Physical and chemical parameter detection device for in-vitro biosynthesis and corresponding reaction system

Abstract

The utility model provides a physical and chemical parameter detection device for in-vitro biosynthesis. The physical and chemical parameter detection device comprises a plurality of physical and chemical parameter sensors, a closed detection box body, a liquid taking pipeline and a liquid returning pipeline, the detection box body is used for accommodating a detection sample from a reaction tank for carrying out in-vitro biosynthesis reaction, and a probe of the sensor is inserted to detect the sample; two ends of the liquid taking pipeline are respectively communicated with the detection box body and the reaction tank, and a detection sample enters the detection box body from the liquid taking pipeline; two ends of the liquid return pipeline are respectively communicated with the detection box body and the reaction tank, and a detection sample in the detection box body is discharged from the liquid return pipeline. The utility model further provides an in-vitro biosynthesis reaction system with the physical and chemical parameter detection device. According to the utility model, the reaction liquid is conveyed into the detection box body outside the reaction tank for real-time detection, the reaction liquid in the detection box body can flow back into the reaction tank, and the sensor is positioned in the detection box body, so that the service life of the sensor is prolonged.

Description

Technical Field

[0001] The utility model relates to the technical field of biosynthesis equipment, in particular to a physical and chemical parameter detection device for in vitro biosynthesis and a corresponding reaction system. Background Art

[0002] The main structure of the reactor used for biosynthesis (such as cell-free protein synthesis) is a reaction tank. The reaction liquid in the tank is a mixture of multiple components. During the reaction, target biological molecules (such as protein molecules) and by-products (such as ethanol) are generated.

[0003] As the biosynthesis reaction continues, the physicochemical parameters of the reaction solution change dynamically. Different types of physicochemical parameters of the reaction solution can characterize different physicochemical characteristics of the reaction solution, and multiple physicochemical characteristics can be used to indirectly determine the yield and activity of biomolecules in the reaction solution. In order to improve efficiency and enable biosynthesis technology to be relatively automated, many detection needs have been derived, including real-time monitoring and detection of liquid data during biosynthesis reactions. However, such technical devices are currently lacking in the market.

[0004] At present, there are at least the following problems in directly installing the corresponding physical and chemical parameter detection sensors in the reaction tank: 1. Due to the small space in the tank, it is very difficult to fix the sensor on the inner wall of the reaction tank. 2. Even if it can be successfully installed, it will destroy the reaction environment in the tank, hinder the liquid flow, and reduce the reaction efficiency. 3. There is a stirring device in the reaction tank. If the sensor is installed below the liquid level of the reaction liquid in the tank, it will interfere with the normal operation of the stirring device and cause damage to both. 4. Harmful byproducts produced by the reaction, such as ethanol, are highly corrosive to the sensor, greatly reducing its service life.

[0005] Based on this, it is necessary to design an alternative installation structure for physical and chemical sensors to fundamentally solve the many problems existing in the direct installation method in the tank. Utility Model Content

[0006] In order to solve the above technical problems, the utility model provides a device for detecting physical and chemical parameters of in vitro biosynthesis, comprising: a plurality of physical and chemical sensors, a sealed detection box body, a liquid collection pipeline and a liquid return pipeline; the detection box body is used to accommodate the reaction liquid from a reaction tank for in vitro biosynthesis reaction as a detection sample, and allows the probe of the sensor to be inserted to detect the detection sample; the two ends of the liquid collection pipeline are respectively connected to the detection box body and the reaction tank, and the detection sample enters the detection box body from the liquid collection pipeline; the two ends of the liquid return pipeline are respectively connected to the detection box body and the reaction tank, and the detection sample in the detection box body is discharged from the liquid return pipeline.

[0007] Specifically, the sensor is a dissolved oxygen sensor, a pH sensor, a turbidity sensor, a conductivity sensor, a liquid concentration sensor, a liquid temperature sensor, a liquid flow sensor or an ethanol concentration sensor.

[0008] Specifically, the detection box body includes: a lower box body, a sealing ring, a box cover and a fixing nut from bottom to top. The box cover is provided with a plurality of holes for the multiple sensors to be detachably installed on the box cover respectively. The box cover and the lower box body are sealed by the sealing ring.

[0009] Specifically, the liquid intake pipeline and the liquid return pipeline are the same, and a bidirectional pump is connected thereto, which has the functions of a liquid intake pump for delivering liquid to the detection box body and a liquid return pump for extracting liquid from the detection box body.

[0010] Specifically, the position of the detection box body for the detection sample to enter is located at approximately 2 / 3 of the height of the side wall thereof, and the position of the detection box body for the detection sample to be discharged is located at the bottom thereof.

[0011] Specifically, it also includes a feed three-way valve and a discharge three-way valve, a liquid pump and a liquid return pump, wherein the feed three-way valve is respectively connected to the liquid intake pipeline, the reaction liquid raw material tank, and the feed pipeline of the reaction tank, and the discharge three-way valve is respectively connected to the liquid return pipeline, the reaction liquid finished product tank, and the discharge pipeline of the reaction tank; the liquid intake pipeline takes samples from the reaction tank through the liquid intake pump, and the liquid return pipeline extracts the detection sample in the detection box through the liquid return pump.

[0012] Specifically, it also includes: a float switch, which is arranged in the detection box body. When the liquid entering the detection box body reaches a safe liquid level, the float switch is triggered to close the liquid extraction pump and start the liquid return pump at the same time.

[0013] Specifically, a portion of the liquid extraction pipeline extends into the reaction tank through a sealing bearing and extends downward.

[0014] Specifically, the length of the liquid extraction pipeline extending into the interior of the reaction tank is equivalent to the radius of the reaction tank.

[0015] Specifically, one end of the liquid return pipeline connected to the reaction tank is connected to the first discharge pipe of the discharge pipeline fixed in the reaction tank through a slip ring.

[0016] Specifically, one end of the first discharge pipe is attached to the wall of the reaction tank and extends toward the circumferential edge along the radial direction of the tank body, and the other end is connected to the rotor interface of the slip ring.

[0017] Specifically, it also includes a gas detection component, which includes: a large ventilation tube, an exhaust pipe, and an ethanol gas concentration detection device; the first end of the large ventilation tube extends into the reaction tank through a closed bearing, and the port of the second end of the large ventilation tube is located outside the reaction tank; the exhaust pipe is partially nested and installed in the large ventilation tube, one end of which extends out of the reaction tank from the port of the second end of the large ventilation tube and is connected to the ethanol gas concentration detection device, and the other end of the exhaust pipe passes through the first end of the large ventilation tube and is located in the reaction tank; preferably, the exhaust pipe extends upward and passes through the first end; the ethanol gas concentration detection device extracts the gas in the reaction tank through the exhaust pipe and inputs it into the ethanol gas concentration detection device to detect the ethanol gas concentration in the extracted gas.

[0018] Specifically, the ethanol gas concentration detection device includes a suction component, a first suction pipe, a transfer detection chamber, and a second suction pipe which are connected in sequence; wherein the transfer detection chamber includes a detection cavity and an ethanol sensor, and the gas extracted from the suction pipe is introduced into the second suction pipe, and the gas detected by the detection cavity is discharged through the discharge point, preferably, discharged through the suction component.

[0019] Specifically, it also includes an online quantitative detection device for reaction products, which includes: a detection chamber, an optical device, a detection device, a sample flow pipeline, and a sample detection tube; a detection port is opened on the detection chamber; the optical device includes a light source, which is located in the detection chamber and is used to excite the reaction liquid from the reaction tank to generate the light to be detected; the sample detection tube is used to contain the reaction liquid, at least part of the sample detection tube is placed in the detection chamber and the at least part is a transparent part, and the reaction liquid is excited by the light source in the transparent part to generate the light to be detected; the detection device collects the light to be detected through the detection port and converts it into an electrical signal; the sample flow pipeline has a liquid inlet section and a liquid outlet section respectively connected to the sample detection tube, the reaction liquid enters the sample detection tube from the liquid inlet section and flows through the transparent part, and then the reaction liquid is discharged from the liquid outlet section; preferably, the two ports of the sample flow pipeline are respectively connected to the liquid collection pipeline and the liquid return pipeline to be connected to the reaction tank.

[0020] Specifically, a liquid temperature sensor is also provided near the reaction tank on the liquid intake pipeline.

[0021] Specifically, it also includes: a controller, which is communicatively connected with the sensor, the liquid extraction pump, and the liquid return pump.

[0022] The utility model also provides an in vitro biosynthesis reaction system, comprising: a reaction tank, and a physical and chemical parameter detection device as described in any one of the above technical solutions.

[0023] Compared with the prior art, the beneficial effects of the utility model are:

[0024] 1. The closed detection box body independently arranged outside the reaction tank provides great convenience for the installation of sensors, and the installation position of the physical and chemical parameter sensor is separated from the reaction tank, which will neither disturb the normal operation of the reaction tank nor destroy the reaction environment in the tank, making the reaction process efficient and stable; the reaction liquid in the reaction tank is then transported to the detection box body through the liquid extraction pipeline, and the reaction liquid in the detection box body can also return to the reaction tank through the reflux pipeline, realizing the liquid circulation path with the rotating reaction tank, and realizing the real-time detection of the physical and chemical parameters of multiple reaction liquids at the same time.

[0025] 2. The volume of the detection box is much smaller than that of the reaction tank. The volume of the reaction liquid entering the detection box is very small, and the amount of harmful by-products contained therein is negligible. The corrosion of the sensor is very limited compared to the case where the sensor is installed in the reaction tank, which greatly improves the service life of the sensor.

[0026] 3. The device can also collect gas in a rotating reaction tank and detect the ethanol gas concentration. The gas in the transfer detection chamber is detected during the process of the gas being drawn into and discharged from the closed transfer detection chamber, which can avoid the problem of low detection accuracy caused by open sampling.

[0027] 4. For substances (such as proteins, nucleic acids, etc.) that can be excited to produce light to be measured (such as fluorescence) as synthetic products, or substances that can be excited to produce light to be measured (such as fluorescence) as synthetic substrates, the concentration of the substance that can be excited to produce light to be measured in the reaction solution can be detected online in real time, so as to understand the reaction process and regulate the reaction, solving the problem that the concentration of the above substances cannot be detected in real time in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solution of the utility model, the following briefly introduces the drawings required for use in the utility model. Obviously, the drawings described below are only some embodiments of the utility model. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0029] Figure 1 It is a structural schematic diagram of an embodiment of the utility model.

[0030] Figure 2 It is an assembly exploded view of the detection box body of the utility model.

[0031] Figure 3 It is a structural sectional view of another embodiment of the utility model.

[0032] Figure 4 It is a structural cross-sectional diagram of the large ventilation pipe of the utility model.

[0033] Figure 5 It is an assembly exploded view of the ethanol gas concentration detection device of the utility model.

[0034] Figure 6 It is a structural block diagram of the online quantitative detection device for reaction products of the utility model.

[0035] Figure 7 It is a specific structural schematic diagram of the online quantitative detection device for reaction products of the utility model.

[0036] Figure 8 yes Figure 7 A cross-sectional view of the light source illumination channel in the structure shown.

[0037] Among them, the reference numerals in the figure are: 1. reaction tank, 2. slip ring, 3. feed pipeline, 4. discharge pipeline, 41. first discharge pipe, 5. liquid extraction pipeline, 6. return liquid pipeline, 7. detection box body, 71. lower box body, 72. sealing ring, 73. box cover, 74. fixing nut, 8. sensor, 9. float switch, 10. sealed bearing, 11. feed pump, 12. liquid extraction pump, 13. return liquid pump, 14. feed three-way valve, 15. discharge three-way valve, 16. discharge Material pump, 17. Large ventilation tube, 18. Large ventilation tube fixing seat, 19. Suction tube, 20. Feed connection sleeve, 21. First suction tube, 22. Transfer detection chamber, 23. Second suction tube, 24. Suction component, 25. Sealing gasket, 26. Ethanol sensor, 27. Detection device, 28. Optical device, 29. Light path setting, 30. Detection chamber, 31. Light source, 32. Sample flow pipeline, 33. Liquid inlet section and liquid outlet section, 34. Sample detection tube. DETAILED DESCRIPTION

[0038] The following will be combined with the accompanying drawings to clearly and completely describe the technical solutions in the utility model. Obviously, the described embodiments are part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0039] The utility model provides a device for detecting physical and chemical parameters of in vitro biosynthesis, comprising: a plurality of physical and chemical parameter sensors 8, a sealed detection box body 7, a liquid collection pipeline 5 and a liquid return pipeline 6; the detection box body 7 is used to contain a reaction liquid from a reaction tank 1 for in vitro biosynthesis reaction as a detection sample, and to allow a probe of the sensor 8 to be inserted to detect the sample; the two ends of the liquid collection pipeline 5 are respectively connected with the detection box body 7 and the reaction tank 1, and the detection sample enters the detection box body 7 from the liquid collection pipeline 5; the two ends of the liquid return pipeline 6 are respectively connected with the detection box body 7 and the reaction tank 1, and the detection sample in the detection box body 7 is discharged from the liquid return pipeline 6. Specifically, the closed detection box body 7 independently arranged outside the reaction tank 1 provides great convenience for installing the sensor 8, and the installation position of the physical and chemical parameter sensor 8 is separated from the reaction tank 1, which will neither disturb the normal operation of the reaction tank 1 nor destroy the reaction environment in the tank, making the reaction process efficient and stable; the reaction liquid in the reaction tank 1 is then transported to the detection box body 7 through the liquid collection pipeline 5, and the reaction liquid in the detection box body 7 can also return to the reaction tank 1 through the reflux pipeline 6, and realize the circulation path of the liquid with the rotating reaction tank 1, so as to realize the real-time detection of the physical and chemical parameters of multiple reaction liquids at the same time. Furthermore, the volume of the detection box body 7 is much smaller than that of the reaction tank 1, and the volume of the reaction liquid entering the detection box body 7 is very small, and the amount of harmful byproducts contained therein is negligible. The corrosion of the sensor 8 is very limited compared with the case where the sensor 8 is installed in the reaction tank 1, which greatly improves the service life of the sensor 8.

[0040] In this embodiment, if Figure 1-3 As shown, there are multiple sensors 8, and the sensor 8 can be a dissolved oxygen sensor, a pH sensor, a turbidity sensor, a conductivity sensor, a liquid concentration sensor, a liquid temperature sensor, a liquid flow sensor or an ethanol concentration sensor.

[0041] In this embodiment, if Figure 2 As shown, the detection box body 7 includes, from bottom to top, a lower box body 71, a sealing ring 72, a box cover 73 and a fixing nut 74. The box cover 73 is provided with a plurality of holes for multiple sensors 8 to be detachably installed on the box cover 73 respectively. The box cover 73 and the lower box body 71 are sealed by the sealing ring 72.

[0042] In one embodiment, Figure 1-3As shown, the position of the test sample entering the detection box body 7 is located at about 2 / 3 of the height of its side wall, and the position of the test sample discharging the detection box body 7 is located at its bottom. The detection box body 7 is a high-position liquid inlet and a bottom liquid outlet, so that when necessary, the liquid in the detection box body 7 can be drained back to the reaction tank 1 without causing waste of the reaction liquid. In this embodiment, the physical and chemical parameter detection device for in vitro biosynthesis also includes: a feed three-way valve 14 and a discharge three-way valve 15, a liquid pump 12 and a liquid return pump 13, wherein the feed three-way valve 14 is respectively connected to the liquid collection pipeline 5, the reaction liquid raw material tank, and the feed pipeline 3 of the reaction tank 1, and the discharge three-way valve 15 is respectively connected to the liquid return pipeline 6, the reaction liquid finished product tank, and the discharge pipeline 4 of the reaction tank 1; the liquid collection pipeline 5 samples from the reaction tank 1 through the liquid collection pump 12, and the liquid return pipeline 6 extracts the test sample in the detection box body 7 through the liquid return pump 13.

[0043] In one embodiment, Figure 1 As shown, the in vitro biosynthesis physicochemical parameter detection device also includes: a float switch 9, which is arranged in the detection box body 7. When the liquid entering the detection box body 7 reaches the safe liquid level, the float switch 9 is triggered to close the liquid pump 12 and start the liquid return pump 13 at the same time. The safe liquid level is the preset maximum liquid level. If the safe liquid level is exceeded, the detection box body 7 is easily overflowed with the detection sample. According to the flow rate of the liquid return pump 13 and the volume of the reaction liquid that can be accommodated in the detection box body 7, the running time of the liquid return pump 13 can be preset in the corresponding controller. After the running time is reached, the liquid return pump 13 is turned off, so that the liquid level in the detection box body 7 reaches the working liquid level, and the liquid pump 12 is turned on again to take liquid. The working liquid level is the lowest liquid level that satisfies the operation of each sensor.

[0044] In one embodiment, Figure 3As shown, a part of the liquid taking pipeline 5 extends into the reactor 1 through the waterproof bearing 10 (the part extending into the reactor 1 is also used by the feed pipeline 3, that is, the liquid taking pipeline 5 and the feed pipeline 3 share the part extending into the reactor 1), and extends downward. The length of the liquid taking pipeline 5 extending into the reactor 1 is equivalent to the radius of the reactor 1. Specifically, the reactor 1 is a horizontal reactor, having a horizontal tank body and two end caps symmetrically arranged. The reactor 1 can be turned over under the driving device to realize the self-stirring function, and the driving device is a motor, and the motor drives the reactor 1 through a pulley transmission mechanism or a gear transmission mechanism. For a small-volume horizontal self-stirring reactor 1, a pulley transmission mechanism can be used, and for a large-volume horizontal self-stirring reactor 1, a gear transmission mechanism can be used. A hollow waterproof bearing 10 is provided at the rotation center of one end cover of the reaction tank 1. When the reaction tank 1 is self-stirred and turned over, the waterproof bearing 10 is provided at the rotation center of the end cover, the hollow part of the waterproof bearing is stationary, and the liquid collection pipeline 5 (including the part thereof extending into the interior of the reaction tank 1) is also stationary. At the same time, the liquid collection pipeline 5 extends downward through the part extending into the interior of the reaction tank 1, which also prevents the reaction liquid from overflowing from the liquid collection pipe 5 due to splashing when the reaction tank 1 is self-stirred and turned over.

[0045] In one embodiment, the liquid intake pipeline 5 and the liquid return pipeline 6 are the same, and a bidirectional pump is connected thereto, which has the functions of a liquid intake pump 12 for delivering liquid to the detection box body 7 and a liquid return pump 13 for extracting liquid from the detection box body 7. In this embodiment, the liquid intake pipeline 5 and the liquid return pipeline 6 are the same, and a portion thereof extends through the waterproof bearing 10 into the reaction tank 1 and extends downward, and the length thereof extending into the interior of the reaction tank 1 is equivalent to the radius of the reaction tank 1. The physical and chemical parameter detection device can also be connected to the reaction tank 1 to form a liquid circulation passage, and liquid can also be extracted for detection when the reaction tank 1 rotates.

[0046] In one embodiment, Figure 3 As shown, one end of the liquid return line 6 connected to the reactor 1 is connected to the first discharge pipe 41 of the discharge line 4 fixed in the reactor 1 through the slip ring 2 (the liquid return line 6 and the discharge line 4 also share part of the line). The rotor of the slip ring 2 is fixed close to the waterproof bearing or the mechanical seal and its axis coincides with the center of rotation. The slip ring 2 consists of two major parts, rotating and stationary. The rotating part is connected to the rotating structure waterproof bearing of the reactor 1 and rotates with it, which is called the "rotor", and the stationary part is connected to the energy source of the fixed structure outside the reactor 1, which is called the "stator". The slip ring 2 has at least one passage for transmitting liquid medium, that is, one corresponding interface on each of the rotor and the stator to connect the inside of the rotating reactor 1 and the outside of the stationary reactor 1, thereby effectively solving the problem of external connection of the reactor 1 in the rotating state. The passages do not interfere with each other, and the transmission media connected in the passages include but are not limited to liquid media, fluid media, current, weak electricity, optical fiber signals and other media.

[0047] In one embodiment, Figure 3 As shown, one end of the first discharge pipe 41 is attached to the wall of the reaction tank 1 and extends to the circumferential edge along the radial direction of the tank body, and the other end is connected to the rotor interface of the slip ring 2. Specifically, because one end of the first discharge pipe 41 is attached to the wall and extends to the circumferential edge along the radial direction of the tank body, and the other end is connected to the rotor interface of the slip ring 2, when the reaction tank 1 is self-stirred and turned over, the first discharge pipe 41 also turns over with the reaction tank 1. In order to ensure that the reaction tank 1 can discharge liquid smoothly, when the reaction tank 1 stops turning over, the port of the first discharge pipe 41 should be at the bottom of the reaction tank 1 to empty the reaction liquid, and a positioning part needs to be set to ensure that the stop angle and position of the reaction tank 1 meet the requirements. The positioning part is used to locate the stop position of the reaction tank 1, and the control component of the reaction tank 1 is respectively communicated with the positioning part and the drive component of the reaction tank 1 to ensure that the stop angle of the reaction tank 1 can meet the following requirements: the nozzle of the first discharge pipe 41 extending to the circumferential edge is at the bottom of the reaction tank 1.

[0048] In one embodiment, Figure 4 As shown, it also includes a gas detection component, which includes: a large ventilation tube 17, an exhaust pipe 19, and an ethanol gas concentration detection device 21; the first end of the large ventilation tube 17 extends into the reaction tank 1 through the closed bearing 10, and the port of the second end of the large ventilation tube 17 is located outside the reaction tank 1; the exhaust pipe 19 is partially nested and installed in the large ventilation tube 17, one end of which extends out of the reaction tank 1 through the port of the second end of the large ventilation tube 17 to be connected to the ethanol gas concentration detection device 21, and the other end of which passes through the first end of the large ventilation tube 17 and is located in the reaction tank 1; preferably, the exhaust pipe 19 extends upward and passes through the first end; the ethanol gas concentration detection device 21 extracts the gas in the reaction tank 1 through the exhaust pipe 19 and inputs it into the ethanol gas concentration detection device 21 to detect the ethanol gas concentration in the extracted gas. Specifically, the large ventilation tube 17 is firstly nested and fixed in the hollow of the slip ring 2 by the sealed bearing 10. When the reaction tank 1 is self-stirred and turned over, the large ventilation tube 17 is stationary, and the air extraction pipe 19 and a part of the liquid extraction pipeline 5 that are arranged in the large ventilation tube 17 are also stationary. The large ventilation tube 17 is constantly exchanging air inside and outside the reaction tank 1, and the air extraction pipe 19 is extended upward in the reaction tank 1, which avoids directly extracting the air that has just been exchanged into the reaction tank 1, resulting in inaccurate detection results of the ethanol gas concentration detection device 21.

[0049] In one embodiment, Figure 5As shown, the ethanol gas concentration detection device includes a suction component 24, a first suction pipe 21, a transfer detection chamber 22, and a second suction pipe 23 connected in sequence; wherein, the transfer detection chamber 22 includes a detection chamber and an ethanol sensor 26, and the gas extracted by the suction pipe 19 is introduced from the second suction pipe 23, and the gas detected by the detection chamber is discharged through the discharge point, preferably, discharged through the suction component 24. Specifically, the part other than the ethanol concentration detection probe of the ethanol sensor 26 is sealed and separated outside the detection chamber by using a sealing gasket 25 at the opening of the detection chamber. The gas in the transfer detection chamber is detected during the process of the gas in the reaction tank 1 being drawn into the closed transfer detection chamber and discharged, which can avoid the problem of low detection accuracy caused by open sampling. At the same time, the suction pipe 19 can also accelerate the discharge of the gas in the reaction tank 1 through the suction component 24, and reduce the ethanol gas concentration below the safety threshold as much as possible.

[0050] In one embodiment, Figure 6-8 As shown, it also includes an online quantitative detection device for reaction products, which includes: a detection chamber 30, an optical device 28, a detection device 27, a sample flow pipeline 32, and a sample detection tube 34; a detection port is opened on the detection chamber 30; the optical device 28 includes a light source 31, which is located in the detection chamber 30, and the light source 31 is used to excite the reaction liquid from the reaction tank 1 to generate the light to be detected; the sample detection tube 34 is used to contain the reaction liquid, at least part of the sample detection tube 34 is placed in the detection chamber 30 and the at least part is a transparent part, and the reaction liquid is excited by the light source 31 in the transparent part to generate the light to be detected; the detection device 27 collects the light to be detected through the detection port and converts it into an electrical signal; the sample flow pipeline 32 has a liquid inlet section and a liquid outlet section 33 respectively connected to the sample detection tube 34, the reaction liquid enters the sample detection tube 34 from the liquid inlet section and flows through the transparent part, and then the reaction liquid is discharged from the liquid outlet section; preferably, the two ports of the sample flow pipeline 32 are respectively connected to the liquid collection pipeline 5 and the liquid return pipeline 6 to be connected to the reaction tank 1. The liquid inlet section and the liquid outlet section 33 of the online quantitative detection device for reaction products can also be independently connected to the reaction tank 1. For substances (such as proteins, nucleic acids, etc.) that can be excited to produce light to be measured (such as fluorescence) as synthetic products, or substances that can be excited to produce light to be measured (such as fluorescence) as synthetic substrates, the concentration of the substance that can be excited to produce light to be measured in the reaction liquid can be detected online in real time, so as to understand the reaction process and regulate the reaction, solving the problem that the concentration of the above substances cannot be detected in real time in the prior art.

[0051] For fluorescence detection, after the reaction liquid is excited by the light source 31, the fluorescent group will emit fluorescence, and then an image is captured by an optical device 28, such as an optical camera or other instrument that can take pictures. The detection device 27 can analyze the concentration of fluorescent substances in the reaction liquid based on the fluorescence conditions displayed on the image, thereby reflecting the amount of reaction products generated. When the light to be detected is Raman light, the optical device 28 also includes an optical path setting 29 that guides the excitation light to the excitation reaction liquid and collects the Raman light generated by the excitation reaction liquid. The detection device 27 has a detector that can split the collected Raman light through the detection port to convert it into an electrical signal to form a Raman spectrum. There are many optical path settings 29 in the prior art that realize Raman spectrum detection, which can be borrowed.

[0052] In one embodiment, a liquid temperature sensor is further provided on the liquid intake pipeline 5 near the reaction tank 1 .

[0053] The utility model also provides an in vitro biosynthesis reaction system, comprising: a controller, wherein the controller is communicatively connected with the sensor, the liquid taking pump 12, and the liquid returning pump 13 respectively.

[0054] It should be noted that "horizontal" includes completely lying flat, that is, the axis of the reaction tank 1 is parallel to the horizontal plane, and also includes partially lying flat, or obliquely lying, that is, there is a certain angle between the axis of the reaction tank 1 and the horizontal plane. The specific form can be adjusted according to actual needs.

[0055] The above description is only a preferred embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A device for detecting physical and chemical parameters of in vitro biosynthesis, characterized in that: include: Multiple physical and chemical sensors, sealed detection box, liquid collection pipeline and liquid return pipeline; The detection box body is used to contain the reaction liquid from the reaction tank for in vitro biosynthesis reaction as a detection sample, and allows the probe of the sensor to be inserted to detect the detection sample; The two ends of the liquid collection pipeline are respectively connected to the detection box body and the reaction tank, and the detection sample enters the detection box body from the liquid collection pipeline; The two ends of the liquid return pipeline are respectively connected to the detection box body and the reaction tank, and the detection sample in the detection box body is discharged from the liquid return pipeline.

2. The physical and chemical parameter detection device according to claim 1, characterized in that: The sensor is a dissolved oxygen sensor, a pH value sensor, a turbidity sensor, a conductivity sensor, a liquid concentration sensor, a liquid temperature sensor, a liquid flow sensor or an ethanol concentration sensor.

3. The physical and chemical parameter detection device according to claim 1, characterized in that: The detection box body includes, from bottom to top, a lower box body, a sealing ring, a box cover and a fixing nut. The box cover is provided with a plurality of holes for the multiple sensors to be detachably mounted on the box cover respectively. The box cover and the lower box body are sealed by the sealing ring.

4. The physical and chemical parameter detection device according to claim 1, characterized in that: The liquid intake pipeline and the liquid return pipeline are the same, and a bidirectional pump is connected thereto, which has the functions of a liquid intake pump for delivering liquid to the detection box body and a liquid return pump for extracting liquid from the detection box body.

5. The physical and chemical parameter detection device according to claim 1, characterized in that: The position of the detection box body for the detection sample to enter is located at approximately 2 / 3 of the height of the side wall thereof, and the position of the detection box body for the detection sample to be discharged is located at the bottom thereof.

6. The physical and chemical parameter detection device according to claim 1 or 5, characterized in that: It also includes a feed three-way valve and a discharge three-way valve, a liquid pump and a liquid return pump, wherein the feed three-way valve is respectively connected to the liquid collection pipeline, the reaction liquid raw material tank, and the feed pipeline of the reaction tank, and the discharge three-way valve is respectively connected to the liquid return pipeline, the reaction liquid finished product tank, and the discharge pipeline of the reaction tank; the liquid collection pipeline samples from the reaction tank through the liquid collection pump, and the liquid return pipeline extracts the detection sample in the detection box through the liquid return pump.

7. The physical and chemical parameter detection device according to claim 4 or 6, characterized in that: Also includes: A float switch is arranged in the detection box body. When the liquid entering the detection box body reaches a safe liquid level, the float switch is triggered to close the liquid extraction pump and start the liquid return pump at the same time.

8. The physical and chemical parameter detection device according to any one of claims 1 to 7, characterized in that: A portion of the liquid extraction pipeline extends into the reaction tank through a sealing bearing and extends downward.

9. The physical and chemical parameter detection device according to claim 8, characterized in that: The length of the liquid extraction pipeline extending into the interior of the reaction tank is equivalent to the radius of the reaction tank.

10. The physical and chemical parameter detection device according to any one of claims 1 to 9, characterized in that: One end of the liquid return pipeline connected to the reaction tank is connected to the first discharge pipe of the discharge pipeline fixed in the reaction tank through a slip ring.

11. The physical and chemical parameter detection device according to claim 10, characterized in that: One end of the first discharge pipe is attached to the wall of the reaction tank and extends toward the circumferential edge along the radial direction of the tank body, and the other end is connected to the rotor interface of the slip ring.

12. The physical and chemical parameter detection device according to claim 1, characterized in that: It also includes a gas detection component, which includes: a large ventilation tube, a suction tube, and an ethanol gas concentration detection device; The first end of the large ventilation tube extends into the reaction tank through a sealed bearing, and the port of the second end of the large ventilation tube is located outside the reaction tank; The exhaust pipe is partially nested in the large ventilation pipe, one end of which extends from the port at the second end of the large ventilation pipe to the reaction tank and is connected to the ethanol gas concentration detection device, and the other end of which passes through the first end of the large ventilation pipe and is located in the reaction tank; The ethanol gas concentration detection device extracts the gas in the reaction tank through the exhaust pipe and inputs it into the ethanol gas concentration detection device to detect the ethanol gas concentration in the extracted gas.

13. The physical and chemical parameter detection device according to claim 12, characterized in that: The air extraction pipe extends upward and passes through the first end.

14. The physical and chemical parameter detection device according to claim 12 or 13, characterized in that: The ethanol gas concentration detection device includes a suction component, a first suction pipe, a transfer detection chamber, and a second suction pipe that are connected in sequence; wherein the transfer detection chamber includes a detection cavity and an ethanol sensor, and the gas extracted from the suction pipe is introduced into the second suction pipe, and the gas detected by the detection cavity is discharged through the discharge point.

15. The physical and chemical parameter detection device according to claim 14, characterized in that: The gas detected by the detection chamber is discharged through the suction component.

16. The physical and chemical parameter detection device according to any one of claims 1 to 15, characterized in that: Also included is an online quantitative detection device for reaction products, the online quantitative detection device for reaction products comprising: a detection chamber, an optical device, a detection device, a sample flow pipeline, and a sample detection tube; The detection chamber is provided with a detection port; The optical device comprises a light source, the light source is located in the detection chamber, and the light source is used to excite the reaction liquid from the reaction tank to generate light to be detected; The sample detection tube is used to contain the reaction liquid, at least a portion of the sample detection tube is placed in the detection chamber and the at least a portion is a transparent portion, and the reaction liquid is excited by the light source in the transparent portion to generate the light to be detected; The detection device collects the light to be detected through the detection port and converts it into an electrical signal; The sample flow pipeline has a liquid inlet section and a liquid outlet section respectively connected to the sample detection tube. The reaction liquid enters the sample detection tube from the liquid inlet section and flows through the transparent part, and then is discharged from the liquid outlet section.

17. The physical and chemical parameter detection device according to claim 16, characterized in that: The two ports of the sample flow pipeline are respectively connected to the liquid collection pipeline and the liquid return pipeline, and thus connected to the reaction tank.

18. The physical and chemical parameter detection device according to any one of claims 1 to 17, characterized in that: The liquid taking pipeline is also provided with a liquid temperature sensor near the reaction tank.

19. The physical and chemical parameter detection device according to claim 4 or 6, characterized in that: Also includes: A controller is communicatively connected with the sensor, the liquid extraction pump, and the liquid return pump.

20. An in vitro biosynthesis reaction system, characterized in that: include: A reaction tank, a physical and chemical parameter detection device as described in any one of claims 1 to 19.

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