionally, the second substrate further includes a conductive layer disposed on a side of the second substrate close to the first substrate, and the conductive layer is connected to a common voltage terminal.

Optionally, the material of the second substrate includes any one of polytetrafluoroethylene and polymethyl methacrylate.

In the second aspect, an embodiment of the present invention provides a microfluidic system, including the above-mentioned microfluidic chip.

Optionally, the above-mentioned microfluidic system further includes: a control unit connected to the driving unit in the microfluidic chip and configured to control the voltage of each driving unit in the microfluidic chip;

The control unit is also connected to the temperature control unit in the microfluidic chip, and is used to control the temperature control unit in the microfluidic chip to heat the second substrate at a position corresponding to the temperature control unit to The preset temperature.

Optionally, the above-mentioned microfluidic system further includes: a cooling system connected to the control unit and configured to reduce the temperature of the second substrate in the microfluidic chip and eliminate the deformation of the second substrate.

Optionally, the cooling system includes: a cooling device and a stepping motor;

The stepping motor is connected to the cooling device and the control unit, and the stepping motor controls the cooling device to contact the second substrate to reduce the temperature of the second substrate.

Optionally, the aforementioned microfluidic system further includes: a circuit control board connected to the control unit, the circuit control board having a plurality of interfaces, and the plurality of interfaces are connected to a plurality of drivers in the microfluidic chip The units are connected one by one, and the control unit controls the voltage of each driving unit through the circuit control board.

Optionally, the control unit includes a programmable power supply and a programmable logic controller.

Optionally, the aforementioned microfluidic system further includes:

The observation system is used to observe the generation state of the neutron droplets of the microfluidic chip.

Optionally, the observation system includes a transparent platform, and the microfluidic chip is arranged on the transparent platform;

The observation system further includes: an image unit, a filter, and a focusing objective lens arranged on the side of the transparent platform away from the microfluidic chip in sequence, and arranged on the side of the microfluidic chip away from the transparent platform The backlight.

Description of the drawings

Fig. 1 is a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention.

Fig. 2 is a schematic diagram of the principle of manipulating the movement of liquid droplets in an embodiment of the present invention.

Fig. 3 is a schematic structural diagram (top view) of a microfluidic chip according to an embodiment of the present invention.

Fig. 4 is a schematic diagram of the principle of the microfluidic chip producing sub-droplets in an embodiment of the present invention.

FIG. 5 is a schematic diagram of the principle of manipulating the splitting of a droplet into sub-droplets in an embodiment of the present invention.

Fig. 6 is a cross-sectional view taken along the A-A' direction in Fig. 5;

Fig. 7 is a cross-sectional view taken along the B-B' direction in Fig. 5;

8 is a schematic diagram of the positive dizziness relationship between the temperature control unit and the driving unit in the microfluidic chip of the embodiment of the present invention on the second substrate.

FIG. 9 is a schematic diagram of the central area of the temperature control unit and the central area of the driving unit in the microfluidic chip of the embodiment of the present invention.

Fig. 10 is a schematic diagram of another embodiment of the microfluidic chip in the embodiment of the present invention.

FIG. 11 is a schematic diagram of the simulation result of the thermal expansion effect of the second substrate in the microfluidic chip in the embodiment of the present invention.

FIG. 12 is a system structure diagram of a microfluidic system provided by an embodiment of the present invention.

Detailed ways

In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.

The shapes and sizes of the components in the drawings do not reflect the true proportions, and are only for the purpose of facilitating the understanding of the content of the embodiments of the present invention.

Unless otherwise defined, the technical terms or scientific terms used in the present disclosure shall have the usual meanings understood by those with ordinary skills in the field to which this disclosure belongs. The "first", "second" and similar words used in the present disclosure do not indicate any order, quantity, or importance, but are only used to distinguish different components. Similarly, similar words such as "a", "one" or "the" do not mean a quantity limit, but mean that there is at least one. "Include" or "include" and other similar words mean that the element or item appearing before the word covers the element or item listed after the word and their equivalents, but does not exclude other elements or items. Similar words such as "connected" or "connected" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Up", "Down", "Left", "Right", etc. are only used to indicate the relative position relationship. When the absolute position of the described object changes, the relative position relationship may also change accordingly.

In the first aspect, as shown in FIG. 1, an embodiment of the present invention provides a microfluidic chip, which includes a first substrate 1 and a second substrate 2 disposed oppositely. The microfluidic chip includes multiple functional areas, such as a droplet splitting area for splitting droplets, a droplet detection area for detecting droplets, and a droplet mixing area for mixing liquids. In the following embodiments of the invention and the drawings, the droplet splitting area is used for description. In the droplet splitting area, a droplet accommodating space 3 for accommodating droplets is defined between the first substrate 1 and the second substrate 2.

Among them, the droplet accommodating space 3 can be divided into a working area S1 and a liquid storage area S2. The liquid storage area S2 is used to store the droplets of the sample to be generated, and the working area S1 is used to generate sub-droplets. The droplet accommodating space 3 can contain any fluid that needs to generate sub-droplets, such as water (H ₂ O) and blood. For the convenience of description, in the embodiment of the present invention, the liquid droplet 31 in the liquid droplet receiving space 3 is taken as an example for description.

Specifically, the first substrate 1 may include a first substrate 11 and a plurality of driving units 12. Wherein, a plurality of driving units 12 are arranged at intervals on the side of the first substrate 11 close to the second substrate 2, and the plurality of driving units 12 are arranged in an area of the first substrate 11 corresponding to the working area S1 of the droplet accommodating space 3. Multiple driving units 12 can be connected to an external power supply, and the voltage of each driving unit 12 can be individually controlled by the external power supply. Based on the dielectric wetting effect, the driving unit 12 can drive the droplet 31 to move after being applied with a voltage by the external power supply.

In some embodiments, as shown in FIGS. 1 and 2, the first substrate 1 may further include a dielectric layer 13, which is disposed on the side of the driving unit 12 close to the second substrate 2. If the dielectric layer 13 has With good liquid repellency, the droplet 31 is in contact with the dielectric layer 13. When the driving unit 12 is not pressurized, the liquid droplet 31 of the dielectric layer 13 has a relatively large surface tension due to its own lyophobic characteristics. The contact angle between the liquid droplet 31 and the dielectric layer 13 is the initial contact angle. The driving unit 12 applies a voltage to cause the dielectric layer 13 to accumulate charges at the position of the driving unit 12 to which the voltage is applied, thereby changing the wetting characteristics between the dielectric layer 13 and the droplets 31 attached to the surface of the dielectric layer 13 , The contact angle between the droplet 31 and the dielectric layer 13 is changed, so that the droplet 31 is deformed, and a pressure difference is generated inside the droplet 31, thereby realizing the manipulation of the droplet 31.

For ease of description, as shown in FIG. 2, taking the first substrate 1 including three driving units 12 arranged at intervals from left to right as an example, the microfluidic chip is described. Of course, this does not constitute an implementation of the present invention. Limitations of examples. The three driving units 12 are respectively a first driving unit 121, a second driving unit 122 and a third driving unit 133. When no voltage is applied to the driving unit 12, the shape of the droplet 31 is symmetrically distributed (as shown by the dotted line in FIG. 2), and the contact angle between the droplet 31 and the first substrate 1 is the first initial contact angle θ ₀ , and the droplet The contact angle between 31 and the second substrate 2 is the second initial contact angle θ _t . If the droplet needs to move to the right, a voltage is applied to the third driving unit 123 on the far right side, and the first driving unit 121 and the second driving unit 122 do not apply voltage or apply a voltage lower than the voltage of the third driving unit 123, Due to the dielectric wetting effect, the contact angle between the right side of the droplet 31 and the position of the third driving unit 123 and the first substrate 1 changes, and the first initial contact angle θ _{0 is} reduced to the dielectric contact angle θ. _V , since the voltage almost only acts on the contact surface between the droplet 31 and the first substrate 1, the contact angle between the droplet 31 and the second substrate 2 (that is, the second initial contact angle θ _t ) hardly changes, so The droplet 31 is deformed asymmetrically, and a pressure difference is generated inside the droplet 31, so that the droplet 31 moves to a position close to the third driving unit 123.

Similarly, as shown in FIG. 3, FIG. 3 is a top view of the microfluidic chip in FIG. The driving unit 12, a plurality of driving units 12 are connected to an external power source through a bonding area, and by applying a voltage to the corresponding driving unit 12, the droplet 31 can be moved in a corresponding direction.

Specifically, the relationship between the contact angle between the droplet 31 and the dielectric layer 13 and the voltage of the driving unit 12 can be expressed as follows:

Among them, ε ₀ is the vacuum dielectric constant, ε _r is the relative dielectric constant of the dielectric layer 13, γ _lg is the surface tension coefficient of the liquid-gas interface, and ΔV is the lower surface of the dielectric layer 13 close to the first substrate 11 and The potential difference between the upper surfaces close to the droplet accommodating space 3, D is the thickness of the dielectric layer 13.

Alternatively, it can be seen from the above formula that if the relative permittivity ε _{r of the} _{dielectric layer 13 increases, the dielectric contact angle θ V of the} droplet 31 will increase when the same voltage V is applied to the driving unit 2 If the relative permittivity ε _{r of} the dielectric layer 13 is too large, the droplet will be easily polarized during the movement process, so that the microfluidic chip can easily control the droplet 31. The manipulation is invalid. Therefore, in the embodiment of the present invention, the dielectric layer 13 can be made of a material with a relative permittivity within a preset range. For example _{, the preset range of the relative permittivity ε r} of the dielectric layer 13 is [2.9, 3.1].

In some embodiments, as shown in FIG. 1, if the dielectric layer 13 is made of a material that does not have liquid repellency, a first liquid repellent layer 14 may be provided on the first substrate 1, and a second hydrophobic layer 14 may be provided on the second substrate 2. The liquid layer 23, the first liquid-repellent layer 14 is provided on the side of the dielectric layer 13 close to the second substrate 2 and the second liquid-repellent layer 23 is provided on the outermost side of the second substrate 21 close to the droplet accommodating space 3. The first liquid-repellent layer 14 and the second liquid-repellent layer 23 are in contact with the liquid droplets 31 in the liquid droplet accommodating space 3, so that the liquid droplets 31 have a relatively large surface tension. The dielectric constant of the first liquid-repellent layer 14 and the second liquid-repellent layer 23 may be the same as or different from the dielectric layer 13, which is not limited here.

Further, as shown in FIGS. 1 and 4, the second substrate 2 may further include a second substrate 21 and a plurality of temperature control units 22. Wherein, the second substrate 21 is made of a material with a high thermal expansion coefficient, so that the second substrate 21 can deform as the temperature rises. A plurality of temperature control units 22 are provided in the second substrate 2, and the temperature control units 22 correspond to the driving units 12 in the first substrate 1 one-to-one. The temperature control unit 22 can heat the temperature of the second substrate 21 corresponding to the temperature control unit 22 to a preset temperature, so that the second substrate 21 is deformed in the position corresponding to the temperature control unit 22, and the direction of the deformation is approximately vertical It extends to both sides of the second substrate 21 in the direction of the first substrate 1, so that the deformed portion of the second substrate 21 squeezes the droplet 31 in the droplet accommodating space 3 to split the droplet 31 into a plurality of sub-droplets.

For ease of description, as shown in FIG. 4, a temperature control unit 22 on the second substrate 2 is taken as an example to describe the microfluidic chip. Of course, this does not constitute a limitation to the embodiment of the present invention. The temperature control unit 22 and the corresponding driving unit 12 on the first substrate 1 are arranged oppositely. When the temperature control unit 22 is not working, as shown in Figure 4 (a), the second substrate 21 is not deformed and the liquid The surface tension distribution of the contact surface between the drop 31 and the second substrate 21 is relatively uniform. If it is necessary to generate two sub-droplets from the droplet 31, the temperature control unit 22 heats the second substrate 21 corresponding to the temperature where the temperature control unit 22 is located to a preset temperature, because the material of the second substrate 21 has high expansion Therefore, as shown in Figure 4(b), the second substrate 21 is deformed at the corresponding part of the temperature control unit 22, and the direction of the deformation is approximately perpendicular to the first substrate 1 toward the second substrate 21. , So that the deformation of the second substrate 21 generates a pressure F ₁ directed from the second substrate 21 to the direction of the first substrate 1 on the droplet 31, and the pressure F ₁ acts on the droplet 31 corresponding to the second substrate The position of the deformation of 21. As shown in FIG. 4 (c), the liquid droplet 31 F ₁ under pressure, the deformation of the droplets 31 at a position corresponding to the recess of the second substrate 21 is generated, in accordance with the principles of interfacial energy minimization, a droplet 31 will Taking the depression as the split point, split into the first sub-droplet 311 and the second sub-droplet 312. Then, as shown in (d) of FIG. 4, the temperature control unit 22 stops heating, and the deformation of the second substrate 21 is eliminated after a certain period of time as the temperature drops. Repeat the process from (a) to (d) above to generate multiple sub-droplets. Similarly, if multiple temperature control units 22 are provided on the second substrate 21, by controlling each temperature control unit 22, the generation of sub-droplets can be completed.

Since a plurality of temperature control units 22 are provided on the second substrate 21, the second substrate 21 can deform as the temperature rises, and the location of each temperature control unit 22 can be regarded as a splitting point that causes the droplets to split. . If the droplets flow through the working area of the droplet accommodating space 3, the temperature control unit 22 on the second substrate 21 is heated by the corresponding temperature control unit 22 to increase its temperature and deform, so that the second substrate is deformed. 21, where the deformation occurs, squeezes the droplet in the droplet accommodating space 3 to split the droplet into a plurality of sub-droplets. The microfluidic chip provided by the embodiment of the present invention can stably generate the driving force for droplet splitting (that is, the pressure generated by the deformation of the second substrate 21 on the droplet), and the droplet has a uniform split point, so it can Improve the stability of sub-droplet generation, and the size of each sub-droplet is more consistent.

It should be noted here that, referring to the above, based on the dielectric wetting effect, in the microfluidic chip provided by the embodiment of the present invention, in addition to controlling the movement of the droplet 31 by applying a voltage to the driving unit 12, it can also be driven by The unit 12 applies a voltage to control the splitting of the droplet 31 into sub-droplets.

For ease of description, as shown in Figures 5-7, Figure 6 is a cross-sectional view taken along the AA' direction in Figure 5, Figure 7 is a cross-sectional view taken along the BB' direction in Figure 5, and Figures 5-7 The black arrow in indicates the direction of the movement trend of the water droplets. Taking the first substrate 1 including three driving units arranged at intervals from left to right as an example, the microfluidic chip is described. Of course, this does not constitute the present invention. Limitations of the embodiment. The three driving units 12 are respectively a first driving unit 121, a second driving unit 122 and a third driving unit 133. The droplet 31 is in contact with the position of the dielectric layer 13 corresponding to the first drive unit 121, the second drive unit 122, and the third drive unit 133. If the droplet 31 is split into two droplets, three drives can be used. The voltage is applied to the first driving unit 121 and the third driving unit 123 on both sides of the unit, and no voltage is applied to the second driving unit 122 in the middle, or the second driving unit 122 is smaller than the other two driving units. If the voltage of the dielectric layer 13 is corresponding to the first driving unit 121 and the third driving unit 123 on both sides, the charges are accumulated, so that the dielectric layer 13 corresponds to the first driving unit 121 and the third driving unit 123 on both sides. The increase in hydrophilicity at the position attracts the droplet 31 to move to both sides, resulting in a _{decrease in the contact angle θ b2 of the} droplet 31 with the first substrate 1 and an increase in the radius of curvature r _{2 of the droplet 31.} Since the second driving unit 122 located in the middle is not applied with a voltage or the applied voltage is small, and the volume of the droplet 31 is constant during the movement of the droplet, the two ends of the droplet 31 will pull the middle part toward the two sides. Moving sideways, the middle part of the droplet 31 gradually becomes thinner until it is pulled off, thereby splitting into two sub-droplets in the direction of the first driving unit 121 and the third driving unit 131 charged on both sides. Similarly, if the first substrate 1 includes a plurality of driving units 12, by controlling the voltage of any three adjacent driving units 12, the voltage of the driving unit 12 in the middle is lower than the voltage of the driving units 12 on both sides. Sub-droplets are generated.

In some embodiments, as shown in FIG. 1 and FIG. 8, FIG. 8 is a schematic diagram of the orthographic projection of the temperature control unit 22 and the driving unit 12 in the second substrate 2 on the first substrate 1. The temperature control unit 22 is on the first substrate 1. The orthographic projection on a substrate 1 is limited to the orthographic projection of the corresponding drive unit 12 on the first substrate 1. The area of the orthographic projection of a temperature control unit 22 on the first substrate 1 is smaller than that of the drive unit 12 on the first substrate 1. The area of the orthographic projection on a substrate. If the droplet is split into sub-droplets only by the voltage of the driving unit 12, the final splitting position of the droplet will be randomly distributed on the driving unit in the middle of the three driving units 12, and the splitting position of the droplet cannot be precisely controlled. However, in the embodiment of the present invention, the second substrate 21 with a high thermal expansion coefficient is deformed by the temperature control unit 22 corresponding to the temperature control unit 22, so that the deformation of the second substrate 21 will squeeze the liquid droplet, and the liquid droplet and The contact surface of the deformed portion of the second substrate 21 forms a depression. According to the principle of minimum interface energy, the droplet will split from the depression into sub-droplets. Therefore, by setting the temperature control unit 22 on the second substrate 21 at a position corresponding to the driving unit 12, the splitting points of the droplets can be accurately set, and the splitting points of the droplets are prevented from being randomly distributed on the driving electrodes, resulting in sub-droplets. The problem of different sizes. Moreover, by adjusting the position of the temperature control unit 22 corresponding to the driving unit 12, the desired position of the droplet splitting can be adjusted, and the accuracy of sub-droplet generation can be improved. In addition, only the voltage of the driving unit 12 may cause the driving force to drive the droplets to split, and the sub-droplets cannot be successfully generated. The microfluidic chip provided by the embodiment of the present invention applies voltage to the driving unit 12 at the same time. , The use of the temperature control unit 22 to make the second substrate 21 squeeze droplets to split the droplets, which can increase the driving force for driving the droplets to split.

In some embodiments, as shown in FIG. 9, the central area of the orthographic projection of the temperature control unit 22 on the first substrate 1 overlaps with the central area of the orthographic projection of the drive unit 12 on the first substrate 1, and the When a sub-droplet is generated, the deformation caused by the heating of the second substrate 12 by the temperature control unit 22 corresponds to the central area of the drive unit 12. Therefore, the split point of the droplet in the droplet accommodating space 3 is that of the droplet corresponding to the drive unit 12 The position of the central region can make the volume of the generated multiple sub-droplets approximately the same, thereby improving the accuracy of generating the sub-droplets. The central area of the driving unit 12 is a circular area defined by a _{predetermined radius R t} with the geometric center p of the orthographic projection of the driving unit 12 on the first substrate 1 as the center of the circle. The central area of the temperature control unit 22 is a circular area defined by a _{predetermined radius Rd} with the geometric center q of the orthographic projection of the temperature control unit 22 on the first substrate 1 as the center of the circle. R _t can be, for example, 1 _{um, and R d} can be, for example, 0.1 um. As a preferred way, R _t =R _d =0 um. The _{smaller the R t} and R _d , the higher the degree of overlap between the geometric center of the orthographic projection of the temperature control unit 22 on the first substrate 1 and the geometric center of the orthographic projection of the driving unit 12 on the first substrate 1, the higher the degree of overlap of the microfluidic control The more accurate the sub-droplets generated by the chip are.

Optionally, the material of the second substrate 21 may include a variety of materials with high thermal expansion coefficients, such as polytetrafluoroethylene (Poly Tetra Fluoroethylene, PTFE), polymethyl methacrylate (Polymethyl Methacrylate, PMMA). Any kind. Of course, it can also be other materials, which is not limited here.

Specifically, the deformation of the second substrate 21 as the temperature increases can be described according to the motion equation of the solid: 0=▽.S;

Where S is the stress tensor: S=C/ε _el ;

Where C is the fourth-order elastic tensor: C=C(ε,υ);

Where υ is Poisson's ratio and ε is the total strain, which can be described by the following formula:

Where u is the displacement vector, Τ is the temperature, and ε _el can be described by the following formula:

ε _el =ε-ε _th

Where ε _th is the thermal strain, which can be described by the following formula:

ε _th ＝α(Τ-Τ _ref )

Where α is the expansion coefficient, and T _ref is the ambient temperature. According to the above formula, the deformation of the second substrate 21 made of different materials with increasing temperature can be obtained at different temperatures.

As shown in FIG. 11, it is a simulation analysis of the thermal expansion effect of the second substrate 21 in the microfluidic chip provided by the embodiment of the present invention by the finite element method, in which the heating device is taken as an example of a thermal resistance, and (a) in FIG. 11 is The top view of the simulation model, Figure 11 (b) is a three-dimensional view of the simulation model. In this model, the second substrate is made ^{of PTFE with an expansion coefficient of 12×10 -5} , the area of the thermal resistance is 0.4mm×0.4mm, the preset heating temperature is 50°C, and the box thickness of the microfluidic chip It is 20um, and the first substrate is a glass substrate. Since the thermal expansion coefficient of the glass substrate is generally on the ^{order of 10-6} , the deformation of the first substrate is ignored when calculating the thermal expansion effect. As shown in Figure 11, through calculation, the second substrate has a deformation M on the surface close to the droplet. The deformation amount of M is about 5um. The thickness of the box where the microfluidic chip corresponds to the thermal resistance changes, becoming 3/4 the thickness of the original box. Therefore, the deformation generated by the microfluidic chip of the embodiment of the present invention will undoubtedly generate pressure on the droplets, causing the droplets to split to generate sub-droplets.

Optionally, as shown in FIG. 1, in the microfluidic chip in the embodiment of the present invention, the temperature control unit 22 may include a temperature-rising device 221 and a temperature-measuring device 222, and the temperature-raising device 221 and the temperature-measuring device 222 are in one-to-one correspondence. The heating device 221 may be disposed on the side of the second substrate 21 close to the first substrate 1, and the heating device 221 is used to heat the position of the second substrate 21 corresponding to the heating device 221 to deform it. The temperature measuring device 222 is arranged on the side of the second substrate 21 away from the first substrate 1, and the temperature measuring device 222 is used to detect the temperature of the position of the second substrate 21 corresponding to the heating device 221, so that the second substrate 21 corresponds to the heating device The position of 221 reaches the preset temperature. The heating device 221 is used as a heat source and is arranged on the side of the second substrate 21 close to the droplet, so that the heat released by the heating device 221 can be concentrated on the side of the second substrate 21 close to the droplet, increasing the temperature of the second substrate 21. The amount of deformation also increases the pressure on the droplets caused by the deformation of the second substrate 21, making it easier for the droplets to split. The temperature measuring device 222 is used as a temperature feedback device to detect the temperature where the second substrate 21 corresponds to the temperature rising device 221 to ensure that the temperature of the second substrate 21 corresponding to the temperature rising device 221 can reach the preset temperature to ensure that the second substrate 21 The bottom 21 corresponds to the required deformation of the place where the heating device 221 is located.

In some embodiments, the heating device 221 includes a thermal resistor, and the temperature measuring device 222 includes a thermocouple. Of course, the heating device 221 and the temperature measuring device 222 may also be other types of devices, which are not limited herein. The thermal resistance is a heat source for heating the second substrate 21 corresponding to the thermal resistance, and the thermocouple is used to detect and feed back the temperature of the second substrate 21 corresponding to the thermal resistance. The size and number of thermal resistors and thermocouples can be designed according to needs. The smaller the size of the thermal resistor, the closer the temperature field distribution of the thermal resistor is to the Gaussian distribution, so that a better heating effect can be achieved. The smaller the size of the thermocouple, the more accurate the temperature detected by the thermocouple. For example, the dimensions of the thermal resistance and thermocouple are both 0.12mm×0.12mm. Since the size of the thermal resistance and thermocouple of the temperature control unit 22 is smaller than that of the drive unit, if the size of the resistance and the thermocouple are both 0.12mm×0.12mm, the size of the drive unit 12 can be larger than 0.12mm×0.12mm, for example, the size of the drive unit 12 It can be 0.4mm×0.4mm.

In some embodiments, as shown in FIG. 1, the central area of the orthographic projection of the heating device 221 on the second substrate 2 overlaps with the central area of the orthographic projection of the temperature measuring device 222 on the second substrate 2, thereby enabling The temperature measured by the temperature measuring device 222 is more accurate, so as to ensure the accuracy of the deformation amount at the deformation of the second substrate 21. The central area of the heating device 221 is a circular area defined by a _{predetermined radius R c} with the geometric center of the orthographic projection of the heating device 221 on the second substrate 2 as the center of the circle. The central area of the temperature measuring device 222 is a circular area defined by a _{predetermined radius R f} with the geometric center of the orthographic projection of the temperature measuring device 222 on the second substrate 2 as the center of the circle. R _c can be, for example, 0.1 um, and R _f can be, for example, 0.1 um. As a preferred way, R _c =R _f =0 um. The _{smaller R c} and R _{f are} , the higher the degree of overlap between the geometric center of the orthographic projection of the temperature measuring device 222 on the second substrate 2 and the geometric center of the orthographic projection of the heating device 221 on the second substrate 2 is, the higher the degree of overlap of the temperature measuring device The temperature measured by 222 is more accurate.

In other embodiments, as shown in FIG. 10, the heating device 221 and the temperature measuring device 222 can also be arranged in a staggered manner, as long as the orthographic projection of the heating device 221 on the second substrate 2 is the same as the temperature measuring device 222 on the second substrate 2. It suffices that there is an overlapping area on the orthographic projection. The dashed frame in FIG. 10 is a top view of the heating device 221 and the temperature measuring device 222. The orthographic projection of the heating device 221 on the second substrate 2 and the orthographic projection of the temperature measuring device 222 on the second substrate 2 have an overlapping area C Therefore, the temperature measuring device 222 can measure the temperature of the second substrate 21 corresponding to the temperature of the heating device 221. The size of the overlapping area C can be set according to measurement needs, and is not limited here.

In some embodiments, as shown in FIG. 1, the area of the orthographic projection of the heating device 221 on the second substrate 2 is the same as the area of the orthographic projection of the temperature measuring device 222 on the second substrate 2, so that the temperature measuring device 222 The detection surface of φ is consistent with the area of the heating device 221, so that the temperature of the second substrate 21 detected by the temperature measuring device 222 corresponding to the temperature of the heating device 221 can be more accurate. In some embodiments, the driving unit 21 may include a first electrode. After the first electrode is applied with a voltage, the voltage drives the droplets in the working area S1 of the droplet accommodating space 3 to move or split.

In some embodiments, as shown in FIG. 1, FIG. 3, and FIG. 8, the first substrate 1 may further include a plurality of second electrodes 15, which are provided on the first substrate 11 in the same layer as the first electrodes serving as the driving unit 12 It is close to the side of the second substrate 2 and the second electrode 15 is arranged in the area of the first substrate 11 corresponding to the liquid storage area S2 of the droplet accommodating space 3. After the voltage is applied to the second electrode, the liquid storage area S2 is driven by the voltage The droplet moves to the working area S1, and the specific way of controlling the movement of the droplet by applying a voltage to the second electrode can refer to the description of the movement of the droplet controlled by the driving unit. Since a plurality of second electrodes 15 are provided on the side of the younger brother substrate 11 close to the second substrate 2, so that after voltage is applied to the second electrode 15, the dielectric layer 13 accumulates charges corresponding to the second electrode 15, so that the droplets are gathered In the area of the droplet accommodating space 3 corresponding to the second electrode 15, that is, the droplets are gathered in the liquid storage area S2, so as to subsequently generate sub-droplets.

In some embodiments, as shown in FIGS. 1, 3, and 8, the area of the orthographic projection of the second electrode 15 on the first substrate 1 is larger than that of the first electrode of the driving unit 12 on the first substrate 1. The area of the orthographic projection. The size of the first electrode and the second electrode 15 corresponds to the size of the liquid droplets driven respectively, the second electrode 15 is arranged at the position of the first substrate 11 corresponding to the liquid storage area S2, and the first electrode as the driving unit 12 is arranged at the first electrode A substrate 11 corresponds to the position of the working area S1. The liquid droplets accumulated in the liquid storage area S2 are the liquid droplets that have not yet been divided. The volume of the liquid droplets is relatively large. The contact surface of 1 is also larger and more difficult to be manipulated, so a larger area of electrode is required to drive the droplets in the liquid storage area S2. After the first electrode 15 cooperates with the second electrode to allow the liquid droplets to flow from the liquid storage area S2 to the working area S1, the working area S1 is the area where the sub-droplets are generated, which is compared with that in the liquid storage area S2. The volume of the droplet is small, and there is no need for a large-area electrode to drive it, so the area of the first electrode can be smaller than the area of the second electrode 15. For example, the size of the second electrode is 2 mm×0.5 mm, and the size of the first electrode is 0.4 mm×0.4 mm.

In some embodiments, as shown in FIG. 1, the second substrate 2 may further include a conductive layer 24, which is disposed on the side of the second substrate 21 close to the first substrate 1. The conductive layer 24 may be connected to a common voltage terminal to conduct electricity. The layer 24 is equivalent to the zero potential surface, which can increase the potential difference between the upper and lower surfaces of the dielectric layer 13.

Further, a plurality of hollow parts S may be provided on the conductive layer 24, the hollow parts S correspond to the temperature-rising device 221 one-to-one, the hollow parts S are used for accommodating the temperature-rising device 221, and each hollow part S is provided with a temperature-rising device 221, and The area of the orthographic projection of the hollow portion S on the second substrate 2 is larger than the area of the orthographic projection of the heating device 221 on the second substrate 2, so that the heating device 221 is arranged in the hollow portion S, and has an edge with the hollow portion S A certain distance is required to prevent the heating device 221 from being interfered by the voltage on the conductive layer 24 and to prevent the conductive layer 24 from being squeezed by the deformation of the second substrate 21.

In some embodiments, as shown in FIG. 1, a fluid with a lubricating effect can also be added to the liquid droplet accommodating space 3 to reduce the damping of the liquid during movement. For example, silicone oil can be added, of course, it can also be other fluids, which is not limited here.

In the second aspect, as shown in FIG. 12, an embodiment of the present invention provides a microfluidic system, including the above-mentioned microfluidic chip.

Optionally, as shown in FIG. 12, the aforementioned microfluidic system may further include a control unit 001, which is connected to the drive unit 12 in the microfluidic chip, and the control unit 001 controls each drive in the microfluidic chip. The voltage of the unit 12 to make the droplets move or split.

The control unit 001 is also connected to the temperature control unit 22 in the microfluidic chip, and the control unit 001 controls the temperature control unit 11 in the microfluidic chip to heat the position of the second substrate 1 corresponding to the temperature control unit 11 to a preset temperature . According to needs, the control unit 03 can control the heating of the corresponding temperature control unit 22 in various orders. For example, if the control unit 03 controls all the temperature control units 22 in the microfluidic chip to heat at the same time, a plurality of heating elements will be generated on the second substrate 21. The deformed place causes the droplet to split into multiple sub-droplets at the same time. Of course, it is also possible to control the temperature control unit through which the droplet flows to be heated sequentially, so that the droplet generates multiple sub-droplets at different times. The details can be set according to needs, and there is no limitation here.

Optionally, as shown in FIG. 12, the control unit includes a programmable power supply and a programmable logic controller, which can control the voltage of each drive unit 12 and the working state of each temperature control unit 22 respectively.

Optionally, as shown in FIG. 12, the above-mentioned microfluidic system may further include a circuit control board 08, the circuit control board 08 is connected to the control unit 001, the circuit control board 08 has multiple interfaces, and the multiple interfaces are connected to the microfluidic chip A plurality of driving units 12 are connected one by one, and the control unit 001 controls the voltage of each driving unit 12 through the circuit control board 08. For example, to control the movement of the droplet, the control unit 001 can apply voltage to the driving unit 12 on the path through the circuit control board in the direction in which the droplet is required to move, so that the droplet is directed to the dielectric layer 13 under the dielectric wetting effect. This corresponds to the movement of the driving unit to which the voltage is applied. Also, the control unit can control the moving speed of the droplets by adjusting the voltage applied to the driving unit 12.

Optionally, as shown in FIG. 12, the above-mentioned microfluidic system may further include a temperature control table 09, the temperature control table 08 is connected to the control unit 03 and the temperature control unit 22 in the microfluidic chip, and the temperature control table 08 is preset If the temperature required for the deformation of the second substrate is determined, if the microfluidic chip is to generate sub-droplets, the control unit 03 controls the heating of the heating device 221 in the corresponding temperature control unit 22 in the microfluidic chip through the temperature control table 08 The second substrate 21, the temperature measuring device 222 detects the temperature of the second substrate 21 corresponding to the temperature control unit 22, and feeds back the detected temperature to the temperature control table 08, and the temperature control table 08 determines whether the detected temperature has reached If the preset temperature reaches the preset temperature, the heating device 221 stops heating; if it does not reach the preset temperature, the heating device 221 continues to heat, and the temperature measuring device 222 continues to feed back the detected temperature.

Optionally, as shown in Figure 12 above, the microfluidic system may also include a cooling system 002, which is connected to the control unit 001. The temperature of the second substrate 2 in the fluidic chip is used to eliminate the deformation of the second substrate 2 so that the microfluidic chip can repeatedly generate sub-droplets.

Optionally, as shown in FIG. 12, the cooling system 002 may include a cooling device 06 and a stepping motor 07. The stepping motor 07 is connected to the cooling device 06 and the control unit 03, and the cooling system 002 is arranged on the side of the microfluidic chip close to the second substrate 2. After the temperature control unit 22 finishes heating, the second substrate in the second substrate 2 21 is deformed, and the stepping motor 07 controls the cooling device 06 to descend toward the second substrate 2 so that the cooling device 06 is in contact with the second substrate 2, so that the cooling device 06 reduces the temperature of the second substrate 2 and eliminates the second substrate 2. Deformation on the substrate 2.

Optionally, the cooling device 06 may be a semiconductor refrigeration sheet, and the semiconductor refrigeration sheet reduces the temperature of the second substrate 2 through heat transfer.

Optionally, as shown in Figure 12 above, the microfluidic system may also include an observation system 003, which is used to observe the generation state of the neutron droplets of the microfluidic chip, so as to adjust the parameters of the droplet generation. .

Optionally, as shown in FIG. 12, the observation system 003 includes a transparent platform 04, and the microfluidic chip 05 is arranged on the transparent platform, so that the microfluidic chip 05 can be observed from both sides of the transparent platform 04. The observation system 003 also includes a plurality of optical components, such as: an image unit 01, a filter 02, and a focusing lens 03 arranged on the side of the transparent platform 04 away from the microfluidic chip 05, and arranged on the microfluidic chip 05 away from the transparent The backlight 012 on the side of the platform 04. The image unit 01, the filter 02, the focusing objective lens 03 and the backlight source 012 are all arranged on a rigid support 013 to ensure that these optical components are coaxially collimated, so that the generation of neutron droplets in the microfluidic chip 05 can be observed situation.

It can be understood that the above implementations are merely exemplary implementations used to illustrate the principle of the present invention, but the present invention is not limited thereto. For those of ordinary skill in the art, various modifications and improvements can be made without departing from the spirit and essence of the present invention, and these modifications and improvements are also deemed to be within the protection scope of the present invention.

Claims

A microfluidic chip includes: a first substrate and a second substrate that are arranged oppositely; the microfluidic chip includes a droplet splitting area for splitting droplets, in the droplet splitting area, A droplet accommodating space is included between the first substrate and the second substrate; wherein the droplet accommodating space includes a working area for generating sub-droplets;

The first substrate includes:

First substrate

A plurality of driving units are arranged at intervals on the side of the first substrate close to the second substrate, and are arranged in an area of the first substrate corresponding to the working area;

The second substrate includes:

The second substrate can deform as the temperature rises;

A plurality of temperature control units corresponding to the driving unit one-to-one, and the temperature control unit is used to cause the second substrate to deform in response to an increase in temperature where the temperature unit is located, so that the second substrate The bottom deformation squeezes the droplet in the droplet accommodating space to split it into at least two sub-droplets.
The microfluidic chip according to claim 1, wherein the orthographic projection of the temperature control unit on the first substrate is limited to the corresponding orthographic projection of the driving unit on the first substrate Inside.
The microfluidic chip according to claim 2, wherein the central area of the orthographic projection of the temperature control unit on the first substrate overlaps with the central area of the orthographic projection of the driving unit on the first substrate .
The microfluidic chip according to claim 2, wherein the shape of the temperature control unit is a square with a side length of 0.12 mm; the shape of the driving unit is a square with a side length of 0.4 mm.
The microfluidic chip according to claim 1, wherein the first substrate further comprises:

The dielectric layer is arranged on the side of the driving unit close to the second substrate;

The first liquid repellent layer is arranged on the side of the dielectric layer close to the second substrate;

The second substrate further includes:

The second lyophobic layer is arranged on the outermost side of the second substrate close to the droplet accommodating space.
The microfluidic chip according to claim 1, wherein the temperature control unit comprises: a temperature rising device and a temperature measuring device;

The heating device is arranged on a side of the second substrate close to the first substrate, and is used to heat the position of the second substrate corresponding to the heating device;

The temperature measuring device is arranged on the side of the second substrate away from the first substrate, and is used to detect the temperature of the position of the second substrate corresponding to the heating device, so that the second substrate corresponds to The position of the heating device reaches a preset temperature.
7. The microfluidic chip according to claim 6, wherein the heating device comprises a thermal resistor; and the temperature measuring device comprises a thermocouple.
The microfluidic chip according to claim 6, wherein the central area of the orthographic projection of the heating device on the second substrate is the same as the center of the orthographic projection of the temperature measuring device on the second substrate Area overlap.
8. The microfluidic chip according to claim 8, wherein the area of the orthographic projection of the heating device on the second substrate is the same as the area of the orthographic projection of the temperature measuring device on the second substrate .
The microfluidic chip according to claim 1, wherein the driving unit comprises a first electrode that drives the droplet in the working area to move or split by a voltage.
10. The microfluidic chip according to claim 10, wherein the droplet accommodating space further comprises a liquid storage area for storing the droplets;

The first substrate further includes a plurality of second electrodes, which are provided on the same layer as the first electrode on the side of the first substrate close to the second substrate, and are provided on the first substrate corresponding to the liquid storage The area of the area, which drives the droplets in the liquid storage area to move to the working area by voltage.
The microfluidic chip according to claim 11, wherein the area of the orthographic projection of the second electrode on the first substrate is larger than the area of the orthographic projection of the first electrode on the first substrate .
The microfluidic chip according to claim 1, wherein the second substrate further comprises a conductive layer disposed on the side of the second substrate close to the first substrate, and the conductive layer is connected to a common voltage terminal .
The microfluidic chip according to claim 1, wherein the material of the second substrate includes any one of polytetrafluoroethylene and polymethyl methacrylate.
A microfluidic system, comprising the microfluidic chip according to any one of claims 1-14.
The microfluidic system according to claim 15, further comprising: a control unit connected to the driving unit in the microfluidic chip and configured to control each of the driving units in the microfluidic chip The voltage of the unit;

The control unit is also connected to the temperature control unit in the microfluidic chip, and is used to control the temperature control unit in the microfluidic chip to heat the second substrate at a position corresponding to the temperature control unit to The preset temperature.
The microfluidic system according to claim 16, further comprising: a cooling system connected to the control unit for reducing the temperature of the second substrate in the microfluidic chip and eliminating the second substrate The deformation.
The microfluidic system according to claim 17, wherein the cooling system comprises: a cooling device and a stepping motor;

The stepping motor is connected to the cooling device and the control unit, and the stepping motor controls the cooling device to contact the second substrate to reduce the temperature of the second substrate.
The microfluidic system according to claim 16, further comprising: a circuit control board connected to the control unit, the circuit control board having a plurality of interfaces, and the plurality of interfaces are connected to the microfluidic chip A plurality of driving units are connected one by one, and the control unit controls the voltage of each driving unit through the circuit control board.
The microfluidic system according to claim 16, wherein the control unit includes a programmable power supply and a programmable logic controller.
The microfluidic system according to claim 15, further comprising:

The observation system is used to observe the generation state of the neutron droplets of the microfluidic chip.
The microfluidic system according to claim 21, wherein the observation system comprises a transparent platform, and the microfluidic chip is arranged on the transparent platform;

The observation system further includes: an image unit, a filter, and a focusing objective lens arranged on the side of the transparent platform away from the microfluidic chip in sequence, and arranged on the side of the microfluidic chip away from the transparent platform The backlight. .