Control device of reactor

Abstract

The invention discloses a control device of a reactor. The control device of the reactor comprises a liquid storage module, a liquid drop generation module and a control module, the liquid storage module is fixedly connected and conducted with the liquid drop generation module, and the control module is controllably communicated with the liquid drop generation module; the liquid storage module is used for storing a liquid sample and liquid drop generation oil, the liquid sample and the liquid drop generation oil are independently stored in the liquid storage module, the liquid drop generation module is at least used for enabling the liquid sample and the liquid drop generation oil to form sample liquid drops and containing the formed sample liquid drops, and the control module is at least used for providing controllable air pressure. When the control module is communicated with the liquid drop generation module, the air pressure can drive a liquid sample and liquid drop generation oil in the liquid storage module to enter the liquid drop generation module and form a sample liquid drop and enable the sample liquid drop to stay in the liquid drop generation module, and the liquid storage module and the liquid drop generation module are respectively provided with an observation structure capable of observing an internal structure.

Description

Technical Field

[0001] The invention particularly relates to a control device for a reactor, and belongs to the technical field of PCR test chips. Background Art

[0002] Currently, the droplet generation scheme based on microfluidic technology is widely used in digital PCR instruments. The principle of the droplet generation chip is to divide each PCR reaction system into tens of thousands of droplets through the oil-in-water method. Each droplet serves as an independent PCR reaction unit. After the amplification is completed, the fluorescent signal of each droplet is judged and the number of negative and positive droplets is counted, thereby realizing quantitative analysis of nucleic acids.

[0003] However, the production cost of the integrated chip on the market is relatively high, and the production process is also very complicated. In addition, since the oil phase and sample need to be added to the corresponding positions of the chip during the droplet generation process, and the droplets need to be transferred to a fixed area after generation, the entire instrument requires a relatively complex pipetting mechanism and control mechanism, which makes the cost of the digital PCR instrument very high.

[0004] Even so, due to the complex micro-pathways contained in the chip structure, dead volume is inevitable during the droplet collection or transfer process, resulting in droplet loss and reduced detection accuracy. In addition, after the droplets are transferred, it is usually difficult to keep them completely still. This means that during the signal acquisition process, when switching between different fluorescent signals, the position of the droplets in the collected images will shift, leading to errors in the analysis results. Summary of the invention

[0005] The main purpose of the present invention is to provide a control device for a reactor, thereby overcoming the shortcomings of the prior art.

[0006] In order to achieve the above-mentioned invention object, the technical solution adopted by the present invention includes: A first aspect of an embodiment of the present invention provides a control device for a reactor, comprising: a liquid storage module, a droplet generation module and a control module, wherein the liquid storage module is fixedly connected and conductive to the droplet generation module, and the control module is controllably connected to the droplet generation module; The liquid storage module is used to store liquid samples and droplet generation oil, and the liquid sample and droplet generation oil are stored separately in the liquid storage module. The droplet generation module is at least used to make the liquid sample and droplet generation oil form sample droplets and accommodate the formed sample droplets. The control module is at least used to provide controllable air pressure to change the air pressure difference between the control module and the liquid storage module. When the control module is connected to the droplet generation module, the air pressure difference can drive the liquid sample and droplet generation oil in the liquid storage module to enter the droplet generation module and form sample droplets, and make the sample droplets stay in the droplet generation module, wherein the liquid storage module and the droplet generation module both have an observation structure for visible internal structure.

[0007] Compared with the prior art, the advantages of the present invention include: A control device for a reactor provided in an embodiment of the present invention quantitatively controls a liquid sample participating in a reaction, thereby ensuring the stability of the reaction system and making the reaction result more reliable; The control device of a reactor provided by the embodiment of the present invention is easy to operate, reduces the operation steps of the experimenter, generates droplets stably, and greatly improves the detection efficiency; A control device for a reactor provided by an embodiment of the present invention has a simple structure, low component cost, simple instrument debugging, and can be stably produced in batches. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0009] Figure 1 It is a schematic diagram of the overall structure of a control device for a reactor provided in a typical implementation case of the present invention; Figure 2 It is a schematic diagram of the overall structure after the liquid storage module and the droplet generation / collection module are assembled in a typical implementation case of the present invention; Figure 3 It is a schematic diagram of the explosion structure of a liquid storage module in a typical implementation case of the present invention; Figure 4 It is a schematic diagram of the internal structure of a liquid storage module in a typical implementation case of the present invention; Figure 5 It is a schematic diagram of the overall structure of a liquid storage module in a typical implementation case of the present invention; Figure 6Schematic diagram of the overall structure of a droplet generation / collection module in a typical implementation case of the present invention; Figure 7 It is a schematic diagram of the internal structure of a liquid storage module in a typical implementation case of the present invention; Figure 8a is a photograph of sample droplets generated when the pressure fluctuation in the gas storage bottle is greater than 2 kPa in a typical implementation case of the present invention; Figure 8b This is a photograph of sample droplets generated when the pressure fluctuation in the gas cylinder is within 2 kPa in a typical implementation case of the present invention. DETAILED DESCRIPTION

[0010] In view of the deficiencies in the prior art, the inventor of this case has proposed the technical solution of the present invention after long-term research and extensive practice. The technical solution, its implementation process and principle will be further explained as follows.

[0011] A first aspect of an embodiment of the present invention provides a control device for a reactor, comprising: a liquid storage module, a droplet generation module and a control module, wherein the liquid storage module is fixedly connected and conductive to the droplet generation module, and the control module is controllably connected to the droplet generation module; The liquid storage module is used to store liquid samples and droplet generation oil, and the liquid sample and droplet generation oil are stored separately in the liquid storage module. The droplet generation module is at least used to make the liquid sample and droplet generation oil form sample droplets and accommodate the formed sample droplets. The control module is at least used to provide controllable air pressure to change the air pressure difference between the control module and the liquid storage module. When the control module is connected to the droplet generation module, the air pressure difference can drive the liquid sample and droplet generation oil in the liquid storage module to enter the droplet generation module and form sample droplets, and make the sample droplets stay in the droplet generation module, wherein the liquid storage module and the droplet generation module both have an observation structure for visible internal structure.

[0012] Further, the liquid storage module has a first storage cavity, a second storage cavity, a first liquid adding port, a second liquid adding port, a first liquid outlet, and a second liquid outlet, the first liquid adding port and the first liquid outlet are connected to the first storage cavity, the second liquid adding port and the second liquid outlet are connected to the second storage cavity, the first storage cavity is used to store liquid samples, the second storage cavity is used to store droplet generation oil, and the surface of the liquid storage module is also covered with a sealing film, and the sealing film at least covers and seals the first liquid adding port and the second liquid adding port; The droplet generation module is fixedly matched with the liquid storage module. The droplet generation module has a droplet generation microfluidic channel, a droplet observation chamber, a negative pressure connecting channel, a first liquid inlet interface, a second liquid inlet interface and a negative pressure connecting port. The first liquid inlet interface and the second liquid inlet interface are respectively connected to the droplet generation microfluidic channel, and the first liquid inlet interface and the second liquid inlet interface are also respectively corresponding to and connected with the first liquid outlet and the second liquid outlet. The droplet generation microfluidic channel is also connected to the droplet observation chamber, and the droplet observation chamber is connected to the negative pressure connecting channel, and the negative pressure connecting channel is connected to the negative pressure connecting port. A sealing rubber plug is arranged in the negative pressure connecting port, and the sealing rubber plug completely seals the negative pressure connecting port, and the sealing rubber plug can be pierced.

[0013] Furthermore, the liquid storage module and the droplet generation module are both transparent components.

[0014] Furthermore, the liquid storage module includes a liquid storage plate and a chip connecting plate, the liquid storage plate and the chip connecting plate are fixed and sealed together, the first storage cavity and the second storage cavity are arranged between the liquid storage plate and the chip connecting plate, the liquid storage plate and the chip connecting plate jointly enclose the first storage cavity and the second storage cavity, the first liquid adding port, the second liquid adding port, the first liquid outlet, and the second liquid outlet are arranged on the chip connecting plate, and the droplet generation module is fixedly matched with the chip connecting plate.

[0015] Furthermore, a connecting slot is also provided on the chip connecting board, the first liquid outlet and the second liquid outlet are arranged at the bottom of the connecting slot, and a part of the droplet generating module where the first liquid inlet interface and the second liquid inlet interface are located is embedded in the connecting slot.

[0016] Furthermore, a sealing ring is provided between the droplet generation module and the groove wall of the connecting groove.

[0017] Furthermore, a buckle structure is provided on the groove wall of the connecting groove and the droplet generating module, and the droplet generating module is fixedly connected to the chip connecting plate through the buckle structure.

[0018] Furthermore, the droplet generation port at the end of the droplet generation microfluidic channel is directly connected to the droplet observation chamber, the negative pressure connection port at the head end of the negative pressure connection channel is directly connected to the droplet observation chamber, and the droplet generation port and the negative pressure connection port are respectively arranged at both ends of a diagonal line of the droplet observation chamber.

[0019] Furthermore, the droplet generation module includes an upper chip and a bottom chip, and the upper chip and the bottom chip are stacked and fixedly combined as a whole, wherein the upper chip is provided with a droplet generation microfluidic groove, and the bottom chip is provided with a droplet observation cavity groove and a negative pressure connecting channel groove, the droplet generation microfluidic groove and the bottom chip are combined to form the droplet generation microfluidic channel, the droplet observation cavity groove, the negative pressure connecting channel groove and the upper chip are combined to form the droplet observation cavity and the negative pressure connecting channel, and the first liquid inlet interface, the second liquid inlet interface and the negative pressure connection port are arranged on the bottom chip.

[0020] Furthermore, the control module includes an air extraction needle, a gas storage bottle, a peristaltic pump, a first solenoid valve, a second solenoid valve and a first filter device, the air extraction needle, the first solenoid valve and the gas storage bottle are connected in sequence via a first gas pipeline, the gas storage bottle and the peristaltic pump are connected via a second gas pipeline, the first solenoid valve, the first filter device and the second solenoid valve are connected in sequence via a third gas pipeline, the first solenoid valve is a two-position three-way solenoid valve, and the second solenoid valve is a two-position two-way solenoid valve; the air extraction needle, the first solenoid valve, the gas storage bottle and the peristaltic pump are configured to form a first gas passage, the air extraction needle, the first solenoid valve, the first filter device and the second solenoid valve are configured to form a second gas passage, and the tail end of the second gas passage is connected to a normal pressure environment.

[0021] In a more specific embodiment, the control device of the reactor also includes: a pressure sensor and a controller, the controller is connected to the pressure sensor and the peristaltic pump, the pressure sensor is used to monitor the pressure in the gas storage bottle, and the controller is at least used to adjust the working state of the peristaltic pump.

[0022] Furthermore, the controller is also connected to the first solenoid valve and the second solenoid valve, and the controller is also used to adjust the working state of the first solenoid valve and the second solenoid valve.

[0023] In a more specific embodiment, the control device of the reactor further includes: a second filtering device, and the second filtering device is connected to the gas outlet of the peristaltic pump.

[0024] The technical solution, its implementation process and principles, etc. will be further explained below in conjunction with the accompanying drawings and specific implementation cases. Unless otherwise specified, the sealing plug, pressure-sensitive membrane, solenoid valve (two-position three-way / two-position two-way solenoid valve), peristaltic pump, filter device, pressure sensor, gas storage bottle, vacuum needle, controller and its control system, circuit board / circuit connection structure, etc. used in the embodiments of the present invention may all be known in the art and may be commercially available, and their specific structures or product models are not limited herein.

[0025] In a typical implementation case, please refer to Figure 1 A control device for a reactor comprises a liquid storage module 100, a droplet generation module 200 and a control module, wherein the liquid storage module 100 is fixedly connected and conducted with the droplet generation module 200, and the control module is controllably connected with the droplet generation module 200; the liquid storage module 100 is used to store a liquid sample and a droplet generation oil, wherein the liquid sample and the droplet generation oil are stored separately in the liquid storage module 100, the droplet generation module 200 is at least used to make the liquid sample and the droplet generation oil form sample droplets and to accommodate the formed sample droplets, and the control module is at least used to provide a controllable gas pressure to change The air pressure difference between the control module and the liquid storage module 100, when the control module is connected to the droplet generation module 200, can drive the liquid sample and droplet generation oil in the liquid storage module 100 into the droplet generation module 200 and form sample droplets, and make the sample droplets stay in the droplet generation module 200, wherein the liquid storage module 100 and the droplet generation module 200 both have an observation structure of visible internal structure, through which the liquid sample, droplet generation oil, sample droplet morphology and position in the liquid storage module 100 and the droplet generation module 200 can be visually observed.

[0026] The specific structures of the liquid storage module 100, the droplet generation module 200 and the control module and their configuration structures with each other will be specifically introduced as follows.

[0027] For details, please refer to Figure 1-Figure 7 The liquid storage module 100 and the droplet generation module 200 are detachably connected or fixedly combined as one, and the liquid storage module 100 has a first storage chamber 111, a second storage chamber 112, a first liquid addition port 121, a second liquid addition port 122, a first liquid outlet 123, and a second liquid outlet 124. The first storage chamber 111 is used to store liquid samples, and the second storage chamber 112 is used to store droplet generation oil. The first liquid addition port 121 and the first liquid outlet 123 are in communication with the first storage chamber 111, and the second liquid addition port 122 and the second liquid outlet 124 are in communication with the second storage chamber 112; The droplet generation module 200 has a droplet generation microchannel 203, a droplet observation chamber 204, a negative pressure connection channel 205, a first liquid inlet interface 201, a second liquid inlet interface 202 and a negative pressure connection port 206. The first liquid inlet interface 201 and the second liquid inlet interface 202 correspond to and are connected with the first liquid outlet 123 and the second liquid outlet 124 respectively. The first liquid inlet interface 201 and the second liquid inlet interface 202 are also connected with the droplet generation microchannel 203 respectively. The droplet generation microchannel 203 is also connected with the droplet observation chamber 204. The droplet observation chamber 204 is connected with the negative pressure connection channel 205. The negative pressure connection channel 205 is connected with the negative pressure connection port 206. A sealing rubber plug 207 is arranged in the negative pressure connection port 206, and the sealing rubber plug 207 completely seals the negative pressure connection port 206. The control module includes an air extraction needle 401, a gas storage bottle 403, a peristaltic pump 406, a first solenoid valve 402, a second solenoid valve 405 and a first filter device 404. The air extraction needle 401, the first solenoid valve 402 and the gas storage bottle 403 are connected in sequence through a first air guide line, the gas storage bottle 403 and the peristaltic pump 406 are connected in sequence through a second air guide line, the first solenoid valve 402, the first filter device 404 and the second solenoid valve 405 are connected in sequence through a third air guide line, the first solenoid valve 402 is a two-position three-way solenoid valve, and the second The solenoid valve 405 is a two-position, two-way solenoid valve; the vacuum needle 401, the first solenoid valve 402, the gas storage bottle 403, and the peristaltic pump 406 are configured to form a first gas passage, and the vacuum needle 401, the first solenoid valve 402, the first filter device 404, and the second solenoid valve 405 are configured to form a second gas passage. The tail end of the second gas passage is connected to a normal pressure environment, and the control module is connected to the negative pressure connection channel 205 inside the droplet generation module 200 by piercing the sealing plug 207 of the droplet generation module 200 through the vacuum needle 401.

[0028] Specifically, the first solenoid valve 402 and the second solenoid valve 405 can prevent the first gas passage and the second gas passage from being turned on at the same time. When the first gas passage is in a turned-on state, the air pressure provided by the control module is negative pressure, the interior of the liquid storage module 100 is at normal pressure, and the pressure difference between the control module and the liquid storage module 100 drives the liquid sample and droplet generation oil in the liquid storage module 100 to flow into the droplet generation module 200, enter the droplet generation module 200 and form sample droplets; when the second gas passage is in a turned-on state, the air pressure provided by the control module is normal pressure, the pressure difference between the liquid storage module 100 and the control module is 0, and the liquid medium (including liquid sample, droplet generation oil, sample droplets) in the liquid storage module 100 and the droplet generation module 200 remains stationary.

[0029] Specifically, the control module further includes a pressure sensor 407 and a controller 408, the controller 408 is connected to the pressure sensor 407 and the peristaltic pump 406, the pressure sensor 407 is used to monitor the pressure in the gas cylinder 403, the controller 408 is at least used to adjust the working state of the peristaltic pump 406, and the controller 408 is also connected to the first solenoid valve 402 and the second solenoid valve 405, and the controller 408 is also used to adjust the working state of the first solenoid valve 402 and the second solenoid valve 405. More specifically, the control module further includes a second filter device, and the second filter device is connected to the gas outlet of the peristaltic pump 406. Exemplarily, the first solenoid valve 402 is a two-position three-way solenoid valve, the second solenoid valve 405 is a two-position two-way solenoid valve, and the first filter device 404 and the second filter device can be filters known in the art, and their specific models are not limited here.

[0030] Specifically, the first storage chamber 111 and the second storage chamber 112 in the liquid storage module 100 are arranged inside the liquid storage module 100, the first storage chamber 111 is used to store liquid samples, so the first storage chamber 111 can also be called a sample storage chamber, the second storage chamber 112 is used to store droplet generation oil, so the second storage chamber 112 can also be called an oil storage chamber; the first liquid adding port 121, the second liquid adding port 122, the first liquid outlet 123, and the second liquid outlet 124 are arranged on the surface of the liquid storage module 100, preferably on the same side, wherein the first liquid adding port 121 is used to inject / add liquid samples into the first storage chamber 111, the first liquid outlet 123 can allow the liquid sample in the first storage chamber 111 to flow out, the second liquid adding port 122 is used to inject / add droplet generation oil into the second storage chamber 112, and the second liquid outlet 124 can allow the droplet generation oil in the second storage chamber 112 to flow out.

[0031] It should be noted that the first liquid adding port 121 and the first liquid outlet 123 can be directly connected to the first storage chamber 111, or they can be connected through the flow channel set inside the liquid storage module 100. Correspondingly, the second liquid adding port 122 and the second liquid outlet 124 can be directly connected to the second storage chamber 112, or they can be connected through the flow channel set inside the liquid storage module 100. The observation structure of the liquid storage module 100 can be a transparent observation window corresponding to the first storage chamber 111 and the second storage chamber 112. When there is a flow channel, the observation structure of the liquid storage module 100 can be a transparent observation window corresponding to the first storage chamber 111, the second storage chamber 112, and the flow channel inside the liquid storage module 100. Through the observation structure, the liquid sample in the first storage chamber 111 and the residual amount, outflow amount, flow state, etc. of the droplet generation oil in the second storage chamber 112 can be observed from the outside. Of course, the liquid storage module 100 can also be a transparent visual structure as a whole. For example, the liquid storage module 100 can be a transparent PC (polycarbonate) component. In addition, there is no specific limitation on the specific structure, shape and volume of the first storage chamber 111, the second storage chamber 112, the first liquid filling port 121, the second liquid filling port 122, the first liquid outlet 123 and the second liquid outlet 124, and they can be set according to specific needs.

[0032] For details, please refer to Figure 3 , Figure 4 and Figure 5 , Figure 3 and Figure 5 The liquid storage module 100 shown in the figure includes a liquid storage plate 110 and a chip connection plate 120, the liquid storage plate 110 and the chip connection plate 120 are fixed and sealed together, the droplet generation module 200 is fixedly matched with the chip connection plate 120, the first storage cavity 111 and the second storage cavity 112 are arranged between the liquid storage plate 110 and the chip connection plate 120, the liquid storage plate 110 and the chip connection plate 120 are jointly enclosed to form the first storage cavity 111 and the second storage cavity 112, and the first liquid filling port 121, the second liquid filling port 122, the first liquid outlet 123, and the second liquid outlet 124 are arranged on the chip connection plate 120. Exemplarily, the liquid storage plate 110 and the chip connection plate 120 can be fixedly combined into one by ultrasonic welding bonding, chemical corrosion bonding or hot pressing bonding, and of course, the liquid storage module 100 can also be integrally processed and formed by 3D printing technology or injection molding technology. Specifically, the liquid reservoir plate 110 and the chip connection plate 120 may both be transparent components. For example, the liquid reservoir plate 110 and the chip connection plate 120 may be transparent PC (polycarbonate) components.

[0033] When the liquid storage module 100 is formed by combining the liquid storage plate 110 and the chip connecting plate 120, the first storage cavity 111, the second storage cavity 112 and the flow channel inside the liquid storage module 100 are enclosed by the two. The specific form is not limited to: the surfaces of the liquid storage plate 110 and the chip connecting plate 120 have multiple functional grooves, and the multiple functional grooves correspond to the first storage cavity 111, the second storage cavity 112 and the flow channel inside the liquid storage module 100 respectively. The liquid storage plate 110 and the chip connecting plate 120 are fixedly combined into one, and the functional grooves of the two are correspondingly combined to form the first storage cavity 111, the second storage cavity 112 and The flow channel inside the liquid storage module 100, of course, the surface of one of the liquid storage plate 110 and the chip connecting plate 120 has multiple functional grooves, and the surface of the other is flat and smooth, and the multiple functional grooves respectively correspond to the first storage cavity 111, the second storage cavity 112 and the flow channel inside the liquid storage module 100, the liquid storage plate 110 and the chip connecting plate 120 are fixedly combined as a whole, and the functional grooves of one cooperate with the smooth surface of the other to form the first storage cavity 111, the second storage cavity 112 and the flow channel inside the liquid storage module 100, which are all known in the art and can be easily implemented, and no further explanation will be given here.

[0034] Specifically, when droplet generation is not performed, the liquid sample and the droplet generation oil are encapsulated inside the overall structure of the combination of the liquid storage module 100 and the droplet generation module 200, and the liquid sample and the droplet generation oil are stationary inside the overall structure of the combination of the liquid storage module 100 and the droplet generation module 200. Therefore, the first liquid adding port 121 and the second liquid adding port 122 need to be blocked. Specifically, a sealing film 300 can be covered on the surface of the first liquid adding port 121 and the second liquid adding port 122. The sealing film 300 can be attached to the chip connecting board 120 where the first liquid adding port 121 and the second liquid adding port 122 are located. When droplet generation and transfer need to be performed, the sealing film 300 can be torn off or punctured to make the first liquid adding port 121 and the second liquid adding port 122 conductive to the normal pressure environment.

[0035] Specifically, the chip connection board 120 is also provided with a connection card slot matching the droplet generation module 200, the first liquid outlet 123 and the second liquid outlet 124 are arranged at the bottom of the connection card slot, and a part of the droplet generation module 200 where the first liquid inlet interface 201 and the second liquid inlet interface 202 are located is embedded in the connection card slot, and through the connection buckle, the droplet generation module 200 can be fixedly connected with the liquid storage module 100, and at the same time, the droplet generation module 200 and the liquid storage module 100 are connected (by the first liquid outlet 123 and the second liquid outlet 124 being arranged at the bottom of the connection card slot, and the first liquid inlet interface 201 and the second liquid inlet interface 202 being arranged in the part of the droplet generation / collection module embedded in the connection card slot). Specifically, in order to further improve the tightness of the connection between the droplet generation module 200 and the liquid storage module 100, a sealing ring (such as a rubber O-ring, etc.) is also arranged between the droplet generation module 200 and the groove wall of the connection card slot. More specifically, in order to improve the stability of the fixed connection structure between the droplet generation module 200 and the liquid storage module 100, a snap structure is also provided on the slot wall connecting the card slot and the droplet generation module 200, and the droplet generation module 200 and the chip connecting plate 120 are fixedly connected by the snap structure. The specific snap structure can adopt various snap structures known in the art, and no specific limitation is made here.

[0036] For details, please refer to Figure 6 and Figure 7 The droplet generation port at the end of the droplet generation microchannel 203 is directly connected to the droplet observation chamber 204, and the negative pressure communication port at the head end of the negative pressure connection channel 205 is directly connected to the droplet observation chamber 204. The droplet generation port and the negative pressure communication port are respectively arranged at the two ends of a diagonal line of the droplet observation chamber 204.

[0037] Specifically, the sealing plug 207 provided in the negative pressure connection port 206 may be a silicone sealing plug. The sealing plug 207 plays a sealing role to prevent the oil phase droplet generation oil and the water phase liquid sample from flowing into the droplet generation module 200 in advance. After the air extraction needle 401 is inserted into the sealing plug 207, negative pressure is provided for sample droplet generation through the negative pressure connection channel 205. After the droplet generation oil and the liquid sample pass through the droplet generation microchannel 203, the formed sample droplets will directly enter the entire droplet observation chamber 204. The droplet generation port and the negative pressure connection port are respectively arranged at the diagonal positions of the droplet observation chamber 204, so that the sample droplets fill the entire droplet observation chamber 204, wherein the depth of the droplet observation chamber 204 is less than or equal to 10% of the diameter of the sample droplets. At the same time, damping is arranged in the negative pressure connection channel 205 (the damping is mainly provided by the circuitous wave structure of the negative pressure connection channel 205) to increase the resistance to the outflow of the sample droplets.

[0038] Specifically, the droplet generation module 200 can also be formed by an integrated process of 3D printing or injection molding. However, in view of the high difficulty of injection molding of the droplet generation microchannel 203 inside the droplet generation module 200, the droplet generation module 200 can be formed by a fixed assembly of an upper chip 220 and a bottom chip 210. Specifically, the upper chip 220 and the bottom chip 210 are stacked and fixedly combined into one, wherein the upper chip 220 is provided with a droplet generation microchannel 203. The flow channel 203 groove, the bottom chip 210 is provided with a droplet observation chamber 204 groove and a negative pressure connecting channel 205 groove, the droplet generation microfluidic channel 203 groove and the bottom chip 210 are enclosed to form a droplet generation microfluidic channel 203, the droplet observation chamber 204 groove, the negative pressure connecting channel 205 groove and the upper chip 220 are enclosed to form a droplet observation chamber 204 and a negative pressure connecting channel 205, and the first liquid inlet interface 201, the second liquid inlet interface 202 and the negative pressure connection port 206 are provided on the bottom chip 210. Through the split design, the upper chip 220 and the bottom chip 210 are fixedly assembled, which can greatly reduce the processing difficulty and greatly improve the production yield rate. Specifically, the upper chip 220 and the bottom chip 210 are both transparent components, and the droplet generation microchannel 203, the droplet observation chamber 204, and the negative pressure connection channel 205 inside the droplet generation module 200 can be directly observed from the outside. Exemplarily, the upper chip 220 and the bottom chip 210 can be transparent COC (cyclic olefin copolymer) components, etc., and the upper chip 220 and the bottom chip 210 can be fixed together by chemical bonding or the like.

[0039] In a typical implementation case, the specific operation process of generating and collecting droplets using a control device of a reactor may include the following process: 1) Provide Figure 1-Figure 7 A control device for a reactor is shown in the figure, wherein the liquid sample and the droplet generation oil are respectively injected into the first storage chamber 111 and the second storage chamber 112 through the first liquid injection port 121 and the second liquid injection port 122 on the liquid storage module 100, and then a sealing film 300 (i.e., a pressure-sensitive film) is attached to seal the liquid sample and the droplet generation oil in the liquid storage module 100. Of course, the liquid sample and the droplet generation oil can also be injected into the liquid storage module 100 in advance; (2) A negative pressure is generated in the gas storage bottle 403 through the peristaltic pump 406, and the pressure in the liquid storage bottle is monitored in real time through the pressure sensor 407. The controller 408 reads the value of the pressure sensor 407 in real time, and adjusts the start and stop, forward and reverse direction, and speed of the peristaltic pump 406 in real time according to the feedback pressure value and the PID algorithm (which are all numerical control methods known in the art), so that the control module can output a stable pressure; (3) Using a puncture needle, puncture the portion of the sealing film 300 of the liquid storage module 100 corresponding to the first liquid adding port 121 and the second liquid adding port 122, so that the first liquid adding port 121 and the second liquid adding port 122 are connected to the atmosphere; (4) Insert the suction needle 401 into the silicone sealing plug of the droplet generation module 200. When the negative pressure of the gas storage bottle 403 reaches the set value, open the first three solenoid valves (the first solenoid valve 402 is powered on, the suction needle 401 is connected to the peristaltic pump 406, the first solenoid valve 402 is powered off, and the suction needle 401 is connected to the waste liquid bottle), so that the gas storage bottle 403 is connected to the droplet generation module 200, thereby generating sample droplets; the rapid stillness and sealing of the droplets after transfer are achieved through the following technical solutions: (5) When the sample droplet generation time reaches the set value (the setting of the generation time can be determined according to the sample amount), the state of the first solenoid valve 402 is switched, so that the pipeline behind the suction needle 401 is connected to the first filter device 404, and the second solenoid valve 405 is opened at the same time, so that the droplet generation module 200 is connected to the atmosphere, so that the negative pressure provided by the control module instantly becomes 0, and the sample droplets lose the power to move forward; (6) The second solenoid valve 405 is closed. At this time, the droplet observation chamber 204 in the droplet generation module 200 is isolated from the atmosphere, and the droplets are completely sealed in the droplet observation chamber 204 for subsequent amplification and observation.

[0040] It should be noted that as the droplet generation proceeds, the pressure in the gas storage bottle will gradually decrease. In order to ensure the stability of droplet generation, the pressure needs to be stably controlled within the accuracy range of ±1kPa. If the pressure fluctuates greatly, the size of the generated droplets will be inconsistent. Figure 8a , Figure 8b As shown, Figure 8a This is a photo of sample droplets generated when the pressure fluctuation in the gas cylinder is greater than 2kPa. Figure 8b This is a photo of sample droplets generated when the pressure fluctuation in the gas cylinder is within 2kPa. The pressure of the gas cylinder can be controlled by reading the value of the pressure sensor and adjusting the speed and number of revolutions of the peristaltic pump in real time through the PID algorithm. The formula for PID algorithm adjustment is as follows:

[0041] The first term in the brackets is the proportional term, the second term is the integral term, the third term is the differential term, and the first term is just a coefficient. In many cases, it only needs to be used in discrete time, so the control can be transformed into:

[0042] These coefficients can be determined by experimental methods. Specifically, the droplet generation time required for different volumes of PCR reaction liquid is obtained through experimental tests, so that the generated droplets can just fill the entire observation cavity, and the first solenoid valve and the second solenoid valve are switched at the same time, so that the negative pressure connection port of the droplet generation module is connected to the atmosphere. At this time, the droplets in the droplet observation cavity of the droplet generation module lose their forward momentum, that is, they will stop immediately, and then after waiting for a certain period of time, the second solenoid valve is closed, so that the droplets in the droplet observation cavity are isolated from the atmosphere and in a sealed state, and then subsequent amplification and photo processing can be carried out.

[0043] A control device for a reactor provided by an embodiment of the present invention integrates a liquid storage structure, a droplet generation structure and an observation structure together. The droplet generation oil can be pre-packaged in the liquid storage module, so that the entire device does not need to design a load-replenishing mechanism for the droplet generation oil. In addition, a control device for a reactor provided by an embodiment of the present invention replaces a liquid transfer device such as a syringe pump with a low-cost peristaltic pump.

[0044] The control device of a reactor provided by an embodiment of the present invention has a simple structure and a simple production process. Liquid samples and droplet generation oil can be pre-installed in advance, thereby avoiding pollution of the operating space environment, reducing false positives, and improving detection accuracy.

[0045] A control device for a reactor provided in an embodiment of the present invention quantitatively controls the liquid samples participating in the reaction, thereby ensuring the stability of the reaction system and reliable results; and, the control device for a reactor provided in an embodiment of the present invention is simple to operate, reduces the operating steps of the experimenter, generates stable droplets, and greatly improves the detection efficiency; in addition, the control device for a reactor provided in an embodiment of the present invention has a simple structure, low component cost, simple instrument debugging, and can be produced stably in batches.

[0046] It should be understood that the above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A control device for a reactor, characterized in that: include: A liquid storage module, a droplet generation module and a control module, wherein the liquid storage module is fixedly connected and conductive to the droplet generation module, and the control module is controllably connected to the droplet generation module; The liquid storage module is used to store liquid samples and droplet generation oil, and the liquid sample and droplet generation oil are stored separately in the liquid storage module. The droplet generation module is at least used to make the liquid sample and droplet generation oil form sample droplets and accommodate the formed sample droplets. The control module is at least used to provide controllable air pressure to change the air pressure difference between the control module and the liquid storage module. When the control module is connected to the droplet generation module, the air pressure difference can drive the liquid sample and droplet generation oil in the liquid storage module to enter the droplet generation module and form sample droplets, and make the sample droplets stay in the droplet generation module, wherein the liquid storage module and the droplet generation module both have an observation structure for visible internal structure.

2. The control device of the reactor according to claim 1, characterized in that: The liquid storage module comprises a first storage cavity, a second storage cavity, a first liquid adding port, a second liquid adding port, a first liquid outlet, and a second liquid outlet, wherein the first liquid adding port and the first liquid outlet are in conduction with the first storage cavity, and the second liquid adding port and the second liquid outlet are in conduction with the second storage cavity, wherein the first storage cavity is used to store liquid samples, and the second storage cavity is used to store droplet generation oil, and a sealing film is further provided on the surface of the liquid storage module, and the sealing film at least covers and seals the first liquid adding port and the second liquid adding port; The droplet generation module is fixedly matched with the liquid storage module, and the droplet generation module has a droplet generation microfluidic channel, a droplet observation chamber, a negative pressure connection channel, a first liquid inlet interface, a second liquid inlet interface and a negative pressure connection port, the first liquid inlet interface and the second liquid inlet interface are respectively connected to the droplet generation microfluidic channel, the first liquid inlet interface and the second liquid inlet interface are also respectively corresponding to and connected with the first liquid outlet and the second liquid outlet, the droplet generation microfluidic channel is also connected to the droplet observation chamber, the droplet observation chamber is connected to the negative pressure connection channel, the negative pressure connection channel is connected to the negative pressure connection port, a sealing rubber plug is arranged in the negative pressure connection port, the sealing rubber plug completely seals the negative pressure connection port, and the sealing rubber plug can be pierced; And / or, the liquid storage module and the droplet generation module are both transparent components.

3. The control device of the reactor according to claim 2, characterized in that: The liquid storage module includes a liquid storage plate and a chip connecting plate, the liquid storage plate and the chip connecting plate are fixed and sealed together, the first storage cavity and the second storage cavity are arranged between the liquid storage plate and the chip connecting plate, the liquid storage plate and the chip connecting plate jointly enclose the first storage cavity and the second storage cavity, the first liquid adding port, the second liquid adding port, the first liquid outlet, and the second liquid outlet are arranged on the chip connecting plate, and the droplet generation module is fixedly matched with the chip connecting plate.

4. The control device of the reactor according to claim 3, characterized in that: The chip connection board is further provided with a connection slot, the first liquid outlet and the second liquid outlet are arranged at the bottom of the connection slot, and a part of the droplet generation module where the first liquid inlet interface and the second liquid inlet interface are located is embedded in the connection slot; And / or, a sealing ring is further provided between the droplet generation module and the groove wall of the connecting groove; And / or, a buckle structure is further provided on the groove wall of the connecting groove and the droplet generating module, and the droplet generating module is fixedly connected to the chip connecting plate via the buckle structure.

5. The control device of the reactor according to claim 2, characterized in that: The droplet generation port at the end of the droplet generation microfluidic channel is directly connected to the droplet observation chamber, the negative pressure communication port at the head end of the negative pressure connection channel is directly connected to the droplet observation chamber, and the droplet generation port and the negative pressure communication port are respectively arranged at the two ends of a diagonal line of the droplet observation chamber.

6. The control device of the reactor according to claim 2 or 5, characterized in that: The droplet generation module includes an upper chip and a bottom chip, which are stacked and fixedly combined as a whole, wherein the upper chip is provided with a droplet generation microfluidic groove, and the bottom chip is provided with a droplet observation cavity groove and a negative pressure connecting channel groove, the droplet generation microfluidic groove and the bottom chip are combined to form the droplet generation microfluidic channel, the droplet observation cavity groove, the negative pressure connecting channel groove and the upper chip are combined to form the droplet observation cavity and the negative pressure connecting channel, and the first liquid inlet interface, the second liquid inlet interface and the negative pressure connecting port are arranged on the bottom chip.

7. The control device of the reactor according to claim 1, characterized in that: The control module includes an air extraction needle, a gas storage bottle, a peristaltic pump, a first solenoid valve, a second solenoid valve and a first filter device. The air extraction needle, the first solenoid valve, and the gas storage bottle are connected in sequence via a first gas guiding pipeline, the gas storage bottle and the peristaltic pump are connected via a second gas guiding pipeline, the first solenoid valve, the first filter device, and the second solenoid valve are connected in sequence via a third gas guiding pipeline, the first solenoid valve is a two-position three-way solenoid valve, and the second solenoid valve is a two-position two-way solenoid valve; the air extraction needle, the first solenoid valve, the gas storage bottle, and the peristaltic pump are configured to form a first gas passage, the air extraction needle, the first solenoid valve, the first filter device, and the second solenoid valve are configured to form a second gas passage, and the tail end of the second gas passage is connected to a normal pressure environment.

8. The control device of the reactor according to claim 7, characterized in that: Also includes: A pressure sensor and a controller, wherein the controller is connected to the pressure sensor and the peristaltic pump, the pressure sensor is used to monitor the pressure in the gas storage bottle, and the controller is at least used to adjust the working state of the peristaltic pump.

9. The control device of the reactor according to claim 8, characterized in that: The controller is also connected to the first solenoid valve and the second solenoid valve, and is also used to adjust the working states of the first solenoid valve and the second solenoid valve.

10. The control device of the reactor according to claim 7, characterized in that: Also includes: A second filtering device is connected to the gas outlet of the peristaltic pump.

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