Microfluidic Controlled CSTR Reaction and Detection System
By designing a microfluidic control CSTR reaction and detection system, the existing CSTR reactors have been solved, and the problem of rough design and monotonous detection methods are achieved when studying biochemical-related oscillations is realized, and the microfluidic control and photoperturbation experiments are met, which is high-quality and refined. development needs.
Patent Information
- Application Number
- CN201711440538.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2017-12-27
- Publication Date
- 2025-02-07
- Estimated Expiration
- 2037-12-27
AI Technical Summary
When studying biochemical-related life systems oscillating, the existing CSTR reactor has problems such as rough design, large size, monotonous detection methods, and inability to conduct microfluidic control and light disturbance experiments, which cannot meet the development trend of high-precision and fineness.
A microfluidic control CSTR reaction and detection system is designed, including a precision injection module, a CSTR module and a microfluidic detection window. It adopts a magnetic stirrer, an ultraviolet light source, a photointensity meter and a flow rate control module to realize microfluidic control, light disturbance and Multi-way controlled experiment.
A variety of experiments have been implemented, including indication, detection and microfluidic control, which meets the indication and detection needs of biochemical substance oscillation, improves experimental efficiency and accuracy, and saves reagents and costs.
Smart Images

Figure CN107991503B_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a micro-flow controlled CSTR reaction and detection system. Background Art
[0002] Since the discovery of chemical oscillation phenomena in large numbers in the last century, the study of nonlinear dynamics has become increasingly urgent. The research on nonlinear dynamics is manifested in two aspects: on the one hand, the study of nonlinear dynamics can explain many nonlinear phenomena in nature; on the other hand, the study of nonlinear dynamics can provide an important methodology for explaining life phenomena. From the early inorganic oscillation phenomena to the organic oscillations and biochemical oscillations discovered in recent years, the study of chemical oscillations is getting closer and closer to life phenomena. Due to the particularity of organic and biological substances, the methods for studying their nonlinear phenomena are also different from before. At first, people studied chemical oscillations in closed systems, such as beakers and measuring cylinders, but only single oscillation phenomena could be observed. The introduction of CSTR (continuous flow stir red tank reactor) in the 1970s has greatly developed the study of chemical oscillations. The most typical CSTR is a device for studying BZ reactions. Calomel-platinum electrodes, pH composite electrodes, temperature sensors, etc. are embedded in the CSTR to detect oscillation phenomena. However, whether in a closed system or a traditional CSTR, the equipment and methods for studying chemical oscillations are no longer suitable for the current study of biochemical-related life system oscillations, because the current CSTR equipment is too simple, crudely designed, large in size, and has a monotonous detection method. It cannot perform microfluidic control, cannot perform light perturbation experiments, cannot perform multiple groups of control experiments simultaneously, cannot meet the indication and detection of biochemical substance oscillations, and does not conform to the development trend of high-precision and refinement. Therefore, there is an urgent need to invent an innovative experimental device and experimental method.
[0003] Microfluidics refers to the science and technology involved in systems that use microchannels (tens to hundreds of microns in size) to process or manipulate tiny fluids (volumes from nanoliters to attoliters). It is an emerging interdisciplinary subject involving chemistry, fluid physics, microelectronics, new materials, biology, and biomedical engineering. Because of its miniaturization and integration, microfluidic devices are usually called microfluidic chips, also known as chip laboratories (LabonaChip) and micro-total analytical systems (micro-Total Analytical System). Microfluidics can achieve a series of micro-machining and micro-operations that are difficult to accomplish with conventional methods. At present, microfluidics is considered to have great development potential and broad application prospects in biomedical research. The greatest difficulty in realizing microfluidic control for CSTR lies in the design and production of this kind of tiny reaction device, and its production technology is a challenge. The traditional CSTR device used for chemical oscillation experiments is a single open reactor, and its stirring, reaction and detection processes are all carried out in an open reaction pool. Its defects are not only the above-mentioned inability to perform ultraviolet detection, dynamic light scattering detection, and the inability to add indicators separately, but also the following defects: its material is mostly optical glass with weak corrosion resistance and poor optical properties, and light perturbation experiments cannot be performed. The dimensions of the pipelines and various parts of the reaction device are too large, and microflow control cannot be performed. The phenomenon of reagent waste during use is very serious. Summary of the invention
[0004] The technical problem to be solved by the present invention is to provide a microfluidic controlled CSTR reaction and detection system, which can not only carry out a variety of experiments, but also perform indication, detection and microfluidic control.
[0005] In order to solve the above technical problems, the present invention adopts the following technical solutions:
[0006] The present invention provides a microfluidic controlled CSTR reaction and detection system, comprising:
[0007] Precision injection module: the precision injection module is a first precision injection pump whose number corresponds to the types of reaction reagents;
[0008] CSTR module: the CSTR module includes a magnetic stirrer and a first reaction tank arranged on the magnetic stirrer, the first reaction tank includes an inner tank and an outer tank, the outer tank is circumferentially arranged on the periphery of the inner tank, a covering plane is arranged on the top of the inner tank, a first channel for fluid circulation is arranged between the inner wall of the outer tank and the outer wall of the inner tank, and the first channel is a cavity structure; the side of the outer tank is provided with a first inlet that is the same in number as the first precision injection pump and is used to connect the inner tank and the outer tank, a second inlet for inputting fluid into the first channel, and a first outlet for outputting the fluid in the first channel, and the top or bottom of the inner tank is provided with a second outlet; and
[0009] Micro-flow detection window: The micro-flow detection window is a cubic structure, an optical second channel is arranged on one opposite side thereof, and a third inlet and a third outlet are arranged on the top thereof;
[0010] The first precision injection pump is connected to the first inlet, and the second outlet is connected to the third inlet via a first pipeline;
[0011] The height of the outer pool is greater than that of the inner pool, and the tops of the outer pool and the inner pool are covered with different optical surfaces or only the top of the inner pool is provided with an optical surface;
[0012] Or the tops of the outer pool and the inner pool are covered with the same optical surface.
[0013] As a further improvement of the present invention, it further comprises a flow rate control module, wherein the flow rate control module is a liquid mass flow controller; the second outlet is connected to the liquid mass flow controller inlet via a second pipeline;
[0014] The number of the first precision injection pumps is at least 2;
[0015] The inner pool is made of quartz material, and the outer pool is made of common optical glass except for the top part which is made of quartz material;
[0016] The outer size of the microfluidic detection window is close to or the same as that of the cuvette, and is covered with a black steel protective frame;
[0017] The second optical channel is made of quartz material with an internal optical path of 1 mm;
[0018] The first inlet, the second inlet, the first outlet and the second outlet are all connected with a hollow stainless steel tube or polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm;
[0019] The first pipe and the second pipe are both polytetrafluoroethylene pipes, and the inner diameter of the polytetrafluoroethylene pipe is 0.5 to 1 mm;
[0020] The fluid is water or an organic reagent, and the organic reagent is alcohol or oil.
[0021] As a further improvement of the present invention, the injection accuracy of the first precision injection pump reaches the level of picoliters per minute to milliliters per minute.
[0022] As a further improvement of the present invention, it also includes a microfluidic stirring module, which includes a microfluidic reaction chip and an adjustable voltage micro DC motor, a digital display DC motor speed regulator, a DC transformer and a non-contact speed meter, all of which are connected by electrical connection;
[0023] The microfluidic reaction chip is a second reaction pool, and the side of the second reaction pool is provided with a fourth inlet for connecting to the second outlet, a fifth inlet for connecting to the second precision injection pump, and a fourth outlet for connecting to the third inlet of the microfluidic detection window;
[0024] The CSTR module further comprises an ultraviolet light source, an adjustable height iron frame, and a light intensity meter provided with a detection head. The ultraviolet light source, the magnetic stirrer, and the light intensity meter are all provided on the adjustable height iron frame. When the tops of the outer pool and the inner pool are covered with the same optical surface, the optical surface is in the same height as the detection head.
[0025] The number of the second precision injection pump is one, and its structure is the same as that of the first precision injection pump, and it is connected to the fifth inlet through a third pipeline, and the third pipeline is a polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm;
[0026] The fluid is water or an organic reagent, and the organic reagent is alcohol or oil; the injection accuracy of the second precision injection pump reaches the level of picoliters per minute to milliliters per minute.
[0027] As a further improvement of the present invention: the microfluidic stirring module also includes a three-layer organic glass frame, the upper layer of the organic glass frame is arranged with a digital display DC motor speed regulator and a DC transformer, the middle layer is fixed with an adjustable voltage micro DC motor, and the bottom layer is fixed with a microfluidic reaction chip;
[0028] The fourth inlet, the fifth inlet and the fourth outlet are all connected with a hollow stainless steel tube or a polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm;
[0029] The height of the outer pool is greater than that of the inner pool, and a cavity is provided at the top of the inner pool and away from the top of the outer pool.
[0030] As a further improvement of the present invention: the digital display DC motor speed regulator includes a switch, a speed control knob, a speed display and a numerical control circuit board, and the motor speed is 0-1600 rpm.
[0031] As a further improvement of the present invention, it also includes a flow rate control module, a microfluidic stirring module and a third precision injection pump;
[0032] The number of the first precision injection pumps is 3, the number of the third precision injection pump is 1, and the structure thereof is the same as that of the first precision injection pump;
[0033] The CSTR module further comprises: an ultraviolet light source, an adjustable height iron stand and a light intensity meter provided with a probe; the tops of the outer pool and the inner pool are provided with the same optical surface or only the top of the inner pool is provided with an optical surface, and the top of the inner pool is provided with a cavity away from the top of the outer pool; the three first precision injection pumps are connected to the first inlet through a first pipeline; a magnetic stirrer is provided in the inner pool; and the magnetic stirrer is provided on the adjustable height iron stand;
[0034] The fluid is water or an organic reagent, and the organic reagent is oil or alcohol; the injection accuracy of the third precision injection pump reaches the level of picoliters per minute to milliliters per minute;
[0035] The flow rate control module is a liquid mass flow controller;
[0036] The microfluidic stirring module: The microfluidic stirring module includes a microfluidic reaction chip and an adjustable voltage micro DC motor, a digital display DC motor speed regulator, a DC transformer and a non-contact speed meter, all of which are connected by electrical connection; the microfluidic reaction chip is the third reaction pool, which has a cylindrical cavity structure; the third outlet is connected to a liquid collecting bottle; the adjustable voltage micro DC motor is provided with a chrome-plated iron stirring shovel, and the stirring shovel extends into the third reaction pool.
[0037] As a further improvement of the present invention, the optical surface is consistent with the probe height, the light intensity meter is fixed on the bottom end of the height-adjustable iron stand, the ultraviolet light source is fixed on the shelf of the height-adjustable iron stand; and the organic reagent is alcohol.
[0038] As a further improvement of the present invention, the volume of the inner pool is 5 μl-50 ml; the volume of the third reaction pool is 7-500 μl;
[0039] The first pipe is a polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm;
[0040] The digital display DC motor speed regulator comprises a switch, a speed regulating knob, a speed display and a numerical control circuit board, and the motor speed is 0-1600 rpm.
[0041] As a further improvement of the present invention: the inner pool is made of quartz material, and the outer pool except the optical surface is made of ordinary optical glass; the third reaction pool is made of quartz material, and its outer material is made of ordinary optical glass.
[0042] The optical channel and the microflow detection window are realized by modifying the cuvette, and its essence is still to play the role of the cuvette, that is, the ultraviolet light channel on the side of the cuvette.
[0043] The inner pool is made of all quartz, and the upper end of the outer pool has a quartz optical surface of the same size as the upper end of the inner pool. Except for the upper end, the other materials of the outer pool are made of ordinary optical glass. The reason is that ordinary optical glass is not transparent to ultraviolet light, while quartz can pass ultraviolet light. Therefore, the quartz optical surface of the outer pool can pass ultraviolet light for ultraviolet interference experiments. The inner pool of the CSTR module is made of quartz, and the upper and lower ends of the inner pool are sealed with quartz. The outer pool is sealed with ordinary glass except for the top of quartz. In this way, a CSTR reactor with a special optical surface is constructed. Since the bottom is facing downward and is not exposed to light, and the ordinary optical glass on the side is not transparent to ultraviolet light, only the quartz surface at the top can pass ultraviolet light, and the rest of the device is not transparent to ultraviolet light. The volume of the CSTR module can range from tens of microliters to hundreds of milliliters according to the requirements of a certain experiment. The connecting pipes of the first inlet, the second inlet, the first outlet and the second outlet of the CSTR module, and the fourth inlet, the fourth outlet and the fifth outlet of the microfluidic reaction chip are all made of stainless steel pipes. The use of stainless steel pipes is relatively easy to implement in the production, but as a preferred solution of the present invention, polytetrafluoroethylene pipes are used instead of stainless steel pipes. The advantage is that when doing kinetic experiments, the catalytic effect of the metal in the stainless steel pipe on the reaction can be avoided.
[0044] The volume of the microfluidic reaction chip can be made in a range of sizes from a few microliters to tens of milliliters according to the requirements of a certain experiment. The liquid mass flow controller can control the flow rate from tens of microliters per minute to milliliters per minute. The inlet and outlet of the CSTR module and the microfluidic reaction chip are connected with hollow stainless steel pipes with an inner diameter of 0.5 to 1 mm. All connecting pipes connected to the precision injection pump use polytetrafluoroethylene pipes with an inner diameter of 0.5 to 1 mm. The interface is sealed with silicone tubes and raw tape. Here, polytetrafluoroethylene can also be replaced by pipes made of other materials that do not react with reagents. In summary, all parameters of the system are microfluidic designs, which can meet the requirements of microfluidic controlled biochemical experiments.
[0045] The present invention combines the nonlinear dynamic characteristics of biochemical substances to provide a microfluidic control reaction and detection system that can be actually made and is widely used in the study of nonlinear dynamics of self-assembly of biochemical substances. It can also be used for a device for microanalysis detection, providing a broad experimental platform and experimental ideas for exploring the nonlinear dynamics of biochemical organic self-assembly. All parts of the present invention adopt microfluidic design, a separate precision injection pump can realize microfluidic injection, a flow rate control module realizes microfluidic control of each branch, and a branch design realizes multi-channel control experiments, saving a lot of experimental time. Quartz, stainless steel, polytetrafluoroethylene (PTFE) and the like with strong corrosion resistance are used as the reaction contact surface material, making the microfluidic device more feasible in technology. A separate micro-agitator is used to add an indicator, and a uniquely designed optical detection window can be used for ultraviolet detection, dynamic light scattering detection, etc. In short, the reaction and detection system realizes microfluidic control, light perturbation, shunt test and detection of self-assembly nonlinear dynamics experiments such as organic chemistry and biochemistry.
[0046] Compared with the prior art, the microfluidic controlled CSTR reaction and detection system provided by the present invention has the following beneficial effects in terms of patent law:
[0047] 1) The present invention adopts microfluidic control design throughout the process, providing an unprecedented, conveniently manufactured, microfluidic reaction and detection system for exploring the nonlinear dynamics of biochemical systems, saving reagents and costs. It provides a broad experimental platform and experimental ideas for exploring the nonlinear dynamics of biochemical organic self-assembly.
[0048] 2) The CSTR module of the present invention can change the wavelength by changing the light source, adjust the light intensity by adjusting the vertical height of the light source from the CSTR optical surface, and use a light intensity meter to detect the light intensity received by the CSTR optical surface. The exterior of other parts of the device are all made of materials that shield ultraviolet light to prevent the light source from interfering with reactants in other devices, thereby realizing ultraviolet light interference experiments at special positions with different light intensities and wavelengths. Different excitation light sources can be selected according to different reaction mechanisms to achieve optical control of self-assembly nonlinear dynamics experiments.
[0049] 3) The microfluidic stirring module independently designed by the present invention can be independently added with an indicator, can control the motor speed and display the motor speed, and achieve the effect of rapid indication.
[0050] 4) The multi-channel microfluidic control design of the present invention can realize the simultaneous exploration of multiple experiments with the same flow rate and the simultaneous conduct of multiple experiments with different flow rates, and can realize the simultaneous conduct of multiple groups of control experiments. Since the nonlinear kinetic reaction rate of biochemical organic self-assembly is extremely slow, and a cycle time is as long as several hours, this design can save a lot of time for doing the same control experiments, improve the experimental efficiency, and eliminate the systematic errors caused by factors such as concentration in the control experiments with flow rate as a variable.
[0051] 5) The optical detection window of the present invention can realize accurate detection in micro-flow conditions, and can meet the detection requirements of ultraviolet visible spectrophotometers and dynamic light scattering instruments.
[0052] 6) The design of each part of the present invention is combined with material selection. The materials in contact with the reaction liquid are all quartz, stainless steel tubes, polytetrafluoroethylene tubes, etc. with strong corrosion resistance and do not react with organic biochemical substances.
[0053] 7) The entire system adopts a microfluidic design to achieve the requirements of microfluidics, economy and precision; the CSTR contains a special optical surface for photochemical experiments; the microfluidic stirring module uses a motor speed regulator to control the motor stirring to make the reaction more complete and uniform; the multi-channel flow rate control design makes it possible to explore the spatiotemporal self-organization phenomenon of multiple groups of control experiments at the same time, saving time and improving experimental efficiency; the unique detection window enables precise detection; the device material uses inert quartz and stainless steel, etc. The combination of material selection and device structure makes the manufacturing process feasible. BRIEF DESCRIPTION OF THE DRAWINGS
[0054] Figure 1 : An overall schematic diagram of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0055] Figure 2 Schematic diagram of the CSTR module structure of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0056] Figure 3 Schematic diagram of the microfluidic stirring module of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0057] Figure 4 Schematic diagram of the control system of the microfluidic stirring module of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0058] Figure 5 Schematic diagram of the microfluidic reaction chip of the microfluidic stirring module of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0059] Figure 6 Schematic diagram of the microfluidic detection window of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0060] Figure 7 Schematic diagram of the perspective structure of the first type of deformation of the CSTR module of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0061] Figure 8 Schematic diagram of the perspective deformation structure of the CSTR module of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0062] Fig. 9 Schematic diagram of the perspective structure of the CSTR module of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0063] Fig.10 : The effect diagram of the microfluidic controlled CSTR reaction and detection system provided by the present invention.
[0064] In the figure: 1-precision injection pump; 2-polytetrafluoroethylene tube (PTFE); 3-stainless steel pipe inlet; 3-1 stainless steel pipe inlet; 3-2 stainless steel pipe inlet; 4-constant temperature water bath channel; 5-CSTR module; 6-magnetic stirring bar; 7-ultraviolet light source; 8-light intensity meter; 8-1 light intensity meter detection head; 9-microfluidic stirring module microfluidic reaction chip; 10-0~12V adjustable voltage micro DC motor; 11-microfluidic stirring module control system; 12-liquid mass flow controller; 13-microfluidic detection window; 14-constant temperature water bath inlet; 14-1 constant temperature water bath outlet; 15-optical surface; 16-CSTR inner pool; 17-stainless steel pipe outlet; 1 8-magnetic stirrer; 19-height-adjustable iron stand; 20-switch; 21-speed display; 22-speed knob; 23-plexiglass stand; 24-microfluidic reaction chip base; 25-non-contact speed meter; 26-12V DC transformer; 27-12V digital display DC motor speed regulator; 28-CNC circuit board; 29-stainless steel pipe inlet; 29-1 stainless steel pipe outlet; 29-2 stainless steel pipe inlet; 30-microfluidic reaction chip inner pool; 31-chrome-plated iron stirring shovel; 32-microfluidic reaction chip inner layer; 33-microfluidic reaction chip outer layer; 34-detection window; 35-black steel protection frame, 36-inlet; 37-outlet. DETAILED DESCRIPTION
[0065] The following is a further and more detailed description of a microfluidic controlled CSTR reaction and detection system provided by the present invention through specific embodiments:
[0066] Example 1
[0067] The microfluidic control CSTR reaction and detection system of this embodiment, please refer to Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 and Figure 6 As shown, including:
[0068] Precision injection module, CSTR module, microfluidic stirring module, flow rate control module and microfluidic detection window module, wherein the precision injection module is four precision injection pumps 1, of which three are first precision injection pumps and one is third precision injection pump, the three first precision injection pumps are used to carry three reactants respectively, the third precision injection pump is used to carry an indicator, and the injection accuracy of the precision injection pump can reach the level of picoliter per minute to milliliter per minute; the specific number of units used is determined according to the type of reaction reagent;
[0069] The CSTR module comprises a CSTR module 5 including an optical surface 15, a magnetic stirrer 18, an ultraviolet light source 7, an adjustable height iron frame 19, and a light intensity meter 8, wherein the optical surfaces of the inner pool and the outer pool of the first reaction tank CSTR module 5 are the same optical surface, as a preferred solution of the present embodiment, in the present embodiment, the lamp tube of the ultraviolet light source 7 is arranged into several S-shaped structures (not shown in the figure) arranged side by side, the purpose is to expand the illumination area and intensity of the ultraviolet light; in addition, considering the radiation hazard of the ultraviolet light source to the human body, as a preferred embodiment, a lampshade is arranged above the ultraviolet light source 7 in the present embodiment, with the area covering the first reaction tank as the standard;
[0070] The microfluidic stirring module includes a microfluidic reaction chip 9, a 0-12V adjustable voltage micro DC motor 10, a 12V digital display DC motor speed regulator 26, a 12V DC transformer 25, a non-contact speed meter 24, and an organic glass stand 23; wherein, the use of the organic glass stand 23 is the preferred solution of this embodiment;
[0071] The flow rate control module is composed of three liquid mass flow controllers 12, and the microflow detection window 13 has an optical channel 33 on the side, two inlets and outlets 35 on the top, and is wrapped with a black steel protective frame 24 on the outside. The flow rate control module is composed of three liquid mass flow controllers. This embodiment takes three branches as an example. The specific branches can be determined by themselves. The three branches can achieve the purpose of controlling the flow rate of each branch separately, and multiple groups of control experiments can be explored at the same time, which significantly improves the experimental efficiency. It is well known that in the actual experimental operation process, the variables of the experiment are difficult to estimate, such as the characteristics of the reactants themselves and the environmental factors of the experiment. Therefore, it is often necessary for the relevant operators to pay more or even unpredictable hard work to explore the experimental parameters, repeat and reproduce the experiment. The operation of setting three branches in this embodiment is extremely rare in the processing of many experiments. Its innovative processing scheme opens a time-saving, labor-saving and efficient outlet for solving problems for cumbersome experimental operations.
[0072] Specifically: three first precision injection pumps 1 are connected to three stainless steel pipe inlets on the side of the outer pool of the CSTR module 5 through polytetrafluoroethylene tubes 2, namely: 3-stainless steel pipe inlet, 3-1 stainless steel pipe inlet and 3-2 stainless steel pipe inlet; the stainless steel outlet 17 at the bottom of the CSTR module 5 is connected to the side inlet of the microfluidic reaction chip 9 through a polytetrafluoroethylene tube, specifically one of the 29-stainless steel pipe inlet and the 29-2 stainless steel pipe inlet; a third precision injection pump is connected to the side inlet of the microfluidic reaction chip 9 through a polytetrafluoroethylene tube, specifically one of the above two inlets, wherein the stainless steel outlet 17 at the bottom of the CSTR module 5 is the second outlet; the stainless steel pipe outlet 29-1 on the side of the microfluidic reaction chip 9 is connected to the liquid mass flow controller 12 through a polytetrafluoroethylene tube, and in addition, the liquid mass flow controller 12 is also connected to the inlet and outlet 35 of the microfluidic detection window 13 through a polytetrafluoroethylene tube. The first pipeline and the third pipeline are both polytetrafluoroethylene tubes, and the following nonlinear dynamics experiments with three reactants and one indicator are taken as examples.
[0073] like Figure 2As shown, the first reaction pool of the CSTR module is placed on the magnetic stirrer 18, and the magnetic stirrer 18 is placed on the chassis of the adjustable height iron frame platform 19. The volume of the inner pool 16 of the CSTR module is 5 microliters-50 milliliters. The outer pool side of the CSTR module has three hollow stainless steel pipe inlets that pass into the inner pool 16 of the CSTR module. The three stainless steel pipe inlets are the first inlets. The inner diameter of the first inlet in the present embodiment is 1 mm. The number of the first inlets can be 2 or 3, and the inlet can be arranged at the bottom of the inner pool for the purpose of facilitating stirring; in the present embodiment, the first inlet is connected with three precision injection pumps 1 equipped with reaction reagents, and the outer pool side has 14-constant temperature water bath inlet and 14-1 constant temperature water bath outlet as the first outlet at the same time, and both are connected to the first channel, i.e., the constant temperature water bath channel 4, wherein the constant temperature water bath inlet and outlet 14 is connected to the constant temperature water bath, and there is an outlet 17 at the bottom of the inner pool. Similarly, the stainless steel outlet 17 as the second outlet can also be arranged at the top of the inner pool, which has the advantage of being convenient for stirring the solution. The inner pool 16 of the CSTR module contains a magnetic stirrer 6. In this embodiment, the inner pool and the outer pool of the CSTR module are covered with the same quartz optical surface 15. The inner pool of the CSTR module 5 is made of quartz, and the bottom and side of the outer pool are made of ordinary optical glass. The CSTR optical surface 15 is consistent in height with the light intensity meter probe 8-1. The light intensity meter 8 and the light intensity meter probe 8-1 are both fixed at the bottom of the adjustable height iron frame 19. The ultraviolet light source 7 is fixed on the frame of the adjustable height iron frame 19. Since the light intensity meter probe 8-1 and the CSTR optical surface 15 are at the same distance from the ultraviolet light source 7, the light intensity received by the optical surface 15 of the CSTR module can be detected. The ultraviolet light source 7 can be replaced with light sources of different wavelengths, and the light intensity received by the CSTR optical surface 15 can be adjusted by adjusting the height of the adjustable height iron frame 19, thereby realizing the light disturbance experiment of different wavelength light sources and different light intensities. In addition, as a preferred embodiment of this embodiment, the stainless steel pipe can be replaced by a polytetrafluoroethylene pipe, the purpose is to avoid the catalytic effect of the metal in the stainless steel pipe on the reaction.
[0074] like Figure 3 As shown, the microfluidic stirring module includes a microfluidic reaction chip 9, a 0-12V adjustable voltage micro DC motor 10, a non-contact speed meter 25, a 12V DC transformer 26; a 12V digital display DC motor speed regulator 27; a CNC circuit board 28; a stainless steel pipe inlet 29; a stainless steel pipe outlet 29-1; a stainless steel pipe inlet 29-2; a microfluidic reaction chip inner pool 30; a chrome-plated iron stirring shovel 31; a microfluidic reaction chip inner layer 32; a microfluidic reaction chip outer layer 33; a detection window 34; a black steel protective frame 35, an inlet 36; and an outlet 37.
[0075] The organic glass stand 23 is divided into three layers, the upper layer is arranged with a 12V digital display DC motor speed regulator 26 and a 12V DC transformer 25, the middle layer is fixed with a 0-12V adjustable voltage micro DC motor 10, and the bottom layer is fixed with a microfluidic reaction chip 9.
[0076] like Figure 4 As shown, the microfluidic stirring module control system includes: 0-12V adjustable voltage micro DC motor 10, 12V digital display DC motor speed regulator 27, non-contact speed meter 25, microfluidic reaction chip base 24, 12V DC transformer 26, 12V digital display DC motor speed regulator 27 includes: switch 20, CNC circuit board 28, speed knob 22, speed display 21, when the 12V DC transformer 26 is plugged in and the switch 20 is turned on, the speed is adjusted by the speed knob 22, the speed display 21 displays the current speed as a percentage of the maximum speed, and the real-time speed of the motor 10 can be measured by the laser emitted by the non-contact speed meter 24. The DC transformer 26 and the 0-12V adjustable voltage micro DC motor are respectively connected to the 12V digital display DC motor speed regulator 27 to form a microfluidic stirring module control system, so as to achieve the purpose of controlling the motor speed, and the speed can be controlled at 0-1600 revolutions per minute.
[0077] like Figure 5 As shown, the microfluidic reaction chip 9 is the third reaction pool, the inner pool body is made of quartz material, and the outer material is ordinary optical glass, so as to prevent ultraviolet radiation. There are two inlets on the side of the microfluidic reaction chip 9, one inlet 29 representing the fourth inlet is connected to the stainless steel pipe outlet 17 on the CSTR module 5 for feeding, one inlet 29-2 representing the fifth inlet is connected to the third precision injection pump equipped with an indicator, and one outlet 29-1 representing the fourth outlet is connected to the inlet 35 on the microfluidic detection window 13. The chrome-plated iron stirring shovel 30 installed in front of the rotating shaft of the motor 10 extends into the microfluidic reaction chip pool, which can quickly stir the indicator and the reaction liquid for indication. There is a stirring shovel at the front end of the rotating shaft of the DC motor and is embedded in the microfluidic reaction chip, and the transformer and the motor speed regulator are fixed on the top of the organic glass stand. In addition, in order to distinguish the microfluidic reaction chip 9 as the second reaction pool or the third reaction pool, the volume of the inner pool body is 7-500 microliters;
[0078] like Figure 6As shown, there is an optical channel as the second optical channel on the side of the microflow detection window 13, specifically a detection window 34, which can be used for optical detection such as a UV-visible spectrophotometer and a dynamic light scattering instrument. There are two entrances and exits on the top, entrance 36; exit 37; entrance 36 is connected to the liquid mass flow controller 12, and exit 37 is connected to a liquid collecting bottle. The outside is wrapped with a black steel protective frame 35, which prevents stray light interference and is not easily broken. Inside is a special colorimetric dish with an optical path of 0.5 to 1 mm. The built-in low optical path design can be used for optical detection under microflow to improve detection accuracy.
[0079] Taking the biochemical self-assembly oscillation experiment of the thiol-amide system as an example, when the experimental parameters are as follows: ① Experimental parameters: UV spectrophotometer parameter settings: cycle number 20,000 times; time interval 3 seconds; online wavelength 412nm; pump 1 / 2: SV = 3.4*10^-4, i.e. 5.1ul / min; pump 3: 102ul / min; pump 4: 918ul / min; ② Experimental process: 11th 14:42-15:42 (0.5h) ③ Reference measurement: air ④ Measurement object: flow system Experimental results are as follows Fig.10 As shown, this embodiment obtains a typical regular and perfect periodic oscillation result.
[0080] The microfluidic controlled CSTR reaction and detection system of this embodiment takes three reactants and one indicator as an example. In actual experiments, the types of reactants may be different, and the indication methods may also be different. The number of stainless steel pipe inlets 3 of the CSTR module 5 can be changed according to the specific experimental reactants. Each reactant and indicator is equipped with a precision injection pump 1 to meet the nonlinear dynamics experimental requirements of different reaction systems.
[0081] The microfluidic control CSTR reaction and detection system of this embodiment, when the experiment does not require the ultraviolet light source 7 to perform a light disturbance experiment, then the CSTR module does not need to install the ultraviolet light source 7, the height-adjustable iron frame 19, and the light intensity meter 8. When a light disturbance experiment is required, they must be installed. In the experiment, the wavelength of the light source can be controlled by replacing the ultraviolet light source 7, the light intensity can be controlled by controlling the power of the ultraviolet light source and the distance between the ultraviolet light source 7 and the optical surface 15 of the CSTR module, and the light intensity meter is used to detect the light intensity received by the optical surface 15 of the CSTR module in real time. In addition to being able to select a simple lamp-type light source, the ultraviolet light source 7 can also be replaced with a variety of more professional light sources.
[0082] Divided into three paths, such as Figure 1 and Figure 8 As shown, by controlling the flow rate of each branch flow through the liquid mass flow controller 12, multiple groups of experiments with different flow rates or the same flow rate can be carried out simultaneously. In the experiment, the number of branches can be determined according to the actual situation, or no branches can be determined.
[0083] When multiplexing is performed, the total flow required increases due to the number of branches. Therefore, a CSTR module 5 that meets the corresponding flow rate size can be manufactured. For example, the size of the CSTR inner pool 16 can range from more than one hundred microliters to several hundred milliliters, and the microfluidic reaction chip 9 can also be adjusted accordingly from a few microliters to hundreds of milliliters. When there is no branching, there is no need to install a liquid mass flow controller 12, and the flow rate can be directly adjusted by the precision injection pump 1.
[0084] like Figure 1 As shown, the microfluidic control CSTR reaction and detection system of this embodiment can determine whether to install a microfluidic stirring module according to the specific reaction system and its detection method. If a dynamic light scattering instrument is used to detect the nonlinear dynamic assembly process, and an indicator is not required, then the microfluidic stirring module can be installed; if an ultraviolet spectrophotometer is used for detection and an indicator is required, then a microfluidic stirring module must be installed to achieve the effect of rapid stirring and color development.
[0085] Example 2
[0086] The microfluidic control CSTR reaction and detection system of this embodiment is basically the same as that of embodiment 1, except that the flow rate is adjusted directly by the precision injection pump 1, and the flow rate control module and the microfluidic stirring module are not provided, that is, it only includes the precision injection module, the CSTR module and the microfluidic detection window module. The connection relationship between the three modules is that the precision injection module is connected to the inlet of the CSTR module, and the CSTR module itself is connected to a constant temperature water bath, and its outlet is connected to the inlet of the microfluidic detection window. The connections between the devices are all connected by polytetrafluoroethylene tubes. Among them, combined with Figure 2 , Figure 6 and Figure 7 As shown, the CSTR module includes a magnetic stirrer 18 and a first reaction tank arranged on the magnetic stirrer 18, the first reaction tank includes an inner tank 103 and an outer tank 106, the outer tank 106 is circumferentially sleeved on the periphery of the inner tank 103, the inner tank 103 and the outer tank 106 share a top surface, a first channel for fluid circulation is arranged between the inner wall of the outer tank 106 and the outer wall of the inner tank 103, the first channel is a cavity structure, and the side of the outer tank 106 is provided with a first inlet 105 that is consistent with the number of the first precision injection pumps and is used to connect the inner tank and the outer tank, a second inlet 107 for inputting fluid into the first channel, and a first outlet for outputting the fluid in the first channel, and a second outlet 101 is arranged on the top of the inner tank; Figure 7 In the embodiment, the marks 101 and 105 are stainless steel pipes or polytetrafluoroethylene pipes arranged at the corresponding port positions. As a preferred embodiment of the present invention, the upper surface of the outer pool 106 of the CSTR module and the bottom of the CSTR module are extended with platforms that help stabilize the overall structure, such as the upper platform 102 and the lower platform 104.
[0087] Example 3
[0088] The microfluidic control CSTR reaction and detection system of this embodiment is basically the same as that of embodiment 1, except that: Figure 8 As shown, the number of the first precision injection pumps is 2, and the first reaction pool 203; in addition, as a variation of this embodiment, the top optical surfaces of the inner pool and the outer pool of the CSTR module are different optical surfaces, and the height of the outer pool is greater than that of the inner pool, and the ultraviolet light irradiation experiment can be realized from the top, and the outlet 201 is set at the top of the inner pool, which has the advantage of being conducive to uniform stirring, and the inlet 202 is used for passing a constant temperature water bath or an organic reagent such as alcohol. In addition, a platform 204 is set on the horizontal surface of the bottom of the inner pool. In the actual production process, a stainless steel inlet is introduced to reach the inner pool through the bottom platform drilling process, which reduces the production difficulty and improves the stability of the overall module structure.
[0089] Example 4
[0090] The microfluidic control CSTR reaction and detection system of this embodiment is basically the same as that of embodiment 3, except that: Fig. 9 As shown, as a variation of the present embodiment, an optical surface is provided only on the top of the inner pool 306 of the CSTR module, the inner pool 306 and the outer pool 302 are separated by the middle partition wall 301, the constant temperature water bath flows between the outer wall of the partition wall 301 and the inner wall of the outer pool 302, and a cavity is provided at the top of the inner pool 306 away from the top of the partition wall 301. The advantage of this treatment is that light can directly irradiate the top of the inner pool 306, avoiding the attenuation of light passing through the water bath and affecting the experiment. Mark 304 is a stainless steel or polytetrafluoroethylene pipe, mark 305 is a base platform for stabilizing the entire device, and mark 303 serves as the entrance or exit of the constant temperature water bath.
[0091] The above-described embodiments are merely descriptions of several embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field shall fall within the protection scope determined by the claims of the present invention.
Claims
1. Microfluidic controlled CSTR reaction and detection system, characterized by include: Precision injection module: the precision injection module is a first precision injection pump whose number corresponds to the types of reaction reagents; CSTR module: the CSTR module includes a magnetic stirrer and a first reaction pool arranged on the magnetic stirrer, the first reaction pool includes an inner pool and an outer pool, the outer pool is circumferentially arranged on the periphery of the inner pool, a covering plane is arranged on the top of the inner pool, a first channel for fluid circulation is arranged between the inner wall of the outer pool and the outer wall of the inner pool, and the first channel is a cavity structure; the side of the outer pool is provided with a first inlet that is the same in number as the first precision injection pump and is used to connect the inner pool and the outer pool, a second inlet for inputting fluid into the first channel, and a first outlet for outputting the fluid in the first channel, and a second outlet is arranged on the top or bottom of the inner pool; and Microfluidic detection window: The microfluidic detection window is a cubic structure, an optical second channel is arranged on one opposite side, a third inlet and a third outlet are arranged on the top, the external size of the microfluidic detection window is close to or the same as that of the cuvette, and a black steel protective frame is arranged on the outside; The first precision injection pump is connected to the first inlet, and the second outlet is connected to the third inlet via a first pipeline; The height of the outer pool is greater than that of the inner pool, and the tops of the outer pool and the inner pool are covered with different optical surfaces or only the top of the inner pool is provided with an optical surface; Or the tops of the outer pool and the inner pool are covered with the same optical surface.
2. The microfluidic controlled CSTR reaction and detection system according to claim 1, characterized in that It also includes a flow rate control module, which is a liquid mass flow controller; the second outlet is connected to the liquid mass flow controller inlet through a second pipeline; The number of the first precision injection pumps is at least 2; The inner pool is made of quartz material, and the outer pool is made of common optical glass except for the top part which is made of quartz material; The second optical channel is made of quartz material with an internal optical path of 1 mm; The first inlet, the second inlet, the first outlet and the second outlet are all connected with a hollow stainless steel tube or polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm; The first pipe and the second pipe are both polytetrafluoroethylene pipes, and the inner diameter of the polytetrafluoroethylene pipe is 0.5 to 1 mm; The fluid is water or an organic reagent, and the organic reagent is alcohol or oil.
3. The microfluidic controlled CSTR reaction and detection system according to claim 1 or 2, characterized in that: The injection accuracy of the first precision injection pump reaches the level of picoliters per minute to milliliters per minute.
4. The microfluidic controlled CSTR reaction and detection system according to claim 1, characterized in that It also includes a microfluidic stirring module, which includes a microfluidic reaction chip and an adjustable voltage micro DC motor, a digital display DC motor speed regulator, a DC transformer and a non-contact speed meter, all of which are connected by electrical connection; The microfluidic reaction chip is a second reaction pool, and the side of the second reaction pool is provided with a fourth inlet for connecting to the second outlet, a fifth inlet for connecting to the second precision injection pump, and a fourth outlet for connecting to the third inlet of the microfluidic detection window; The CSTR module further comprises an ultraviolet light source, an adjustable height iron frame, and a light intensity meter provided with a detection head. The ultraviolet light source, the magnetic stirrer, and the light intensity meter are all provided on the adjustable height iron frame. When the tops of the outer pool and the inner pool are covered with the same optical surface, the optical surface is in the same height as the detection head. The number of the second precision injection pump is one, and its structure is the same as that of the first precision injection pump, and it is connected to the fifth inlet through a third pipeline, and the third pipeline is a polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm; The fluid is water or an organic reagent, and the organic reagent is alcohol or oil; the injection accuracy of the second precision injection pump reaches the level of picoliters per minute to milliliters per minute.
5. The microfluidic controlled CSTR reaction and detection system according to claim 4, characterized in that: The microfluidic stirring module also includes a three-layer organic glass frame, the upper layer of the organic glass frame is arranged with a digital display DC motor speed regulator and a DC transformer, the middle layer is fixed with an adjustable voltage micro DC motor, and the bottom layer is fixed with a microfluidic reaction chip; The fourth inlet, the fifth inlet and the fourth outlet are all connected with a hollow stainless steel tube or a polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm; When the height of the outer pool is greater than that of the inner pool, a cavity is provided at the top of the inner pool and away from the top of the outer pool.
6. The microfluidic controlled CSTR reaction and detection system according to claim 4 or 5, characterized in that: The digital display DC motor speed regulator comprises a switch, a speed regulating knob, a speed display and a numerical control circuit board, and the motor speed is 0-1600 rpm.
7. The microfluidic controlled CSTR reaction and detection system according to claim 1, characterized in that It also includes a flow rate control module, a microfluidic stirring module and a third precision injection pump; The number of the first precision injection pumps is 3, the number of the third precision injection pump is 1, and the structure thereof is the same as that of the first precision injection pump; The CSTR module further comprises: an ultraviolet light source, an adjustable height iron stand and a light intensity meter provided with a probe; the tops of the outer pool and the inner pool are provided with the same optical surface or only the top of the inner pool is provided with an optical surface, and the top of the inner pool is provided with a cavity away from the top of the outer pool; the three first precision injection pumps are connected to the first inlet through a first pipeline; a magnetic stirrer is provided in the inner pool; and the magnetic stirrer is provided on the adjustable height iron stand; The fluid is water or an organic reagent, and the organic reagent is oil or alcohol; the injection accuracy of the third precision injection pump reaches the level of picoliters per minute to milliliters per minute; The flow rate control module is a liquid mass flow controller; The microfluidic stirring module: The microfluidic stirring module includes a microfluidic reaction chip and an adjustable voltage micro DC motor, a digital display DC motor speed regulator, a DC transformer and a non-contact speed meter, all of which are connected by electrical connection; the microfluidic reaction chip is the third reaction pool, which has a cylindrical cavity structure; the third outlet is connected to a liquid collecting bottle; the adjustable voltage micro DC motor is provided with a chrome-plated iron stirring shovel, and the stirring shovel extends into the third reaction pool.
8. The microfluidic controlled CSTR reaction and detection system according to claim 7, characterized in that: When the optical surface is consistent with the probe height, the light intensity meter is fixed on the bottom end of the height-adjustable iron stand, and the ultraviolet light source is fixed on the shelf of the height-adjustable iron stand; the organic reagent is alcohol.
9. The microfluidic controlled CSTR reaction and detection system according to claim 7, characterized in that: The volume of the inner pool is 5 μl-50 ml; the volume of the third reaction pool is 7-500 μl; The first pipe is a polytetrafluoroethylene tube with an inner diameter of 0.5 to 1 mm; The digital display DC motor speed regulator comprises a switch, a speed regulating knob, a speed display and a numerical control circuit board, and the motor speed is 0-1600 rpm.
10. The microfluidic controlled CSTR reaction and detection system according to claim 7, characterized in that: The inner pool is made of quartz material, and the outer pool except the optical surface is made of ordinary optical glass; the third reaction pool is made of quartz material, and its outer material is made of ordinary optical glass.
Citation Information
Patent Citations
Miniflow control CSTR reaction and detection system
CN207689508U