TW201740111A - Microfluidic device - Google Patents

Abstract

The microfluidic device comprises a base plate, a cover plate, a plurality of micro-channels formed therebetween, and a bubble trap chamber. The microfluidic device has an input region, a micro-channel region and an output region. The micro-channels are disposed in the micro-channel region and formed by assembling the base plate and the cover plate. Each micro-channel stretches along a first direction and has a plurality of ribs on at least one surface of the micro-channel. The ribs stretch along a second direction in a serpent manner. The bubble trap chamber is disposed in the input region and formed by assembling the base plate and the cover plate.

Description

Microchannel device

BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to a microchannel device, and more particularly to a microchannel device that increases the target adsorption rate.

Microfluidic device technology is a technology that automates the entire process of analyzing the basic operations of sample preparation, reaction, separation and detection of biological, chemical and medical analysis processes onto a micron-scale wafer. In recent years, microfluidic wafers and microfluidic devices have become increasingly important applications in biomedical testing, pharmaceutical, environmental and food safety monitoring. In the research of clinical tests, new drug synthesis and screening, and the relationship between human genes and diseases in biomedicine, the samples to be tested, such as human blood, have low concentration of side substances and high concentration of interference components. It is difficult to improve the sensitivity of detection by conventional analytical methods. . The microchannel analysis system can significantly improve the analysis efficiency and sensitivity of the sample, and has been widely used in the research and analysis of cell culture.

The basic features and greatest advantages of microfluidic wafers are the ability to arbitrarily design a variety of cell modules on a wafer platform to perform different tasks. The manipulation of fluids in microfluidic wafers is on the order of micrometers, between the macroscale and the nanoscale, where fluid motion exhibits duality. On the one hand, the micrometer scale is still much larger than the mean free path of the molecule in the usual sense. Therefore, for the fluid therein, the continuum theorem holds and the continuity equation is available. On the other hand, relative to the macroscopic scale, the influence of inertial force on the micrometer scale is reduced, the influence of viscous force is increased, and the laminar flow characteristics are obvious. The mass transfer process is mainly from convection to diffusion, and the aspect ratio is increased. The surface effects of adhesion, surface tension and heat transfer are enhanced, the edge effect is increased, and the three-dimensional effect is not negligible.

How to improve the mixing uniformity of microchannel liquids at the microscopic scale is one of the goals of researchers in the field of microchannels. In order to achieve high-efficiency mixing of microfluids in the shortest time, it is customary to use pressure, temperature, electrodynamics, magnetic fields, ultrasonic waves, etc. to increase the contact area between different liquid streams to improve the mixing effect, but such effects are Not obvious. On the other hand, the bubbles caused by the liquid inlet process directly affect the transport control, biochemical reaction and detection of the liquid in the microfluidic channel, which is also a problem that the sensitivity of the existing microchannel device needs to be overcome. Therefore, there is still a need for a novel microchannel device that is improved in response to the above problems.

The present invention thus provides a microchannel device capable of increasing the collision probability of a sample to be tested and a microchannel chamber in a fluid to be tested, and reducing bubble entry into the microchannel, thereby increasing overall sensitivity.

According to one embodiment of the invention, the microchannel device comprises a substrate and a cover, a plurality of microchannels, and a defoaming chamber. The microchannel device has an injection zone, a microchannel zone, and an output zone. a micro flow channel is disposed in the micro flow channel region and is formed by the substrate and the cover plate, each micro flow channel extending along a first direction, and having a plurality of spines disposed on at least one side of each of the micro flow channels The spines extend curvedly in a second direction. A defoaming chamber is disposed in the implantation zone and is formed by the substrate and the cover.

The microchannel device provided by the invention is characterized in that the special spine structure can increase the disturbance of the liquid in the microchannel, thereby increasing the capture rate of the object to be tested, and the bubble removing chamber can prevent the bubbles from entering the microchannel. The arc-shaped dendritic approach avoids the accumulation of fluid at the corners, thus improving the sensitivity of the overall microchannel device.

In order to enable those skilled in the art to further understand the present invention, the constituents of the present invention and the effects desired to be achieved are described in detail below. Sufficient details have been disclosed below to enable those skilled in the art to implement it.

Please refer to FIG. 1 , which is a schematic diagram of one embodiment of a micro-channel device according to the present invention. As shown in FIG. 1, the micro-channel device 300 of the present invention comprises a substrate 302 and a cover plate 304. When the cover plate 304 is correspondingly attached to the substrate 302, the chamber formed between the two can be allowed. The fluid to be tested (such as blood) passes. In general, the chamber is formed generally over the cover plate 304, but may be formed on the substrate 302. In an embodiment, the cover plate 304 can be divided into three regions according to functions: an injection zone 400, a micro runner zone 500, and an exit zone 600. The implanted region 400 includes an injection port 402 and a dendritic approach 404. When the fluid to be tested (not shown) is input from the injection port 402, the drainage may be distributed through the dendritic approach 404, and then evenly entered into the plurality of microchannels 502 in the microchannel region 500 to be in the microflow. Various detection reactions are performed in the track 502; subsequently, it flows to the dendrite path 604 of the exit zone 600, and finally merges to the output port 602 to output the fluid to be tested.

The substrate 302 and the cover plate 304 may use different or the same materials depending on different functions. In one embodiment, substrate 302 and cover plate 304 can each be fabricated using a suitable material. For example, the cover plate 304 can be fabricated using an elastomer such as polydimethylsiloxane (PDMS) and the substrate 302 can be fabricated using glass, polydimethyl siloxane or other elastomers. If the substrate 302 and the cover plate 304 are made of the same material, in addition to the above materials, a plastic material such as polymethylmethacrylate (PMMA), polycarbonate (Polycarbonate, PC), or a cyclic olefin copolymer may be included. Cyclo olefin copolymer (COC), but not limited thereto. For example, other materials having optical properties, fluorescent properties, or special functional groups may be included according to the requirements of product design. In other embodiments of the present invention, the substrate 302 and the cover plate 304 may also be integrally formed according to different fabrication techniques.

Please refer to FIG. 2, which is a schematic diagram of a micro flow channel in one embodiment of the present invention. When the cover plate 304 and the substrate 302 are bonded together, the patterns of the cover plate 304 and/or the substrate 302 are combined to form the micro flow path 502. As shown in FIG. 2, the micro flow channel 502 has a top surface 502T, two side surfaces 502S, and a bottom surface 502B. The top surface 502T and the two side surfaces 502S are located on the cover plate 304, and the bottom surface 502B is located on the substrate 302. . However, in other embodiments, the various faces or walls of the microchannel 502 may be arbitrarily disposed on the substrate 302 or the cover plate 304 as long as the chamber capable of forming the micro flow channel 502 is combined, and the wall or surface thereof is not limited. Four sides, but can be smaller or more. As shown in the enlarged view on the right side of FIG. 2, one of the features of the present invention is that any one of the microchannels 502, for example, the top surface 502T has a plurality of ribs 504 projecting downwardly into the microchannels 502. The spine 504 can be a long bump, a rounded bump, a triangular bump, or a bump of other geometric shapes. The spine 504 is generally perpendicular to the direction of the microchannel 502, that is, the microchannel 502 extends in the first direction 306 (from the first view, the first direction 306 refers to the direction of the injection port 402 toward the output port 602) The spine 504 extends in the second direction 308, and the first direction 306 is not equal to the second direction 308. Preferably, the first direction 306 is perpendicular to the second direction 308. In a preferred embodiment of the invention, the spine 504 may also have a serpent or zig-zag shape when extending in the second direction, a detailed embodiment of which is described below.

Please refer to FIG. 3, which is a schematic diagram showing the efficacy of having a spine and no spine in a microchannel device. As shown in the lower diagram of FIG. 3, the surface of the microchannel 502 (top surface 502T, side surface 502S, bottom surface 502B) preferably has a coating layer 506, and the coating layer 506 has an adsorbent detectable substance 700. Uniquely combined. In one embodiment, the sorbate is, for example, an antibody, a magnetic bead, or the like, but is not limited thereto. The coating layer 506 may also have different adsorbates as appropriate, which are respectively coated in different walls of the microchannels or in different microchannels. The present invention can increase the probability that the analyte 700 (such as cancer cells) in the fluid to be tested (such as blood cells) collides with the wall of the microchannel 502 due to the structure provided with the spine 504. As shown in the lower diagram of FIG. 3, since the directions of the spine 504 and the microchannel 502 are not parallel, a disturbance collision occurs when the sample to be tested 700 flows, and the adsorbate in the coating layer 506 can be increased to grasp the object to be tested. The chance. In the case where there is generally no spine, as shown in the upper diagram of FIG. 3, the object to be tested 700 uniformly flows through the microchannel 502, and is less in contact with the coating layer 506.

Please refer to FIG. 4 to FIG. 8 , which are schematic diagrams showing different embodiments of the spine of the micro-channel device of the present invention, wherein the top of each figure is a plan view, the middle is an enlarged size mark diagram, and the lower part is a partial section size. Tag map. In order to increase the turbulence of the spine 504, in a preferred embodiment, the spine 504 has a serpent or zig-zag pattern on the plane, and more specifically, the spine 504 will follow the Two directions 308, and one or more mode wobbles are present within a fixed pitch of the first direction 306. As shown in FIG. 4, the width of the overall microchannel 502 is about 2 mm. The spine 504 exhibits a wave shape of "large wave 504A, wavelet 504B" along the first direction 306, wherein the length and width of the large wave 504A ( Along the second direction 308 is defined as being long, defined as a width along the first direction 306 of about 0.125 mm or 0.1 mm, and the length and width of the wavelet 504B is about 0.05 mm; the width and adjacent width of each vertebra 504 The ratio of the distance between the ridges 504 is about 1:1.66. For example, each vertebra 504 is about 0.075 mm wide and about 0.125 mm apart from the adjacent vertebra 504. In the cross-sectional view, the spine 504 is higher than the upper spine. The ratio of the height of the bottom of 504 to the height of the substrate 302 is about 1:2, for example, the height of the spine 504 is 35 micrometers (μm), and the height of the bottom of the spine 504 and the substrate 302 is 70 micrometers.

In another embodiment, as shown in FIG. 5, the width of the whole microchannel 502 is about 2 mm, and the spine 504 exhibits a wave shape of "large wave 504A, wavelet 504B" along the first direction 306, wherein the large wave 504A The length and width are about 0.2 mm, and the length and width of the wavelet 504B are about 0.1 mm; the ratio of the width of each vertebra 504 to the distance between the adjacent two vertebrae 504 is about 1:1, for example, the width of each vertebra 504 is about 0.05. The distance from the adjacent spine 504 is about 0.05 mm; in the cross-sectional view, the ratio of the height of the spine 504 to the height of the upper spine 504 to the base plate 302 is about 1:2, for example, the height of the spine 504 is At 35 microns, the height of the bottom of the spine 504 and the substrate 302 is 70 microns.

In another embodiment, as shown in FIG. 6, the width of the overall microchannel 502 is about 2 mm, and the spine 504 exhibits a wave shape of "large wave 504A, wavelet 504B" along the first direction 306, wherein the large wave 504A The length and width are about 0.3 mm or 0.35 mm, and the length and width of the wavelet 504B are about 0.15 mm; the ratio of the width of each vertebra 504 to the distance between the adjacent two vertebrae 504 is about 1:2, for example, each vertebra 504 is about 0.1 mm wide and about 0.2 mm apart from the adjacent spine 504; in the cross-sectional view, the ratio of the height of the spine 504 to the height of the upper spine 504 to the base 302 is about 1:2, such as a ridge. The bone 504 is 35 microns high and the bottom of the spine 504 is 70 microns high from the base plate 302.

In another embodiment, as shown in FIG. 7, the width of the overall microchannel 502 is about 2 mm, and the spine 504 exhibits a wave shape of "large wave 504A, wavelet 504B" along the first direction 306, wherein the large wave 504A The length and width are about 0.2 mm, and the length and width of the wavelet 504B are about 0.1 mm; the ratio of the width of each vertebra 504 to the distance between the adjacent two vertebras 504 is about 1:1.75, for example, each vertebra 504 is about 0.04 wide. The distance from the adjacent spine 504 is about 0.07 mm; in the cross-sectional view, the ratio of the height of the spine 504 to the height of the upper spine 504 to the base plate 302 is about 1:2, for example, the height of the spine 504 is At 35 microns, the height of the bottom of the spine 504 and the substrate 302 is 70 microns.

In another embodiment, as shown in FIG. 8, the width of the entire microchannel 502 is about 2 mm, and the spine 504 exhibits a wave shape of "large wave 504A, wavelet 504B" along the first direction 306, wherein the large wave 504A The length and width are about 0.2 mm, and the length and width of the wavelet 504B are about 0.1 mm; the ratio of the width of each vertebra 504 to the distance between the adjacent two vertebras 504 is about 1:1, for example, each vertebra 504 is about 0.08 wide. The distance from the adjacent spine 504 is about 0.08 mm; in the cross-sectional view, the ratio of the height of the spine 504 to the height of the upper spine 504 to the base plate 302 is about 1:2, for example, the height of the spine 504 is At 35 microns, the height of the bottom of the spine 504 and the substrate 302 is 70 microns.

According to the above embodiment, in a preferred embodiment of the present invention, the spine 504 has an arrangement of "large wave 504A, small wave 504B", wherein the length ratio or width ratio of the wavelet 504B to the upper large wave 504A is about 1:1.5 to 1:2.5. The width of the spine 504 is about 1:1~1:2.5 from the spacing of the adjacent spine 504, and the ratio of the height of the spine 504 to the height of the bottom of the upper spine 504 and the height of the substrate 302 is about 1:2. Perturb the state and increase the target capture rate. According to experiments, using the microchannel device of the embodiment of Fig. 4, it is possible to have a cell capture rate of up to 83%. However, it can be understood that the ratios presented in the above embodiments are only preferred embodiments of the present invention. In other cases, those skilled in the art can arbitrarily combine the arrangement of "large wave 504A, wavelet 504B". The length and width, or the distance between adjacent vertebrae 504, or the height of the spine 504, are adjusted to produce different embodiments.

In one embodiment, the microchannel device 300 of the present invention also has a defoaming structure and a special dendritic approach to increase the overall sensitivity of the device. Please refer to FIG. 9 , which is a schematic diagram of the injection port, the dendritic approach and the defoaming structure of the injection zone of the present invention. As shown in Fig. 9, the defoaming chamber 406 is preferably disposed between the injection port 402 and the dendritic approach 404 (refer to Fig. 1 again), which is circular from the top view, but may be other The shape, as shown in Fig. 10, the upper view of the defoaming chamber 406 may be rectangular. The defoaming chamber 406 is characterized by a top surface 406A having a height of about 200 to 300 microns, and a height of about 100 microns compared to the chambers of the microchannel 502 and the dendritic approach 404. :2~1:3. The defoaming chamber 406 is provided with a plurality of cylinders 406B extending up and down through the defoaming chamber 406. Preferably, the cylinders 406A are evenly distributed in the defoaming chamber 406. Due to the higher top surface 406A and the column 406B, if there is a bubble in the fluid to be tested, the bubble will be retained in the defoaming chamber 406 through the defoaming chamber 406 without flowing into the dendritic approach. 404. In other embodiments of the invention, the defoaming chamber 406 may also be disposed in the dendrite 404, which may be adjusted depending on the product design. In one embodiment of Figure 9 of the present invention, the circular defoaming chamber 406 has a top surface height of 270 microns, an area of 22 square meters, and a volume of 6 microliters (μL), which can successfully retain 4 microliters of air bubbles.

In addition, as shown in FIG. 9, the dendritic approach 404 is characterized by having a circular corner 404A disposed between the plurality of approach 404B, 404C, such as along the first direction 306 of the approach 404B and along the Between the two directions 308 between the approach 404C. Thereby, the smoothness of the flow of the fluid to be tested can be increased, and the situation that the turning point is easily retained in the conventional turning point can be avoided. Further, the aforementioned circular arc angle 404A may also be disposed at a similar position in the output area 600.

In summary, the present invention provides a microchannel device characterized in that a special spine structure can increase the target capture rate of the microchannel, and the defoaming chamber can prevent bubbles from entering the microchannel, and the arc shape The dendritic approach avoids accumulation of fluid at the corners. With the above design, the sensitivity of the overall microchannel device can be improved. The above are only the preferred embodiments of the present invention, and all changes and modifications made to the scope of the present invention should be within the scope of the present invention.

300‧‧‧Microchannel device
500‧‧‧microchannel area
302‧‧‧Substrate
502‧‧‧microchannel
304‧‧‧ cover
502T‧‧‧ top surface
306‧‧‧First direction
502S‧‧‧ side
308‧‧‧second direction
502B‧‧‧ bottom
400‧‧‧Injection area
504‧‧‧Spine
402‧‧‧Injection
504A‧‧‧大波
404‧‧‧dendritic approach
504B‧‧‧ Wavelet
404A‧‧‧ corner
506‧‧‧coating layer
404B, 404C‧‧‧ Approach
600‧‧‧Output area
406‧‧‧Debuying chamber
602‧‧‧ output
406A‧‧‧ top surface
604‧‧‧dendritic approach
406B‧‧‧Cylinder
700‧‧‧Test object

FIG. 1 is a schematic view showing a micro flow path device according to an embodiment of the present invention. FIG. 2 is a schematic view showing a micro flow path in one embodiment of the present invention. Figure 3 is a schematic diagram showing the efficacy of having a spine and no spine in a microchannel device. 4 to 8 are schematic views showing different embodiments of the spine of the microchannel device of the present invention. Figure 9 is a schematic view showing the injection port, the dendritic approach and the defoaming structure of the injection zone of the present invention. Figure 10 is a schematic view showing another embodiment of the injection port, the dendritic approach and the defoaming structure of the injection zone of the present invention.

300‧‧‧Microchannel device

302‧‧‧Substrate

304‧‧‧ cover

306‧‧‧First direction

308‧‧‧second direction

400‧‧‧Injection area

402‧‧‧Injection

404‧‧‧dendritic approach

406‧‧‧Debuying chamber

500‧‧‧microchannel area

502‧‧‧microchannel

600‧‧‧Output area

602‧‧‧ output

604‧‧‧dendritic approach

Claims (10)

A microchannel device comprising: a substrate and a cover having an implantation region, a microchannel region, and an output region; a plurality of microchannels disposed in the microchannel region and configured by the substrate and the substrate a cover plate is formed, each of the micro flow channels extending along a first direction, and having a plurality of ribs disposed on at least one side of each of the micro flow channels, the spines being curved along a second direction Extending; and a defoaming chamber disposed in the implantation zone and formed by the substrate and the cover. The microchannel device of claim 1, wherein the spine exhibits a large wave and a wavelet repeating wave pattern along the second direction. The microchannel device of claim 2, wherein the ratio of the length to the width of the wavelet is 1:1.5 to 1:2.5. For example, the microchannel device of claim 1 wherein the width of the spine and the distance between adjacent vertebrae are 1:1 to 1:2.5. The microchannel device of claim 1, wherein the ratio of the height of the spine to the height of the substrate between the bottom of the spine and the microchannel is 1:2. The microchannel device of claim 1, wherein the substrate of the microchannel has a coating layer on the substrate or the substrate, and the coating layer has an antibody. The microchannel device of claim 1, wherein the injection region comprises a dendritic approach, the dendritic approach having a plurality of corners, and the corner is a circular corner. The microchannel device of claim 7, wherein the top surface of the defoaming chamber is higher than the top surface of the dendritic approach. The microchannel device of claim 1, wherein the defoaming chamber has a plurality of columns extending up and down through the defoaming chamber. The microchannel device of claim 1, wherein the defoaming chamber is circular or rectangular as viewed from above.