Device, method and program

Abstract

SOLUTION: A device comprises: a detection part for detecting a fluid spectrum that is a spectrum of light indicating a state of a fluid flowing in a flow path; a differentiation part for deriving a differential spectrum by differentiating the fluid spectrum; an extraction part for extracting a first solvent spectrum by principal component analysis of the solvent of the fluid; a calculation part for calculating a difference spectrum between the differential spectrum and the first solvent spectrum; and a prediction part for predicting a state of the fluid, by using data related to a peak of the calculated difference spectrum.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an apparatus, a method, and a program. [Background technology]

[0002] Patent documents 1 and 2 describe "an optical analysis system and an optical analysis method that can non-destructively analyze information about the optical isomerism of a target substance synthesized in a chemical reaction system without the need to extract a sample." [Prior art document] [Patent documents] Patent Document 1: Patent No. 7087696 Patent Document 2: Patent No. 7192473 Summary of the Invention

[0003] In a first aspect of the present invention, an apparatus is provided that includes a detection unit that detects a fluid spectrum, which is a spectrum of light that indicates the state of a fluid flowing through a flow path; a differentiation unit that differentiates the fluid spectrum to derive a differential spectrum; an extraction unit that extracts a first solvent spectrum of the fluid solvent using principal component analysis; a calculation unit that calculates a difference spectrum between the differential spectrum and the first solvent spectrum; and a prediction unit that predicts the state of the fluid using data related to the peaks of the calculated difference spectrum.

[0004] The above-mentioned device may further include a generation unit that generates a model for predicting the state of the fluid using the difference spectrum in response to input of data regarding the peak of the difference spectrum of the fluid, and the prediction unit may input the data regarding the peak of the difference spectrum into the model to predict the state of the fluid.

[0005] Any of the above devices may further include an acquisition unit that acquires a second solvent spectrum corresponding to the solvent, and the extraction unit may use the second solvent spectrum to extract the first solvent spectrum from the differential spectrum by principal component analysis.

[0006] In the above-described device, the acquisition unit may acquire a second solvent spectrum according to the pH or temperature of the fluid, and the extraction unit may use the second solvent spectrum to extract the first solvent spectrum from the differential spectrum by principal component analysis.

[0007] In the above device, the acquisition section may estimate the pH or temperature of the fluid and acquire the second solvent spectrum according to the estimated pH or temperature.

[0008] In the above device, the acquisition unit may estimate the pH or temperature of the fluid based on a peak in the fluid spectrum that corresponds to water or a solvent in the fluid, and acquire a second solvent spectrum according to the estimated pH or temperature.

[0009] Any of the above devices may further include a memory unit that stores a plurality of second solvent spectra corresponding to a plurality of pH values ​​or a plurality of temperatures, and the acquisition unit may acquire from the memory unit a second solvent spectrum corresponding to the pH or temperature of the fluid from among the plurality of second solvent spectra.

[0010] In any of the above devices, the acquisition section may acquire the second solvent spectrum in which the peak is corrected according to the pH or temperature of the fluid.

[0011] In any of the above devices, the prediction unit may predict the reaction amount of a reaction in the fluid as the state of the fluid, using data relating to the peak of the difference spectrum.

[0012] In the above-described device, the prediction unit may predict the remaining amount of the raw material in the fluid using data relating to the peak of the difference spectrum.

[0013] The above-described device may further comprise an abnormality determination unit that determines that the reaction of the fluid is progressing when the remaining amount of the raw material in the fluid predicted by the prediction unit is less than a predetermined threshold value.

[0014] In a second aspect of the present invention, there is provided a method comprising the steps of detecting a fluid spectrum, which is a spectrum of light indicating the state of a fluid flowing through a flow path; differentiating the fluid spectrum to derive a differential spectrum; extracting a first solvent spectrum for the solvent of the fluid by principal component analysis; calculating a difference spectrum between the differential spectrum and the first solvent spectrum; and predicting the state of the fluid using data regarding the peaks of the calculated difference spectrum.

[0015] In a third aspect of the present invention, there is provided a program that is executed by a computer and causes the computer to function as a detection unit that detects a fluid spectrum, which is a spectrum of light that indicates the state of a fluid flowing through a flow path, a differentiation unit that differentiates the fluid spectrum to derive a differential spectrum, an extraction unit that extracts a first solvent spectrum for the fluid solvent using principal component analysis, a calculation unit that calculates a difference spectrum between the differential spectrum and the first solvent spectrum, and a prediction unit that predicts the state of the fluid using data related to the peaks of the calculated difference spectrum.

[0016] The above summary of the invention does not list all of the necessary features of the present invention, and subcombinations of these features may also constitute inventions. [Brief explanation of the drawings]

[0017] [Figure 1] 1 is a schematic diagram of a reaction system 10 according to the present embodiment. [Figure 2] A block diagram of the control device 30 is shown. [Figure 3] 1 shows an example of the flow of the second solvent spectrum detection operation of the reaction system 10. [Figure 4] An example of the flow of the reaction operation of the reaction system 10 is shown. [Figure 5] FIG. 1 shows an explanatory diagram of an example of a database storing second solvent spectra. [Figure 6] FIG. 10 is an explanatory diagram of another example of a database storing second solvent spectra. [Figure 7]FIG. 10 shows an explanatory diagram of an example of a derivative spectrum. [Figure 8] FIG. 1 shows an explanatory diagram of an example of a first solvent spectrum. [Figure 9] FIG. 10 shows an explanatory diagram of an example of a difference spectrum. [Figure 10] 22 illustrates an example computer 2200 in which aspects of the present invention may be embodied, in whole or in part. DETAILED DESCRIPTION OF THE INVENTION

[0018] The present invention will be described below through embodiments of the invention, but the following embodiments do not limit the scope of the invention according to the claims. Furthermore, not all of the combinations of features described in the embodiments are necessarily essential to the solution of the invention.

[0019] 1 is a schematic diagram of a reaction system 10 according to this embodiment. The reaction system 10 produces a target substance such as a peptide. The reaction system 10 includes a reaction device 20 and a control device 30.

[0020] The reaction device 20 is connected to the control device 30. The reaction device 20 may be, for example, a flow reactor such as a microflow reactor that produces a target substance by flow synthesis or the like. The reaction device 20 includes a first raw material tank 100, a first pump 102, a first liquid supply pipe 104, a second raw material tank 110, a second pump 112, a second liquid supply pipe 114, a third raw material tank 120, a third pump 122, a third liquid supply pipe 124, a fourth raw material tank 130, a fourth pump 132, a fourth liquid supply pipe 134, a first mixer 140, a first reaction pipe 142, and a second mixer 144. The reaction system includes a first reaction tube 150, a second reaction tube 152, a third mixer 160, a third reaction tube 162, a target tank 170, a first sensor unit 180, a second sensor unit 182, a third sensor unit 184, a fourth sensor unit 186, a fifth sensor unit 188, a sixth sensor unit 190, a seventh sensor unit 192, an eighth sensor unit 194, a ninth sensor unit 196, and a tenth sensor unit 198. In the following description, one or more of the first sensor unit 180, the second sensor unit 182, the third sensor unit 184, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, and the tenth sensor unit 198 will also be simply referred to as a sensor unit or a plurality of sensor units. The liquid transfer pipe and the reaction pipe in the reaction device 20 form a flow path from the raw material tank to the target product tank 170 .

[0021] The first raw material tank 100 is connected to the first mixer 140 via a first pump 102 and a first liquid supply pipe 104. The first raw material tank 100 contains a solvent containing a first raw material such as an amino acid. The first pump 102 supplies the solvent containing the first raw material from the first raw material tank 100 to the first liquid supply pipe 104 at a flow rate or flow rate according to preset reaction conditions. The first liquid supply pipe 104 forms a flow path therein. The first liquid supply pipe 104 may be a through-hole or a tube formed in a plate-like cell made of metal or resin. The first raw material fluid, which is the solvent containing the first raw material, flows into one of the inlets of the first mixer 140 through the flow path of the first liquid supply pipe 104.

[0022] The second raw material tank 110 is connected to the first mixer 140 via a second pump 112 and a second liquid supply pipe 114. The second raw material tank 110 contains a solvent containing the second raw material. The second pump 112 supplies the solvent containing the second raw material from the second raw material tank 110 to the second liquid supply pipe 114 at a flow rate or flow rate according to preset reaction conditions. The second liquid supply pipe 114 forms a flow path therein. The second liquid supply pipe 114 may be a through-hole or a tube formed in a plate-like cell made of metal or resin. The second raw material fluid, which is the solvent containing the second raw material, flows into the other inlet of the first mixer 140 through the flow path of the second liquid supply pipe 114.

[0023] The third raw material tank 120 is connected to the second mixer 150 via a third pump 122 and a third liquid supply pipe 124. The third raw material tank 120 contains a solvent containing the third raw material. The third pump 122 supplies the solvent containing the third raw material from the third raw material tank 120 to the third liquid supply pipe 124 at a flow rate or flow rate according to preset reaction conditions. The third liquid supply pipe 124 forms a flow path therein. The third liquid supply pipe 124 may be a through-hole or a tube formed in a plate-like cell made of metal or resin. The third raw material fluid, which is a solvent containing the third raw material, flows into one of the inlets of the second mixer 150 through the flow path of the third liquid supply pipe 124.

[0024] The fourth raw material tank 130 is connected to the third mixer 160 via a fourth pump 132 and a fourth liquid supply pipe 134. The fourth raw material tank 130 contains a solvent containing the fourth raw material. The fourth pump 132 supplies the solvent containing the fourth raw material from the fourth raw material tank 130 to the fourth liquid supply pipe 134 at a flow rate or flow rate according to preset reaction conditions. The fourth liquid supply pipe 134 has an internal flow path. The fourth liquid supply pipe 134 may be made of metal or resin and may be a through-hole formed in a tube or plate-like cell. The fourth raw material fluid, which is the solvent containing the fourth raw material, flows into one inlet of the third mixer 160 through the flow path of the fourth liquid supply pipe 134. Here, the first raw material, the second raw material, the third raw material, and the fourth raw material may be different raw materials, and the solvents may be the same or different types.

[0025] The first mixer 140 has an outlet connected to one end of the first reaction tube 142. The first mixer 140 may be a static mixer such as a T-shaped mixer or a Y-shaped mixer. The first mixer 140 mixes the first and second raw material fluids flowing in from two inlets, and discharges the mixture into the first reaction tube 142 as a first reaction fluid.

[0026] The other end of the first reaction tube 142 is connected to the second mixer 150. The first reaction tube 142 may be a through-hole or a tube formed in a plate-like cell made of metal or resin. A first reaction fluid flows through an internal flow path of the first reaction tube 142, and the first reaction fluid is discharged to the other inlet of the second mixer 150. A reaction of the first reaction fluid progresses while flowing through the first reaction tube 142, and an intermediate target product is produced by the reaction. The length, width, or shape of the reaction section in the first reaction tube 142 where the reaction progresses may be set in order to adjust reaction conditions such as reaction time.

[0027] The second mixer 150 has an outlet connected to one end of the second reaction tube 152. The second mixer 150 may be a static mixer such as a T-shaped mixer or a Y-shaped mixer. The second mixer 150 mixes the first reaction fluid and the third raw material fluid flowing in from two inlets, and discharges the mixture into the second reaction tube 152 as the second reaction fluid.

[0028] The other end of the second reaction tube 152 is connected to the third mixer 160. The second reaction tube 152 may be a through-hole or a tube formed in a plate-like cell made of metal or resin. The second reaction tube 152 allows a second reaction fluid to flow through an internal flow path and discharges the second reaction fluid to the other inlet of the third mixer 160. The second reaction fluid undergoes a reaction while flowing through the second reaction tube 152, and an intermediate target product is produced by the reaction. The length, width, or shape of the reaction section in the second reaction tube 152 where the reaction proceeds may be set to adjust reaction conditions such as reaction time.

[0029] The third mixer 160 has an outlet connected to one end of the third reaction tube 162. The third mixer 160 may be a static mixer such as a T-shaped mixer or a Y-shaped mixer. The third mixer 160 mixes the second reaction fluid and the fourth raw material fluid flowing in from two inlets, and discharges the mixture into the third reaction tube 162 as a third reaction fluid.

[0030] The other end of the third reaction tube 162 is connected to the target product tank 170. The third reaction tube 162 may be a through-hole or a tube formed in a plate-like cell made of metal or resin. The third reaction tube 162 allows a third reaction fluid to flow through an internal flow path and discharges the third reaction fluid into the target product tank 170. The third reaction fluid undergoes a reaction while flowing through the third reaction tube 162, and a final target product is produced by the reaction. The reaction section in the third reaction tube 162 where the reaction proceeds may have a length, width, or shape set to adjust reaction conditions such as reaction time.

[0031] The target product tank 170 contains the third reaction fluid discharged from the third reaction tube 162. Note that, between the third reaction tube 162 and the target product tank 170, a device such as a filter may be disposed to separate by-products and the final target product from the third reaction fluid and extract the final target product.

[0032] The first sensor unit 180 is disposed in the first liquid supply tube 104 and detects the state of the fluid in the first liquid supply tube 104. The first sensor unit 180 may detect at least one of the optical spectrum, pressure, flow velocity, flow rate, pH, or temperature of the fluid in the first liquid supply tube 104. The first sensor unit 180 may include at least one of an ultraviolet spectrometer, a visible spectrometer, a near-infrared spectrometer, or an infrared spectrometer for detecting the optical absorption spectrum of the fluid, a fluorescence spectrometer for detecting the emission spectrum of the fluid, or a Raman spectrometer for detecting Raman scattered light of the fluid. Here, the optical absorption and emission spectra of the fluid may be optical absorption, emission, or Raman spectra in the ultraviolet region (10 nm to 380 nm), visible region (380 nm to 800 nm), near-infrared region (wavelength 800 nm to 2500 nm), or infrared region (wavelength 2500 nm to 25000 nm), and the same applies hereinafter. In the following, only the optical absorption spectrum will be described.

[0033] The second sensor unit 182 is disposed in the second liquid feed tube 114 and detects the state of the fluid in the second liquid feed tube 114. The second sensor unit 182 may detect at least one of the optical spectrum, pressure, flow velocity, flow rate, pH, or temperature of the fluid in the second liquid feed tube 114. The second sensor unit 182 may have a similar configuration to the first sensor unit 180 and perform a similar operation.

[0034] The third sensor unit 184 is disposed in the third liquid feed tube 124 and detects the state of the fluid in the third liquid feed tube 124. The third sensor unit 184 may detect at least one of the optical spectrum, pressure, flow velocity, flow rate, pH, or temperature of the fluid in the third liquid feed tube 124. The third sensor unit 184 may have a similar configuration to the first sensor unit 180 and perform a similar operation.

[0035] The fourth sensor unit 186 is disposed in the fourth liquid feed tube 134 and detects the state of the fluid in the fourth liquid feed tube 134. The fourth sensor unit 186 may detect at least one of the optical spectrum, pressure, flow velocity, flow rate, pH, or temperature of the fluid in the fourth liquid feed tube 134. The fourth sensor unit 186 may have a similar configuration to the first sensor unit 180 and perform a similar operation.

[0036] The fifth sensor unit 188 is disposed in the first reaction tube 142 and detects the state of the fluid in the first reaction tube 142. The fifth sensor unit 188 may be disposed immediately before the second mixer 150, for example, at a position downstream of the reaction section where the reaction in the first reaction tube 142 progresses (i.e., a position where the reaction in the first reaction tube 142 is completed). The fifth sensor unit 188 may detect at least one of the optical spectrum, pressure, flow velocity, flow rate, pH, or temperature of the fluid in the first reaction tube 142. The fifth sensor unit 188 may have a configuration similar to that of the first sensor unit 180 and perform a similar operation.

[0037] The sixth sensor unit 190, the seventh sensor unit 192, and the eighth sensor unit 194 are disposed in the second reaction tube 152 and detect the state of the fluid in the second reaction tube 152. The sixth sensor unit 190, the seventh sensor unit 192, and the eighth sensor unit 194 may each detect at least one of the optical spectrum, pressure, flow velocity, flow rate, pH, and temperature of the fluid in the second reaction tube 152. The sixth sensor unit 190, the seventh sensor unit 192, and the eighth sensor unit 194 may be disposed at different positions in the second reaction tube 152 and perform detection at different positions in the second reaction tube 152. The sixth sensor unit 190, the seventh sensor unit 192, and the eighth sensor unit 194 may be disposed at three different positions downstream of the reaction zone where the reaction proceeds in the second reaction tube 152 (i.e., the position where the reaction in the second reaction tube 152 is completed), or may be disposed at the reaction zone where the reaction proceeds and downstream of the reaction zone, respectively. The sixth sensor unit 190, the seventh sensor unit 192, and the eighth sensor unit 194 may each have the same configuration as the first sensor unit 180 and perform the same operation.

[0038] The ninth sensor unit 196 is disposed in the third reaction tube 162 and detects the state of the fluid in the third reaction tube 162. The ninth sensor unit 196 may be disposed at a position downstream of the reaction section where the reaction in the third reaction tube 162 progresses (i.e., a position where the reaction in the third reaction tube 162 is completed). The ninth sensor unit 196 may detect at least one of the optical spectrum, pressure, flow velocity, flow rate, pH, and temperature of the fluid in the third reaction tube 162. The ninth sensor unit 196 may have a configuration similar to that of the first sensor unit 180 and perform a similar operation.

[0039] The tenth sensor unit 198 is disposed in the target tank 170 and detects the state of the target in the target tank 170. The tenth sensor unit 198 may detect a measurement value indicative of at least one of the light spectrum, pH, or temperature of the target in the target tank 170. The tenth sensor unit 198 may have a similar configuration to the first sensor unit 180 and perform a similar operation.

[0040] The control device 30 is connected to each component of the reactor 20. The control device 30 may be a computer such as a PC, tablet PC, smartphone, workstation, server computer, or general-purpose computer, or may be a computer system in which multiple computers are connected. Such a computer system is also considered a computer in a broad sense. The control device 30 may also be implemented by one or more virtual computer environments executable within a computer. Alternatively, the control device 30 may be a dedicated computer designed for the flow reactor, or may be dedicated hardware realized by dedicated circuits. The control device 30 may also be realized by cloud computing.

[0041] The control device 30 receives measurement results indicating the state of the fluid in the flow path of the reaction device 20 from at least one of the first sensor unit 180, the second sensor unit 182, the third sensor unit 184, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, or the tenth sensor unit 198. The control device 30 may predict the state of the fluid from the measurement results and control the reaction device 20 according to the prediction result.

[0042] FIG. 2 shows a more detailed block diagram of the control device 30. In this embodiment, the control device 30 extracts a first solvent spectrum corresponding to the solvent of the fluid from the fluid spectrum using principal component analysis or multivariate spectral decomposition (MCR-ALS), and predicts the state of the fluid from the fluid spectrum and the first solvent spectrum measured from the fluid. The control device 30 uses, for prediction, measurement results detected by a second solvent spectrum detection operation in which only the solvent is flowed through the flow path in the reaction device 20, and measurement results detected by a reaction operation in which a solvent containing raw materials is flowed through the flow path. The control device 30 includes a detection unit 200, a differentiation unit 210, a memory unit 220, an acquisition unit 230, an extraction unit 240, a calculation unit 250, a generation unit 260, a prediction unit 270, an abnormality determination unit 280, and an output unit 290.

[0043] The detection unit 200 is connected to the reaction device 20. The detection unit 200 detects a fluid spectrum, which is a spectrum of light that indicates the state of a fluid flowing through a flow path during a reaction operation. The detection unit 200 may receive measurement results that indicate the state of the fluid from at least one of the first sensor unit 180, the second sensor unit 182, the third sensor unit 184, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, or the tenth sensor unit 198. The detection unit 200 may calculate a fluid spectrum from the received measurement results, or may receive a fluid spectrum calculated in the reaction device 20. In the second solvent spectrum detection operation, the detection unit 200 may detect a second solvent spectrum, which is a spectrum of light indicating the state of a fluid consisting of only the solvent, from at least one of the first sensor unit 180, the second sensor unit 182, the third sensor unit 184, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, or the tenth sensor unit 198, similar to the reaction operation.

[0044] The differentiation unit 210 is connected to the detection unit 200. In a reaction operation, the differentiation unit 210 differentiates the fluid spectrum n-th order (n is a rational number) to derive a derivative spectrum (second-order differentiation will be described below as an example). The differentiation unit 210 may derive a derivative spectrum by performing second-order differentiation on the fluid spectrum detected by the detection unit 200. In a second solvent spectrum detection operation, the differentiation unit 210 may perform second-order differentiation on the second solvent spectrum in the same way as in the reaction operation.

[0045] The memory unit 220 is connected to the differentiation unit 210. The memory unit 220 may store a second solvent spectrum corresponding to a solvent of the fluid. The memory unit 220 may store the second solvent spectrum obtained by second-order differentiation by the differentiation unit 210 in the second solvent spectrum detection operation. The memory unit 220 may store a plurality of second solvent spectra corresponding to a plurality of pH values ​​or a plurality of temperatures, respectively.

[0046] The acquisition unit 230 is connected to the storage unit 220. The acquisition unit 230 acquires a second solvent spectrum corresponding to a solvent of a fluid during a reaction operation. The acquisition unit 230 may acquire a second solvent spectrum according to the pH or temperature of the fluid.

[0047] The extraction unit 240 is connected to the differentiation unit 210 and the acquisition unit 230. The extraction unit 240 extracts a first solvent spectrum from a fluid solvent by principal component analysis during a reaction operation. The extraction unit 240 may perform principal component analysis using the second solvent spectrum acquired by the acquisition unit 230, and extract the first solvent spectrum from the differential spectrum derived by the differentiation unit 210.

[0048] The calculation section 250 is connected to the differentiation section 210 and the extraction section 240. The calculation section 250 calculates a difference spectrum between the derivative spectrum derived by the differentiation section 210 and the first solvent spectrum extracted by the extraction section 240.

[0049] The generation unit 260 is connected to the calculation unit 250. The generation unit 260 uses the difference spectrum to generate a state prediction model that predicts the state of the fluid in response to input data related to the peaks in the difference spectrum of the fluid. In a learning operation, the generation unit 260 may generate the state prediction model from the relationship between the data related to the peaks in the difference spectrum calculated by the calculation unit 250, acquired through experiments or the like, and the measurement results of the fluid state. In the learning operation, the generation unit 260 may generate the state prediction model using data related to the peaks in the difference spectrum when the anomaly determination unit 280 does not determine an anomaly. In response to input of the intensity (e.g., absorbance) of the peaks in the difference spectrum in a predetermined wavenumber range corresponding to the target or raw material of the reaction, or the wavenumber at which the peaks in the difference spectrum occur, the generation unit 260 may generate a state prediction model that predicts whether the reaction of the fluid is in an abnormal state, the remaining amount of raw material, or the amount of the target produced in the reaction. In the difference spectrum of the fluid, a peak occurs in a wavenumber range corresponding to the type of target, and the greater the peak intensity, the greater the amount of the target. Furthermore, the generating unit 260 may generate a state prediction model that predicts at least one of the temperature, pressure, and raw material concentration of the fluid in response to input data related to the peak of the difference spectrum calculated by the calculating unit 250. The generating unit 260 may generate the state prediction model using Partial Least Square (PLS), Principle Component Regression (PCR), Multivariable Linear Regression (MLR), or the like. The generating unit 260 may also generate the state prediction model using logistic regression, neural networks, support vector machines, classification trees, change-point detection, k-nearest neighbors, k-means, or the like.

[0050] The prediction unit 270 is connected to the calculation unit 250 and the generation unit 260. The prediction unit 270 predicts the state of the fluid using data related to the peak of the difference spectrum calculated by the calculation unit 250. The prediction unit 270 may input the data related to the peak of the difference spectrum into the state prediction model generated by the generation unit 260 to predict the state of the fluid. The prediction unit 270 may determine, as the state of the fluid, at least one of the concentration of the target substance of the reaction in the fluid, whether or not the target substance has been produced, or whether or not an abnormal reaction has occurred, which is output in response to inputting into the state prediction model the intensity of the peak of the difference spectrum in a predetermined wavenumber range corresponding to the target substance of the reaction or the wavenumber at which the peak of the difference spectrum occurs.

[0051] The abnormality determination unit 280 is connected to the prediction unit 270. The abnormality determination unit 280 determines, from the state of the fluid predicted by the prediction unit 270, whether or not a reaction abnormality has occurred in the reaction device 20.

[0052] The output unit 290 is connected to the abnormality determination unit 280 and the reaction device 20. The output unit 290 outputs control data to the reaction device 20 according to the determination result in the abnormality determination unit 280. The output unit 290 may transmit display data for displaying the determination result in the abnormality determination unit 280 to an external display device or the reaction device 20.

[0053] FIG. 3 shows an example of the flow of the second solvent spectrum detection operation of the reaction system 10. In step S300, the conditions for the second solvent spectrum detection operation (such as the flow rate, flow velocity, pressure, temperature, and type of solvent in each flow path) are set by user input or the like. The conditions for the second solvent spectrum detection operation may be the same as those for the reaction operation. However, the reaction apparatus 20 may supply only a solvent (for example, an organic solvent such as MTHP (methyltetrahydropyran) or DMF (dimethylformamide) or water) to each flow path of the first liquid feed pipe 104, the second liquid feed pipe 114, the third liquid feed pipe 124, and the fourth liquid feed pipe 134. The reaction apparatus 20 may supply the same solvent as that used in the reaction operation, but without the raw materials (such as amino acids) in the reaction operation, to each flow path under set conditions using the first pump 102, the second pump 112, the third pump 122, and the fourth pump 132, respectively.

[0054] In the second solvent spectrum detection operation, the reaction device 20 may flow the solvent through the flow path at multiple temperatures within a predetermined temperature range or multiple pHs within a predetermined pH range. By flowing the solvent through the flow path while changing the temperature or pH, the reaction device 20 can detect multiple second solvent spectra corresponding to multiple temperatures or multiple pHs in each of the flow paths of the first liquid feed tube 104, the second liquid feed tube 114, the third liquid feed tube 124, the fourth liquid feed tube 134, the first reaction tube 142, the second reaction tube 152, and the third reaction tube 162. The predetermined temperature range may be a control temperature range of the fluid to be controlled in the reaction operation. The reaction device 20 may flow the solvent through the flow path so that the temperature of the solvent fluid is within the control temperature range of the fluid's set temperature ±α, the set temperature ±2α, . . . , and the set temperature ±nα (α > 0, n ≥ 2). The predetermined pH range may also be a control pH range of the fluid to be controlled in the reaction operation. The reactor 20 may flow the solvent through the flow path so that the pH of the solvent fluid is within the controlled pH range of the fluid at a set pH±β, a set pH±2β, . . . , and a set pH±mβ (β>0, m≧2).

[0055] In step S310, the detection unit 200 receives second solvent spectra, which indicate the optical absorption spectra of only the solvent flowing through the flow path in which each sensor unit is arranged, from the first sensor unit 180, the second sensor unit 182, the third sensor unit 184, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, and the tenth sensor unit 198. The detection unit 200 may receive, from the reaction device 20, the second solvent spectra, along with identification information of the sensor unit or tube that detected the second solvent spectrum.

[0056] As an example, the third sensor unit 184 guides irradiation light having a wavelength in the ultraviolet region (10 to 380 nm), visible region (380 nm to 800 nm), near-infrared region (wavelength 800 nm to 2500 nm), or infrared region (wavelength 2500 nm to 25000 nm) from a light source such as a semiconductor laser into the inside of the flow channel via a light-guiding component such as an optical fiber, and irradiates the fluid. The third sensor unit 184 guides the measurement light that has passed through the inside of the flow channel to a photodetector such as a photodiode via another light-guiding component, and the photodetector detects a light absorption spectrum that indicates the intensity or light absorption amount for each wave number (wavelength) of the measurement light. The first sensor unit 180, the second sensor unit 182, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, and the tenth sensor unit 198 may each detect an optical absorption spectrum, similar to the third sensor unit 184. Furthermore, the tenth sensor unit 198 may detect an optical absorption spectrum by inserting a light-guiding component such as an optical fiber into the target tank and irradiating it with irradiation light, thereby detecting measurement light.

[0057] The detection unit 200 may receive, from the sensor unit, second solvent spectra measured under a plurality of conditions in each of the flow paths of the first liquid feed tube 104, the second liquid feed tube 114, the third liquid feed tube 124, the fourth liquid feed tube 134, the first reaction tube 142, the second reaction tube 152, and the third reaction tube 162. The detection unit 200 may receive, from the sensor unit, the second solvent spectra measured for each temperature or pH (e.g., the theoretical pH value). The detection unit 200 may receive, from the reaction device 20, set values ​​for the temperature or pH of the fluid corresponding to each of the second solvent spectra. Furthermore, in the second solvent spectrum detection operation, the detection unit 200 may receive, from the sensor unit, set values ​​for at least one of the temperature and pH of the fluid flowing through each flow path.

[0058] In step S320, the reaction device 20 performs preprocessing on the second solvent spectrum. The reaction device 20 may perform the same preprocessing on the second solvent spectrum as the preprocessing performed on the fluid spectrum in the reaction operation. The detection unit 200 may perform preprocessing on the second solvent spectrum, including median filtering, FFT filtering, and smoothing using the Savitzky-Golay algorithm. The differentiation unit 210 may perform second-order differentiation on the second solvent spectrum.

[0059] In step S330, the memory unit 220 stores the second solvent spectrum for each detected flow path or for each type of solvent. The memory unit 220 may store the second solvent spectrum in association with at least one of the temperature and pH of the fluid in each flow path. The memory unit 220 may store the set value or measured value of the temperature of the fluid, and may store the set value or measured value of the pH of the fluid.

[0060] After storing the second solvent spectrum, the control device 30 may terminate the second solvent spectrum detection operation and proceed to a reaction operation.

[0061] FIG. 4 shows an example of the flow of a reaction operation in the reaction system 10. In the reaction operation of FIG. 4, as an example, in the reaction apparatus 20 shown in FIG. 1, organic solvents containing different raw materials such as amino acids are supplied to each flow path from the first raw material tank 100, the second raw material tank 110, the third raw material tank 120, and the fourth raw material tank 130 to synthesize a peptide. (Hereinafter, in the reaction operation, the solvent containing raw materials such as amino acids or the target substance flowing through each flow path is also referred to as a mixed fluid, and the mixed fluid refers to either a raw material fluid or a reaction fluid.)

[0062] The reactor 20 starts a reaction according to the reaction conditions (temperature, flow rate, flow velocity, pressure, etc. of the fluid in the flow path) set by the user. The reactor 20 operates the first pump 102, the second pump 112, the third pump 122, and the fourth pump 132 according to the set values ​​(for example, discharge rate, pressure, or rotation speed, etc.) set in the reaction conditions to flow each mixed fluid through the flow path.

[0063] In step S400, the detection unit 200 receives measurement values ​​indicating the state of the flow path through which the mixed fluid flows from each of the first sensor unit 180, the second sensor unit 182, the third sensor unit 184, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, and the tenth sensor unit 198. The detection unit 200 detects measurement values ​​indicating the fluid spectrum of the mixed fluid in the flow path from each of the first sensor unit 180, the second sensor unit 182, the third sensor unit 184, the fourth sensor unit 186, the fifth sensor unit 188, the sixth sensor unit 190, the seventh sensor unit 192, the eighth sensor unit 194, the ninth sensor unit 196, and the tenth sensor unit 198. Each sensor unit may measure an optical absorption spectrum as the fluid spectrum of the mixed fluid, similar to step S310. Furthermore, the detection unit 200 may receive at least one of the temperature, flow rate, and pressure of the mixed fluid detected by each sensor unit. The detection unit 200 may receive, together with the measurement value, identification information of the sensor unit or tube that detected the measurement value from the reaction device 20.

[0064] As in step S320, the detection unit 200 may perform preprocessing on the fluid spectrum, such as median filtering, FFT filtering, or smoothing using the Savitzky-Golay method.

[0065] In step S410, the differentiation unit 210 performs second-order differentiation on the fluid spectrum detected by the detection unit 200 to derive a derivative spectrum. As an example, the differentiation unit 210 can calculate the second-order derivative value x″(t) of the derivative spectrum at wavenumber t by taking the difference between the intensity x(t) at wavenumber t in the fluid spectrum and the intensities x(t+w) and x(tw) at ±w with wavenumber t as the base, and dividing the difference by the differentiation interval h, and then dividing the difference between the values ​​obtained by dividing the difference by the differentiation interval h ((x″(t)=(x(t+w)+x(tw)−2x(t)) / h 2 The differentiation section 210 may calculate second-order derivatives over the wavenumber range of the measured fluid spectrum to derive a derivative spectrum. This allows the differentiation section 210 to clearly identify change points in the fluid spectrum.

[0066] In step S420, the acquisition unit 230 acquires a second solvent spectrum corresponding to the solvent of the mixed fluid. The acquisition unit 230 may acquire a second solvent spectrum for the same solvent as the solvent of the mixed fluid (a solvent of at least one of the same type or the same mixing ratio). The acquisition unit 230 may acquire a second solvent spectrum detected in the same flow path or by the same sensor unit as the flow path that detected the fluid spectrum, using identification information of the tube or the sensor unit. The acquisition unit 230 may acquire a second solvent spectrum corresponding to the pH or temperature of the mixed fluid from among the multiple second solvent spectra stored in the memory unit 220.

[0067] The acquisition unit 230 may estimate the pH or temperature of the fluid and acquire a second solvent spectrum corresponding to the estimated pH or temperature. For example, the acquisition unit 230 may estimate the pH or temperature of the fluid based on peaks corresponding to water or a solvent in the fluid in the fluid spectrum and acquire a second solvent spectrum corresponding to the estimated pH or temperature. The acquisition unit 230 may estimate the pH or temperature of the fluid from at least one of the wavenumbers or intensities of peaks within a predetermined wavenumber range corresponding to water or an organic solvent in the fluid spectrum. For example, the acquisition unit 230 may perform the estimation using a table or function indicating the relationship between the pH or temperature of the fluid and at least one of the wavenumbers or intensities of peaks within a predetermined wavenumber range corresponding to water or an organic solvent. Alternatively, the acquisition unit 230 may estimate the pH or temperature using an estimation model that estimates the pH or temperature of the fluid based on at least one of the wavenumbers or intensities of peaks within a predetermined wavenumber range corresponding to water or an organic solvent. In the learning operation, the generation unit 260 may generate an estimation model using at least one of the wavenumbers or intensities of peaks within a predetermined wavenumber range of the fluid spectrum, obtained through experiments or the like, and measurement results of the pH or temperature of the fluid in the corresponding flow path. Peaks in the wavenumber range corresponding to water or organic solvents in the fluid spectrum are shifted by an amount corresponding to the pH or temperature. The generation unit 260 may generate the estimation model using logistic regression, neural networks, support vector machines, classification trees, change-point detection, k-nearest neighbors, k-means, or the like. The acquisition unit 230 may estimate the pH or temperature of the fluid based on peaks corresponding to water or organic solvents in the fluid in the differential spectrum, using a method similar to that for the fluid spectrum.

[0068] The acquisition section 230 may also acquire the second solvent spectrum from the storage section 220 in accordance with the temperature or pH value of the mixed fluid measured by the sensor section that detected the target fluid spectrum.

[0069] The acquisition unit 230 may acquire a second solvent spectrum in which peaks have been corrected according to the pH or temperature of the fluid. The acquisition unit 230 may receive a second solvent spectrum corresponding to the solvent of the mixed fluid from the storage unit 220 and perform the correction. If there is a peak shift according to the difference between the pH or temperature when the second solvent spectrum is detected and the pH or temperature (estimated or measured) of the fluid in the fluid spectrum, the acquisition unit may acquire a corrected second solvent spectrum by shifting at least one of the multiple peaks in the second solvent spectrum by the shifted wavenumber. The acquisition unit 230 may shift all of the multiple peaks in the second solvent spectrum by the same wavenumber, or may shift the multiple peaks in the second solvent spectrum by different wavenumbers. The acquisition unit 230 may shift the peaks of the second solvent spectrum by a larger wavenumber the greater the difference in pH or temperature. The acquisition unit 230 may determine the wavenumber to shift using a table or function indicating the relationship between the difference between the pH or temperature when the second solvent spectrum is detected and the pH or temperature of the fluid in the fluid spectrum, and the wavenumber to shift. The acquisition section 230 may use a table or a function acquired in advance through an experiment or the like.

[0070] In step S430, the extraction unit 240 extracts the first solvent spectrum from the differential spectrum by principal component analysis. The extraction unit 240 may extract the first solvent spectrum from the differential spectrum by using a second solvent spectrum in the same flow path as the flow path in which the differential spectrum was detected. For example, the extraction unit 240 may extract the first solvent spectrum from the differential spectrum by principal component analysis by using a second solvent spectrum detected by the same sensor unit as the sensor unit that detected the differential spectrum, or a second solvent spectrum detected in the same tube (liquid feed tube or reaction tube) as the tube in which the differential spectrum was detected.

[0071] As an example, the extraction unit 240 performs principal component analysis on the intensities at each wavenumber of the second solvent spectrum and creates a principal component analysis model for calculating principal component loadings and principal component scores. The extraction unit 240 applies this principal component analysis model to the differential spectrum to calculate loadings and scores corresponding to principal components specific to the solvent of the mixed fluid (e.g., principal components whose loading signs match those of the second solvent spectrum in the wavenumber range where the absolute value of the score is largest). The extraction unit 240 extracts the first solvent spectrum by reconstructing it using the calculated loadings and scores.

[0072] In step S440, the calculation unit 250 calculates a difference spectrum between the derivative spectrum and the first solvent spectrum extracted from the derivative spectrum by principal component analysis. The calculation unit 250 may calculate the difference between the value of the derivative spectrum and the value of the first solvent spectrum at any wavenumber within the wavenumber range of the measurement light. The calculation unit 250 can calculate the distribution of the difference spectrum by calculating the difference while changing the wavenumber across the wavenumber range of the measurement light.

[0073] When the detection unit 200 detects fluid spectra at multiple positions in one flow path (e.g., the second reaction tube), the calculation unit 250 may calculate a difference spectrum between an average spectrum of multiple derivative spectra derived from the multiple fluid spectra and the first solvent spectrum extracted from the average spectrum by the extraction unit. For example, the calculation unit 250 may calculate the difference spectrum by calculating the difference between a derivative spectrum derived from the average spectrum of the fluid spectra detected by the detection unit 200 from each of the sixth sensor unit 190, the seventh sensor unit 192, and the eighth sensor unit 194 arranged in the second reaction tube 152, and the first solvent spectrum extracted from the derivative spectrum. By using the average spectrum, the calculation unit 250 can reduce the influence of detection errors of the sensor units on the difference spectrum.

[0074] In step S450, the prediction unit 270 predicts the state of the fluid using data related to the peaks of the difference spectrum. The prediction unit 270 may predict the reaction amount of each of the reactions in the first, second, and third reaction tubes (e.g., the concentration of the target substance in the fluid, the presence or absence of the target substance, or the remaining amount of raw material). The prediction unit 270 may predict the amount of the target substance in the fluid corresponding to the calculated difference spectrum using a state prediction model that outputs the amount of the target substance in response to input of the value of the difference spectrum in a wavenumber range corresponding to the target substance of the reaction (e.g., the intensity of the peak or the wavenumber at which the peak occurs). The prediction unit 270 may use the state prediction model generated by the generation unit 260 or a state prediction model generated by an external learning device. For example, the prediction unit 270 may input the peak intensity of the difference spectrum in a wavenumber range corresponding to the target substance of the reaction in the second reaction tube 152 calculated by the calculation unit 250 into the state prediction model to predict the concentration of the target substance produced by the reaction in the second reaction tube 152.

[0075] The prediction unit 270 may predict the reaction amount of the fluid using multiple difference spectra in one flow path. The prediction unit 270 may predict multiple reaction amounts from the multiple difference spectra and calculate a reaction change rate from the multiple reaction amounts. The prediction unit 270 may calculate the reaction change rate by dividing the difference in reaction amount between corresponding measurement positions by the interval (length of the flow path) between multiple measurement positions of the multiple fluid spectra. For example, the prediction unit 270 may predict the concentration of the target substance produced by the reaction in the second reaction tube 152 from the state prediction model using the fluid spectra acquired from the sixth sensor unit 190, the seventh sensor unit 192, or the eighth sensor unit 194. The prediction unit 270 may calculate the reaction change rate by dividing the difference between the target substance concentration predicted from the fluid spectrum detected by the sixth sensor unit 190 and the target substance concentration predicted from the fluid spectrum detected by the seventh sensor unit 192 by the length of the flow path between the arrangement positions of the sixth sensor unit 190 and the seventh sensor unit 192. Similarly, the prediction unit 270 may calculate the reaction change rate by dividing the difference between the target substance concentration predicted from the fluid spectrum detected by the seventh sensor unit 192 and the target substance concentration predicted from the fluid spectrum detected by the eighth sensor unit 194 by the length of the flow path between the arrangement positions of the seventh sensor unit 192 and the eighth sensor unit 194. The prediction unit 270 may also calculate the average value of the predicted reaction amounts.

[0076] In addition, the prediction unit 270 may use a state prediction model to predict at least one of the temperature, pressure, or raw material concentration of the raw material fluid flowing through each of the first, second, and third liquid supply tubes from data regarding the peaks of the differential spectrum.

[0077] In step S460, the abnormality determination unit 280 determines whether a reaction abnormality has occurred in the flow path based on the predicted fluid state. The abnormality determination unit 280 may determine that a reaction abnormality has occurred if the predicted reaction amount of the fluid is less than a predetermined threshold. For example, the abnormality determination unit 280 may determine that the reaction of the fluid is progressing (no reaction abnormality) if the remaining amount of a raw material in the fluid predicted by the prediction unit 270 is less than a predetermined threshold (for example, the remaining amount is 0). The abnormality determination unit 280 may determine that a reaction abnormality has occurred if the reaction change rate calculated by the prediction unit 270 is less than a predetermined threshold. Here, the predetermined threshold may be determined by a user or the like according to the theoretical value of the reaction amount of the fluid. The abnormality determination unit 280 may determine that a reaction abnormality has occurred if at least one of the temperature, pressure, or raw material concentration of the raw material fluid is outside a predetermined threshold range. The predetermined threshold range may be determined by a user or the like according to the setting values ​​of the preset reaction conditions.

[0078] In addition, the control device 30 may predict the state of the fluid for each flow path of the reaction device 20, and the abnormality determination unit 280 may identify a liquid transfer tube or a reaction tube that shows an abnormal state among the multiple liquid transfer tubes and multiple reaction tubes.

[0079] If the abnormality determination unit 280 determines that the reaction is abnormal (Yes in FIG. 4), the controller 30 proceeds to step S470, and if the abnormality determination unit 280 determines that the reaction is not abnormal (No in FIG. 4), the controller 30 proceeds to step S400 and continues the reaction. In response to the abnormality determination unit 280 determining that the reaction is not abnormal in the upstream flow path (for example, the first reaction tube 142), the controller 30 may control the third pump 122 to start driving in order to supply the raw material from the third raw material tank 120 to the downstream flow path (for example, the second reaction tube 152).

[0080] In step S470, the output unit 290 may transmit display data indicating that a reaction abnormality has occurred to the reaction device 20. For example, the output unit 290 may transmit display data indicating a liquid transfer tube or a reaction tube showing an abnormal state among the plurality of liquid transfer tubes and the plurality of reaction tubes to the reaction device 20. In addition, the output unit 290 may transmit control data to the reaction device 20 to stop the reaction operation in the reaction device 20.

[0081] FIG. 5 shows an example of a database storing second solvent spectra. The database is stored in the storage unit 220. The database stores spectral data of second solvent spectra corresponding to multiple temperatures in association with the identification information of the sensor unit. As an example, the database in FIG. 5 stores second solvent spectrum 1 when the temperature is 20 degrees, second solvent spectrum 2 when the temperature is 21 degrees, ..., and second solvent spectrum 10 when the temperature is 29 degrees, all detected by the fifth sensor unit 188. The spectral data indicates the distribution of absorbance in the wavenumber range of the measurement light, which has been second-order differentiated by the differentiation unit 210 in the second solvent spectrum detection operation.

[0082] FIG. 6 shows another example of a database storing second solvent spectra. The database stores spectral data of second solvent spectra corresponding to multiple pH values ​​in association with tube identification information. As an example, the database in FIG. 6 stores second solvent spectrum 1 when the pH is 6.5, second solvent spectrum 2 when the pH is 6.6, ..., and second solvent spectrum 10 when the pH is 7.4, all of which are detected in the first reaction tube 142. The spectral data indicates the distribution of absorbance in the wavenumber range of the measurement light, which has been second-order differentiated by the differentiation unit 210 in the second solvent spectrum detection operation.

[0083] FIG. 7 is an explanatory diagram of an example of a derivative spectrum. As an example, FIG. 7 shows the second derivative of the optical absorption spectrum measured by the fifth sensor unit 188 as a derivative spectrum, with the horizontal axis representing wavenumber and the vertical axis representing absorbance. The fifth sensor unit 188 irradiates the first reaction fluid flowing through the flow path in the first reaction tube 142 with irradiation light, detects the measurement light transmitted through the fluid, and can measure the absorbance of the measurement light at each wavenumber. The derivative spectrum has multiple peaks depending on the raw materials, such as amino acids, and the solvent in the first reaction fluid.

[0084] FIG. 8 is an explanatory diagram of an example of a first solvent spectrum. FIG. 8 shows, as an example, a first solvent spectrum extracted by the extraction unit 240 from the differential spectrum of FIG. 7, with the horizontal axis representing wavenumber and the vertical axis representing absorbance. The second solvent spectrum used to extract the first solvent spectrum of FIG. 8 is obtained by the second solvent spectrum detection operation in which the fifth sensor unit 188 irradiates a fluid consisting only of the solvent flowing through the flow path in the first reaction tube 142 with irradiation light, detects measurement light transmitted through the fluid, and measures the absorbance of the measurement light at each wavenumber. The first solvent spectrum has multiple peaks caused by the solvent.

[0085] FIG. 9 is an explanatory diagram of an example of a difference spectrum. As an example, FIG. 9 shows a difference spectrum between the differential spectrum of FIG. 7 and the first solvent spectrum of FIG. 8, with the horizontal axis representing wavenumber and the vertical axis representing absorbance. The calculation unit 250 calculates the difference in absorbance between the differential spectrum and the first solvent spectrum at each wavenumber, and can calculate a difference spectrum in the wavenumber range of the measurement light as shown in FIG. 9. As shown in FIG. 9, the solvent components have been removed from the difference spectrum, and peaks resulting from the raw material or target substance are clearly defined.

[0086] According to this embodiment, by using the difference spectrum between the first solvent spectrum extracted by principal component analysis and the differential spectrum of the fluid to predict the state of the fluid, it is possible to eliminate the influence of changes in solvent concentration caused by fluctuations in the fluid flow rate, temperature, etc., on the state prediction, thereby enabling the control device 30 to predict the state of the fluid with high accuracy.

[0087] The fluid spectrum, differential spectrum, first solvent spectrum, second solvent spectrum, and difference spectrum may be a distribution of the intensity (absorbance, etc.) of the measurement light in a wavenumber range, or may be the intensity (absorbance, etc.) of the measurement light at a predetermined wavenumber.

[0088] Various embodiments of the present invention may be described with reference to flowcharts and block diagrams, where the blocks may represent (1) stages of a process in which operations are performed or (2) sections of an apparatus responsible for performing the operations. Particular stages and sections may be implemented by dedicated circuitry, programmable circuitry provided with computer-readable instructions stored on a computer-readable medium, and / or a processor provided with computer-readable instructions stored on a computer-readable medium. Dedicated circuitry may include digital and / or analog hardware circuitry, and may include integrated circuits (ICs) and / or discrete circuits. Programmable circuitry may include reconfigurable hardware circuitry, including logical AND, OR, XOR, NAND, NOR, and other logical operations, flip-flops, registers, memory elements such as field programmable gate arrays (FPGAs), programmable logic arrays (PLAs), and the like.

[0089] A computer-readable medium may include any tangible device capable of storing instructions that are executed by an appropriate device, such that the computer-readable medium having instructions stored thereon comprises an article of manufacture containing instructions that can be executed to create means for performing the operations specified in the flowcharts or block diagrams. Examples of computer-readable media may include electronic, magnetic, optical, electromagnetic, and semiconductor storage media. More specific examples of computer-readable media may include floppy disks, diskettes, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), electrically erasable programmable read-only memory (EEPROM), static random access memory (SRAM), compact disc read-only memory (CD-ROM), digital versatile disc (DVD), Blu-ray disc, memory stick, integrated circuit card, and the like.

[0090] The computer readable instructions may include either assembler instructions, Instruction Set Architecture (ISA) instructions, machine instructions, machine-dependent instructions, microcode, firmware instructions, state-setting data, or source or object code written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Smalltalk®, JAVA®, C++, etc., and conventional procedural programming languages ​​such as the “C” programming language or similar programming languages.

[0091] The computer-readable instructions may be provided to a processor or programmable circuitry of a programmable data processing apparatus, such as a general-purpose computer, special-purpose computer, or other computer, either locally or over a wide-area network (WAN) such as a local area network (LAN), the Internet, etc., which executes the computer-readable instructions to create means for performing the operations specified in the flowcharts or block diagrams. Examples of processors include computer processors, processing units, microprocessors, digital signal processors, controllers, microcontrollers, etc.

[0092] 10 illustrates an example of a computer 2200 in which aspects of the present invention may be embodied, in whole or in part. Programs installed on the computer 2200 may cause the computer 2200 to function as or perform operations associated with an apparatus or one or more sections of the apparatus according to embodiments of the present invention, and / or to perform a process or steps of a process according to embodiments of the present invention. Such programs may be executed by the CPU 2212 to cause the computer 2200 to perform specific operations associated with some or all of the blocks of the flowcharts and block diagrams described herein.

[0093] A computer 2200 according to this embodiment includes a CPU 2212, a RAM 2214, a graphics controller 2216, and a display device 2218, which are interconnected by a host controller 2210. The computer 2200 also includes input / output units such as a communication interface 2222, a hard disk drive 2224, a DVD-ROM drive 2226, and an IC card drive, which are connected to the host controller 2210 via an input / output controller 2220. The computer also includes legacy input / output units such as a ROM 2230 and a keyboard 2242, which are connected to the input / output controller 2220 via an input / output chip 2240.

[0094] The CPU 2212 operates according to programs stored in the ROM 2230 and RAM 2214, thereby controlling each unit. The graphics controller 2216 acquires image data generated by the CPU 2212 into a frame buffer or the like provided in the RAM 2214 or into the graphics controller 2216 itself, and causes the image data to be displayed on the display device 2218.

[0095] The communications interface 2222 communicates with other electronic devices via a network. The hard disk drive 2224 stores programs and data used by the CPU 2212 in the computer 2200. The DVD-ROM drive 2226 reads programs or data from the DVD-ROM 2201 and provides the programs or data to the hard disk drive 2224 via the RAM 2214. The IC card drive reads programs and data from an IC card and / or writes programs and data to an IC card.

[0096] The ROM 2230 stores therein a boot program or the like that is executed by the computer 2200 upon activation, and / or programs that depend on the hardware of the computer 2200. The input / output chip 2240 may also connect various input / output units to the input / output controller 2220 via a parallel port, a serial port, a keyboard port, a mouse port, etc.

[0097] The programs are provided by a computer-readable medium such as a DVD-ROM 2201 or an IC card. The programs are read from the computer-readable medium, installed in the hard disk drive 2224, RAM 2214, or ROM 2230, which are also examples of computer-readable media, and executed by the CPU 2212. Information processing described in these programs is read by the computer 2200, and brings about cooperation between the programs and the various types of hardware resources described above. An apparatus or method may be configured by realizing information manipulation or processing in accordance with the use of the computer 2200.

[0098] For example, when communication is performed between the computer 2200 and an external device, the CPU 2212 may execute a communication program loaded into the RAM 2214 and instruct the communication interface 2222 to perform communication processing based on the processing described in the communication program. Under the control of the CPU 2212, the communication interface 2222 reads transmission data stored in a transmission buffer processing area provided in the RAM 2214, the hard disk drive 2224, the DVD-ROM 2201, or a recording medium such as an IC card, and transmits the read transmission data to the network, or writes reception data received from the network to a reception buffer processing area or the like provided on the recording medium.

[0099] The CPU 2212 may also cause all or a necessary portion of a file or database stored on an external recording medium such as the hard disk drive 2224, the DVD-ROM drive 2226 (DVD-ROM 2201), an IC card, etc. to be read into the RAM 2214, and perform various types of processing on the data on the RAM 2214. The CPU 2212 then writes back the processed data to the external recording medium.

[0100] Various types of information, such as various types of programs, data, tables, and databases, may be stored on the recording medium and may undergo information processing. The CPU 2212 may perform various types of processing on data read from the RAM 2214, including various types of operations, information processing, conditional judgment, conditional branching, unconditional branching, information search / replacement, etc., as described throughout this disclosure and specified by the instruction sequences of the programs, and write the results back to the RAM 2214. The CPU 2212 may also search for information in a file, database, etc. on the recording medium. For example, if multiple entries each having an attribute value of a first attribute associated with an attribute value of a second attribute are stored on the recording medium, the CPU 2212 may search for an entry that matches a condition specified by the attribute value of the first attribute from among the multiple entries, read the attribute value of the second attribute stored in the entry, and thereby obtain the attribute value of the second attribute associated with the first attribute that satisfies a predetermined condition.

[0101] The above-described programs or software modules may be stored in a computer-readable medium on or near the computer 2200. A recording medium such as a hard disk or RAM provided in a server system connected to a dedicated communication network or the Internet can also be used as a computer-readable medium, thereby providing the programs to the computer 2200 via the network.

[0102] Although the present invention has been described above using embodiments, the technical scope of the present invention is not limited to the scope described in the above embodiments. It will be apparent to those skilled in the art that various modifications and improvements can be made to the above embodiments. It is clear from the claims that such modifications and improvements can also be included within the technical scope of the present invention.

[0103] It should be noted that the execution order of each process, such as operations, procedures, steps, and stages, in the devices, systems, programs, and methods shown in the claims, specifications, and drawings is not specifically stated as "before," "prior to," etc., and that the processes can be performed in any order unless the output of a previous process is used in a subsequent process. Even if the operational flow in the claims, specifications, and drawings is described using "first," "next," etc. for convenience, this does not mean that the processes must be performed in this order. [Explanation of symbols]

[0104] 10. Reaction System 20 Reactor 30 Control device 100 First raw material tank 102 First Pump 104 First liquid supply pipe 110 Second raw material tank 112 Second Pump 114 Second liquid supply pipe 120 Third raw material tank 122 Third Pump 124 Third liquid supply pipe 130 4th raw material tank 132 4th Pump 134 No. 4 liquid supply pipe 140 First Mixer 142 First Reaction Tube 150 Second Mixer 152 Second Reaction Tube 160 3rd Mixer 162 Third Reaction Tube 170 Destination Tank 180 First sensor section 182 Second sensor section 184 Third Sensor Unit 186 4th Sensor Unit 188 5th Sensor Section 190 6th Sensor Section 192 7th Sensor Section 194 8th Sensor Unit 196 9th Sensor Section 198 10th Sensor Section 200 Detector 210 Differential part 220 Storage section 230 Acquisition Department 240 Extraction part 250 Calculation Unit 260 Generation part 270 Prediction Department 280 Abnormality determination section 290 Output section 2200 Computer 2201 DVD-ROM 2210 host controller 2212 CPU 2214 RAM 2216 Graphics Controller 2218 Display Device 2220 Input / Output Controller 2222 communication interface 2224 hard disk drive 2226 DVD-ROM drive 2230 ROM 2240 I / O chip 2242 keyboard

Claims

1. a detection unit for detecting a fluid spectrum, which is a spectrum of light indicating the state of a fluid flowing through a flow path; a differentiation unit that differentiates the fluid spectrum to derive a differential spectrum; an extraction unit that extracts a first solvent spectrum from a solvent of the fluid by principal component analysis; a calculation unit that calculates a difference spectrum between the derivative spectrum and the first solvent spectrum; a prediction unit that predicts the state of the fluid using data related to the peak of the calculated difference spectrum; Equipped with Device.

2. a generation unit that generates a model for predicting a state of the fluid using the difference spectrum in response to input of data related to a peak of the difference spectrum of the fluid; The prediction unit inputs data relating to the peak of the difference spectrum into the model to predict the state of the fluid.

10. The apparatus of claim 1.

3. an acquisition unit that acquires a second solvent spectrum corresponding to the solvent; The extraction unit extracts the first solvent spectrum from the differential spectrum by principal component analysis using the second solvent spectrum.

10. The apparatus of claim 1.

4. the acquisition unit acquires the second solvent spectrum according to a pH or a temperature of the fluid; The extraction unit extracts the first solvent spectrum from the differential spectrum by principal component analysis using the second solvent spectrum.

4. The apparatus of claim 3.

5. The acquisition unit estimates a pH or a temperature of the fluid and acquires the second solvent spectrum according to the estimated pH or temperature.

5. The apparatus of claim 4.

6. The acquisition unit estimates a pH or a temperature of the fluid based on a peak in the fluid spectrum corresponding to water or a solvent in the fluid, and acquires the second solvent spectrum according to the estimated pH or temperature.

6. The apparatus of claim 5.

7. a storage unit configured to store a plurality of second solvent spectra corresponding to a plurality of pH values ​​or a plurality of temperatures; The acquisition unit acquires, from the storage unit, the second solvent spectrum corresponding to the pH or the temperature of the fluid, from the plurality of second solvent spectra.

4. The apparatus of claim 3.

8. The acquisition unit acquires the second solvent spectrum with peaks corrected according to the pH or temperature of the fluid.

5. The apparatus of claim 4.

9. The prediction unit predicts the reaction amount of the reaction in the fluid as the state of the fluid using data related to the peak of the difference spectrum.

10. The apparatus of claim 1.

10. The prediction unit predicts the remaining amount of the raw material in the fluid using data related to the peak of the difference spectrum.

10. The apparatus of claim 9.

11. The apparatus further includes an abnormality determination unit that determines that a reaction of the fluid is progressing when the remaining amount of the raw material in the fluid predicted by the prediction unit is less than a predetermined threshold.

11. The apparatus of claim 10.

12. detecting a fluid spectrum, which is a spectrum of light indicative of the state of the fluid flowing through the flow path; differentiating the fluid spectrum to derive a derivative spectrum; extracting a first solvent spectrum from a solvent of the fluid by principal component analysis; calculating a difference spectrum between the derivative spectrum and the first solvent spectrum; and predicting the state of the fluid using data relating to the peaks of the calculated difference spectrum. method.

13. The method is executed by a computer, causing the computer to: a detection unit for detecting a fluid spectrum, which is a spectrum of light indicating the state of a fluid flowing through a flow path; a differentiation unit that differentiates the fluid spectrum to derive a differential spectrum; an extraction unit that extracts a first solvent spectrum from a solvent of the fluid by principal component analysis; a calculation unit that calculates a difference spectrum between the derivative spectrum and the first solvent spectrum; a prediction unit that predicts the state of the fluid using data related to the peak of the calculated difference spectrum; A program that functions as a

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