CN114526373A

CN114526373A - Single-layer micro-fluidic pneumatic micro-valve and micro-fluidic chip

Info

Publication number: CN114526373A
Application number: CN202210012235.7A
Authority: CN
Inventors: 陈畅; 熊春阳; 瞿佳楠; 方旭; 林峰
Original assignee: Peking University
Current assignee: Peking University
Priority date: 2022-01-06
Filing date: 2022-01-06
Publication date: 2022-05-24

Abstract

The invention relates to a single-layer micro-fluidic pneumatic micro-valve and a micro-fluidic chip, comprising: the chip layer sets up the same one deck lead to liquid passageway, bulge, elasticity wall and pneumatic passage in the chip layer, pneumatic passage's end intercommunication bulge, the elasticity wall sets up between the bottom of bulge and pneumatic passage's a side, atmospheric pressure entry, liquid inlet and liquid outlet have still been seted up to the chip layer, atmospheric pressure entry and pneumatic passage's top intercommunication, liquid inlet and liquid outlet communicate with the both ends that lead to the liquid passageway respectively. Compared with the deformation of a lateral flow resistor in the prior art, the single-layer micro-fluidic pneumatic micro-valve and the micro-fluidic chip disclosed by the invention have the advantages that the deformation capacity of the valve area is greatly improved by adjusting the proportional size of the elastic wall, so that the liquid passage can be completely closed.

Description

Single-layer micro-fluidic pneumatic micro-valve and micro-fluidic chip

Technical Field

The invention relates to a single-layer microfluidic pneumatic micro-valve and a microfluidic chip, and belongs to the technical field of microfluidic chips.

Background

In the microfluidic chip, the pneumatic micro valve is driven by the pressure of the soft material to deform, so that the liquid is blocked or released to flow into a micro system.

In the development process of the technical route of the microfluidic chip, a research subject group provides a sandwich chip to form a pneumatic micro valve in a micro channel, and the chip is of a multilayer chip structure of a pneumatic layer, a thin film wall and a liquid channel layer from top to bottom. The middle of the air path and the liquid path of the chip is separated by a layer of film wall and is vertically and crossly distributed in the overlooking direction, and the cross part is a micro valve area. When the pneumatic channel applies pressure, the channel of the fluid layer can be selectively compressed and blocked, thereby realizing fluid motion control. There are also other plunger-type microvalves that have been developed, in which the fluid inlet and outlet are located in different fluid path layers, and in which the microchannels are connected by a porous layer. The pneumatic layer can control the deformation of the membrane wall to allow or inhibit fluid flow through the porous layer. The two valve systems are in a normally open switch structure.

Further research has led to the development of "gasket" type microvalves, also referred to as "sandwich" valves having fluid and pneumatic channels, which are normally closed, i.e. in the rest state, the fluid channel is blocked by a membrane wall. When the valve is opened, a negative pressure must be applied to the pneumatic network to deform the middle membrane against the pneumatic layer, thereby removing the membrane wall and allowing fluid to flow through the valve area. Further, developers have developed "curtain" style microvalves as another type of normally closed valve design, as opposed to microvalves of the gasket design, where the channel barrier curtain valve is a microstructure that is integral with the membrane layer rather than the channel layer. At zero pressure, the membrane is flush with the valve and blocks the flow channel. By pulling a vacuum on the pneumatic layer, the membrane and barrier are lifted upwards and open the fluid channel.

The pneumatic micro valves of various types developed above are widely applied to the fields of microfluidic PCR, protein separation and cell sorting, however, as the chip is composed of three layers, the chip needs to be aligned and secondarily bonded during processing, and the requirements on the processing precision and the processing cleanness are higher. Meanwhile, in the process of processing the pneumatic micro valve, because the bottom layer channel faces upwards, the thin film wall at the bottom of the channel cannot avoid a certain thickness (generally larger than 1mm), and the chip is not beneficial to high power lens imaging and single cell level research. To enable the valve to be completely closed, the microchannels in a multilayer microvalve are typically designed to have a semicircular cross-section. The semicircular channel creates a circular interface of liquid water bonding to the membrane wall joint, acting as a lens. The lens can severely distort the image in the transmitted light microscope mode (e.g., phase contrast field). In practice, the only viable cell imaging option is a fluorescence microscope that does not require a light source, however, dyes and uv lamps and filters add cost and the signal diminishes with time of exposure to light. With current lateral deflection membrane microvalves, however, this design is not a true valve in nature because it does not completely seal the flow channel, but rather is a flow resistor. In addition, there are three types of sidewall effect channel cavities inside: top, bottom and side surfaces determine the deflection behavior of the deflection membrane, making the system more difficult to model than a three-layer membrane microvalve.

In summary, the various types of pneumatic microvalves of the prior art have several disadvantages, which are summarized as follows: 1. the multilayer pneumatic micro valve needs to be aligned during processing, and the processing and preparation process is complex; 2. the imaging of the multilayer micro-valve is influenced by the pneumatic layer, and the multilayer micro-valve is only suitable for a fluorescence microscope and is expensive; 3. the multilayer micro valve has a thicker bottom surface, which is not beneficial to high power lens imaging; 4. the existing micro valve has small deformation and cannot completely close a liquid channel; 5. the existing micro-valve has different side wall effects and is difficult to model. In view of the above technical deficiencies, it is necessary to provide a new microfluidic pneumatic micro valve and a new microfluidic chip structure.

Disclosure of Invention

The invention provides a single-layer microfluidic pneumatic micro valve, which aims to at least solve one of the technical problems in the prior art.

The technical scheme of the invention is a single-layer microfluidic pneumatic micro valve, which comprises: the chip layer sets up the same one deck lead to liquid passageway, bulge, elasticity wall and pneumatic passage in the chip layer, pneumatic passage's end intercommunication bulge, the elasticity wall sets up between the bottom of bulge and pneumatic passage's a side, atmospheric pressure entry, liquid inlet and liquid outlet have still been seted up to the chip layer, atmospheric pressure entry and pneumatic passage's top intercommunication, liquid inlet and liquid outlet communicate with the both ends that lead to the liquid passageway respectively.

Furthermore, the chip layer and the elastic wall are both made of PDMS film materials.

Further, the inner diameter of the projection from the top end to the bottom end is gradually increased in size.

Further, the ratio of the length dimension to the thickness dimension of the elastic wall ranges from 6: 1 to 15: 1.

Furthermore, the cross section of the protruding portion is trapezoidal, one side of the lower bottom of the protruding portion is connected with the top surface of the elastic wall, and the tops of the waist lines on the two sides of the protruding portion are connected with the two side walls of the pneumatic channel.

Further, the openings of the air pressure inlet, the liquid inlet and the liquid outlet are circular.

Furthermore, the pneumatic channel comprises a first bending channel and a second bending channel, one end of the first bending channel is vertically communicated with one end of the second bending channel, the other end of the first bending channel is communicated with the top end of the protruding portion, and the other end of the second bending channel is communicated with the air pressure inlet.

The invention also discloses a mold, which comprises: a male mold for creating the above-described microvalve.

The invention also discloses a microfluidic chip, which comprises: the glass sheet and the micro valve are characterized in that the chip layer is in bonding connection with the glass sheet coated with the PDMS coating, when gas is introduced into the gas pressure inlet and flows to the bottom end of the protruding portion through the pneumatic channel, the gas extrudes the elastic wall to expand elastic deformation, and one side edge of the liquid passage is cut off and closed.

Further, the air pressure inlet is communicated with an air inlet of the air pressure pump.

Further, the PDMS coating is uniformly coated on the surface of the glass sheet.

The invention has the beneficial effects that:

1. compared with the existing pneumatic micro-valve with a multilayer structure, the micro-fluidic pneumatic micro-valve can generate light path transmission, has only one layer of structure, and eliminates the influence of light on micro-valve imaging.

2. Compared with the lateral flow resistor in the prior art, the deformation amount of the lateral flow resistor is smaller, and the liquid through channel cannot be completely cut off.

3. The chip layer and the glass sheet are made of the same PDMS material, and the chip layer and the glass sheet have the same material property when being bonded, so that the boundary conditions of the chip layer and the glass sheet are simpler, and the conditions for obtaining an analytic solution by valve modeling are given.

Drawings

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

Fig. 2 is a bottom view of a single layer microfluidic pneumatic microvalve according to an embodiment of the present invention.

Figure 3 is a perspective view of a male mold according to an embodiment of the present invention.

Fig. 4 is a first state diagram of deformation of a valve region according to an embodiment of the present invention.

Fig. 5 is a second state diagram of deformation of a valve region according to an embodiment of the present invention.

Fig. 6 is a third state diagram of deformation of a valve region according to an embodiment of the present invention.

Fig. 7 is a fourth state diagram of deformation of a valve region according to an embodiment of the present invention.

Fig. 8 is a fifth state diagram of deformation of a valve region according to an embodiment of the present invention.

Fig. 9 is a flowchart of a method of manufacturing a microfluidic chip according to an embodiment of the present invention.

Detailed Description

The conception, the specific structure and the technical effects of the present invention will be clearly and completely described in conjunction with the embodiments and the accompanying drawings to fully understand the objects, the schemes and the effects of the present invention. It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict.

It should be noted that, unless otherwise specified, when a feature is referred to as being "fixed" or "connected" to another feature, it may be directly fixed or connected to the other feature or indirectly fixed or connected to the other feature. Furthermore, the descriptions of upper, lower, left, right, top, bottom, etc. used in the present invention are only relative to the positional relationship of the components of the present invention with respect to each other in the drawings.

Furthermore, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any combination of one or more of the associated listed items.

It will be understood that, although the terms first, second, third, etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element of the same type from another. For example, a first element could be termed a second element, and, similarly, a second element could be termed a first element, without departing from the scope of the present disclosure. It should also be noted that all numerical ranges or proportional value ranges mentioned in the following examples are intended to cover the upper limit value or the lower limit value of the numerical range or proportional value range.

Referring to fig. 1 to 8, in some embodiments, the present disclosure discloses a single layer microfluidic pneumatic microvalve comprising: the chip layer 100, the liquid passage 110, the protrusion 120, the elastic wall 130 and the pneumatic passage 140 are disposed on the same layer in the chip layer 100.

Referring to fig. 1 and 2, the above components are part of a chip layer, and the main liquid channel 110 and the pneumatic channel 140 are respectively and independently integrated in the chip layer 100 of the same layer. The end of the pneumatic channel 140 is connected to the protrusion 120, and the elastic wall 130 is disposed between the bottom end of the protrusion 120 and one side of the pneumatic channel 140. As shown in fig. 2, the flexible wall 130 separates the fluid passage 110 and the pneumatic passage 140. The elastic wall 130 has a property of deformation elasticity, and as shown in fig. 2, the upper protrusion 120 and the lower valve area of the liquid passage 110 of the elastic wall 130 function as a closing or starting function, and the microvalve is a normally open valve structure.

Referring to fig. 1 and fig. 2, the chip layer 100 further has an air pressure inlet 141, a liquid inlet 111 and a liquid outlet 112, the air pressure inlet 141 is communicated with the beginning of the air channel 140, and the liquid inlet 111 and the liquid outlet 112 are respectively communicated with two ends of the liquid channel 110.

Referring to fig. 1 to 8, in some embodiments, the present disclosure discloses a microfluidic chip comprising: a chip layer 100 and a glass sheet 200. The liquid channel 110, the protrusion 120, the elastic wall 130 and the pneumatic channel 140 are disposed in the same layer of the chip layer 100. The end of the pneumatic channel 140 is connected to the protrusion 120, and the elastic wall 130 is disposed between the bottom end of the protrusion 120 and one side of the pneumatic channel 140. Similarly, the liquid channel 110 and the pneumatic channel 140 are independently integrated in the chip layer 100 of the same layer. The chip layer 100 is further provided with an air pressure inlet 141, a liquid inlet 111 and a liquid outlet 112, the air pressure inlet 141 is communicated with the beginning end of the pneumatic channel 140, and the liquid inlet 111 and the liquid outlet 112 are respectively communicated with two ends of the liquid channel 110.

Referring to fig. 1, the surface of the glass sheet 200 is coated with the PDMS coating 210, and the chip layer 100 is bonded to the glass sheet 200 coated with the PDMS coating 210, so that one side surfaces of the liquid channel 110, the protrusion 120, the elastic wall 130, and the pneumatic channel 140 are matched with the PDMS coating 210 to form a closed cavity. The PDMS coating 210 is uniformly coated on the surface of the glass sheet 200, so that the chip layer 100 and the elastic wall 130 made of the same material as the PDMS are easier to bond, and the PDMS coating 210 on the glass sheet 200 is easier to deform, so that the elastic wall 130 in the valve region, the PDMS coating 210 at the bottom of the periphery of the elastic wall 130, and the small part of the chip layer 100 at the top are deformed in several directions to large scales, and further the elastic wall 130 seals the liquid through channel 110.

The air pressure inlet 141 is communicated with an air inlet of an air pressure pump, and the input air pressure is controlled by adopting a precise air pressure pump. The micro-fluidic chip is a normally open valve structure, when the micro-valve needs to be opened, the air pressure inlet 141 does not apply air pressure to deform the elastic wall 130, the fluid in the fluid passage channel 110 normally flows, and the fluid passage channel 110 is in a unblocked state, namely a state that the elastic wall in the valve area is not elastically deformed in fig. 4; when the micro valve needs to be closed, the precise air pressure pump is adjusted to introduce air into the air pressure inlet 141, and when the air is introduced into the air pressure inlet 141 and flows to the bottom end of the protrusion 120 through the air pressure channel 140, so that a pressure difference exists between the protrusion 120 and the liquid through channel 110 on both sides of the elastic wall 130, the air extrudes the elastic wall 130 to expand and elastically deform toward the liquid through channel 110, so as to block one side of the liquid through channel 110 from being closed, so as to block the flow of the fluid, i.e., the elastic wall in the valve region in fig. 5 to 8 is gradually subjected to the state change of elastic deformation.

The whole chip layer is made of elastic membrane material, and the chip layer 100 and the elastic wall 130 are made of PDMS membrane material. The ratio of the length dimension to the thickness dimension of the elastic wall 130 of the PDMS film material ranges from 6: 1 to 15: 1. Wherein, preferably, the ratio of the length dimension to the thickness dimension of the elastic wall 130 in fig. 4 to 8 is 6: 1. The elastic wall 130 can be laterally deformed by changing the size range in combination with the air pressure input from the pneumatic channel 140. Besides the above-mentioned material of the elastic wall 130 is PDMS, the elastic wall 130 can be made of other thermoplastic or cold-plastic elastic materials.

Referring to fig. 1 in conjunction with fig. 2, the inner diameter of the protrusion 120 gradually increases from the top to the bottom, and in particular, the cross-sectional shape of the protrusion 120 is trapezoidal, one side of the bottom of the protrusion 120 is connected to the top of the elastic wall 130, and the top of the two side waistlines of the protrusion 120 are connected to the two side walls of the pneumatic channel 140. The elastic wall and the pneumatic channel are in transition through the protruding portion, the opening with the smaller diameter relative to the tail end of the pneumatic channel is directly connected with the elastic wall, the bottom end of the protruding portion is connected with the elastic wall with the larger diameter, the elastic wall and the protruding portion are compared in scheme, the elastic wall is longer in length, the deformation amplitude of the elastic wall is larger, and the liquid passing channel can be cut off more thoroughly as shown in fig. 8.

Referring to fig. 2, the openings of the air pressure inlet 141, the liquid inlet 111 and the liquid outlet 112 are circular, the circular inlets are respectively abutted to the common circular air inlet and the liquid outlet, and the sealing performance of the connection position is better.

Referring to fig. 2, the pneumatic channel 140 includes a first meandering channel 142 and a second meandering channel 143. One end of the first bending passage 142 is vertically communicated with one end of the second bending passage 143, the other end of the first bending passage 142 is communicated with the top end of the protrusion 120, and the other end of the second bending passage 143 is communicated with the air pressure inlet 141. The pneumatic channel 140 may be designed with a two-segment bent connection structure.

The scheme is applicable to, but not limited to, fluid dynamics control in a microfluidic chip, including flow control and flow resistance regulation; the change of the inner appearance of the chip comprises the opening and closing of a reaction cavity and the formation of a narrow area; and applying pressure to the surface of the cells or particles. The application occasions comprise: flow resistors, Polymerase Chain Reaction (PCR) and cell screening.

The preparation method of the microfluidic chip comprises the steps of preparing the microfluidic chip with the structure, and the preparation method comprises the following steps:

step 1: mixing PDMS material and curing agent to prepare PDMS solution;

step 2: providing a glass sheet 200, pouring part of the PDMS solution obtained in the step 1 onto a silicon wafer, rotating the silicon wafer to spin-coat the PDMS solution on one side of the glass sheet 200, and coating a PDMS coating 210 on one side of the glass sheet 200;

and step 3: providing a male mold 300, manufacturing a micro valve pattern on the male mold 300, pouring part of the PDMS solution obtained in the step 1 onto the micro valve pattern, and removing bubbles in the PDMS solution;

and 4, step 4: heating the glass sheet 200 processed in the step 2 and the male mold 300 processed in the step 3, and curing the heated PDMS coating 210 on the glass sheet 200 to solidify PDMS solution on the male mold 300 into a chip layer 100, wherein a liquid passage 110, a protrusion 120, an elastic wall 130 and a pneumatic passage 140 are formed in the same layer in the chip layer 100;

and 5: demolding the chip layer 100 from the male mold 300 in the step 4, and opening an air pressure inlet 141 at the starting end of the pneumatic channel 140 of the chip layer 100 and opening a liquid inlet 111 and a liquid outlet 112 at both ends of the liquid channel 110 of the chip layer 100 by using a punching tool;

step 6: after the glass sheet 200 coated with the PDMS coating 210 in the step 4 and the chip layer 100 in the step 5 are cleaned at high power, the chip layer 100 is bonded to the surface of the glass sheet 200 coated with the PDMS coating 210, so that the liquid passage 110, the protrusion 120, the elastic wall 130, and the bottom side of the pneumatic passage 140 form a cavity with a portion of the PDMS coating 210.

Compared with the existing common pneumatic micro valve, the preparation method of the micro-fluidic chip usually comprises the pneumatic layer, the chip layer and the liquid layer, secondary bonding is needed, and the multiple bonding process needs to be aligned to ensure the generation of the micro valve area so that the pneumatic layer and the liquid path layer generate an ideal overlapping area. Because the liquid passage, the elastic wall and the pneumatic passage are all designed in the same chip layer, the components are generated simultaneously in the soft photoetching process, and only need to be bonded and aligned with the glass sheet for one time without secondary bonding and alignment, thereby greatly saving the processing time of the chip.

Specifically, the mixing ratio of the PDMS material and the curing agent in step 1 ranges from 10: 1 to 25: 1. Preferably, the ratio of the PDMS material to the curing agent is 20: 1, and the chip layer, the PDMS coating layer, and the elastic wall made of the mixture have soft texture, so that the elastic wall is more easily deformed, thereby achieving large-sized deformation in all directions and further closing the channel.

And 3, removing bubbles in the PDMS solution by using a vacuum pump, so that the bubbles are removed when the chip layer is molded and the PDMS coating on the glass sheet is coated.

In step 4, the male mold 300 and the glass sheet 200 are placed on a flat heater and heated at about 100 ℃ for 1 hour, so that the molding of the chip layer and the curing of the PDMS coating on the glass sheet can be accelerated.

In step 6, the glass sheet 200 and the chip layer 100 are placed in a plasma cleaning machine for cleaning for 30 seconds.

Referring to a specific structure of the male mold 300 in fig. 3, the male mold 300 is patterned by photolithography, and in step 3, the male mold 300 is provided with a first protrusion 310, a second protrusion 320, and a trapezoid 330. One end of the middle part of the second protrusion part 320 is connected with the trapezoid part 330, a groove 340 is arranged between the tail end of the trapezoid part 330 and one side surface of the first protrusion part 310, the male die has a flat surface in other areas except for the two protrusion parts and the protrusion of the trapezoid part, and the protrusion heights can be the same or different.

In step 4, the chip layer 100 is demolded from the first protrusion 310, the trapezoid 330, the groove 340, and the second protrusion 320 to form the liquid channel 110, the protrusion 120, the elastic wall 130, and the pneumatic channel 140.

In order to meet the requirement of the composite proportion of the elastic wall manufactured by the male mold, the length dimension of the bottom surface of the trapezoidal section 330 and the width dimension of the groove 340 in step 3 can be combined in any proportion, depending on the processing precision and the required deformation degree. Preferably, the ratio may range from 6: 1 to 15: 1.

The present invention is not limited to the above embodiments, and any modifications, equivalent substitutions, improvements, etc. within the spirit and principle of the present disclosure should be included in the scope of the present disclosure as long as the technical effects of the present invention are achieved by the same means. Are intended to fall within the scope of the present invention. The invention is capable of other modifications and variations in its technical solution and/or its implementation, within the scope of protection of the invention.

Claims

1. A single layer microfluidic pneumatic microvalve, comprising:

a chip layer (100) comprising a plurality of chips,

the liquid passing channel (110), the protruding part (120), the elastic wall (130) and the pneumatic channel (140) are arranged on the same layer in the chip layer (100), the tail end of the pneumatic channel (140) is communicated with the protruding part (120), the elastic wall (130) is arranged between the bottom end of the protruding part (120) and one side edge of the pneumatic channel (140),

the chip layer (100) is further provided with an air pressure inlet (141), a liquid inlet (111) and a liquid outlet (112), the air pressure inlet (141) is communicated with the initial end of the pneumatic channel (140), and the liquid inlet (111) and the liquid outlet (112) are respectively communicated with two ends of the liquid channel (110).

2. Single-layer microfluidic pneumatic microvalve according to claim 1,

the chip layer (100) and the elastic wall (130) are both made of PDMS film materials.

3. Single-layer microfluidic pneumatic microvalve according to claim 1,

the inner diameter of the protrusion (120) increases from the top end to the bottom end.

4. Single-layer microfluidic pneumatic microvalve according to claim 1,

the ratio of the length dimension to the thickness dimension of the flexible wall (130) ranges from 6: 1 to 15: 1.

5. Single-layer microfluidic pneumatic microvalve according to claim 1,

the openings of the air pressure inlet (141), the liquid inlet (111) and the liquid outlet (112) are circular, the cross section of the protrusion (120) is trapezoidal, one side of the lower bottom of the protrusion (120) is connected with the top surface of the elastic wall (130), and the tops of the waist lines on two sides of the protrusion (120) are connected with two side walls of the pneumatic channel (140).

6. Single-layer microfluidic pneumatic microvalve according to claim 1,

the pneumatic channel (140) comprises a first bending channel (142) and a second bending channel (143), one end of the first bending channel (142) is vertically communicated with one end of the second bending channel (143), the other end of the first bending channel (142) is communicated with the top end of the protruding portion (120), and the other end of the second bending channel (143) is communicated with the air pressure inlet (141).

7. A mold, comprising: a male mold for producing the microvalve of any one of claims 1 to 6.

8. A microfluidic chip, comprising: glass sheet (200) and the microvalve of any one of claims 1 to 6,

the chip layer (100) is bonded and connected with the glass sheet (200) coated with the PDMS coating (210), and when gas is introduced from the gas pressure inlet (141) to the bottom end of the protruding part (120) through the pneumatic channel (140), the gas extrudes the elastic wall (130) to expand and elastically deform so as to cut off one side of the liquid through channel (110) to be closed.

9. The microfluidic chip according to claim 8,

the air pressure inlet (141) is communicated with an air inlet of the air pressure pump.

10. The microfluidic chip according to claim 8,

the PDMS coating (210) is uniformly coated on the surface of the glass sheet (200).