JP6492501B2 - Determination apparatus, determination method, and computer program - Google Patents

Description

  The present invention relates to a method for determining the presence or absence of a reaction of a substance to be inspected with respect to a test piece to which a plurality of probes are fixed, and particularly relates to a determination apparatus, a determination method, and a computer program capable of improving the accuracy of a determination result.

  The specimen-derived liquid is infiltrated into a test piece fixed with multiple types of substances called probes that change color when a specific reaction occurs with the substance to be examined, and the presence or absence of reaction in each probe is determined by color development. Tests for identifying specimens by color development patterns of a plurality of probes are widely performed. For example, in the medical field, there are urine tests, blood tests and genetic tests, and in other fields, water quality tests and the like.

  In particular, in the medical field, a genetic test using a test piece for identifying a mutant form of a gene is performed (Patent Document 1, etc.), and in particular, use of a test kit for a drug susceptibility test for Mycobacterium tuberculosis group. Therefore, it is expected to speed up the highly accurate inspection (Patent Document 2 etc.). A large number of probes are fixed to the test pieces used in these genetic tests in order to identify various mutant genes, and there are many types of color development patterns.

  The reaction of the specimen to each probe is a chemical change. The degree of color development of the probe can change due to minute differences in the inspection conditions such as the temperature of the inspection environment and the inspection procedure. Also, the characteristics of the plurality of probes are various, such as those in which the color development becomes excessively sharp due to the difference in conditions, or those that become unclear and difficult to discriminate. Depending on the subtle differences in the test environment and procedure, it may be necessary to determine the presence or absence of a reaction by comparison with the color of the probe in another test piece that has developed color at the same time. Until now, the presence or absence of color development on each probe of the test piece has been determined based on the visual observation of the observer. However, it is difficult to identify the color patterns of a large number of probes with high accuracy in consideration of the color development conditions that can change depending on the above-described conditions and the color development characteristics that differ from probe to probe. .

  In view of this, a method has been proposed in which a computer performs image processing on test piece image data obtained by imaging a test piece that has undergone an inspection procedure, thereby uniformly determining the presence or absence of coloration of each probe ( Patent Documents 3 and 4). Patent Document 3 discloses a measuring apparatus including a specific transport device that can sequentially image a plurality of test pieces and determine the presence or absence of color development without any problem. In Patent Document 4, a test piece is imaged by using a widely used portable terminal device with an imaging unit without using a specific measurement device as disclosed in Patent Document 3, and imaging is performed. A system is disclosed in which image data is transmitted from a terminal device to a server device, the server device performs analysis based on captured image data, and the server device returns an analysis result to the terminal device.

JP 2007-064927 A JP 2011-087465 A JP 2007-212262 A JP 2012-202989 A

  When the determination is made by performing processing on the data of the test piece image obtained by imaging the test piece, the accuracy is higher than in the case of making an artificial judgment by visual observation. However, the high accuracy is maintained only on the assumption that the imaged piece image data is obtained under uniform imaging conditions. When using a specific measurement device as disclosed in Patent Document 3, the uniformity of the imaging conditions is satisfied, but in a system that does not require a specific measurement device as disclosed in Patent Document 4, Due to the difference in imaging conditions such as the illuminance of the imaging environment by the terminal device or the color temperature of the illumination, or the characteristics of the imaging device, even if it is imaged piece image data obtained by imaging the same object, the color strength and color balance depend on the imaging conditions. Or brightness etc. differ and may cause a misjudgment.

  The present invention has been made based on such circumstances, and it is possible to improve the accuracy of the determination result when determining based on image processing on test piece image data without using a dedicated device for measuring the test piece. An object is to provide a possible determination device, determination method, and computer program.

  The determination apparatus according to the present invention acquires image data obtained by imaging a test piece on which a plurality of detection bodies that develop color depending on whether or not there is a reaction with a substance to be inspected, and a plurality of images based on the acquired image data In the determination apparatus for determining presence / absence of a reaction in the plurality of detection bodies based on an image including pixels, based on a pixel value for each pixel in the image, a luminance value or a gradation value indicating one or a plurality of colors. Corresponding to a pixel value in each detection body region for each detection body region specified as a region where each of the plurality of detection bodies in the image is captured, and a reference value calculation means for calculating a determination reference value The conversion means for converting the gradation value indicating the level of brightness or the shade of one or more colors into a relative value using the determination reference value, and predetermined for each of the plurality of detection bodies for each detection body region. Threshold Comparing means for comparing the relative values, on the basis of the comparison result by the comparison means, characterized in that it comprises a determination means for determining presence or absence of reaction for each of the plurality of detector.

  The conversion means of the determination apparatus according to the present invention is characterized in that a ratio of the gradation value to the determination reference value is calculated.

  The reference value calculation means of the determination device according to the present invention includes a means for specifying the gradation value for each of the detection object areas, an extraction means for extracting a part from the detection object areas of the plurality of detection objects, Means for calculating the determination reference value using the gradation value specified for the extracted part of the detected body region.

  The extraction means of the determination apparatus according to the present invention is characterized in that a detection body region in which a gradation value greater than a predetermined value is specified is extracted.

  The reference value calculation means of the determination apparatus according to the present invention is characterized in that the plurality of detection bodies are classified into a plurality of groups, and the determination reference value is calculated for each of the classified groups.

  In the determination apparatus according to the present invention, the substance to be detected is a gene sample, and the plurality of detection bodies are probes including oligonucleotides that hybridize with the gene sample.

  The determination apparatus according to the present invention is characterized in that the substance to be detected is Mycobacterium tuberculosis, and the plurality of detection bodies are probes including oligonucleotides that hybridize with the Mycobacterium tuberculosis.

  According to the determination method of the present invention, a computer capable of acquiring information from an imaging apparatus has image data of a test piece on which a plurality of detection bodies that develop color depending on the presence or absence of a reaction with a substance to be examined are fixed. In the determination method for determining whether or not there is a reaction in the plurality of detection bodies based on an image including a plurality of pixels based on the acquired image data, the luminance based on the pixel value for each pixel in the image A detection reference value for each test piece is calculated for each test piece, and a detection object that is specified as an area where each of the plurality of detection objects is imaged is calculated. For each region, a gradation value indicating the level of brightness corresponding to the pixel value in each detection body region or the shade of one or more colors is converted into a relative value using the determination reference value, and the detection body region Every, Compared serial with the plurality of detector separately predetermined in Aru threshold and the relative value, based on the comparison result, and judging the presence or absence of a reaction for each of the plurality of detector.

  The computer program according to the present invention is an image data of a test piece in which a plurality of detection bodies that are colored according to the presence or absence of a reaction with a substance to be examined are fixed to a computer capable of acquiring information from an imaging device. In the computer program for determining the presence or absence of reaction in the plurality of detection bodies from an image composed of a plurality of pixels based on the acquired image data, based on the pixel value for each pixel in the image, A step of calculating a reference value for each test piece with respect to a gradation value indicating brightness level or gradation of one or a plurality of colors, and a region where each of the plurality of detectors in the image is captured. For each detection body region, a gradation value indicating the level of brightness corresponding to the pixel value in each detection body region or the shade of one or more colors is used as the determination reference value. The step of converting the relative value using, and, on the detector for each region, characterized in that to perform the step of comparing said plurality of detector separately predetermined in Aru threshold and the relative value.

  In the present invention, a determination reference value corresponding to the imaging conditions of individual image data such as brightness and color balance of the entire image is calculated from pixel values in the image based on the captured image data obtained by imaging the test piece. The gradation value based on the pixel value in each of the detection body regions is converted into a relative value based on the determination reference value, and then compared with the threshold value. Thereby, when making a determination based on a fixed threshold value, it is possible to reduce the influence of errors due to the imaging conditions of individual imaging devices having different imaging elements or imaging environments, and improve the determination accuracy. In the present invention, the relative value converted by the determination reference value is compared with a threshold value determined for each detection object instead of a single threshold value. Thereby, individual determinations according to the characteristics of the respective detection bodies that cause a chemical reaction are possible, and the determination accuracy can be improved.

  The relative value obtained by the conversion may be a ratio to the determination reference value. In addition, it is not restricted only to a ratio, The adjustment with respect to the calculated criterion value etc. may be sufficient.

  In the present invention, the detection region of the detection body that is clearly colored is extracted, and the determination reference value is calculated based on the gradation value in the detection body region of the detection body that can be determined to be colored. Based on the determination reference value, the presence or absence of a reaction in each detector is determined. Thereby, it is possible to reduce the influence of the gradation value on the determination reference value in the detection region of the detection body that is not clearly colored, and improve the determination accuracy.

  Whether or not the color is clearly developed is determined by whether or not the gradation value indicating the level of luminance or the shade of a specific color is a predetermined value or more, that is, whether or not the luminance is higher than the predetermined luminance, Judgment is made based on whether the color is darker than a predetermined darkness. The predetermined value is empirically determined in advance as a minimum value as a value that must be exceeded when color is developed under any imaging condition. The determination may be made based on whether the luminance is less than the predetermined value, whether the luminance is within a predetermined range, or whether the specific color is within a predetermined darkness range. You may make it do.

  In the present invention, the criterion value is calculated for each group. A determination reference value can be calculated for each detection object region of detection objects having similar characteristics. Thereby, it is possible to reduce the mutual influence of the luminance or color in the detection body region of another detection body having completely different color development characteristics, and to improve the determination accuracy.

  In the present invention, a specific detection body (special detection body) is provided in the plurality of detection bodies, and the presence or absence of a reaction in the specific detection body is determined. Thereby, many types of determination results can be output, and determination accuracy can be improved.

  In this invention, when a test piece is used for a tuberculosis microbe test | inspection, the more excellent effect is exhibited. Test strips used for M. tuberculosis testing have many detectors (probes) depending on the number of mutants, so there are many color patterns that must be distinguished, and the tester can visually check them. When judging, it was easy to invite a false judgment. An accurate determination result can be obtained even by using an existing imaging device used by the inspector by performing a highly accurate determination based on the captured image data regardless of the imaging conditions.

  Of course, the test pieces are not limited to those used for the tuberculosis test, HPV (human papilloma) test, HLA (human leukocyte antigen) test, MRSA (methicillin-resistant Staphylococcus aureus) detection, Staphylococcus (Staphylococcus aureus) group detection , Helicobacter Pylori (H. pylori) detection, Clostridium difficile (Clostridial spp.) Detection, E. coli (E. coli) detection, etc. Moreover, it is not restricted to what is used for a genetic test | inspection, The various thing which determines the presence or absence of reaction by the color development of the detection body in an antigen antibody reaction may be used. For example, HIV (human immunodeficiency virus) test, HCV (hepatitis C virus) test and the like can be mentioned.

  In the case of the present invention, the influence of the error due to the imaging condition is reduced, and furthermore, individual determination according to the characteristics of each detection body is possible. Therefore, captured image data obtained by imaging apparatuses with different imaging conditions is used. However, a highly accurate determination result that does not depend on the imaging conditions can be obtained.

It is explanatory drawing for demonstrating the outline | summary of this invention. 1 is a block diagram illustrating a configuration of an information processing device in Embodiment 1. FIG. It is a flowchart which shows an example of the process sequence performed by the control part of information processing apparatus. It is a flowchart which shows an example of the process sequence which determines negative / positive of each probe. It is explanatory drawing explaining one of the calculation examples of a determination reference value. It is explanatory drawing explaining one of the calculation examples of a relative value. 10 is a flowchart illustrating an example of a processing procedure for determining negative / positive of each probe in Modification 1. 10 is a flowchart illustrating an example of a processing procedure for determining negative / positive of each probe in Modification 2. 6 is a block diagram showing a configuration of a determination system in Embodiment 2. FIG. It is a flowchart which shows an example of the process sequence performed by the control part of a central apparatus.

  FIG. 1 is an explanatory diagram for explaining the outline of the present invention. In FIG. 1, reference numeral 1 denotes an information processing apparatus. The information processing apparatus 1 is a so-called smartphone including an imaging unit, a display unit 13, and an operation unit 14, and is a general-purpose device having various functions in addition to the function as a determination device according to the present invention.

  In FIG. 1, reference numeral 2 is an example of a test piece. The test piece 2 is produced by physically or chemically fixing a substance that causes a specific reaction between the strip-shaped substrate 20 and the substance to be inspected called probes 21 and 22 in a line shape. . Each probe 21 and 22 develops a predetermined color when a reaction occurs, and negative / positive determination is possible by color development. For example, the test piece 2 is obtained by fixing a plurality of oligonucleotides having different properties as probes 21 to a substrate 20 made of polyethylene terephthalate as a material, and is a test piece for identifying various mutant genes of Mycobacterium tuberculosis. In addition, the test piece 2 may be one in which test papers to be inspected that are different from each other are affixed to a paper base 20 as a probe 21, and may be used for urinalysis. In addition, the test piece 2 may be for various tests such as a blood test or a water quality test. A specific probe 22 that develops a color when the test is properly performed is fixed to the test piece 2. In addition to the probes 21 and 22, the test piece 2 is formed with a marker for identifying the substance to be inspected. The marker is formed, for example, by applying paint in the same line shape as the probes 21 and 22 at a predetermined interval between the plurality of probes 21 and 22.

  The inspection practitioner performs a treatment suitable for the test on the substance to be inspected as necessary, creates a liquid (or gas) derived from the substance to be inspected, and supplies the liquid to the probe 21 on the test piece 2. , 22. The inspection practitioner uses the information processing apparatus 1 to perform an operation of imaging the test piece 2 after contact with the inspection target substance as shown in FIG. The information processing apparatus 1 executes a determination process for determining the presence / absence (negative / positive) of the reaction of the probes 21 and 22 on the test piece 2 after contact with respect to the captured image data, and an inspection based on the determination result The result is displayed on the display unit 13. The examiner can obtain a highly accurate determination result using the existing information processing apparatus 1 without using a specific measuring apparatus. Hereinafter, the configuration of the information processing apparatus 1 for making it possible to obtain a highly accurate determination result will be described in detail.

(Embodiment 1)
FIG. 2 is a block diagram illustrating a configuration of the information processing apparatus according to the first embodiment. As described above, the information processing apparatus 1 uses, for example, a smartphone, but may be a tablet PC (Personal Computer). The information processing apparatus 1 includes a control unit 10, a storage unit 11, a temporary storage unit 12, a display unit 13, an operation unit 14, an imaging unit 15, and a communication unit 16.

  The control unit 10 uses a CPU (Central Processing Unit). The control unit 10 reads and executes the determination application program 1P stored in the storage unit 11, thereby causing the information processing apparatus 1 to function as the determination device according to the present invention.

  The storage unit 11 uses a flash memory. In the storage unit 11, various computer programs including the determination application program 1P read by the control unit 10 are stored in a rewritable manner. The determination application program 1P is received by the control unit 10 from an external device (for example, a server device) via the communication unit 16 and stored in the storage unit 11, or the control unit 10 communicates from a wired-connected external device. It is acquired and stored. The storage unit 11 stores captured image data. Of course, the storage unit 11 may use a storage device other than the flash memory.

  The storage unit 11 stores information to be referred to when the control unit 10 executes processing based on the determination application program 1P together with the determination application program 1P. For example, various numerical information such as a set value used as a reference for determination, information on a marker pattern for specifying the type of the test piece 2, and a test piece 2 for identifying the probes 21 and 22 on the test piece 2 Identification information for each. Note that information referred to when the control unit 10 executes processing based on the determination application program 1P may be acquired from an external device (for example, a server device) via the communication unit 16.

  The temporary storage unit 12 uses a RAM such as a DRAM (Dynamic Random Access Memory). The temporary storage unit 12 temporarily stores information generated by the processing of the control unit 10.

  The display unit 13 uses a touch panel built-in display. The display unit 13 displays various operation screens including objects such as text and icons based on the control processing of the control unit 10. The display unit 13 may not be a touch panel built-in type.

  The operation unit 14 uses a touch panel built in the display of the display unit 13 and a button group provided on the housing of the information processing apparatus 1. The operation unit 14 notifies the control unit 10 of the contact by the user and the position information of the contact location on the touch panel. The operation unit 14 notifies the control unit 10 of information such as button presses and press times.

  The imaging unit 15 uses a complementary metal oxide semiconductor (CMOS) image sensor. The imaging unit 15 outputs color captured image data to the control unit 10. The captured image data is stored in the temporary storage unit 12 or the storage unit 11 and displayed on the display unit 13 under the control of the control unit 10. The imaging unit 15 is provided at one end of the wide surface opposite to the display unit 13 of the information processing apparatus 1. The imaging unit 15 may use not only a CMOS image sensor but also a CCD (Charge Coupled Device) image sensor.

  The communication unit 16 includes a communication unit that implements telephone communication and wireless communication. The control unit 10 can communicate with a base station for telephone communication or an access point for wireless communication through the communication unit 15.

  In the information processing apparatus 1 configured as described above, the control unit 10 reads out and starts the determination application program 1P from the storage unit 11 in accordance with the operation of the examiner, and displays the determination application operation screen 30 as illustrated in FIG. Display on the unit 13. The determination application operation screen 30 includes a monitor screen 31 and an imaging icon 32, and real-time images captured by the imaging unit 15 are sequentially displayed on the monitor screen 31. The examiner can tap the imaging icon 32 while confirming the real-time image on the monitor screen 31. When the imaging icon 32 is tapped by the examiner, the control unit 10 detects the tap by the operation unit 14, acquires captured image data output from the imaging unit 15, and executes processing described below.

  FIG. 3 is a flowchart illustrating an example of a processing procedure executed by the control unit 10 of the information processing apparatus 1. As described above, in the information processing apparatus 1 in which the determination application program 1P is activated, the following processing procedure is performed by tapping the imaging icon 32 in the determination application operation screen 30 displayed on the display unit 13. When detected by the control unit 10, the control unit 10 executes.

  The control unit 10 acquires captured image data from the imaging unit 15 (step S1). The control part 10 extracts the test piece area | region where the test piece 2 is reflected among the images based on the acquired captured image data (step S2). In step S2, the control unit 10 may automatically perform trimming to exclude an area corresponding to the background such as a table on which the test piece 2 is placed.

  Next, the control part 10 specifies the kind of the test piece 2 based on the pixel value (RGB value) of each pixel contained in the extracted test piece area | region (step S3). In step S3, the control unit 10 refers to, for example, the marker pattern information described above for the pixel values in the range corresponding to the test piece 2, and stores the type of the test piece 2 stored in association with the matched pattern. And information for identifying the type of each probe 21, 22 included in the type of test piece 2 is read from the storage unit 11.

  The control unit 10 performs a process of determining negative / positive in each probe 21 and 22 of the test piece 2 for each specified type (step S4), and based on the negative / positive pattern in each probe 21 and 22 The inspection result is specified (step S5). The control unit 10 causes the display unit 13 to display an image or character information indicating the specified inspection result (step S6), stores the inspection result together with the acquired captured image data in the storage unit 11 (step S7), and ends the process. To do.

  Details of the determination processing in step S4 will be described. FIG. 4 is a flowchart illustrating an example of a processing procedure for determining negative / positive of the probes 21 and 22.

  The control unit 10 extracts the probe areas corresponding to the probes 21 and 22 on the test piece 2 in association with the information for identifying the probes 21 and 22 from the test piece area in the image (step S401). . In step S <b> 401, for example, the control unit 10 temporarily stores the RGB values of the pixel group in the probe area corresponding to each probe 21, 22 in association with the identification information of each probe 21, 22 specified from the type of the test piece 2. Store in unit 12.

  The control unit 10 specifies the gradation value of the luminance (Luminance) for each of the probes 21 and 22 from the extracted probe region (step S402). In step 402, for example, the control unit 10 calculates the average value of RGB values in the pixel group in the probe area corresponding to each of the probes 21 and 22, and calculates the average value of R values, the average value of G values, and the B value. Is applied to a predetermined conversion formula to obtain a luminance gradation value, and the gradation value is stored in the temporary storage unit 12 in association with the identification information of each probe 21, 22. At this time, the luminance gradation value is a larger numerical value as the luminance is higher. In step S402, the control unit 10 may specify a gradation value of brightness. In addition, the control unit 10 may specify the gradation value of the saturation of the specific color in order to determine the color development of the specific color. A plurality of gradation values with different index values, such as gradation values by other expression systems, may be specified and used. It is not limited to the average value, and may be a median value, a mode value, or the like.

  The control unit 10 determines whether or not the gradation value corresponding to the specific probe 22 among the gradation values specified in step S402 is equal to or greater than a predetermined value (step S403). The specific probe 22 develops a predetermined color when the test is properly performed. Therefore, in step S403, the control unit 10 may determine whether the gradation value is a value that can be determined to be a predetermined color, whether it is within a predetermined range, or a predetermined value. You may make it judge by whether it is less than.

  When it is determined in step S403 that the gradation value is less than the predetermined value (S403: NO), the control unit 10 determines that the specific probe 22 is negative (step S404), that is, the test is appropriate. Therefore, the determination process is terminated, and the process returns to step S5 in the flowchart of FIG.

  If it is determined in step S403 that the gradation value is equal to or greater than the predetermined value (S403: YES), the control unit 10 determines that the specific probe 22 is positive (step S405). In other words, the control unit 10 refers to the gradation value of the brightness associated with each of the plurality of probes 21 and assumes that the test is properly performed, and the set value stored in the storage unit 11 is greater than or equal to the set value. A certain gradation value is extracted (step S406). Specifically, in step S406, the control unit 10 selects one by one from the identification information of each of the plurality of probes 21 stored in the temporary storage unit 12, and the corresponding luminance gradation value is greater than or equal to the set value. It is determined whether or not it exists, and only the gradation value determined to be greater than or equal to the set value is stored.

  The control unit 10 determines whether there is at least one gradation value that is equal to or greater than the set value (step S407). When it is determined in step S407 that there is no gradation value that is equal to or greater than the set value (S407: NO), the control unit 10 determines that all of the plurality of probes 21 are negative (step S408). The process returns to step S5 in the flowchart of FIG.

  When it is determined in step S406 that there is at least one gradation value that is equal to or greater than the set value (S407: YES), the control unit 10 calculates a determination reference value based on the gradation value that is equal to or greater than the set value ( Step S409). Specifically, in step S409, an average value of gradation values equal to or greater than a set value is calculated, and the average value is determined as a determination reference value. The calculation method of the determination reference value is not limited to a method of simply calculating and determining an average value, and may be a method of determining after performing statistical processing such as excluding outliers, or a median value, A method of calculating and determining a mode value or the like may be used.

  Next, the control unit 10 converts the gradation values into relative values with respect to all of the plurality of probes 21 using the determination reference value as a reference (step S410). Specifically, in step S410, the control unit 10 calculates a ratio (gradation value / determination reference value) of the gradation value specified for the corresponding probe region to the determination reference value. In addition, in step S410, the control unit 10 may calculate addition / subtraction (gradation value−determination reference value) of the corresponding gradation value from the determination reference value.

  The control unit 10 selects one of the plurality of probes 21 (step S411), and compares the relative value corresponding to the selected probe 21 and the relative value stored in advance in the identification information of the selected probe 21. The threshold value is compared (step S412), and negative / positive is determined based on the comparison result (step S413). Specifically, in step S413, the control unit 10 determines, for example, whether or not the relative value of the selected probe 21 is greater than or equal to a threshold value stored in advance. When it is determined that the threshold value is greater than or equal to the threshold value, the control unit 10 determines that the selected probe 21 is positive, and when it is determined that the value is less than the threshold value, the control unit 10 is negative for the selected probe 21. Is determined.

  Next, the control unit 10 determines whether negative / positive has been determined for all the probes 21 (step S414). If it is determined in step S414 that all the probes have not been determined (S414: NO), the control unit 10 returns the process to step S411 and performs the processes for the remaining probes 21.

  When it is determined in step S414 that all the probes 21 have been determined to be negative / positive (S414: YES), the control unit 10 ends the process of determining the negative / positive of each probe 21, and the flowchart of FIG. The process returns to step S5.

  Next, the determination reference value, the set value, the relative value, and the threshold value used in the above determination process will be described in detail. FIG. 5 is an explanatory diagram for explaining one example of calculation of the determination reference value. FIG. 5 shows an example of the gradation value of each probe 21 by a numerical value and a bar graph. The broken line in FIG. 5 indicates the magnitude of the setting value with respect to the gradation value. Among the bar graphs in FIG. 5, the bar graphs indicated by hatching correspond to gradation values greater than or equal to the set value. In the example of FIG. 5, the gradation values specified for the five probes 21 “A” to “E” are “100”, “200”, “150”, “50”, and “10”, respectively. An example of the setting value shown in FIG. 5 is “60”. In the detailed description of step S409 described above, the control unit 10 calculates the average value of the gradation values that are equal to or greater than the set value, and determines the average value as the determination reference value. In the specific example shown in FIG. 5, the control unit 10 sets the gradation values “100”, “200”, and “150” of the three probes 21 of “A”, “B”, and “C” that are “60” or more. The average value “150” is calculated and determined as a determination reference value. The calculation of such a criterion value is clearly negative by extracting the probe 21 that has developed a certain color reaction from a plurality of probes 21 and using the gradation value in the probe region of the extracted probe. This is performed to reduce the influence of the gradation value in the probe region of the probe 21 that is not colored. For example, depending on the type of substance to be inspected, it may be correct that many probes 21 do not develop color. In this case, since the number of probes 21 that are not colored is large, the determination reference value is determined when the average value is calculated and determined as the determination reference value without extracting the probes 21 that are clearly colored. There is a possibility that it may become smaller and cause an erroneous determination. As shown in FIG. 5, a probe 21 whose gradation value is equal to or higher than a set value, that is, a probe 21 that is clearly colored is extracted, and a determination reference value is obtained from the gradation value corresponding to the extracted probe 21. By calculating, it is possible to make a determination according to different imaging conditions for each test piece 2.

  FIG. 6 is an explanatory diagram for explaining one example of calculating a relative value. FIG. 6 shows an example of the relative value obtained based on the gradation value of each probe 21 in a bar graph, and shows a threshold value stored in advance for each probe 21 and an example of a determination result under each relative value. ing. The example of FIG. 6 corresponds to the gradation value of each probe 21 shown in FIG. For the calculated determination reference value “150”, the gradation values “100”, “200”, “150”, “50”, “50” of the five probes 21 “A” to “E” shown in FIG. A ratio (percentage) of 10 ”is obtained as a relative value. As shown in FIG. 6, the relative values of the five probes 21 of “A” to “E” are “67”, “133”, “100”, “33”, “6.7”, respectively. Negative / positive is determined depending on whether or not each of the five probes 21 of “E” to “E” is equal to or greater than a threshold value stored in advance. For example, in the probe 21 of “D”, the specified gradation value “50” is smaller than the set value “60” shown in FIG. 5, but the relative value is equal to or greater than the threshold value and is determined to be positive (+). Yes. This is because the probe 21 of “D” has a characteristic that should be determined to be positive when the color is even a little.

  As described above, the gradation value specified for each probe 21 is converted into a relative value, and compared with the threshold value set for each probe 21, individually according to the characteristics of each probe 21 causing a chemical reaction. Negative / positive determination is possible, and when converting to a relative value, each probe 21 is subjected to different information processing by changing a determination reference value serving as a reference for determining color development according to imaging conditions. Even if the apparatus 1 is used for imaging, the influence of errors due to imaging conditions can be reduced and the determination accuracy can be improved.

(Modification 1)
Depending on the characteristics of the probe 21 fixed to the test piece 2, the determination accuracy may not be good when one test piece 2 is converted to a relative value with one determination reference value. Therefore, the plurality of probes 21 on the test piece 2 may be classified into a plurality of groups according to the characteristics, the determination reference value may be calculated for each group, and negative / positive may be determined for each group.

  In Modification 1, when the probes 21 are classified into a plurality of groups for each test piece 2, the identification information of each probe 21 is stored in the storage unit 11 for each group. Specifically, group identification information for identifying a group is stored for each type of the test piece 2, and further, the group identification information is associated with the identification information of the probe 21 for each test piece 2 and stored in the storage unit 11. Keep it.

  FIG. 7 is a flowchart illustrating an example of a processing procedure for determining negative / positive of each of the probes 21 and 22 in the first modification. Of the processing procedures shown in the flowchart of FIG. 7, the same step numbers are assigned to the processes common to the flowchart of FIG. 4, and detailed description thereof is omitted.

  In step S403, it is determined that the gradation value of the specific probe 22 is greater than or equal to a predetermined value (S403: YES), and if the control unit 10 determines that the specific probe 22 is positive (S405), it is specified. One group is selected according to the type of the test piece 2 (step S421). The control unit 10 refers to the tone value of the probe 21 associated with the selected group, extracts a tone value equal to or greater than the set value (S406), and for each group, the tone value equal to or greater than the set value. It is determined whether or not there is at least one (S407). When it is determined that there is no gradation value that is equal to or greater than the set value (S407: NO), the control unit 10 determines that all of the plurality of probes 21 corresponding to the selected group are negative (Step S407). S422), the process proceeds to step S425.

  When it is determined in step S407 that there is one or more gradation values that are equal to or greater than the set value (S407: YES), the control unit 10 calculates a determination reference value in the selected group (step S423). In step S423, the control unit 10 calculates an average value of gradation values equal to or higher than the set value among the gradation values of the probe 21 associated with the selected group, and determines the determination reference value. For each group, the control unit 10 performs conversion to a relative value (S410) and determination for each probe 21 (S411 to S413). After the determination, it is determined whether or not the determination has been made for all the probes 21 in the selected group. Judgment is made (step S424).

  If it is determined in step S424 that determination has not been made for all the probes 21 in the selected group (S424: NO), the control unit 10 returns the process to step S411, and other probes in the selected group. 21 is selected and a determination process is performed (S411 to S413).

  If it is determined in step S424 that determination has been made for all the probes 21 in the selected group (S424: YES), the control unit 10 determines whether determination has been performed for all groups (step S425). .

  If it is determined in step S425 that determination has not been made for all groups (S425: NO), the control unit 10 returns the process to step S421, selects another group, and performs determination processing for each group ( S406 to S424) are executed.

  If it is determined in step S425 that determination has been made for all groups (S425: YES), the control unit 10 ends the process of determining negative / positive of each probe 21, and step S5 in the flowchart of FIG. Return processing to.

  Thus, by classifying the probes 21 on the test piece 2 into groups and calculating different criteria for each group, it is possible to accurately determine negative / positive according to the classification of the characteristics of the probes 21. It becomes.

(Modification 2)
When the test strip 2 is a test strip that identifies various mutated genes of Mycobacterium tuberculosis, there are cases where the test includes a gene amplification process and needs to be examined at different stages in the amplification process. In this case, a special probe for determining whether or not the amplification reaction has been normally performed is further fixed to the test piece 2. If the determination result of the special probe is negative, it indicates that there is an inhibiting factor for the amplification process. However, depending on the substance to be inspected, an effective test result may be obtained. For this, special probe negative / positive determination processing is required. Modification 2 shows an example of a determination processing procedure for the test piece 2 including such a special probe.

  FIG. 8 is a flowchart illustrating an example of a processing procedure for determining negative / positive of the probes 21 and 22 in the second modification. Of the processing procedures shown in the flowchart of FIG. 8, the same steps as those in the flowchart of FIG.

  In the second modification, when it is determined in step S407 that there is no gradation value equal to or greater than the set value (S407: NO), the control unit 10 is specified for the special probe described above. It is determined whether or not the gradation value is greater than or equal to a predetermined value (step S431).

  When it is determined in step S431 that the gradation value is equal to or greater than the predetermined value (S431: YES), the control unit 10 determines that the special probe is positive (step S432), and the negative / insensitive of each probe 21 is determined. The process for determining positive is terminated, and the process returns to step S5 in the flowchart of FIG.

  When it is determined in step S431 that the gradation value is less than the predetermined value (S431: NO), the control unit 10 determines that the special probe is negative (step S433), and negative / The process for determining positive is terminated, and the process returns to step S5 in the flowchart of FIG.

  As shown in the modified example 2, even if all the probes 21 are negative, an effective test result may be obtained depending on the negative / positive determination result of the special probe. Misjudgments can be avoided by making negative / positive judgments for special probes separately.

(Embodiment 2)
In the first embodiment, the determination process is executed by the information processing apparatus 1 based on the determination application program 1P. In contrast, in the second embodiment, a client server system is used to transmit captured image data from a terminal device to the central device, and the central device that has received the captured image data executes a determination process based on a determination program, and determines the determination result. The data is transmitted to the terminal device, and the determination result is obtained by the terminal device.

  FIG. 9 is a block diagram illustrating a configuration of a determination system according to the second embodiment. The system includes a terminal device 3, a central device 4, and a network 5. The terminal device 3 is a so-called smartphone. The terminal device 3 includes a control unit 30, a storage unit 31, a temporary storage unit 32, a display unit 33, an operation unit 34, an imaging unit 35, and a communication unit 36.

  The control unit 30 uses a CPU. The control unit 30 reads the determination application program (not shown) stored in the storage unit 31 and executes it, thereby communicating the terminal device 3 with the central device 4 and acquiring the determination result for the test piece 2. Function as a device capable of

  The storage unit 31 uses a flash memory. The storage unit 31 stores various computer programs read by the control unit 30 in a rewritable manner. The storage unit 31 stores captured image data. Of course, the storage unit 31 may use a storage device other than the flash memory. The temporary storage unit 32 uses a RAM such as a DRAM. The temporary storage unit 32 temporarily stores information generated by the processing of the control unit 30.

  The display unit 33 uses a display with a built-in touch panel. The display unit 33 displays various operation screens including objects such as text and icons based on the control processing of the control unit 30. The display unit 33 may not be a touch panel built-in type.

  The operation unit 34 uses a touch panel built in the display of the display unit 33 and a button group provided on the casing of the terminal device 3. The operation unit 34 notifies the control unit 30 of the contact information by the user and the position information of the contact location on the touch panel. The operation unit 34 notifies the control unit 30 of information such as button presses and press times.

  The imaging unit 35 uses a CMOS image sensor. The imaging unit 35 outputs color captured image data to the control unit 30. The captured image data is stored in the temporary storage unit 32 or the storage unit 31 and displayed on the display unit 33 under the control of the control unit 30. The imaging unit 15 may use not only a CMOS image sensor but also a CCD image sensor.

  The communication unit 36 includes a communication unit that implements telephone communication and wireless communication. The control unit 30 can communicate with the central apparatus 4 by connecting to the telephone communication base station 51 or the wireless communication access point 52 in the network 5 by the communication unit 35.

  In the terminal device 3 configured as described above, the determination application program is activated in accordance with the operation of the tester. The examiner operates the terminal device 3 to perform an operation of imaging the test piece 2 by the imaging unit 35, and performs an operation of executing the determination. By the control of the control unit 30 based on the determination application program, the captured image data obtained from the imaging unit 35 is transmitted to the central device 4 via the communication unit 36 and is executed by the central device 4 as described later. The obtained inspection result is transmitted from the central device 4 to the terminal device 3. The terminal device 3 transmits the captured image data based on the determination application program, and displays the inspection result transmitted from the central device 4 on the display unit 33 in a predetermined format in response thereto.

  The central device 4 uses a server computer. The central device 4 includes a control unit 40, a storage unit 41, a temporary storage unit 42, and a communication unit 43.

  The control unit 40 uses the CPU to read and execute the determination program 4P stored in the storage unit 41, thereby causing the central device 1 to function as the determination device according to the present invention.

  The storage unit 41 uses a hard disk. The storage unit 41 stores various computer programs including the determination program 4P read by the control unit 40. The determination program 4P is a program that the control unit 40 receives and stores from an external device via the communication unit 43, or a program that is read and stored by the control unit 40 from a recording medium. The storage unit 41 stores captured image data. Of course, the storage unit 41 may use a storage device other than the hard disk.

  The storage unit 41 stores information to be referred to when the control unit 40 executes a process based on the determination application program 1P together with the determination program 4P. For example, various numerical information such as a set value used as a reference for determination, information on a marker pattern for specifying the type of the test piece 2, and a test piece 2 for identifying the probes 21 and 22 on the test piece 2 Identification information for each.

  The temporary storage unit 42 uses a RAM such as a DRAM. The temporary storage unit 42 temporarily stores information generated by the processing of the control unit 40.

  The communication unit 43 includes a communication unit that implements telephone communication and wireless communication. The control unit 40 can communicate with the terminal device 3 by connecting to the telephone communication base station 51 or the wireless communication access point 52 in the network 5 through the communication unit 43.

  When the central device 4 configured in this way establishes a communication connection with the terminal device 3, the central device 4 executes the following processing. FIG. 10 is a flowchart illustrating an example of a processing procedure executed by the control unit 40 of the central apparatus 4.

  The control unit 40 receives the captured image data transmitted from the terminal device 3 by the communication unit 43 (step S101). The control unit 40 extracts a test piece region in which the test piece 2 is captured from an image based on the captured image data acquired by reception (step S102).

  The control unit 40 specifies the type of the test piece 2 based on the pixel value (RGB value) of each pixel included in the extracted test piece region (step S103). In step S103, the control unit 40 refers to, for example, the marker pattern information described above for the pixel values in the range corresponding to the test piece 2, and stores the type of the test piece 2 stored in association with the matched pattern. And identification information indicating the type of each probe 21, 22 included in the type of test piece 2 is read from the storage unit 41.

  The control unit 40 performs a process of determining negative / positive in each of the probes 21 and 22 of the test piece 2 for each specified type (step S104), and based on the negative / positive pattern in each of the probes 21 and 22 The inspection result is specified (step S105). Since the determination process in step S104 is the same as the content of the determination process executed by the control unit 10 of the information processing apparatus 1 in the first embodiment, detailed description thereof is omitted. The detailed procedure of the processing in step S104 may be any of the processing procedures shown in the flowchart of FIG. 4, FIG. 7, or FIG.

  The control unit 40 transmits the specified inspection result to the terminal device 3 via the communication unit 43 (step S106), stores the inspection result together with the acquired captured image data in the storage unit 41 (step S107), and ends the process.

  As shown in the second embodiment, the processing in the terminal device 3 is configured by transmitting the captured image data captured by the terminal device 3 to the central device 4 and executing the determination process in the central device 4. The load can be reduced, and the data amount of the determination application program to be stored in the terminal device 3 can be reduced. In addition, by centralizing the processing in the central device 4, it is possible to improve the determination accuracy in common.

  It should be thought that embodiment disclosed this time is an illustration and restrictive at no points. The scope of the present invention is intended to include all modifications within the scope of the claims and the scope equivalent to the scope of the claims.

1 Information processing device (judgment device)
DESCRIPTION OF SYMBOLS 10 Control part 11 Memory | storage part 12 Temporary memory | storage part 15 Imaging part 1P Judgment application program (computer program)
2 Test piece 20 Base 21 Probe 22 Special probe 3 Terminal device 4 Central device (judgment device)
40 control unit 41 storage unit 43 communication unit 4P determination program (computer program)

Claims (9)

Acquire image data obtained by imaging a test piece on which a plurality of detection bodies that develop color depending on whether or not there is a reaction with a substance to be inspected, and the plurality of pixels based on an image composed of a plurality of pixels based on the acquired image data. In the determination device for determining the presence or absence of a reaction in the detection body,
Based on the pixel value for each pixel in the image, the determination reference value used for the determination of the gradation value indicating the level of brightness or the shade of one or more colors is the average value of the gradation value, outlier exclusion, A reference value calculation means for calculating by either median or mode calculation ;
For each detection body region that is specified as an area where the plurality of detection bodies in the image are respectively captured, the brightness level corresponding to the pixel value in each detection body region or the shade of one or more colors is displayed. Conversion means for converting the gradation value to be displayed into a relative value that is a ratio to the determination reference value or a difference from the determination reference value ;
Comparison means for comparing the relative value with a predetermined threshold value for each of the plurality of detection bodies for each detection body region;
As a result of comparison by the comparison means, for each of the plurality of detection bodies , it is determined that there is a reaction when the relative value is greater than or equal to a threshold value, and there is no response when the relative value is less than the threshold value, or the relative value is And a determination unit that determines that there is no response when the threshold value is equal to or greater than a threshold value, and that determines that there is a response when the relative value is less than the threshold value . The determination device according to claim 1, wherein the conversion unit calculates a ratio of the gradation value to the determination reference value. The reference value calculation means includes
Means for specifying the gradation value for each of the detection body regions;
Extraction means for extracting an arbitrary part from the detection body region of each of the plurality of detection bodies;
3. The determination apparatus according to claim 1, further comprising: a unit that calculates the determination reference value using a gradation value specified for an arbitrary part of the extracted detection body region. The determination device according to claim 3, wherein the extraction unit is configured to extract a detection body region in which a gradation value greater than or equal to a predetermined value is specified. The reference value calculation means includes
The determination apparatus according to claim 1, wherein the plurality of detection objects are classified into a plurality of groups, and the determination reference value is calculated for each of the classified groups. The determination apparatus according to claim 1, wherein the substance to be detected is a gene sample, and the plurality of detection bodies are probes including oligonucleotides that hybridize with the gene. . The determination apparatus according to claim 6, wherein the substance to be detected is Mycobacterium tuberculosis, and the plurality of detection bodies are probes including oligonucleotides that hybridize with the Mycobacterium tuberculosis. A computer capable of acquiring information from the imaging device acquires image data of a test piece to which a plurality of detection bodies that develop color depending on the presence or absence of a reaction with a substance to be inspected is fixed from the imaging device, In the determination method of determining the presence or absence of reaction in the plurality of detection bodies by an image composed of a plurality of pixels based on the acquired image data,
Based on the pixel value for each pixel in the image, the determination reference value used for the determination of the gradation value indicating the level of brightness or the shade of one or more colors is the average value of the gradation value, outlier exclusion, Calculate for each specimen by either median or mode calculation,
For each detection body region that is specified as an area where the plurality of detection bodies in the image are respectively captured, the brightness level corresponding to the pixel value in each detection body region or the shade of one or more colors is displayed. The gradation value shown is converted into a relative value that is a ratio to the determination reference value or a difference from the determination reference value ,
For each of the detection body regions, the threshold value that is predetermined for each of the plurality of detection bodies is compared with the relative value,
Based on the comparison result, for each of the plurality of detection bodies , it is determined that there is a response when the relative value is equal to or greater than a threshold value, and there is no response when the relative value is less than the threshold value, or the relative value is equal to or greater than the threshold value. It is determined that there is no response in some cases, and it is determined that there is a response when the relative value is less than a threshold value . A computer capable of acquiring information from the imaging device causes the imaging device to acquire image data of a test piece on which a plurality of detection bodies that develop color depending on the presence or absence of a reaction with a substance to be examined are fixed, In a computer program for determining the presence or absence of reaction in the plurality of detection bodies by an image composed of a plurality of pixels based on the acquired image data,
Based on the pixel value for each pixel in the image, the determination reference value used for the determination of the gradation value indicating the level of brightness or the shade of one or more colors is the average value of the gradation value, outlier exclusion, Calculating for each specimen by either median or mode calculation ,
For each detection body region that is specified as an area where the plurality of detection bodies in the image are respectively captured, the brightness level corresponding to the pixel value in each detection body region or the shade of one or more colors is displayed. Converting the gradation value to be displayed into a relative value that is a ratio to the determination reference value or a difference from the determination reference value ; and
Comparing the relative value with a predetermined threshold for each of the plurality of detection bodies for each detection body region ; and
Based on the comparison result, for each of the plurality of detection bodies, it is determined that there is a response when the relative value is equal to or greater than a threshold value, and there is no response when the relative value is less than the threshold value, or the relative value is equal to or greater than the threshold value. A computer program for executing a step of determining that there is no response in some cases and determining that there is a response when the relative value is less than a threshold value .

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