Synthesis apparatus and synthesis method
The synthesis apparatus and method address the challenge of controlling chemical reactions during transient phases by using sensors to detect and adjust parameters, ensuring stable and conforming product production through feedback control.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- YOKOGAWA ELECTRIC CORP
- Filing Date
- 2023-03-14
- Publication Date
- 2026-05-26
AI Technical Summary
Conventional chemical synthesis technologies face challenges in controlling reaction conditions during unsteady operations, particularly during transient phases such as startup, due to difficulties in defining control ranges and detecting abnormalities, leading to unstable reactions and non-conforming product production.
A synthesis apparatus and method that utilizes a sensor to detect time-series data of reaction properties, stores reference time-series data, and employs a control device to minimize differences between detected and reference data by adjusting controllable parameters, enabling feedback control during non-steady-state operations.
The apparatus and method enable more appropriate control during non-steady-state operations, reducing the production of non-conforming products by stabilizing the reaction process before reaching steady-state operation.
Smart Images
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Abstract
Description
Technical Field
[0001] The present invention relates to a synthesis apparatus and a synthesis method, and particularly to one for synthesizing a target compound by an organic chemical reaction.
Background Art
[0002] In a synthesis apparatus for synthesizing a target compound by a chemical synthesis reaction from a plurality of raw materials, it is known to adjust reaction conditions by performing feedback control.
[0003] Patent Document 1 describes a technique for continuously controlling reaction conditions by measuring infrared spectral absorption in the synthesis process of a synthetic polymer resin.
[0004] Patent Document 2 describes a technique for performing closed-loop feedback control of catalytic polymerization using an MFI measuring viscometer in polymer process control.
Prior Art Documents
Patent Documents
[0005]
Patent Document 1
Patent Document 2
Summary of the Invention
Problems to be Solved by the Invention
[0006] However, the conventional technology has a problem that it is difficult to perform appropriate control during unsteady operation.
[0007] During chemical synthesis, the expected chemical reaction may not proceed correctly due to the influence of parameters that are difficult to control completely (such as ambient temperature, humidity, and raw material composition). Especially during transient operations such as startup, the synthesis reaction is unstable, making it difficult to determine whether the reaction is proceeding as intended. Therefore, it takes time before appropriate control can be implemented.
[0008] The technologies described in Patent Documents 1 and 2 both involve detecting the state of a synthesis reaction using sensors and performing feedback control. While these methods are effective when controlling within a control range during steady-state operation, defining the control range is difficult during transient operation before the process stabilizes, making it difficult to appropriately detect abnormalities and perform control.
[0009] This invention was made to solve these problems and aims to provide a synthesis apparatus and synthesis method that can perform more appropriate control during non-steady-state operation. [Means for solving the problem]
[0010] An example of a synthesis apparatus according to the present invention is: A synthesis apparatus for synthesizing target products through organic chemical reactions, A sensor for detecting the properties of the aforementioned synthetic target material, A control device that performs control based on detection time series data, which is time series data of characteristics detected by the aforementioned sensor, Equipped with, The control device is The system stores reference time-series data of the properties of the aforementioned synthetic target product. The synthesis device is controlled based on the detected time series data and the reference time series data. Furthermore, an example of the synthesis method according to the present invention is: A synthesis method for synthesizing a target product by an organic chemical reaction, The steps include storing reference time-series data of the properties of the aforementioned synthetic target product, The steps include obtaining detection time series data, which is time series data of the detected characteristics, A step of controlling the synthesis apparatus based on the detected time series data and the reference time series data, It is equipped with.
[0011] In one example, the control device controls the synthesis apparatus after it has started operating but before it reaches a steady-state operation. In one example, the sensor continuously detects the characteristics. In one example, the synthesis apparatus is a flow synthesis apparatus. In one example, the organic chemical reaction is an amidation reaction. In one example, the product to be synthesized is a peptide. In one example, the sensor includes at least one of an infrared spectroscopic absorption analyzer, an HPLC, and a soft sensor. In one example, the synthesis apparatus further includes a mixer or reaction vessel for reacting two or more raw materials. In one example, the control device calculates the difference between the detected time series data and the reference time series data as the difference in values at a specific time, the difference in the integral value from a specific time to a predetermined time, or the difference in the slope of change from a specific time to a predetermined time, and controls the combining device so that the difference is minimized. In one example, the control device controls the synthesis apparatus by changing one of the controllable parameters to reduce the difference, based on a model that calculates the characteristics based on time and one or more controllable parameters. In one example, the synthesis apparatus includes a raw material supply device for supplying raw materials, and the control device controls the raw material supply device based on the detected time series data and the reference time series data. [Effects of the Invention]
[0012] The synthesis apparatus and synthesis method according to the present invention can perform more appropriate control during non-steady-state operation.
[0013] As a specific example, by performing process control before the process is completely stabilized, the production of non-conforming products can be suppressed.
Brief Description of the Drawings
[0014] [Figure 1] Schematic configuration of the synthesizer according to Embodiment 1 of the present invention. [Figure 2] Example of a graph representing the concentration of the synthesis target that changes over time. [Figure 3] Flowchart showing the processing flow of the control device in FIG. 1. [Figure 4] Schematic configuration of the synthesizer according to Embodiment 2 of the present invention. [Figure 5] Schematic configuration of the synthesizer according to Embodiment 3 of the present invention. [Figure 6] Schematic configuration of the synthesizer according to Embodiment 4 of the present invention.
Modes for Carrying Out the Invention
[0015] Hereinafter, embodiments of the present invention will be described based on the accompanying drawings. [Embodiment 1] FIG. 1 shows a schematic configuration of a synthesizer 101 according to Embodiment 1. The synthesizer 101 synthesizes a synthesis target by a chemical synthesis reaction of a plurality of raw materials. The chemical synthesis reaction is, for example, an organic chemical reaction, and a more specific example is an amidation reaction.
[0016] The "synthesis target" is not limited to the final product, and may be, for example, a raw material for another synthesis process. The synthesis target is, for example, a peptide, but is not limited thereto.
[0017] Also, the configuration in FIG. 1 may be a part of the synthesizer 101, and components other than those shown may be provided. For example, a configuration for manufacturing raw materials or a configuration for further processing the synthesis target may be provided.
[0018] The synthesis apparatus 101 includes a raw material supply device for supplying raw materials. In this embodiment, pumps 11 and 12 are provided as raw material supply devices to supply two types of raw materials. Pumps 11 and 12 supply, for example, different raw materials. Three or more raw material supply devices (for example, three or more pumps) may be provided. In this embodiment, all raw materials are assumed to be in the form of a fluid (gas, liquid, or mixture thereof) or a flowable form, but the form of the raw materials is not limited thereto.
[0019] The synthesis apparatus 101 is equipped with a reaction apparatus for reacting two types of raw materials. In this embodiment, a mixer 20 is used as the reaction apparatus. Pumps 11 and 12 are connected to the mixer 20 and supply the raw materials to the mixer 20, respectively. The mixer 20 reacts these raw materials, for example, by mixing and / or stirring, thereby synthesizing the target product. If three or more pumps are provided, the mixer 20 may react three or more types of raw materials.
[0020] The synthesis apparatus 101 may be a flow synthesis apparatus, that is, it may continuously synthesize the product to be synthesized. For example, if both the raw materials and the product to be synthesized are in a fluid or flowable form, the product to be synthesized can be synthesized continuously.
[0021] The synthesis apparatus 101 is equipped with a sensor for detecting the properties of the product to be synthesized by the mixer 20. In this embodiment, an infrared spectroscopic absorption analyzer 30 is used as the sensor, and the concentration is measured as a property of the product to be synthesized. The infrared spectroscopic absorption analyzer 30 is installed, for example, in the flow path of the product to be synthesized, but it may also be installed anywhere other than the flow path, as long as infrared spectroscopic absorption measurement can be performed on the product to be synthesized.
[0022] The synthesis apparatus 101 includes a control device 40 that controls the operation of the synthesis apparatus 101. The control device 40 is connected to the pumps 11 and 12 and the infrared spectroscopic absorption measuring device 30, and controls their operation by sending and receiving information between them.
[0023] The control device 40 can be configured using, for example, a computer equipped with arithmetic means and storage means. The arithmetic means may include, for example, a processor, and the storage means may include, for example, storage media such as semiconductor memory devices and magnetic disk devices. Some or all of the storage media may be non-transitory storage media.
[0024] Furthermore, a computer may be equipped with input / output means. These input / output means may include, for example, input devices such as a keyboard and mouse, output devices such as a display and printer, and communication devices such as a network interface.
[0025] The storage means may store a program. The processor may execute this program, thereby allowing the computer to perform the functions described in this embodiment.
[0026] The control device 40 controls the flow rates of pumps 11 and 12 based on the concentration detected by the infrared spectroscopic absorption measuring device 30. In particular, in this embodiment, the control is performed based on time-series data of the detected concentration. This control can be implemented, for example, as feedback control. The time-series data may be what is called "trend data".
[0027] Figure 2 is an example of a graph showing the concentration of the target product to be synthesized, which changes over time. The concentration values fall within either the transient range 61 or the steady range 62. The steady range 62 is the range of concentrations during steady operation of the synthesis apparatus 101. This can be described as the range of concentrations when the synthesis reaction in the synthesis process is continuing stably, and is a range that can be controlled using only the most recent concentration value, for example, without referring to time-series data of the concentration.
[0028] The non-steady range 61 is the range other than the steady range 62. As described above, conventional control assumes the steady range 62, and proper control is difficult when the synthesizer 101 is operating in the non-steady range 61.
[0029] In Figure 2, the reference time series data 51 is the time series data (model data) that serves as the basis for control regarding concentration. For example, the data obtained when the startup operation of the synthesis apparatus 101 is successful can be used as the reference time series data 51. The detection time series data 52 is the time series data of the concentration actually detected by the infrared spectroscopic absorption analyzer 30 (measured data).
[0030] In this example, a difference 53 occurs between the reference time series data 51 and the detected time series data 52. For example, if the synthesis reaction does not proceed as expected due to factors that are difficult to control (such as ambient temperature, humidity, raw material composition, etc.), the detected time series data 52 will differ from the reference time series data 51, resulting in a difference 53. It is preferable to implement control measures to reduce this difference 53.
[0031] For example, the concentration of the target product after a certain period of time has elapsed since the start of the startup operation may be lower than the reference time series data 51. Differences in time series data can be detected even before the startup operation of the synthesis apparatus 101 is completed, and in particular, can be detected immediately after the start of the reaction.
[0032] Figure 3 is a flowchart showing the processing flow of the control device 40. The operation of the synthesis apparatus 101 will be explained below using Figure 3. This flowchart represents the synthesis method according to this embodiment.
[0033] First, the control device 40 stores reference time series data 51 (step S1). The reference time series data 51 includes concentration data in a non-steady range 61 (for example, during startup operation). It may also include concentration data in a steady range 62.
[0034] The processing in step S1 can be completed, for example, before the synthesis process of the target material is started, but variations that are stored or updated after the start of the synthesis process are not particularly excluded. The format of the reference time series data 51 is arbitrary, but it can be stored, for example, as a function of time, or as a searchable table based on a key that includes time.
[0035] After step S1, the synthesis process of the target product may be initiated.
[0036] After step S1, the control device 40 acquires detection time-series data 52 while the synthesis process of the target product is being carried out (step S2). This is done, for example, via the infrared spectroscopic absorption analyzer 30 as described above. For example, the infrared spectroscopic absorption analyzer 30 continuously detects the concentration and transmits the detected concentration to the control device 40. The control device 40 can generate and acquire detection time-series data 52 by associating the reception time with the data received from the infrared spectroscopic absorption analyzer 30 and storing it. Here, "continuously detecting" means performing detection at a frequency that can generate time-series data usable for control, for example, and includes cases where the process is repeated periodically.
[0037] Next, the control device 40 calculates the difference between the detected time series data and the reference time series data (step S3). The definition of "difference" can be arbitrarily determined by a person skilled in the art, but for example, the difference may be calculated as the difference in values at a specific time, the difference may be calculated as the difference in integral values from a specific time to a predetermined time, or the difference may be calculated as the difference in the slope of change from a specific time to a predetermined time.
[0038] Next, the control device 40 controls the synthesis apparatus 101 so that the difference calculated in step S3 becomes smaller (step S4). For example, as shown in Figure 2, if the concentration in the detection time series data 52 is smaller than the concentration in the reference time series data 51, the difference 53 can be reduced by controlling the apparatus to increase the concentration of the product to be synthesized.
[0039] The specific processing details for realizing such control can be designed by those skilled in the art based on publicly known technologies in the field of control, but a specific example is described below.
[0040] For example, the control device 40 stores a model for calculating concentration. This model calculates concentration based on time (more precisely, the time of day) and one or more controllable parameters. The controllable parameters include, for example, the flow rate at a predetermined location in the synthesis apparatus 101 (e.g., pumps 11 and 12, but not limited to these). They also include, for example, the temperature at a predetermined location in the synthesis apparatus 101 (e.g., mixer 20, but not limited to this). Other parameters may also be included.
[0041] This model can be, for example, a function that gives a concentration that includes time and all controllable parameters as variables, or a table that allows searching for concentrations based on time and all controllable parameters, or a trained model that outputs a concentration based on an input that includes time and all controllable parameters. The model itself may be designed by a person skilled in the art based on publicly available technology.
[0042] Based on this model, the control device 40 controls the synthesis apparatus 101 by changing any of the controllable parameters to reduce the difference. For example, the pumps 11 and / or 12 may be controlled in a direction that reduces the difference (specifically by changing their outputs to change the flow rate), the mixer 20 may be controlled (specifically by changing its temperature), or the temperature of the flow path of the raw materials or the product to be synthesized may be controlled.
[0043] Thus, in steps S3 and S4, the control device 40 provides feedback control to the synthesis device 101 based on the reference time series data 51 and the detected time series data 52. This makes it possible to control the device in a way that bridges the difference 53 between the reference time series data 51 and the detected time series data 52. In particular, by including data in the non-steady range 61 in the reference time series data 51, the control device 40 can appropriately control the synthesis device 101 even after the synthesis device 101 has started operating but before it reaches steady-state operation.
[0044] Note that step S4 does not necessarily have to be configured to be executed after step S3; for example, it may be configured to be executed only if a predetermined condition is met. Specifically, step S4 may be executed only if the difference 53 is greater than a predetermined threshold.
[0045] After step S4 is executed, the control device 40 determines whether the synthesis process has finished (step S5). If the synthesis process has finished, the process shown in Figure 3 ends. If the synthesis process has not finished, the process returns to step S2.
[0046] Thus, the synthesis apparatus 101 according to Embodiment 1 allows for more appropriate control even during non-steady-state operation. Therefore, for example, the production of non-conforming products can be suppressed.
[0047] In the above-described embodiment 1, as shown in Figure 3, the loop processing is limited to returning from step S5 to step S2, but the loop structure of steps S2 to S4 can be modified as appropriate by those skilled in the art. For example, step S2 may be executed multiple times before step S3 is executed. Alternatively, the processing of step S2 may be executed in parallel with the processing of steps S3 and S4.
[0048] Furthermore, the control by the control device 40 is applicable not only when transitioning from transient operation (transient range 61) to steady-state operation (steady-state range 62) as shown in Figure 2, but also when transitioning from steady-state operation to other operating states. For example, it can be applied to transient operation when the items to be produced are continuously changed after reaching steady-state operation (for example, when changing the grade of the synthesis target).
[0049] [Embodiment 2] Embodiment 2 is a modification of Embodiment 1 in which the reaction apparatus is changed. Hereafter, descriptions of parts common to Embodiment 1 may be omitted.
[0050] Figure 4 shows a schematic configuration of the synthesis apparatus 102 according to Embodiment 2. The synthesis apparatus 102 is equipped with a reaction tank 21 instead of the mixer 20 in Figure 1 as a reaction apparatus for reacting two or more raw materials. With this configuration, it is possible not only to mix the raw materials but also to maintain the solution. Even with this configuration, the control device 40 is capable of performing the process shown in Figure 3.
[0051] Thus, since control can be performed during transient operation regardless of the specific configuration of the reactor, the same effects as in Embodiment 1 can be obtained in Embodiment 2 as in Embodiment 1.
[0052] [Embodiment 3] Embodiment 3 is a modification of Embodiment 2 in which the sensor has been changed. Hereafter, descriptions of parts common to Embodiment 1 or 2 may be omitted.
[0053] Figure 5 shows a schematic configuration of the synthesis apparatus 103 according to Embodiment 3. The synthesis apparatus 103 is equipped with an online HPLC 31 as a sensor, instead of the infrared spectroscopic absorption analyzer 30 shown in Figure 4. HPLC is an abbreviation for high-performance liquid chromatograph. Even with this configuration, the control device 40 is capable of performing the process shown in Figure 3.
[0054] Thus, even when using online analysis, control can be performed during non-steady-state operation, and the same effects as in Embodiment 1 or 2 can be obtained in Embodiment 3.
[0055] [Embodiment 4] Embodiment 4 is also a modification of Embodiment 2, with the sensor changed. Hereafter, parts common to any of Embodiments 1 to 3 may be omitted from the explanation.
[0056] Figure 6 shows a schematic configuration of the synthesis apparatus 104 according to Embodiment 4. The synthesis apparatus 104 is equipped with a soft sensor 32 as a sensor, instead of the infrared spectroscopic absorption measuring device 30 shown in Figure 4.
[0057] In this embodiment, another sensor (not shown) is provided in the reaction vessel 21, which detects process parameters and transmits them to the soft sensor 32. Based on the received process parameters, the soft sensor 32 can continuously estimate the concentration of the target product to be synthesized. Even with this configuration, the control device 40 can perform the process shown in Figure 3.
[0058] Thus, since control can be performed during non-steady-state operation regardless of the specific configuration of the sensor, the same effects as in any of the embodiments 1 to 3 can be obtained in Embodiment 4 as well.
[0059] [Differentiation] In Embodiments 1 to 4, concentration was used as a property of the target product for synthesis. However, any property that can be used for measurement and control can be used instead of concentration, or in addition to concentration. For example, various physical quantities of the target product for synthesis, such as temperature, viscosity, humidity, and density, can be measured and controlled as properties.
[0060] Furthermore, the sensor configuration can be changed. In each of the above embodiments, the sensor includes at least one of the infrared spectroscopic absorption analyzer 30, HPLC 31, and soft sensor 32, but these may be used in combination, or other sensors may be used. In particular, an appropriate type of sensor can be used depending on the characteristics to be measured. For example, an ultraviolet spectroscopic absorption analyzer, a viscometer, etc. may be used.
[0061] Furthermore, the raw materials may not be in a fluid form, but may be in the form of powder, particles, solids, etc. Depending on the composition of the raw materials, an appropriate raw material supply device can be used instead of pumps 11 and 12.
[0062] Furthermore, devices other than the mixer 20 and reaction vessel 21 may be used as reaction equipment. In particular, appropriate reaction equipment can be used depending on the raw materials and the product to be synthesized.
[0063] Furthermore, those skilled in the art may optionally add, modify, or delete components within the scope of the present invention in each of the embodiments described above. [Explanation of Symbols]
[0064] 11, 12… pump 20… Mixer 21…Reaction vessel 30…Infrared spectroscopy absorption measuring device (sensor) 31…Online HPLC (sensor) 32... Soft sensor (sensor) 40…Control device 51…Reference time series data 52…Detection time series data 53…Difference 61…Non-stationary range 62... Steady-state range 101~104…Synthesizer
Claims
1. A synthesis apparatus for synthesizing target products through organic chemical reactions, A sensor for detecting the properties of the aforementioned synthetic target material, A control device that performs control based on detection time series data, which is time series data of characteristics detected by the aforementioned sensor, Equipped with, The control device is The system stores reference time-series data of the properties of the aforementioned synthetic target product. Based on the detected time series data and the reference time series data, the synthesis device is controlled. The aforementioned reference time-series data describes the characteristics of the product to be synthesized when the startup operation of the synthesis apparatus is successful. The reference time-series data includes data describing the properties of the product to be synthesized in a steady-state range where the synthesis apparatus is operating steadily, and data describing the properties of the product to be synthesized in a non-steady-state range other than the steady-state range. The aforementioned transient range includes the period during which the synthesis apparatus is in startup operation. The control device controls the synthesis apparatus to reduce the difference between the detected time series data and the reference time series data in the non-stationary range. Synthesizer.
2. The synthesis apparatus according to claim 1, wherein the control device controls the synthesis apparatus after it starts operating but before it reaches steady-state operation.
3. The synthesis apparatus according to claim 1, wherein the sensor continuously detects the characteristics.
4. The synthesis apparatus according to claim 1, wherein the synthesis apparatus is a flow synthesis apparatus.
5. The synthesis apparatus according to claim 1, wherein the organic chemical reaction is an amidation reaction.
6. The synthesis apparatus according to claim 1, wherein the target product for synthesis is a peptide.
7. The synthesis apparatus according to claim 1, wherein the sensor includes at least one of an infrared spectroscopic absorption measuring device, an HPLC, and a soft sensor.
8. The synthesis apparatus according to claim 1, further comprising a mixer or reaction vessel for reacting two or more raw materials.
9. The control device is The difference between the detected time series data and the reference time series data is calculated as the difference in values at a specific time, the difference in the integral value from a specific time to a predetermined time, or the difference in the slope of change from a specific time to a predetermined time. Control the synthesis apparatus so that the aforementioned difference is reduced. The synthesis apparatus according to claim 1.
10. The control device controls the synthesis apparatus by changing one of the controllable parameters to reduce the difference, based on a model that calculates the characteristics based on time and one or more controllable parameters. The synthesis apparatus according to claim 9.
11. The synthesis apparatus is equipped with a raw material supply device for supplying raw materials, The control device controls the raw material supply device based on the detected time series data and the reference time series data. The synthesis apparatus according to claim 1.
12. A synthesis method for synthesizing a target product by an organic chemical reaction, The steps include storing reference time-series data of the properties of the aforementioned synthetic target product, The steps include obtaining detection time series data, which is time series data of the detected characteristics, A step of controlling the synthesis apparatus based on the detected time series data and the reference time series data, Equipped with, The aforementioned reference time-series data describes the characteristics of the product to be synthesized when the startup operation of the synthesis apparatus is successful. The reference time-series data includes data describing the properties of the product to be synthesized in a steady-state range where the synthesis apparatus is operating steadily, and data describing the properties of the product to be synthesized in a non-steady-state range other than the steady-state range. The aforementioned transient range includes the period during which the synthesis apparatus is in startup operation. In the control step, the combining device is controlled to reduce the difference between the detected time series data and the reference time series data in the non-stationary range. Synthesis method.
13. The control device controls at least one of the flow rate or temperature at a predetermined position in the synthesis apparatus within the transient range. The synthesis apparatus according to claim 1.
14. In the control step, control at least one of the flow rate or temperature at a predetermined position of the synthesis apparatus in the transient range. The synthesis method according to claim 12.