Integrated stepped T-shaped microreactor and high-throughput microsphere preparation method

Abstract

The invention discloses an integrated stepped T-shaped microreactor and a high-throughput microsphere preparation method, and belongs to the technical field of droplet microreactors. The device comprises a plurality of continuous phase channel units and a plurality of dispersed phase channel units which are arranged on a single-layer substrate, each continuous phase channel unit comprises a main channel and a plurality of main split channels, and the main split channels form 2N main split channels through a multi-stage bifurcated structure; each dispersed phase channel unit comprises a branch channel and a plurality of branch splitting channels, and the branch splitting channels form 2N branch splitting channels through a multi-stage two-branch structure; the 2N main splitting channels and the 2N branch splitting channels are in one-to-one correspondence, and a liquid drop generation channel is formed at the intersection; wherein every two adjacent liquid drop generation channels are intersected at the same collection opening, every two adjacent main splitting channels and every two adjacent branch splitting channels are arranged in a mirror symmetry mode with the liquid drop generation unit as the center, and the micro-reactor is high in integration degree and good in liquid drop uniformity.

Description

Technical Field

[0001] This invention relates to the field of droplet microreactor technology, specifically to an integrated stepped T-type microreactor and a method for high-throughput preparation of microspheres. Background Technology

[0002] Droplet microfluidics, with its ability to precisely control the generation of micron-sized droplets, has shown broad application prospects in fields such as functional microsphere preparation, drug delivery, and single-cell analysis. Microspheres prepared using microfluidics have advantages such as uniform size, tunable structure, and good batch-to-batch reproducibility, effectively overcoming the problems of poor stability and wide size distribution associated with traditional mechanical stirring and emulsion polymerization methods.

[0003] As microfluidic technology moves from laboratory research to industrial production, increasing the production throughput of microspheres has become a key bottleneck restricting its commercial application. While single-channel microfluidic chips can generate highly monodisperse droplets, their yield is typically only in the milliliter range per hour, far from meeting the demands of industrial production. To address this, researchers have proposed various integrated and parallelized microfluidic chip designs to significantly increase yield while maintaining droplet uniformity.

[0004] To improve throughput, current technologies often employ multi-layer channel structures for parallelization. This requires precise alignment and bonding of multiple substrates, resulting in complex packaging processes. Furthermore, the height differences created by the stacked layers can lead to uneven pressure distribution between layers, affecting the uniformity of droplet size. Existing channel designs used to reduce overall flow resistance typically occupy a large chip area, limiting further dense integration of droplet production units within a limited area. Simultaneously, each droplet production unit usually corresponds to an independent output channel. As the number of units increases significantly, the complexity of the output channels and packaging difficulty also rise sharply, hindering further increases in throughput.

[0005] Therefore, how to provide an integrated droplet microreactor that is simple in structure, easy to process, and easy to expand, while ensuring the uniformity of fluid distribution and droplet uniformity, and achieving higher integration and greater throughput, remains a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0006] The purpose of this invention is to overcome the problems in the prior art and provide an integrated double-layer stepped microreactor and a method for high-throughput preparation of microspheres.

[0007] To address the above problems, the present invention provides an integrated stepped T-type droplet microreactor, comprising a single-layer substrate and multiple continuous phase channel units and multiple dispersed phase channel units disposed on the single-layer substrate; Each of the aforementioned continuous phase channel units includes a main channel and multiple main split channels. The main split channels are connected to the main channel through a multi-level bifurcation structure. The multi-level bifurcation structure has N levels, and each inlet channel of each level of the bifurcation structure corresponds to two outlet channels. After N levels of successive diversion, two phase channels are formed. N The aforementioned main split channel; Each of the dispersed phase channel units includes one branch channel and multiple branch split channels. The branch split channels are connected to the branch channel through a multi-level bifurcation structure. The multi-level bifurcation structure has N levels, and each inlet channel of each level of the bifurcation structure corresponds to two outlet channels. After N levels of successive diversion, 2 N The branch split channel; The 2 N The main splitting channel and the 2 N Each branch splitting channel is paired one-to-one, and a droplet generation channel is formed at the intersection of each pair of main splitting channels and branch splitting channels. In this configuration, the two droplet generation channels corresponding to every two adjacent main split channels and every two adjacent branch split channels converge into the same droplet generation channel, and the outlets of the two droplet generation channels are connected to a common collection port. The two adjacent main split channels and the two adjacent branch split channels are arranged in a mirror symmetry with respect to the droplet generation unit as the center.

[0008] Preferably, all the main split channels at the same level have the same length, and all the branch split channels at the same level have the same length.

[0009] Preferably, the multi-level binary branching structure is a completely symmetrical binary tree-shaped branching structure, in which the main branching channels and branch branching channels at each level of branching node are arranged axially symmetrically with respect to the branching node.

[0010] The microreactor is composed of multiple basic unit structures arranged in an array. Each basic unit structure includes a continuous phase channel unit, a dispersed phase channel unit, four droplet generation channels, and two collection ports. The continuous phase channel unit and the dispersed phase channel unit are symmetrically arranged, and each of the continuous phase channel unit and the dispersed phase channel unit corresponds to a set of split channels formed by a two-stage bifurcation structure.

[0011] The droplet generation channel is a stepped T-shaped channel. The stepped T-shaped channel has a rounded corner structure at the intersection of the main split channel and the branch split channel. The outlet of the droplet generation channel has an enlarged section channel structure, which is connected to the collection port.

[0012] All the connections of the bifurcation structures described in the multi-level series are provided with rounded corners.

[0013] The single-layer substrate is integrally formed using photolithography. The continuous phase channel unit and the dispersed phase channel unit are microchannel structures etched on the single-layer substrate. The single-layer substrate is covered with a removable or bonded cover plate.

[0014] This invention also discloses a method for high-throughput microsphere preparation using the aforementioned integrated stepped T-type microreactor, comprising the following steps: introducing a continuous phase fluid through the main channel and introducing a dispersed phase fluid through the branch channels; the continuous phase fluid is progressively split through an N-stage bifurcation structure and uniformly distributed to 2 N One main splitting channel; the dispersed phase fluid is progressively split through an N-stage bifurcation structure and evenly distributed to 2 N Each main split channel has a branch splitting channel; at the intersection of each pair of main splitting channels and branch splitting channels, the continuous phase fluid and the dispersed phase fluid generate microdroplets; the microdroplets generated by every two adjacent droplet generation channels are collected through the same collection port; the collected microdroplets are solidified to form microspheres.

[0015] Compared with the prior art, the beneficial effects of the present invention are: This invention employs an N-stage binary bifurcation structure for progressive flow splitting. Each stage divides each channel of the previous stage into two channels, ultimately forming 2 N One main split channel and 2 N The split-channel design maximizes the number of channels within a limited planar space, significantly increasing the integration density of the microreactor and providing a structural basis for high-throughput droplet generation. In this invention, the continuous phase channel unit and the dispersed phase channel unit are arranged in a mirror-symmetric manner around the droplet generation unit, ensuring that each droplet generation unit receives the same flow rate of continuous and dispersed phases, which is beneficial for generating droplets with uniform size and height.

[0016] This invention utilizes a design where every two adjacent main splitting channels and every two adjacent branch splitting channels share the same droplet generation unit. This reduces the number of droplet generation units to half the number of droplet generation channels, significantly increasing the droplet generation throughput per unit area within the same substrate area. Simultaneously, it reduces chip packaging complexity, simplifies the layout of external collection channels, facilitates automated collection, and improves the overall reliability and operability of the device.

[0017] In this invention, all channel structures are disposed on a single-layer substrate and etched in one step using photolithography, eliminating the need for multi-layer alignment and complex bonding processes. This not only avoids the problem of uneven pressure distribution caused by the height difference between layers in multi-layer stacked structures, but also significantly reduces processing difficulty and manufacturing costs, and improves the long-term operational stability and product yield of the chip. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the integrated stepped T-shaped microreactor structure in an embodiment of the present invention.

[0019] Figure 2 This is a schematic diagram of the independent unit structure of the integrated stepped T-shaped microreactor in an embodiment of the present invention.

[0020] Figure 3 This is a schematic diagram of the continuous phase channel unit, the dispersed phase channel unit, and the droplet generation unit in an embodiment of the present invention.

[0021] Figure 4 Scanning electron microscopy of the chromatographic packing microspheres prepared in Example 1 of this invention Figure 1 .

[0022] Figure 5 Scanning electron microscopy of the chromatographic packing microspheres prepared in Example 1 of this invention Figure 2 .

[0023] Figure 6 This is a scanning electron microscope image of the chromatographic packing microspheres prepared in Example 2 of the present invention.

[0024] Figure 7 This is a scanning electron microscope image of the chromatographic packing microspheres prepared in Example 3 of the present invention.

[0025] Explanation of reference numerals in the attached figures: 1. Dispersed phase channel unit; 1-1. Branch channel; 1-2. Branch splitting channel; 2. Continuous phase channel unit; 2-1. Main channel; 2-2. Main splitting channel; 3. Droplet generation unit; 3-1. Droplet generation channel; 4. Droplet collection channel; 5. Continuous phase fluid inlet; 6. Dispersed phase fluid inlet. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0027] Unless otherwise defined, the technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains. The terms “first,” “second,” and similar terms used in this invention do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Terms such as “comprising” or “including” indicate that the elements or objects preceding “comprising” or “including” encompass the elements or objects listed following “comprising” or “including” and their equivalents, and do not exclude other elements or objects. Terms such as “connected” or “linked” are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. Terms such as “upper,” “lower,” “left,” and “right” are used only to indicate relative positional relationships; when the absolute position of the described objects changes, the relative positional relationship may also change accordingly.

[0028] This invention provides an integrated stepped T-type droplet microreactor, comprising a single-layer substrate and multiple continuous phase channel units and multiple dispersed phase channel units disposed on the single-layer substrate; Each of the aforementioned continuous phase channel units includes a main channel and multiple main split channels. The main split channels are connected to the main channel through a multi-level bifurcation structure. The multi-level bifurcation structure has N levels, and each inlet channel of each level of the bifurcation structure corresponds to two outlet channels. After N levels of successive diversion, two phase channels are formed. N The aforementioned main split channel; Each of the dispersed phase channel units includes one branch channel and multiple branch split channels. The branch split channels are connected to the branch channel through a multi-level bifurcation structure. The multi-level bifurcation structure has N levels, and each inlet channel of each level of the bifurcation structure corresponds to two outlet channels. After N levels of successive diversion, 2 N The branch split channel; The 2 N The main splitting channel and the 2 N Each branch splitting channel is paired one-to-one, and a droplet generation channel is formed at the intersection of each pair of main splitting channels and branch splitting channels. In this configuration, the two droplet generation channels corresponding to every two adjacent main split channels and every two adjacent branch split channels converge in the same droplet generation unit, and the outlets of the two droplet generation channels are connected to a common collection port. The two adjacent main split channels and the two adjacent branch split channels are arranged in a mirror symmetry with the droplet generation unit as the center.

[0029] This invention achieves a high degree of integration of microreactors through a multi-stage binary bifurcation structure with a fission-type channel layout. It employs an N-stage binary bifurcation structure for progressive flow splitting, with each stage dividing each channel of the previous stage into two channels. The number of channels increases geometrically with the number of stages, forming a 2... N One main split channel and 2 N Each channel is a split channel. This fission-style layout maximizes the number of channels within a limited planar space, significantly increasing the integration density of the microreactor and providing a structural basis for high-throughput droplet generation. In this invention, every two adjacent droplet generation channels converge in the same droplet generation unit, and the outlets of these two droplet generation channels are connected to a common collection port, reducing the number of collection ports to only half the number of droplet generation channels. This design not only reduces the number of openings on the substrate and lowers the packaging difficulty, but also simplifies the subsequent droplet collection piping system, improving the overall reliability and operability of the device.

[0030] This invention achieves dynamic pressure balance of multiple fluid streams within a confined space by sharing a single droplet generation unit between every two adjacent main split channels and every two adjacent branch split channels. When flow fluctuations occur in a single channel, the fluids in adjacent channels generate a resistance effect within the same unit, suppressing the transmission of fluctuation amplitude to the droplet generation process. Simultaneously, the symmetrically arranged channel structure ensures pressure matching between the fluids on the left and right sides, making the flow resistance of each channel tend to be consistent. The pressure of the continuous phase fluid and the dispersed phase fluid is balanced at each droplet generation unit, ensuring high uniformity of droplet size generated in each unit. Therefore, this invention can maintain excellent droplet size uniformity while significantly increasing the number of channels and integration, overcoming the technical problem of decreased uniformity accompanied by increased throughput in traditional stacked integration schemes.

[0031] In this invention, all channel structures are disposed on a single-layer substrate, which can be etched and formed in one step using photolithography, eliminating the need for multi-layer alignment and complex bonding processes. This not only significantly reduces processing difficulty and manufacturing costs, but also avoids the problem of uneven pressure distribution caused by the height difference between layers in multi-layer stacked structures, thereby improving the long-term operational stability of the chip.

[0032] In a preferred embodiment, all main split channels at the same level have equal lengths, and all branch split channels at the same level have equal lengths. This geometrically ensures consistent flow resistance across all branch channels, thereby achieving uniform fluid distribution.

[0033] In a preferred embodiment, the multi-level binary bifurcation structure is a completely symmetrical binary tree-shaped flow branching structure. The main branching channels and branch branching channels at each flow branching node are arranged axially symmetrically with respect to the flow branching node. That is, at each flow branching node, the length, width, and depth of the left and right branching channels are exactly the same, and they are arranged axially symmetrically relative to the flow branching node. This further ensures that the inlet fluid is precisely divided into two at each flow branching node. After N levels of flow branching, the final flow is... N Each main split channel receives the same amount of traffic.

[0034] In a preferred embodiment, the microreactor is composed of multiple basic unit structures arranged in an array. Each basic unit structure includes one continuous phase channel unit, one dispersed phase channel unit, two droplet generation units, four droplet generation channels, and two collection ports. The continuous phase channel unit and the dispersed phase channel unit are symmetrically arranged, and each of the continuous phase channel unit and the dispersed phase channel unit corresponds to a set of split channels formed by a two-stage bifurcated structure.

[0035] This invention uses a basic unit structure as the smallest functional module, and the overall throughput of the microreactor can be linearly expanded through array arrangement without redesigning a complex fluid distribution network. This modular design significantly reduces design difficulty and cycle time, and facilitates customized production for different throughput requirements. Within each basic unit, the continuous phase channel unit and the dispersed phase channel unit are sequentially branched through a two-stage bifurcation structure, and the two are arranged symmetrically. This design ensures that the four continuous phase fluids and four dispersed phase fluids entering the two droplet generation units have completely equal flow resistance, achieving optimal flow distribution uniformity, which is beneficial for generating droplets with highly uniform size. Each basic unit structure requires only one continuous phase channel unit and one dispersed phase channel unit to supply liquid to the two droplet generation units, realizing the reuse of the liquid supply channel. Under the same substrate area, the number of droplet generation units can be multiplied, significantly improving the integration density and unit area capacity of the microreactor.

[0036] In another preferred embodiment, the droplet generation channel is a stepped T-shaped channel. The stepped T-shaped channel has a rounded corner structure at the confluence of the main splitting channel and the branch splitting channel. The outlet of the droplet generation channel has an enlarged section channel structure, which communicates with the collection port. This invention, by setting the rounded corner structure, ensures a smooth flow transition, eliminates flow dead zones, guarantees long-term unobstructed flow, and significantly improves the stability and reliability of the microreactor operation.

[0037] In another preferred embodiment, the connection points of the multi-stage bifurcated structures are all provided with rounded corners. The rounded corners at the connection points of the bifurcated structures enable a smooth transition of the streamlines, reducing flow resistance while eliminating the inherent flow stagnation area at the right-angle bifurcation. Cells, microgel particles, and impurities pass smoothly with the fluid and do not accumulate at the bifurcation, significantly reducing the risk of chip blockage.

[0038] In another preferred embodiment, the single-layer substrate is integrally formed using photolithography, and the continuous phase channel unit and the dispersed phase channel unit are microchannel structures etched on the single-layer substrate; a removable or bonded cover plate covers the single-layer substrate. This invention's single-layer design avoids the inherent interlayer alignment problems of multi-layer stacking, eliminates cumulative errors, and ensures all channels are on the same plane, eliminating interlayer pressure differences caused by height differences in multi-layer structures. Combined with a design of equal length at the same level, it enables uniform flow distribution among the droplet generation units.

[0039] This invention also discloses a method for high-throughput microsphere preparation using the aforementioned integrated stepped T-type microreactor, comprising the following steps: introducing a continuous phase fluid through the main channel and introducing a dispersed phase fluid through the branch channels; the continuous phase fluid is progressively split through an N-stage bifurcation structure and uniformly distributed to 2 N One main splitting channel; the dispersed phase fluid is progressively split through an N-stage bifurcation structure and evenly distributed to 2 N Each main split channel has a branch splitting channel; at the intersection of each pair of main splitting channels and branch splitting channels, the continuous phase fluid and the dispersed phase fluid generate microdroplets; the microdroplets generated by every two adjacent droplet generation channels are collected through the same collection port; the collected microdroplets are solidified to form microspheres.

[0040] The multi-stage bifurcation structure of this invention causes the fluid to be uniformly divided into two at each stage, ultimately resulting in 2 N The equal flow rate of each channel ensures a uniform fluid supply to each droplet generation unit, providing a foundation for droplet size uniformity. The design of sharing a single collection port between every two droplet generation channels halves the number of collection ports, simplifying the collection system structure and reducing chip packaging difficulty and external piping complexity. Furthermore, 2 N The parallel operation of multiple channels enables the total microdroplet generation rate to reach 2 times that of a single channel. NThis method achieves a significant increase in throughput and precise size adjustment while maintaining the excellent monodispersity of the microspheres. Furthermore, by adjusting the flow rate of the two-phase flow, the microsphere size can be continuously controlled within the range of 5-500 μm to meet diverse application requirements. It is also applicable to various curing methods such as chemical crosslinking, photocrosslinking, thermosensitive curing, and hydrolysis condensation, enabling the preparation of various functional microspheres, including chromatographic packing microspheres, cell-carrying microgels, and polymer microspheres, demonstrating excellent versatility and scalability. Therefore, this method achieves an order-of-magnitude increase in throughput and precise size adjustment while maintaining the excellent monodispersity of the microspheres, providing efficient and reliable technical support for the large-scale production and commercial application of functional microspheres.

[0041] like Figures 1-3 As shown, the integrated stepped T-shaped microreactor provided by the present invention includes a substrate on which a dispersed phase channel unit 1, a continuous phase channel unit 2, and a droplet generation unit 3 are formed. The dispersed phase channel unit 1 includes branch channels 1-1 and 2. N Each branch channel 1-2 is connected to the inlet of all branch channels 1-2 and the outlet of branch channel unit 1-1. Continuous phase channel unit 2 includes main channels 2-1 and 2-2. N There are one main splitting channel 2-2, and the inlet of all main splitting channels 2-2 is connected to the outlet of the main channel unit 2-1. In this embodiment, both the main splitting channel 2-2 and the branch splitting channel 1-2 are designed with two levels of splitting; that is, there are two main splitting channels 2-2 and two branch splitting channels 1-2 in the first level; and four main splitting channels 2-2 and four branch splitting channels 1-2 in the second level. In the four channels of the second level, the outlets of the main splitting channels 2-2 and the outlets of the branch splitting channels 1-2 are connected in pairs, and a droplet generating channel 3-1 is formed at the intersection of each pair of main splitting channels and branch splitting channels. Two adjacent droplet generating channels 3-1 converge at the collection port. As shown in the figure, the lengths of the main splitting channels 2-2 and the branch splitting channels 1-2 in each level are the same in this embodiment. The droplet generating unit 3 includes multiple droplet generating channels 3-1, and every two droplet generating channels 3-1 are connected to a collection port 4.

[0042] In operation, the continuous phase fluid is introduced into the main channel unit, while the dispersed phase fluid is introduced into the branch channel unit. The continuous phase fluid is evenly distributed to all the main split channels through the main channel unit, and the dispersed phase fluid is also evenly distributed to all the branch split channels through the branch channel unit. The continuous and dispersed phase fluids come into contact through one main split channel and one corresponding branch split channel, eventually merging at the interface of the stepped-T-shaped channel. Due to the shear-compression effect between the two phases, as well as the difference in viscosity and interfacial tension between the continuous and dispersed phase fluids, the dispersed phase fluid is sheared by the continuous phase fluid, thus generating microdroplets. The generated microdroplets enter the droplet generation channel through a droplet generation channel at the connection between the main split channel and the branch split channel. The microdroplets flow within the corresponding droplet generation channel, flow out along the collection channel, and finally flow into the collection port connected to the droplet generation channel. In this system, every two droplet generation channels are of the same length and their outlets are connected to a collection port. Multiple collection ports correspond to droplet generation channels of the same length, forming microdroplets of the same size. Uniform microdroplets are obtained at multiple collection ports.

[0043] After the microdroplets are collected, the dispersed phase undergoes a hydrolysis-condensation reaction, thereby solidifying the droplets to form microspheres. By controlling the flow rates of the two phases, the size of the microspheres can be precisely controlled.

[0044] The specific steps for preparing chromatographic packing microspheres using the integrated stepped T-shaped droplet microreactor described in this embodiment are as follows: Dispersed phase preparation: First, prepare a 0.1 mol / L glacial acetic acid solution and store it under refrigeration. Under ice bath conditions, add 13 wt% tetraoxomethylsilane to a round-bottom flask, then add 4 wt% of the 0.1 mol / L glacial acetic acid solution, mix thoroughly, then add 38 wt% deionized water, mix thoroughly again, and then add 2 wt%-8 wt% polyethylene glycol (PEG 200, PEG 8000, or other molecular weights), and react for 1 hour. Subsequently, add 45 wt% urea, mix thoroughly, and set aside. By changing the molecular weight and mass fraction of polyethylene glycol, the pore morphology and size of the final microspheres can be controlled.

[0045] Continuous phase preparation: Prepare a continuous phase solution containing 0.1-10 wt% surfactant (one or more of polyglycerol fatty acid ester, Span 80, and EM90) and 99.9-90 wt% oil phase (one or more of mineral oil, n-hexadecane, silicone oil, and fluorinated oil). In this embodiment, a paraffin oil solution containing 3 wt% Span 80 is preferably used as the continuous phase.

[0046] Droplet generation: The continuous phase solution is introduced through the continuous phase inlet, and the dispersed phase solution is introduced through the dispersed phase inlet. The flow rates of both phases are controlled by precision injection pumps. By adjusting the flow rate ratio of the two phases, the size of the generated microdroplets can be controlled.

[0047] Droplet collection and solidification: The generated microdroplets were collected in petri dishes and slowly transferred to a 40°C oven for drying for 12 hours. During the drying process, each droplet acted as an independent microreactor, where tetraoxomethylsilane underwent hydrolysis under the catalysis of acid and condensation under the catalysis of the alkali produced by urea decomposition, forming gel microspheres.

[0048] After curing, the unvolatile oil phase was extracted, and the microspheres were repeatedly washed with n-hexane to remove residual oil and surfactants, followed by rinsing twice with ethanol. Then, the microspheres were centrifuged at 5000 rpm for 5 minutes, repeated twice. The centrifuged microspheres were then placed back into an oven to dry.

[0049] The dried microspheres were calcined at 300℃ for 6 hours to remove the organic template agent, and then calcined at 600℃ for 12 hours to obtain the chromatographic packing microspheres.

[0050] The silica chromatographic packing microspheres prepared in this embodiment have a uniform particle size distribution (CV<3%), and the pore size can be controlled by the molecular weight and mass fraction of polyethylene glycol, making them suitable for high-performance liquid chromatography separation.

[0051] Example 1: A 5 wt% methylsilane solution of PEG 8000 was used as the dispersed phase solution, and a 3 wt% paraffin oil solution of Span 80 was used as the continuous phase solution. The dispersed phase solution was placed in a 10 mL syringe, and the continuous phase solution was placed in a 50 mL syringe. The continuous phase solution was injected into the continuous phase fluid inlet at a flow rate of 50 μL / min using a precision injection pump, and the dispersed phase solution was injected into the dispersed phase fluid inlet at a flow rate of 10 μL / min using a precision injection pump. After collection, the microdroplets are solidified, cleaned, centrifuged, dried and calcined to form chromatographic packing microspheres.

[0052] Example 2: A 3 wt% methylsilane solution of PEG 8000 was used as the dispersed phase solution, and a 3 wt% paraffin oil solution of Span 80 was used as the continuous phase solution. The dispersed phase solution was placed in a 10 mL syringe, and the continuous phase solution was placed in a 50 mL syringe. The continuous phase solution was injected into the continuous phase fluid inlet at a flow rate of 70 μL / min by a precision injection pump, and the dispersed phase solution was injected into the dispersed phase fluid inlet at a flow rate of 10 μL / min by a precision injection pump. After collection, the microdroplets are solidified, cleaned, centrifuged, dried and calcined to form chromatographic packing microspheres.

[0053] Example 3: A 5 wt% methylsilane solution of PEG200 was used as the dispersed phase solution, and a 3 wt% paraffin oil solution of Span80 was used as the continuous phase solution. The dispersed phase solution was placed in a 10 mL syringe, and the continuous phase solution was placed in a 50 mL syringe. The continuous phase solution was injected into the continuous phase fluid inlet at a flow rate of 80 μL / min by a precision injection pump, and the dispersed phase solution was injected into the dispersed phase fluid inlet at a flow rate of 10 μL / min by a precision injection pump. After collection, the microdroplets are solidified, cleaned, centrifuged, dried and calcined to form chromatographic packing microspheres.

[0054] Example 4: A 5 wt% methylsilane solution of PEG 200 was used as the dispersed phase solution, and a 3 wt% paraffin oil solution of Span 80 was used as the continuous phase solution. The dispersed phase solution was placed in a 10 mL syringe, and the continuous phase solution was placed in a 50 mL syringe. The continuous phase solution was injected into the continuous phase fluid inlet at a flow rate of 80 μL / min by a precision injection pump, and the dispersed phase solution was injected into the dispersed phase fluid inlet at a flow rate of 3 μL / min by a precision injection pump. After collection, the microdroplets are solidified, cleaned, centrifuged, dried and calcined to form chromatographic packing microspheres.

[0055] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An integrated stepped T-shaped microreactor, characterized in that, It includes a single-layer substrate and a plurality of continuous phase channel units and a plurality of dispersed phase channel units disposed on the single-layer substrate; Each of the aforementioned continuous phase channel units includes a main channel and multiple main split channels. The main split channels are connected to the main channel through a multi-level bifurcation structure. The multi-level bifurcation structure has N levels, and each inlet channel of each level of the bifurcation structure corresponds to two outlet channels. After N levels of successive diversion, two phase channels are formed. N The aforementioned main split channel; Each of the dispersed phase channel units includes one branch channel and multiple branch split channels. The branch split channels are connected to the branch channel through a multi-level bifurcation structure. The multi-level bifurcation structure has N levels, and each inlet channel of each level of the bifurcation structure corresponds to two outlet channels. After N levels of successive diversion, 2 N The branch split channel; The 2 N The main splitting channel and the 2 N Each branch splitting channel is paired one-to-one, and a droplet generation channel is formed at the intersection of each pair of main splitting channels and branch splitting channels. In this configuration, the two droplet generation channels corresponding to every two adjacent main splitting channels and every two adjacent branch splitting channels converge at the same collection port. The two adjacent main splitting channels and the two adjacent branch splitting channels are arranged in a mirror symmetry with respect to the droplet generation unit as the center.

2. The integrated stepped T-shaped microreactor as described in claim 1, characterized in that, All the main split channels at the same level have the same length, and all the branch split channels at the same level have the same length.

3. The integrated stepped T-shaped microreactor as described in claim 1, characterized in that, The multi-level binary branching structure is a completely symmetrical binary tree-shaped branching structure. The main branching channels and branch branching channels at each level of branching node are arranged axially symmetrically with the branching node as the center.

4. The integrated stepped T-shaped microreactor as described in claim 1, characterized in that, The microreactor is composed of multiple basic unit structures arranged in an array. Each basic unit structure includes a continuous phase channel unit, a dispersed phase channel unit, four droplet generation channels, and two collection ports. The continuous phase channel unit and the dispersed phase channel unit are symmetrically arranged, and each of the continuous phase channel unit and the dispersed phase channel unit corresponds to a set of split channels formed by a two-stage bifurcation structure.

5. The integrated stepped T-shaped microreactor as described in claim 1, characterized in that, The droplet generation channel is a stepped T-shaped channel. The stepped T-shaped channel has a rounded corner structure at the intersection of the main split channel and the branch split channel. The outlet of the droplet generation channel has an enlarged section channel structure, which is connected to the collection port.

6. The integrated stepped T-shaped microreactor as described in claim 1, characterized in that, The connections of the multi-level bifurcated structure are all equipped with rounded corners.

7. The integrated stepped T-shaped microreactor as described in claim 1, characterized in that, The single-layer substrate is integrally formed using photolithography. The continuous phase channel unit and the dispersed phase channel unit are microchannel structures etched on the single-layer substrate. The single-layer substrate is covered with a removable or bonded cover plate.

8. A method for high-throughput preparation of microspheres using an integrated stepped T-type microreactor as described in any one of claims 1-7, characterized in that, Includes the following steps: The continuous phase fluid is introduced through the main channel, and the dispersed phase fluid is introduced through the branch channel; The continuous phase fluid is progressively branched through an N-stage bifurcated structure and evenly distributed to 2 N One main split channel; The dispersed phase fluid is progressively split through an N-stage bifurcated structure and uniformly distributed to 2 N Individual branch split channels; At the intersection of each pair of main splitting channels and branch splitting channels, the continuous phase fluid and the dispersed phase fluid generate microdroplets; the microdroplets generated by every two adjacent droplet generation channels are collected through the same collection port. The collected microdroplets are solidified to form microspheres.

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