Preparation method of micro-flow pipeline with ultra-large aspect ratio

Abstract

The invention discloses a preparation method of a micro-flow pipeline with an ultra-large aspect ratio, which comprises the following steps: preparing a flexible block body by adopting a flexible material, forming a micro-flow groove on one surface of the flexible block body, and forming an inlet / outlet communicated with the micro-flow groove on the other surface of the flexible block body; a substrate is bent, and volatile liquid is contained in the bent concave surface; the face, provided with the micro-flow groove, of the flexible block makes contact with the bent concave face, and the micro-flow groove is automatically filled with the volatile liquid under the action of surface tension; when the flexible block body is kept in contact with the substrate, the substrate is restored to be straight, and the flexible block body is attached to the substrate; the flexible block and the substrate are subjected to molecular bonding in a heating mode to form a micro-flow pipeline, and meanwhile the volatile liquid is volatilized. According to the invention, the micro-flow pipeline with an ultra-large aspect ratio can be prepared.

Description

Technical Field

[0001] The invention belongs to the technical field of microfluidic pipelines, and in particular relates to a method for preparing a microfluidic pipeline with an ultra-large aspect ratio. Background Art

[0002] Microfluidics refers to the technology of using microfluidic pipes to operate or process microfluids. It is an emerging interdisciplinary subject involving multiple disciplines.

[0003] The preparation of microfluidic channels is the foundation of microfluidic technology and industry. In the prior art, polydimethylsiloxane (PDMS) has become the preferred material for preparing microfluidic channels due to its advantages such as strong plasticity, simple process, stable performance, and good biocompatibility. However, since polydimethylsiloxane is a flexible material, when the aspect ratio of the microfluidic channel is too large (for example, >10:1), channel collapse is likely to occur during the preparation of the microfluidic channel.

[0004] In order to prevent the collapse of microfluidic pipes with ultra-large aspect ratios, hard materials such as glass, quartz, and PAAm (polyacrylamide) are usually used in the prior art to process microfluidic pipes. However, the cost of using the above hard materials to prepare microfluidic pipes is much higher than the cost of using polydimethylsiloxane to prepare microfluidic pipes. Summary of the invention

[0005] In order to solve the above problems existing in the prior art, the present invention provides a method for preparing a microfluidic pipeline with an ultra-large aspect ratio.

[0006] The technical problem to be solved by the present invention is achieved through the following technical solutions:

[0007] A method for preparing a microfluidic pipeline with an ultra-large aspect ratio, comprising:

[0008] Step 1: prepare a flexible block using a flexible material, and form a microfluidic channel on one side of the flexible block, and form an inlet and outlet connected to the microfluidic channel on the other side;

[0009] Step 2, bending a base, and filling a volatile liquid in the curved concave surface;

[0010] Step 3, contacting the side of the flexible block having the microfluidic groove with the curved concave surface, so that the volatile liquid automatically fills the microfluidic groove under the action of surface tension;

[0011] Step 4: while maintaining the contact between the flexible block and the substrate, restore the substrate to be straight, so that the flexible block and the substrate are in contact;

[0012] Step 5: The flexible block is molecularly bonded to the substrate to form a microfluidic channel by heating, and the volatile liquid is volatilized at the same time.

[0013] Optionally, the preparation method further comprises:

[0014] Before step three, the side of the flexible block having the microfluidic channel and the side of the substrate to form the curved concave surface are both activated to increase the molecular bonding force between the flexible block and the substrate in step five.

[0015] Optionally, the volatile liquid contained in the curved concave surface is sufficient to cover the notch of the microfluidic channel.

[0016] Optionally, the method further comprises:

[0017] Before step three, a glass slide is attached to the opposite surface of the flexible block having the microfluidic channel to increase the bending rigidity of the flexible block.

[0018] Optionally, the step five includes:

[0019] The substrate is heated by using a hot stage while the substrate and the flexible block are kept in contact with each other, so that the flexible block and the substrate are molecularly bonded to form a microfluidic channel, and the volatile liquid is volatilized at the same time.

[0020] Optionally, the preparation method further comprises:

[0021] After step five, the bonded flexible block and substrate are placed in an oven for baking to increase the bonding strength between the two.

[0022] Optionally, the flexible material includes: polydimethylsiloxane.

[0023] Optionally, the flexible material includes: polydimethylsiloxane;

[0024] The substrate includes a hard substrate and a flexible material coating coated on the hard substrate.

[0025] In the preparation method of the ultra-large aspect ratio microfluidic pipeline provided by the present invention, firstly, a flexible block is prepared by using a flexible material, and a microfluidic groove is formed on one side of the flexible block, and an inlet and outlet connected to the microfluidic groove are formed on the other side, and then a volatile liquid is placed on a curved substrate, and the side of the flexible block with the microfluidic groove is brought into contact with the curved concave surface of the substrate, so that the volatile liquid fills the microfluidic groove under the action of surface tension; then, while maintaining the contact between the flexible block and the substrate, the substrate is restored to be straight, and the flexible block and the substrate are molecularly bonded by heating, so that the microfluidic groove and the substrate are sealed together to form a microfluidic pipeline, and the volatile liquid can also be volatilized while heating, which does not affect the subsequent use of the microfluidic pipeline. Among them, the microfluidic pipeline is supported by the volatile liquid during the forming process, so that the pipeline is not easy to collapse, so the preparation method of the present invention can prepare an ultra-large aspect ratio microfluidic pipeline.

[0026] Moreover, the main material for preparing the ultra-large aspect ratio microfluidic pipeline in the present invention is a flexible material, so the microfluidic pipeline can be prepared using flexible materials such as polydimethylsiloxane that have strong plasticity, strong air permeability, strong ductility, and easy stacking, which is not available in the hard materials commonly used in the prior art. Therefore. The method of the present invention can not only prepare ultra-large aspect ratio microfluidic pipelines for biological applications, but also can be used to prepare complex multilayer chips.

[0027] The present invention will be further described in detail below with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a flowchart of a method for preparing a microfluidic pipeline with an ultra-large aspect ratio provided by an embodiment of the present invention;

[0029] Figure 2(a) to Figure 2(g) is a graphical flow chart of preparing a microfluidic conduit in an embodiment of the present invention;

[0030] Figure 3 It is a flowchart of another method for preparing a microfluidic pipeline with a large aspect ratio provided by an embodiment of the present invention;

[0031] Figure 4 The present invention is a scanning image obtained by scanning and photographing a cross section of a microfluidic channel with an ultra-large aspect ratio prepared in an embodiment of the present invention using a fluorescent confocal microscope. DETAILED DESCRIPTION

[0032] The present invention is further described in detail below with reference to specific embodiments, but the embodiments of the present invention are not limited thereto.

[0033] The embodiment of the present invention provides a method for preparing a microfluidic pipeline with a large aspect ratio. Figure 1 As shown, the method comprises the following steps:

[0034] Step 1: prepare a flexible block using a flexible material, and form a microfluidic channel on one side of the flexible block, and form an inlet and outlet connected to the microfluidic channel on the other side.

[0035] In step 1, the flexible block, microfluidic channel and inlet and outlet can be prepared by integral molding, or the flexible block can be prepared first, and then the microfluidic channel is etched on its surface and the inlet and outlet connected to the microfluidic channel are opened.

[0036] The flexible material may include polydimethylsiloxane (PDMS), polytetrafluoroethylene (PTFE) or epoxy resin, etc. Here, polydimethylsiloxane and epoxy resin have certain air permeability and can be applied in the embodiments of the present invention to prepare a microfluidic conduit with an ultra-large aspect ratio for biological applications.

[0037] The embodiment of the present invention does not limit the specific shape of the flexible block, as long as it meets the use requirements in the preparation process. Among them, the side forming the inlet and outlet only needs to be different from the side forming the microfluidic channel, and it is not limited that the two sides must be opposite.

[0038] After the completion of step 1, the obtained flexible block can be seen in FIG2(a), wherein the structure marked 1 is the flexible block, the structure marked 2 is the microfluidic channel, and the microfluidic channel is formed on the lower surface of the flexible block 1. The structures marked A and B are the inlets and outlets of the microfluidic channel. FIG2(b) shows the flexible block in FIG2(a). Figure 1 The cross section in the XZ plane is outlined by the dashed line.

[0039] Step 2: bend a base and fill the volatile liquid in the curved concave surface.

[0040] The bending degree of the substrate should ensure that the substrate will not break or crack, and should ensure that the volatile liquid contained in the curved concave surface is sufficient to cover the notch of the microfluidic channel. Generally speaking, the normal deformation of a microfluidic channel with a normal aspect ratio can reach the millimeter level, and the height of a microfluidic channel with a large aspect ratio will not be greater than 100 microns, that is, the normal deformation of a microfluidic channel with a large aspect ratio is less than 100 microns.

[0041] Exemplarily, the substrate may be a hard substrate with a thickness of less than 0.5 mm, and the hard substrate with such a thickness can be bent to a small extent, which is sufficient to meet the use requirements in the implementation of the present invention. For example, the substrate may be a glass sheet or a silicon sheet with a thickness of less than 0.5 mm. Alternatively, the substrate may include a hard substrate with a thickness of less than 0.5 mm and a flexible material coating coated on the hard substrate. The flexible material used in the flexible material coating is the same as the material of the flexible block.

[0042] The volatile liquid may include deionized water or glycerol, etc. This ensures that the liquid in the curved concave surface will not evaporate quickly, and can evaporate in the subsequent steps where it is required to evaporate.

[0043] After the second step is completed, the state of the substrate is shown in FIG. 2( c ), wherein the structure marked as 3 is the substrate and the volatile liquid is marked as 4 .

[0044] Step 3: contact the side of the flexible block having the microfluidic groove with the curved concave surface, so that the volatile liquid automatically fills the microfluidic groove under the action of surface tension.

[0045] It is understandable that since the contact surfaces of the flexible block and the substrate have a certain degree of hydrophilicity after activation treatment, after the side of the flexible block having the microfluidic groove contacts the curved concave surface, the volatile liquid can automatically fill the microfluidic groove under the action of surface tension.

[0046] It should be noted that after the execution of step 3, a small amount of air in the microfluidic channel does not affect the final effect of the embodiment of the present invention. This is because most of the space in the microfluidic channel has been occupied by the volatile liquid, and the curvature of the small air gap is not enough to deform the microfluidic channel and cause it to collapse.

[0047] In step three, a schematic diagram of bringing one side of the flexible block having the microfluidic groove into contact with the curved concave surface is shown in FIG2(d), and the state after the two are in contact is shown in FIG2(e), where it can be seen that the volatile liquid 4 has filled the microfluidic groove 2.

[0048] Step 4: While maintaining the contact between the flexible block and the substrate, restore the substrate to be straight, so that the flexible block and the substrate are in contact.

[0049] It is understandable that in order to avoid misalignment between the flexible block and the substrate, and to prevent the volatile liquid in the microfluidic channel from flowing out of the microfluidic channel due to shaking, it is best to slowly restore the substrate to a straight state in step four.

[0050] After step 4 is completed, the state in which the substrate and the flexible block are bonded is shown in FIG. 2( f ).

[0051] Step 5: Heat the flexible block to form a microfluidic channel by molecular bonding with the substrate, and evaporate the volatile liquid at the same time.

[0052] It is understandable that step five bonds the flexible block to the substrate by heating, which can promote molecular bonding between the flexible block and the substrate on the one hand, and help accelerate the volatilization of the volatile liquid on the other hand, and there is no need to clean the pipeline again after the microfluidic channel is formed.

[0053] There are many specific implementation methods for achieving molecular bonding between the flexible block and the substrate by heating to form a microfluidic channel.

[0054] Exemplarily, in one implementation, the substrate is heated by a hot plate while the substrate and the flexible block are kept in contact with each other, so that the flexible block 1 and the substrate 3 are molecularly bonded to form a microfluidic channel, and the volatile liquid is volatilized at the same time. The volatile liquid 4 can be volatilized from the inlet and outlet A and B on the flexible block 1 that are connected to the microfluidic channel 2. Of course, at this time, the microfluidic channel 2 and the substrate have been bonded together to form a microfluidic channel.

[0055] For example, assuming that the substrate is a glass sheet with a thickness of less than 0.5 mm, when the substrate is placed on a hot plate for heating, the temperature of the hot plate can be set to 90 degrees Celsius and the heating time can be 3 minutes.

[0056] In another implementation, laser may be used to heat the bonding portion between the flexible block and the substrate, thereby bonding the two together.

[0057] After step five is completed, a microfluidic channel is obtained as shown in FIG. 2( g ), wherein the structure marked with 5 is a microfluidic channel formed by the microfluidic groove and the substrate.

[0058] In the method for preparing a microfluidic pipeline with an ultra-large aspect ratio provided by an embodiment of the present invention, a flexible block is first prepared using a flexible material, and a microfluidic groove is formed on one side of the flexible block, and an inlet and outlet connected to the microfluidic groove are formed on the other side. Then, a volatile liquid is placed on a curved substrate, and the side of the flexible block with the microfluidic groove is brought into contact with the curved concave surface of the substrate, so that the volatile liquid fills the microfluidic groove under the action of surface tension; then, while maintaining the contact between the flexible block and the substrate, the substrate is restored to be straight, and the flexible block and the substrate are molecularly bonded by heating, so that the microfluidic groove and the substrate are sealed together to form a microfluidic pipeline, and the volatile liquid can also be volatilized while heating, which does not affect the subsequent use of the microfluidic pipeline. Among them, the microfluidic pipeline is supported by the volatile liquid during the formation process, so it is not easy for the pipeline to collapse. Therefore, the method of the embodiment of the present invention can prepare a microfluidic pipeline with an ultra-large aspect ratio.

[0059] It is worth mentioning that when a microfluidic channel having a channel height greater than or equal to 0.5 micrometer is prepared using the embodiment of the present invention, the upper limit of the channel width-to-height ratio is 1200:1.

[0060] In addition, the main material for preparing the ultra-large aspect ratio microfluidic pipeline in the embodiment of the present invention is a flexible material, so the microfluidic pipeline can be prepared using flexible materials such as polydimethylsiloxane that are highly plastic, air-permeable, ductile, and easy to stack, which is not available in the hard materials commonly used in the prior art. Therefore, the method of the embodiment of the present invention can not only prepare ultra-large aspect ratio microfluidic pipelines for biological applications, but also can be used to prepare complex multi-layer chips.

[0061] In practical applications, the execution time of the above steps 2 to 4 can be determined experimentally based on the selected volatile liquid and its volume. Two factors should be considered comprehensively when determining: on the one hand, the bonding efficiency between the substrate and the flexible block should be considered; on the other hand, it should be ensured that the volatile liquid will not evaporate prematurely due to too long a time.

[0062] In one embodiment, the method for preparing a microfluidic pipeline with a large aspect ratio provided by the embodiment of the present invention may further include:

[0063] Before step three, the side of the flexible block having the microfluidic groove and the side of the substrate to be formed into a curved concave surface are both activated to increase the molecular bonding force between the flexible block and the substrate in step five.

[0064] Exemplarily, the activation treatment step can be achieved using a plasma cleaner or other chemical methods; after the activation treatment, the side of the flexible block having the microfluidic groove and the side of the substrate to form the curved concave surface both have a certain hydrophilicity.

[0065] Among them, the total time required from the activation treatment step to the completion of step four should also comprehensively consider the bonding efficiency between the substrate and the flexible block and the fact that the volatile liquid does not evaporate prematurely, which will not be repeated here.

[0066] In one embodiment, the method for preparing a microfluidic pipeline with a large aspect ratio provided by the embodiment of the present invention may further include:

[0067] Before step three, a glass slide is attached to the opposite surface of the flexible block having the microfluidic channel to increase the bending rigidity of the flexible block.

[0068] The purpose of doing so is to avoid the flexible block from being distorted due to the material being too soft. Of course, if the width of the flexible block is wide enough, such distortion will hardly occur, so the slide glass is not necessarily used.

[0069] In one embodiment, the method for preparing a microfluidic pipeline with a large aspect ratio provided by the embodiment of the present invention may further include:

[0070] After step five, the bonded flexible block and substrate are placed in an oven for baking to increase the bonding strength between the two.

[0071] Exemplarily, the oven temperature may be set at 80° C. and the baking time may be 12 hours, but this is not limiting.

[0072] In a preferred example, see Figure 3 As shown, the method for preparing a microfluidic pipeline with a super-large aspect ratio provided by an embodiment of the present invention may specifically include the following steps:

[0073] S10: preparing a flexible block using a flexible material, and forming a microfluidic channel on one side of the flexible block, and forming an inlet and outlet connected to the microfluidic channel on the other side;

[0074] S20: activating a surface of the flexible block having the microfluidic channel and a surface of the substrate;

[0075] S30: bending the activated side of the substrate inwardly, and placing a volatile liquid in the curved concave surface;

[0076] S40: attaching a glass slide to the opposite surface of the flexible block having the microfluidic groove to increase the bending rigidity of the flexible block, and then contacting the surface of the flexible block having the microfluidic groove with the curved concave surface, so that the volatile liquid fills the microfluidic groove under the action of surface tension;

[0077] S50: while maintaining the contact between the flexible block and the substrate, restoring the substrate to be straight, so that the flexible block and the substrate are in contact;

[0078] S60: heating the substrate using a hot plate while keeping the flexible block in contact with the substrate, removing the glass slide on the flexible block during the process, so that the flexible block and the substrate are molecularly bonded to form a microfluidic channel, and the volatile liquid is volatilized;

[0079] S70: placing the bonded flexible block and substrate into an oven for baking to increase the bonding strength between the two.

[0080] Thus, a microfluidic channel with an ultra-large aspect ratio is prepared.

[0081] The method for preparing a microfluidic channel with an ultra-large aspect ratio provided in an embodiment of the present invention innovatively adopts a process for preparing a microfluidic channel using liquid phase filling packaging, which can prepare a microfluidic channel with an ultra-large aspect ratio, and the prepared microfluidic channel is not easy to collapse, and can be used for the preparation of a microfluidic chip.

[0082] In order to better illustrate the beneficial effects of the embodiments of the present invention, a microfluidic channel with a width of 150 microns and a height of only 3 microns was prepared using the method for preparing a microfluidic channel with a large aspect ratio provided by the embodiments of the present invention. After the microfluidic channel was prepared, an aqueous solution of fluorescent molecule FITC was filled into the channel, and three different cross sections of the channel were scanned and photographed using a fluorescence confocal microscope. The scanned images are shown in FIG. Figure 4 As shown. Figure 4 It can be seen that the fluorescent molecular solution in the pipeline is evenly distributed, indicating that the pipeline has not collapsed, proving the effectiveness of the embodiment of the present invention.

[0083] It should be noted that the terms "first", "second", etc. are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present disclosure described herein can be implemented in an order other than those illustrated or described herein. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present disclosure. Instead, they are merely examples of devices and methods consistent with some aspects of the present disclosure.

[0084] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine different embodiments or examples described in this specification.

[0085] Although the present application is described herein in conjunction with various embodiments, in the process of implementing the claimed application, those skilled in the art can understand and implement other changes to the disclosed embodiments by viewing the drawings and the disclosed content. In the description of the present invention, the term "comprising" does not exclude other components or steps, "one" or "an" does not exclude multiple situations, and the meaning of "multiple" is two or more, unless otherwise clearly and specifically limited. In addition, certain measures are recorded in different embodiments, but this does not mean that these measures cannot be combined to produce good results.

[0086] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0087] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0088] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0089] The above contents are further detailed descriptions of the present invention in combination with specific preferred embodiments, and it cannot be determined that the specific implementation of the present invention is limited to these descriptions. For ordinary technicians in the technical field to which the present invention belongs, several simple deductions or substitutions can be made without departing from the concept of the present invention, which should be regarded as falling within the protection scope of the present invention.

Claims

1. A method for preparing a microfluidic channel with an ultra-large aspect ratio, characterized in that: include: Step 1: prepare a flexible block using a flexible material, and form a microfluidic channel on one side of the flexible block, and form an inlet and outlet connected to the microfluidic channel on the other side; Step 2, bending a base, and filling a volatile liquid in the curved concave surface; Step 3, contacting the side of the flexible block having the microfluidic groove with the curved concave surface, so that the volatile liquid automatically fills the microfluidic groove under the action of surface tension; Step 4: while maintaining the contact between the flexible block and the substrate, restore the substrate to be straight, so that the flexible block and the substrate are in contact; Step 5: The flexible block is molecularly bonded to the substrate to form a microfluidic channel by heating, and the volatile liquid is volatilized at the same time.

2. The preparation method according to claim 1, characterized in that: The preparation method further comprises: Before step three, the side of the flexible block having the microfluidic channel and the side of the substrate to form the curved concave surface are both activated to increase the molecular bonding force between the flexible block and the substrate in step five.

3. The preparation method according to claim 1, characterized in that: The volatile liquid contained in the curved concave surface is sufficient to cover the notch of the microfluidic channel.

4. The preparation method according to claim 1, characterized in that: The method further comprises: Before step three, a glass slide is attached to the opposite surface of the flexible block having the microfluidic channel to increase the bending rigidity of the flexible block.

5. The preparation method according to claim 1, characterized in that: The step five comprises: The substrate is heated by using a hot stage while the substrate and the flexible block are kept in contact with each other, so that the flexible block and the substrate are molecularly bonded to form a microfluidic channel, and the volatile liquid is volatilized at the same time.

6. The preparation method according to claim 1, characterized in that: The preparation method further comprises: After step five, the bonded flexible block and substrate are placed in an oven for baking to increase the bonding strength between the two.

7. The preparation method according to claim 1, characterized in that: The flexible material includes: polydimethylsiloxane.

8. The preparation method according to claim 1, characterized in that: The flexible material includes: polydimethylsiloxane; The substrate includes a hard substrate and a flexible material coating coated on the hard substrate.

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