JP7192473B2 - Optical analysis system and optical analysis method - Google Patents

Description

The present disclosure relates to optical analysis systems and optical analysis methods.

Techniques related to chemical reaction systems for synthesizing different raw materials to obtain products have been known for some time.

For example, Patent Literature 1 discloses a sugar chain synthesizer having separation means for separating reaction products from unreacted substances and by-products in eluates from one or more reaction columns. For example, Patent Literature 2 discloses an apparatus and method relating to a microfluidic system that can be used as a means of synthesizing compounds.

In conventional chemical reaction systems, synthetic experiments are performed under various conditions to determine the optimal chemical reaction conditions that result in high product yields. Several calculation methods are known for calculating the yield. One calculation method is to qualitatively confirm whether or not the target product is obtained by a nuclear magnetic resonance (NMR) method, and then calculate the amount of the product extracted by the purification process. It is a method of direct measurement. Another calculation method is a method of relatively calculating the yield from the peak area of the light absorption spectrum of the product by High Performance Liquid Chromatography (HPLC).

In a conventional chemical reaction system, the product may include a pair of compounds having an optical isomer relationship with each other. Several analytical methods are known for analyzing such pairs of compounds with different optical activities. One analytical method is the HPLC method using a chiral column. Another analytical method is a method using a circular dichroism spectrometer.

Japanese Patent No. 4005557 Japanese Patent No. 5859393

Conventionally, when calculating or analyzing parameters related to chemical reactions including product yields and their changes over time, and information related to chemical reactions including information related to optical isomerism of products, etc., after the completion of the chemical reaction, or during the chemical reaction It is necessary to extract a sample for measurement at Additionally, extracted samples were processed for calculation or analysis and discarded after calculation or analysis.

An object of the present disclosure is to provide an optical analysis system and an optical analysis method that can non-destructively analyze information about chemical reactions without the need to extract samples.

In an optical analysis system according to some embodiments, in a chemical reaction system for synthesizing a first raw material and a second raw material to obtain a product, irradiation light is applied to each of the first raw material and the second raw material before the start of synthesis. and an irradiation unit that irradiates the mixture after the start of synthesis containing the first raw material, the second raw material, and the product with irradiation light every a plurality of reaction times, and the irradiated by the irradiation unit a detection unit for detecting the measurement light based on the irradiation light, the measurement light including information on the spectral spectra of the first raw material, the second raw material, and the mixture; and the first raw material and the second raw material. , and a calculation unit that calculates the spectral spectrum of each of the mixtures and calculates the spectral spectrum of the product based on each spectral spectrum, wherein the calculation unit calculates the spectral spectrum of the product for each of a plurality of reaction times Based on the spectroscopy spectrum of the product, changes over time in parameters relating to the chemical reaction are calculated. Changes over time in parameters relating to chemical reactions obtained by chemical synthesis can be calculated based on the spectroscopic spectrum of the product calculated by the calculation unit. Therefore, according to the optical analysis system according to the embodiment, it is possible to non-destructively analyze changes in parameters related to chemical reactions over time without extracting samples.

In one embodiment, the computing unit may calculate the spectral spectrum of the product by subtracting the spectral spectra of the first raw material and the second raw material from the spectral spectrum of the mixture. Thereby, the spectroscopic spectrum of the product buried in the spectroscopic spectrum of the mixture is extracted. Therefore, the accuracy of the calculation of changes over time in parameters relating to chemical reactions based on spectroscopic spectra is improved.

In one embodiment, the chemical reaction system may include a flow-type synthetic reaction system in which the first raw material, the second raw material, and the mixture each flow inside a channel. As a result, even in a flow-type synthesis reaction system in which it is difficult to extract a sample for measurement, the optical absorption spectrum can be measured in a non-contact manner by an optical technique without the need to extract a sample. Therefore, it is possible to calculate the temporal change of the parameters related to the chemical reaction in real time.

In one embodiment, the irradiation unit may irradiate the irradiation light at each of a plurality of positions along the flow path through which the mixture flows. As a result, even in a flow-type synthetic reaction system in which a mixture flows inside a channel, the spectroscopic spectrum of the product can be calculated for each of a plurality of reaction times. Therefore, it is possible to calculate changes over time in parameters relating to chemical reactions in real time in a non-destructive manner by an optical method without the need to extract samples.

In one embodiment, parameters relating to the chemical reaction may include the yield of the product. This makes it possible to analyze changes in product yield over time in a chemical reaction system.

In one embodiment, each of said first source and said second source may comprise an amino acid and said product may comprise a compound formed by a peptide bond. This makes it possible to analyze peptides composed of multiple amino acids.

In one embodiment, the wavelength band of the measurement light may be included in the near-infrared region from 1800 nm to 2500 nm. Thereby, the optical analysis system can calculate the spectroscopic spectrum due to the predetermined structure of the compound appearing in the near-infrared region.

In one embodiment, the measurement light may include transmitted light based on the irradiation light that has passed through the first raw material, the second raw material, and the mixture, and the spectral spectrum may include a light absorption spectrum. . For example, in other spectroscopic methods, such as fluorescence spectroscopy and Raman spectroscopy, the intensity of measurement light, such as fluorescence and Raman light, is weak and detection of the measurement light is not easy. On the other hand, the use of absorption spectroscopy increases the intensity of the measurement light, facilitating the detection of the measurement light. Therefore, the optical analysis system can easily calculate the spectroscopic spectrum.

In the optical analysis method according to some embodiments, in a chemical reaction system in which a first raw material and a second raw material are synthesized to obtain a product, irradiation light is applied to each of the first raw material and the second raw material before the start of synthesis. and irradiating the mixture after the synthesis initiation containing the first raw material, the second raw material, and the product with irradiation light every a plurality of reaction times, and measuring based on the irradiated irradiation light a step of detecting the measurement light, which is light and includes information on the spectral spectra of each of the first raw material, the second raw material, and the mixture; calculating a spectroscopic spectrum, calculating a spectroscopic spectrum of the product based on each spectroscopic spectrum, and calculating a parameter related to a chemical reaction based on the spectroscopic spectrum of the product calculated for each of a plurality of reaction times; and calculating a change over time. Changes over time in parameters related to chemical reactions obtained by chemical synthesis can be calculated based on the calculated spectroscopic spectrum of the product. Therefore, according to the optical analysis method according to the embodiment, it is possible to non-destructively analyze changes in parameters related to chemical reactions over time without extracting samples.

In one embodiment, in the step of calculating the spectroscopic spectrum of the product, the spectroscopic spectrum of the product is calculated by subtracting the spectroscopic spectrum of each of the first raw material and the second raw material from the spectroscopic spectrum of the mixture. may Thereby, the spectroscopic spectrum of the product buried in the spectroscopic spectrum of the mixture is extracted. Therefore, the accuracy of the calculation of changes over time in parameters relating to chemical reactions based on spectroscopic spectra is improved.

According to the present disclosure, it is possible to provide an optical analysis system and an optical analysis method that can non-destructively analyze information about chemical reactions without the need to extract samples.

It is a mimetic diagram showing an example of composition of an optical analysis system concerning a 1st embodiment. 2 is a block diagram of the optical analysis system of FIG. 1; FIG. It is a schematic diagram which shows an example of the optical absorption spectrum of a 1st raw material. It is a schematic diagram which shows an example of the optical absorption spectrum of a 2nd raw material. It is a schematic diagram which shows an example of the light absorption spectrum of a mixture. It is a schematic diagram which shows an example of the optical absorption spectrum of a product. It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P1. It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P2. FIG. 4 is a schematic diagram showing an example of the light absorption spectrum of the product at position P3. It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P4. It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P5. 2 is a flow chart showing an example of the operation of the optical analysis system of FIG. 1; It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P1. It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P2. FIG. 4 is a schematic diagram showing an example of the light absorption spectrum of the product at position P3. It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P4. It is a schematic diagram which shows an example of the optical absorption spectrum of the product in the position P5. FIG. 11 is a diagram showing an example of temporal changes in parameters relating to chemical reactions calculated by the computing unit of the optical analysis system according to the third embodiment. 10 is a flow chart showing an example of the operation of the optical analysis system according to the third embodiment; FIG. 4 is a block diagram of a modification of the optical analysis system according to the first to third embodiments; FIG.

(First embodiment)
A first embodiment of the present disclosure will be mainly described. In a first embodiment, the information about the chemical reaction is primarily product yield. In the first embodiment, description will be made mainly focusing on the yield of the product. First, the problems of the prior art will be explained.

The NMR method is commonly used as a method for confirming whether or not a product is synthesized in a chemical reaction. An NMR spectrum obtained by the NMR method shows characteristic peaks based on functional groups present in, for example, organic compounds. By analyzing whether an NMR spectrum peculiar to the product is obtained, the operator can ascertain whether the product has been synthesized.

In order to calculate the yield of the product, it is necessary to calculate the ratio of the amount of product actually obtained to the amount of product when chemical synthesis proceeds to completion. The most direct method for calculating the product yield is to purify the product and measure the amount directly. Since the amount of product when the chemical synthesis has proceeded to completion can be theoretically easily calculated, the yield of the product can be easily calculated by directly measuring the amount of product.

On the other hand, the HPLC method is used when product purification is difficult. The HPLC method is a method in which a product and contaminants are separated by using differences in chemical properties of compounds, such as hydrophobic interactions, and the amount of the product is calculated from the absorption of ultraviolet rays. Using the HPLC method, ultraviolet absorption spectra of the product and contaminants are obtained. A numerical value obtained by adding up all the peak areas of the ultraviolet absorption spectrum indicates the amount of all compounds present in the chemical reaction system to be analyzed. Therefore, by measuring the peak area based on the product and calculating the ratio of the peak area to the total peak area, the yield of the product is calculated.

In the prior art, it is necessary to extract a sample for measurement after the chemical reaction is completed or during the chemical reaction and apply it to an analyzer. Therefore, there is a time lag between when the chemical reaction is in progress and when the analytical results are known. Accordingly, the operator cannot measure the amount of the product in real time in the target chemical reaction system. In addition, extracted samples were processed for analysis and were discarded after analysis. That is, destructive analysis was performed in the prior art. Further, when the chemical reaction system is, for example, a flow-type synthesis reaction system, it is originally difficult to extract a sample for measurement from the solution flowing inside the channel.

In the prior art, synthetic experiments are performed under various conditions to determine the optimal chemical reaction conditions that give high product yields. At this time, the operator needs to repeat procedures such as NMR analysis, product purification and amount measurement, or HPLC analysis for each synthesis experiment. Therefore, the work steps for optimizing the chemical reaction conditions are increased, and the work efficiency for optimization is lowered.

Prior art techniques using NMR methods require large-scale equipment to generate the nuclear magnetic resonance required for NMR analysis. Therefore, the analyzer is expensive, and the maintenance cost is also high. When a certain level of purity is required for analysis, a purification process for analysis is required, further increasing the cost required for analysis. Similarly, prior art techniques using HPLC methods require columns and mechanisms for routing solutions. Therefore, the analyzer is expensive, and the maintenance cost is also high.

The optical analysis system 1 according to the first embodiment of the present disclosure solves these problems and measures the amount of the product AB synthesized in the chemical reaction system 30 without the need to extract a sample and nondestructively. can be analyzed. An optical analysis system 1 according to a first embodiment of the present disclosure will be described below with reference to the accompanying drawings.

FIG. 1 is a schematic diagram showing an example of the configuration of an optical analysis system 1 according to the first embodiment. FIG. 2 is a block diagram of the optical analysis system 1 of FIG. The configuration and functions of the optical analysis system 1 according to the first embodiment will be mainly described with reference to FIGS. 1 and 2. FIG.

The optical analysis system 1 is installed, for example, in a chemical reaction system 30 that synthesizes a first raw material A and a second raw material B to obtain a product AB. The optical analysis system 1 irradiates the chemical reaction system 30 with irradiation light L1 including irradiation light L1a, L1b, and L1c. The optical analysis system 1 spectroscopy each of the first raw material A before the start of synthesis, the second raw material B before the start of synthesis, and the mixture C after the start of synthesis containing the first raw material A, the second raw material B, and the product AB. Calculate the spectrum. The optical analysis system 1 calculates the spectroscopic spectrum of the product AB based on each spectroscopic spectrum.

The chemical reaction system 30 has a liquid transfer pump 31 , a flow chemical reaction tube 32 and a microreactor 33 . The chemical reaction system 30 includes, for example, a first raw material A before the start of synthesis, a second raw material B before the start of synthesis, and a mixture C after the start of synthesis containing the first raw material A, the second raw material B, and the product AB. contains a continuous flow synthetic reaction system flowing inside a flow chemistry reaction tube 32 . The first raw material A and the second raw material B are respectively delivered by different liquid-sending pumps 31 and passed through different flow chemical reaction tubes 32 to be introduced into the microreactor 33 . At this time, the first raw material A and the second raw material B are instantaneously mixed to start chemical synthesis. The mixture C containing the first source material A, the second source material B, and the product AB after the start of synthesis further flows inside the flow chemical reaction tube 32 on the downstream side of the microreactor 33 . The chemical synthesis is then completed.

Each of the first raw material A and the second raw material B in the chemical reaction system 30 contains an arbitrary compound. Each of the first raw material A and the second raw material B may contain, for example, an amino acid. Similarly, product AB includes any compound such as a polymer or oligomer. The product AB may include, for example, compounds formed by amide bonds, and compounds formed by peptide bonds based on multiple amino acids.

The optical analysis system 1 is installed in the chemical reaction system 30 as described above. The optical analysis system 1 has an optical measurement device 10 and an optical analysis device 20 .

The optical measuring device 10 includes, for example, any measuring instrument capable of measuring the light absorption amount for each wavelength of the measuring light L2 including the measuring lights L2a, L2b, and L2c, which will be described later. As shown in FIG. 2 as an example, the optical measurement device 10 has an irradiation section 11 , a detection section 12 , a control section 13 , a communication section 14 and a storage section 15 . The optical measurement device 10 measures measurement light L2 having a wavelength band included in the near-infrared region from 1800 nm to 2500 nm, for example, based on irradiation light L1 emitted from the irradiation unit 11 toward the inside of the flow chemical reaction tube 32. Measure the amount of light absorption for each wavelength. The measurement light L2 includes transmitted light based on the irradiation light L1 that has passed through the first raw material A, the second raw material B, and the mixture C, respectively. That is, the irradiation light L1 emitted from the irradiation unit 11 passes through the first raw material A, the second raw material B, and the mixture C, and is detected by the detection unit 12 as the measurement light L2.

The irradiation unit 11 has an arbitrary light source such as a semiconductor laser, and an arbitrary light guide component such as an optical fiber that guides the irradiation light L1 emitted from the light source into the flow chemical reaction tube 32 . The irradiation unit 11 irradiates the inside of the flow chemical reaction tube 32 of the chemical reaction system 30 with irradiation light L1 having a wavelength band included in the near-infrared region from 1800 nm to 2500 nm, for example.

More specifically, the irradiation unit 11 irradiates the first raw material A and the second raw material B before the start of synthesis with the irradiation light L1a and L1b, respectively. The irradiation unit 11 irradiates the mixture C after the start of synthesis with the irradiation light L1c. As an example, the irradiation unit 11 irradiates the irradiation light L1c at each of five positions P1, P2, P3, P4, and P5 in the flow chemical reaction tube 32 on the downstream side of the microreactor 33 . Five positions P 1 , P 2 , P 3 , P 4 and P 5 in the flow chemical reaction tube 32 are separated from the microreactor 33 in order. That is, from position P1 to P5, the ratio of first raw material A and second raw material B in mixture C decreases, and the ratio of product AB in mixture C increases.

The detection unit 12 has, for example, an arbitrary photodetector such as a photodiode, and an arbitrary light guide component such as an optical fiber that guides the measurement light L2 transmitted through the flow chemical reaction tube 32 to the photodetector. The detection unit 12 detects measurement light L2 having a wavelength band included in the near-infrared region from 1800 nm to 2500 nm, which has passed through the inside of the flow chemical reaction tube 32, for example.

More specifically, the detection unit 12 detects the measurement lights L2a and L2b that have passed through the first raw material A and the second raw material B before the start of synthesis, respectively. The detection unit 12 detects the measurement light L2c that has passed through the mixture C after the start of synthesis. As an example, the detection unit 12 detects the measurement light L2c at each of five positions P1, P2, P3, P4, and P5 in the flow chemical reaction tube 32. FIG. In this way, the detection unit 12 measures the measurement light L2 based on the irradiation light L1 emitted by the irradiation unit 11, which includes information on the respective spectral spectra of the first raw material A, the second raw material B, and the mixture C. Light L2 is detected.

Control unit 13 includes one or more processors. For example, controller 13 includes a processor that enables processing relating to optical measurement device 10 . The control unit 13 is connected to each component constituting the optical measurement device 10 and controls and manages the entire optical measurement device 10 including each component. The control unit 13 acquires detection information of the measurement light L2 detected by the detection unit 12 from the detection unit 12 . Based on the detection information acquired from the detection unit 12, the control unit 13 measures the light absorption amount for each wavelength of the measurement light L2. The control unit 13 outputs the acquired light absorption amount data for each wavelength to the communication unit 14 and causes the optical analysis device 20 to transmit the data. The control unit 13 stores the acquired light absorption amount data for each wavelength in the storage unit 15 as necessary.

The communication unit 14 includes a communication interface compatible with any communication standard via wire or wireless. The communication unit 14 can be communicatively connected to the optical analysis device 20 via, for example, a data communication cable 40 . The communication unit 14 transmits, for example, the light absorption amount data for each wavelength acquired from the control unit 13 to the optical analysis device 20 via the data communication cable 40 . The communication unit 14 receives from the optical analysis device 20, for example, setting information regarding the measurement of the light absorption amount for each wavelength of the measurement light L2, which is set by the operator using the optical analysis device 20. FIG.

The storage unit 15 is, for example, an HDD (Hard Disk Drive), an SSD (Solid State Drive), an EEPROM (Electrically Erasable Programmable Read-Only Memory), a ROM (Read-Only Memory), and a RAM (Random) memory. of memory. The storage unit 15 stores various data and programs processed by the optical measurement device 10 . The storage unit 15 may function, for example, as a main storage device, an auxiliary storage device, or a cache memory. The storage unit 15 is not limited to one built in the optical measurement device 10, and may be an external storage device connected via a digital input/output port such as a USB. The storage unit 15 acquires light absorption amount data for each wavelength from the control unit 13 as necessary, and stores this data.

The optical analyzer 20 can be any general-purpose electronic device such as, for example, a mobile phone, smart phone, tablet PC, desktop computer, and mobile computer, as well as dedicated information specialized for processing the measurement data acquired by the optical measuring device 10. Including processing equipment. The optical analysis device 20 has a communication section 21 , a calculation section 22 , a display section 23 , an operation section 24 and a storage section 25 . The optical analysis device 20 analyzes measurement data acquired by the optical measurement device 10 .

The communication unit 21 includes a communication interface compatible with any communication standard via wire or wireless. The communication unit 21 can be communicatively connected to the optical measurement device 10 via, for example, a data communication cable 40 . The communication unit 21 receives, for example, light absorption amount data for each wavelength acquired by the optical measurement device 10 from the optical measurement device 10 via the data communication cable 40 . For example, the communication unit 21 transmits, to the optical measurement apparatus 10, setting information regarding the measurement of the light absorption amount for each wavelength of the measurement light L2, which is set by the operator using the operation unit 24. FIG.

The computing unit 22 includes one or more processors. More specifically, the computing unit 22 includes arbitrary processors such as general-purpose processors and dedicated processors specialized for specific processing. The computing unit 22 specializes in processing measurement data acquired by a processor installed in any general-purpose electronic device such as a mobile phone, a smartphone, a tablet PC, a desktop computer, and a mobile computer, and by the optical measurement device 10. It may also include a processor mounted on a dedicated information processing device. The computing unit 22 is connected to each component constituting the optical analysis device 20, and controls and manages the entire optical analysis device 20 including each component.

The calculation unit 22 performs various processes on the measurement data obtained by the optical measurement device 10 through the communication unit 21 . For example, the calculation unit 22 calculates the respective spectral spectra of the first raw material A before the start of synthesis, the second raw material B before the start of synthesis, and the mixture C after the start of synthesis. The calculation unit 22 calculates the spectrum of the product AB based on each spectrum. Spectral spectrum includes, for example, optical absorption spectrum. For example, the calculation unit 22 calculates each light absorption spectrum based on the light absorption amount data for each wavelength acquired by the optical measurement device 10 .

The calculation unit 22 may determine whether or not the product AB is obtained based on the calculated light absorption spectrum. For example, the calculation unit 22 determines whether the product AB is obtained by determining whether the height of the light absorption spectrum peak at a predetermined wavelength set by the operator exceeds a predetermined value. You may When determining that the product AB is obtained, the calculation unit 22 may further calculate the yield of the product AB. The determination of whether the product AB is obtained and the calculation of the yield of the product AB described here need not be performed by the optical analysis device 20 . In this case, the determination of whether the product AB is obtained and the calculation of the yield of the product AB may be performed by the operator himself.

The calculation unit 22 outputs information on each calculated light absorption spectrum to the display unit 23 to display each light absorption spectrum as necessary. The calculation unit 22 receives, for example, an operator's arbitrary operation on the light absorption spectrum displayed on the display unit 23 via the operation unit 24 . The calculation unit 22 stores information on each calculated light absorption spectrum in the storage unit 25 as necessary.

The display 23 includes any output interface that affects the operator's vision. An output interface that configures the display unit 23 includes, for example, any display device such as a liquid crystal display. The display unit 23 may include, for example, a liquid crystal display that is integral with the mobile computer. The display unit 23 displays each light absorption spectrum calculated by the calculation unit 22 as necessary.

The operation unit 24 includes arbitrary input interfaces such as a keyboard, mouse, touch pad, and microphone for inputting various instructions by voice. The operation unit 24 may be configured integrally with a liquid crystal display that constitutes the display unit 23 as a touch panel, for example. The operation unit 24 receives, for example, an operator's arbitrary operation on the light absorption spectrum displayed on the display unit 23 . In addition, the operation unit 24 receives, for example, an input operation of setting information regarding measurement using the optical measurement device 10 from the operator.

The storage unit 25 includes, for example, any storage device such as HDD, SSD, EEPROM, ROM, and RAM. The storage unit 25 stores various information and programs processed by the optical analysis device 20 . The storage unit 25 may function, for example, as a main storage device, an auxiliary storage device, or a cache memory. The storage unit 25 is not limited to one built in the optical analysis device 20, and may be an external storage device connected via a digital input/output port such as a USB. The storage unit 25 acquires information on each calculated light absorption spectrum from the calculation unit 22 as necessary, and stores this information.

3A is a schematic diagram showing an example of the light absorption spectrum of the first raw material A. FIG. 3B is a schematic diagram showing an example of the light absorption spectrum of the second raw material B. FIG. 3C is a schematic diagram showing an example of the light absorption spectrum of the mixture C. FIG. FIG. 3D is a schematic diagram showing an example of the light absorption spectrum of product AB. 3C and 3D show, as an example, optical absorption spectra of mixture C and product AB at center position P3 among five positions P1, P2, P3, P4, and P5 in flow chemical reaction tube 32, respectively. .

The compounds constituting each of the first raw material A, the second raw material B, and the product AB have multiple light absorption spectra based on complex energy level structures including electronic levels, vibrational levels, and rotational levels. It is common to show peaks. However, in FIGS. 3A, 3B, and 3D, only one optical absorption spectrum is illustrated for convenience of explanation.

A graph based on light absorption data for each wavelength of the measurement light L2 acquired by the optical measurement device 10 shows a dip at a specific absorption transition wavelength of the energy level structure of the compound through which the measurement light L2 is transmitted. The optical analysis device 20 processes such measurement data from the optical measurement device 10 to calculate optical absorption spectra as shown in FIGS. 3A to 3D.

The resulting light absorption spectrum reflects the amount of given structure in the compound. Predetermined structures of compounds include, for example, amide bonds, peptide bonds, and the like. That is, the higher the amount of a given structure in a compound, the higher the light absorption spectral peak. In addition, the energy levels resulting from a given structure of a compound vary depending on the weights of the molecules that make up the left and right sides of that structure. Therefore, the wavelength positions of the light absorption spectrum peaks caused by the first raw material A, the second raw material B, and the product AB are generally different from each other.

For example, in the near-infrared region from 1800 nm to 2500 nm, there are optical absorption spectral peaks indicative of amide bonds or peptide bonds. By measuring the light absorption amount of the measurement light L2 in the near-infrared light absorption spectrum band of the wavelength region, the amount of amide bond or peptide bond in the product AB at the measurement point can be quantitatively calculated. By calculating the amount of amide bonds or peptide bonds, the optical analysis system 1 can calculate the yield of the product AB in the chemical reaction system 30 in real time.

For example, referring to FIG. 3A, the light absorption spectrum peak of the first raw material A appears on the shorter wavelength side in the near-infrared region from 1800 nm to 2500 nm. For example, referring to FIG. 3B, the light absorption spectrum peak of the second raw material B appears on the longer wavelength side in the near-infrared region from 1800 nm to 2500 nm.

For example, since the chemical synthesis is incomplete at position P3, a large amount of the first raw material A and the second raw material B remain in the mixture C. Therefore, as shown in FIG. 3C, in the light absorption spectrum measurement of the mixture C, a plurality of peaks corresponding to the light absorption spectrum peaks of the first raw material A and the second raw material B appear. In addition to this, the proportion of product AB in mixture C increases at position P3. Therefore, in the optical absorption spectrum shown in FIG. 3C, there is an optical absorption spectral peak attributed to the product AB.

When the light absorption spectrum peak of the product AB is sufficiently higher than the light absorption spectrum peaks of the first raw material A and the second raw material B, the light absorption spectrum of the product AB is clearly prominent in the light absorption spectrum of the mixture C. , which is easy to measure. However, when the height of the light absorption spectrum peak of the product AB is about the same or less than the light absorption spectrum peaks of the first raw material A and the second raw material B, the light absorption spectrum of the product AB is the light of the mixture C. Buried in the absorption spectrum, its measurement is difficult.

In order to facilitate the measurement of the light absorption spectrum of product AB even when the light absorption spectrum of product AB is buried in the light absorption spectrum of mixture C, operation unit 22 extracts the light absorption spectrum of mixture C from The optical absorption spectra of each of the first raw material A and the second raw material B are subtracted. Thereby, the calculation unit 22 calculates the optical absorption spectrum of the product AB as shown in FIG. 3D. For example, the calculation unit 22 multiplies the peaks of the light absorption spectra of the first raw material A and the second raw material B shown in FIGS. The height is approximately equal to the height of the light absorption spectrum peak. After that, the calculation unit 22 subtracts the light absorption spectrum of each of the first raw material A and the second raw material B from the light absorption spectrum of the mixture C.

Thus, in the optical analysis system 1, for example, the calculation unit 22 calculates the yield of the product AB based on the height of the light absorption spectrum peak of the product AB. The method for calculating the yield of product AB is not limited to this, and may include any method. For example, the calculation unit 22 may calculate the yield of the product AB in consideration of the width of the light absorption spectrum in addition to the height of the light absorption spectrum peak.

FIG. 4A is a schematic diagram showing an example of the light absorption spectrum of product AB at position P1. FIG. 4B is a schematic diagram showing an example of the light absorption spectrum of product AB at position P2. FIG. 4C is a schematic diagram showing an example of the light absorption spectrum of product AB at position P3. FIG. 4D is a schematic diagram showing an example of the optical absorption spectrum of product AB at position P4. FIG. 4E is a schematic diagram showing an example of the optical absorption spectrum of product AB at position P5.

For example, as shown in FIG. 1, by performing measurements at a plurality of positions P1 to P5 in the flow chemical reaction tube 32, a plurality of detection units 12 are used to measure the light absorption of the product AB each time the reaction time elapses. A spectrum is obtained. This allows quantitative calculation of the amount of the given structure of the compound for the product AB at each point. Therefore, it is possible to grasp the temporal change of the light absorption spectrum of the product AB, and as a result, it is possible to quantitatively calculate the temporal change of the amount of the predetermined structure of the compound related to the product AB.

For example, referring to FIGS. 4A through 4E in sequence, as the proportion of product AB in mixture C gradually increases from position P1 to position P5, the optical absorption spectral peak of product AB becomes progressively higher. there is At this time, the proportions of the first raw material A and the second raw material B in the mixture C gradually decrease, so that the light absorption spectrum peaks of the first raw material A and the second raw material B gradually decrease.

Suppose that the flow velocity of the solution inside the flow chemical reaction tube 32 is high, and the time from immediately after the mixing of the first source material A and the second source material B to the completion of the chemical synthesis is very high, such as 0.1 s to 0.5 s. It is difficult to specify the reaction time when extracting a sample for measurement when the reaction time is short. On the other hand, in the optical analysis system 1 according to the first embodiment, optical analysis is possible without extracting the sample, so it is possible to accurately grasp how many seconds after mixing the state is being analyzed. It is possible.

FIG. 5 is a flow chart showing an example of the operation of the optical analysis system 1 of FIG. A main flow of an optical analysis method using the optical analysis system 1 will be described with reference to FIG.

In step S101, the optical analysis system 1 uses the irradiation unit 11 of the optical measurement device 10 to irradiate each of the first raw material A and the second raw material B before the start of synthesis with irradiation light L1, and the mixture after the start of synthesis C is irradiated with irradiation light L1.

In step S102, the optical analysis system 1 uses the detection unit 12 of the optical measurement device 10 to detect the measurement light L2 including information on the spectral spectra of the first raw material A, the second raw material B, and the mixture C.

In step S<b>103 , the optical analysis system 1 uses the calculation unit 22 of the optical analysis device 20 to calculate the spectral spectra of the first raw material A, the second raw material B, and the mixture C, respectively.

In step S104, the optical analysis system 1 uses the calculation unit 22 of the optical analysis device 20 to calculate the spectrum of the product AB. At this time, the calculation unit 22 subtracts the spectral spectra of the first raw material A and the second raw material B from the spectral spectrum of the mixture C to calculate the spectral spectrum of the product AB.

According to the optical analysis system 1 according to the first embodiment as described above, the yield of the product AB obtained by chemical synthesis can be calculated based on the spectroscopic spectrum of the product AB calculated by the calculation unit 22. be. Therefore, according to the optical analysis system 1 according to the first embodiment, the amount of the product AB synthesized in the chemical reaction system 30 can be analyzed non-destructively without the need to extract a sample. According to the optical analysis system 1, the optical absorption spectrum is measured by an optical method in a non-contact manner using the optical measurement device 10, so the yield of the product AB can be calculated in real time. According to optical analysis system 1, it is not necessary to separate product AB from mixture C to determine the amount of product AB, and based on the optically separated light absorption spectrum, the yield of product AB is calculated quickly and easily.

According to the optical analysis system 1, non-destructive analysis is possible without affecting the chemical reaction system 30, so the disposal cost of the sample to be analyzed is suppressed. According to the optical analysis system 1, there is no need to use an expensive analyzer, and maintenance costs are also suppressed. That is, a simple and low-cost analysis system including the optical measurement device 10 and the optical analysis device 20 can be realized.

According to the optical analysis system 1, the work process for optimizing chemical reaction conditions is simplified, and the work efficiency for optimization is improved. More specifically, when monitoring the amount of predetermined structures in a compound, the optical analysis system 1 detects other peaks in the light absorption spectrum even though the light absorption spectrum peaks indicating these predetermined structures have not changed. By detecting a change in , it can be determined that an undesired side reaction other than the main reaction is proceeding. Therefore, according to the optical analysis system 1, rapid detection of reaction abnormality is possible. This allows the operator to quickly acquire information for optimizing chemical reaction conditions. Such information can be used by the operator to improve the yield of product AB.

In the first embodiment, the calculation unit 22 may subtract the spectral spectra of the first raw material A and the second raw material B from the spectral spectrum of the mixture C to calculate the spectral spectrum of the product AB. Thereby, the spectral spectrum of the product AB buried in the spectral spectrum of the mixture C is extracted. Therefore, the accuracy of calculating the yield of the product AB based on the spectroscopic spectrum is improved.

In the first embodiment, the chemical reaction system 30 may include a flow-type synthesis reaction system in which the first raw material A, the second raw material B, and the mixture C each flow inside the flow path. As a result, even in a flow-type synthesis reaction system in which it is difficult to extract a sample for measurement, the optical absorption spectrum can be measured in a non-contact manner by an optical technique without the need to extract a sample. Therefore, the yield of product AB can be calculated in real time.

(Second embodiment)
A second embodiment of the present disclosure will be mainly described. In the second embodiment, the information on the chemical reaction is primarily information on the optical isomerism of the product AB. In the second embodiment, description will be made mainly focusing on the information on the optical isomerism of the product AB. First, the problems of the prior art will be explained.

Conventionally, for example, when the product contains a compound formed by a peptide bond, i.e., a peptide, the peptide is analyzed based on the above-described analytical methods including the HPLC method using a chiral column and the method using a circular dichroism spectrometer. Information about the optical isomerism of the constituent amino acids is analyzed. Information on optical isomerism includes, for example, whether or not each of a pair of compounds having an optical isomer relationship with each other is produced, the abundance ratio of each when both of the pair of compounds are produced, and the amount of each. include.

In order to analyze information on the optical isomerism of amino acid residues constituting a peptide, first, amino acids are cut out one by one by hydrolysis from the N-terminal side of the peptide to be analyzed. The cleaved amino acid is then subjected to, for example, an HPLC analyzer with a chiral column. Depending on whether the sample amino acid applied to the chiral column constitutes the D-form or the L-form, the interaction time with the chiral column differs. Therefore, the elution time differs depending on whether the D-isomer or L-isomer is formed. This time difference is used to analyze information on optical isomerism.

On the other hand, for example, also in the method using a circular dichroism spectrometer, an operation of cleaving amino acids is performed in the same manner as in the HPLC method using a chiral column. A circular dichroism spectrum is then obtained for each amino acid solution. Based on the optical rotatory power of the optically active substance, the light absorption amounts for right-handed circularly polarized light and left-handed circularly polarized light are different. Right-handed circularly polarized light and left-handed circularly polarized light are irradiated at wavelengths corresponding to absorption transitions possessed by the analyte, and a circular dichroism spectrum is measured based on the difference in the amount of absorption. Analysis of the circular dichroism spectrum makes it possible to distinguish whether the optically active substance is in the D-form or the L-form.

In such conventional techniques, when analyzing information on optical isomerism of amino acids that constitute a peptide, it is necessary to extract a sample for measurement and hydrolyze and cut out the amino acids from the peptide. Therefore, the analysis work was complicated and the work time was increased. In addition, extracted samples were processed for optical isomer analysis and discarded after analysis. That is, destructive analysis was performed in the prior art. Such destructive analysis was costly when the analytes were rare.

The optical analysis system 1 according to the second embodiment of the present disclosure solves these problems, and provides information on the optical isomerism of the product AB synthesized in the chemical reaction system 30 without the need to extract a sample and without can be destructively analyzed. An optical analysis system 1 according to a second embodiment of the present disclosure will be described below with reference to the accompanying drawings.

The configuration and functions of the optical analysis system 1 according to the second embodiment are the same as those described above regarding the first embodiment described with reference to FIGS. 1 to 3D and FIG. Accordingly, the corresponding content described in the first embodiment applies equally to the second embodiment. Differences from the first embodiment will be mainly described below.

3A-3D did not consider the isomerization of the compounds that make up the product AB in order to explain the basic processing by the optical analysis system 1. FIG. The isomerization of the compounds that make up the product AB will be explained with reference to Figures 6A to 6E.

FIG. 6A is a schematic diagram showing an example of the light absorption spectrum of product AB at position P1. FIG. 6B is a schematic diagram showing an example of the light absorption spectrum of product AB at position P2. FIG. 6C is a schematic diagram showing an example of the light absorption spectrum of the product AB at position P3. FIG. 6D is a schematic diagram showing an example of the optical absorption spectrum of product AB at position P4. FIG. 6E is a schematic diagram showing an example of the optical absorption spectrum of product AB at position P5.

Depending on the chemical reaction conditions in the chemical reaction system 30, the compounds constituting the product AB are isomerized, and the product AB includes a pair of compounds having an optical isomer relationship with each other. In the following, with reference to FIGS. 6A to 6E, consider the case where product AB includes a pair of compounds having an optical isomer relationship with each other.

At this time, for example, as shown in FIG. 6C, in the optical absorption spectrum of product AB, in addition to the peaks shown in FIG. 3D that appear when isomerization does not occur, new peaks appear at different wavelengths. That is, the light absorption spectrum peak caused by the product AB1 and the light absorption caused by the product AB2 composed of the optical isomer c2 of the compound c1 constituting the product AB1 corresponding to the peaks shown in FIG. 3D A spectral peak appears. At this time, product AB includes product AB1 and product AB2.

Thus, the present disclosure shows that when isomerization occurs in product AB, interactions with other chemicals such as solvents present in the environment differ between compound c1 and optical isomer c2, and absorption It is based on the new finding that the transition wavelengths are different from each other. Interactions include, for example, any interaction that affects the vibrational state of a molecule, and means the action of attractive or repulsive forces, the formation of bonds, and changes in the degree of bond strength. Interactions include, for example, the action of van der Waals forces, hydrogen bonding, ionic bonding, and the like.

For example, when there is no other chemical substance around each of the compound c1 and the optical isomer c2 and each exists alone, the light absorption spectrum of the compound c1 and the light absorption spectrum of the optical isomer c2 match each other. do. The difference between the interaction between the compound c1 and the other chemical substance and the interaction between the optical isomer c2 and the other chemical substance causes a difference in the change in the energy level structure of each. Due to this difference, peaks appear at different wavelength positions in the light absorption spectrum of compound c1 and the light absorption spectrum of optical isomer c2.

For example, when isomerization occurs during the reaction of consecutively linking amino acids in chemical peptide synthesis, differences in interaction with peripheral molecules as described above occur. Due to such a difference in interaction, a difference in optical absorption spectrum shape occurs in the near-infrared region with wavelengths from 1800 nm to 2500 nm. Therefore, the amount of the optical isomer c2 of the synthesized peptide can be quantitatively calculated by measuring the light absorption of the measurement light L2 in the near-infrared light absorption spectrum band from 1800 nm to 2500 nm.

For example, as shown in FIG. 1, by performing measurements at a plurality of positions P1 to P5 in the flow chemical reaction tube 32, using a plurality of detection units 12, the product AB1 and the product Absorption spectra of AB2 are obtained. As a result, information on the optical isomerism of the product AB synthesized by the chemical reaction system 30 can be quantitatively analyzed at each point. Therefore, it is possible to grasp the temporal change of the information on the optical isomerism of the product AB. For example, changes over time in the amounts of compound c1 and optical isomer c2 can be quantitatively calculated.

For example, referring to FIGS. 6A through 6E in sequence, as the proportion of product AB1 and product AB2 in mixture C gradually increases from position P1 to position P5, each optical absorption spectral peak becomes progressively higher. It's becoming At this time, the proportions of the first raw material A and the second raw material B in the mixture C gradually decrease, so that the light absorption spectrum peaks of the first raw material A and the second raw material B gradually decrease.

Suppose that the flow velocity of the solution inside the flow chemical reaction tube 32 is high, and the time from immediately after the mixing of the first source material A and the second source material B to the completion of the chemical synthesis is very high, such as 0.1 s to 0.5 s. It is difficult to specify the reaction time when extracting a sample for measurement when the reaction time is short. On the other hand, in the optical analysis system 1 according to the second embodiment, optical analysis is possible without extracting the sample, so it is possible to accurately grasp how many seconds after mixing the state is being analyzed. It is possible.

According to the optical analysis system 1 according to the second embodiment as described above, the information on the optical isomerism of the product AB obtained by chemical synthesis is analyzed based on the spectroscopic spectrum of the product AB calculated by the calculation unit 22. It is possible. Therefore, according to the optical analysis system 1 according to the second embodiment, information on the optical isomerism of the product AB synthesized in the chemical reaction system 30 can be analyzed non-destructively without the need to extract a sample. Product AB includes either a non-isomerized compound or a pair of compounds having an optical isomer relationship with each other, as described above. For example, according to the optical analysis system 1, the amount of the optical isomer c2 in the peptide chemical reaction system 30 can be quantitatively calculated based on the peak separated from the light absorption spectrum peak of the compound c1.

According to the optical analysis system 1, the optical absorption spectrum is measured by an optical method in a non-contact manner using the optical measurement device 10, so the yield of the product AB can be calculated in real time. According to optical analysis system 1, it is not necessary to separate product AB from mixture C to determine the amount of product AB, and based on the optically separated light absorption spectrum, the yield of product AB is calculated quickly and easily.

According to the optical analysis system 1, non-destructive analysis is possible without affecting the chemical reaction system 30, so the disposal cost of the sample to be analyzed is suppressed. According to the optical analysis system 1, there is no need to use an expensive analyzer, and maintenance costs are also suppressed. That is, a simple and low-cost analysis system including the optical measurement device 10 and the optical analysis device 20 can be realized.

According to the optical analysis system 1, the work process for optimizing chemical reaction conditions is simplified, and the work efficiency for optimization is improved. More specifically, when monitoring the amount of predetermined structures in a compound, the optical analysis system 1 detects other peaks in the light absorption spectrum even though the light absorption spectrum peaks indicating these predetermined structures have not changed. By detecting a change in , it can be determined that an undesired side reaction other than the main reaction is proceeding. Therefore, according to the optical analysis system 1, rapid detection of reaction abnormality is possible. This allows the operator to quickly acquire information for optimizing chemical reaction conditions. Such information can be used by the operator to improve the yield of product AB or to reduce the incidence of isomerization.

According to the optical analysis system 1, the optical absorption spectrum of the obtained product AB reflects the interaction with other chemical substances such as solvents present in the surroundings. For example, the optical absorption spectrum of product AB has peaks at wavelength positions reflecting such interactions. Therefore, for example, it is possible to measure changes in interactions due to hydrogen bonding between biomolecules such as peptides and peripheral molecules. Thereby, the optical analysis system 1 can be used, for example, when it is necessary to measure changes in the hydrogen bonding state, and such changes can be measured in real time.

In the second embodiment, the calculation unit 22 may subtract the spectral spectra of the first raw material A and the second raw material B from the spectral spectrum of the mixture C to calculate the spectral spectrum of the product AB. Thereby, the spectral spectrum of the product AB buried in the spectral spectrum of the mixture C is extracted. Therefore, the analytical accuracy of the information on the optical isomerism of the product AB based on the spectroscopic spectrum is improved.

In the second embodiment, the chemical reaction system 30 may include a flow-type synthetic reaction system in which the first raw material A, the second raw material B, and the mixture C each flow inside a channel. As a result, even in a flow-type synthesis reaction system in which it is difficult to extract a sample for measurement, the optical absorption spectrum can be measured in a non-contact manner by an optical technique without the need to extract a sample. Therefore, information about the optical isomerism of product AB can be analyzed in real time.

In the second embodiment, the wavelength band of the measurement light L2 may be included in the near-infrared region from 1800 nm to 2500 nm. Thereby, the optical analysis system 1 can calculate the spectroscopic spectrum caused by the optical isomerism of the product AB appearing in the near-infrared region.

(Third embodiment)
A third embodiment of the present disclosure will be mainly described. In the third embodiment, the information about chemical reactions is mainly changes over time in parameters about chemical reactions. In the third embodiment, description will be given mainly focusing on changes over time in parameters relating to chemical reactions. Parameters relating to chemical reactions include, for example, the yield of product AB.

In conventional techniques, if one wishes to measure a parameter related to a chemical reaction at a particular time, it is common to extract a sample and separately measure the extracted sample with an analytical instrument. Therefore, in order to understand the temporal change of parameters related to chemical reactions, it was necessary to extract samples at multiple reaction times and measure them using various analytical instruments. Thus, conventional measurement methods are very complicated.

The optical analysis system 1 according to the third embodiment of the present disclosure solves such problems, and changes over time in parameters related to chemical reactions in the chemical reaction system 30 without the need to extract samples and nondestructively can be analyzed. An optical analysis system 1 according to a third embodiment of the present disclosure will be described below with reference to the accompanying drawings.

The configuration and functions of the optical analysis system 1 according to the third embodiment are the same as those described above regarding the first embodiment described with reference to FIGS. 1 to 3D and FIG. Accordingly, the corresponding content described in the first embodiment applies equally to the third embodiment. In the following, the change over time in the amount of the predetermined structure of the compound related to the product AB, that is, the yield of the product AB described in the first embodiment will be described in more detail. The following description applies equally to a second embodiment in which the product AB comprises a product AB1 and a product AB2 composed of the optical isomer c2 of the compound c1 which constitutes the product AB1.

As described in the first embodiment, the irradiation unit 11 is provided at a plurality of positions P1, P2, P3, P4, and P5 respectively along the flow chemical reaction tube 32 downstream of the microreactor 33, where the mixture C flows. , the irradiation light L1c is emitted. Five positions P 1 , P 2 , P 3 , P 4 and P 5 in the flow chemical reaction tube 32 are separated from the microreactor 33 in order. That is, the reaction time in mixture C increases from position P1 to P5. The irradiation unit 11 irradiates the mixture C after the start of synthesis with the irradiation light L1c for each of a plurality of reaction times. The reaction time may be calculated, for example, by dividing the distance from the microreactor 33 to each position by the flow velocity of the solution flowing inside the flow chemical reaction tube 32 .

FIG. 7 is a diagram showing an example of temporal changes in parameters relating to chemical reactions calculated by the computing unit 22 of the optical analysis system 1 according to the third embodiment. In the graph shown in FIG. 7, the vertical axis indicates, for example, the yield of product AB. The horizontal axis, for example, indicates the reaction time in mixture C, with reaction times t1, t2, t3, t4, and t5 corresponding to positions P1, P2, P3, P4, and P5, respectively, on a scale.

4A to 4E, based on the spectroscopic spectrum of the product AB calculated for each of a plurality of reaction times t1, t2, t3, t4, and t5, the parameters related to the chemical reaction over time Calculate change. For example, the calculation unit 22 calculates the yield of the product AB based on the peak height for the light absorption spectrum at the position P1 as shown in FIG. 4A. Similarly, the computing unit 22 calculates the yield of the product AB based on the peak heights for the optical absorption spectra at positions P2, P3, P4, and P5 as shown in FIGS. 4B, 4C, 4D, and 4E, respectively. Calculate the rate. The calculation unit 22 associates each calculated yield of the product AB with each reaction time, and calculates the temporal change in the yield of the product AB. The calculation unit 22 may store the calculated temporal change in the yield of the product AB in the storage unit 25 .

The computing unit 22 may, for example, perform a simulation of changes over time in parameters relating to the chemical reaction based on information input by the operator obtained from the operating unit 24 before the chemical reaction is started. The computing unit 22 may store the simulation result in the storage unit 25 .

When the chemical reaction is started after the simulation result is obtained, the calculation unit 22 further calculates the simulation result stored in the storage unit 25 and the actually calculated yield of the product AB for each reaction time. may be associated. As shown in FIG. 7, the calculation unit 22 may cause the display unit 23, for example, to display the simulation result and the actual change in the yield of the product AB over time in association with each other. In FIG. 7, for example, the solid line indicates the simulation results, and the dots indicate changes in the yield of the actual product AB over time.

In FIG. 7, the simulation results show that, for example, as the reaction time increases, the yield of product AB increases at a substantially constant rate, and at a predetermined reaction time, the graph inverts and the yield of product AB increases. It shows how it becomes substantially constant with time. For example, the actual calculated yields of product AB for each reaction time t1, t2, t3, t4, and t5 show a similar behavior. More specifically, at reaction times t1, t2, and t3, the yield of product AB increases at a substantially constant rate with increasing reaction time. The graph bends between reaction times t3 and t4. At reaction times t4 and t5, the yield of product AB becomes approximately constant with reaction time.

The operator sets chemical reaction conditions for the chemical reaction based on the results of the simulation performed by the computing unit 22, and starts the chemical reaction based on the set chemical reaction conditions. The operator can confirm, for example, how the yield of the actual product AB follows the simulation result over time on the display unit 23 . In addition, the operator can grasp the time when the chemical reaction will end based on the inflection point of the graph. In addition, the operator can check the consistency of the actual product AB yield over time with the simulation results, optimize the chemical reaction conditions, and optimize the inference model for simulation. Become. The operator can confirm the consistency of the actual yield of the product AB over time with the simulation result by an optical method using the optical analysis system 1 in a non-contact manner in real time. Therefore, according to the optical analysis system 1, the work process for optimizing chemical reaction conditions and the like is simplified, and the work efficiency for optimization is improved.

For example, the operation unit 22 may perform the work by the worker as described above by machine learning. The computing unit 22 may have any configuration for learning processing in order to perform such processing.

FIG. 8 is a flow chart showing an example of the operation of the optical analysis system 1 according to the third embodiment. A main flow of an optical analysis method using the optical analysis system 1 will be described with reference to FIG.

In step S201, the optical analysis system 1 uses the irradiation unit 11 of the optical measurement device 10 to irradiate the first raw material A and the second raw material B before the start of synthesis with irradiation light L1, and the mixture after the start of synthesis C is irradiated with irradiation light L1 for each of a plurality of reaction times.

In step S202, the optical analysis system 1 uses the detection unit 12 of the optical measurement device 10 to detect the measurement light L2 including information on the spectral spectra of the first raw material A, the second raw material B, and the mixture C.

In step S<b>203 , the optical analysis system 1 uses the calculation unit 22 of the optical analysis device 20 to calculate the spectral spectra of the first raw material A, the second raw material B, and the mixture C.

In step S204, the optical analysis system 1 uses the calculation unit 22 of the optical analysis device 20 to calculate the spectrum of the product AB. At this time, the calculation unit 22 subtracts the spectral spectra of the first raw material A and the second raw material B from the spectral spectrum of the mixture C to calculate the spectral spectrum of the product AB.

In step S205, the optical analysis system 1 uses the calculation unit 22 of the optical analysis device 20 to calculate changes over time in parameters related to chemical reactions based on the spectrum of the product AB calculated for each of a plurality of reaction times. do.

According to the optical analysis system 1 according to the third embodiment as described above, it is possible to calculate the change over time of the parameters relating to the chemical reaction based on the spectroscopic spectrum of the product AB calculated by the calculator 22 . Therefore, according to the optical analysis system 1 according to the third embodiment, it is possible to non-destructively analyze changes over time in parameters relating to chemical reactions in the chemical reaction system 30 without the need to extract samples. According to the optical analysis system 1, the optical measurement device 10 is used to measure the light absorption spectrum by an optical technique in a non-contact manner, so changes over time in parameters relating to chemical reactions can be calculated and monitored in real time. For example, the operator and the optical analysis system 1 can estimate in real time the time at which the chemical reaction is completed. According to the optical analysis system 1, it is not necessary to separate the product AB from the mixture C in order to calculate the change in the parameters related to the chemical reaction over time, and based on the optically separated light absorption spectra, the parameters related to the chemical reaction is calculated quickly and easily.

According to the optical analysis system 1, non-destructive analysis is possible without affecting the chemical reaction system 30, so the disposal cost of the sample to be analyzed is suppressed. Since the optical analysis system 1 is based on measurement technology that does not affect the chemical reaction system 30, there is no need to stop the chemical reaction system 30 for the purpose of measurement.

According to the optical analysis system 1, there is no need to use an expensive analyzer, and maintenance costs are also suppressed. That is, a simple and low-cost analysis system including the optical measurement device 10 and the optical analysis device 20 can be realized.

In the third embodiment, the parameters related to the chemical reaction include, for example, the yield of product AB, and the change over time of product AB has been mainly described. Parameters related to chemical reactions are not limited to these, and may include other arbitrary parameters. For example, the parameters relating to the chemical reaction may include the temperature in the chemical reaction system 30, more specifically the flow chemical reaction tube 32 downstream of the microreactor 33, and the purity of the product AB.

When the parameter related to the chemical reaction is the temperature of the chemical reaction system 30, the optical analysis system 1 indicates, for example, the temperature of the chemical reaction system 30 for each reaction time due to reaction heat based on the chemical reaction. Calculate the change in temperature over time. For example, the calculation unit 22 calculates the temperature of the chemical reaction system 30 based on the peak height of the light absorption spectrum at each position as shown in FIGS. 4A to 4E. In addition, for example, the calculation unit 22 may calculate the temperature of the chemical reaction system 30 based on the wavelength position of the peak for the light absorption spectrum at each position as shown in FIGS. 4A to 4E.

If the temperature change over time of the chemical reaction system 30 is obtained by the optical analysis system 1, the operator and the optical analysis system 1 can analyze how the temperature change in the chemical reaction system 30 affects the chemical reaction. can be done. The operator and the optical analysis system 1 are also facilitated in optimizing the chemical reaction conditions, e.g. with respect to temperature, such that the yield of product AB is better. The operator and the optical analysis system 1 determine whether an undesired side reaction other than the main reaction is progressing based on a criterion such as whether the temperature of the chemical reaction system 30 is rising due to an exothermic reaction, for example. It is also possible to determine that

In the third embodiment, the optical analysis system 1 is described as calculating parameters for chemical reactions at five positions P1, P2, P3, P4, and P5 in order to calculate changes over time in parameters for chemical reactions. The number of measurement points is not limited to this, and may be at least two.

It will be apparent to those skilled in the art that the present disclosure can be embodied in certain other forms than those described above without departing from the spirit or essential characteristics thereof. Accordingly, the preceding description is exemplary, and not limiting. The scope of the disclosure is defined by the appended claims rather than by the foregoing description. Any changes that fall within the range of equivalence are intended to be included therein.

For example, the shape, arrangement, orientation, number, and the like of each component described above are not limited to the contents illustrated in the above description and drawings. The shape, arrangement, orientation, number, and the like of each component may be arbitrarily configured as long as the function can be realized.

In the first to third embodiments, the calculation unit 22 subtracts the light absorption spectra of the first raw material A and the second raw material B from the light absorption spectrum of the mixture C to calculate the spectral spectrum of the product AB. However, the calculation method is not limited to this. If the light absorption spectrum of the product AB can be clearly measured even in the light absorption spectrum of the mixture C, the calculation unit 22 does not need to perform the process of subtracting the light absorption spectrum. At this time, in the light absorption spectrum of the mixture C, the calculation unit 22 may determine a predetermined peak different from the light absorption spectrum peaks of the first raw material A and the second raw material B as the light absorption spectrum peak of the product AB. .

Instead of or in addition to the process of subtracting the light absorption spectrum, the calculation unit 22 may highlight the light absorption spectrum of the product AB using any display method. The display method includes, for example, a method of displaying a cursor and a vertical line according to the light absorption spectrum peak, a method of changing the display color of the entire light absorption spectrum, and a method of blinking the entire light absorption spectrum.

In the first to third embodiments, the chemical reaction system 30 has been described as including a flow-type synthesis reaction system that flows inside the flow chemical reaction tube 32, but is not limited to this. Chemical reaction system 30 may include a batch synthesis reaction system. For example, when the chemical reaction system 30 is a batch-type synthesis reaction system, the irradiating unit 11 uses a plurality of It is not necessary to irradiate the irradiation light L1 at one position, and the irradiation light L1 may be irradiated only at one position.

In the first to third embodiments, the wavelength band of the measurement light L2 was described as being included in the near-infrared region from 1800 nm to 2500 nm, but it is not limited to this. The measurement light L2 may have any wavelength band that allows the optical analysis system 1 to analyze the light absorption spectrum of the product AB. For example, the wavelength band of the measurement light L2 may be included in any wavelength region including ultraviolet, visible, mid-infrared, and far-infrared regions.

In the first to third embodiments, the measurement light L2 includes transmitted light based on the irradiation light L1, and the spectral spectrum includes the light absorption spectrum, but the present invention is not limited to this. The optical analysis system 1 may calculate the spectroscopic spectrum of the product AB using any spectroscopic method other than such absorption spectroscopic method. Spectroscopy may include, for example, fluorescence spectroscopy and Raman spectroscopy. For example, in fluorescence spectroscopy, the measurement light L2 includes fluorescence based on the illumination light L1, and the spectral spectrum includes the fluorescence spectrum. For example, in Raman spectroscopy, the measurement light L2 includes Raman light based on the illumination light L1, and the spectral spectrum includes a Raman spectrum.

FIG. 9 is a block diagram of a modification of the optical analysis system 1 according to the first to third embodiments. In the first to third embodiments, the optical analysis system 1 has been described as being composed of a plurality of different devices with separate functions based on the optical measurement device 10 and the optical analysis device 20 . The configuration of the optical analysis system 1 is not limited to this. For example, as shown in FIG. 9, the optical analysis system 1 according to the modification may be configured by one device in which the functions of each component are integrated.

The optical analysis system 1 according to the modification includes a calculation unit 16 that integrates the functions of the control unit 13 and the calculation unit 22 in the first to third embodiments, and the storage unit 15 in the first to third embodiments. and a storage unit 17 that integrates the functions of the storage unit 25, an irradiation unit 11, a detection unit 12, a display unit 23, and an operation unit 24. For the function of each component of the optical analysis system 1 according to the modification, the same description as that of the corresponding component of the first to third embodiments is applied.

According to the optical analysis system 1 according to the modification as described above, the same effects as those of the first to third embodiments can be obtained. In addition, the optical analysis system 1 has a simpler configuration because processing such as the measurement of the light absorption amount for each wavelength of the measurement light L2 and the calculation of the spectroscopic spectrum are performed by one apparatus.

For example, the functions included in each step of the optical analysis method described above can be rearranged so as not to be logically inconsistent, and multiple steps can be combined into one or divided. .

Although the optical analysis system 1 and the optical analysis method have been mainly described above, the present disclosure is a program executed by a processor included in each of the control unit 13, the calculation unit 22, and the calculation unit 16, or a storage medium recording the program It can also be realized as It should be understood that the scope of the present disclosure includes these as well.

1 optical analysis system 10 optical measurement device 11 irradiation unit 12 detection unit 13 control unit 14 communication unit 15 storage unit 16 calculation unit 17 storage unit 20 optical analysis device 21 communication unit 22 calculation unit 23 display unit 24 operation unit 25 storage unit 30 chemistry Reaction system 31 Liquid sending pump 32 Flow chemical reaction tube (flow path)
33 Microreactor 40 Data communication cable A First raw material B Second raw material AB, AB1, AB2 Product C Mixture c1 Compound c2 Optical isomers L1, L1a, L1b, L1c Irradiation light L2, L2a, L2b, L2c Measurement light P1, P2, P3, P4, P5 Position t1, t2, t3, t4, t5 Reaction time

Claims (10)

In a chemical reaction system for obtaining a product by synthesizing a first raw material and a second raw material, each of the first raw material and the second raw material before the start of synthesis is irradiated with irradiation light, and the first raw material and the second raw material are irradiated with irradiation light. an irradiating unit that irradiates a mixture containing two raw materials and the product after the start of synthesis with irradiation light every a plurality of reaction times;
a detection unit that detects the measurement light based on the irradiation light emitted by the irradiation unit, the measurement light containing information on the respective spectral spectra of the first raw material, the second raw material, and the mixture;
a calculation unit that calculates the spectral spectrum of each of the first raw material, the second raw material, and the mixture, and calculates the spectral spectrum of the product based on each spectral spectrum;
with
The calculation unit calculates changes over time in parameters related to chemical reactions based on the spectroscopic spectra of the products calculated for each of a plurality of reaction times,
Optical analysis system. The calculation unit calculates the spectral spectrum of the product by subtracting the spectral spectrum of each of the first raw material and the second raw material from the spectral spectrum of the mixture.
An optical analysis system according to claim 1. The chemical reaction system includes a flow-type synthetic reaction system in which the first raw material, the second raw material, and the mixture each flow through a channel,
3. An optical analysis system according to claim 1 or 2. The irradiation unit irradiates the irradiation light at each of a plurality of positions along the flow path through which the mixture flows,
An optical analysis system according to claim 3. parameters relating to the chemical reaction include the yield of the product;
5. An optical analysis system according to any one of claims 1-4. Each of the first raw material and the second raw material contains an amino acid,
the product comprises a compound formed by a peptide bond;
6. An optical analysis system according to any one of claims 1-5. The wavelength band of the measurement light is included in the near-infrared region from 1800 nm to 2500 nm.
7. An optical analysis system according to any one of claims 1-6. The measurement light includes transmitted light based on the irradiation light that has passed through each of the first raw material, the second raw material, and the mixture,
The spectroscopic spectrum includes a light absorption spectrum,
8. An optical analysis system according to any one of claims 1-7. In a chemical reaction system for obtaining a product by synthesizing a first raw material and a second raw material, each of the first raw material and the second raw material before the start of synthesis is irradiated with irradiation light, and the first raw material and the second raw material are irradiated with irradiation light. a step of irradiating a mixture containing two raw materials and the product after the initiation of synthesis with irradiation light every a plurality of reaction times;
a step of detecting measurement light based on the irradiated irradiation light, the measurement light including information on spectral spectra of each of the first raw material, the second raw material, and the mixture;
calculating spectral spectra of each of the first raw material, the second raw material, and the mixture, and calculating the spectral spectrum of the product based on each spectral spectrum;
calculating changes over time in parameters related to chemical reactions based on the spectroscopic spectra of the products calculated for each of a plurality of reaction times;
including,
Optical analysis method. In the step of calculating the spectroscopic spectrum of the product, the spectroscopic spectrum of the product is calculated by subtracting the spectroscopic spectrum of each of the first raw material and the second raw material from the spectroscopic spectrum of the mixture.
The optical analysis method according to claim 9.

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