JP2008014680A - Inspection device, inspection system, and inspection program of selective bonding substance immobilizing carrier - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an inspection device, an inspection method, and an inspection program of a selective bonding substance immobilizing carrier capable of accurately inspecting a target even when it is an uneven carrier. <P>SOLUTION: The inspection device evaluates a spot by storing spot image data on a carrier detected by a detecting means; partitioning a plurality of protrusions one by one on an image, storing mask data of outside and inside of cross sections in each partition; binarizing the image data stored by setting in the case that a detecting intensity by the detecting means in each pixel is more than the threshold for binarization as 1, and as 0 in case that is less than the threshold for binarization; creating inspecting image data by overlapping the binarized image data and the mask data based on a protrusion configuration; counting the number of pixels set as 1 for every partition for all partitions of created mask images; and evaluating the counted number using the threshold for evaluating the inside of the cross section. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an inspection apparatus, an inspection method, and an inspection program for a selective binding substance-immobilized carrier, and in particular, an uneven selective binding substance-immobilized support in which a plurality of convex portions are arranged in a concave portion on the surface of the carrier. The present invention relates to an inspection apparatus, an inspection method, and an inspection program for a selective binding substance-immobilized carrier for inspecting whether or not the selective binding substance to be immobilized on the carrier surface is spotted on the upper end surface of the convex portion.

  In recent years, a new analysis method called a DNA microarray method (DNA chip method) has been developed and attracts attention as a method for analyzing many gene expressions at once. These methods are in principle the same as conventional methods in that they are nucleic acid detection / quantification methods based on a nucleic acid / nucleic acid hybridization reaction. These methods can be applied to the detection and quantification of proteins and sugar chains based on specific reactions between proteins / proteins or between sugar chains / sugar chains or between sugar chains / proteins. These technologies have a great feature in that a large number of DNA fragments, proteins, and sugar chains are aligned and fixed on a flat glass substrate called a microarray or DNA chip at a high density. As a specific method of using a DNA chip, for example, a sample in which a gene expressed in a cell to be studied is labeled with a fluorescent dye is hybridized on a flat substrate piece, and complementary nucleic acids (DNA or RNA) are bound to each other. There are a method of reading the part at high speed with a high resolution detection device (scanner) and a method of detecting a response such as a current value based on an electrochemical reaction. In this way, the amount of each gene in the sample can be quickly estimated. The application field of DNA chips is highly expected not only as a gene expression analysis for estimating the amount of expressed gene but also as a means for detecting single base substitution (SNP) of a gene.

  Conventionally, the selective binding substance-immobilized carrier such as the above-described DNA microarray (hereinafter, also referred to as “biochip” in the specification) is generally flat because it is easy to manufacture. It was. However, with the conventional selective binding immobilization carrier, when hybridization is performed, the specimen sample is inevitably adsorbed nonspecifically on a portion other than the spot. When fluorescence detection is performed with an apparatus called a scanner, this non-specifically adsorbed specimen is also detected, resulting in a problem that noise increases and consequently S / N deteriorates.

  Therefore, in order to prevent the above S / N deterioration and provide a base material on which a selective binding substance with high detection sensitivity is immobilized, the base material is provided with an uneven portion, and the selective binding substance Is disclosed on a carrier on which a selective binding substance is immobilized, which is immobilized on a plurality of convex portions of the concavo-convex portion (see Patent Document 1).

  If the carrier having the uneven portion is used for a specimen, a very good result of the S / N ratio can be obtained as compared with the conventional one.

JP 2004-264289 A

  However, in the conventional inspection apparatus, inspection method, and inspection program, when a selective binding substance-immobilized carrier having irregularities is to be inspected, it is checked against the master pattern and masked based on the convex structure. Since there is no means, there is a problem that measurement error due to misalignment is large. In addition, there is a problem that there is no means for eliminating inspection and measurement errors peculiar to the structure of the carrier having irregularities.

  In addition, in order to make the most of the technical merit of using a carrier having irregularities, quality control is important, but there is a problem that there is no highly accurate inspection means. That is, when a carrier having a selective binding substance fixed on the upper end surface of the convex portion is scanned using a device called a scanner during analysis, the laser beam is focused on the upper surface of the convex portion of the concave and convex portions. This is because the light is blurred and it is difficult to detect undesired fluorescence (noise) of the specimen adsorbed nonspecifically in the concave portion. In order to take advantage of the technical merit peculiar to the carrier having such irregularities, it is necessary to remove the carrier (defective product) in which the selective binding substance is fixed to the concave portion at the time of shipment.

  In summary, there is no means for quality control of a carrier having such irregularities in the manufacturing stage, and in providing a carrier having irregularities, in order to further improve the reliability of the product, the selective binding property having the irregularities is provided. There has been a problem that an inspection means suitable for the substance-immobilized carrier has to be developed.

  The present invention has been made in view of the above, and a selective binding substance-immobilized carrier inspection apparatus and inspection that can be inspected with high precision even if the object to be inspected is a selective binding substance-immobilized carrier having irregularities. It is an object to provide a method, an inspection program, and a recording medium.

  In order to achieve such an object, the inspection apparatus, the inspection method, or the program for the selective binding substance-immobilized carrier according to claim 1, 2, or 3, respectively, includes a plurality of convex portions in the concave portion of the surface of the carrier. A storage unit and a control unit for inspecting whether or not the selective binding substance-immobilized carrier having irregularities disposed thereon is spotted on the upper end surface of the convex part. An inspection apparatus for the selective binding substance-immobilized carrier comprising at least, or an inspection method or program executed in the inspection apparatus, wherein the storage unit detects the spot on the carrier detected by a detection means Spot image storage means for storing the image data of the image, and the plurality of convex portions on the image are partitioned one by one, and the outer cross-sectional mask data masking the outer surface of the convex portion in each of the sections. A mask storage means for storing in-section mask data for masking the inside of the cross section of the data or the convex portion, and the control section uses the image data stored in the spot image storage means for predetermined binarization. For each pixel, a threshold is set to “1” when the detection intensity by the detection means is equal to or higher than the binarization threshold, and “0” is set to be less than the binarization threshold. Binarization means (step) for binarization by the above, image data binarized by the binarization means, the intra-sectional mask data or the non-cross-sectional mask data stored by the spot image storage means, Are superposed on the basis of the convex portion arrangement to create inspection image data and store it in the storage unit, and a mask processing means (step) for storing the inspection image data created by the mask processing means. For all sections in the data, the number of pixels set to “1” by the binarization means is counted for each section, and the inspection image data based on the out-of-section mask data is equal to or greater than a predetermined threshold for evaluation in the section. A spot evaluation means (step) for evaluating a spot by allowing the inspection image data based on the in-cross-section mask data to be less than a predetermined threshold for evaluation outside the cross-section. (Included).

  According to this invention, the storage unit stores the image data of the spot on the carrier detected by the detection unit, and partitions the plurality of convex portions one by one on the image, and in each partition, the convex cross section Stores out-of-section mask data that masks the outside or in-section mask data that masks the inside of the convex section, and the control unit stores the stored image data on a pixel-by-pixel basis using a predetermined threshold for binarization. In addition, when the detection intensity by the detection means is equal to or greater than the binarization threshold value, “1” is set, and when the detection intensity is less than the binarization threshold value, “0” is set to binarize, The inspection image data is created by superimposing the stored image data and the stored in-section mask data or out-of-section mask data on the basis of the convex portion arrangement, stored in the storage unit, and the created mask image All compartments Accordingly, the number of pixels set to “1” is counted for each section, and the inspection image based on the non-cross-sectional mask data allows a value that is equal to or greater than a predetermined threshold for cross-sectional evaluation, or the above-described intra-sectional mask data. Since the spot is evaluated by allowing the inspection image less than the predetermined threshold for out-of-section evaluation in the inspection image according to the above, the uneven selective binding substance immobilization having a plurality of convex portions arranged in the concave portion of the carrier surface is performed. Even if it is a carrier, the quality can be checked by checking whether or not the selective binding substance to be immobilized on the carrier surface is spotted on the upper end surface of the convex portion. In addition, by using a selective binding substance-immobilized carrier having irregularities in which a plurality of convex parts are arranged in the concave portions on the surface of the carrier, the convex region can be specified as compared to a selective binding substance-immobilized carrier without irregularities, The position to be spotted can be specified more accurately, and more precise product management can be performed. Moreover, not only the spot position can be confirmed, but also a structural defect of the carrier base can be found at the same time.

  The present invention also relates to a recording medium, wherein the program according to claim 3 is recorded.

  According to this recording medium, the program described in claim 3 can be realized using a computer by causing the computer to read and execute the program recorded on the recording medium. Similar effects can be obtained.

  According to the present invention, even if the object to be inspected is a carrier having irregularities, a defective product in which the selective binding substance is immobilized on an undesired portion other than the upper end surface of the convex portion can be removed before shipment. A more reliable and precise biochip (selective binding substance-immobilized carrier) product in which a selective binding substance is fixed to the upper end surface of the part can be supplied.

  Embodiments of an inspection apparatus, an inspection method, an inspection program, and a recording medium for a selective binding substance-immobilized carrier according to the present invention will be described below in detail with reference to the drawings. Note that the present invention is not limited to the embodiments. In particular, in the following embodiments, the inspection object of the present invention will be described as an uneven biochip in which cylindrical protrusions are arranged. However, the object of the present invention is not limited to this, and is a semicircular, hexagonal column, square column. The present invention can also be applied to a biochip having irregularities in which convex portions having a shape such as a triangular prism, a cone, a quadrangular pyramid, and a triangular pyramid are arranged.

[Outline of the present invention]
Hereinafter, the outline of the present invention will be described with reference to FIGS. 1 to 4, and then the configuration and processing of the present invention will be described in detail. FIG. 1 is a perspective view showing an example of a concavo-convex selective binding substance-immobilized carrier that is an object of inspection of the present invention. FIG. 2 is a conceptual diagram showing an outline of the biochip inspection process of the present invention.

  As an example, as shown in FIG. 1, the test object of the present invention is a biochip 1 having a concavo-convex portion 12 in which a plurality of convex portions 11 are arranged in a concave portion 10 on the surface of a carrier. The spots on the biochip 1 are detected by the detection means and stored as image data in the storage unit of the present invention. In the description of the present embodiment, the upper end surface of the convex portion 11 on which the selective binding substance is to be immobilized on the biochip is referred to as “convex upper end surface”, and the selective binding substance is immobilized on the biochip. A plane of the recess 10 that is detected as noise and is not desirable is referred to as a “recess plane”. Here, the upper end surface of the convex portion to which the selective binding substance is immobilized is preferably a substantially flat surface, but the spot accuracy of the selective binding substance on the upper end surface is improved and / or the base of the selective binding substance is selected. In order to increase the amount of immobilization on the material surface, the upper end surface may be roughened or have a dent to the extent possible for inspection in the present invention.

  First, as shown in FIG. 2, the present invention calls a spot image stored in the spot image file 106d and performs binarization processing (step SA-1). The binarization process uses a preset binarization threshold value, and for each pixel, “1” indicates that the detection intensity is equal to or higher than the binarization threshold value, and “0” indicates that the detection intensity is less than the binarization threshold value. ”Is set. The purpose of binarization is that in the evaluation of the spot quality control stage, it is sufficient that the detection intensity by the detection means is above a certain level, and in which range the spot is spotted, that is, the selective binding substance is convex. This is because it is important that the spot is correctly spotted on the upper end surface of the portion.

  Next, the mask data is called from the mask file 106c, overlapped with the binarized image, and masked (step SA-2). There are two types of mask data: mask data for masking the outside of the cross section and mask data for masking the inside of the cross section. The out-of-section / in-section mask data will be described with reference to FIG. FIG. 3 is a conceptual diagram showing the relationship between an image and an out-of-section / in-section mask in a single section. In the present invention, the “cross section” means a region occupied by the upper end surface of the convex portion in the concave plane on the image, particularly a region corresponding to a portion to be spotted on the image.

As shown in FIG. 3, when the convex part is cylindrical, when the carrier surface is viewed from above, the cross section of the columnar 11 to be spotted looks circular, and the plane of the concave part 10 is visible around it. In the spot detection image by the detection means, the range corresponding to the cross section of the columnar convex portion is indicated by a broken-line circle. At this time, as shown in FIG. 3, in the intra-section mask, in each section, the pixel corresponding to the circle is “0” (illustrated in black), the pixel outside the circle is “1” (illustrated in white), and conversely outside the section In the mask, pixels that fall within a circle are set to “1” (white), and pixels that fall outside the circle are set to “0” (black). Corresponding to the pixel radius R of the image, the cross-sectional outer mask pixel radius r _o, the case where the pixel radius r _i of the cross section in the mask, ideally, is a R = r _o = r _i, in positioning In consideration of the error, it may be set somewhat larger or smaller.

  Next, “superposition” means that an AND process is performed for each corresponding pixel in terms of computer processing. In the binarized image data, each pixel is composed of “0” and “1” by binarization. On the other hand, as described above, in the mask data, the pixel corresponding to the mask portion is “0”, and each pixel in the unmasked portion is “1”. If the pixels corresponding to each other are “0” on the mask data and “0” on the image data, “0” is output by AND processing. If it is “0” on the mask data and “1” on the image data, “0” is output by AND processing. If the mask data is “1” and the image data is “0”, “0” is output by AND processing. If the mask data is “1” and the image data is “1”, “1” is output by AND processing. This will be conceptually described with reference to FIG. FIG. 4 is a conceptual diagram on an image when AND processing by superposition is performed.

  As shown in FIG. 4, when the pixel set to “0” is illustrated in black and the pixel set to “1” is illustrated in white, the non-cross-section mask data (D) and the intra-section mask data (E) are It looks like the figure. Here, the section m1 is an example of being correctly spotted on the upper end surface of the convex portion. At this time, the pixel (white) set to “1” remains in the out-of-section mask process (A · D), but when the in-section mask process is performed (A · E), all the pixels set to “0”. (Black). Moreover, the section m2 is a failure example in which the spot is mistakenly spotted from the upper end portion of the convex portion to the concave portion plane. At this time, the pixel (white) set to “1” remains in both the case where the mask processing outside the cross section (B · D) and the case where the mask processing within the cross section (B · E) is performed. Further, the section m3 is a failure example in which a spot on the upper end surface of the convex portion is missing. At this time, when the mask processing outside the cross section is performed (C / D), the number of pixels (white) where the spot is sufficiently set to “1” is small, and when the mask processing within the cross section is performed (C / E), only black is displayed. .

  Returning to FIG. 2 again, the spot evaluation process is performed by counting the number of pixels set to “1” in the masked inspection image (step SA-3). In the spot evaluation process, the inspection image subjected to the out-of-cross-section mask processing is allowed to be equal to or higher than the in-section evaluation threshold, and the inspection image subjected to the in-section mask processing is less than the out-of-section evaluation threshold. This is done by allowing things. The “threshold evaluation threshold” means an evaluation threshold for evaluating a spot in the cross section. “Outside cross-sectional evaluation threshold” refers to an evaluation threshold for evaluating a spot outside a cross-section. Here, the spot evaluation will be described with reference to FIG. 4 again.

  As shown in FIG. 4, in the section m1 correctly spotted on the upper end surface of the convex portion, the out-of-section mask image (A · D) is equal to or greater than the in-section evaluation threshold, and the in-section mask image (A · E). Is less than the threshold for cross-sectional evaluation (possible). Further, in the section m2 spotted by mistake from the upper end of the convex portion to the concave plane, the out-of-section mask image (B · D) is equal to or greater than the in-section evaluation threshold, but the in-section mask image (B · E). Becomes greater than or equal to the threshold for evaluation outside the cross section (impossible). Further, in the section m3 in which the spot on the upper end surface of the convex portion is missing, the out-of-section mask image (C / D) does not exceed the in-section evaluation threshold (impossible), and the in-section mask image (C / E) is evaluated outside the section. Less than the threshold for use (possible).

  Finally, spot evaluation processing is executed for all sections, and the quality of the selective binding substance-immobilized carrier is inspected based on the evaluation result. The above is the outline of the present invention.

[System configuration]
First, the configuration of this system will be described. FIG. 5 is a block diagram showing an example of the system configuration to which the present invention is applied, and conceptually shows only a part related to the present invention in the configuration.

  In FIG. 5, the biochip test apparatus 100 schematically includes a control unit 102 such as a CPU that controls the entire biochip test apparatus 100 and a communication apparatus such as a router connected to a communication line (not shown). ) Connected to the communication control interface unit 104, the input / output control interface unit 108 connected to the input device 112 and the output device 114, and the storage unit 106 for storing various databases and tables. These units are communicably connected via an arbitrary communication path. Further, the biochip inspection apparatus 100 is communicably connected to the network 300 via a communication device such as a router and a wired or wireless communication line such as a dedicated line.

  Various databases and tables (master image file 106a to inspection image file 106e) stored in the storage unit 106 are storage means such as a fixed disk device, and various programs, tables, files, databases, and webs used for various processes. Stores pages etc.

  Among these components of the storage unit 106, the master image file 106a is a master image storage unit that stores a carrier-based image for creating a master pattern.

  The master pattern file 106b is a master pattern data storage unit that stores master pattern data created from master image data. Here, the master pattern data will be described with reference to FIG. FIG. 6 is a conceptual diagram showing an example of master pattern data.

  As shown in FIG. 6, the master pattern data includes data related to the number, position, size, and range of convex portions of the carrier base. A square frame represents a section of a certain convex portion. In the case of this example, the carrier base has a total of 96 cylindrical protrusions in 8 rows and 12 columns. In addition to this, sub-block information may be included, which will be described later.

  The mask file 106c is a mask data storage unit that stores mask data generated from master pattern data. Here, the mask data will be described with reference to FIG. FIG. 7 is a diagram illustrating an example of in-section / out-section mask data.

  As shown in FIG. 7, in addition to the information of the master pattern data, the mask data is “0” (shown in black) in the cross section and “1” outside the cross section in the cross section mask data. Conversely, in the mask data outside the cross section, the corresponding pixel is set to “0” (shown in black) outside the cross section and “1” (shown in white) within the cross section. Contains pixel information.

  The spot image file 106d is image storage means for storing spot information imaged by the detection means.

  Here, the “detection means” means inspection means for specifying the position where the selective binding substance is spotted, such as a fluorescence microscope camera. In this case, it can be detected by adding a trace amount of fluorescent dye or the like to the spot solution in advance. Alternatively, when the selective binding substance is DNA, a small amount of a DNA binding fluorescent substance may be incorporated to detect the spot. Further, an absorption wavelength unique to DNA may be detected. Even if the selective binding substance is a protein, sugar chain, etc., detection is performed using techniques such as absorption wavelength, fluorescent substance, radioisotope, hybridization, and antigen-antibody reaction, depending on the nature of the selective binding substance. You may make it do.

  In FIG. 5, an inspection image file 106e is inspection image storage means for storing an inspection image that has been binarized and masked.

  The mask file 106c is mask storing means for storing mask data created based on the master pattern data.

  In FIG. 5, the communication control interface unit 104 performs communication control between the biochip inspection apparatus 100 and the network 300 (or a communication apparatus such as a router). That is, the communication control interface unit 104 has a function of communicating data with other terminals via a communication line.

  In FIG. 5, the input / output control interface unit 108 controls the input device 112 and the output device 114. Here, a monitor (including a home television) is generally used as the output device 114 (hereinafter, the output device 114 is described as a monitor).

  As the input device 112, a keyboard, mouse, microphone, magnetic card reader, CD-ROM drive, IC card reader, image scanner, CCD camera, or the like can be used. In particular, for spot images or master images detected by the detection means, image data may be input using an image scanner or a CCD camera.

  In FIG. 5, the control unit 102 has a control program such as an OS (Operating System), a program that defines various processing procedures, and an internal memory for storing necessary data. Information processing for executing various processes is performed. The control unit 102 includes a master pattern generation unit 102a, a mask generation unit 102b, a binarization unit 102c, a mask processing unit 102d, a spot evaluation unit 102e, a screen display unit 102f, and an inspection result processing unit 102g in terms of functional concept. Configured.

  Among these, the master pattern generation unit 102a is a master pattern generation unit for generating a master pattern from a master image.

  The mask generation unit 102b is mask data generation means for generating mask data based on the master pattern data stored in the master pattern file 106b.

  Among these, the binarization unit 102c uses the predetermined binarization threshold for the stored image data, and the detection intensity by the detection unit is equal to or higher than the binarization threshold for each pixel. This is binarization means for binarizing by setting “1” in the case of “1” and setting “0” in the case of less than the binarization threshold.

  Further, the mask processing unit 102d creates inspection image data by superimposing the binarized image data and the stored in-section mask data or out-of-section mask data based on the convex portion arrangement, Mask processing means stored in the storage unit.

  In addition, the spot evaluation unit 102e counts the number of pixels set to “1” for each section of the created mask image, and the predetermined in-section evaluation is performed on the inspection image based on the non-section mask data. It is a spot evaluation means that evaluates a spot by allowing a value that is equal to or greater than a threshold for use, or allowing an image that is less than a predetermined cross-sectional evaluation threshold in the inspection image based on the in-section mask data.

  The screen display unit 102f is a screen display unit that displays an operation screen, an evaluation result, and the like when the present invention is realized on a computer.

  The inspection result processing unit 102g is an inspection result processing unit that processes the inspection result.

  Further, as shown in FIG. 5, the present system schematically provides an external program such as an external database or an inspection program related to the biochip inspection apparatus 100 and image data or master pattern data obtained by the detection means. The external system 200 is configured to be communicably connected via the network 300.

  In FIG. 5, a network 300 has a function of connecting the biochip testing apparatus 100 and the external system 200 to each other, and is, for example, the Internet. In FIG. 5, an external system 200 is connected to the biochip inspection apparatus 100 via a network 300, and the user provides an external program such as an image database, a master pattern database, or an inspection program related to the biochip. An image database, a master pattern database, an inspection program, or the like may be obtained by accessing a website.

System processing
Next, an example of the processing of the system according to the present embodiment configured as described above will be described in detail with reference to FIGS.

[Mask data creation processing]
Here, the details of the mask data creation processing will be described with reference to FIG. FIG. 8 is a flowchart for creating mask data from master pattern data.

  As shown in FIG. 8, the mask generation unit 102b first calls the master pattern data stored in the master pattern file 106b (step SB-1). Next, the mask generation unit 102b determines whether to create intra-section mask data or out-section mask data based on the initial setting input by the user (step SB-2). When it is determined that the in-section mask data is to be created (step SB-2, Yes), the pixel located within the section is set to “0”, and the pixel located outside the section is set to “1” (step SB). -3), and stored in the mask file 106c as intra-section mask data (step SB-4). On the other hand, when it is determined that the mask data outside the cross section is to be created (step SB-2, No), the pixel located within the cross section is set to “1”, and the pixel located outside the cross section is set to “0” (step SB). -5), and stored in the mask file 106c as out-of-section mask data (step SB-6).

  This completes the mask data creation process. Note that the step (step SB-2) of determining whether to create the in-section mask data or to create the out-of-section mask data based on the initial setting input by the user is performed at the program configuration stage. One or both of the processes may be defined to be processed uniquely.

[Binarization processing]
Next, details of the binarization processing will be described with reference to FIG. FIG. 9 is a flowchart of the biochip inspection process in the present embodiment.

  First, the binarization unit 102c calls spot image data from the spot image file 106d (step SC-1). Next, the binarization unit 102c uses the predetermined binarization threshold for the stored image data, and the detection intensity by the detection unit is greater than or equal to the binarization threshold for each pixel. Is set to “1”, and binarization is performed by setting “0” when it is less than the binarization threshold (step SC-2). The threshold for binarization is set according to the detection intensity when a spot containing the selective binding substance is detected by the detection means.

  This completes the binarization process. Note that a mask process may be performed before the binarization process. At that time, the mask image data before binarization is called from the storage unit 106 and the binarization process is performed.

[Mask processing]
Next, details of the mask process will be described with reference to FIG.

  As shown in FIG. 9, when the binarization unit 102c finishes the binarization process (step SC-2), the mask processing unit 102d calls the mask data from the mask file 106c (step SC-3). Next, the binarized image data and mask data are aligned (step SC-4). That is, image data and mask data (master plate data) are associated with each other by the set upper left column coordinates, mask start position, and mask end position. Then, the image data and the mask data are superimposed (step SC-5).

  Positioning by the convex arrangement is performed by collating the corresponding coordinates of the mask data and the image data on the data. For example, the coordinates (for example, (x, y) = (354, 517)) corresponding to the upper left convex portion on the image are set as the coordinates of the upper left convex portion of the master pattern file.

  The positioning is not limited to the above, and the surface structure of the carrier base may be imaged with visible light at the same time when the image data is acquired using the detection means. Further, a point that becomes a positioning standard other than the convex portion may be labeled with a fluorescent material or the like and collated with a point on the master data.

  Here, after positioning, image data and mask data overlay processing will be described with reference to FIG. FIG. 10 is a conceptual diagram showing an overlay processing method in each section.

  As shown in FIG. 10, the mask processing unit 102d extracts a range corresponding to a section from (binarized) image data for a section m to be inspected (1). Next, the mask processing unit 102d similarly extracts a portion corresponding to the section m from the mask data (2). Then, the image data and the mask data are superimposed (3).

  Returning again to FIG. 9, the mask processing unit 102d stores the mask image data in the inspection image file 106e as an inspection image (step SC-6). Next, the mask processing unit 102d stores the processed image as an inspection image (step SC-7). Then, when the binarization process and the mask process are finished in FIG. 9, the spot evaluation process is subsequently performed.

[Spot evaluation process]
Next, details of the spot evaluation process will be described with reference to FIGS. FIG. 11 is a flowchart showing the entire spot evaluation process.

  As shown in FIG. 11, the spot evaluation unit 102e clears the section number m and sets 0 (step SD-1). Next, the spot evaluation unit 102e increments m by one (step SD-2). And the spot evaluation part 102e sets the division m (step SD-3), and performs spot evaluation of a corresponding image (step SD-4). Here, the spot evaluation process in the section m will be described with reference to FIG. FIG. 12 is a flowchart showing an example of spot evaluation in a certain section.

  As shown in FIG. 12, the spot evaluation unit 102e calls the inspection image data stored in the inspection image file 106e (step SE-1). In this embodiment, an image that has undergone out-of-section mask processing is used. Next, the spot evaluation unit 102e counts the number of pixels of the image in the called section m (step SE-2). Specifically, the number of pixels set to “1” on the data is counted. Next, it is determined whether or not the counted value is greater than or equal to the in-section evaluation threshold (step SE-3). And when it is judged that it is more than the threshold for evaluation in a section (Step SE-3, Yes), it progresses to Step SE-4 and outputs "OK", and when it judges that it is less than the threshold for evaluation in a section (Step SE-3, No) outputs “NG” (step SE-5). This completes the spot evaluation in the section m (end of step SD-4).

  Here, an example of spot evaluation of a masked inspection image will be described with reference to FIG. FIG. It is a figure which shows the example of the spot evaluation in 1196, 1218, 1197, 1234, 1246 and 1247.

  As shown in FIG. 14, the section 1218 in which a part of the spot in the cross section is missing does not satisfy the threshold for evaluation in the cross section (= 154), and “NG” is output, and the other sections 1196, 1197, 1234, For 1246 and 1247, the in-section evaluation threshold is satisfied and “OK” is output.

  FIG. 13 is a flowchart showing another example of spot evaluation in a certain section. The embodiment of the spot evaluation is not limited to the example shown in FIG. 12, but after the spot evaluation unit 102e performs the out-of-section evaluation (step SF-3), as shown in FIG. (Step SF-3, Yes), the inspection image subjected to the out-of-section mask process may be called (step SF-4), and the in-section mask evaluation may be performed. In other words, “OK” is output only when it is less than the threshold for evaluation outside the cross section (step SF-3, Yes) and is equal to or higher than the threshold for evaluation within the cross section (step SF-6, Yes) (step SF-7). If it is equal to or greater than the threshold for evaluation outside the section (step SF-3, No) or less than the threshold for evaluation within the section (step SF-6, No), “NG” is output (step SF-8), and a certain section You may make it finish the spot evaluation process in m (step SD-4 end).

  Alternatively, only the section that the spot evaluation unit 102e determines to be equal to or greater than the threshold for intra-section evaluation may be permitted using the image subjected to intra-section mask processing by the mask generation unit 102b (not illustrated).

  Returning to FIG. 11 again, when the spot evaluation unit 102e finishes the spot evaluation process in the section m (step SD-4), the spot evaluation section 102e determines whether the section m has reached q (step SD-5). q is the number of sections to be evaluated, and is generally the number of convex portions on the carrier. If m has not reached q (step SD-5, No), the process returns to step SD-2, and the spot evaluation unit 102e increments m by one and repeats the above processing until m reaches q.

  When m reaches q (step SD-5, Yes), the spot evaluation unit 102e determines whether or not all evaluated sections are “OK” (step SD-6). If all the sections are “OK” (step SD-6, Yes), the carrier to be inspected is determined to be non-defective (step SD-7), while if there is at least one “NG” (step SD) -6, No), it is determined that the carrier to be inspected is a defective product (step SD-8).

  This completes the spot evaluation process. In the realization of the present invention, when determining whether the product is a non-defective product or a defective product (step SD-6), it is not necessary that all sections are “OK”. That is, for example, in the case of a product in which a plurality of the same types of selective binding substances are spotted, one of them may be missing (“NG”). Further, even if the convex portion (negative control) on which the selective binding substance is not fixed is “NG”, it is not appropriate to judge it as a defective product. Therefore, the determination in step SD-6 can be freely configured according to the form of the product (biochip).

[Example]
An embodiment in which the present invention is realized as program software is illustrated below in the order of master pattern data creation procedure, inspection screen setting procedure, inspection processing, and inspection result display processing while performing operations on a computer screen. A description will be given with reference to FIGS. The operation screen will be described with reference to FIGS.

[Create master pattern data]
First, a procedure for creating master pattern data will be described with reference to FIGS. FIG. 15 is a flowchart illustrating an example of a master pattern data creation procedure of the system according to the present embodiment.

  As shown in FIG. 15, first, the master pattern generation unit 102a reads a master image from the master image file 106a (step S1-1). The master image to be read can be used when creating mask data from the master pattern data by using a bright-field carrier-based image or the like that can read the uneven structure at the same field of view and magnification when the spot is imaged by the detection means. Position correction and size correction become unnecessary. The master pattern data is defined by the convex arrangement pattern (number of convex parts (row / column), central coordinates of convex parts, X pitch, Y pitch, etc.) as shown below.

  Next, the screen display unit 102f displays the upper left column coordinate input screen on the monitor, and allows the user to input the upper left column coordinate (step S1-2). The upper left column is a columnar convex portion located on the uppermost left side on the carrier substrate.

  The screen display unit 102f displays a sub-block setting screen on the monitor, and allows the user to input the pitch and number of the sub-block in the X direction and the pitch and number in the Y-direction (step S1-3). Here, the “sub-block” is obtained by roughly dividing the entire spot, and one block, which is the entire spot, is composed of sub-blocks of several rows and several columns. A sub-block definition method will be described with reference to FIGS. FIG. 21 is a diagram illustrating a sub-block definition method. FIG. 22 is a diagram illustrating a sub-block setting method.

  In the example shown in FIG. 21, one block is composed of a total of 48 sub-blocks of 12 rows and 4 columns, and one sub-block is composed of a total of 196 spots of 14 rows and 14 columns. In the example shown in FIG. 28, one block is composed of a total of 4 sub-blocks of 2 rows and 2 columns. In this case, on the monitor sub-block setting screen, settings such as X-pitch 10, Y-pitch 10, X-sub-block number 2, Y-sub-block number 2 are set.

  Returning to FIG. 15 again, the screen display unit 102f displays the in-subblock data setting screen, and informs the user of the pitch and number of columnar protrusions in the X direction (in the subblock), the pitch and number in the Y direction, And the columnar convex part cross-sectional radius is input (step S1-4).

  FIG. 23 is a diagram showing an example of a master data creation screen displayed on the monitor. As shown in FIG. 23, the master data creation screen includes an image file name input area MA-1, an upper left column coordinate input area MA-2, an image update button MA-3, an image display screen MA-4, and an X-pitch of the sub block. Y-pitch input areas MA-5, 6, X sub-block number input area MA-7, Y sub-block number input area MA-8, X-pitch within sub-block, Y-pitch input areas MA-9, 10, (Columnar cross section) Radius input area MA-11, X column number MA-12, Y column number MA-13, screen update button MA-14, read button MA-15, save button MA-16, and return button MA-17 Consists of including.

  In FIG. 23, when the user inputs the file name of the reference destination in the image file name input area MA-1 via the input device 112 and clicks the read button MA-15, the master image is displayed on the image display screen MA-4. Is displayed.

  In addition, the user can set the coordinates of the upper left column by inputting a numerical value (pixel) into the upper left column coordinate input area MA-2 via the input device 112. The upper left column coordinates can be acquired by clicking the upper left column on the master image displayed on the image display screen MA-4 with the mouse.

  Next, in FIG. 23, the user inputs the sub-block X-pitch, Y-pitch input areas MA-5, 6, X sub-block number input area MA-7, and Y sub-block number via the input device 112. A sub-block is set by inputting a numerical value in the area MA-8.

  Further, in FIG. 23, the user enters the sub-block X-pitch, Y-pitch input area MA-9, 10, (columnar cross-section) radius input area MA-11, and X column number MA- 12, setting in the sub-block is performed by inputting a numerical value to the number of Y pillars MA-13.

  After the user sets a sub-block or a setting in the sub-block via the input device 112, the user clicks the screen update button MA-14 to display a cross and a cross-section representing the center of each convex portion. The result is reflected in MA-4 in a circle. Further, when the user clicks on the save button MA-16, the master pattern data is saved in the master pattern file 106b.

[Inspection screen settings]
Next, the operation procedure of the inspection screen will be described with reference to FIGS. 16 and 17 and FIGS. FIG. 16 is a flowchart illustrating an example of an inspection screen setting procedure of the system according to the present embodiment.

  As shown in FIG. 16, first, the screen display unit 102f displays an image file selection screen and allows the user to select an image file (step S2-1). The image to be read is spot image data imaged by the inspection means.

  Further, as shown in FIG. 16, the screen display unit 102f displays a master pattern file selection screen and allows the user to select a master pattern file (step S2-2).

  In FIG. 16, the screen display unit 102f displays a product name registration screen and a lot name registration screen, and allows the user to register the product name and lot name (steps S2-3 and S2-4).

  In FIG. 16, the screen display unit 102f displays the upper left column coordinate registration screen and allows the user to register the upper left column coordinates (step S2-5).

  Finally, in FIG. 16, the screen display unit 102f displays an inspection condition setting screen and allows the user to set inspection conditions (step S2-6).

  Details of the procedure for setting the inspection conditions will be described with reference to FIG. FIG. 17 is a flowchart showing details of an example of an inspection condition setting procedure.

  As shown in FIG. 17, the screen display unit 102f displays a binarization threshold setting screen on the monitor, and allows the user to set the binarization threshold (step S2-6-1).

  Further, as shown in FIG. 17, the screen display unit 102f displays a spot reference pixel number setting screen on the monitor, and allows the user to set the spot reference pixel number (step S2-6-2).

  Next, in FIG. 17, the screen display unit 102f displays a determination criterion setting screen on the monitor, and allows the user to set the determination criterion (step S2-6-3).

  In FIG. 17, the screen display unit 102f displays a mask point setting screen on the monitor, and allows the user to input the start position and end position of the mask point (step S2-6-4). In the procedure for setting the inspection conditions, the procedure can be omitted from the second time by saving the conditions.

  Here, FIGS. 24 to 28 are diagrams illustrating an example of an inspection screen displayed on the monitor. As shown in FIGS. 24 to 28, the inspection screen includes an image file name input area MB-1, a master pattern file name input area MB-2, a mark display / non-display check area MB-3, and a coordinate acquisition button MB-4. , Product name MB-5, lot name MB-6, upper left column coordinate input area MB-7, 8, update button MB-9, image display screen MB-10, threshold value input area for binarization MB-11, update button MB-12, spot reference pixel number input area MB-13, determination reference input area MB-14, mask start position input area MB-15, mask end position input area MB-16, condition read button MB-17, update button MB -18, a condition save button MB-19, a measurement start button MB-20, and a return button MB-21.

  In FIG. 24, when the user inputs a reference destination file in the image file name input area MB-1 via the input device 112 and clicks the update button MB-9, the image is displayed in MB-10 as shown in FIG. Is displayed. In FIG. 24, the user can register the product name and lot name via the input device 112.

  In FIG. 25, the user inputs the upper left column coordinates in the upper left column coordinate input areas MB-7 and 8, so that the positioning with the master pattern is set. Also, as shown in FIG. 26, by clicking the coordinate acquisition button MB-4 and clicking the upper left column on MB-10, the upper left column coordinate of the point displayed with the clicked “x” is acquired. be able to.

  As shown in FIG. 27, the user inputs the reference destination file name in the master pattern file name input area MB-2 via the input device 112, and puts a check in the mark display / non-display check area MB-3. Then, the master pattern is displayed superimposed on the MB-10 image. This master pattern is developed on the image with the coordinates input in the upper left column coordinate input area MB-7, 8 as the origin.

  As shown in FIG. 28, when the user inputs a binarization threshold value into the binarization threshold value input area MB-11 and clicks the update button MB-12 or the like, the binary is displayed in the image display area MB-10. The converted image is displayed.

  In FIG. 28, the user inputs a spot reference pixel in the spot reference pixel number input area MB-13, inputs a determination reference in the determination reference input area MB-14, and clicks a condition reading button MB-18. By doing so, the inspection conditions are set. The user can also save the inspection conditions by clicking the condition save button MB-19.

  In FIG. 28, when the user inputs a mask start position and a mask end position in the mask start position input area MB-15 and the mask end position input area MB-16, the masked area is changed accordingly. This input can also be input by dragging and dropping from the start position to the end position using the mouse.

  This completes the operation screen setting procedure. In FIG. 28, when the user clicks the measurement start button MB-20 or the like, the process of the present invention is executed on the computer.

[Inspection process]
Next, the flow of the inspection process will be described with reference to FIGS. 18 to 20, FIG. 28, and FIG. FIG. 18 is a flowchart showing the overall flow of processing in the system of the present invention.

  As shown in FIG. 18, first, the mask generation unit 102b creates a mask image (step S3-1). That is, based on the master pattern data stored in the master pattern file 106b, mask data is created and stored in the mask file 106c. Then, the image data stored in the binarized spot image file 106d is overlaid to create a mask image. The mask image is stored in the inspection image file 106e as an inspection image. Here, the superposition may be performed by masking image data before binarization, binarizing it, and storing it as an inspection image in the inspection image file 106e.

  In FIG. 18, after the mask image is created (step S3-1), the mask processing unit 102d calls the mask data stored in the mask file 106c, superimposes it on the image data, and then converts the inspection image to the mask data. Create (step S3-2).

  In FIG. 18, when an inspection image is created by the mask processing unit 102d (step S3-2), the spot evaluation unit 102e performs a spot inspection for each section (step S3-3). Here, the flow of spot inspection in each section will be described with reference to FIG. FIG. 19 is a flowchart showing the inspection procedure for each section.

  As shown in FIG. 19, the spot evaluation unit 102e determines whether or not there is a spot in the section (step S3-3-1). Next, the spot evaluation unit 102e counts the number of pixels set to “1” (step S3-3-2). Next, the spot evaluation unit 102e compares the determination criteria (step S3-3-3) and determines whether the spot is good or bad (step S3-3-4).

  As in the example shown in FIG. 28, when the user inputs the reference pixel number (= 100) of the spot and the determination criterion (= 50), the threshold for evaluation in the cross section is set. The reference pixel number of the spot means the number of pixels when correctly spotted on the upper end surface of the convex portion to be fixed. The judgment criterion is a set value of what percentage is acceptable. In this case, a product (100 × 50% = 50) obtained by multiplying the reference pixel number of the spot and the determination criterion (%) corresponds to the “threshold value for intra-section evaluation”.

[Inspection result display processing]
Next, the display procedure of the inspection result when the biochip inspection apparatus 100 finishes the spot evaluation of all sections will be described with reference to FIGS. FIG. 20 is a flowchart of an inspection result display procedure. FIG. 29 is an example of an inspection result screen showing the result of spot evaluation (“OK” or “NG”) for each section.

  As shown in FIG. 20, the inspection result processing unit 102g displays the inspection result (step S4-1). FIG. 29 is a display screen showing an example of the inspection result at this time. The original image display screen MC-1, the binarized image display screen MC-2, the inspection result display area MC-3, and the all display button MC- 4. Only NG display button MC-5, move button MC-6, CSV output button MC-7, and return button MC-8. In the present embodiment, since the threshold for evaluation in the cross section is set to 50 in FIG. 7 and no. 23 is displayed as “NG”.

  Next, as shown in FIG. 20, the inspection result processing unit 102g outputs the inspection result in an Excel format (step S4-2). As shown in FIG. 29, the user can save the inspection result in the inspection image file 106e by clicking the CSV output button MC-7.

  In FIG. 20, the screen display unit 102f displays a move button (step S4-3). As shown in FIG. 29, the user selects a section to be displayed from the search result display area MC-3, and clicks the move button MC-6, so that the original image display screen MC-1 and two are displayed. The selected section can be displayed in a rectangular shape on the digitized image display screen MC-2.

[Other embodiments]
Although the embodiments of the present invention have been described so far, the present invention can be applied to various different embodiments in addition to the above-described embodiments within the scope of the technical idea described in the claims. May be implemented.

  For example, in the above-described embodiment, only the biochip having a columnar convex portion having a circular cross section has been described. However, the cross section is not limited to a circular shape, and may be an ellipse, a rectangle, a triangle, or the like. It may be a shape.

  Moreover, although the case where the biochip inspection apparatus 100 performs processing in a stand-alone form has been described as an example in the above embodiment, in response to a request from a client terminal configured with a separate casing from the biochip inspection apparatus 100 The processing result may be processed, and the processing result may be returned to the client terminal.

  In addition, among the processes described in the embodiment, all or a part of the processes described as being automatically performed can be manually performed, or all of the processes described as being manually performed can be performed. Alternatively, a part can be automatically performed by a known method.

  In addition, the processing procedures, control procedures, specific names, information including parameters such as registration data and search conditions for each processing, example screens, and database configuration shown in the above document day and night drawings, unless otherwise specified. It can be changed arbitrarily.

  In addition, regarding the biochip inspection apparatus 100, each illustrated component is functionally schematic and does not necessarily need to be physically configured as illustrated.

  For example, regarding the processing functions provided in each device of the biochip testing apparatus 100, in particular, each processing function performed by the control unit 102, all or any part thereof is interpreted by a CPU (Central Processing Unit) and the CPU. It can be realized by a program to be executed, or can be realized as hardware by wired logic. The program is recorded on a recording medium to be described later, and is mechanically read by the biochip inspection apparatus 100 as necessary. In other words, the storage unit 106 such as ROM or HD stores a computer program for performing various processes by giving instructions to the CPU in cooperation with an OS (Operating System). This computer program is executed by being loaded into the RAM, and constitutes a control unit in cooperation with the CPU.

  The computer program may be stored in an application program server connected to the biochip inspection apparatus 100 via an arbitrary network 300, and may be downloaded in whole or in part as necessary. Is possible.

  The program according to the present invention can also be stored in a computer-readable recording medium. Here, the “recording medium” means any “portable physical medium” such as a flexible disk, a magneto-optical disk, a ROM, an EPROM, an EEPROM, a CD-ROM, an MO, and a DVD, or a LAN, WAN, or Internet. It includes a “communication medium” that holds the program in a short period of time, such as a communication line or a carrier wave when the program is transmitted via a network represented by

  The “program” is a data processing method described in an arbitrary language or description method, and may be in any format such as source code or binary code. The “program” is not necessarily limited to a single configuration, but is distributed in the form of a plurality of modules and libraries, or in cooperation with a separate program represented by an OS (Operating System). Including those that achieve the function. Note that a well-known configuration and procedure can be used for a specific configuration for reading a recording medium, a reading procedure, an installation procedure after reading, and the like in each device described in the embodiment.

  Various databases and the like (master image file 106a to inspection image file 106e) stored in the storage unit 106 are storage means such as a memory device such as a RAM and a ROM, a fixed disk device such as a hard disk, a flexible disk, and an optical disk. Stores various programs, tables, databases, web page files, and the like used for various processes and website provision.

  In addition, the biochip test apparatus 100 is connected to an information processing apparatus such as a personal computer or workstation at the base, and software (including a program, data, etc.) for realizing the method of the present invention is installed in the information processing apparatus. May be realized.

  Furthermore, the specific form of distribution / integration of the devices is not limited to the one shown in the figure, and all or a part thereof is configured to be functionally or physically distributed / integrated in an arbitrary unit according to various additions. can do.

  As described above in detail, according to the present invention, the defective product in which the selective binding substance is fixed to an undesired portion other than the upper end surface of the convex portion can be removed before shipping, and the upper end surface of the convex portion can be removed. A more reliable and precise biochip (selective binding substance-immobilized carrier) product in which a selective binding substance is immobilized can be supplied.

It is a perspective view which shows an example of the uneven | corrugated selective binding substance fixed support | carrier with an unevenness | corrugation which is a test object of this invention. It is a conceptual diagram which shows the outline | summary of the biochip test | inspection process of this invention. It is the conceptual diagram which showed the relationship between the image in a single division, and the cross-sectional / in-cross section mask. It is a conceptual diagram on an image at the time of performing AND processing by superposition. It is a block diagram which shows an example of this system structure with which this invention is applied. It is a conceptual diagram which shows an example of master pattern data. It is a figure which shows an example of cross-sectional / out-cross-section mask data. It is a flowchart which creates mask data from master pattern data. It is a flowchart of the biochip test | inspection process in this embodiment. It is a conceptual diagram which shows the superimposition processing method in each division. It is a flowchart which shows the whole spot evaluation process. It is a flowchart which shows an example of the spot evaluation in a certain division. It is a flowchart which shows the other example of spot evaluation in a certain division. Section No. It is a figure which shows the example of the spot evaluation in 1196, 1218, 1197, 1234, 1246 and 1247. It is a flowchart which shows an example of the master pattern data creation procedure of this system in this embodiment. It is a flowchart which shows an example of the test | inspection screen setting procedure of this system in this embodiment. FIG. 17 is a flowchart showing details of an example of an inspection condition setting procedure. It is a flowchart which shows the flow of the whole process in this system of this invention. It is a flowchart which shows the test | inspection procedure for every division. It is a flowchart of a test result display procedure. It is a figure which shows the definition method of a subblock. It is a figure which shows the setting method of a subblock. It is a figure which shows an example of the master data creation screen displayed on a monitor. It is a figure which shows an example of the test | inspection screen displayed on a monitor. It is a figure which shows an example of the test | inspection screen displayed on a monitor. It is a figure which shows an example of the test | inspection screen displayed on a monitor. It is a figure which shows an example of the test | inspection screen displayed on a monitor. It is a figure which shows an example of the test | inspection screen displayed on a monitor. It is a figure which shows an example of the test result screen which shows the result ("OK" or "NG") of the spot evaluation about each division.

Explanation of symbols

1 Biochip (selective binding substance immobilization carrier)
DESCRIPTION OF SYMBOLS 10 Concave part 11 Convex part 12 Uneven part 100 Biochip inspection apparatus
102 Control unit
102a Master pattern generation unit
102b Mask generation unit
102c Binarization part
102d Mask processing unit
102e Spot Evaluation Department
102f Screen display part
102g Inspection result processing part
104 Communication control interface unit
106 Storage unit
106a Master image file
106b Master pattern file
106c Mask file
106d Spot image file
106e Inspection image file
108 Input / output control interface
112 Input device
114 Output device 200 External system 300 Network

Claims (3)

Concerning the uneven selective binding substance-immobilized carrier in which a plurality of convex portions are arranged in the concave portion of the carrier surface, whether or not the selective binding substance to be immobilized on the carrier surface is spotted on the upper end surface of the convex portion. In the inspection apparatus for the selective binding substance-immobilized carrier comprising at least a storage unit and a control unit,
The storage unit
Spot image storage means for storing image data of the spot on the carrier detected by the detection means;
A mask storing means for partitioning the plurality of convex portions one by one on the image, and storing in each of the sections cross-sectional mask data for masking a convex cross section outside or a cross sectional mask data for masking a convex cross section inside; ,
With
The control unit
The image data stored in the spot image storage means is “1” when the detection intensity by the detection means is equal to or higher than the binarization threshold for each pixel using a predetermined threshold for binarization. And binarizing means for binarizing by setting “0” when the value is less than the binarization threshold;
Inspection image by superimposing the image data binarized by the binarization unit and the intra-cross-sectional mask data or the non-cross-sectional mask data stored by the mask storage unit based on the convex portion arrangement Mask processing means for creating data and storing it in the storage unit;
For all sections in the inspection image data created by the mask processing means, the number of pixels set to “1” by the binarization means is counted for each section, and the inspection image data by the non-cross-sectional mask data is counted. Can evaluate a spot by allowing a value that is greater than or equal to a predetermined threshold for evaluation in a cross section, or by allowing inspection image data based on the above-mentioned mask data in a cross section to be less than a predetermined threshold for evaluation outside a cross section. Spot evaluation means to
And an inspection device for inspecting the quality of the selective binding substance-immobilized carrier based on the evaluation result by the spot evaluation means. Concerning the uneven selective binding substance-immobilized carrier in which a plurality of convex portions are arranged in the concave portion of the carrier surface, whether or not the selective binding substance to be immobilized on the carrier surface is spotted on the upper end surface of the convex portion. An inspection method realized in the inspection apparatus for the selective binding substance-immobilized carrier comprising at least a storage unit and a control unit,
The storage unit
Spot image storage means for storing image data of the spot on the carrier detected by the detection means;
A mask storing means for partitioning the plurality of convex portions one by one on the image, and storing in each of the sections cross-sectional mask data for masking a convex cross section outside or a cross sectional mask data for masking a convex cross section inside; ,
With
Executed in the control unit,
The image data stored in the spot image storage means is “1” when the detection intensity by the detection means is equal to or higher than the binarization threshold for each pixel using a predetermined threshold for binarization. And a binarization step of binarizing by setting “0” when less than the binarization threshold;
Inspection is performed by superimposing the image data binarized by the binarization step and the intra-cross-section mask data or the non-cross-section mask data stored by the spot image storage means based on the convex portion arrangement. A mask processing step of creating image data and storing it in a storage unit;
For all sections in the inspection image data created by the mask processing step, the number of pixels set to “1” by the binarization step is counted for each section, and the inspection image data by the non-cross-sectional mask data is counted. Can evaluate a spot by allowing a value that is greater than or equal to a predetermined threshold for evaluation in a cross section, or by allowing inspection image data based on the above-mentioned mask data in a cross section to be less than a predetermined threshold for evaluation outside a cross section. A spot evaluation step to
And testing the quality of the selective binding substance-immobilized carrier based on the evaluation result of the spot evaluation step. Concerning the uneven selective binding substance-immobilized carrier in which a plurality of convex portions are arranged in the concave portion of the carrier surface, whether or not the selective binding substance to be immobilized on the carrier surface is spotted on the upper end surface of the convex portion. An inspection program realized in the inspection apparatus for the selective binding substance-immobilized carrier having at least a storage unit and a control unit,
The storage unit
Spot image storage means for storing image data of the spot on the carrier detected by the detection means;
A mask storing means for partitioning the plurality of convex portions one by one on the image, and storing in each of the sections cross-sectional mask data for masking a convex cross section outside or a cross sectional mask data for masking a convex cross section inside; ,
With
Executed in the control unit,
The image data stored in the spot image storage means is “1” when the detection intensity by the detection means is equal to or higher than the binarization threshold for each pixel using a predetermined threshold for binarization. And a binarization step of binarizing by setting “0” when less than the binarization threshold;
Inspection is performed by superimposing the image data binarized by the binarization step and the intra-cross-section mask data or the non-cross-section mask data stored by the spot image storage means based on the convex portion arrangement. A mask processing step of creating image data and storing it in a storage unit;
For all sections in the inspection image data created by the mask processing step, the number of pixels set to “1” by the binarization step is counted for each section, and the inspection image data by the non-cross-sectional mask data is counted. Can evaluate a spot by allowing a value that is greater than or equal to a predetermined threshold for evaluation in a cross section, or by allowing inspection image data based on the above-mentioned mask data in a cross section to be less than a predetermined threshold for evaluation outside a cross section. A spot evaluation step to
An inspection program for inspecting the quality of the selective binding substance-immobilized carrier based on the evaluation result of the spot evaluation step.

Images