RNA (Ribonucleic Acid) reaction bag

Abstract

The utility model belongs to the technical field of mRNA production and manufacturing, and discloses an RNA reaction bag and an IVT reaction monitoring method. The RNA reaction bag comprises a bag body and a detection assembly, the bag body comprises a flexible part and a transparent hard part, a detection vessel is formed through structuring of the transparent hard part, and in the IVT reaction process, the detection vessel is used as a cuvette to receive IVT reaction liquid, and the detection assembly is used for detecting the IVT reaction liquid. Meanwhile, optical detectors arranged on the two opposite sides of the detection vessel are used for detection, so that detection of the IVT reaction liquid in the detection vessel can be achieved, real-time relevant information of reaction raw materials and / or products in the IVT reaction liquid is obtained, and pH value information and temperature information detected by a pH detector and a temperature detector are matched; the real-time monitoring of the IVT reaction process in the RNA reaction bag is realized, the reaction condition can be adjusted in time, and the raw materials can be supplemented in time to maintain an ideal reaction state, so that the amplification of the IVT reaction is realized, the large-scale production of RNA is realized, and the method has a good application prospect.

Description

Technical Field

[0001] This invention belongs to the technical field of mRNA production and manufacturing, and particularly relates to an RNA reaction bag. Background Technology

[0002] Messenger ribonucleic acid (mRNA) is a single-stranded ribonucleic acid molecule transcribed from DNA. It can efficiently translate the genetic information it carries into corresponding proteins on ribosomes within cells. mRNA vaccines / drugs utilize specific delivery systems to deliver RNA molecules encoding specific antigen targets, enabling the expression of corresponding proteins in vivo or directly altering intracellular protein expression. This, in turn, stimulates a specific immune response or alters the body's metabolism, thereby achieving disease prevention and / or treatment. mRNA vaccines / drugs respond rapidly to changes in disease conditions and pathogens, have a simple production process, and are easily mass-produced, showing broad application prospects.

[0003] Currently, mRNA production mainly involves the design and production of linear plasmids, in vitro transcription (IVT) of mRNA, mRNA purification, and encapsulation. IVT is a crucial step in mRNA production, involving the transcription synthesis of mRNA using linear plasmids as templates in a cell-free system. Parameters such as pH, enzyme activity, substrate concentration, product concentration, and temperature during in vitro transcription significantly affect the efficiency and quality of mRNA synthesis. Therefore, the in vitro transcription reaction must be rigorously monitored to ensure timely replenishment of raw materials or adjustment of reaction conditions, such as pH and temperature. However, there is a gap in existing technologies for real-time, sample-free monitoring of the IVT reaction process. Therefore, developing a method and device capable of real-time monitoring of the IVT reaction process without sampling is of great significance. Utility Model Content

[0004] Addressing the gap in existing technologies for real-time, sample-free monitoring of IVT reaction processes, the inventors of this invention, through extensive and in-depth research, creatively designed the structure of the RNA reaction bag. A transparent, rigid section was introduced into the RNA reaction bag structure and structured to form a detection dish. This detection dish serves as an optical detection container (colorimetric dish) to hold the IVT reaction solution. During the IVT reaction, the IVT reaction solution in the detection dish is updated in real time. Optical detectors located on both sides of the detection dish monitor the IVT reaction solution in real time, allowing for the acquisition of relevant information about the reactants and / or products in the IVT reaction solution without sampling. Furthermore, pH and temperature information obtained from pH and temperature detectors within the bag further enhances the accuracy of the IVT reaction process, offering advantages such as accuracy, convenience, and high efficiency. Based on this, the technical solution of this invention was obtained.

[0005] The purpose of this invention is to provide an RNA reaction bag. This RNA reaction bag has a specific structural design that integrates a detection component containing multiple detectors, including an optical detector, a pH detector, and a temperature detector. This detection component monitors changes in pH, temperature, dNTP concentration, mRNA concentration, and phosphate concentration in real time during the IVT reaction. This allows for timely adjustment of reaction conditions and replenishment of raw materials to maintain an ideal reaction state, facilitating the scale-up of the IVT reaction and enabling large-scale RNA production.

[0006] Specifically, the RNA reaction bag provided by this utility model includes: a bag body, the bag body including a flexible part and a transparent rigid part, the transparent rigid part being structured to form a detection dish, the detection dish being connected to the interior of the bag body to receive the IVT reaction solution; a detection assembly, the detection assembly including an optical detector, a pH detector and a temperature detector; the pH detector and the temperature detector being disposed inside the bag body; the optical detector including an emitter and a receiver, the emitter and the receiver being disposed opposite to each other on both sides of the detection dish, the detection light emitted by the emitter passing through the detection dish and the IVT reaction solution being received by the receiver.

[0007] Furthermore, the transparent rigid part is structured to form a detection dish that protrudes from the bag body, and a connector is provided on the outside of the detection dish. The optical detection assembly is detachably connected to the bag body through the connector.

[0008] Furthermore, the transparent rigid part is structurally formed into M detection dishes protruding from the bag body, where M is an integer not less than 2; the detection dishes are spaced apart, and a first receiving groove is formed between two adjacent detection dishes; the connector is disposed in the first receiving groove; and the transmitter and / or receiver is detachably disposed in the first receiving groove.

[0009] Furthermore, the transparent rigid part is structurally formed into N second receiving grooves recessed in the bag body, where N is an integer not less than 2; the second receiving grooves are spaced apart, and a detection dish is formed between two adjacent second receiving grooves; the transmitter and / or receiver are detachably disposed in the second receiving grooves.

[0010] Furthermore, a flow guide is provided around the opening of the detection dish.

[0011] Furthermore, the material of the transparent rigid portion is selected from one or more of quartz, optical glass, and rigid optical plastic.

[0012] Furthermore, the optical detector is selected from one or more of Fourier transform infrared spectrometers, in-situ Raman spectrometers, and particle image analyzers.

[0013] Furthermore, the RNA reaction bag includes an autosampler that is connected to the bag body.

[0014] Beneficial effects:

[0015] The RNA reaction bag provided by this utility model includes a bag body and a detection component. The bag body includes a flexible part and a transparent rigid part. The transparent rigid part is structured to form a detection dish. During the IVT reaction, this detection dish is used as a cuvette to receive the IVT reaction solution. At the same time, the IVT reaction solution in the detection dish can be detected by optical detectors set on opposite sides of the detection dish, and real-time information related to the reaction raw materials and / or products in the IVT reaction solution can be obtained. Combined with the pH value information and temperature information detected by pH detector and temperature detector, the IVT reaction process in the RNA reaction bag can be monitored in real time. This allows for timely adjustment of reaction conditions and replenishment of raw materials to maintain a relatively ideal reaction state, which is conducive to the scale-up of the IVT reaction and thus realizes the large-scale production of RNA, showing good application prospects. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the structure of the RNA reaction bag provided in the first embodiment of this utility model;

[0017] Figure 2 for Figure 1 Sectional view of AA;

[0018] Figure 3 This is a schematic cross-sectional view of the RNA reaction bag provided in the second embodiment of the present invention;

[0019] Figure 4 This is a schematic cross-sectional view of the RNA reaction bag provided in the third embodiment of the present invention.

[0020] Figure 5 This is a cross-sectional structural diagram of the RNA reaction bag provided in the fourth embodiment of this utility model.

[0021] Reference numerals: 1. Bag body; 101. Flexible part; 102. Transparent rigid part; 2. Detection component; 201. Optical detector; 202. pH detector; 203. Temperature detector; 3. Detection dish; 4. Emitter; 5. Receiver; 6. Flow guide; 7. Autosampler. Detailed Implementation

[0022] Although the present invention can be readily embodied in various forms, only some specific embodiments are shown in the accompanying drawings and will be described in detail in this specification. It is understood that this specification should be regarded as an exemplary illustration of the principles of the present invention and is not intended to limit the present invention to what is described herein.

[0023] Therefore, a feature pointed out in this specification is used to describe one feature of one embodiment of the present invention, and does not imply that every embodiment of the present invention must have the described feature. Furthermore, it should be noted that this specification describes many features. Although certain features may be combined to illustrate possible system designs, these features may also be used in other combinations not explicitly stated. Therefore, unless otherwise stated, the described combinations are not intended to be limiting.

[0024] In the embodiments shown in the accompanying drawings, the directional indications (such as up, down, left, right, front, and back) used to explain the structure and movement of the various elements of this invention are relative rather than absolute. These descriptions are appropriate when these elements are in the positions shown in the drawings. If the descriptions of the positions of these elements change, these directional indications also change accordingly.

[0025] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention.

[0026] Please see Figures 1 to 2 , Figure 1 This is a schematic diagram of the structure of the RNA reaction bag according to the first embodiment of this utility model. Figure 2 yes Figure 1 A cross-sectional view of AA. The RNA reaction bag provided by this utility model includes a bag body 1 and a detection component 2.

[0027] The bag body 1 can be divided into a flexible part 101 and a transparent rigid part 102 according to its hardness. The transparent rigid part 102 is structured to form a detection dish 3 protruding from the bag body, and the opening of the detection dish 3 faces the inside of the bag body 1 to achieve communication with the inside of the bag body 1. During the IVT reaction, the IVT reaction solution in the bag body 1 can enter the detection dish 3, and with the shaking of the bag body 1 and / or the stirring of the IVT reaction solution in the bag body 1, the IVT reaction solution in the detection dish 3 can be updated in real time, so that the IVT reaction solution in the detection dish 3 maintains a high degree of consistency with the overall IVT reaction solution in the bag body 1.

[0028] The material of the flexible part 101 is a material commonly used in the prior art for preparing bioreactor bags. Those skilled in the art can make adaptive choices according to actual needs, and this utility model does not impose any particular limitations on it. In some specific embodiments, specific examples of the material of the flexible part 101 include, but are not limited to, one or more of the following: polyethylene terephthalate, low-density polyethylene, polyethylene, polypropylene, polyvinyl alcohol, and polyvinyl chloride.

[0029] The material of the transparent rigid portion 102 is a material commonly used in the prior art for preparing cuvettes. Those skilled in the art can make adaptive choices according to actual needs, and this invention does not impose any particular limitations on it. In some specific embodiments, the material of the transparent rigid portion 102 is preferably selected from one or more of quartz, optical glass, and rigid optical plastics. Specific examples of rigid optical plastics include, but are not limited to, one or more of polymethyl methacrylate, polystyrene, polycarbonate, styrene-acrylonitrile, and transparent polyamide.

[0030] The detection component 2 includes an optical detector 201, a pH detector 202, and a temperature detector 203. The pH detector 202 and temperature detector 203 are detachably installed inside the bag body 1. The optical detector 201 includes a transmitter 4 and a receiver 5. A protruding snap-fit ​​block is structurally formed on the transparent rigid portion 102 on opposite sides of the detection dish 3. The transmitter 4 and receiver 5 are each provided with a snap-fit ​​groove, allowing them to be detachably installed on opposite sides of the detection dish 3 via the snap-fit ​​groove and snap-fit ​​block.

[0031] During the IVT reaction, the transmitter 4 in the optical detector 201 emits detection light that passes through the side wall of the detection dish 4 and the IVT reaction solution within it, and is received by the receiver 5. Based on the optical signal received by the receiver 5, analysis and calculation are performed to obtain relevant information about the raw materials and / or products in the IVT reaction solution in a sampling-free and contactless manner. At the same time, the pH value and temperature of the IVT reaction solution are measured in real time using the pH detector 202 and temperature detector 203 inside the bag 1, which are in direct contact with the IVT reaction solution. By combining the relevant information about the raw materials and / or products in the IVT reaction solution with the physicochemical information such as pH and temperature of the IVT reaction solution, real-time monitoring of the IVT reaction process in the RNA reaction bag can be achieved. Based on this real-time monitoring result, the reaction conditions can be adjusted in a timely manner and raw materials can be added to maintain a relatively ideal reaction state, which is conducive to the scale-up of the IVT reaction and thus realizes the large-scale production of RNA, showing good application prospects.

[0032] The optical detector 201 is a type of instrument commonly used in the prior art that utilizes the absorption and / or reflection of specific light by substances to determine information such as the chemical composition, concentration, and purity of a solution. In this RNA reaction bag, based on a profound understanding of the substances present in the IVT reaction system and the relationship between their changes and the IVT reaction process, the inventor preferably selects one or more instruments from Fourier transform infrared spectroscopy, in-situ Raman spectroscopy, and particle image analyzer as the optical detector to more accurately obtain relevant information about the raw materials and / or products in the IVT reaction solution.

[0033] The pH detector 202 is a type of instrument commonly used in the prior art to determine the acidity or alkalinity of a solution. Those skilled in the art can make an adaptive selection according to the actual needs of use, and this utility model does not impose any special limitations on it.

[0034] Among them, the temperature detector 203 is a type of instrument commonly used in the prior art to measure the temperature of a solution. Those skilled in the art can make an adaptive selection according to the actual needs of use, and this utility model does not impose any special limitations on it.

[0035] It should be noted that, Figure 1 and Figure 2The dimensions of the detection dish 3 and the bag 1 shown are for illustrative purposes only and do not represent their actual size relationship. In some actual products, the volume of the detection dish 3 is preferably much smaller than the volume of the bag 1. More specifically, the volume of the detection dish 3 is preferably set to 0.7–7 mL, such as 0.7 mL, 0.8 mL, 1 mL, 1.5 mL, 2 mL, 3 mL, 5 mL, 7 mL, or any value between them. The optical path length of the detection dish 3 is preferably set to 0.5–2 mm, such as 0.5 mm, 0.8 mm, 1 mm, 1.2 mm, 1.5 mm, 2 mm, or any value between them. In the first embodiment, the volume of the detection dish 3 is 0.7 mL, and the optical path length is 2 mm.

[0036] In the IVT reaction process, compared with direct optical detection of bag 1, detection of IVT reaction solution in detection dish 3 has the advantages of small detection solution volume and short detection light path, which makes the interference of solution shaking and flow less. Therefore, the optical signal received by receiver 5 can better reflect the relevant information of reaction raw materials and / or products in IVT reaction solution, and the detection results have higher accuracy and reliability.

[0037] In the first embodiment, a flow guide 6 is preferably provided on the periphery of the opening of the detection dish 3. The flow guide 6 guides the IVT reaction liquid in the bag 1 to flow to the detection dish 3, which is beneficial to realize the real-time updating of the IVT reaction liquid in the detection dish 3 during the IVT reaction process.

[0038] In the first embodiment, the RNA reaction bag preferably also includes an autosampler 7, which is connected to the bag body 1 via a pipe. During the IVT reaction, the autosampler 7 can accurately add the reaction raw materials, and can also replenish the corresponding reaction raw materials according to the IVT reaction progress measured by the detection component 2, which is conducive to the realization of automated large-scale RNA production.

[0039] Among them, the automatic sampler 7 is a type of instrument commonly used in the prior art for quantitatively feeding raw materials into the reaction vessel. Those skilled in the art can make adaptive selections according to actual needs, and this utility model does not impose any special limitations on it.

[0040] The pipe on the bag body 1 that is connected to the autosampler 7 is preferably located on the bag body 1 away from the transparent rigid part 102, which can reduce the interference of raw material injection on the optical detection results of the IVT reaction solution in the detection dish 3.

[0041] It should be noted that the detection dish 3 formed by the structured transparent rigid portion 102 provided in the above embodiments is only one example of this utility model. The transparent rigid portion 102 of this utility model can form M detection dishes 3 protruding from the bag body 1 in the same structural manner, where M is an integer not less than 2. That is, any technical solution that forms one or more detection dishes 3 protruding from the bag body 1 by structuring the transparent rigid portion of the bag body 1 on the RNA reaction bag is covered within the protection scope of the claims of this utility model.

[0042] Please see Figure 3 . Figure 3 This is a cross-sectional structural diagram of the RNA reaction bag according to the second embodiment of the present invention. Compared with the first embodiment, in this embodiment, the transparent rigid part 102 is structured to form two detection dishes 3 protruding from the bag body 1, and the two detection dishes 3 are spaced apart to form a first receiving groove. The sidewall of the first receiving groove is structured to form a protruding snap-fit ​​block, and a protruding snap-fit ​​block is also structured to form on the transparent rigid part 102 where the two detection dishes 3 are facing away from each other; the transmitter 4 is correspondingly provided with a snap-fit ​​groove, and the transmitter 4 is detachably installed in the first receiving groove through the snap-fit ​​groove and the snap-fit ​​block; the number of receivers 5 is set to two, and each receiver 5 is correspondingly provided with a snap-fit ​​groove, and the two receivers 5 are detachably installed on the side of the two detection dishes 3 facing away from each other through the snap-fit ​​groove and the snap-fit ​​block.

[0043] The transmitter 4 preferably has multiple windows capable of emitting detection light, allowing it to simultaneously emit detection light into multiple detection dishes 3. In some practical products, the transmitter 4 preferably emits the same detection light into different detection dishes 3 simultaneously, enabling parallel and repeated testing of the IVT reaction solution, reducing the interference of errors on the detection results, and obtaining more accurate information about the raw materials and / or products in the IVT reaction solution. In other practical products, the transmitter 4 preferably emits different detection lights into different detection dishes 3, and the receiver 5 is configured as an instrument capable of receiving the corresponding detection light, enabling the detection of multiple targets. This results in more comprehensive information about the raw materials and / or products in the IVT reaction solution, facilitating more precise monitoring of the IVT reaction process.

[0044] It should be noted that the detection dish 3 formed by the structured transparent rigid portion 102 provided in the above embodiments is only one example of this utility model. The transparent rigid portion 102 described in this utility model can be used to form detection dishes 3 with different structural relationships to the bag body 1 in different structural ways. That is, the technical solutions of forming a structure with cuvette function by structuring the transparent rigid portion of the bag body 1 itself on the RNA reaction bag are all covered within the protection scope of the claims of this utility model.

[0045] Please see Figure 4 . Figure 4 This is a cross-sectional structural diagram of the RNA reaction bag according to the third embodiment of the present invention. Compared with the first embodiment, in this embodiment, the portion of the transparent rigid portion 102 near the edge of the bag body 1 is structured to form a second receiving groove recessed into the bag body 1. The second receiving groove and the bag body 1 enclose the aforementioned detection dish 3. That is, the detection dish 3 in this embodiment is indirectly formed by structuring the spatial structural relationship between the second receiving groove formed by the transparent rigid portion 102 and the bag body 1.

[0046] The second receiving groove has a structured sidewall with a protruding snap-fit ​​block, and the outer surface of the detection dish 3 on the side away from the second receiving groove has a structured snap-fit ​​block with a protruding snap-fit ​​block; the transmitter 4 and the receiver 5 are respectively provided with snap-fit ​​grooves. The transmitter 4 can be detachably installed in the second receiving groove through the snap-fit ​​groove and the snap-fit ​​block, and the receiver 5 can be detachably installed on the outer surface of the detection dish 3 through the snap-fit ​​groove and the snap-fit ​​block.

[0047] Please see Figure 5 . Figure 5 This is a cross-sectional structural diagram of the RNA reaction bag according to the fourth embodiment of the present invention. Compared with the first embodiment, in this embodiment, the transparent rigid portion 10 is structurally formed to create two second receiving grooves recessed in the bag body 1, and the two second receiving grooves are spaced apart and surround to form the detection dish 3 described above. That is, the detection dish 3 in this embodiment is indirectly formed through the spatial structural relationship between the multiple second receiving grooves formed by the structured transparent rigid portion 102.

[0048] The sidewall of the second receiving slot is structured to form a protruding threaded post. The transmitter 4 and receiver 5 are respectively provided with threaded holes. The transmitter 4 and receiver 5 can be detachably installed in the two second receiving slots by screwing the threaded post and the threaded hole.

[0049] In this embodiment, the transmitter 4 and receiver 5 in the optical detector 201 have a closer and more stable connection with the bag body 1, which can effectively reduce the positional deviation between the optical detector 201 and the detection dish 3 caused by mechanical forces such as shaking during the detection process, and further improve the accuracy and reliability of the detection results.

[0050] It should be noted that the terms "first" and "second" in the "first receiving groove" and "second receiving groove" mentioned in the above embodiments are only for distinguishing purposes and for ease of description, and do not limit the scope of protection of this utility model.

[0051] In the RNA reaction bags provided in the first to fourth embodiments above, the optical detector is set as a Fourier transform infrared spectrometer. The same volume of IVT reaction solution is placed in each RNA reaction bag and subjected to IVT reaction on a shaker at 100 rpm. The absorbance changes corresponding to phosphate and mRNA in the IVT reaction solution are monitored in real time using the Fourier transform infrared spectrometer, and the absorbance trends are converted into absolute concentration curves of phosphate and mRNA. Simultaneously, during the IVT reaction, three samples are taken at different time points for the following tests:

[0052] (1) Detection of phosphoric acid concentration: The phosphoric acid concentration of the sample was detected using a phosphoric acid fluorescence detection kit (Beyotime, catalog number S0192S) and in accordance with the instructions.

[0053] (2) Detection of mRNA concentration: 2 μL of IVT reaction solution was diluted 20-fold, 50-fold, and 100-fold with DEPC water, and 4 μL of each dilution was analyzed by electrophoresis on a 1% non-denaturing agarose gel. RiboRuler high-range RNA molecular weight standard (Thermo Fisher Scientific, SM1821) was used as a positive control, and 1×TAE was used as the electrophoresis buffer. Electrophoresis was performed at 150V for 30 min. A positive control band with a molecular weight similar to that of the mRNA being tested was used as a reference to convert the grayscale value and concentration of the mRNA product being tested. The test results are shown in Table 1.

[0054] Table 1.

[0055]

[0056] As shown in Table 1, the test results indicate that when the detection dish 3 in the RNA reaction bag provided in the first to fourth embodiments of this utility model is used as the detection container, the measured phosphate and mRNA concentrations are highly consistent with the results obtained by traditional methods, and the detection results have high reliability.

[0057] This invention also provides a method for monitoring an IVT reaction. In this embodiment, the IVT reaction is performed within the RNA reaction bag provided in the above embodiment. The detection method utilizes the detection component 2 in the RNA reaction bag to detect the IVT reaction solution, specifically including the following steps:

[0058] The detection component is used to detect the IVT reaction solution inside the bag to obtain one or more IVT reaction parameters, including raw material concentration, solution aging state, phosphate concentration, mRNA production, pH value, and temperature; the reaction conditions of the IVT reaction are adjusted based on the IVT reaction parameters.

[0059] The method for adjusting IVT reaction conditions based on the IVT reaction parameters includes: maintaining the pH value of the IVT reaction system at 7-8; controlling the deviation of the real-time temperature from the preset reaction temperature during the IVT reaction to be 0-0.5℃; and supplementing dNTP and Mg when the dNTP concentration in the IVT reaction system decreases to 10-30% of the initial concentration. 2+ Cap analogues and inorganic pyrophosphatase were added to 75%–100% of the initial concentration; when precipitation occurred in the IVT reaction system, the Mg content was adjusted. 2+ The concentration was increased to 75%–100% of the initial concentration; the IVT reaction was stopped when the mRNA production was 10–20 mg / mL.

[0060] Although the present invention has been described with reference to several typical embodiments, it should be understood that the terminology used is descriptive and exemplary, and not restrictive. Since the present invention can be embodied in many forms without departing from the spirit or essence of the invention, it should be understood that the above embodiments are not limited to any of the foregoing details, but should be interpreted broadly within the spirit and scope defined by the appended claims. Therefore, all variations and modifications falling within the scope of the claims or their equivalents should be covered by the appended claims.

Claims

1. An RNA reaction bag, characterized in that, The RNA reaction bag includes: The bag body includes a flexible part and a transparent rigid part, the transparent rigid part being structured to form a detection dish, the detection dish being connected to the interior of the bag body to receive the IVT reaction solution; The detection assembly includes an optical detector, a pH detector, and a temperature detector; the pH detector and the temperature detector are disposed inside the bag; the optical detector includes an emitter and a receiver, which are disposed opposite to each other on both sides of the detection dish, and the detection light emitted by the emitter passes through the detection dish and the IVT reaction solution and is received by the receiver.

2. The RNA reaction bag according to claim 1, characterized in that, The transparent rigid part is structured to form a detection dish that protrudes from the bag body. A connector is provided on the outside of the detection dish, and the optical detector is detachably connected to the bag body through the connector.

3. The RNA reaction bag according to claim 2, characterized in that, The transparent rigid part is structurally formed into M detection dishes protruding from the bag body, where M is an integer not less than 2; the detection dishes are spaced apart, and a first receiving groove is formed between two adjacent detection dishes; the connector is disposed in the first receiving groove; and the transmitter and / or receiver is detachably disposed in the first receiving groove.

4. The RNA reaction bag according to claim 1, characterized in that, The transparent rigid part is structurally formed into N second receiving grooves recessed in the bag body, where N is an integer not less than 2; the second receiving grooves are spaced apart, and a detection dish is formed between two adjacent second receiving grooves; the transmitter and / or receiver are detachably disposed in the second receiving grooves.

5. The RNA reaction bag according to claim 4, characterized in that, A flow guide is provided around the opening of the detection dish.

6. The RNA reaction bag according to claim 1, characterized in that, The material of the transparent rigid part is selected from one or more of quartz, optical glass, and rigid optical plastic.

7. The RNA reaction bag according to claim 1, characterized in that, The optical detector is selected from one or more of the following: Fourier transform infrared spectrometer, in-situ Raman spectrometer, and particle image analyzer.

8. The RNA reaction bag according to claim 1, characterized in that, The RNA reaction bag includes an autosampler, which is connected to the bag body.

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