Evaluation method, evaluation program, and evaluation device

Abstract

To improve the technology for evaluating the types of stimuli necessary to change the color of a substance. [Solution] The evaluation method includes the steps of: acquiring a video image of a substance whose color changes in response to the applied stimulus when a stimulus is applied to the substance; acquiring a correspondence between the time progression in the video image and the time change of the stimulus pattern; and evaluating the stimulus pattern for changing the color of the substance by acquiring the stimulus pattern at the time the color of the substance changes in the video image by referring to the correspondence.

Description

Technical Field

[0001] The present disclosure relates to an evaluation method, an evaluation program, and an evaluation apparatus for evaluating the mode of stimulation necessary for changing the color of a substance.

Background Art

[0002] Substances whose color changes in response to external stimuli are known. For example, a thermoresponsive polymer that undergoes a phase transition between hydrophilic and hydrophobic states in response to a temperature change and changes color is expected to be applied to drug delivery, sensors, actuators, and the like.

[0003] The temperature at which the color of a thermoresponsive polymer changes (phase transition temperature) can be adjusted by the composition of the monomers used in the polymerization. Conventionally, differential scanning calorimetry (DSC), an ultraviolet-visible spectrophotometer, or the like has been used to evaluate the phase transition temperature of a thermoresponsive polymer (see, for example, Patent Document 1).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] In order to obtain a polymer having a phase transition temperature suitable for an application, it is necessary to repeatedly perform trial and error of predicting the composition of a polymer having a desired phase transition temperature, preparing the polymer, evaluating the phase transition temperature of the prepared polymer, and predicting again the composition of a polymer having a desired phase transition temperature based on the evaluation result.

[0006] In order to efficiently obtain a substance having a desired phase transition temperature, improvement of a technique for evaluating the mode of stimulation necessary for changing the color of the substance is desired.

[0007] This disclosure is made in view of these challenges and aims to improve techniques for evaluating the types of stimuli necessary to change the color of a substance. [Means for solving the problem]

[0008] To solve the above problems, an evaluation method in one aspect of the present disclosure includes the steps of: acquiring a video image of a substance whose color changes in response to an applied stimulus when a stimulus is applied to the substance; acquiring a correspondence between the time progression in the video image and the time change of the stimulus pattern; and evaluating the stimulus pattern for changing the color of the substance by acquiring the stimulus pattern at the time the color of the substance changes in the video image by referring to the correspondence.

[0009] Another aspect of the present disclosure is an evaluation device. This device includes: a video acquisition unit that acquires video images of a substance whose color changes in response to an applied stimulus when a stimulus is applied to the substance; a correspondence acquisition unit that acquires a correspondence between the time progression in the video and the time change of the stimulus pattern; and a stimulus pattern evaluation unit that evaluates the stimulus pattern for changing the color of a substance by acquiring the stimulus pattern at the time the color of the substance changes in the video by referring to the correspondence.

[0010] Another aspect of this disclosure is also an evaluation device. This device comprises an application unit for applying a stimulus to a substance, an imaging unit for capturing a moving image showing how the color of the substance changes in response to the stimulus applied by the application unit, and a recording unit for recording the correspondence between the time progression in the moving image and the time progression of the stimulus. [Effects of the Invention]

[0011] According to this disclosure, it is possible to improve the technology for evaluating the types of stimuli necessary to change the color of a substance. [Brief explanation of the drawing]

[0012] [Figure 1] This figure shows the configuration of the evaluation device according to the embodiment of the present disclosure. [Figure 2] This figure shows the configuration of the analysis device provided in the evaluation device according to the embodiment of this disclosure. [Figure 3] This flowchart shows the procedure for the evaluation method according to the embodiment of this disclosure. [Figure 4] This flowchart shows the procedure for the evaluation method according to the embodiment of this disclosure. [Figure 5] This figure shows a sample held in a well plate. [Figure 6] Figures 6(a), (b), (c), and (d) show the changes in the color of the sample. [Figure 7] This figure shows the time change in the difference in brightness values ​​of the samples. [Figure 8] This figure shows the relationship between the time progression in a video and the temperature of the sample. [Figure 9] This figure shows the relationship between the mole fraction of AAm and the phase transition temperature of the polymer. [Modes for carrying out the invention]

[0013] As an embodiment of this disclosure, a technique for evaluating the type of stimulus necessary to change the color of a substance whose color changes in response to an applied stimulus will be described.

[0014] The evaluation device of this disclosure acquires a video image of a substance taken when a stimulus is applied, the correspondence between the time progression in the video and the time change of the stimulus, and the stimulus at the point in time when the color of the substance changes in the video, by referring to the correspondence between the time progression in the video and the time change of the stimulus, thereby evaluating the stimulus for changing the color of a substance.

[0015] As stimuli for changing the color of a substance, there are temperature, light, electricity, mechanical stimuli, pressure, solvents, magnetic fields, etc. In the case of a substance having thermochromism in which the color changes according to temperature, the evaluation apparatus evaluates, as an aspect of the stimulus for changing the color of the substance, the temperature (phase transition temperature) at which the color of the substance changes. In the case of a substance having photochromism in which the color changes according to light, the evaluation apparatus evaluates, as an aspect of the stimulus for changing the color of the substance, the wavelength, light amount, etc. of the light at which the color of the substance changes. In the case of a substance having electrochromism in which the color changes according to electricity, the evaluation apparatus evaluates, as an aspect of the stimulus for changing the color of the substance, the voltage, current, power, etc. at which the color of the substance changes. In the case of a substance having mechanochromism or piezochromism in which the color changes according to mechanical stimuli or pressure, the evaluation apparatus evaluates, as an aspect of the stimulus for changing the color of the substance, the magnitude of the force, pressure, etc. at which the color of the substance changes. In the case of a substance having solvatochromism in which the color changes by a solvent, the evaluation apparatus evaluates, as an aspect of the stimulus for changing the color of the substance, the type, amount, etc. of the solvent at which the color of the substance changes. In the case of a substance in which the color changes according to a magnetic field, the evaluation apparatus evaluates, as an aspect of the stimulus for changing the color of the substance, the magnitude, direction, etc. of the magnetic field at which the color of the substance changes.

[0016] In the following embodiments, mainly, the case of evaluating the phase transition temperature of a substance whose color changes according to temperature will be described, but the same applies to the case of evaluating the aspect of the stimulus for changing the color of a substance whose color changes according to other stimuli.

[0017] FIG. 1 shows the configuration of an evaluation apparatus 1 according to an embodiment of the present disclosure. The evaluation apparatus 1 includes a measurement apparatus 2 that measures a change in color when a stimulus is applied to a substance, and an analysis apparatus 3 that analyzes the measurement result by the measurement apparatus 2 and evaluates an aspect of the stimulus for changing the color of the substance.

[0018] The measuring device 2 includes a holding unit 4 for holding a sample, a heating unit 5 for heating the sample, a recording unit 6 for recording the temperature change of the sample, a photographing unit 7 for taking a moving image of the sample, and a housing 8 for housing these components. The heating unit 5 is an example of an applying unit that applies a stimulus to a substance.

[0019] The holding unit 4 includes a well plate 11 and an acrylic plate 12. The well plate 11 holds a sample 10 containing a solution of a substance to be evaluated. The holding unit 4 may have any shape capable of holding the sample 10. The holding unit 4 may hold one sample 10 or may be configured to hold a plurality of samples 10. The acrylic plate 12 is installed above the well plate 11 to prevent the solvent from evaporating from the solution of the substance held in the well plate 11. The acrylic plate 12 may be formed of a material such as an acrylic resin or glass that transmits visible light. When the sample 10 does not have a solvent or when the solvent does not evaporate even when heated to near the phase transition temperature of the substance contained in the sample 10, the acrylic plate 12 may not be installed.

[0020] The heating unit 5 includes a heater 20, a support 21, an oil bath 22, a DC stabilized power supply 23, and a DAQ board 24. The heater 20 generates heat when energized. The heater 20 may be any type of heater such as a silicone rubber heater. The support 21 is installed on the heater 20 and supports the oil bath 22 and the holding unit 4. The support 21 may be formed of a material such as aluminum with high thermal conductivity. The oil bath 22 uniformly heats the holding unit 4 with a heat medium. The heat medium is heated by the heat transmitted from the support 21. The heat medium may be grease, silicone oil, water, or the like. The DC stabilized power supply 23 converts a commercial AC power supply into a DC voltage and supplies it to the heater 20. The DAQ board 24 measures the DC voltage output from the DC stabilized power supply 23 and controls the DC stabilized power supply 23.

[0021] The recording unit 6 includes a thermocouple 30 and a logger 31. The thermocouple 30 measures the temperature of the sample 10. The temperature of the sample 10 may also be measured by a thermographic camera or the like. In this case, the holding unit 4 may include a plate made of a material that transmits both infrared and visible light instead of the acrylic plate 12. The recording unit 6 may include multiple thermocouples 30. In this case, the temperature distribution on the well plate 11 may be calculated based on the temperatures measured at multiple locations on the well plate 11. The logger 31 records the temperature of the sample 10 measured by the thermocouple 30 and the measurement timing in a storage device. The measurement timing may be expressed as a time or as elapsed time from the start of measurement.

[0022] The imaging unit 7 captures a video showing how the color of the sample 10 changes in response to temperature changes. The imaging unit 7 may be a general digital camera using an image sensor that converts visible light sensitivity into electrical signals. The imaging unit 7 records a video containing multiple frames in which the color of the substance is discernible. The imaging unit 7 may output data in a RAW format or other format without image processing such as image compression.

[0023] The housing 8 houses at least the holding part 4 and the thermocouple 30 and insulates them from the surroundings. If insulation is not required, the housing 8 may not be used.

[0024] Figure 2 shows the configuration of an analysis device 3 provided in an evaluation device 1 according to an embodiment of the present disclosure. The analysis device 3 comprises a communication device 51, a display device 52, an input device 53, a storage device 80, and a processing device 60. The analysis device 3 may be a server device, a device such as a personal computer, or a mobile terminal such as a mobile phone terminal, smartphone, or tablet terminal.

[0025] The communication device 51 controls communication with other devices. The communication device 51 may communicate using any communication method, such as wired or wireless. The display device 52 displays a screen generated by the processing device 60. The display device 52 may be a liquid crystal display device, an organic EL display device, or the like. The input device 53 transmits instructions from the user of the analysis device 3 to the processing device 60. The input device 53 may be a mouse, keyboard, touchpad, or the like. The display device 52 and the input device 53 may be implemented as a touch panel. The storage device 80 stores programs, data, etc., used by the processing device 60. The storage device 80 may be a semiconductor memory, a hard disk, or the like.

[0026] The processing unit 60 comprises a calibration unit 71, a measurement control unit 72, a correspondence acquisition unit 73, a moving image acquisition unit 74, a color change determination unit 75, and a stimulus type evaluation unit 76. These configurations can be implemented as hardware using arbitrary circuits, a computer CPU, memory, or other LSIs. These configurations can also be implemented as software using programs loaded into memory. Here, we are illustrating the functional blocks realized through the cooperation of these components. Therefore, it will be understood by those skilled in the art that these functional blocks can be implemented in various forms, such as hardware only or a combination of hardware and software.

[0027] The calibration unit 71 calibrates the recording unit 6. Prior to measurement by the measuring device 2, the calibration unit 71 measures the temperature of the sample 10 when it is heated by the heater 20 using a thermographic camera or the like, and calibrates the difference between this temperature and the measurement result from the thermocouple 30. The calibration unit 71 may record the difference between the measurement result from the thermographic camera and the measurement result from the thermocouple 30, and in the measurement by the measuring device 2, it may calibrate and record the measurement result from the thermocouple 30 based on the recorded difference. The calibration unit 71 may evaluate the sample 10 held in one of the multiple positions in the holding unit 4 where the sample 10 can be held, specifically the position where the difference between the measurement result from the thermographic camera and the measurement result from the thermocouple 30 is less than or equal to a predetermined value.

[0028] The measurement control unit 72 controls each component of the measuring device 2 to cause the measuring device 2 to measure the change in the color of the substance when a stimulus is applied. The measurement control unit 72 synchronizes the capture of moving images by the imaging unit 7 with the recording of the temperature of the sample 10 by the recording unit 6.

[0029] The correspondence acquisition unit 73 acquires the correspondence between the time progression in the video captured by the imaging unit 7 and the time change in the temperature of the sample 10 recorded by the recording unit 6 from the measuring device 2 and stores it in the storage device 80.

[0030] The video acquisition unit 74 acquires the video image captured by the imaging unit 7 when the sample 10 is heated by the heating unit 5 from the measuring device 2 and stores it in the storage device 80.

[0031] The color change determination unit 75 analyzes the video footage stored in the storage device 80 to determine the point in time when the color of the sample 10 changed in the video footage. The color change determination unit 75 analyzes the frame before the color of the sample 10 changed, for example, the first frame, from among the frames that make up the video footage stored in the storage device 80, and identifies the position of the sample 10 using edge detection technology or the like. The color change determination unit 75 identifies a boundary line by extracting pixels where the difference in brightness between adjacent pixels is greater than or equal to a predetermined value, and identifies the position of each well in the well plate 11 by drawing a perfect circle that approximates the identified boundary line. For each frame at a predetermined interval, the color change determination unit 75 calculates the average value of the pixel values ​​at the position of each well, and determines the point in time when the color of the substance changed based on the average value of the pixel values. For example, the point in time when the difference in the average value of the pixel values ​​between frames is the largest may be determined as the point in time when the color of the substance changed. The color change determination unit 75 may also determine the point in time when the color of the substance changed to be midway between the start and end points of the peak in a graph representing the time change of the difference in the average value of the pixel values. The color change determination unit 75 may determine that the time point at which half the area of ​​the peak in the graph representing the time change of the difference in the average values ​​of the pixel values ​​corresponds to the time point at which the color of the substance has changed. The pixel values ​​may be luminance values, RGB, HSV, HSL, CMK, CMYK, etc.

[0032] The stimulus mode evaluation unit 76 evaluates the stimulus mode for changing the color of a substance by obtaining the stimulus mode at the point in time when the color of the sample 10 changes in the video, by referring to the correspondence between the time progression in the video and the time change in the temperature of the sample 10. If the holding unit 4 is configured to hold multiple samples 10, the stimulus mode evaluation unit 76 evaluates the stimulus mode at the point in time when the color of each of the multiple samples 10 changes. As a result, the stimulus modes for changing the color of multiple substances can be evaluated simultaneously in a single measurement, thereby significantly reducing the time and effort required for evaluation.

[0033] Figure 3 is a flowchart showing the procedure of the evaluation method according to an embodiment of the present disclosure. This figure shows the procedure in which the measuring device 2 measures the change in the color of a substance.

[0034] The calibration unit 71 of the analysis device 3 calibrates the recording unit 6 of the measuring device 2 (S10). The measurement control unit 72 of the analysis device 3 causes the imaging unit 7 of the measuring device 2 to capture a moving image of the substance (S12) and also causes the heating unit 5 of the measuring device 2 to apply a stimulus to the substance (S14). The recording unit 6 of the measuring device 2 records the manner and timing of the stimulus applied to the substance (S16). The measurement continues, returning to S12, until the color of all the substances held in the holding unit 4 of the measuring device 2 changes (N in S18). When the color of all the substances has changed (Y in S18), the measurement is terminated.

[0035] Figure 4 is a flowchart showing the procedure of the evaluation method according to an embodiment of the present disclosure. This figure shows the procedure for the analyzer 3 to evaluate the manner of stimulation for changing the color of a substance.

[0036] The video acquisition unit 74 acquires video images captured by the imaging unit 7 when a stimulus is applied to the substance by the heating unit 5 from the measuring device 2 (S20). The correspondence acquisition unit 73 acquires the correspondence between the time progression in the video images captured by the imaging unit 7 and the time changes in the nature of the stimulus recorded by the recording unit 6 from the measuring device 2 (S22).

[0037] The color change determination unit 75 acquires the point in time when the color of the substance changes in the video (S24). The stimulus mode evaluation unit 76 evaluates the stimulus mode for changing the color of the substance by referring to the correspondence between the time progression in the video and the time change of the stimulus mode, and acquiring the stimulus mode at the point in time when the color of the substance changes in the video (S26). The evaluation continues back to S24 until the evaluation of all substances captured in the video is completed (N in S28). When the evaluation of all substances is completed (Y in S28), the analysis is terminated.

[0038] The technology disclosed herein allows for the precise evaluation of the type of stimulus required to change the color of a substance. Furthermore, since the change in the substance's color can be measured with a simple configuration, the cost of evaluation can be reduced. In addition, because the change in the substance's color is measured directly, the type of stimulus required to change the substance's color can be evaluated even for substances that do not undergo exothermic, endothermic, or phase transition reactions in conjunction with the color change.

[0039] Furthermore, when multiple substances are held simultaneously in the holding section 4 of the measuring device 2, multiple substances can be evaluated at once, significantly reducing the time and effort required for evaluation. This enables high-throughput evaluation, drastically reducing the time and effort required to search for substances with phase transition temperatures suitable for the application. In addition, it allows for the efficient generation of large amounts of training data necessary for training artificial intelligence to estimate phase transition temperatures from the structure and manufacturing method of substances.

[0040] [Examples] Using the evaluation apparatus 1 according to the embodiment of this disclosure, the phase transition temperatures of five polymer solutions with different phase transition temperatures, prepared using two monomers, N-isopropylacrylamide (NIPA) and acrylamide (AAm), were evaluated simultaneously.

[0041] [Evaluation of temperature unevenness] Prior to evaluating the phase transition temperature, the temperature unevenness of the 96-well plate was investigated. Water was placed in each well and heated by the heating unit 5, and the temperature of each well was measured using a thermographic camera. Wells where the temperature difference with the well where the thermocouple 30 was installed was 50°C or less and 0.5°C or less were used for the following measurements.

[0042] [Measurement of color changes] Figure 5 shows the sample 10 held in the well plate 11. It is known that the phase transition temperature of polymers containing NIPA and AAm as monomers is higher when the AAm content is higher. Samples 10a, 10b, 10c, 10d, and 10e, with molar ratios of NIPA to AAm of 100:0, 92:8, 84:16, 76:24, and 0:100, respectively, were placed in the well plate 11. The mole fractions of AAm were 0%, 8%, 16%, 24%, and 100%, respectively.

[0043] Figure 6 shows the color changes of sample 10. Figure 6(a) shows an image taken approximately 2 hours after the start of heating. The color of sample 10a has changed. Figure 6(b) shows an image taken approximately 3 hours after the start of heating. The color of sample 10b has changed. Figure 6(c) shows an image taken approximately 4 hours after the start of heating. The color of sample 10c has changed. Figure 6(d) shows an image taken approximately 5.5 hours after the start of heating. The color of sample 10d has changed. The color of sample 10e did not change.

[0044] [Analysis of measurement results] Figure 7 shows the time evolution of the difference in luminance values ​​for sample 10. The average value of the luminance value for each sample 10 was calculated, and the difference in luminance values ​​between frames was calculated. It was determined that the color of sample 10 had changed when the difference in luminance values ​​between frames was maximum.

[0045] Figure 8 shows the correspondence between the time progression in the video and the temperature of sample 10. Referring to the correspondence shown in Figure 8, the temperature of sample 10 was obtained when the color of sample 10 changed.

[0046] Figure 9 shows the relationship between the mole fraction of AAm and the phase transition temperature of the polymer. The circles indicate the phase transition temperature evaluated from measurements taken in this example at a heating rate of approximately 0.06°C per minute, the triangles indicate the phase transition temperature evaluated from measurements taken using DSC at a heating rate of 0.06°C per minute, and the squares indicate the phase transition temperature evaluated from measurements taken using DSC at a heating rate of 3°C per minute. It was confirmed that the method of this example yields results similar to those obtained with DSC for the phase transition temperature.

[0047] The present disclosure has been explained above based on examples. These examples are illustrative, and it will be understood by those skilled in the art that various modifications are possible in combinations of their components and processing processes, and that such modifications are also within the scope of the present disclosure. [Explanation of symbols]

[0048] 1 Evaluation device, 2 Measurement device, 3 Analysis device, 4 Holding unit, 5 Heating unit, 6 Recording unit, 7 Imaging unit, 8 Housing, 10 Sample, 11 Well plate, 12 Acrylic plate, 20 Heater, 21 Support, 22 Oil bath, 23 DC stabilized power supply, 24 DAQ board, 30 Thermocouple, 31 Logger, 51 Communication device, 52 Display device, 53 Input device, 60 Processing device, 71 Calibration unit, 72 Measurement control unit, 73 Correspondence acquisition unit, 74 Moving image acquisition unit, 75 Color change determination unit, 76 Stimulus type evaluation unit, 80 Storage device.

Claims

1. A step of acquiring a moving image of a substance whose color changes in response to the applied stimulus when the stimulus is applied to the substance, The steps include obtaining the correspondence between the time progression in the aforementioned video and the time change in the manner of the aforementioned stimulus, The steps include: evaluating the mode of the stimulus for changing the color of the substance by obtaining the mode of the stimulus at the time the color of the substance changes in the video image by referring to the correspondence relationship; An evaluation method that includes this.

2. By obtaining the mode of the stimulus at the point when the color of each substance changes in a video image of the substances taken when the stimulus is applied to multiple different substances simultaneously, by referring to the correspondence relationship, the modes of the stimulus for changing the color of each substance can be evaluated collectively. The evaluation method according to claim 1.

3. The stimulus includes at least one of temperature, light, electricity, pressure, solvent, and magnetic field. The evaluation method according to claim 1 or 2.

4. The aforementioned video image includes a plurality of frames captured in a manner that allows the color of the substance to be identified. The evaluation method according to claim 1 or 2.

5. Based on the pixel values ​​of the substance in frames at multiple points in time, the point in time when the color of the substance changed is determined. The evaluation method according to claim 4.

6. Based on the difference in the pixel values ​​of the substance between frames, the point in time when the color of the substance changed is determined. The evaluation method according to claim 5.

7. On the computer, A step of acquiring a moving image of a substance whose color changes in response to the applied stimulus when the stimulus is applied to the substance, The steps include obtaining the correspondence between the time progression in the aforementioned video and the time change in the manner of the aforementioned stimulus, The steps include: evaluating the mode of the stimulus for changing the color of the substance by obtaining the mode of the stimulus at the time the color of the substance changes in the video image by referring to the correspondence relationship; An evaluation program to execute the program.

8. A motion image acquisition unit acquires motion images of a substance whose color changes in response to the applied stimulus when the stimulus is applied to the substance, A correspondence acquisition unit that acquires the correspondence between the time progression in the aforementioned video and the time change in the manner of the aforementioned stimulus, A stimulus mode evaluation unit evaluates the stimulus mode for changing the color of the substance by obtaining the stimulus mode at the time the color of the substance changes in the aforementioned video image by referring to the correspondence relationship, An evaluation device including a device.

9. An application unit that applies a stimulus to a substance, A shooting unit that captures a moving image showing how the color of the substance changes in response to a stimulus applied by the application unit, A recording unit that records the correspondence between the time progression in the aforementioned video and the time change in the manner of the aforementioned stimulus, An evaluation device equipped with the following features.

10. A motion image acquisition unit acquires motion images of a substance whose color changes in response to the applied stimulus when the stimulus is applied to the substance, A correspondence acquisition unit that acquires the correspondence between the time progression in the aforementioned video and the time change in the manner of the aforementioned stimulus, A stimulus mode evaluation unit evaluates the stimulus mode for changing the color of the substance by obtaining the stimulus mode at the time the color of the substance changes in the aforementioned video image by referring to the correspondence relationship, The evaluation apparatus according to claim 9, comprising:

Images