Microreactor, preparation method thereof and biological product preparation device

Abstract

The invention relates to the technical field of biomedical engineering, in particular to a microreactor, a preparation method thereof and a biological product preparation device. The microreactor comprises a base plate and a cover plate, a groove extending along the surface of the base plate is formed in the base plate, and the cover plate is attached to the surface, provided with the groove, of the base plate to form at least one flow channel; a capturing structure is arranged in the flow channel and used for capturing the biological material in the fluid so that the fluid can shear the biological material to generate the biological product. Due to the fact that the capturing structure is arranged in the flow channel, megakaryocytes in fluid can be captured, efficient shearing and stretching can be applied to the marginal area of the megakaryocytes on the micro scale under the action of the fluid in the flow channel, differentiation of the megakaryocytes is promoted, then platelets are generated, the generation efficiency of the platelets is improved, and the blood platelet generation efficiency is improved. The large-scale production of the platelets is favorably promoted.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical engineering, and particularly to a microreactor, a preparation method thereof, and a biological product preparation device. Background Art

[0002] As an important kind of anucleate cells, platelets play a key role in inhibiting bleeding. However, since the supply of platelets mainly depends on obtaining from donors, there are a series of problems. First, the blood source is limited and it is difficult to meet the large-scale demand for platelets, such as in cases of a large number of burn patients, wounded patients, or large-scale regional disasters (such as wars, biochemical disasters). Second, the cost of the existing platelet preparation method using human blood separation is high, resulting in difficulties for general patients in need of platelet supplementation (such as chemotherapy patients) to obtain platelets due to price issues.

[0003] In the prior art, a vortex reactor can also be used to prepare platelets, but the platelet yield is not high, the process is uncontrollable, and the economy is poor, which brings certain troubles to platelet research and large-scale production. Therefore, it is urgent to develop a more controllable, efficient, and economic in vitro platelet production technology to meet the growing clinical demand for platelets. Summary of the Invention

[0004] The purpose of the present invention is to provide a microreactor, a preparation method thereof, and a biological product preparation device to increase the yield of platelets.

[0005] The microreactor of the present invention includes a substrate and a cover plate;

[0006] A groove extending along the surface of the substrate is provided on the substrate, and the cover plate is attached to the surface of the substrate provided with the groove to form at least one flow channel. The flow channel has an inlet for fluid to enter and an outlet for fluid to flow out;

[0007] A capture structure is provided in the flow channel. The capture structure is used to capture biomaterials in the fluid so that the fluid shears the biomaterials to generate biological products.

[0008] Further, the capture structure includes a plurality of protrusions arranged at intervals in the flow channel. A capture area is formed on the side of the protrusion facing away from the fluid, and the capture area is used for the captured biomaterials to stay.

[0009] Further, the protrusions are arranged in an array. Except for the protrusions located at the edge of the array, each protrusion is circumferentially surrounded by a plurality of other protrusions at intervals.

[0010] Further, the distance between any two adjacent protrusions is the same.

[0011] Further, a coating factor film layer is provided on the protrusion, and the coating factor film layer is used to confine the biological material in the capture area.

[0012] Further, the protrusion is a cylindrical micro-convex structure, and the axis of the cylindrical micro-convex structure is perpendicular to the surface of the substrate.

[0013] Further, the diameter size of the cylindrical micro-convex structure is in the range of 0.01 - 0.05 mm, the distance size between the axes of two adjacent cylindrical micro-convex structures is in the range of 0.06 - 0.16 mm, and the height of the cylindrical micro-convex structure is set according to the depth of the flow channel.

[0014] Further, there are multiple flow channels. The diameters of the multiple cylindrical micro-convex structures in the same flow channel are the same, the diameters of the cylindrical micro-convex structures in different flow channels are different from each other, and the spacings of the cylindrical micro-convex structures in different flow channels are different from each other and are positively correlated with the diameter of the cylindrical micro-convex structure.

[0015] Further, the width size of the flow channel is in the range of 1 - 5 mm, and the depth size of the flow channel is in the range of 0.03 - 0.3 mm.

[0016] Further, the flow channel is a linear flow channel and is symmetrically arranged.

[0017] Further, the middle section of the flow channel where the capture structure is arranged is straight.

[0018] Further, both the cover plate and the substrate are made of biocompatible materials, and the substrate and the cover plate are bonded together.

[0019] Further, a transparent window is provided on the cover plate.

[0020] Further, the cover plate is made of a transparent material to form the transparent window.

[0021] Further, the cover plate is made of transparent glass or PDMS, and the substrate is made of PDMS.

[0022] Further, grooves are provided on both the substrate and the cover plate. The grooves on the substrate cooperate with the grooves on the cover plate to form a flow channel, and the capture structure in the flow channel is partially formed on the substrate and partially formed on the cover plate.

[0023] Further, the biological material is megakaryocytes, and the biological product is platelets.

[0024] The present invention also provides a biological product preparation device, including: a collection pool, a circulation pump, and the micro-reactor described in any one of the above technical solutions;

[0025] The outlet of the flow channel of the microreactor is connected to the inlet of the collection tank, the outlet of the collection tank is connected to the inlet of the flow channel of the microreactor, and the circulation pump is arranged between the microreactor and the collection tank to drive the fluid to circulate between the microreactor and the collection tank.

[0026] The present invention also provides a method for preparing a microreactor, which is used for preparing biological products, including:

[0027] Manufacturing a mold according to the flow channel and its capture structure of the microreactor;

[0028] Coating PDMS on the mold;

[0029] After curing, peeling off the PDMS to form a substrate;

[0030] Providing a cover plate and attaching the cover plate to the substrate to form a flow channel;

[0031] Wherein, a capture structure is arranged in the flow channel, and the capture structure is used to capture biological materials in the fluid so that the fluid shears the biological materials to generate biological products.

[0032] Further, after attaching the cover plate to the substrate to form a flow channel, it further includes: injecting a coating factor into the flow channel to form a coating factor film layer on each protrusion of the capture structure.

[0033] Compared with the prior art, the present invention has at least the following beneficial effects:

[0034] When the above microreactor is used to generate platelets, that is, the biological product is platelets and the biological material is a fluid containing megakaryocytes for generating platelets, the fluid is introduced into the flow channel by a pump. Since a capture structure is arranged in the flow channel, megakaryocytes in the fluid can be captured, facilitating precise operation of the megakaryocytes. Since the megakaryocytes for generating platelets have an irregular shape, the cytoplasm is filled with thick purple-red granules, the cell membrane is unclear, mostly in a pseudopod shape, and platelets can usually be formed in its marginal area. Therefore, under the action of the fluid in the flow channel, high-efficiency shearing and stretching can be applied to the marginal area of the megakaryocytes at a micro scale, which is conducive to promoting the differentiation of megakaryocytes and then generating platelets, thereby improving the generation efficiency of platelets and facilitating the large-scale production of platelets. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 It is a schematic structural diagram of an embodiment of the microreactor of the present invention;

[0036] Figure 2 ForFigure 1 Schematic diagram for comparing partial enlarged views of the capture structures at positions A, B, C, and D in

[0037] Figure 3 is Figure 1 the cross-sectional view taken along the E-E direction in

[0038] Figure 4 is Figure 3 the partial enlarged view at position F in

[0039] Reference numerals:

[0040] 100, substrate;

[0041] 200, cover plate;

[0042] 301, first flow channel; 302, second flow channel; 303, third flow channel; 304, fourth flow channel;

[0043] 310, inlet; 320, outlet; 330, cylindrical micro-convex structure. Detailed implementation manners

[0044] The micro-reactor of the present invention, its preparation method, and the biological product preparation device will be described below with reference to the schematic diagrams. The preferred embodiments of the present invention are shown, and it should be understood that those skilled in the art can modify the present invention described herein while still achieving the advantageous effects of the present invention. Therefore, the following description should be understood as a broad guidance for those skilled in the art and not as a limitation to the present invention.

[0045] The serial numbers assigned to the components herein, such as "first", "second", etc., are only used to distinguish the described objects and do not have any sequential or technical meanings. The "connection" and "coupling" mentioned in this application, unless otherwise specified, both include direct and indirect connection (coupling). In the description of the present invention, it should be understood that the orientation or positional relationship indicated by the terms "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation to the present invention.

[0046] In the present invention, unless otherwise clearly defined and limited, the first feature being "on" or "under" the second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature being "above", "over" and "on top of" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply indicates that the horizontal height of the first feature is higher than that of the second feature. The first feature being "under", "beneath" and "underneath" the second feature may mean that the first feature is directly below or obliquely below the second feature, or simply indicates that the horizontal height of the first feature is less than that of the second feature.

[0047] In the following paragraphs, the present invention will be described more specifically by way of example with reference to the accompanying drawings. The advantages and features of the present invention will become clearer according to the following description and claims. It should be noted that the drawings are all in a very simplified form and use non-precise scales, only for the purpose of facilitating and clearly assisting in explaining the embodiments of the present invention.

[0048] The following combines the specification appendix Figures 1 to 4 , and introduces the microreactor of the first aspect embodiment of the present invention.

[0049] In one of the embodiments, as Figure 1 , Figure 2 , Figure 3 and Figure 4 shown, the microreactor includes a substrate 100 and a cover plate 200. Grooves extending along the surface of the substrate 100 are provided on the substrate 100. The cover plate 200 is attached to the surface of the substrate 100 where the grooves are provided to form at least one flow channel. The flow channel has an inlet 310 for fluid to enter and an outlet 320 for fluid to flow out. Both the inlet 310 and the opening are provided on the cover plate 200, or on the substrate 100. Of course, one of them can also be provided on the cover plate 200 and the other on the substrate 100.

[0050] A capture structure is provided in the flow channel. The capture structure is used to capture biomaterials in the fluid so that the fluid shears the biomaterials to generate biological products.

[0051] When the above-mentioned microreactor is used to generate platelets, that is, the biological product is platelets and the biological material is a fluid containing megakaryocytes for generating platelets, the fluid is introduced into the flow channel by a pump. Since a capture structure is provided in the flow channel, megakaryocytes in the fluid can be captured to facilitate precise manipulation of the megakaryocytes. Since the megakaryocytes for generating platelets have an irregular shape, their cytoplasm is filled with thick purple-red granules, their cell membranes are unclear, they are mostly in the form of pseudopodia, and platelets can usually be formed in their marginal regions. Therefore, under the action of the fluid in the flow channel, efficient shearing and stretching can be applied to the marginal regions of megakaryocytes at a microscale, which is conducive to promoting the differentiation of megakaryocytes and then generating platelets, thereby improving the generation efficiency of platelets and facilitating the large-scale production of platelets.

[0052] For example, when the existing vortex reactor is used for platelet generation, only about 80 platelets can be differentiated from a single megakaryocyte, while the microreactor of the present invention can differentiate about 200 platelets from a single megakaryocyte, showing a relatively obvious advantage in terms of yield.

[0053] It should be noted that the above process is carried out at a microscale. To adapt to megakaryocytes of different sizes, the width dimension of the flow channel is in the range of 1-5 mm, preferably in the range of 2-4 mm, and the depth dimension of the flow channel is in the range of 0.03-0.3 mm, preferably in the range of 0.05-0.1 mm.

[0054] In other embodiments, grooves can also be provided on both the substrate and the cover plate. The grooves on the substrate cooperate with the grooves on the cover plate to form a flow channel, and part of the capture structure in the flow channel is formed on the substrate and part is formed on the cover plate.

[0055] In one embodiment, the flow channel is a linear flow channel and is symmetrically arranged. Preferably, the middle section of the flow channel provided with the capture structure is straight, and the fluid can pass through quickly, thereby improving the production efficiency. In other embodiments, the middle section provided with the capture structure can also be curved.

[0056] In one embodiment, the capture structure includes a plurality of protrusions staggered in the flow channel. A capture area is formed on the side of the protrusion facing away from the fluid, and the capture area is used for the captured biological material to stay. Due to the presence of the protrusions, when the fluid flows through the channel, on the side of the protrusion facing away from the fluid, the flow velocity of the fluid is relatively low. When the megakaryocytes move near the capture area, they are likely to attach to the capture area of the protrusion and thus are captured by the protrusion. In use, as time goes by, the earliest captured megakaryocytes have completed differentiation and entered the collection pool. At this time, the vacated protrusions can continue to capture new megakaryocytes, enabling continuous and rapid production and avoiding waste of megakaryocytes.

[0057] In one embodiment, the protrusions are arranged in an array. Except for the protrusions located at the edge of the array, each protrusion is circumferentially surrounded by a plurality of other protrusions at intervals. This surrounding configuration can improve the capture efficiency of megakaryocytes.

[0058] Furthermore, in one embodiment, the distance between any two adjacent protrusions is the same. That is, the connection lines between any three adjacent protrusions can form an equilateral triangle, so that each protrusion is circumferentially surrounded by six protrusions at equal intervals, which is beneficial to making the flow field distribution in the flow channel relatively uniform, so that each protrusion has a relatively similar capture effect.

[0059] In one embodiment, in order to further improve the capture effect, a coating factor film layer is provided on the protrusion. The coating factor film layer can improve the adsorption effect of the protrusion on megakaryocytes, so that the protrusion can more easily capture megakaryocytes and confine the megakaryocytes in the capture area. The coating factor film layer can be made of von Willebrand factor, or can also be made of bovine serum albumin. In other embodiments, it can also be made of other materials that can improve the capture effect.

[0060] In one embodiment, preferably, the protrusion is a cylindrical micro-convex structure 330, and the axis of the cylindrical micro-convex structure is perpendicular to the surface of the substrate 100, thus forming a micro-column array in the flow channel. The cylindrical micro-convex structure has a smooth outer peripheral surface, which can prevent megakaryocytes from being easily broken, is beneficial to improving the utilization rate of megakaryocytes, and further improves the production efficiency of platelets. In other embodiments, the protrusion can also be a frustum-shaped protrusion or other shapes.

[0061] In one embodiment, both the cover plate and the substrate are made of biocompatible materials, and the substrate and the cover plate are bonded together.

[0062] Preferably, the substrate 100 can be made of PDMS (i.e., polydimethylsiloxane) material. The mold for making the substrate 100 can be processed by etching to form a cavity for generating the flow channel and the microcolumn array on the mold. After the mold is made, the substrate 100 is formed by pouring. The PDMS material has good biocompatibility and will not cause toxicity to cells. In addition, the PDMS material also has good hydrophobicity and will not form a rough surface during the curing process, which means that when megakaryocytes flow through the flow channel, they will only be captured by the microcolumns and will not remain on the surface of the flow channel to cause blockage.

[0063] In other embodiments, the substrate 100 can also be made of COP (i.e., cycloolefin polymer) material, glass or acrylate and other materials.

[0064] In one of the embodiments, a transparent window is provided on the cover plate 200, and the experimenter can observe and record the shear stretching process of megakaryocytes and the movement of megakaryocytes in the flow channel in real time through an optical microscope. On the one hand, it is convenient to adjust the test plan in time. On the other hand, effective parameters can be obtained to facilitate the progress of subsequent R & D work.

[0065] Preferably, the cover plate 200 is made of a transparent material to form the transparent window. Specifically, the cover plate 200 is made of glass, and both the inlet 310 and the outlet 320 are provided on the cover plate 200. The glass material also has good biocompatibility and will not cause toxicity to cells. In other embodiments, the cover plate can also be made of PDMS material.

[0066] In one of the embodiments, the substrate 100 and the cover plate 200 are bonded together, so that the substrate 100 and the cover plate 200 can be connected together. In other embodiments, the substrate 100 and the cover plate 200 can also be connected together by glue or other means.

[0067] In one of the embodiments, in order to adapt to megakaryocytes of different sizes, the diameter size of the cylindrical micro-convex structure 330 is in the range of 0.01 - 0.05 mm, preferably in the range of 0.02 - 0.04 mm, and the distance size between the axes of two adjacent cylindrical micro-convex structures 330 is in the range of 0.06 - 0.16 mm, preferably in the range of 0.075 - 0.15 mm. The height of the cylindrical micro-convex structure 330 is set according to the depth of the flow channel.

[0068] Since the size of the cylindrical micro-convex structures 330 in the flow channel can be precisely controlled to the micron level, the device can be made more compact and efficient, saving costs and resources. This provides higher sensitivity and lower consumption for biological samples under study, especially those precious samples with limitations, offering a more effective option for conducting biological experiments under resource-constrained conditions. In particular, in the study of rare cells or limited available samples, it opens up new possibilities for efficient experiments and analysis.

[0069] In one embodiment, to facilitate the study and differentiation of megakaryocytes of different sizes, reduce manufacturing costs, and improve production efficiency, there are multiple flow channels. The diameters of the multiple cylindrical micro-convex structures 330 in the same flow channel are the same, the diameters of the cylindrical micro-convex structures 330 in different flow channels are different from each other, and the spacings between the cylindrical micro-convex structures 330 in different flow channels are different from each other and are positively correlated with the diameters of the cylindrical micro-convex structures 330.

[0070] Taking an embodiment with four flow channels as an example, as Figure 1 and Figure 2 shown, the substrate 100 and the cover plate 200 are bonded to form four flow channels, named the first flow channel 301, the second flow channel 302, the third flow channel 303, and the fourth flow channel 304 respectively. The widths of the four flow channels are preferably 2 mm, and the spacing between two adjacent flow channels is preferably 1 mm. In other embodiments, the spacing between two adjacent flow channels can be other dimensions, such as 1 - 2 mm.

[0071] Although micro-column arrays are provided in all four flow channels, the diameters of the cylindrical micro-convex structures 330 in the four flow channels are different from each other, and the distances between the cylindrical micro-convex structures 330 are also different. Specifically, the diameter of the cylindrical micro-convex structures 330 in the first flow channel 301 is preferably 0.03 mm, and the diameters of the cylindrical micro-convex structures 330 in the second flow channel 302, the third flow channel 303, and the fourth flow channel 304 increase by 0.02 mm in sequence, being 0.05 mm, 0.07 mm, and 0.09 mm respectively. The spacing between the cylindrical micro-convex structures 330 in the first flow channel 301 is 0.15 mm, and the spacings between the cylindrical micro-convex structures 330 in the second flow channel 302, the third flow channel 303, and the fourth flow channel 304 increase by 0.025 mm in sequence, being 0.175 mm, 0.2 mm, and 0.225 mm respectively. Of course, the above dimensions can also be arranged in a non-arithmetic progression manner, as long as the diameters of the cylindrical micro-convex structures 330 in each flow channel are different from each other, and the distances between the cylindrical micro-convex structures 330 are also different.

[0072] When applied to a test scenario, multiple flow channels can process multiple samples simultaneously, improving the test throughput, accelerating the test speed, and facilitating high-throughput screening and analysis efficiently. When applied to the production process, it can significantly increase the production speed.

[0073] Of course, the above embodiment with four flow channels is only an example. The number of flow channels in the microreactor of the present invention can be set to various numbers according to requirements, such as three, five, or eight, etc., and will not be exemplified one by one here.

[0074] During the process development of platelet separation from megakaryocytes, there are differences in individual cells. By setting multiple flow channels with different densities of microcolumn arrays in different flow channels, the fluids in different flow channels can have different flow rates and shear rates, so that cells of different sizes can be used for tests. At the same time, it can also be used to test the differences in platelets generated in different flow channels, which facilitates researchers to quickly obtain the desired test results to accelerate the research and development progress; at the same time, it can also lock the parameters of the microreactor as soon as possible to prepare for large-scale development.

[0075] In addition, in order to measure the yield of platelets produced by megakaryocytes and prevent undifferentiated or incompletely differentiated megakaryocytes from entering the collection pool and no longer separating platelets, the above flow channels can also be used in a cyclic manner. For example, when the fluid after passing through the flow channels enters the collection pool, a circulation pump is used to re-introduce the fluid into the flow channels. Among them, it can be introduced into the same flow channel for multiple cycles, or it can be introduced into other flow channels. For example, it can be introduced into a flow channel with a smaller diameter of the cylindrical microprotrusion structure 330 until it is observed that there are no longer large-diameter megakaryocytes in the flow channel, thus avoiding cell waste and being able to measure the platelet yield more accurately.

[0076] It should be noted that the microreactor of the present invention is not limited to generating platelets, and can also be used for cell stretching, cell sorting, microsphere crushing, sample preliminary screening, etc. The corresponding biological materials can be, for example, bone marrow cells, stem cells, bone marrow cells, etc. The above cells can be human cells or non-human cells.

[0077] An embodiment of the second aspect of the present invention provides a biological product preparation device, including a collection pool, a circulation pump, and a microreactor. The structure of the microreactor is the same as that of any of the microreactors in the above embodiments of the first aspect, and will not be elaborated here.

[0078] Among them, the flow channel outlet of the microreactor is connected to the inlet of the collection pool, the outlet of the collection pool is connected to the flow channel inlet of the microreactor, and the circulation pump is arranged between the microreactor and the collection pool for driving the fluid to circulate between the microreactor and the collection pool.

[0079] In use, after the fluid passing through the flow channel enters the collection tank, a circulation pump is used to introduce the fluid into the flow channel again. Among them, it can be introduced into the same flow channel for multiple cycles, or into other flow channels. For example, it can be introduced into a flow channel with a smaller diameter of the cylindrical microprotrusion structure until it is observed that there are no megakaryocytes with a large diameter in the flow channel, thus avoiding cell waste and being able to accurately measure the platelet yield.

[0080] An embodiment of the third aspect of the present invention provides a method for preparing a microreactor, which can be used to prepare the microreactor in the first aspect embodiment above. The microreactor is used for preparing biological products and includes:

[0081] Fabricate a mold according to the flow channel and its capture structure of the microreactor;

[0082] Coat PDMS on the mold;

[0083] After curing, peel off the PDMS to form a substrate;

[0084] Provide a cover plate and attach the cover plate to the substrate to form a flow channel;

[0085] Among them, a capture structure is arranged in the flow channel, and the capture structure is used to capture biological materials in the fluid so that the fluid shears the biological materials to generate biological products.

[0086] Specifically, the mold can be processed and formed by etching. Since the PDMS material has good biocompatibility and will not cause toxicity to cells, the formed substrate has good biocompatibility. In addition, the PDMS material also has good hydrophobicity and will not form a rough surface during the curing process, which means that when megakaryocytes flow through the flow channel, they will only be captured by the capture structure and will not remain on the surface of the flow channel to cause blockage.

[0087] The microreactor prepared by using the method for preparing a microreactor of the present invention, when in use, can apply high-efficiency shearing and stretching to the marginal area of megakaryocytes at a micro scale, thus facilitating the differentiation of megakaryocytes and then generating platelets, thereby improving the platelet generation efficiency and facilitating the large-scale production of platelets.

[0088] In another embodiment, two molds can be fabricated respectively according to the flow channels and the capture structures of the microreactor, and PDMS can be coated on the two molds respectively to form a substrate and a cover plate. Grooves and microcolumn arrays are provided on both the formed substrate and the cover plate. The grooves on the substrate cooperate with the grooves on the cover plate to form flow channels. Part of the capture structure in the flow channels is formed on the substrate and part is formed on the cover plate. Compared with the method of only providing grooves and microcolumn arrays on the substrate, providing grooves and microcolumn arrays on the substrate and the cover plate respectively can further increase the arrangement density of the capture structure.

[0089] In one embodiment, in order to further improve the capture effect, after the cover plate is attached to the substrate to form a flow channel, it further includes: injecting a coating factor into the flow channel to form a coating factor film layer on each protrusion of the capture structure.

[0090] A coating factor film layer is provided on the protrusion. The coating factor film layer can improve the adsorption effect of the protrusion on megakaryocytes, so that the protrusion can more easily capture megakaryocytes and confine the megakaryocytes in the capture area. The coating factor film layer can be made of von Willebrand factor or bovine serum albumin. In other embodiments, it can also be made of other materials that can improve the capture effect.

[0091] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these changes and modifications.

Claims

1. A microreactor for preparing biological products, characterized in that, Comprising: A substrate and a cover plate; A groove extending along the surface of the substrate is provided on the substrate, and the cover plate is attached to the surface of the substrate where the groove is provided to form at least one flow channel, and the flow channel has an inlet for fluid to enter and an outlet for fluid to flow out; A capture structure is provided in the flow channel, and the capture structure is used to capture biological materials in the fluid so that the fluid shears the biological materials to generate biological products.

2. The microreactor according to claim 1, wherein The capture structure includes a plurality of protrusions arranged at intervals in the flow channel, and a capture area is formed on the side of the protrusion facing away from the fluid, and the capture area is used for the captured biological materials to stay.

3. The microreactor according to claim 2, characterized in that, The protrusions are arranged in an array, and except for the protrusions located at the edge of the array, a plurality of other protrusions are spaced around the circumference of each protrusion.

4. The microreactor according to claim 3, characterized in that, The distance between any two adjacent protrusions is the same.

5. The microreactor according to claim 2, characterized in that, A coating factor film layer is provided on the protrusion, and the coating factor film layer is used to confine the biological materials in the capture area.

6. The microreactor according to claim 2, characterized in that, The protrusion is a cylindrical micro-convex structure, and the axis of the cylindrical micro-convex structure is perpendicular to the surface of the substrate.

7. The microreactor according to claim 6, characterized in that, The diameter dimension of the cylindrical micro-convex structure is in the range of 0.01 - 0.05 mm, the distance dimension between the axes of two adjacent cylindrical micro-convex structures is in the range of 0.06 - 0.16 mm, and the height of the cylindrical micro-convex structure is set according to the depth of the flow channel.

8. The microreactor according to claim 6, wherein There are multiple flow channels, the diameters of the plurality of cylindrical micro-convex structures in the same flow channel are the same, the diameters of the cylindrical micro-convex structures in different flow channels are different from each other, and the spacings of the cylindrical micro-convex structures in different flow channels are different from each other and are positively correlated with the diameters of the cylindrical micro-convex structures.

9. The microreactor according to claim 1, characterized in that, The width dimension of the flow channel is in the range of 1 - 5 mm, and the depth dimension of the flow channel is in the range of 0.03 - 0.3 mm.

10. The microreactor according to claim 1, wherein The flow channel is a linear flow channel and is symmetrically arranged.

11. The microreactor according to claim 10, characterized in that, The middle section of the flow channel where the capture structure is provided is straight.

12. The microreactor according to claim 1, wherein, Both the cover plate and the substrate are made of biocompatible materials, and the substrate and the cover plate are attached by bonding.

13. The microreactor according to claim 12, characterized in that, A transparent viewing window is provided on the cover plate.

14. The microreactor according to claim 13, characterized in that, The cover plate is made of a transparent material to form the transparent viewing window.

15. The microreactor according to claim 14, wherein The cover plate is made of transparent glass or PDMS, and the substrate is made of PDMS.

16. The microreactor according to claim 1, characterized in that, Grooves are provided on both the substrate and the cover plate, and the grooves on the substrate cooperate with the grooves on the cover plate to form a flow channel, and the capture structure in the flow channel is partially formed on the substrate and partially formed on the cover plate.

17. The microreactor according to claim 1, characterized in that, The biological material is megakaryocytes, and the biological product is platelets.

18. A biological product preparation device, characterized in that, Comprising: A collection pool, a circulation pump, and a microreactor as described in any one of claims 1 to 17; The outlet of the flow channel of the microreactor is connected to the inlet of the collection pool, the outlet of the collection pool is connected to the inlet of the flow channel of the microreactor, and the circulation pump is arranged between the microreactor and the collection pool to drive the fluid to circulate between the microreactor and the collection pool.

19. A method for preparing a microreactor, the microreactor being used for preparing biological products, characterized in that, Comprising: Manufacturing a mold according to the flow channel of the microreactor and its capture structure; Coating PDMS on the mold; After curing, peel off the PDMS to form a substrate; Provide a cover plate and attach the cover plate to the substrate to form a flow channel; Wherein, a capture structure is arranged in the flow channel, and the capture structure is used to capture biomaterials in the fluid so that the fluid shears the biomaterials to generate biological products.

20. The preparation method of the microreactor according to claim 19, characterized in that, After attaching the cover plate to the substrate to form a flow channel, it further includes: injecting a coating factor into the flow channel to form a coating factor film layer on each protrusion of the capture structure.

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