Preparation method of microfluidic pipe with super large width-height ratio

Abstract

The application discloses a preparation method of a micro-flow pipe with super large width-height ratio, which comprises the following steps: a flexible block is prepared by using a flexible material, and a micro-flow groove is formed on one side of the flexible block, and an outlet and an inlet communicating with the micro-flow groove are formed on the other side; a base is bent, and a volatile liquid is filled in the bent concave surface; the side of the flexible block with the micro-flow groove is contacted with the bent concave surface, so that the volatile liquid is automatically filled in the micro-flow groove under the action of surface tension; the base is restored to be flat while the flexible block is kept in contact with the base, so that the flexible block is attached to the base; the flexible block and the base are molecularly bonded by heating to form a micro-flow pipe, and the volatile liquid is volatilized. The micro-flow pipe with super large width-height ratio can be prepared.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of microfluidic channel, and particularly relates to a preparation method of a microfluidic channel with an ultra-large width-to-height ratio. BACKGROUND

[0002] Microfluidic technology refers to a technology for operating or processing microfluids by using microfluidic channels, and is a newly emerging interdisciplinary subject.

[0003] Preparation of microfluidic channels is the basis of microfluidic technology and industry. In the prior art, polydimethylsiloxane (PDMS) is the first choice for preparing microfluidic channels due to its strong plasticity, simple process, stable performance, good biocompatibility and other advantages. However, since polydimethylsiloxane is a flexible material, when the width-to-height ratio of the microfluidic channel is too large (for example, > 10:1), the channel is prone to collapse during preparation.

[0004] In order to avoid the collapse of the microfluidic channel with an ultra-large width-to-height ratio, hard materials such as glass, quartz and PAAm (polyacrylamide) are usually used to process microfluidic channels in the prior art. However, the cost of using the above hard materials to prepare microfluidic channels is much higher than that of using polydimethylsiloxane to prepare microfluidic channels. SUMMARY

[0005] In order to solve the above problems existing in the prior art, the present application provides a preparation method of a microfluidic channel with an ultra-large width-to-height ratio.

[0006] The technical problem to be solved by the present application is solved by the following technical scheme:

[0007] A preparation method of a microfluidic channel with an ultra-large width-to-height ratio, comprising:

[0008] Step one, 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 communicating with the microfluidic groove are formed on the other side;

[0009] Step two, a base is bent, and a volatile liquid is filled in the bent concave surface;

[0010] Step three, the side of the flexible block with the microfluidic groove is contacted with the bent concave surface, so that the volatile liquid is automatically filled in the microfluidic groove under the action of surface tension;

[0011] Step four, while keeping the contact between the flexible block and the base, the base is restored to be flat, so that the flexible block is attached to the base;

[0012] Step five, the flexible block and the base are molecularly bonded to form a microfluidic channel by heating, and the volatile liquid is volatilized.

[0013] Optionally, the method further comprises:

[0014] Before the step three, the flexible block and the substrate to be formed with the curved concave surface are activated to increase the molecular bonding force between the flexible block and the substrate in the step five.

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

[0016] Optionally, the method further comprises:

[0017] Before the step three, a glass slide is attached to the opposite surface of the flexible block with the micro flow channel to increase the bending stiffness of the flexible block.

[0018] Optionally, the step five comprises:

[0019] The substrate is heated by a hot stage while the substrate and the flexible block are attached, so that the flexible block and the substrate are molecularly bonded to form a micro flow conduit, and the volatile liquid is volatilized.

[0020] Optionally, the method further comprises:

[0021] After the step five, the bonded flexible block and substrate are baked in an oven to increase the bonding strength.

[0022] Optionally, the flexible material comprises polydimethylsiloxane.

[0023] Optionally, the flexible material comprises polydimethylsiloxane;

[0024] The substrate comprises a hard substrate and a poly-flexible material coating layer coated on the hard substrate.

[0025] The preparation method of the micro flow conduit with super large width-to-height ratio provided by the present application comprises the following steps: first, a flexible block is prepared by using a flexible material, a micro flow channel is formed on one surface of the flexible block, and an inlet and outlet communicating with the micro flow channel are formed on the other surface; then, a volatile liquid is filled in a curved substrate, and the surface of the flexible block with the micro flow channel is contacted with the curved concave surface of the substrate, so that the volatile liquid fills the micro flow channel under the action of surface tension; then, the substrate is restored to be flat while the flexible block and the substrate are kept in contact, and the flexible block and the substrate are molecularly bonded by heating, so that the micro flow channel and the substrate are sealed together to form a micro flow conduit, and the volatile liquid is volatilized at the same time, which does not affect the subsequent use of the micro flow conduit. In the forming process of the micro flow conduit, there is a volatile liquid to support the micro flow conduit, so that the collapse of the micro flow conduit is less likely to occur. Therefore, the preparation method of the present application can be used to prepare a micro flow conduit with super large width-to-height ratio.

[0026] And, the main material for preparing the microfluidic channel with super large width-height ratio in the present application is flexible material, so the flexible material with strong plasticity, strong air permeability, strong ductility and easy superposition such as polydimethylsiloxane can be used to prepare the microfluidic channel, which is not possessed by the hard material commonly used in the prior art. Therefore, the method of the present application can not only be used to prepare the microfluidic channel with super large width-height ratio for biological application, but also be used to prepare complex multi-layer chips.

[0027] The present application will be further described in detail below in combination with the drawings and the present application. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is a flow chart of a method for preparing a microfluidic channel with super large width-height ratio provided by an embodiment of the present application;

[0029] Figures 2(a) to 2(g) is a graphical flow chart for preparing a microfluidic channel in an embodiment of the present application;

[0030] Figure 3 is a flow chart of another method for preparing a microfluidic channel with super large width-height ratio provided by an embodiment of the present application;

[0031] Figure 4 is a scanning image of scanning and photographing the cross section of a microfluidic channel with super large width-height ratio prepared by an embodiment of the present application by using fluorescence confocal microscopy. DETAILED DESCRIPTION

[0032] The present application will be further described in detail below in combination with specific embodiments, but the embodiments of the present application are not limited thereto.

[0033] An embodiment of the present application provides a method for preparing a microfluidic channel with super large width-height ratio. As shown in the figure, Figure 1 the method comprises the following steps:

[0034] Step one, a flexible block is prepared by using flexible material, and a microfluidic groove is formed on one side of the flexible block, and an inlet and outlet communicating with the microfluidic groove are formed on the other side.

[0035] In this step one, the flexible block, the microfluidic groove and the inlet and outlet can be prepared by one-piece molding, or the flexible block can be prepared first, and then the microfluidic groove is etched on the surface of the flexible block and the inlet and outlet communicating with the microfluidic groove are opened.

[0036] The flexible material can include polydimethylsiloxane (PDMS), polytetrafluoroethylene (PTFE) or epoxy resin, etc. Here, polydimethylsiloxane and epoxy resin have certain air permeability and can be applied in the embodiment of the present application, so as to prepare the microfluidic channel with super large width-height ratio for biological application.

[0037] The embodiments of this invention do not limit the specific shape of the flexible block, as long as it meets the usage requirements during the preparation process. The side forming the inlet / outlet only needs to be different from the side forming the microfluidic channel; the two sides are not required to be opposite each other.

[0038] After step one is completed, the resulting flexible block can be seen in Figure 2(a), where the structure marked 1 is the flexible block, the structure marked 2 is the microfluidic channel formed on the lower surface of the flexible block 1, and the structures marked A and B are the inlet and outlet of the microfluidic channel, respectively. Figure 2(b) shows the flexible block in... Figure 1 The cross section within the XZ plane outlined by the dashed line.

[0039] Step 2: Bend a base and fill the concave surface of the bend with a volatile liquid.

[0040] The degree of curvature of the substrate should ensure, on the one hand, that it will not break or crack, and on the other hand, that the volatile liquid contained within the concave surface of the curvature is sufficient to cover the opening of the microfluidic channel. Generally speaking, the normal deformation of microfluidic channels with ordinary aspect ratios can reach the millimeter level, while the height of microfluidic channels with large aspect ratios will not exceed 100 micrometers, meaning that the normal deformation of microfluidic channels with large aspect ratios is less than 100 micrometers.

[0041] For example, the substrate can be a rigid substrate with a thickness of less than 0.5 mm. A rigid substrate of this thickness can be bent to a small extent, sufficient to meet the usage requirements in the implementation of this invention. For instance, the substrate can be a glass sheet or silicon wafer with a thickness of less than 0.5 mm. Alternatively, the substrate can include a rigid substrate with a thickness of less than 0.5 mm and a flexible material coating applied to the rigid substrate. The flexible material used in the flexible material coating is the same material as the flexible block.

[0042] The volatile liquid can include deionized water or glycerin, etc. This ensures that the liquid inside the concave surface does not evaporate quickly and can be evaporated in subsequent steps where evaporation is required.

[0043] After step two is completed, the state of the substrate is shown in Figure 2(c), where the structure marked 3 is the substrate and the volatile liquid is marked 4.

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

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

[0046] It should be noted that the presence of a small amount of air within the microfluidic channel after step three is completed does not affect the final effect of this embodiment of the invention. This is because most of the space in the microfluidic channel is occupied by volatile liquid, and the curvature of the small amount of air gap is insufficient to deform the microfluidic channel and cause it to collapse.

[0047] In step three, the schematic diagram of contacting the side of the flexible block with the microfluidic channel with the curved concave surface is shown in Figure 2(d), and the state after the two are in contact is shown in Figure 2(e). It can be seen that the volatile liquid 4 has filled the microfluidic channel 2.

[0048] Step 4: While maintaining contact between the flexible block and the substrate, restore the substrate to a flat position so that the flexible block fits snugly against the substrate.

[0049] Understandably, in order to avoid misalignment between the flexible block and the substrate, and to prevent volatile liquids in the microfluidic channel from flowing out of the microfluidic channel due to shaking, it is best to slowly restore the substrate to a flat position in step four.

[0050] After step four is completed, the state of the substrate and the flexible block being in contact is shown in Figure 2(f).

[0051] Step 5: The flexible block is heated to achieve molecular bonding with the substrate to form microfluidic channels, while the volatile liquid evaporates.

[0052] Understandably, step five uses heating to bond the flexible block to the substrate. This can promote molecular bonding between the flexible block and the substrate, and also help accelerate the evaporation of volatile liquids, eliminating the need to clean the pipes again after the microfluidic channel is formed.

[0053] There are various specific ways to achieve molecular bonding between a flexible block and a substrate to form a microfluidic channel through heating.

[0054] For example, in one implementation, the substrate is heated using a hot stage while maintaining its contact with the flexible block 1, causing the flexible block 1 and the substrate 3 to achieve molecular bonding and form a microfluidic channel, while simultaneously causing the volatile liquid 4 to evaporate. The volatile liquid 4 can evaporate through inlets A and B on the flexible block 1, which are connected to the microfluidic channel 2. At this point, the microfluidic channel 2 and the substrate are already bonded together, forming a microfluidic channel.

[0055] For example, assuming 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, a laser can be used to heat the bonding area between the flexible block and the substrate, thereby bonding the two together.

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

[0058] In the method for fabricating ultra-large aspect ratio microfluidic channels provided in this invention, a flexible block is first prepared using a flexible material. A microfluidic channel is formed on one side of the flexible block, and an inlet / outlet connecting the microfluidic channel is formed on the other side. A volatile liquid is then placed on a curved substrate, and the side of the flexible block with the microfluidic channel is brought into contact with the curved concave surface of the substrate, allowing the volatile liquid to fill the microfluidic channel under surface tension. While maintaining contact between the flexible block and the substrate, the substrate is restored to a straight state, and molecular bonding is achieved between the flexible block and the substrate through heating. This seals the microfluidic channel and the substrate together to form a microfluidic channel. Heating also allows the volatile liquid to evaporate, without affecting the subsequent use of the microfluidic channel. Because the microfluidic channel is supported by the volatile liquid during its formation, it is less prone to collapse. Therefore, the method of this invention can fabricate ultra-large aspect ratio microfluidic channels.

[0059] It is worth mentioning that when using the embodiments of the present invention to prepare microfluidic channels with a channel height greater than or equal to 0.5 micrometers, the upper limit of the channel width-to-height ratio is 1200:1.

[0060] Furthermore, the main material used to prepare the ultra-large aspect ratio microfluidic channels in the embodiments of this invention is a flexible material. Therefore, flexible materials with high plasticity, high permeability, high ductility, and easy stacking, such as polydimethylsiloxane, can be used to prepare microfluidic channels, which are not possessed by the rigid materials commonly used in the prior art. Therefore, the method of the embodiments of this invention can not only prepare ultra-large aspect ratio microfluidic channels for biological applications, but also can be used to prepare complex multilayer chips.

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

[0062] In one embodiment, the method for fabricating an ultra-large aspect ratio microfluidic channel provided by this invention may further include:

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

[0064] For example, the above activation process can be achieved using a plasma cleaner or other chemical methods; after activation, both the side of the flexible block with microfluidic channels and the side of the substrate to be formed with a curved concave surface have a certain degree of hydrophilicity.

[0065] The total time required from the start of the activation process to the completion of step four should also take into account both 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 elaborated here.

[0066] In one embodiment, the method for fabricating an ultra-large aspect ratio microfluidic channel provided by this invention may further include:

[0067] Before step three, glass slides are attached to the opposite surfaces of the flexible block with microchannels to increase the bending stiffness of the flexible block.

[0068] The purpose of this is to prevent the flexible block from twisting and deforming due to its excessively soft material. Of course, if the width of the flexible block is wide enough, such twisting and deformation will hardly occur, so this slide is not necessary.

[0069] In one embodiment, the method for fabricating an ultra-large aspect ratio microfluidic channel provided by this invention may further include:

[0070] After step five, the bonded flexible block and substrate are placed in an oven to bake, thereby increasing the bond strength between them.

[0071] For example, the oven temperature can be set to 80°C and the baking time to 12 hours, but it is not limited to this.

[0072] In a preferred example, see Figure 3 As shown, the method for fabricating ultra-large aspect ratio microfluidic channels provided in this embodiment of the invention may specifically include the following steps:

[0073] S10: A flexible block is prepared using a flexible material, and a microfluidic channel is formed on one side of the flexible block, while an inlet and outlet connecting the microfluidic channel are formed on the other side.

[0074] S20: Activate both the side of the flexible block with microchannels and the side with a substrate.

[0075] S30: Bend the activated side of the substrate inward and fill the concave surface of the bend with a volatile liquid;

[0076] S40: A glass slide is attached to the opposite side of the flexible block with microchannels to increase the bending stiffness of the flexible block. Then, the side of the flexible block with microchannels is brought into contact with the above-mentioned curved concave surface, so that the volatile liquid fills the microchannels under the action of surface tension.

[0077] S50: While maintaining contact between the flexible block and the substrate, restore the substrate to a flat position so that the flexible block fits the substrate.

[0078] S60: While keeping the flexible block in contact with the substrate, the substrate is heated using a hot stage. During the process, the glass slide on the flexible block is removed, so that the flexible block and the substrate achieve molecular bonding to form microfluidic channels, while the volatile liquid evaporates.

[0079] S70: The bonded flexible block and substrate are placed in an oven and baked to increase the bond strength between them.

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

[0081] The method for fabricating ultra-large aspect ratio microfluidic channels provided in this invention innovatively employs a process that utilizes liquid-phase filling and encapsulation to fabricate microfluidic channels. This method can produce ultra-large aspect ratio microfluidic channels that are not easily collapsed and can be used for the fabrication of microfluidic chips.

[0082] To better illustrate the beneficial effects of the embodiments of the present invention, a microfluidic channel with a width of 150 micrometers and a height of only 3 micrometers was prepared using the method for preparing ultra-large aspect ratio microfluidic channels provided in the embodiments of the present invention. After the microfluidic channel was prepared, an aqueous solution of the 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 below. Figure 4 As shown. From Figure 4 As can be seen, the fluorescent molecule solution is uniformly distributed inside the pipe, indicating that the pipe has not collapsed, thus proving the effectiveness of the embodiments 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 such data can be interchanged where appropriate so that the embodiments of this disclosure described herein can be implemented in orders other than those illustrated or described herein. The implementations described in the following exemplary embodiments do not represent all implementations consistent with this disclosure. Rather, they are merely examples of apparatuses and methods consistent with some aspects of this disclosure.

[0084] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features or characteristics described may be combined in any suitable manner in one or more embodiments or examples. In addition, those skilled in the art can combine and integrate the different embodiments or examples described in this specification.

[0085] Although this application has been described herein in conjunction with various embodiments, those skilled in the art, by reviewing the accompanying drawings and the disclosure, will understand and implement other variations of the disclosed embodiments in carrying out the claimed application. In the description of this invention, the word "comprising" does not exclude other components or steps, "a" or "an" does not exclude a plurality, and "a plurality" means two or more, unless otherwise explicitly specified. Furthermore, while different embodiments may describe certain measures, this does not mean that these measures cannot be combined to produce good results.

[0086] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," and "counterclockwise," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0087] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0088] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0089] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. A method for fabricating 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 connecting the microfluidic channel on the other side; Step 2: Bend a base and fill the concave surface of the bend with a volatile liquid; Step 3: Place the side of the flexible block with the microfluidic channel into contact with the curved concave surface, so that the volatile liquid automatically fills the microfluidic channel under the action of surface tension; Step 4: While maintaining contact between the flexible block and the substrate, restore the substrate to a flat position so that the flexible block fits snugly against the substrate; Step 5: The flexible block is heated to form a microfluidic channel by molecular bonding with the substrate, while the volatile liquid evaporates.

2. The preparation method according to claim 1, characterized in that, The preparation method further includes: Before step three, the side of the flexible block with the microfluidic channel and the side of the substrate to be formed with the curved concave surface are 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 within the curved concave surface is sufficient to cover the opening of the microfluidic channel.

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

5. The preparation method according to claim 1, characterized in that, Step five includes: While keeping the substrate and the flexible block in contact, the substrate is heated using a hot stage, causing the flexible block and the substrate to achieve molecular bonding to form microfluidic channels, while the volatile liquid evaporates.

6. The preparation method according to claim 1, characterized in that, The preparation method further includes: After step five, the bonded flexible block and substrate are placed in an oven to bake, thereby increasing the bond strength between them.

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 rigid substrate and a polyurethane flexible material coating applied to the rigid substrate.

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