Microfluidic cleaning system for biochemical synthesis and synthesis system

Abstract

The utility model discloses a microfluidic cleaning system for biochemical synthesis and a synthesis system. The microfluidic cleaning system comprises a bearing device which comprises a supporting piece and a bearing piece; a pressing plate lifting device is arranged on the bearing part and comprises a power assembly and a pressing plate assembly with lifting freedom degree; a sealing runner device is arranged below the pressing plate assembly and comprises a partitioned runner main body, a sealing ring and a sealing pressing plate, a stepped bulge is arranged on the outer side of the partitioned runner main body, and the sealing ring is matched with the stepped bulge; the sealing pressing plate is used for fixing the sealing ring; the sealing ring is provided with a plurality of sub-rings; the parts, protruding out of the sealing pressing plate, of the sub-rings and the pressed chip form a plurality of sealed reaction cavities; and the liquid path system comprises a liquid supply unit, a gas supply unit and a waste liquid collection unit which are respectively connected with the plurality of sealed reaction cavities. According to the system, through partitioned sealing and partitioned fluid control, uniform liquid injection, clean cleaning and clean purging can be realized, and the synthesis requirements of high-flux and large-size chips are met.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the technical field of biochemical synthesis, in particular to a microfluidic cleaning system and a synthesis system for biochemical synthesis. BACKGROUND

[0002] In the technology of synthesizing DNA base chains based on chip surfaces, four chemical reactions are mainly involved, coupling, capping, oxidation and deprotection. Among them, coupling is usually achieved by printing technology, and capping, oxidation and deprotection need to be achieved by other fluid control devices. For a high-throughput synthesis chip, the reaction area is generally large, so it is very difficult to achieve the three reactions of capping, oxidation and deprotection by fluid control, and the three reactions involve multiple reagents with different physicochemical properties, and there are also high requirements for the adaptability of materials. The fluid reaction control device disclosed in the prior art can achieve multiple reactions, but there are problems such as uneven injection of large-area reaction area, incomplete cleaning, incomplete purging, and cannot meet the synthesis reaction requirements of high-throughput large-size chips. CONTENT OF THE UTILITY MODEL

[0003] Therefore, the present disclosure provides a microfluidic cleaning system and a synthesis system for biochemical synthesis, which at least partially solves the problems of uneven injection of large-area reaction area, incomplete cleaning, incomplete purging, and inability to meet the synthesis reaction requirements of high-throughput large-size chips in the prior art.

[0004] In a first aspect, the present disclosure provides a microfluidic cleaning system for biochemical synthesis, comprising:

[0005] A bearing device comprising a support and a bearing mounted on the top of the support, the bearing and the support being connected by a horizontal adjustment assembly, and the bearing having a horizontal adjustment degree of freedom;

[0006] A press plate lifting device mounted on the bearing, comprising a power assembly and a press plate assembly mounted on the power output end of the power assembly, the press plate assembly having a degree of freedom of lifting along the longitudinal axis of the power output end of the power assembly;

[0007] A sealed flow channel device mounted below the press plate assembly, comprising a partitioned flow channel body, a sealing ring and a sealing press plate, the side of the partitioned flow channel body away from the press plate assembly having a stepped protrusion, and the sealing ring being matched with the stepped protrusion; the sealing press plate is mounted on the peripheral side of the sealing ring and is fixedly connected with the partitioned flow channel body; the sealing ring has a plurality of sub-rings, and the plurality of sub-rings protrude from the sealing press plate; the protruding portions of the plurality of sub-rings and the pressed chip form a plurality of sealed reaction cavities;

[0008] The liquid path system comprises a liquid supply unit, a gas supply unit and a waste liquid collection unit, the liquid supply unit is connected with the sealing reaction cavities through a liquid supply pipeline assembly; the gas supply unit is connected with the sealing reaction cavities through a gas supply pipeline assembly; the waste liquid collection unit is connected with the sealing reaction cavities through a liquid extraction pipeline assembly.

[0009] Optionally, the support comprises two supports, and the bearing member is a horizontal plate, and the horizontal plate and the two supports form a gantry structure;

[0010] The horizontal plate is provided with three leveling member mounting portions arranged in a triangular shape;

[0011] The horizontal adjustment assembly comprises three sets of leveling assemblies respectively mounted on the three leveling member mounting portions;

[0012] Each set of leveling assemblies comprises a knuckle bearing, an adjusting screw and a bearing mounting plate, the bearing mounting plate is provided with a threaded hole, one end of the adjusting screw is fixedly connected with the knuckle bearing and the horizontal plate, and the other end of the adjusting screw is threadedly connected with the threaded hole, and the adjusting screw has a freedom of movement along the longitudinal center axis of the threaded hole.

[0013] Optionally, the horizontal plate is provided with a motor mounting hole and a column mounting hole;

[0014] The power assembly comprises a servo motor and a speed reducer mounted on the power output end of the servo motor, the speed reducer is fixedly arranged in the motor mounting hole, and the power output end of the speed reducer is provided with a T-shaped screw nut and a T-shaped screw rod, the T-shaped screw nut is fixedly connected with the power output end of the speed reducer, and the T-shaped screw rod is rotationally arranged in cooperation with the T-shaped screw nut;

[0015] The pressing plate assembly comprises a bearing assembly mounted on the free end of the T-shaped screw rod, a plurality of uniform pressure plates arranged below the bearing assembly and a plurality of guide members;

[0016] One end of each guide member is arranged on at least two uniform pressure plates, and the other end penetrates through the column mounting hole;

[0017] The longitudinal center axis of the guide member is parallel to the longitudinal center axis of the T-shaped screw rod.

[0018] Optionally, the bearing assembly comprises a bearing member and a bearing seat for bearing the bearing member;

[0019] The uniform pressure plates are arranged in three, and the three uniform pressure plates are fixedly arranged in parallel and at equal intervals on the bottom of the bearing seat;

[0020] The guide member is a ball spline, and the ball spline is provided with four ball splines;

[0021] Two said ball spline are installed on both sides of the two said voltage equalizing plates, and the spline sleeve of the ball spline is fixedly connected with the horizontal plate.

[0022] Optionally, each said sealed reaction cavity has a liquid inlet and a liquid outlet, and the liquid inlet and the liquid outlet are arranged through the partition flow channel body and the stepped protrusion.

[0023] Optionally, the sealing pressure plate comprises a first pressure plate, a second pressure plate, a third pressure plate and a fourth pressure plate arranged in sequence with their ends abutting against each other, and the first pressure plate, the second pressure plate, the third pressure plate and the fourth pressure plate form an annular structure for pressing the sealing ring.

[0024] Optionally, the height of the several sub-rings protruding from the sealing pressure plate in a natural state is H, and 0.3mm≤H≤0.35mm.

[0025] The height of the several sub-rings protruding from the sealing pressure plate when pressing the chip is consistent with the height of the liquid film. Optionally, the length and width of the sealing pressure plate are arranged to be consistent with the length and width of the partition flow channel body.

[0026] The area of the sealing pressure plate is arranged to match the area of the chip to be pressed.

[0027] Optionally, the microfluidic cleaning system further comprises a gas-liquid pipe lifting device fixedly connected with the pressure plate assembly.

[0028] The gas-liquid pipe lifting device comprises a bridge plate, a gas source conveying pipe, a waste liquid collecting pipe, a first hollow pipe containing the gas source conveying pipe, a second hollow pipe containing the waste liquid collecting pipe, and a lifting drag chain.

[0029] The bridge plate is fixedly connected with the side of the voltage equalizing plate.

[0030] The first hollow pipe and the second hollow pipe are fixedly connected with the bridge plate.

[0031] One end of the lifting drag chain is fixedly arranged with the side of the support, and the other end is fixedly connected with the bridge plate.

[0032] In a second aspect, the application discloses a synthesis system for the synthesis of a DNA chip, which comprises a general control center and the microfluidic cleaning system for biochemical synthesis, and the pressure plate lifting device and the liquid path system are signal connected with the general control center.

[0033] The microfluidic cleaning system for biochemical synthesis disclosed in the application, the carrying device is connected with the carrier through the horizontal adjusting assembly, so that the carrier has the horizontal adjusting freedom; the pressing plate lifting device realizes the accurate lifting of the pressing plate through the power assembly, which can ensure consistent sealing effect when processing chips of different sizes and shapes, thereby improving the reaction efficiency and consistency; the stepped protrusions of the partition flow channel main body are matched with the sealing ring to ensure the sealing property of the reaction cavity, and the protruding sealing ring further enhances the sealing effect, avoids fluid leakage, and ensures the reliability and efficiency of the cleaning and reaction process; the protruding part of the sealing ring and the pressed chip constitute a sealed reaction cavity, which can effectively isolate different reaction areas, prevent cross contamination between different reactions, and improve the purity of the reaction and the accuracy of the results; the liquid path system includes a liquid supply unit, a gas supply unit and a waste liquid collection unit, which are connected with each of the sealed reaction cavities through respective pipeline assemblies, which not only can realize accurate control of different reaction steps, but also can simplify the cleaning and waste treatment process, and can effectively improve the overall efficiency and operation convenience of the system; through the respectively connected liquid supply pipeline assembly, gas supply pipeline assembly and liquid pumping pipeline assembly, independent control of multiple reaction cavities can be realized, which meets the synthesis requirements of high-throughput and large-size chips and meets the requirements of complex DNA synthesis reactions.

[0034] The above description is only a summary of the technical solutions of the present disclosure, in order to more clearly understand the technical means of the present disclosure, the content of the specification can be implemented, and in order for the above and other purposes, features and advantages of the present disclosure to be more obvious and easy to understand, the following preferred embodiments are described in detail below, and the accompanying drawings are described as follows. BRIEF DESCRIPTION OF DRAWINGS

[0035] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the following will briefly introduce the drawings needed to be used in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present disclosure, and those skilled in the art can obtain other drawings according to these drawings without creating any creative labor.

[0036] Figure 1 The schematic diagram of the microfluidic cleaning system for biochemical synthesis disclosed in the application.

[0037] Figure 2 The Figure 1 The perspective view of the carrying device.

[0038] Figure 3 The Figure 1 The perspective view of the pressing plate lifting device.

[0039] Figure 4 The Figure 1A perspective view of a sealing flow channel device.

[0040] Figure 5 is Figure 1 An assembly view of a gas-liquid pipe lifting device.

[0041] Explanation of reference signs:

[0042] 100, bearing device; 110, support; 111, gantry bottom plate; 112, gantry vertical plate; 120, cross plate; 121, motor mounting hole; 122, column mounting hole; 130, knuckle bearing; 140, bearing mounting plate; 150, decorative plate;

[0043] 200, pressing plate lifting device; 211, servo motor; 212, speed reducer; 220, T-shaped nut; 230, T-shaped screw; 240, bearing assembly; 250, equalizing plate; 260, ball spline; 270, locking gland;

[0044] 300, sealing flow channel device; 310, partitioned flow channel main body; 320, sealing pressing plate; 330, liquid inlet; 340, liquid outlet;

[0045] 400, gas-liquid pipe lifting device; 410, bridging plate; 420, first hollow pipe; 430, second hollow pipe; 440, lifting drag chain. DETAILED DESCRIPTION

[0046] The present disclosure will be described in further detail below with reference to the drawings and embodiments. It can be understood that the specific embodiments described herein are only used to explain the related content, and not to limit the present disclosure. In addition, it should be noted that only parts related to the present disclosure are shown in the drawings for ease of description.

[0047] It should be noted that the embodiments in the present disclosure and the features in the embodiments can be combined with each other without conflict. The technical solutions of the present disclosure will be described in detail below with reference to the drawings and in combination with the embodiments.

[0048] Unless otherwise specified, the exemplary embodiments / instances shown will be understood to provide exemplary features of various details that can implement the technical concepts of the present disclosure in practice. Therefore, unless otherwise specified, the features of various embodiments / instances can be additionally combined, separated, interchanged and / or rearranged without departing from the technical concepts of the present disclosure.

[0049] The use of cross-hatching and / or shading in the drawings is generally used to illustrate the boundaries and / or transitions from one portion of a part to another portion of the part. As such, unless specified, the presence of cross-hatching or shading in no way supercedes, or otherwise clarifies, any aspect of the parts described as being clear, transparent, opaque, solid, formed, unformed, etc. Moreover, in the drawings, the size and relative sizes of parts can be exaggerated for clarity. When exemplary embodiments can be carried out in different ways, the specific sequential order described can be performed in a different order. For example, two sequentially described processes can be performed at about the same time or in the reverse order than described. Additionally, like reference numerals can denote like parts throughout the description.

[0050] When a part is referred to as being "on" or "over" another part, "connected to" or "coupled to" another part, it can be directly on, directly connected to, or directly coupled to the other part, or intervening parts can be present. In contrast, when an part is referred to as being "directly on," "directly connected to," or "directly coupled to" another part, there are no intervening parts present. For example, the term "connected" can refer to physical or electrical connection, whether direct or through intervening parts.

[0051] For purposes of the description hereinafter, spatial or directional terms, such as "below," "lower," "down," "upright," "above," "upper," "over," "higher," and "side" (e.g., as in "sidewall") are used with reference to the orientation of the device as shown in the drawings. The spatial or directional terms are intended to encompass different orientations of the device in use, operation, and / or manufacture, depending on the particular spatial or directional term used. For example, if the device in the drawings is turned over, then the part described as "below" or "under" other parts or features would then be oriented "above" the other parts or features. Thus, the exemplary term "below" can encompass both an orientation of above and below. Moreover, the device can be oriented in different ways (e.g., rotated 90 degrees or at other orientations) and, as such, the spatial or directional terms are interpreted accordingly.

[0052] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, to the extent that the terms "comprising," "including," "containing," and / or "having" and variations thereof are used herein, such terms are intended to be inclusive, in an aspect, it is noted that the terms "substantial," "approximately," and other similar terms are used as terms of approximation and not as terms of degree, accordingly, they are utilized to account for inherent deviations in measurements, calculations, and / or provided values that would be recognized by those of ordinary skill in the art.

[0053] Referring to Figure 1 The present application discloses a microfluidic cleaning system for biochemical synthesis, comprising a bearing device 100, a pressing plate lifting device 200, a sealing flow channel device 300 and a liquid path system, the pressing plate lifting device 200 and the sealing flow channel device 300 are both installed on the bearing device 100, the pressing plate lifting device 200 is used to control the sealing of the sealing flow channel device 300 and the to-be-pressed chip placed in the preset position, and a plurality of sealed reaction cavities are formed after the sealing flow channel device 300 is sealed with the to-be-pressed chip; the liquid path system comprises a liquid supply unit, a gas supply unit and a waste liquid collection unit which are independently arranged, the liquid supply unit is connected with the plurality of sealed reaction cavities through a liquid supply pipeline assembly and is used to provide reagents corresponding to each sealed reaction cavity, the gas supply unit is connected with the plurality of sealed reaction cavities through a gas supply pipeline assembly and can clean the corresponding cavities by providing gas, and the waste liquid collection unit is connected with the plurality of sealed reaction cavities through a liquid pumping pipeline assembly and is used to collect the reacted liquid in the corresponding cavities; wherein the liquid supply unit and the gas supply unit are switched through a gas-liquid path switching unit.

[0054] In this embodiment, by partition sealing and partition fluid control, a large-area reaction area is divided into a plurality of independent small reaction areas (i.e. a plurality of sealed reaction cavities), and the matching chip forms an openable and closable reaction cavity, so that different reagents can be controlled to complete the reaction process required by the process in the corresponding sealed reaction cavities, and a smaller liquid film thickness can be controlled, after the reaction is completed, the corresponding sealed reaction cavities can be quickly cleaned, effectively solving the problems of uneven liquid injection, incomplete cleaning and incomplete cleaning of the large-area reaction area in the prior art, so that the high-throughput large-size chip synthesis reaction is more easily realized.

[0055] Referring to Figure 2 The bearing device 100 comprises a support and a bearing installed on the top of the support, the bearing and the support are connected through a horizontal adjustment assembly, and the bearing has a horizontal adjustment degree of freedom.

[0056] In this embodiment, the support comprises two supports 110, and the support is a horizontal plate 120 which forms a gantry structure with the two supports 110.

[0057] The support 110 comprises a gantry bottom plate 111 and a gantry vertical plate 112 which are arranged in an L shape, and the gantry bottom plate 111 and the gantry vertical plate 112 are fixed by screws to ensure the stability of the support 110. The two supports 110 are arranged oppositely, i.e., the two L-shaped gantry bottom plates 111 are arranged outwardly.

[0058] The horizontal plate 120 has three leveling piece mounting portions arranged in an acute triangle. The horizontal adjustment assembly comprises three sets of leveling assemblies respectively mounted on the three leveling piece mounting portions.

[0059] Each set of leveling assemblies comprises a knuckle bearing 130, an adjusting screw and a bearing mounting plate 140. The bearing mounting plate 140 is fixed with the gantry vertical plate 112 by screws, and the bearing mounting plate 140 is provided with a threaded hole.

[0060] One end of the adjusting screw is fixedly connected with the knuckle bearing 130 through a locking cap, and the end portion protrudes out of the knuckle bearing 130 and is threadedly connected with the horizontal plate 120 and locked by a nut. The other end of the adjusting screw is threadedly connected with the threaded hole and can rotate, i.e., the adjusting screw has the freedom of moving along the longitudinal center axis of the threaded hole. Specifically, the horizontal adjustment of the horizontal plate 120 can be realized by adjusting the rotatable end of the adjusting screw through a hexagon wrench.

[0061] In this embodiment, when the left side of the horizontal plate 120 is lower than the horizontal plane, the distance between the knuckle bearing 130 and the corresponding bearing mounting plate 140 is increased by adjusting the position of the two knuckle bearings 130 on the left side. Since the bearing mounting plate 140 is fixed, it is equivalent to adjusting the left side of the horizontal plate 120 to be raised, so that the whole horizontal plate 120 meets the preset levelness. Similarly, when the right side of the horizontal plate 120 is lower than the horizontal plane, the distance between the knuckle bearing 130 and the corresponding bearing mounting plate 140 is increased by adjusting the position of the knuckle bearing 130 on the right side. Since the bearing mounting plate 140 is fixed, it is equivalent to adjusting the right side of the horizontal plate 120 to be raised, so that the whole horizontal plate 120 meets the preset levelness. Of course, the horizontal adjustment of the corresponding position of the horizontal plate 120 can also be realized by adjusting the two knuckle bearings 130 on the left side.

[0062] After the horizontal adjustment of the horizontal plate 120 is completed, the rotatable end of the knuckle bearing 130 is locked by a nut, and the horizontal plate 120 can be fixedly connected with the gantry vertical plate 112 by screws and a jack.

[0063] Further, the horizontal plate 120 is further provided with a decorative plate 150 for decoration.

[0064] Referring to Figure 2 and Figure 3 The pressing plate lifting device 200 is arranged on the bearing member, and the pressing plate lifting device 200 comprises a power assembly, a pressing plate assembly arranged on the power output end of the power assembly, and the pressing plate assembly has a lifting degree along the longitudinal axis of the power output end of the power assembly.

[0065] The cross plate 120 is provided with a motor mounting hole 121 and a column mounting hole 122. The power assembly comprises a servo motor 211 and a speed reducer 212 arranged on the power output end of the servo motor 211, and the speed reducer 212 is fixedly arranged on the motor mounting hole 121. The power output end of the speed reducer 212 is provided with a T-shaped nut 220 and a T-shaped lead screw 230, the T-shaped nut 220 is fixedly connected with the power output end of the speed reducer 212, and the T-shaped lead screw 230 is rotationally matched with the T-shaped nut 220, that is, when the servo motor 211 is started, the T-shaped nut 220 is driven to rotate through the speed reducer 212, and then the T-shaped lead screw 230 is driven to ascend or descend.

[0066] The speed reducer 212 is a high-precision spiral bevel gear speed reducer.

[0067] The pressing plate assembly comprises a bearing assembly 240 arranged on the free end of the T-shaped lead screw 230, a plurality of uniform pressing plates 250 arranged below the bearing assembly 240, and a plurality of guide members. Under the driving of the power assembly, the plurality of uniform pressing plates 250, the plurality of guide members and the bearing assembly 240 ascend or descend synchronously with the T-shaped lead screw 230.

[0068] One end of the plurality of guide members is arranged on at least two uniform pressing plates 250, and the other end penetrates the column mounting hole 122, thereby providing guidance for the lifting of the plurality of uniform pressing plates 250, the plurality of guide members and the bearing assembly 240.

[0069] The longitudinal central axis of the guide member is parallel to the longitudinal central axis of the T-shaped lead screw 230.

[0070] In this embodiment, the bearing assembly 240 comprises a bearing member and a bearing seat bearing the bearing member. Specifically, the bearing member is an angular contact bearing, which is installed in the bearing seat and is pressed by a locking gland 270.

[0071] Preferably, three uniform pressing plates 250 are arranged, and the three uniform pressing plates 250 are arranged in parallel and at equal intervals on the bottom of the bearing seat. The middle uniform pressing plate 250 is arranged directly below the T-shaped lead screw 230, and the two uniform pressing plates 250 on both sides are symmetrically arranged relative to the middle uniform pressing plate 250.

[0072] The guide is preferably a ball spline 260, and four ball splines 260 are provided; two ball splines 260 are mounted on each of the two side pressing plates 250, and the spline sleeve of the ball spline 260 is fixedly connected with the horizontal plate 120. The spline sleeve of the ball spline 260 has the freedom of moving along the spline shaft axis direction, while keeping the circumferential positioning unchanged. In this embodiment, the spline sleeve is fixedly connected with the corresponding column mounting hole 122, so that when the spline sleeve is fixed, the spline shaft can move up and down relative to the spline sleeve.

[0073] In addition, the plurality of pressing plates 250, the plurality of guides, and the bearing assembly 240 can also be manually controlled to move up and down, that is, the servo motor 211 is not moved, and the T-shaped lead screw 230 is driven to rotate and move up and down by a hexagonal wrench. This mode is used for manual testing and fault handling.

[0074] In this embodiment, the switching between manual control and automatic control by the servo motor 211 is realized by a locking gland 270, which is fixed on the bearing seat by a screw to press the angular contact bearing, and the locking gland 270 can lock or release the T-shaped lead screw 230. When the T-shaped lead screw 230 is locked, the electric mode is realized; when the T-shaped lead screw 230 is released, the manual mode is realized.

[0075] Further, the top of the horizontal plate 120 can also be provided with a first position detector, and the bottom of the horizontal plate 120 can be provided with a second position detector, which is used to detect the up-and-down position of the ball spline 260, that is, the up-and-down position of the pressing plate 250.

[0076] Referring to Figure 4 The sealing flow channel device 300 is arranged below the pressing plate assembly, and the sealing flow channel device 300 comprises a partitioned flow channel body 310, a sealing ring, and a sealing pressing plate 320. The partitioned flow channel body 310 has a stepped protrusion on the side away from the pressing plate assembly, and the sealing ring is arranged in matching with the stepped protrusion. The sealing pressing plate 320 is arranged on the circumferential side of the sealing ring and is fixedly connected with the partitioned flow channel body 310. The sealing ring has a plurality of sub-rings, and the plurality of sub-rings protrude from the sealing pressing plate 320. The protruding portions of the plurality of sub-rings and the pressed chips form a plurality of sealing reaction cavities.

[0077] Each sealing reaction cavity has a liquid inlet 330 and a liquid outlet 340, and the liquid inlet 330 and the liquid outlet 340 are arranged through the partitioned flow channel body 310 and the stepped protrusion. Specifically, the liquid inlet 330 and the liquid outlet 340 are arranged close to the two edge ends to facilitate sufficient reaction. In this embodiment, the liquid inlet 330 is a straight hole perpendicular to the plane of the partitioned flow channel body 310, one end of the straight hole is on the upper plane of the partitioned flow channel body 310, and the other end penetrates through the stepped protrusion and communicates with the corresponding sealing reaction cavity. The liquid outlet 340 is an L-shaped hole, one end of the L-shaped hole is on the side of the partitioned flow channel body 310, and the other end penetrates through the stepped protrusion and communicates with the corresponding sealing reaction cavity, which is used to output the reacted reagent.

[0078] The sealing pressing plate 320 is provided with a groove matched with the circumferential edge of the sealing ring, so as to ensure the compression and fixation of the circumferential side of the sealing ring.

[0079] In the assembled state, the sealing ring of the sealing pressing plate 320 protrudes out of the rear convex part of the sealing pressing plate 320, and when the sealing flow channel device 300 is pressed against the chip to be pressed, the protruding part of the sealing ring out of the sealing pressing plate 320 is tightly attached to the surface of the chip, and the surface of the chip is divided into a plurality of sealing reaction cavities by a plurality of sub-rings.

[0080] The height of the plurality of sub-rings protruding from the sealing pressing plate 320 is H, and 0.3mm≤H≤0.35mm, which refers to the natural state; when the chip is pressed, the height of the plurality of sub-rings protruding from the sealing pressing plate 320 is 0.1±0.02mm, which is the height of the liquid film. The number of sealing reaction cavities is consistent with the number of sub-rings.

[0081] In this embodiment, the shape and area of the plurality of sub-rings can be the same or different, and can be flexibly set according to actual needs, which is within the protection scope of the present application; the length and width of the sealing pressing plate 320 are consistent with the length and width of the partition flow channel main body 310; the area of the sealing pressing plate 320 is matched with the area of the chip to be pressed; the consistency of the flow channel state is more conducive to the stability of fluid control, thereby ensuring the completion of the set reaction according to the process requirements.

[0082] In this embodiment, the partition sealing ring is used to realize the separation of the sub-flow channel reaction area. The sealing flow channel structure actually separates a large reaction area into a plurality of small reaction areas, which is more conducive to the process control of fluid injection, purging and bubble removal.

[0083] With reference to Figure 5 The microfluidic cleaning system for biochemical synthesis disclosed in the present application further comprises a gas-liquid pipe lifting device 400 fixedly connected with the pressing plate assembly, which is used to move synchronously with the pressing plate assembly to avoid the bending damage of the gas pipe and liquid pipe during long-distance movement of the mechanism, and improve the sealing performance and service life.

[0084] Specifically, the gas-liquid pipe lifting device 400 comprises a bridge plate 410, a gas source conveying pipe, a waste liquid collecting pipe, a first hollow pipe 420 containing the gas source conveying pipe, a second hollow pipe 430 containing the waste liquid collecting pipe, and a lifting drag chain 440; the bridge plate 410 is fixedly connected with the side of the pressure equalizing plate 250; the first hollow pipe 420 and the second hollow pipe 430 are fixedly connected with the bridge plate 410; one end of the lifting drag chain 440 is fixedly arranged on the side of the support 110, and the other end is fixedly connected with the bridge plate 410 and lifts together with the bridge plate 410; some cables are mainly arranged in the lifting drag chain 440.

[0085] The first hollow tube 420 is sleeved in the first linear bearing, the first linear bearing is installed on the first linear bearing mounting plate 140, and the first linear bearing mounting plate 140 is fixedly connected with the bridging plate 410. The second hollow tube 430 is sleeved in the second linear bearing, the second linear bearing is installed on the second linear bearing mounting plate 140, and the second linear bearing mounting plate 140 is fixedly connected with the bridging plate 410. In this embodiment, the first hollow tube 420 and the second hollow tube 430 can slide up and down in the first linear bearing and the second linear bearing, respectively.

[0086] The two ends of the first hollow tube 420 are respectively provided with an air inlet joint and an air outlet joint, and the two ends of the second hollow tube 430 are respectively provided with liquid pipe joints. The air inlet joint, the air outlet joint and the liquid pipe joint are fixedly connected with the bridging plate 410.

[0087] The gas-liquid path switching unit is connected with the waste liquid collection pipe through a pipeline and a joint.

[0088] In this embodiment, the first hollow tube 420 is provided with two first hollow tubes, the two first hollow tubes are connected with the air inlet joint at the bottom and the air outlet joint at the top, and the two first hollow tubes provide a gas source for high-pressure purging of the liquid path system. The second hollow tube 430 is provided with two second hollow tubes, the upper and lower ends of the two second hollow tubes are connected with liquid path joints, and the liquid path joints are connected with the bridging plate 410. The waste liquid pipe from the sealing flow channel structure directly passes through the two second hollow tubes 430 and is connected with the waste liquid collection unit.

[0089] Further, the gas-liquid path switching unit is a unit including a multi-way valve and a solenoid valve, which can realize rapid switching, rapid cleaning and rapid purging of various reagents, has no cross contamination, and can ensure that the reaction is completed according to the process requirements. By setting different process parameters, different process flows can be realized, and the flexibility of the process is ensured. The liquid path system also has rich functions such as liquid path preparation, waste liquid collection and liquid path cleaning.

[0090] In this embodiment, by analyzing the physicochemical properties of various reaction reagents and a large number of resistance tests, for the components and devices contacted by the reagents, appropriate corrosion-resistant materials are selected to ensure the safety and stability of the liquid path system.

[0091] In this embodiment, the liquid path system can deliver different reagents and gases with different pressures to the sealed flow channel structure and the sealed reaction cavity formed after the chip is pressed, thereby completing the processes of reagent filling, reagent reaction, and blowing. The switching of different reagents and gases is completed by a multi-way valve in the gas-liquid path switching unit, and the switching process has no cross contamination and negligible trace residual contamination. The liquid supply is in the form of pressurizing the inert gas in the reagent bottle to press out the reagent, and the waste liquid collection is standardized. All waste liquid and gas pipelines are integrated into the barrel cover, and the replacement of the waste liquid barrel only requires the replacement of the barrel body. In addition, by setting different process parameters, different process flows can be realized to ensure the flexibility of the process.

[0092] In this embodiment, the gantry structure is the basic framework of the microfluidic cleaning system, has the functions of high rigidity, corrosion resistance, and adjustable level, and the main purpose of level adjustment is to ensure uniform sealing after the sealed flow channel structure is pressed with the chip to prevent leakage and to form a reaction liquid film with the same thickness to ensure the consistency of the reaction and blowing.

[0093] It should be noted that the present application can realize independent control of each sealed reaction cavity, or can realize synchronous control of several combinations thereof. The partition control can better realize the fluid function, which is within the protection scope of the present application, and thus will not be described herein again. In addition, for waste liquid collection, low-pressure or high-pressure purge gas can also be provided for the sealed reaction cavity to discharge the liquid in the cavity through the liquid pumping pipeline assembly.

[0094] The microfluidic cleaning system for biochemical synthesis disclosed in the present application is characterized in that the carrying device is connected to the carrier through the level adjustment assembly, so that the carrier has the freedom of level adjustment; the press plate lifting device realizes the precise lifting of the press plate through the power assembly, which can ensure consistent sealing effect when processing chips with different sizes and shapes, thereby improving the reaction efficiency and consistency; the stepped protrusions of the partition flow channel main body are matched with the sealing ring to ensure the sealing property of the reaction cavity, and the protruding sealing ring further enhances the sealing effect, avoids fluid leakage, and ensures the reliability and efficiency of the cleaning and reaction process; the protruding part of the sealing ring and the pressed chip constitute a sealed reaction cavity, which can effectively isolate different reaction areas, prevent cross contamination between different reactions, and improve the purity of the reaction and the accuracy of the results; the liquid path system includes a liquid supply unit, a gas supply unit, and a waste liquid collection unit, which are connected to each sealed reaction cavity through respective pipeline assemblies, which not only realizes the precise control of different reaction steps, but also simplifies the cleaning and waste treatment process, and can effectively improve the overall efficiency and operation convenience of the system; through the respectively connected liquid supply pipeline assembly, gas supply pipeline assembly, and liquid pumping pipeline assembly, independent control of multiple reaction cavities can be realized to adapt to the synthesis requirements of high-throughput and large-size chips and meet the requirements of complex DNA synthesis reactions.

[0095] The microfluidic cleaning system for biochemical synthesis disclosed in the present application divides a large-area reaction region into several independent small reaction regions (i.e., several sealed reaction cavities) through partition sealing and partition fluid control, and forms openable and closable reaction cavities by matching chips, so that different reagents can complete the reaction process required by the process in the corresponding sealed reaction cavities, and a small liquid film thickness can be controlled. After the reaction is completed, the corresponding sealed reaction cavities can be quickly cleaned, effectively solving the problems of uneven liquid injection, incomplete cleaning, and incomplete purging in the large-area reaction region in the prior art, so that high-throughput large-size chip synthesis reaction can be more easily realized.

[0096] The microfluidic cleaning system for biochemical synthesis disclosed in the present application divides a large-area reaction region into several small reaction regions (i.e., sealed reaction cavities), and then precisely controls the small volume of each small reaction region. Through partition sealing and partition fluid control, openable and closable multi-partition reaction cavities can be formed, different reagents can complete the reaction process required by the process in the reaction cavities, and waste liquid can be completely removed. The device structure of the microfluidic cleaning system for biochemical synthesis disclosed in the present application is precise and stable, the reagent contact material has strong reagent resistance, multi-partition control can realize large-area synthesis reaction, and flexible reaction process can be realized. The device structure of the microfluidic cleaning system for biochemical synthesis disclosed in the present application is precise and stable, the reagent contact material has strong reagent resistance, multi-partition control can realize large-area synthesis reaction, and flexible reaction process can be realized. In the process of biological synthesis, especially DNA synthesis, it plays a key role.

[0097] In a second aspect, the present application discloses a synthesis system for the synthesis of a DNA chip, characterized in that it comprises a general control center and the microfluidic cleaning system for biochemical synthesis, and the pressing plate lifting device and the liquid path system are signal connected with the general control center.

[0098] In the description of the present application, the description of the terms "one embodiment / way", "some embodiments / ways", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in connection with the embodiment / way or example are included in at least one embodiment / way or example of the present application. In the present application, the illustrative description of the above terms does not necessarily refer to the same embodiment / way or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments / ways or examples. In addition, the skilled in the art can combine and combine the features of different embodiments / ways or examples described in the present application without contradiction.

[0099] In addition, the terms "first", "second", etc. are used only for the purpose of description, and should not be understood as indicating or implying relative importance or a specific number of the technical features indicated. Thus, the features defined with "first", "second" can explicitly or implicitly include at least one of the features. In the description of the present application, the meaning of "a plurality of" is at least two, such as two, three, etc., unless otherwise explicitly and specifically limited.

[0100] Those skilled in the art will understand that the above-mentioned embodiments are only for the purpose of clearly illustrating the present disclosure, and are not intended to limit the scope of the present disclosure. Other changes or modifications can be made on the basis of the above disclosure, and these changes or modifications are still within the scope of the present disclosure.

Claims

1. A microfluidic washing system for biochemical synthesis, characterized in that, The application relates to a bearing device, a press plate lifting device, a sealing flow channel device, a liquid path system and a support. The bearing device comprises a support and a bearing part installed on the top of the support, the bearing part is connected with the support through a horizontal adjusting assembly, and the bearing part has a horizontal adjusting freedom; The press plate lifting device is installed on the bearing part and comprises a power assembly, a press plate assembly installed on the power output end of the power assembly, and the press plate assembly has a lifting freedom along the longitudinal axis of the power output end of the power assembly; The sealing flow channel device is installed below the press plate assembly and comprises a partition flow channel body, a sealing ring and a sealing press plate, the side of the partition flow channel body away from the press plate assembly is provided with a stepped protrusion, the sealing ring is arranged in matched mode with the stepped protrusion, the sealing press plate is installed on the circumferential side of the sealing ring and is fixedly connected with the partition flow channel body, the sealing ring is provided with a plurality of sub-rings, the sub-rings protrude from the sealing press plate, the protruding parts of the sub-rings and the press-chip form a plurality of sealing reaction cavities; The liquid path system comprises a liquid supply unit, a gas supply unit and a waste liquid collection unit, the liquid supply unit is connected with the sealing reaction cavities through a liquid supply pipeline assembly, the gas supply unit is connected with the sealing reaction cavities through a gas supply pipeline assembly, and the waste liquid collection unit is connected with the sealing reaction cavities through a liquid pumping pipeline assembly.

2. The microfluidic washing system for biochemical synthesis of claim 1, wherein, The support comprises two supports, the bearing part is a horizontal plate, and the horizontal plate and the two supports form a gantry structure; The horizontal plate is provided with three leveling part installation parts arranged in a triangular shape; The horizontal adjusting assembly comprises three sets of leveling assemblies installed on the three leveling part installation parts respectively; Each set of the leveling assemblies comprises a joint bearing, an adjusting screw and a bearing mounting plate, the bearing mounting plate is provided with a threaded hole, one end of the adjusting screw is fixedly connected with the joint bearing and the horizontal plate, and the other end of the adjusting screw is threadedly connected with the threaded hole, and the adjusting screw has a freedom of moving along the longitudinal central axis of the threaded hole.

3. The microfluidic washing system for biochemical synthesis of claim 2, wherein, The horizontal plate is provided with a motor mounting hole and a column mounting hole; The power assembly comprises a servo motor and a speed reducer installed on the power output end of the servo motor, the speed reducer is fixedly arranged on the motor mounting hole, the power output end of the speed reducer is provided with a T-shaped screw nut and a T-shaped screw rod, the T-shaped screw nut is fixedly connected with the power output end of the speed reducer, and the T-shaped screw rod is arranged in rotational cooperation with the T-shaped screw nut; The press plate assembly comprises a bearing assembly installed on the free end of the T-shaped screw rod, a plurality of uniform press plates arranged below the bearing assembly and a plurality of guide parts; One end of each of the guide parts is arranged on at least two of the uniform press plates, and the other end penetrates through the column mounting hole; The longitudinal central axis of the guide part is parallel to the longitudinal central axis of the T-shaped screw rod.

4. The microfluidic washing system for biochemical synthesis of claim 3, wherein, The bearing assembly comprises a bearing part and a bearing seat bearing the bearing part; The uniform press plates are arranged in parallel and at equal intervals on the bottom of the bearing seat; The guide part is a ball spline, and the ball spline is provided with four rods. Two said equalizing plates are installed with two said ball spline on both sides, and the spline sleeve of the ball spline is fixedly connected with the horizontal plate.

5. The microfluidic washing system for biochemical synthesis of claim 4, wherein, Each said sealed reaction cavity has a liquid inlet and a liquid outlet, and the liquid inlet and the liquid outlet are arranged through the partition flow channel body and the stepped protrusion.

6. The microfluidic washing system for biochemical synthesis of claim 1, wherein, The sealing pressure plate comprises a first pressure plate, a second pressure plate, a third pressure plate and a fourth pressure plate arranged in sequence from head to tail, and the first pressure plate, the second pressure plate, the third pressure plate and the fourth pressure plate form an annular structure for pressing the sealing ring.

7. The microfluidic washing system for biochemical synthesis of claim 6, wherein, The height of the several sub-rings protruding from the sealing pressure plate in a natural state is H, and 0.3mm≤H≤0.35mm; The height of the several sub-rings protruding from the sealing pressure plate when pressing the chip is consistent with the height of the liquid film.

8. The microfluidic washing system for biochemical synthesis of claim 6, wherein, The length and width of the sealing pressure plate are consistent with the length and width of the partition flow channel body. The area of the sealing pressure plate is matched with the area of the chip to be pressed.

9. The microfluidic washing system for biochemical synthesis of claim 3, wherein, The microfluidic cleaning system further comprises a gas-liquid pipe lifting device fixedly connected with the pressure plate assembly; The gas-liquid pipe lifting device comprises a bridge plate, a gas source conveying pipe, a waste liquid collecting pipe, a first hollow pipe containing the gas source conveying pipe, a second hollow pipe containing the waste liquid collecting pipe, and a lifting drag chain; The bridge plate is fixedly connected with the side of the equalizing plate; The first hollow pipe and the second hollow pipe are fixedly connected with the bridge plate; One end of the lifting drag chain is fixedly connected with the side of the support, and the other end is fixedly connected with the bridge plate.

10. A synthesis system for synthesis of a DNA chip, characterized by The microfluidic cleaning system for biochemical synthesis comprises a total control center and the pressure plate lifting device, the liquid path system and the total control center are signal connected.

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