WO2009082863A1

WO2009082863A1 - A method for forming micro-dots array in micro-channels

Info

Publication number: WO2009082863A1
Application number: PCT/CN2008/000191
Authority: WO
Inventors: Jiahuan Jiang; Yuefei Jia; Yuan Li; Paul K-L Sung; Yunpeng Wu
Original assignee: Chongqing University
Priority date: 2007-12-29
Filing date: 2008-01-28
Publication date: 2009-07-09
Also published as: CN101274469A

Abstract

This invention provides a method for forming micro-dots array in micro-channels. The method includes: across setting micro- threads on the surface of a substrate in a container, pouring liquid polymer into the container and solidifying the said polymer, ridding the threads but saving at least one of micro-thread in the solidified polymer , so the dots crossing the ridded and the saved micro-threads are exposed in the formed micro-channels, and obtaining the micro-dots or micro-dots array in the micro channels.

Description

Micro-array micro-array array construction method

The invention relates to the technical field of microchannel processing, and in particular to a processing method of a microchannel and an internal microarray array thereof.

Background technique:

In the public literature, in order to adapt to various applications, some technical approaches or clues that may be combined between microchannels and microarray arrays have been proposed. For example, US Patent 20070116607 published on May 24, 2007 [Wang, William X.; Yi, Jun; Ke, Sheng; Halmela, Maria; Lahteenmaki, Pertti; Kihara, Kazuma: Microsystems that integrate three-dimensional microarray and multi- Layer microfluidics for combinatorial detection of bioagent at single molecule level] in the described technique, trying to integrate the microfluidic component with the microarray component, obviously this can also greatly promote the efficiency of microarray processing, but this The tricky technology is that the separately fabricated microfluidic components are interfaced with the microarray components, so that the tight integration of the two technical advantages is obviously not effectively reflected. Chinese patent 00119003.2 (Lu Zuhong, He Nongyue: Compound microchannel array chip and its preparation method, April 11, 2001) disclosed microchannel array chip and its preparation method are pre-arranged in tiny through holes or capillaries The surface is coated with the desired specific chemical composition, and a sheet is formed by longitudinal cutting to form an array of short channels arranged in a two-dimensional direction. Such a technical form, although in the form of a micro-dot array or micro-channel, obviously does not reflect the technical functions and advantages of the combination of the micro-array array and the micro-flow channel.

For example, after forming a micro-dot array on a surface, another micro-channel open chip that has been micro-machined is embossed to construct a micro-array micro-array array [eg: Zhang Zhixiang, et al.: Protein DNA hybrid microarray Integration with microfluidic chips, Acta Chimica Sinica, Vol. 63(18): 1743-1746, 2005], or by printing probe spots on an area of a micro-groove (or covered with another material) and forming an array Then, its open face is closed [Mikkel Noerholm, Henrik Bruus, Mogens H. Jakobsen, Pieter Telleman and Niels B. Ramsing: Polymer microfluidic chip for online monitoring of microarray Hybridizations, LabChip, 2004, 4, 28-37]. Dhananjay Dendukuri et al. proposed using an optical device to stop etching in a microfluidic channel to process a polymer microdot array in a microchannel [Dhananjay Dendukuri, Shelley S. Gu, Daniel C. Pregibon, T. Alan Hatton and Patrick S'. Doyle: Stop-flow lithography in a microfluidic device, Lab Chip, 2007, 7, 818-828]. However, there are obviously some shortcomings in this kind of method. For example, the micro-type is difficult to register; the surface problem is not easy to solve; the equipment used by some methods is costly and difficult to grasp; the sealing can not be solved above a certain flow pressure threshold, if The use of plasma to achieve permanent closure is detrimental to the micro-point material of the array.

One way to disclose a patent is to infuse a certain substance (in a certain order) into a pre-prepared microchannel, such as a test reagent [US Patent, United States Patent 20030203366 (Application NumberlO/132575), Lim, Drahoslav, Anderson , Norman G., Braatz, James A.: Microarray channel devices produced by a block mold process], photonic particles [China Patent 200410041365.5 Southeast University Gu Zhongze; Liu Zhaobin; Zhao Xiangwei; Zhang Hong; Lu Yihong, microchannel array using photon particle coding Biochips and application methods], etc., these processing methods have a certain degree of microfluidic and microarray combined technical forms, but they have limited functional extensions under the microfluidic concept, such as the large number of surfaces in the microchannels are not utilized, The dead volume of the device is still mostly, and so on. The same deficiencies are also found in other published patents, for example, U.S. Patent 6,645,432 [Anderson, et al Microfluidic systems including three-dimensionally arrayed channel networks, Nov 11, 2003] discloses a three-dimensional arrangement. The micro-flow system of the channel network of the cloth, the micro-flow system processed therein contains intersecting micro-flow channels and their networks, and the inner surface of the micro-channels only plays a simple role of flow guiding restriction. This deficiency makes it difficult to extend the active control capability within the microfluidic channel. Obviously, in view of the inertia of the conventional technology in the prior art, there are many shortcomings in the manufacturing methods for tightly combining the microchannel and the micro-dot array in the methods disclosed in the above-mentioned various documents, and the related technical application fields are urgently needed. A technical form of combining microfluidic performance with microarray high throughput advantages has been developed.

Summary of the invention:

The object of the present invention is to overcome the problems encountered in the prior art described above, and to provide a flexible and convenient processing method for constructing a micro-array array in a microchannel, and in particular, to provide a micro-molding process. A technology that combines (or integrates) channels with micro-dot arrays. The micro-array array in the microchannel constructed by the processing method or the technical route provided by the invention can further develop a new technical form in which the microfluidic and micro-solid control technologies are closely integrated with the microarray technology. Provide an important platform to greatly expand the practical application of the microsystem principle.

For the purpose of the present invention, a method for constructing a micro-array array in a microchannel according to the present invention includes, for example, The main steps of the next order:

The first step, cross cloth: arrange at least two microwires on the surface of a substrate, each microwire has at least one microfilament intersecting there, and at least one intersection has a contact point;

The second step, casting curing: pouring a liquid polymer on the surface of the above-mentioned cloth substrate, submerging at least one of the intersections, and then curing the liquid polymer;

The third step, the wire removal point: selectively removes one or a plurality of microfilaments in the polymer block in which the cross microfilament is solidified, and at least one microfilament is retained therein to enable curing Forming a microchannel or microchannel array in the polymer block, while the intersections of the microfilaments and the remaining microwires are exposed in the formed microchannels, ie, micro-dots or micro-dots in the microchannels are formed. Array.

The substrate of the present invention may be made of a plastic material, may be a metal or an alloy, may be other solid materials, and meet the requirements of a softening or melting temperature higher than the curing temperature of the polymer being cast. In the practice of the present invention, plexiglass is preferably used to satisfy the conditions in which the cast polymer of the present invention is preferentially cured by polydimethylsiloxane (PDMS). Further, the substrate of the present invention may have a surface shape which may be a flat surface or a surface having a embossed pattern structure, the main purpose of which is to provide a support surface for pouring the liquid polymer. In some cases, the substrate may even be the microfilament itself. The microwire according to the present invention may be made of metal, such as stainless steel microfilament, platinum microfilament, etc., or may be a polymer such as nylon microfilament, biodegradable polylactic acid or polycaprolactone. The wound microfilaments, even the biological hair, may also be in the form of these microfilaments after physical pressure, which may be in the form of microfilaments after surface adsorption or chemical modification, etc., depending on the application. set.

In the practice of the present invention, it is further required that the microfilament constituting material is chemically incapable of cross-linking with the polymer for casting, but to some extent, a certain reaction may occur between the two to facilitate the present invention. Further application. The temperature range of the solid or glassy state of the constituent material of the microfilament of the present invention is required to be compatible with the curing temperature range of the casting polymer; in principle, the melting temperature of the microfilament is required to be higher than the curing temperature of the liquid polymer. For example, the curing temperature of PDMS is generally 60 to 120 ° C, which can be used as an important reference for selecting suitable microfilaments and substrate materials in the practice of the present invention. The liquid polymer for casting according to the present invention may be a thermosetting polymer which can be chemically reacted under heat, pressure or under the action of a curing agent or ultraviolet light, and is cross-linked and cured into a poorly soluble refractory substance. status. Such polymers have been widely used in micromachining processes such as injection molding processes, press processes, microcontact imprinting or stamping processes, and the molding processes involved in the present invention, and the like. It They are inexpensive and exhibit chemical inertness in most applications. In the embodiment of the present invention, a silicone rubber-based polymer (or a silicone-based polymer, silicones) is preferably used, and a typical representative thereof is polydimethylsiloxane (PDMS). Such polymers are probably the most versatile polymers found to date, and a large number of such polymers have been commercialized. For PDMS, Dow Corning (Midland, Michigan, USA) Sylgard 184, GE Silicones (Waterford, New York, USA) RTV 615, and other specifications have been widely used in the research and development of micro-nano technology. Additionally, epoxy resins, polyisoprene based thermoset polymers, and the like can also be employed in some embodiments of the invention.

The method for removing microfilaments in the cured polymer according to the present invention includes physical methods, chemical methods, and the like. The most straightforward physical method is to apply an appropriate amount of force to the end of the microfilament to be removed in the polymer to be removed, and it is necessary to directly extract it. Of course, this requires that the microfilament has a certain tensile strength. Alternatively, after curing, the polymer block is immersed in a solvent suitable for expansion to soak. For example, PDMS is soaked in a solution of absolute ethanol or acetone or triethylamine to smoothly extract the microfilaments solidified therein; however, it is better not to pull other retained microfilaments at this time, after being removed by the microfilaments. Gradient desolvation, the polymer (as in the case of PDMS) can still be used to tightly seal the remaining microfilaments. The chemical method means that after curing, the polymer block is placed in a specific solution for chemical etching or electrochemical etching of the removed microfilament, or is connected to the microfluidic driving device to perform chemical etching in a microfluidic manner. In this process, it is required that the etching solution itself does not react with the cured polymer, but the microwires solidified in the polymer can be corroded. For example, when PDMS is used to cure stainless steel microfilaments, it can be corroded with a strong acid to remove stainless steel microfilaments to form channels; and to speed up the corrosion, an electrochemical method can also be used. Another effective method is to use a laser focusing method to burn the microfilament to be removed in the cured polymer, supplemented by a mechanical method to achieve the purpose of wire removal.

The radial dimension of the microwires selectable in the practice of the present invention is less than 1 mm; the acquisition of the conventional minimum size microfilaments depends on the manufacturing process of the commercially available different material microfilaments, such as commercially available circular cross section stainless steel micro The wire diameter can be as small as 18 microns.

The cross-section of the microwires selectable in the practice of the present invention may be circular, rectangular or other irregular shape; for example, the stainless steel microwires (usually circular) are radially extruded between the hard planes to form an approximation The cross section of the rectangular football field shape (further, this extrusion can even reduce the radial dimension of the stainless steel microwire to the nanometer scale).

The flexible diversity of the method of the invention is also reflected in the fact that it can be used with different geometries The microfilament arrangement with the shape or combination thereof is cured in the polymer to achieve microchannel cross-sections, micro-dots with different sizes and geometries. Therefore, the "micro-dots" of the present invention are essentially physical faces having a certain topological geometry and area. The physical micro-points obtained based on the implementation of the method of the present invention are an important platform for further development of various types of applications including biological, chemical, and hydrodynamics.

Obviously, the method of the present invention provides a simple process route to realize a geometric topology complex micro-array array and its connected micro-flow technology method, which makes the micro-channel inner surface patterning direct and simple. It can be processed into complex discontinuous microchannel structures in the block, and the micro-patterns in the channel can be easily interfaced with some macroscopic physical functions outside the channel. The existing life sciences are also improved from a simple technical point of view. , chemical science, materials science and other fields to build micro-array processing methods. The most obvious technical effect brought by the invention is that the micro dot arrays are directly combined and processed in an integrated manner in a microchannel or microchannel array. Based on this, microfluidic manipulation combined with microchannels can realize many kinds of practical Application purpose. For example, under microfluidic conditions, the same or different functional components can be combined by physical adsorption or chemical reaction at each or a part of the micro-dots, including biological materials for controlling cells, etc., and the amount of binding can also be obtained. Quantitative adjustment. Further, by manipulating the hydrodynamic properties of the droplets or liquid columns in the microchannel, the ability to selectively bind different species on the microdots can be achieved, thereby processing complex material patterns on the surface of each microdots. Thus, the micro-array in this microchannel is a technology platform that can be developed for a variety of functional applications. On this technology platform, it will be possible to develop new techniques for high-throughput manipulation of the combined functional components, as well as to facilitate the interaction between microfluidic inclusions and conjugates on microarray arrays, even It will be easy to develop newer technical features that integrate microfluidics with microsolids. Further, in the processing technique of the present invention, the materials involved in the microfilaments and auxiliary devices are widely selected, and most of them have been highly commercialized and inexpensive, and thus are suitable for mass production of many specific embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS:

Figure 1 is a top plan view of the microfilaments arranged in a crisscross pattern on the surface of the substrate.

Figure 2 is a front elevational view of the microwires arranged in a crisscross pattern on the surface of the substrate.

Figure 3 is a top plan view of the process of casting a polymer into a microfilament.

Figure 4 is a front elevational view of the process of casting a polymer into a microfilament.

Figure 5 is a schematic illustration of an in-channel microdot array of a microchannel array. Figure 6 is a schematic illustration of the intersection of a circular cross-section microfilament crossing contact point as a micro-dot when forming a channel. Figure 7 is a schematic illustration of a micro-array array within a single microchannel.

Fig. 8 is a schematic view showing the cross arrangement of the micro-filaments having a rectangular cross section.

Figure 9 is a schematic diagram of a micro-dot array of micro-rectangular surfaces in a micro-rectangular cross-sectional channel array formed by rectangular cross-section microfilaments as a template.

Fig. 10 is a schematic illustration of a microdot array constructed using a sinusoidal curved circular section microwire as a channel template.

Figure 11 is a schematic illustration of a microarray array of helical arrangements within a microchannel.

Figure 12 is a schematic diagram of a microchannel array of microchannels arranged in parallel according to a sandwich.

Figure 13 is a schematic diagram of a microchannel array in a microchannel based on a sandwich-type cross arrangement.

Figure 14 is a schematic diagram of an arc-shaped micro-dot array in a microchannel.

In the above figures, 1 is a recessed structure, 2 is a base, 3 is the upper surface of the substrate, 4 is the first type of microfilament, 5 is the first microfilament array, 6 is the second type of microfilament, and 7 is the second microfilament. The array, 8 is the intersection of the microwires arranged in two different directions, 9 is a through-hole of the gland piece, 10 is a gland piece, and 11 is a through hole formed by the gland piece and the base 2 being fixed together, 12 For casting polymers, 13 is a cured polymer sheet, 14 is a microchannel and its array, and 15 is a microchannel internal microdot array.

detailed description:

The present invention is further described below in conjunction with the accompanying drawings and embodiments as follows:

Example 1:

As shown in Figures 1 through 6, the process of constructing a microdot array within a planar microchannel array in accordance with the method of the present invention is described. The specific instructions are as follows:

First step, cross cloth: As shown in FIG. 1 and FIG. 2, on the upper surface 3 of the substrate 2 having the recessed structure 1 at the center, the first type of microfilaments 4 are arranged at a pitch of 90 μm in one direction and fixed. Forming the first microfilament array 5, and arranging the second microfilament 6 in the other direction to form the second microfilament array 7; the first microfilament array 5 and the second microfilament array 7 are crossed in two, each There is a contact point 8 at one intersection. Then, the gland sheet 10 of the central opening through hole 9 is pressed over the upper surface 3 of the substrate 2 so that the first microfilament 4 and the second microfilament 6 are formed in the first step. The wire array 5 and the second microfilament array 7 are sandwiched therebetween, and the through holes 9 are corresponding to the positions of the recessed structures 1 on the substrate 2, and then the gland 10 is fixed to the substrate 2, as shown in FIG. Show. The second step, casting curing: As shown in Fig. 3 and Fig. 4, in the through hole structure 11 formed after the gland 10 and the substrate 2 are fixed, the polymer material 12 is cast and cured. Then, the fixed relationship between the both ends of the first type of microwires 4 in the gland sheet 10, the first microfilament array 5, and the two ends of the second type of microwires 6 in the second microfilament array 7 is released. The polymer sheet 13 which has been circumferentially joined to the intersecting first microfilament array 5 and second microfilament array 7 is taken out from the recessed structure 1.

The third step, the wire removal point: as shown in FIG. 5 and FIG. 6, the second type II microwires 6 of the second microfilament array 7 are removed from the polymer sheet 13 to form the microchannel array 14; Within each of the microchannels and at each intersection 8 of each of the first microfilaments 4 in the first microfilament array, a microdot array 15 in the microchannel is formed.

For the fixing manner of the first kind of microfilament 4 and the second kind of microfilament 6 on the upper surface 3 of the substrate 2, various methods can be taken, such as fixing with a daily smooth mouth clamp, or winding the microfilament The end of the base 2 is fixed by screwing. It is also possible to adopt a method in which the microwires are arranged in advance at a certain interval, and the length is fixed at both ends, and then removed and fixed to the substrate 2.

After removing the second type microfilament 6 or its second microfilament array 7 in one direction, the original intersection 8 of the first type of microwire 4 or its first microfilament array 5 is exposed, and its surface orientation Within the microchannel 14, thereby forming the microchannels within the microchannels of the present invention and their array 15.

Further, after removing the second microfilament array 7, if any one of the first kinds of microfilaments 4 is removed in the first microwire array 5, the microchannels 14 and the micro-dots 15 inside thereof can be all Communication on the flow, thus essentially forming a micro-flowing network.

The effective length of the microchannel 14 can be determined or adjusted by varying the length of the recessed structure 1 on the substrate 2 in the corresponding direction of the through hole 9 of the gland sheet 10, typically no more than 50 mm. The channel density of the microchannel array 14 can be determined by the arrangement density of the second type of microwires 6 in the second microfilament array 7, and the arrangement pitch of the adjacent two second type microfilaments 6 is generally not more than 50 mm. The dot density of the micro dot array 15 in the microchannel array can be determined by the number of intersections of the first microwire array 5 and the second microfilament array 7. The geometry and size of these microdots 15 may vary with the geometry and size of the first microfilament 4, the second microfilament 6, and the cast polymer 12 and the first microfilament 4 and/or The interaction state between the surfaces of the second type of microfilaments 6 during the curing process depends. For example, ideally, if the first type of microfilament 4 is in contact with the second type of microfilament 6 The cross section of each of the bare microdots 15 is circular, and the circular diameter is smaller than the smaller microfilament diameter; if the cross section of the first microfilament 4 is circular, in contact with it The surface of the second type of microwire 6 is a flat surface, and the vertical projection of the formed bare micro-dots 15 is a minute rectangle whose length is the lateral width of the flat surface of the second type of microfilaments 6, and the width thereof is smaller than the first type The diameter of the microfilaments 4; and so on can be reasonably derived from the geometric relationship. According to the experiment, when the PDMS is used as the casting material, the minimum geometry of the bare microdots 15 can reach the nanometer level. Thus, the geometry of the microdots 15 that can be provided by the present invention will be varied and its size can vary over the micronanoscale range.

Example 2:

As shown in Figure 7, this figure depicts a single microchannel internal microdot array fabricated in accordance with the teachings of the present invention. On the upper surface 3 of the plexiglass substrate 2 having a rectangular groove (or recessed structure 1), a 40 micron diameter nylon thread (as the second type of microfilament 6) is arranged in one direction and fixed, in another Dozens of platinum wire (as the first type of microfilament 4) having a diameter of 20 micrometers are arranged in parallel at a pitch of 10 micrometers in the direction and fixed, and then have a rectangular shape having the same size as the rectangular groove (or the recessed structure 1) described above. The plexiglass cover sheet 10 of the hole 9 is placed over the substrate 2 and the groove 1 and the through hole 2 are aligned to be fixed.

The PDMS prepolymer and the curing agent are mixed in a weight ratio of 10:1, uniformly mixed, and then evacuated in a vacuum pumping tank for about 40 minutes to remove the air in the polymer, and then fixed on the cover sheet 10 and the substrate 2 In the through hole 11 formed later, the liquid PDMS polymer 12 was cast and cured by heating at 90 ° C for 30 minutes.

After the corresponding fixing is released, the cured polymer sheet 13 is taken out from the rectangular groove (or the recessed structure 1), and together with the platinum wire (the first kind of microfilament 4) and the nylon wire (the second kind) The microfilament 6), placed in absolute ethanol for 30 minutes, and then the nylon filament (the second microfilament 6) is withdrawn from the polymer to form a circular cross-section microchannel 14 having an inner diameter of 40 μm. An array of ten micro platinum points 15 .

Example 3:

As shown in Figures 8 and 9, the two figures depict the formation of a rectangular microdot array within a microchannel in accordance with the teachings of the present invention. Taking stainless steel microwires of the same rectangular cross section (ie, the first type of microfilaments 4 and the second type of microfilaments 6), and arranging them in an orthogonal array (ie, forming the first microfilament array 5 and the second microfilament array 7) Fixed on the plexiglass substrate 2; the pressure cover sheet 10 is aligned on the substrate 2 The recessed portion is fixed and cast, PDMS is cast, and cured, as shown in FIG. 8; after curing, the II microfilament array 7 arranged above is extracted, that is, the micro dot array 15 formed in the microchannel 14 is formed in the shape of a dot. The rectangle has a length which is the width of the first type of microwire 4 arranged below, and the width is the width of the second type of microwire 6 arranged above, as shown in FIG.

Example 4:

As shown in Figure 10, this figure depicts the integration of microchannels with microflow arrays with microflow mixing. According to the method of the present invention, a row of stainless steel microwires (as the first microfilament array 5) are longitudinally arranged on a plane, and then the same stainless steel microwires (as the second type of microfilaments 6) are laterally arranged in a sine shape thereon. The curve form and its array (as the II microfilament array 7) and fixed; then directly cast PDMS and solidified, and then removed from the plane together with the two stainless steel microwire arrays 5 and 7 which are in cross-contact inside, such as the bottom PDMS The curing thickness is insufficient, and a certain thickness of PDMS can be cured again on the bottom surface; then it is expanded in a hexane solvent for 3 hours, the microwires arranged in a sinusoidal curve are removed, and then placed in water to reduce PDMS, thereby forming a sine The curved microchannel 14 and the stainless steel microarray 15 therein. If two different solutions are introduced into the sinusoidal channel, this sinusoidal channel acts as a micromixer, and the continuously mixed solution will flow through the already exposed stainless steel microdot array 15 .

Example 5

A microarray array of spiral arrangements within a microchannel. According to the method of the present invention, on the outer surface of the capillary having an outer diameter of 0.5 cm and a length of 3 cm, a diameter of 40 μm and a length are arranged in parallel along the axial direction at an interval of 60 μm along the axial direction as shown in FIG. 5 cm of stainless steel microfilament 6, both ends are fixed; then two 40 micron stainless steel microfilaments 4 are placed on the microwire 6 of the above-mentioned parallel arrangement, and the inner axial length of 2 cm is spirally wound. , making it cross-contact with each of the parallel arranged microfilaments 6 and fixed at both ends; then coating the outer surface of the capillary with the microfilaments coated with a Sylgard 184 PDMS liquid prepolymer mixed in a ratio of 10:1, or The above-mentioned microwire-filled cylinder is directly poured into the PDMS liquid prepolymer and pulled out, so that the PDMS liquid layer masks the contact intersections, degassing and heating and solidifying, and removing the spirally wound microfilaments 4 That is, an array of hundreds to thousands of micro-dots in a spiral-oriented circular microchannel having a diameter of 40 micrometers is formed.

Example 6:

A microchannel array of microchannels arranged in parallel according to a sandwich. According to the method of the present invention, as shown in FIG. Illustrated, (1) by electrochemically polymerizing a number of stainless steel microfilaments having a 100 nm polypyrrole layer in a parallel direction in the X direction with a surface having a diameter of 20 μm; (2) on the parallel microfilaments formed above , using a number of 20 micron stainless steel microfilaments that are flattened to 5 microns thick, and straighten the rows in the Y direction; (3) on the parallel microfilaments formed in the Y direction (2), and then In the same way, a plurality of stainless steel microfilaments having a polypyrrole-modified layer are arranged in a straight line, so that the microfilament arrays formed in (1), (2) and (3) are sandwiched in parallel cross-contact nets. And (1) and (2) are completely vertically aligned, wherein the spacing between adjacent contact points is 75 microns. The sandwich parallel cross-contact net is solidified in a PDMS block in a conventional manner, and then the 5 micrometer thick stainless steel microwire array sandwiched therebetween is removed, and the crucible can be formed into a microchannel having a height of 5 micrometers and a width of about 63 micrometers. A micro dot array form arranged up and down.

Example 7

A microchannel array of microchannels based on a sandwich-type cross arrangement. According to the method of the present invention, as shown in Fig. 13, 20 micron stainless steel microwires are arranged in a weaving manner by 20 micron stainless steel microwires to form a sandwich cross-contact net, wherein the spacing between adjacent contact points is At 75 microns, it is cured in a PDMS block in the conventional manner described above, and then the parallel-stitched stainless steel microwires are removed to form a micro dot array in a staggered arrangement in a channel having a diameter of 20 microns.

Example 8

An arc-shaped micro dot array in a microchannel. According to the method of the present invention, a spin-coated PDMS prepolymer is added dropwise on the surface of a glass slide to a thickness of 30 μm; a nylon microfilament 4 having a diameter of 60 μm is arranged thereon, and the nylon microfilament 4 is made into a liquid state. The upper surface of the PDMS was immersed from top to bottom, and the exposed surface was not stuck to PDMS; then it was baked at 50 C for 2 hours, and after taking out, stainless steel microwires having a diameter of 20 μm were arranged at regular intervals along the vertical direction of the nylon microfilament 4. 6; recast the PDMS prepolymer and bake at 50 ° C for 3 hours, take out, and remove the nylon microfilament 4, that is, form a circular arc micro dot array with a radius of 30 microns in the obtained microchannel, as shown in the figure 14 is intended.

Example 9

A method of constructing a micro-array array in a microchannel using a hair of a living body. According to the method of the invention, a certain length of hair and stainless steel microfilaments are taken, ultrasonically washed with acetone, ethanol and ultrapure water, and N _{2 is} blown dry. They are then placed in different directions, in a similar manner as described above, in a cross-contact arrangement and fixed at the desired spacing. Ratio of PDMS prepolymer and curing in a weight ratio of 10:1 The mixture was uniformly mixed and then evacuated in a vacuum pumping tank for about 40 minutes to remove air from the liquid polymer, cast on the above-mentioned arranged cross-filaments, and then baked at 45 ° C for 4 hours. Remove the cured PDMS polymer sheet (in this case together with the wire and hair), place it in absolute ethanol for about 10 minutes, then extract the stainless steel microfilament from the polymer sheet, leaving the microchannel An array of filaments of several organisms.

Example 10

A method of constructing micro-array arrays in microchannels by electrochemical etching. According to the method of the present invention, a rigid substrate and a cover sheet are processed by polymethyl methacrylate (PMMA), the stainless steel wires are arranged in one direction on the substrate and fixed, and the Teflon filaments are arranged in the other direction and fixed, and then the cover is covered. The upper cover sheet is fixed in alignment with the substrate, the prepolymer is poured, such as PDMS, and solidified, and then the removed polymer is placed in a 50% hydrochloric acid solution together with the cured cross-contact microfilament array, and DC gas is passed until the stainless steel wire is passed. After being etched, the microchannel array formed by the rinsing is constructed to construct a Teflon microdot array in the PDMS microchannel.

Example 11

A microchannel array of microchannels is fabricated using a photocurable polymer. According to the method of the present invention, after the fixed clean stainless steel microwire array is arranged in the first direction, the surface of the microfilament is treated with oxygen plasma (0 ₂ pressure 0.5 MPa, 70 W) for 5 minutes, and placed in a vacuum aspirator. Evaporate tridecafluoro-1, 1, 2,2-tetrahydrooctyl- 1 -trichlorosilane, and make it surface stone and then arrange the clean stainless steel microwire array in the second direction. Next, an epoxy resin prepolymer (such as EP-TEK from Epoxy Technology, MA) can be injected and allowed to stand in air for 1 hour, in ultraviolet light (including wavelengths of 365mn, 406nm and 436nm, and intensity of about 10 mW/cm). ² ) After about 20 minutes of irradiation, the curing is achieved, and then the microwire in the first direction is extracted, and the microwire remaining in the second direction in the polymer sheet is exposed in the microchannel, that is, the microchannel is realized. Construction of an inner stainless steel microdot array.

Claims

A microchannel in-micropoint array construction method, characterized in that the method comprises the following sequence of steps:

The second step, casting solidification: pouring a liquid polymer on the surface of the above-mentioned cloth substrate to submerge at least one of the cross-contact points, and then curing the liquid polymer;

2. The method of claim 1 wherein: said microwires have a radial dimension of less than 1 mm.

3. The method of claim 1 wherein: the maximum spacing between adjacent two micro-dots in the array of micro-dots does not exceed 50 millimeters.

4. The method of claim 1 wherein: the removed microfilaments are capable of being detached from the cured polymer.

5. The method of claim 1 wherein: said liquid polymer is a thermally or photocurable polymer.