JP2005257652A - Detecting apparatus and analyzing method for biological sample - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To realize a simple monitoring tool to facilitate electrophoresis experiments; notifications of the beginning, the end or the like of an objective electrophoresis experiment by recognizing prescribed colors, with respect to electrophoretic patterns; a pouch-type gel, conditioned easily and its heating method by suitably utilizing a general-purpose heating tool, such as microwave oven or the like; and a predictive measurement of isoelectric points, by using the electrophoresis speed of a sample, in the case of an isoelectric point electrophoresis or the like, wherein a long period of electrophoresis time is needed. <P>SOLUTION: An electrophoresis-observing device is made up of a member covering the periphery of a biological sample so as to block external light and having a side plane, at least a portion of which is made flexible. The electrophoretic patterns are identified optically, thereby carrying out identifications as to the distance at the electrophoresis experiments. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

The present invention mainly relates to a biological sample containing nucleic acids, proteins, lipids, saccharides, vitamins, coenzymes, etc. for life science research and testing, or a non-biological component detection device and analysis such as drugs contained therein. Regarding the method.

Conventionally, in order to elucidate life phenomena, a method of optically labeling biomolecules and detecting a small amount of optical signals using a medium such as a film in a dark room is generally used. Recently, as digital cameras have become more accurate, a method of recording data as a digital image without using a film has become widespread. However, since the optical signal is often weak, there is no change in using a dark room that can block outside light.
In addition, a small dark box having a dark room effect has been put into practical use so that the above experiment can be performed even in research institutions and educational institutions where dark room facilities are not available. In the simplest configuration, a detection target such as a biological sample is covered with a metal or resin hood, and generally there are many observation and photographing holes in the upper part. More advanced ones, such as those equipped with a lens or camera, those equipped with a mouth to be able to operate inside, those equipped with an internal light source, etc. have been put into practical use. .

In Japanese Patent Laid-Open No. 2003-240756, the inventors can irradiate ultraviolet light from the lower part of the hood part and supply power to the inside of the hood so that the electrophoresis apparatus for separating biomolecules can be driven inside. Devised an observation device with a unique structure.
Further, the image or optical data obtained by these observation and recording devices is finally converted into digital data and analyzed using a computer. Since data handled in the field of life science is generally a large amount of image data, it is fundamental that analysis software can display image data first. As a file format of image data, formats such as bitmap, TIFF, and JPEG are common. Image data includes separation patterns by electrophoresis and thin-layer chromatography, light emission or color development of labeling substances used in nucleic acid hybridization and protein antigen-antibody reactions, and natural or intentionally generated intracellular luminescence. It can be obtained from phenomena, decomposition color reaction by enzyme, color reaction specific to protein, nucleic acid, lipid, saccharide, partial carbonization image (yellowish brown image) by sulfuric acid treatment of various organic substances. In many cases, a plurality of regions that exist at different positions in an image and have different shapes are analyzed, and lightness, saturation, color components, and the like in the regions are handled as information. The functions of mathematical analysis, numerical data output and graphing are functions of general analysis software. Recently, with the diversification and sophistication of experiments, the types and amounts of data handled have become enormous, so software that focuses on data management and enables data sharing via a network has been developed. ing.
JP2003-240756 JP 04-17708

As described above, in the field of life science, in order to obtain high-quality optical data, external light blocking equipment such as a dark room or a dark box is indispensable. However, a darkroom that can be used by a person not only requires a large space, but may not be used by another person while one person is using it. It is difficult. Therefore, many small instruments such as dark boxes are commercially available, but all are made of metal or resin. For this reason, there are problems such as heavy weight, high danger at the time of dropping, poor air permeability and flexibility, limited use, difficulty in cleaning or replacement, and inability to change the size of the light shielding space and the entire device. Yes.

In addition, analysis software needs to be improved because the contents of data required in life sciences are changing. In particular, conventionally, it is sufficient to confirm the presence or absence of a specific biomolecule, its fragment, drug, etc. by a combination of operations such as electrophoresis, thin layer chromatography, hybridization, various blots, and antigen-antibody reactions. In recent experiments, gene expression analysis has frequently been conducted, and quantitative information on the molecule is often required. However, there are many analysis softwares that are currently available on the market that cannot reach the required accuracy, such as those that simply integrate and calculate density information in a specific region. In addition, there are many cases where hardware for detecting a sample and analysis software are put into practical use separately, which causes inconsistencies between hardware and software, and monotonous analysis work cannot be automated. There are also issues such as having to repeat the same operation.

  As described above, many problems remain in both the biological sample detection device and the analysis software at the present stage, but these combine the device as a detection device and the improvement of the analysis software for processing it. Some cannot be solved without it. Therefore, the present invention solves the problem as a system combining them while individually improving the detection device and analysis method of the biological sample. In addition, by improving the equipment and equipment used in combination with the system, the accuracy, quickness, and simplicity are improved comprehensively.

Definition In the following description, expressions used repeatedly are defined as follows in order to avoid duplication of description.
The “ultraviolet light transmissive material” means a glass such as quartz, or an ultraviolet light transmissive resin such as polycarbonate, polymethylpentene, polyolefin, cycloolefin, and methacryl (PMMA). Moreover, even if it is not contained in these materials, if it can obtain sufficient transmittance | permeability by making it into a thin film form, it will be included in an ultraviolet light transmissive material. As physical properties, it is desirable to have a transmittance of 40% or more with respect to at least a part of wavelengths in the range of 250 to 390 nm mainly used in life science research, but it is not limited to these properties depending on the application. When these materials are applied to an apparatus that requires a high voltage such as an electrophoresis apparatus, a flame retardant may be mixed for use for safety.
The “ultraviolet light source” means an ultraviolet fluorescent tube which is usually wavelength-converted by a mercury lamp and a paint inside the mercury lamp. In addition, semiconductors such as light-emitting diodes and semiconductor lasers (compounds mainly containing elements such as gallium, aluminum, indium, nitrogen, arsenic, phosphorus, zinc, and selenium, such as AlGaN and AlGaInN) devices, nonlinear optics A wavelength conversion material having characteristics and the like, an organic electroluminescence material, and the like are included. Depending on the application, it may be medium to large in size, such as a gas laser. Further, the light source itself may include a wavelength component not only in the ultraviolet but also in the visible region and the infrared region, or may be one that can be extracted with the ultraviolet component as the center by combination with a bandpass filter. As the wavelength band, one having an emission peak in the range of 250 to 390 nm is desirable, but it is not limited to this characteristic depending on the application. The light source includes a combination of a plurality of light sources as necessary.
“Heat-resistant material” is a heat-resistant resin such as glass, metal, polyarylate, etc. that does not show significant deformation or modification when used in an autoclave (eg 120 ° C) frequently used in life science research. Means. Depending on the application, it may be sufficient to have resistance up to the boiling point of water.

The biological sample detection device of the present invention is a small dark room device mainly for obtaining optical data from a biological sample, but it is not only for obtaining optical data but also for general work performed in a dark room. Devise to make it easy and highly accurate. Specifically, the periphery of the object to be observed and analyzed is covered with a soft and light material for light shielding. As a result, it is possible to solve the problems such as the danger of a dark box made of metal or resin, large weight, poor air permeability, and size invariance. Since the material for shading is flexible, it is very easy to handle even when operating with hands. A light source is installed inside the apparatus to detect a biological sample. The light source is usually an ultraviolet light source, but it can be replaced with a light source capable of irradiating wavelengths other than those in the ultraviolet region depending on the purpose.

The biological sample analysis software of the present invention is mainly designed to be optimized as a system in consideration of the characteristics of the biological sample detection device. Specifically, since the fluorescent lamp is used as the light source in the detection device, the illuminance non-uniformity can be corrected. In addition, speeding up the entire experiment (acceleration, increase in volume and number of processes) is also an important issue, and this will also be solved. For example, when data is recorded by the detection device, a label, a barcode, or the like is pasted on the object to be photographed and recorded together as information such as numerical values or images. This is recognized by analysis software and automatically analyzed. If it is a frequently performed experiment or inspection, this method can greatly speed up the analysis work. Furthermore, in response to the growing need for handling enormous amounts of data, an efficient information retrieval method as a database system is realized.
In addition, devices and instruments for use in combination with the detection devices and software described above are also devised. The main purpose is to improve accuracy, speed up and simplify experiments.
In order to improve accuracy, it is important not only to correct the illuminance non-uniformity but also to make the detection light source uniform. For this purpose, a light guide plate having a transmittance gradation according to the distance from the light source is used, or a method of performing detection while sliding the light source is used. In the case of sliding scanning, since irradiation is partially performed, image processing is performed on the software side so that the position relative to the whole can be grasped.
For speeding up the experiment, we will devise a camera-equipped processing tool that facilitates the task of cutting out the detection target. In addition, since it is important to speed up the processing after the experiment, an experimental instrument capable of simple cleaning with a photocatalytic material is devised by utilizing the fact that ultraviolet light is often used as a light source.
The simplification of the experiment is realized by using an assembly-type experimental instrument or an experimental instrument formed of a material having excellent light transmittance and heat resistance. In addition, because there are many experiments where management by a timer is not appropriate, we devised a state detector that detects and stops the reaction color and dye movement, not the time, and automatically performs more accurate experiment management. To do.

  As described above, in the biological sample detection device of the present invention, a part or the whole of the light shielding cover is made of a flexible material, thereby reducing weight, space saving, high degree of freedom of shape, expandability by replacement, etc. The effect can be given. Furthermore, by devising the structure of the light source system, the accuracy of the experiment such as the uniformity of irradiation can be improved. Further, the biological sample analysis method of the present invention can realize the accuracy of the experiment, the time reduction, the noise reduction, and the like in addition to assisting the function of the detection apparatus with a focus on image processing. Furthermore, by using instruments that assist these, a reproducible experiment can be easily and accurately performed as an integrated system.

First, the biological sample detection apparatus of the present invention (hereinafter referred to as “the present detection apparatus”) will be described.
FIG. 1A shows the frame structure of the present detection apparatus. A top plate 1 made of metal or resin is installed on the top, and a lens 2 is installed on the top plate 1. The lens 2 is usually attached to the lens housing 3 and can be exchanged with other lenses such as those having different focal lengths or sizes, and the vertical position can be adjusted. Since detection light such as ultraviolet light is usually used for detection of a biological sample, it is desirable that the lens 2 for observation and photographing has a characteristic of cutting the detection light and transmitting a signal from the sample. . When the material itself of the lens 2 does not have the characteristic of cutting the detection light, the lens surface is coated with the detection light cut or an optical filter having such a characteristic is installed above or below the lens 2. If it is not necessary to enlarge the image, the lens 2 may be omitted and only an optical filter may be installed. In that case, the lens housing 3 is not necessary, and a simple filter installation tool may be used. The lens housing 3 is threaded or perforated so that the vertical position can be adjusted, but the position can be adjusted by the frame or the sample stage (stage) installed inside. If possible, lens position adjustment may not be necessary. Further, the lens housing 3 can be detached from the top plate 1, and in that case, since the top plate 1 has a hole, the inside can be directly observed. In some cases, a deaeration pump is attached to the hole so that the inside is dried and evacuated or dust-free. In this case, it is better to cover the entire frame with a sealable material. The advantage of eliminating dust is that light can be prevented from being scattered in the dust and causing data noise. On the contrary, by sending gas from this hole, it may be used as a small draft or pressurizer. This method is effective because it may be detected by evacuation, deoxygenation, bactericidal gas ventilation such as formalin fumigation, pressurization, heating, or cooling in some experiments.

The upper fixing member 4 is formed of a material such as a velcro tape, a bar magnet, a rubber magnet, a metal plate, or a spring, and is used to fix a material that covers the frame. Correspondingly, magic tape, magnets, metal plates, etc. are attached to the cover material side. There may be a case where the upper fixing member 4 is unnecessary, for example, the top plate 1 itself is made of metal. The upper fixing member 4 may be a screw, a double-sided tape, an adhesive, or the like, but is not preferable because the cover material cannot be easily removed. However, when sealing properties such as evacuation and pressurization are important, these are also selected as appropriate. As will be described later, this detection device is characterized by the cover material being a flexible material such as a black curtain, so if at least the lower part of the cover material is removable, it can be opened and closed by turning it up. Is possible. The upper fixing member 4 is also formed of a slidable member such as a curtain rail, and can be opened and closed by sliding left and right, for example. In any case, it is not necessary to move and open the frame structure itself, which is effective for space saving.

The light source 5 is usually an ultraviolet light source. However, for example, when using a detection reagent that emits light or develops color in the visible light region or the infrared region, one having a wavelength region suitable for the reagent, such as a white light or a blue light, is selected. These light sources are often used particularly in applications where it is not desired to damage the biological sample. In addition, when you want to photograph a biological sample in color under natural light, use a white light-emitting diode with a stable output (preferably one with a spectrum close to natural light with a relatively high red component ratio). Sometimes used. In addition, for the purpose of recording colors precisely under white light, a plurality of light sources (for example, three primary colors of blue, green, red, and four colors consisting of cyan, magenta, etc.) are installed, and the target is set for each light source. Objects are photographed or light absorption is measured, and then they are synthesized by image processing.

For example, when three data shot (measured) with three light sources of blue, green, and red are superimposed, the three primary color component data of the object is obtained as a result. The same image (data) is generated. In this case, a monochromatic image sensor, a single-color photodiode, or a combination of them can be used for shooting (recording), so the mechanism is simplified compared to when using a recording device with a color filter. As a result, not only is the cost reduced, but there is an advantage that the accuracy is increased. It is also possible to record as a video (moving image) by repeating photographing (recording) while sequentially turning on a plurality of light sources. Also, even if the light source is the same color, if the surface of the object has irregularities when illuminated from different positions, the way the shadows change will change. It is also possible to generate an image (three-dimensional structure data). By repeating such photographing, it is also possible to record the three-dimensional structure data as a video (moving image).

Since the three-dimensional structure data can be obtained by scanning using reflection measurement with a laser light source, or by performing X-ray diffraction measurement by crystallizing a sample, which one to select depends on the detection target. Biological samples to be detected can range from microscopic samples such as nucleic acids, proteins, organelles and cells to large parts such as teeth, fingers, hands, feet, faces, and their patterns and irregularities. Is done. In particular, when some kind of chemical reaction is caused or surgery such as excision is performed, it is desirable to record and save the data as 3D structure data in advance. It would be ideal if the system could be restored by inputting it into Conversely, if such a system is established, it is not necessary to store the original shape as a model, and it is only necessary to restore it as needed. Handles large-scale structures that have significant significance for pre-deformation (aging, surgery, etc.) preservation as medical charts, and those that easily change over time (deterioration or corrosion), such as biological samples Ideal for. A plurality of light sources are arranged symmetrically around the lens position so that the light source 5 is irradiated as uniformly as possible. Since the ultraviolet light source has not only the detection of a biological sample but also a sterilizing effect, an object may be placed in the apparatus for the purpose of an ultraviolet irradiator.

Furthermore, there is a case where an object is placed on a photocatalyst material such as titanium oxide which has an action of being decomposed and purified with high efficiency by a light source such as ultraviolet rays. If the light source 5 is a fluorescent tube, it can be easily replaced because it is attached with a socket. Moreover, it is desirable that the position of the light source 5 can be changed according to the purpose, or that the light source unit can be attached and detached. For example, when observing and photographing a specific area, the light source 5 is arranged as close as possible to the detection target, and when it is desired to irradiate a wide range for the purpose of sterilization by ultraviolet rays, it is arranged near the top plate 1. In the case where the light source 5 is a fluorescent tube, a reflection plate having a radiation shape or the like may be provided on the back side thereof so as to have directivity, and the structure may be configured such that the region is focused and irradiated intensively. When irradiating a narrower area, the light source 5 is preferably a light source with strong directivity, such as a light emitting diode or a semiconductor laser. On the contrary, when it is desired to perform uniform irradiation in the apparatus, a uniform surface light source body such as an organic electroluminescence element may be irradiated from below.

  FIG. 1B is a cross-sectional view of the frame structure of FIG. The lens 2a installed on the top plate 1a is fitted in the lens housing 3a. If the lens 2a is circular, the lens housing 3a is also cylindrical (the cross section in the horizontal direction is circular, Is not necessarily uniform). Since the vertical height of the object is indefinite, it is preferable that this lens position can also be moved up and down, and the lens housing 3a is not a simple ring but a cylindrical shape. The lens housing 3a and the top plate 1a are engaged with each other with a screw structure, and the vertical position can be changed or removed by rotating. Even if it does not have a screw structure, it is sufficient if the position can be fixed by another screw or the like. Furthermore, it is desirable to attach a filter 4a for cutting detection light such as ultraviolet light to the back side of the top plate 1a. If the filter 4a is also commercially available for a camera or the like, it is fitted into the filter housing 5a, and the filter housing 5a is usually formed with a screw structure. If a screw structure is also formed on the back side, it can be rotated and attached. In the case of a rectangular or square filter, the filter housing 5a has a structure matching that, or is directly attached to the top plate 1a without using the housing. The filter 4a may be attached above the lens, but since it is often necessary to observe without the lens, it is usually better to attach it on the opposite side of the lens. In FIG. 1B, a cross section is drawn so that the filter 4a fits into the filter housing 5a. However, if the filter 4a can be slid and inserted in such a configuration, replacement according to the detection target is performed. Is easy and convenient. Since the light source and the leg are the same as those in FIG. 1A, the drawing and description in FIG. 1B are omitted.

FIG. 2 shows a structure of a generally used irradiator, which is also a kind of surface light source body. The irradiator 21 usually has a plurality of ultraviolet fluorescent tubes 22 arranged in parallel inside, and an ultraviolet light transmission filter 23 is installed on the top. Thereby, ultraviolet light is irradiated from the lower part, and an optical signal from the biological sample is detected from the upper part. Since the fluorescent tube itself is not planar, it cannot irradiate light uniformly. When uniformity is important, a diffusion plate may be installed above or below the filter 23, but the irradiation intensity will be reduced. The filter 23 may be a plate-like or film-like material having a high light transmittance, a film that cuts a wavelength component serving as a background, or a material applied thereto. Further, the filter 23 is not limited to a solid material, and may be liquid. Specifically, a liquid that mainly controls light transmission characteristics is sealed in a material such as glass, resin, or film that transmits a necessary wavelength. This liquid may contain a single ion or soluble substance, or may contain a plurality of ions or soluble substances. Further, the liquid may be in a state where particles of insoluble substances are dispersed. The advantage of being liquid is that it is easy to exchange the liquid inside, and that it is possible to easily create a filter with new light transmission (absorption) characteristics by mixing liquids with certain characteristics. is there.

Further, as shown in FIG. 3, the light sources may not be arranged in parallel but may be arranged in an L shape or surrounding the peripheral portion, and the light source 31 itself is a straight line such as an L shape, a U shape, a circle, a sphere, or a rectangle. Other shapes may be used. Arranging the light sources in this way is advantageous because the required number of light sources can be reduced and the shade of the light source that is the background of the detection target cannot be seen. However, in order to increase the amount of irradiation light reaching the detection target, it is desirable to provide the light guide plate 32 having a high transmittance with respect to a necessary wavelength. When the light source 31 is an ultraviolet light source, it is made of an ultraviolet light transmissive material. On the back surface of the light guide plate 32 (the side on which the detection target is not installed), it is desirable to dispose a reflective material 33 made of a material such as aluminum and having a reflectance of 90% or more with respect to a necessary wavelength. The reflecting material 33 may be mixed with magnesium or fluorine or used for surface coating in order to prevent a decrease in reflectance due to oxidation. When the detection target is smaller than the light guide plate 32, a reflective material may be disposed on a part of the surface of the light guide plate 32 (the side on which the detection target is installed). A structure in which an optical fiber or the like is disposed between the light source 31 and the light guide plate 32 and light is introduced into the light guide plate 32 with high efficiency may be employed. In addition, in order to cut a wavelength component which is a detection background such as a visible component of a light source, a filter for cutting an unnecessary component is added between the end face of the light guide plate 32 and the light source, or the same effect as the filter is used. In some cases, a coating having Covering the entire surface of the light guide plate with a filter is very expensive due to the large area, but if it is only the end surface, the cost is very low and the detection target is not placed on the filter, so it is difficult to be damaged. . For the same purpose, a filter may be applied to the surface of the light source 31 (a portion where light rays are output), or coating having the same effect as the filter may be performed. Furthermore, it is better to provide a reflection plate for the effective wavelength of the light source on the end surface opposite to the light source. In addition, when it is difficult to apply a filter to the end face of the light guide plate 32, a filter that cuts unnecessary wavelength components is disposed on the upper portion (side where the detection target is installed) as necessary. The light guide plate 32 or the filter may be formed with a transmittance gradation structure in which the transmittance is partially different. That is, since the amount of light irradiated by the light source arrangement form becomes non-uniform, the uniformity of the amount of irradiated light is improved by increasing the transmittance of the portion where the amount of light before passing through the gradation structure is smaller. Such a structure has the thickness of the light guide plate 32 (the thickness on the side close to the light source is large and it is desirable to increase the light entrance efficiency), the surface structure (change in diffusivity, etc.), the bubble density, and the content This is achieved by partially changing the material density.

When using irradiation means from below as described above, the irradiator is installed in the detection device, or the detection device is placed on the irradiator. Furthermore, the irradiation unit and the detection unit may be integrated. In particular, when placed on the irradiator, it is desirable that the detection device be lightweight, and it is effective to reduce the weight by using a flexible material as described later. On the upper surface of the irradiator, a wavelength conversion sheet or container, a sheet having a light transmission hole only in a necessary portion, a photocatalytic sheet for sterilization or decomposition of impurities (preferably one having high efficiency with respect to the wavelength of the light source) In some cases, a fluorescent indicator member or the like is installed to facilitate focusing at the time of photographing. Note that these sheets and members may be simply installed in the detection device as long as they exhibit the same effect even when irradiated from above. Also, instead of using a filter, the characteristics of the optical signal that you want to detect can be generated by creating a modulation characteristic with a constant or arbitrary period in the output of the light source, performing irradiation very momentarily, or having a polarization characteristic. Filters may not be necessary if they are physically distinguishable.

A frame is connected to the top plate 1 of FIG. 1A in order to form a space for installing a medium containing a sample and performing a detection operation. The frame is composed of an upper frame 6 and a lower frame 7. These frames have a nested structure, and the height can be adjusted by using an adjusting screw 8. Note that the adjustment screw 8 is not necessarily required as long as it can be fixed at different height positions. The frame is not divided into upper and lower parts, but may have a structure such as a leg having a plurality of joints such as a bellows shape or a foldable leg. Such a structure can be folded into a small size when not in use or carried, which is convenient. As will be described later, in the present invention, since the frame is covered with a flexible material, there is no space for outside light to enter even if the height is changed.

A lower fixing member 9 is installed on the lower frame 7 as necessary. The lower fixing member 9 is for fixing the cover member of the frame similarly to the upper fixing member 4 and is formed of a magic tape, a magnet, a metal, a viscous substance, an adhesive substance or the like. However, when a sample or the like is put in and out of the detection apparatus, the lower part is usually opened frequently, so it is easiest to use a plate-like magnet rather than a magic tape that is quickly consumed. If the lower frame 7 is made of metal, the lower fixing member 9 may be unnecessary. In addition, although the leg of the frame in Fig. 1 (a) is four, in terms of operability when putting your hand, it may be easier to handle without the legs on both sides, the front leg is Only one in the center may be used. The top plate 1 and the upper frame 6 and the lower frame 7 are materials that are highly resistant to chemicals frequently used in life science research such as dilute acetic acid, dilute sulfuric acid, alcohol, or materials that have been made resistant to chemicals by a coating process. Created. . The space formed by these is approximately 20 to 50 cm in width, 20 to 50 cm in depth, and about 15 to 35 cm in height, but is also a height-adjustable structure and can vary depending on the purpose. Since the bottom part may use an irradiator from below, it basically has an open structure. However, this is not the case when a sealing member is required to install the sheet member as described above, or to apply pressure or pressure.

In addition, since the fluorescent tube is installed in this detection apparatus, the power supply cord 10 for supplying electric power to this is needed except the case where the charging mechanism and the electric power generation mechanism are incorporated. The electric power obtained through the power cord is first supplied to an inverter board installed on the top board 1 and boosted by the inverter board to light the fluorescent tube. If power from the power cord 10 is also supplied to a socket or an outlet in the detection device, it is convenient to use experimental equipment or an irradiator in the detection device. In this case, it is desirable that a general-purpose power cord insertion port is provided in the detection device like a tap of an outlet.
FIG. 4 shows a structure in which the frame structure of FIG. 2 is covered with a light shielding cover member. A major feature of the present detection apparatus is that the cover member 41 is formed of a flexible material such as a dark curtain. As a result, the weight can be significantly reduced, and it is safe and easy to carry. In particular, if the frame is foldable, the whole can be folded small. When the fluorescent tube is turned on or an electric device is used in the detection device, the temperature in the device tends to rise, but if covered with a flexible material, it is possible to easily achieve both light shielding properties and air permeability.

  The cover member 41 is fixed to the top plate and the frame of the detection device by a fixing member 42. The fixing member 42 is formed of a magic tape, a magnet, a metal or the like corresponding to the fixing member on the top plate and the frame side. As a result, not only can it be easily opened and closed with a single touch, but it can also be opened directly above, thus realizing space saving. Further, when the cover member is dirty or deteriorated, it can be easily removed and cleaned or replaced. Since the cover member is flexible, it is easy to put the hand inside the detection device and perform processing, but the fixing member around the part where the hand is put is flexible and has an appropriate adhesive property like a rubber magnet. Forming with the material which has it is convenient because the movement of the hand is not hindered while keeping the light shielding property. Moreover, if the fixing member 42 is installed on both the back and front surfaces, the inner surface and the outer surface of the cover member 41 can be easily reversed. For example, if one side is made of a material with high absorbance and the other side is made of a material with high reflectivity, the surface with high absorbance will be on the inside during detection, and the surface with high reflectivity will be used when sterilizing with ultraviolet rays in the device. It is effective to set the inside.

  The cover member 41 is not limited to a flexible material, and a heat insulating material may be used if heating or cooling is necessary, or a metal may be used if sealing is important. Note that it is not necessary to cover the four sides of the detection device with a flexible material. Only the surface or part where the experimental equipment or detection object is placed is covered with a flexible material, and the other surface or part is not covered. May be made of a rigid material such as metal or resin. The light shielding member 43 is for preventing external light from entering when a hand is put into the detection apparatus and is operated. The light shielding member 43 is combined with the cover member 41 to form a space 44 for putting a hand. The cover member 41 and the light shielding member 43 may be integrated. In order to improve the light-shielding property, the space 44 may be covered with an elastomer member such as rubber or sponge to improve adhesion to the hand. Since the cover member 41 is a flexible material, it is advantageous that the mobility does not decrease even if the cover member 41 is brought into close contact with the hand. If the cover member 41 has a sufficient length for light shielding, the lower portion may not be fixed. The hood 45 covers a hole formed in the cover member 41 for observing the inside of the detection device from the side or taking a picture with a camera, and keeps the light shielding property. Velcro, filters, lenses, etc. are attached as necessary. Moreover, pressure reduction, pressurization, intake air, ventilation, dehumidification, or humidification may be performed by a pump from this hole.

  Since this detection apparatus often uses ultraviolet light, it is desirable that the light source is automatically turned off when the cover member 41 is opened. For example, by arranging a magnet switch in the power supply circuit to the light source and attaching a magnet for conducting the switch to the cover member, the power supply to the light source stops when the cover member is opened. Keep it. Alternatively, a device such as a photocoupler or phototransistor that operates when it receives a certain amount of light is used to detect the opening by a change in the amount of light in the detection device and stop the operation of the light source. Also good.

  Next, the detection method by this detection apparatus is demonstrated. As already described, this detection apparatus adopts a dark room structure, and is based on detecting an optical signal from a biological sample. For detection recording, digital cameras, polaroid cameras, video cameras and other cameras or dedicated measuring devices are usually used, but those recorded on a highly sensitive medium such as an X-ray film using a dark room structure are used. It can also be read and used by an image input device such as an image scanner. In this case, it is desirable that the top plate 1 of FIG. 1 (a) is attached not with a lens or a filter that transmits a signal from a biological sample but with a filter that transmits only a wavelength at which the film is not exposed, so that the inside can be observed. As an image recorded by the camera, not only a still image but also a moving image (including still images taken continuously) is used. It is experimentally useful to install a display on the top board 1 or connect a camera to a nearby computer or monitor so that it can be operated while viewing photos and videos.

  In addition to photographing, high-precision irradiation means is also required. As described above, with a commonly used transilluminator, it is not possible to irradiate light uniformly on the detection target, and there are also problems with the life and stability of the fluorescent tube. Even a signal can change the signal. Furthermore, a light source filter having ultraviolet transmission characteristics and visible light transmission characteristics is very expensive and it is difficult to produce a large area filter. In order to solve these problems, an optical scanner as shown in FIG. 5 is devised. In the optical scanner of FIG. 5, a light source 52 and a detector 53 are disposed below the light transmission plate 51 and slid in the same direction, and optical signals from the detection target 54 on the light transmission plate 51 are received. Record it. The light source and the detector may be upside down, and may be arranged side by side if there is no problem in detection. The detector usually has a configuration in which a plurality of light receiving elements are arranged in a direction perpendicular to the sliding direction. However, in order to reduce the number of light receiving elements, a lens is arranged between the light sources and condensed. By adopting a method in which the light source moves in this way, the area can be made very small because the light source filter is applied to the light source and moved together with the light source. The light transmitting plate 51 that transmits ultraviolet rays is formed of an ultraviolet light transmissive material as long as it is for an ultraviolet light source. However, if it is desired to transmit light completely, a hole may be formed at a position where a detection target is installed. The thickness may be reduced only at that position. Depending on the purpose, a wavelength conversion plate or the like may be used, or a light diffusion effect may be provided by surface treatment or the like.

In any case, as long as the material simply transmits ultraviolet light, it may be a thin transparent film, and the area can be easily increased. As described in the case of the filter 23, the light transmission plate 51 is not limited to a solid material but may include a liquid material as a constituent element. The light source 52 is usually an ultraviolet light source, but this is not the case when the light transmission plate 51 has a wavelength conversion function or when the light source required for detection requires a wavelength other than ultraviolet light. . The light source 52 irradiates from above or below the detection target 54. If the light source 52 has a strong directivity such as a semiconductor laser or a light emitting diode, the light source 52 may be irradiated from the lateral direction. The horizontal direction here means that the detection light enters in parallel to the surface to be scanned for the detection target. In a light source with strong directivity and a very narrow irradiation range, it is usually necessary to scan the detection target surface two-dimensionally. However, if the irradiation is from the lateral direction, the scanning direction may be one direction. Since the light source 52 cannot irradiate the entire detection target 54 at a time, the entire light source 52 irradiates while performing slide movement and rotational movement. In particular, it is desirable to move the slide because uniformity of irradiation can be obtained. The moving range is specified as a specification, but may be input by a user using a computer or the like.

Since the scanning range can be easily changed, the larger the detection area, the more advantageous than the method using a filter having a corresponding area. The detector 53 is for detecting an optical signal (including a differential signal generated by absorbing the light source wavelength) emitted from the detection target 54 by irradiation of the light source 52, and is a photodiode and an image sensor suitable for the signal. And a photomultiplier tube. The detector 53 also slides in accordance with the light source 52, but movement may not be necessary as long as it can record a wide range at once, such as an image sensor or film. Since light from the light source becomes the background during detection, the detector 53 is usually equipped with a filter suitable for transmitting only the signal from the detection target 54. However, if the detector 53 is configured by a photodiode or the like and is not sensitive to the wavelength of the light source 52, a filter is not necessary. In addition to the filter, a lens may be provided. The use of a lens is not only effective for close-up photography and detection of minute areas, but also by repeating detection and recording while changing the focus in the vertical direction with respect to the same plane area, the three-dimensional structure information of the detection target 54 is also obtained. Can be obtained. This can be particularly important data in quantitative processing.
Further, the detection light source and the detector may not move integrally as shown in FIG. 5, but may move or move separately. For example, as shown in FIG. 6, the detection target 61 is irradiated with detection light from the transmission light source 62, and the light signal is detected by the light receiving element 63. At this time, if the transmissive light source 62 rotates without changing the position, and a light signal is received by the light receiving element 63 rotating or sliding in accordance with the movement, the detection target by the rotating surface of the transmissive light source 62 is detected. A light signal can be detected for each of the cross sections. If such a detection is repeated by shifting the rotation surface of the transmissive light source 62 in a direction perpendicular to the surface or rotating the rotation surface, the optical signal of the entire detection target is finally measured. be able to. The light source is not limited to the transmissive light source, and a reflected light source 64 may be used. In this case as well, the reflected light source 64 does not move but only rotates, and the light receiving element 63 moves correspondingly, whereby the entire detection target can be monitored. If the surface of the detection target is uniform, the light receiving element 63 may simply slide in accordance with the rotation of the light source. However, when the surface of the detection target is large and the reflected light needs to be measured. Since the reflection angle cannot be determined only by the angle of the detection light, the position and angle of the light receiving element 63 cannot be uniquely determined. In such a case, the detection is performed while sliding and / or rotating the light receiving element with respect to one angle of the reflected light source 64, and the position where the light signal becomes the largest is recorded, thereby the unevenness of the detection target surface. It is also necessary to calculate the structure. By repeating such measurement while changing the angle and position of the reflection light source, the surface structure of the detection target and the optical signal distribution can be measured. In the system as shown in FIG. 6, not only the light source for detection but also the light receiving element can be miniaturized. If the light receiving element can be reduced in size, not only the cost of the element itself can be reduced, but also the coating process and the filter mounting on the light receiving surface of the light receiving element can be easily and uniformly performed, and the cost can be reduced.
The invention according to this example was made by the inventors Aoki, Aizawa and Sato.

  Next, the biological sample analysis method of the present invention will be described. This analysis method supports the detection apparatus described in the first embodiment, and is basically computer analysis software (hereinafter referred to as “this software”) focusing on image processing. However, this software includes not only those that are installed and used by users on computers, but also those that run on computers that are accessed via a network, programs that are built into sensors and control devices of measuring instruments ( Algorithm). Each function of this software will be described in turn. Further, the chip is not limited to what is stored and executed in hardware, but may be a logic IC chip, which is included in the software shown in the present embodiment.

First, the data handled by this software is mainly text data composed of numerical values, image data such as photographs and three-dimensional images (including coordinate data), moving image data such as video, and audio data. Also included are management data such as the relationship between these data, creator, date, analysis processing record, and access (reference) record. In addition, an analog input signal, a quantized signal obtained by sampling the analog signal, a program used for software processing and device control, and the like are also included.
The software shown in the present embodiment is temporarily or continuously stored in, for example, a computer, and is used and executed. For example, the progress of execution and the result are displayed on a monitor.
This software has basic functions for performing processing such as deletion, addition, modification, replacement, update, change, calculation, and illustration of these data. It also has a function of saving data that has undergone these processes. In particular, since the data handled mainly is image data, high processing performance for images is important. Hereinafter, each item will be described in detail.

Image data correction processing In handling image data, the most basic is size change and rotation processing. Regarding the size change, when an image is selected and the vertical and horizontal sizes and resolutions are numerically input, conversion is generally performed in accordance with the size, and this software also enables this. Further, in organizing and presenting data, there are many cases where it is desired to arrange all data to a specific image size and resolution. Therefore, not only the numerical input as described above but also a process of designating one image and matching the other selected image to the characteristics of the image can be performed. This saves the trouble of checking the size of the image to be aligned and checking the resolution.
Also, for rotation processing, it is common to input a numerical value for the rotation angle. In this case, however, after actually rotating, trial and error must be repeated while visually checking. Regarding this problem, if the image can be rotated in accordance with the movement of the hand using the mouse of the computer while viewing the image on the display, it can be easily rotated to a desired angle. Therefore, in the case of rotating an image with this software, not only numerical value input but also a function that can be rotated by hand movement while viewing the image is provided. It may be more convenient to change the size of an image while viewing the image, and this function can be applied.

Image data superposition processing Discussions using images are usually performed while comparing a plurality of images, and generally a plurality of images are displayed vertically and horizontally. Since this software handles images as digital data, it not only arranges a plurality of images, but also superimposes them for display. For the calculation of superimposition, each image is semi-transparently processed (for example, the brightness of each image is corrected to a value divided by the number of images to be superimposed) and added. And take the difference. Such applications, for example, a plurality of the image captured at a different time timing, there is a case where tracking displacement and deformation of the particular region. As described in Example 1, the same sample may be separately photographed (recorded) with different light sources and detectors.
In this case, one or a plurality of photographing means are provided. As a photographing means, a camera having a CCD image sensor or a CMOS image sensor can be suitably used. When multiple images need to be processed, for example, using a camera having a single color image sensor, a configuration required for color imaging such as three primary colors of blue, green, and red (or a combination of these complementary colors) May be taken with a light source, and the images may be combined to form a color image. Single-color sensors have the advantage of being highly accurate without being affected by variations in color filter characteristics and differences in degradation, enabling high-precision processing, high-speed processing for moving images, and shooting with different light sources. Thus, these advantages can be used for color images as they are.

  Furthermore, there may be a case where a plurality of signals having different detection methods and conditions are simultaneously used for the same sample and later superimposed as an image. For example, in order to examine the expression level of multiple RNAs and proteins simultaneously, use labels with different detection wavelengths for each biomolecule (for example, those that bind to different side chains of proteins. Applying a different label to RNA having a complementary sequence to the RNA in advance, etc.), and shooting separately with a light source of a wavelength suitable for each label, the expression state between tissues and cells If there is a difference, by synthesizing them, the difference in the expression state can be easily visualized. In addition, when the emission detection measurement (imaging) and absorption detection measurement (imaging) are performed separately, even if the sample is in the same state, if the absorption site and the emission site are different, the relationship between those sites (physical A simple linkage state or chemical signal linkage). In this case as well, the related situation can be seen in more detail by superimposing the obtained images. In this way, when each captured image is taken into a computer as image data and superimposed as image data, the difference in expression state between tissues and cells in the same living body is displayed as the amount of change in color (signal) Therefore, effects such as easy viewing on the monitor can be obtained. Of course, the difference between different living tissues and cells is often compared. In such a case, if a gene is incorporated so that a photoprotein such as GFP with a different wavelength is expressed, and the expression of the photoprotein is started together with the gene whose expression is to be detected, a different color can be obtained. Since the difference in the expression state is obtained as an image, there is a use in which the images are superposed for easy viewing.

Even if the three-dimensional image processing light source, the detector (camera), and the detection target are the same and unchanged, it may be effective to process a plurality of images. For example, it is a case where the position of the light source is changed for shooting or a plurality of the same light sources are arranged in advance and the same object is shot from a plurality of directions. Even if brightness shading appears on an image taken from one direction, it cannot be determined whether it is due to the color of the detection object itself or due to the three-dimensional structure of the surface. However, if there is a difference in shading when images are taken from a plurality of directions with the same light source, the shading is not the color of the detection target itself, but the way in which the shadow is generated changes depending on the three-dimensional structure of the surface. Can be recognized. For a plurality of images obtained in this way, instead of superimposing, a change in shading (shadow) is detected, a three-dimensional image is calculated based on the data and the angle of the light source, and displayed. Like that.

When the processing optical data of a moving image (video) is obtained as a moving image (video) instead of a still image, a function for tracking movement of a specific pattern, shape, and color is provided. For example, it has a function of tracking the displacement or enlargement state of a certain part and showing how the part is displaced or deformed on the image with a vector (arrow) group or displaying a locus. These vectors and trajectories can be displayed and deleted at the user's will. In addition, since a modulation characteristic is given to the light source or the signal may have a temporal periodicity, it has a function of deleting or extracting a part having a specified time change characteristic from a moving image. Even if it is not specified, automatic processing may be performed on a part that changes periodically. In addition, as described in the case of image data superposition, there are cases in which measurement (photographing) is performed on the same detection target while changing the light source wavelength and position, and such changes in wavelength and position are periodically performed. By repeating the above, it is possible to shoot a moving image (video) of a color image or a stereoscopic image. Therefore, in this software, a color image or a three-dimensional image is synthesized from a plurality of images, and further, a process of connecting the synthesized images into a moving image (video) is also performed.

As described in the first embodiment, the detection apparatus may use a fluorescent tube or a general illuminator as a basic light source. In this case, uniform irradiation is performed. Can not. Therefore, in order to perform quantitative processing, it is necessary to perform processing for correcting the amount of irradiation light with this software. Specifically, first, a plate material capable of monitoring the irradiation light amount distribution is installed in the detection apparatus. The plate material is formed of a material such as a photosensitive film that emits light with respect to a light source, such as a fluorescent acrylic plate, or changes color with respect to the wavelength of the light source. Or you may use the apparatus which can measure the irradiation light quantity of the wavelength of a light source partially or entirely, and may obtain irradiation light quantity distribution by measuring the irradiation light quantity of each site | part of a detection target. As the range for obtaining the irradiation light amount distribution, it is sufficient to carry out at least the range in which the detection target is installed. In this case, for example, for an ultraviolet light source, a light receiving element such as a photodiode having sensitivity to ultraviolet light is on the light source side (or a cable is connected to the light receiving element and can be directed to the light source side) A measuring device arranged so that the display of irradiation light amount data can be seen from the user side is desirable. Measured Slide scanning light-receiving element, it may be automatically obtain illumination light quantity distribution device. In any case, it is desirable that the irradiation light amount distribution is easily obtained accurately, and ideally, the same light emitting substance is uniformly coated on the same material as the detection target.

FIG. 6 is an example of the light quantity distribution obtained in this way, and the line density on the image 61 indicates the light quantity density. Further, a portion indicated by a broken line is the detection target installation area 62. This area may be specified by the user when using this software, but can be automatically recognized if a sign is included in the image 61 in advance. In this software, the light amount (luminance or density) is corrected based on the light amount distribution image data of the area 62 on the image 61 with respect to the detection target image.
The simplest example is to photograph a plate material excellent in the characteristics of reflection, absorption light emission, and discoloration to a light source, such as a fluorescent acrylic plate or a photosensitive film, and use the image as a light quantity distribution image. In order to further increase the strictness, the light receiving element is scanned to detect the light amount of each part and convert it into an electric signal. For example, an amplitude value (or a digital value corresponding to the amplitude value) of the electric signal is a light amount value when the light source is irradiated on the part in advance, and the reference amplitude of the electric signal corresponding to the reference light amount value A value (or a digital value corresponding to the amplitude value) is stored in the storage means, and in use, the reference amplitude value is called from the storage means and compared, and the detected amplitude value is a predetermined threshold value based on the reference amplitude value. If the value is within the threshold value, no correction is made. If the value is outside the threshold value, a correction algorithm for correcting the threshold value to the reference value is set.
After that, the sample on the carrier illuminated by this light source, and correction of the value of the received light quantity obtained for the part of the correction algorithm application area by the correction algorithm, for example, the correction algorithm when the light quantity is small, If the received light value is smaller than the actual light amount of the light source, correction is made by subtracting the actual light amount parameter.
An image used for correction is not limited to an irradiation light amount distribution image, and an image that is included as noise during data recording such as shooting is also used. For example, there are cases where a damaged filter is used or the shape of a light source such as a fluorescent tube is unavoidably reflected in an image. If you record an image that reveals the nature of the position and shape of these noises, you can make corrections using this software based on the recorded image.For example, when the light-receiving color changes suddenly in a narrow area of the image By replacing this part with the light receiving color of the adjacent part, an image from which noise has been eliminated can be obtained. The correction data such as the irradiation light amount distribution image and the noise image described so far may be created by the experimenter if possible.

Further, as long as it can be theoretically derived, the irradiation light amount distribution may be mathematical data such as a function, numerical data, or an algorithm instead of an image. Furthermore, the correction data is not only used for light intensity adjustment and noise elimination, but also for the purpose of selectively extracting necessary information such as extracting / erasing a part of an image or searching for a specific pattern, color, or shape. It may be used. In particular, in the analysis mainly intended for inspection, the latter may be the center. The correction result is output and stored as a corrected image or numerical data. The correction data does not need to be acquired or input at every experiment, but may be stored in an area where the software can be used and recalled and used when necessary. In any correction, the irradiation light amount and the signal amount are not necessarily in a proportional relationship. Therefore, when the function data of the signal amount with respect to the irradiation light amount is obtained experimentally or theoretically, the function data Is used for correction. That is, from the signal amount actually obtained, the actual irradiation light amount is first obtained based on this function data, then the irradiation light amount is corrected based on the irradiation light amount distribution, and again from the corrected irradiation light amount using the function data. The correction signal amount is obtained. Of course, if the data before correction is image data, the corrected data is also displayed and output as an image.

Whole image creation and mapping from partial image data

If the scanning system as shown in FIG. 5 is used, the uniformity of the amount of light is ensured, but in this case, since only a limited area to be detected can be irradiated with light, for example, when it is desired to cut out the target area, It is difficult to handle during operations that require a grasp of the overall position. This also needs to be supplemented with this software. Specifically, the optical data (partial image data) obtained by scanning is arranged according to the scanning position, and one whole image 71 as shown in FIG. 7 is created. A plurality of optical signals 72 are usually distributed on the entire image 71. Further, an optical data (image) region 73 obtained at the current irradiation (measurement) position by the light source and the detector is indicated on the image by a broken line or a color frame. The image area 73 may be recognized by matching the data obtained from the detector with the data used in creating the entire image by this software. However, when the image is complicated, the position information may be obtained and recognized directly from the scanning system. If the entire image and the currently irradiated area are displayed at the same time in this way, it is easy to grasp where the currently irradiated (measured) area is in the entire image, and operations such as clipping can be performed accurately. Can be done.

Furthermore, such an imaging method is also useful when performing operations such as clipping on invisible signal regions such as ultraviolet, infrared, and temperature changes. That is, the process of generating a sample signal such as invisible infrared light, the process of generating a visible indicator (partial image) with a visible light source on the detection target, the sample signal visualized and the eye By combining the process of synthesizing the visible indicators into a whole image, you can work while checking the whole image. If the current image area 73 changes with respect to the entire image 71, the current image is preferentially displayed if the operation is mainly performed.
In any case, if such an imaging method is used, even if the light source irradiates a very narrow area like a semiconductor laser, the position relative to the whole can be accurately grasped. Accordingly, it is possible to use a special light source that performs a wavelength or strong irradiation that is impossible with a fluorescent tube. In the observation or processing of the detection target where countless fine spots are distributed, such as E. coli colony group and two-dimensional electrophoresis spot group, it is rather difficult to grasp the target position if the whole is irradiated, In some cases, irradiation of a limited area may be effective.

Specify analysis area

In this software, analysis focusing on quantification is performed on the optically accurate image obtained by the above processing. What is important in this case is the method of specifying the analysis region. In this software, there is an area designation method as shown in FIG. Specifically, the area designation is performed by an input device such as a mouse connected to the computer. For the analysis target image 81, first, a rectangle designation 82 and an ellipse (perfect circle) designation 83 can be basically set. In addition, a region having a complicated shape can be surrounded by an arbitrary shape while clicking a plurality of points with the mouse. It is also possible to increase or decrease the number of points later, change the position, and generate a curve fitted to each point by the least square method or the like. Furthermore, after determining one shape, it is possible to designate a region having a shape highly homologous thereto by automatic recognition. This is convenient when a highly correlated region is found from within an image or when regularly arranged detection objects such as a two-dimensional array are handled. Also, an analysis direction designation line 85 can be designated, and depending on the analysis processing, the analysis direction designation line 85 is performed along this line. This line is determined by specifying two or more points, and a curve fitted to each point can be generated. It is also possible to specify an appropriate area width 86 around this line.

Reading analysis information

Usually, some external information is required for analysis of measurement data (image). For example, in the case of an electrophoresis pattern image, the molecular weight of the molecular size marker and the substance amount of the standard sample are input, and the molecular weight and substance amount of the detection sample are calculated based on the input. If the marker or standard sample is general, numerical data can be set in advance or registered by the user himself, but even in that case, which one is actually used It is necessary to specify this. Such input and designation work is particularly troublesome when it is necessary to repeat the same work, such as for inspection purposes, and an input error can be fatal. Therefore, in this software, as shown in FIG. 8, a label 87 describing information necessary for analysis is arranged (pasted or printed) at a position where it can be recorded (photographed) on or together with the detection target. If this is the case, this is also subject to analysis. The label 87 is represented by a character, an image, a symbol, a barcode, a two-dimensional dot array, a two-dimensional color dot array, etc., and any of them can acquire information by image analysis. In this detection apparatus, since the light quantity is uniformized and a correction method is devised, it is particularly effective to increase the density of information by using a color.

For example, if dots expressed in 256-tone colors are arranged in 50 columns in both vertical and horizontal directions, it is possible to input over 600,000 types of information. Therefore, not only the type of marker but also the numerical information contained in the marker can be input as it is, and a completely new one can be used without registering in advance. If not only markers and standard samples but also experimental information and analysis procedure information such as reagent names and number of samples are described, it is possible to read the information with this software and perform automatic analysis. Therefore, it is particularly suitable for large-scale monotonous analysis processing and inspection applications where no mistakes are allowed. The information described includes not only experimental conditions but also properties such as differences between lots of experimental media, structure information and reagent information formed in advance on the experimental media. The structural information is important when a plurality of biomolecules and chemical substances react while passing through complicated flow paths, such as a chemical reaction chip as an experimental medium. Regarding the lot information of the experimental medium, not only the property is expressed by the numerical value itself, but also an error relative to the basic value may be expressed as a percentage. In this case, there is an effect that the amount of information is greatly compressed.
Note that the label 87 may include not only information that does not change with time but also information that changes with time. Specifically, the temperature, humidity, pH value, current value, electrical resistance value, chemical substances or the presence of ions, or materials that change color, emit light, or deform due to light irradiation constitute at least part of the label, and experiments on temperature, etc. It is possible to devise such that it is possible to discriminate conditions, detection targets, deterioration conditions such as filters, etc. as images. Information can be input to this software even when using information that can be obtained using magnetism or a communication circuit instead of optical information such as an integrated circuit chip as a label.

Analysis method of electrophoresis

Here, an analysis example for a region selected as shown in FIG. 8 or automatically recognized will be described. This software can analyze the position and shape of detection areas such as light signals obtained from dot blots, slot blots, microarrays, etc., and the position or detection of detection areas such as patterns by separation or transfer by electrophoresis. Examples include those whose time is indefinite but the shape is almost constant, those in which the position and shape of the detection region are indefinite, such as two-dimensional electrophoresis and colony observation, and moving images thereof. Of course, the higher the degree of freedom of position and shape, the higher the difficulty of analysis.
Also, the analysis method varies depending on the purpose even for the same image. For example, a schematic diagram of an electrophoretic separation pattern image is shown in FIG. In the image of FIG. 9, a sample separation pattern 92 and a migration marker separation pattern 93 are recognized on a migration carrier 91 such as a gel. The sample separation pattern 92 includes a sample installation position 92s and bands 92a and 92b. The migration marker separation pattern 93 includes migration marker placement positions 93s and bands 93a, 93b, 93c, and 93d.

When quantitatively processing the density of one band for such a pattern image, one band region may be selected. However, in practice, it is necessary to select and compare other bands with known concentrations in order to quantify the concentration. Also, in the analysis for calculating the molecular weight of a certain band, a plurality of band regions must be processed. Specifically, as shown in FIG. 1 (a) 0, the migration distance (or the logarithm thereof) and the molecular weight are plotted for the marker bands 93a, 93b, 93c, and 93d having known molecular weights. Next, the migration distance of the sample bands 92a and 92b is plotted on a curve generated from the marker band plot, and the molecular weight is calculated. Although it is not always necessary to create a graph as shown in FIG. 10, many analysis softwares have a creation function. In this way, a reference function (including a simple linear interpolation between data) is created using a control sample for which numerical data is known, and the numerical data is interpolated by substituting the measured values of the unknown sample into the function. The analysis of extrapolation and calculation is sometimes a very common method in the life science field, and therefore this software also has a standard function.

Similarly, a function may be created from the electrophoretic separation pattern to obtain numerical data other than the molecular weight. For example, in FIG. 11, protein electrophoresis is performed under a certain pH condition, and marker bands a, b, c, and d having known isoelectric points are plotted with respect to (a function of) the migration distance. Further, the unknown sample bands x and y are plotted on the reference function. In electrophoresis of proteins that are not denatured, even under the same pH conditions, depending on the electrical properties of the protein, it is charged positively or negatively, so the migration distance can also take positive and negative values, The analysis method is the same as in the case of FIG. In the analysis of FIG. 11, not the molecular weights of the samples x and y, but the isoelectric points (pH values at which protein charge becomes 0) Px and Py are obtained. Further, even if the same protein is used, it may be possible to estimate the pH value at which the migration speed becomes 0, that is, the isoelectric point, by utilizing the fact that the migration speed varies depending on the pH value of the electrophoresis carrier. . For example, as shown in FIG. 12, electrophoresis is performed in an environment with different pH conditions, the relationship between the migration distance and the pH value under each pH condition is plotted, and the pH value at which the migration distance becomes 0 is obtained by interpolation or extrapolation. This is the isoelectric point of the protein. In this method, the electrophoresis is performed at a constant speed in comparison with the normal isoelectric focusing method in which the electrophoresis becomes slower as the protein approaches the isoelectric point in a carrier having a pH gradient. It is an advantage that it is required, and it is also effective for proteins that denature as they approach the isoelectric point. In addition, even proteins with the same isoelectric point have different migration distances under the same pH conditions due to differences in charged state and three-dimensional structure, so this method will appear as different spots and can be separated. This is also a big advantage. Therefore, the migration distance (usually relative to the marker) under each pH condition is also an important parameter, and it is desirable to record it. In the case of a sample containing many kinds of proteins, those having the same concentration of spots separated under each pH condition are recognized as the same protein spot. Alternatively, a compound or peptide that specifically binds to a specific amino acid sequence or three-dimensional structure is combined with a dye or fluorescent label as a probe, and reacted with these probes after electrophoretic separation to identify each spot. it can. Furthermore, in many samples with many types of proteins, there are many spots that overlap without being separated only by running under each pH condition. Therefore, after running under each pH condition, the protein is denatured using a surfactant or the like. In some cases, two-dimensional development by electrophoresis according to molecular weight (molecular length) is performed in a direction perpendicular to the migration direction. After two-dimensional development, separation based on protein-derived structure and retained charge in one-dimensional direction, and separation based on molecular weight in the direction perpendicular to it, are complete, so each protein that can be regarded as the same molecular weight under each pH condition By grouping and narrowing down for each molecular weight group, using the results of separation under each pH condition, and performing the isoelectric point analysis described above, it is substantially equivalent to a normal two-dimensional electrophoresis method, etc. Analysis based on electrical point and molecular weight can be performed.

  In practice, including the above method, it is not easy to keep the pH values of the electrophoresis carrier and the buffer solution constant. As described above, this software also includes a label for monitoring the experimental environment as an analysis target, such as the label 87 in FIG. 8, and therefore, a label such as a litmus paper for monitoring the pH value can be used. is there. It is desirable that the pH value label is of a size that allows the entire electrophoresis system to be monitored, and it is desirable that the pH value change (distribution) be obtained graphically, such as a color change (distribution). Devices). In order to accurately grasp and analyze the electrophoresis environment, it is desirable that parameters such as current value, voltage value, temperature, etc. are obtained in an experimental system, such as a probe, a Hall element, a thermocouple, Measurements should be made as appropriate using platinum resistance thermometers, thermography, and combinations of these.

Control and notification method from analysis software

In addition, this software not only receives and analyzes information, but also has a function to change the operation of the detector and measuring device based on the analysis result. For example, there are experiments in which the light emission (coloring) region changes over time, such as electrophoresis, the development of E. coli colonies, and the time-varying label described above. If it becomes, control such as stopping the experimental device and power supply, turning on the light source, shooting, and voice notification are performed. It is desirable that the user designates an area on the image in advance so that a change expected to occur in the area and a control method for the change can be designated. Alternatively, if the user installs the detector (detection site) so that a predetermined area is detected, an effect equivalent to the area designation may be obtained. These are desirably performed in combination with the detector described in detail in the fifth embodiment.
In the case of an experimental medium such as a chemical reaction chip, information for controlling a chemical reaction performed on the experimental medium may be transmitted to the experiment (detection) apparatus side. Specifically, when an experimenter inputs (programs) a name that is handled like a biomolecule name or chemical substance name (chemical formula) and their quantity, reaction formula, conditional branching, etc., this software translates it. Then, an operation command set (reagent arrangement, voltage application position and timing, etc.) that can be recognized by the apparatus controlling the experimental medium is created, and the apparatus is operated. In computer programming, it is similar to the function of inputting in a language that is easy for humans to understand and for the compiler to translate it into machine language.

Detailed quantification method

Further, in quantitative analysis, an error occurs even when the image is not focused at the time of image capturing. Since there are some experiments in which shooting cannot be performed again, such an image must be processed. At this time, when a clue that can be used to estimate the degree of defocus, such as the above-described label or fluorescent label, is photographed together, it has a function of correcting the entire image so that it becomes its original image. Further, in the scanning system shown in FIG. 5, when a plurality of optical data (including image data) is obtained while changing the focus, a function for adding (integrating) these and calculating quantitative data is provided. Have. In addition, as described with reference to FIG. 4, the detection apparatus can record images from above and from the lateral direction. Therefore, based on images obtained by photographing one detection target from a plurality of directions, an optical signal can be recorded. It also has a function to estimate quantitative data by inferring a three-dimensional structure.

Information search and management method using network

In the case of proteins, if the isoelectric point and molecular weight are determined, the protein can be identified by connecting to a public database via a network, so a function that can refer to the database as software is necessary. The ability to create a database in a LAN or computer is also essential. Furthermore, it is important to be able to refer not only to such numerical data but also to image data, book data such as papers, and file data such as HTML. Specifically, image data, video data, book title, book number, applicable page, date, keyword, text, author name, experimenter name, experiment title, experiment record, network address, etc. can be input and saved It has a function that can create a database system that can be searched with keywords and the like. Since this database system also handles image data, it is possible to compare a certain image with brightness, saturation, shape pattern, etc., and arrange the image data in descending order of homology, or display the degree of similarity numerically. Since data such as keywords are attached to the image and managed, keyword search is naturally possible.
In addition, when the amount of information is enormous, information cannot be narrowed down with a simple keyword, and it is troublesome to input a large number of keywords. Even for the same keyword, the required information and image are often different depending on the user. Therefore, in this database system, when the user specifies the keyword X, the related word group RX of the keyword X can be specified in advance. For example, by specifying “reagent” as the keyword X and specifying the related word group RX = {“fluorescence”, “label”, “alcohol”}, the user can select “reagent” when performing an information search. If entered, the database system searches only the information of “reagents” related to the related word group RX and provides it to the user, or at least lists information that is closely related. In addition to related word groups, non-related word groups can also be specified. When an unrelated word group is specified, information related to the group is removed and provided to the user. Even if the related word group is not specified first, among the information searched for a certain keyword, other keywords included in the information actually referred to by the user are statistically processed to automatically select the related word group. You may create it.

In addition, when the search target information is an image, it is very difficult to search using keywords. For example, when searching with the keyword “blue”, it is because the subject matter of the user determines how much blue component is included in what content. In this regard, in this database system, a reference image can be designated for a keyword. For example, if one of the electrophoretic pattern images is specified for the keyword “blue”, the brightness, saturation, blue component content, etc. of the image is analyzed and converted into numerical data, and the image included in the database Search for images with similar characteristics from the data and provide them to the user. In addition, a subjective test may be performed instead of specifying the reference image. This is a method in which a plurality of reference images are displayed to a user, and the keyword of the user and image numerical data are linked by allowing a user to input a sense of the image as a keyword or answering a question.
The method of quantifying the user's subjectivity and linking it to the keyword is not limited to color, but can be used for various data such as contrast, shape, degree of change, magnitude of displacement, volume and quality of speech. Can do. Since it is inefficient to analyze these data every time a user registers a keyword, it is desirable that the data side also has information added to the data. When using a database system based on the user's subjectivity in this way, the user can log on by entering a password or inserting an identification device when accessing the system (software) so that the user can be identified. Keep it. In some cases, it can be automatically identified by network technologies such as cookies.

  It should be noted that such a subjective database system is important not only for text information but also for general network systems such as the Internet where images (including moving images) and audio information are rapidly increasing. is there. In this case, the subject matter-based keyword group includes not only physics and chemistry subjects but also those relating to senses such as taste and hearing, thoughts, and hobbies. In any case, the sense of text, images, and speech varies greatly depending on the subjectivity of the individual, so as a search method, it is necessary to quantify the subjectivity of the individual first through tests, etc., and to change the search conditions for each user. There is.

Apart from whether or not to extend the connection range to the Internet, this database system also has a function that can be shared by multiple users via a network. When focusing on the database management function via the network as described above, this software does not necessarily run on the user's computer, but runs on the host computer. A method of transmitting or receiving data to this software may be used. When you need a high-performance computer to perform an analysis with a very heavy load on the hardware, or when you want extremely high security for data management, or when it is important to synchronize information among multiple users This is because it is preferable to operate on dedicated hardware.

In addition, when using multiple experimental devices, data input devices, computers, authentication systems, etc. as a networked system, it is necessary for the unique IP address of each device connected to the network, device authentication, or personal authentication. This software authenticates users and devices using various information input devices (such as cards) and driver software, automatically restricts access to the system, reads individual usage settings, and other necessary functions. It is desirable to start up.

In software that operates while connected to the network in this way (including operations that are performed on the user's system and only the usage status can be obtained as information via the network), the number of times the software is accessed (used), It is also possible to configure a billing system that collects charges according to time. Furthermore, it is possible not only to collect a fee, but also to provide useful information and provide a user with a reduction in usage fee or a reward to a user who has benefited other users.

In addition, the administrator of this software or a third party other than the user may bear a part of the user's system usage fee through advertisements or sales. In other words, a person who makes a profit by viewing the information content such as an advertisement, purchasing a device, or answering a questionnaire by intentionally clicking with the mouse, etc. To pay a part of or give a reward. Unlike general advertisements and the like that are provided regardless of the user's intention, the user himself / herself benefits from the information content provider by selecting specific information content at the user's intention.

As mentioned above, when the information content is very useful to the user, the user gives the information content provider (which may be the user) a benefit such as a fee or a reward. It is possible that This form is particularly useful in systems used for extremely limited purposes, such as life science research. Information content includes information such as text, sound, images, and video, data, programs, and the like. At this time, if the user's software (system) access record is managed, it is possible to prevent a situation in which the user must repeat the same action to duplicate the charge burden. In addition, the access record may be meaningful not only for fee management but also for the record itself. In other words, by managing the experiment records, information disclosure date and time, contents, considerations, and ideas as a system, it becomes a system that can prove the results and ideas of the user. Furthermore, it is desirable for the certification system to record and manage not only records relating to information provision, but also history of changes, additions and modifications, and information on when other users have accessed the information.

In addition, in order to fully implement usage status and access records, there is also a method for recognizing the user by exercising some kind of hardware (device) to the system instead of a software method such as password entry. It is possible. For example, when the user has a dedicated card and the system is equipped with a card reader (information reader), or when using a device that reads the user's eye movements, fingerprints, voiceprints, and other physical features is there. If the system is equipped with an input terminal that can recognize the connection of the device at any time timing (such as output may be possible), such as a USB port that is common in computers, the user can use USB As long as you have an input device such as a memory or USB key, you don't need any other hardware. In addition, if the purpose of the system is premised on a large number of input objects such as inspection, an input device is attached to each inspection object instead of a user unit, such as an IC tag (integrated circuit chip). It is better to have. For example, when an input device such as an IC tag or barcode is attached to each food item and food delivery and inspection proceed simultaneously, the input device recognizes the target object after the inspection is completed, and then inputs the result. If inspection results are confirmed from a plurality of delivery destinations using the same input device, the inspection and delivery can proceed promptly and without error.
In any case, the system as described above enables detailed management of various information, from user achievements, ideas and contributions to inspection results of objects, and proof of information.
The invention according to the second embodiment is made by Aoki who is the inventor.

In this detection apparatus, the detection target to be handled is mainly a biological sample that emits an optical signal such as fluorescence or is labeled, and the excitation light is mainly ultraviolet light. Therefore, it is desirable to optimize the experimental equipment or the experimental equipment so as to meet such a purpose, and a specific example thereof will be described here.
First of all, it is desirable that the instruments for holding the detection target are formed of an ultraviolet light transmissive material in principle, and pressurization, heating, low temperature (such as liquid nitrogen temperature), various drugs (particularly dilute acetic acid, Experiments under harsh conditions by using materials that can withstand dilute sulfuric acid, alcohol, phenols), photocatalytic materials that exhibit a high decomposition function when irradiated with ultraviolet light, or by using them in some parts such as coatings and built-in parts. It is possible to realize an instrument that can be applied to the above, or can be easily sterilized or purified by pressurization, heating, or irradiation with ultraviolet light, and the temperature in the apparatus can be controlled.

  Examples of instruments include petri dishes used for culturing E. coli, electrophoresis devices used for sample separation, containers such as containers for injecting liquid fluorescent reagents, flat plates on which detection targets are installed, and those provided with handles. is there. By selecting these materials and instruments, a petri dish that is easy to observe colonies with ultraviolet light, an environment for observing the fluorescence spectrum in detail by cooling with liquid nitrogen, a container that can confirm fluorescent labels with ultraviolet light without taking out the detection target, Construct equipment and equipment such as a gel preparation device and a gel support that can be easily heat-sterilized after the experiment, a gel preparation device that can melt the gel such as agarose at high temperature in a microwave oven or autoclave, and solidify it as it is. These can all be used effectively in the detection apparatus.

  FIG. 13 (c) shows an example of an auxiliary device made of a heat-resistant material. The inventors have devised a configuration in Japanese Patent Application No. 2002-299543 that can be used by forming a gel for electrophoresis into a pack, dissolving it by heating with a microwave oven, an autoclave, or the like, and solidifying it into an arbitrary shape. However, if the pack is heated rapidly in a microwave oven, the pack may burst and be dangerous. Therefore, as shown in FIG. 13C, the non-open side of the pack 1303 is sandwiched between the container 1301 formed of a heat-resistant material and the lid 1302, and the open side is fixed to face the bottom of the container. If heating is performed with a microwave oven or an autoclave in this state, the gel 1304 can be dissolved in a short time because the container is a heat-resistant material. Although the gel alone may be put in the container, it may be scattered by rapid heating, so the necessity of the lid 1302 or the pack 1303 is determined by the experimenter. In addition, if a gel support member (also formed of a heat-resistant material) used for electrophoresis is installed in this container 1301 and the gel 1304 is dissolved thereon, it is allowed to cool as it is after dissolution and is necessary for the experiment. It is also possible to solidify into various shapes. It is also possible to configure a gel dissolver (or sterilizer) in which a heat-resistant container 1301 is connected to a heater that directly heats the container. If the heater can be cooled like a Peltier element, it can be gelled in a short time by controlling the temperature after heating, or gelled under optimum temperature conditions.

  In addition, there are a wide variety of appliances that have additional effects due to ultraviolet light and heating, as described above, so ultraviolet light transmissive materials, heat resistant materials, cold resistant materials, moisture resistant materials, chemical resistant materials, photocatalytic materials, and It is also preferable to make it a component that can be assembled into an arbitrary shape if necessary. For example, as shown in FIG. 13A, a basic plate-like component 131 is configured to be fitted into the groove 133 of the connecting component 132, and an arbitrary shape is created. It is desirable that the groove 133 of the connection component 132 is formed not only in one direction but also on the back side and in the vertical direction. A groove may be formed in the plate-like component 131. In addition, liquids are often used as laboratory instruments, so even if waterproofing is improved by sandwiching rubber and foam materials such as adhesion and flexibility, or highly elastic materials between the connection parts and screwing them together. Good. The basic parts are not only plate-shaped but also rod-shaped, arc-shaped and case-shaped, and the connecting part 132 not only connects the basic parts but also has a functional shape such as a handle. Also good. In addition, since it is only necessary to have a special function such as ultraviolet light transmission, other parts may be made of a normal material such as a metal. Such an assembled structure not only has a high degree of freedom in shape, but also has the advantage of being easy to disassemble and clean. This is because impurities easily adhere to the corners of the container and are difficult to clean, but if they are disassembled, the corner structure disappears and can be easily cleaned.

Furthermore, as an assembly structure, not only a three-dimensional structure but also a combination of two-dimensional structures may be performed. For example, as shown in FIG. 13 (b), plate members having various shapes of flow paths 1311, holes 1312 for injecting and extracting samples, reactors 1313 for mixing and reacting a plurality of samples and substances, and the like are arbitrarily combined. This is a case where a system suitable for each experiment is constructed. Accompanying these, an uneven structure 1314 for connecting the plates to each other and a seal member for covering the surface are also required. Instead of connecting the plate members directly, a method of fitting the plate members on a frame or a substrate may be used. In particular, if you want to use a terminal (needle) for measuring current or pH value or a tube (pipe) for taking in or out liquid or gas in a hole or channel, the plate member is equipped from the beginning. It is more convenient to use, and the method of fitting such a plate member is easy to handle. In consideration of detection and post-processing, the member group is desirably formed of an ultraviolet light transmissive material or a heat resistant material. The channel may be formed inside the member, or a hole penetrating in the vertical direction may be formed, and these can be combined three-dimensionally to constitute a high-density and efficient experimental system. is there. As described above, a method for realizing a complicated structure by a combination of simple structural members is particularly effective in a fine structure such as a microstructure or a nanostructure that is difficult to process.
The invention according to the third embodiment is made by the inventors Aoki and Aizawa.

Further, in this detection apparatus, a detection target can be operated by putting a hand inside. A lens can be attached to the upper part for magnified observation, but there is a limit to increasing the magnification rate due to the structure. Therefore, in order to compensate for this, a processing instrument with a camera as shown in FIG. 14 is used. A processing tool 142 such as a cutter, a scalpel, a cutting tip, tweezers, scissors, a laser, and an injection needle is attached to the support 141 and can be exchanged as necessary. Further, an image sensor 143 is installed on the support 141 or the processing tool 142, and thus an image can be recorded. This video is transmitted to a display device such as a computer, a television, or a liquid crystal display via a cable 144. When the display device is attached to the support 141 or when the video can be transmitted by communication, The cable 144 is not necessary. In addition, the structure which attaches image pick-ups, such as an image sensor, directly to the processing tool 142 may be sufficient, and the support body 141 is not especially required in that case.

The image sensor 143 can not only perform close-up photography, but can also have a lens to obtain an enlarged image. Thereby, operation with respect to the fine area | region on a detection target can be performed confirming with a display. The image sensor 143 may be installed at an angle at which not only the vicinity of the tip of the processing tool 142 but also the entire processing tool can be imaged as necessary. For example, in addition to the processing tool 142 described above, when a chip for injecting or sucking liquid is connected, if the entire image can be taken, the liquid amount can be calculated by image analysis. Since the entire image is a video, the current liquid volume is displayed on the display, and the liquid volume used in the experiment is recorded, or conversely, the operation is performed to obtain a predetermined liquid volume. It can also be increased. Since ultraviolet light is often used for detection, it is desirable that a filter for cutting detection light such as ultraviolet light be provided at the front of the image sensor. If the image sensor has the property of detecting invisible light such as ultraviolet light and infrared light, and the signal from the sample can be obtained by light emission, color development or absorption in these wavelength ranges, it is rather positive. It is necessary to transmit these lights. If invisible light can be detected, it is extremely useful because it can handle contents that cannot be operated because it is invisible in a simple darkroom structure.

In addition, a light source necessary for detection may be attached to the processing instrument. As the light source, a small light emitting diode, a semiconductor laser, or the like is preferable. Usually, an ultraviolet light source is used, but not limited thereto. If a light source is attached, operation can be performed in a simple dark room or dark place. If the light source is in the ultraviolet region, it is useful as a camera that uses it as a flash. In addition, although the cutting tip is included in the processing tool 142 described above, this is a hollow member 151 formed of a resin or the like as shown in FIG. 15, and when this is inserted into a detection target and pulled out. A part of the detection target is cut out and pulled out from the hollow portion 152. When the operating instrument has a light source, if the light is introduced into the cutting tip, an image of the tip can be formed on the detection target, so that the target portion can be cut out accurately. Although the cutting chip needs to have sufficient light transmittance, the image of the chip may not necessarily be the wavelength for detection but may be visible light, so the choice of materials is wide.
The invention according to the present embodiment is made by Aoki who is the inventor.

  Furthermore, in life science research, it is very important to perform the same experiment several times and statistically process or confirm reproducibility. On the other hand, repeating a monotonous experiment many times is extremely burdensome for researchers. Many recent experimental equipment has a timer function, and temporal management can be performed relatively easily. However, since the results vary depending on various conditions such as ambient temperature, humidity, and brightness, managing only the time often does not make sense. Also, in many cases, the experiment should be terminated with a certain unique state rather than making the time constant. For example, in electrophoresis, the experiment is terminated when the marker dye migrates to a certain distance, or the experiment is terminated when a predetermined color density is reached by a color reaction by an enzyme or the like. In such an experiment, the parameter to be managed is not a time but a condition (state) to be detected. Moreover, such parameters vary depending on the purpose of the user, and it is difficult to attach a management mechanism to each experimental device.

In order to solve the above-described problems, an experiment may be performed using a state detector that detects and notifies a desired state instead of time. It should be noted that the state detection function and the processing function such as notification corresponding thereto do not necessarily have to be integrated.
A flowchart of the experiment is shown in FIG. First, the experimenter installs the state detector (or its sensor unit) at a position where it is desired to be detected. Next, since the performance of the light source and sensor of the state detector may be changed, the correction is performed. This is done by actually detecting standard colors or standard samples. When correction is complete, set the state you want to detect. Again, it is desirable to use a reference color or sample. Next, what kind of notification is to be performed when the set state is reached is set. The notification method is generally by voice, and it is convenient to allow the user to set the content. Alternatively, a method may be used in which character information is sent to the user for notification. Note that detector correction, detection state setting, and notification content setting are omitted unless particularly necessary. If the settings up to the notification content have been completed, the experiment is started. Detection is repeatedly performed based on a predetermined time interval or program, and when the detection target is set, notification by the state detector is executed. In addition, as a function of the state detector, control such as automatically stopping other devices or changing the operation state according to a program may be performed. The user may complete the experiment at the stage of notification, but if it is necessary to detect another state, the experiment is continued.

In this way, instead of a timer method that stops the operation when a predetermined time elapses or notifies by voice, etc., if it is a method to stop the operation or notify when it reaches a predetermined state, It is advantageous not only for experiments but also for applications such as inspection. For example, when measuring blood component concentrations such as blood sugar levels by color development using an enzymatic degradation reaction, if the measurement time is set to a certain level in advance, color development occurs before the measurement time elapses for a sample with a very high component value. The concentration is saturated. On the other hand, with a specimen having a very low component value, the color density necessary for measurement cannot be obtained even when the measurement time has elapsed. Therefore, in any case, an accurate concentration cannot be obtained. On the other hand, according to the method of the present state detector, the time required to reach the optimum concentration for measurement can be used as a parameter, so that an accurate concentration can be calculated for any sample. It can be done.
In addition, some samples may be affected by being denatured or decomposed by a stimulus such as detection light. In such a case, use a marker that indicates the state of the experiment (for example, a mobility marker in electrophoresis, which changes or moves at a position different from the sample), and set the detector accordingly. Thus, the sample can be used without affecting the sample. Alternatively, as described in Example 2, since a label for monitoring a change in the experimental environment rather than the sample itself, such as a temperature change, may be used, the present state detector also applies to such a label that changes. It may be used.

  A specific configuration of the above state detector is shown in FIG. The state detector in FIG. 17A has a sensor 172 on the front surface or at least a part of the housing 171. The sensor 172 detects a state of light, electromagnetic waves, sound, or the like including a photodiode, an image sensor, a microphone, and a piezoelectric sensor (for example, detecting vibration caused by sound as a pressure change). Combine several. The sensor 172 may be connected to the tip of a flexible or articulated cord (having a light guide such as an optical fiber or a mirror inside) that communicates with the housing 171. In addition, when the sensor 172 detects light, it is desirable to have a light source 173. The light source 173 includes a light emitting diode, a semiconductor laser, an organic electroluminescence element, a fluorescent tube, and the like, and a plurality of light sources are combined as necessary. When the detection target or detection area is very small, a lens may be added to the light source 173 to concentrate the light on the small area.

In addition, electromagnetic waves such as X-rays, ultraviolet rays, infrared rays, and radio waves are also included in the light source in a broad sense. If it is assumed that the light source is used in a bright place, the light source 173 may be omitted. Conversely, when measuring in a place with a lot of external light (noise) such as a bright place, the output from the light source 173 (including a detection signal source such as a sound source in some cases) has a modulation characteristic and is linked with a sensor or software. In some cases, a configuration for removing noise is required. The light source 173 may be housed together with the sensor 172 in the casing 171 or in a cord that leads to it. However, when it is desired to change the distance from the object to be detected, as shown in FIG. It is connected to 174 so that the direction can be adjusted by a screw structure 175 or the like. Various combinations of the sensor 172 and the light source 173 are selected depending on the detection target. For example, if the detection target is a marker dye for electrophoresis or a specific color development in the visible range such as a decomposition color reaction by an enzyme, the sensor 172 is a photodiode, a CCD (or CMOS) image sensor, etc. Those that are sensitive to wavelengths in the visible range are selected. In order to increase sensitivity to signals, a sensor may be provided with a bandpass filter that selectively transmits a desired wavelength, or a filter that cuts off reflected light or diffracted light from a light source. The filter is not limited to an optical filter with high accuracy, and a colored film such as ultra-color (Rosco) is also sufficient. It is also convenient to use a sensor in which these filters are integrated.

For light that is colored in the visible range, the light source 173 is preferably a light emitting diode that contains white or a wavelength component that has a high absorbance by the detection target, and a light emitting element or a light emitter having such characteristics. An element in which a sensor and a light source are integrated is also commercially available and may be used. When a light source having no wavelength characteristics such as white light is used, it is better to use a filter or the like so that the sensitivity to a specific wavelength is increased on the sensor side. On the contrary, if the light source has many specific wavelength components, it is not necessary to limit the wavelength on the sensor side. For example, when detecting a blue dye used in electrophoresis, if a white light source is used as the light source, a yellow filter (a large absorption signal due to the blue dye) should be installed on the sensor side. If a yellow light source is used as the light source, the sensor side does not need to have a filter or the like. Further, if it is assumed to be used in a bright room, the light source 173 may be unnecessary. Further, even when the light source 173 is necessary, it is not necessarily integrated with the sensor 172. This is because, depending on the detection target, it is often convenient to place the detection target between the light source 173 and the sensor 172 and measure the transmittance of the transmitted light. When the detection target has a characteristic such that light is emitted by light excitation, the sensor 172 may be the same as described above, but a light source having an emission wavelength suitable for light excitation, such as an ultraviolet light emitting diode, is selected. If the detection target emits sound, the sensor 172 can detect sound such as a microphone. If the detection target generates heat, the sensor 172 can detect a temperature change such as a thermometer or a thermal sensor. Select as appropriate. Of course, you may have two or more of these sensors and light sources.

Further, the sensor 172 does not need to be separated from the detection target, and may be in contact. For example, the detection target is a liquid or a gas, and a substance that adheres to the surface of the sensor is detected in the detection target. In particular, the amount of body fluid such as blood that can be collected is limited, and it is very difficult to detect trace substances such as cancer marker proteins contained therein. Moreover, such a trace substance has a great significance in detecting it while it is in a trace amount. For this purpose, the sensor should be inserted directly into a site where it can come into contact with bodily fluids such as blood vessels. This is because, by utilizing the circulation of bodily fluids, the sensor can be brought into contact with bodily fluids around the whole body, which eliminates the problem that trace substances are difficult to detect because only a finite amount of bodily fluids can be collected. is there. Such a sensor configuration is such that if the substance to be detected is a protein, compound, or ion, a protein (peptide), compound, ion, or the like that can be specifically bound to it by an antigen-antibody reaction or hydrogen bonding is placed on the surface. Thus, if the substance to be detected is a nucleic acid such as RNA, a nucleic acid having a sequence that can specifically bind to it is arranged on the surface. If sufficient selectivity cannot be obtained by simply placing it on the surface, or if it is structurally difficult, a permeation membrane that selectively permeates ions, molecules, and substances to be detected, or ions that interfere with detection Alternatively, a non-permeable membrane or a catalyst that does not allow molecules or substances to permeate or decomposes may be added to the sensor unit. When the detection target substance is extremely small, it is necessary to wait until a certain amount of substance is bound instead of making the detection time constant. Become a thing. In some cases, sufficient circulation cannot be detected unless the circulation is completed several times. Therefore, the total amount of body fluid contacted by the sensor, the detected amount of the target substance, and the reaction (adhesion) are parallel to the measurement with a blood flow meter. In some cases, it may be necessary to convert the concentration into consideration taking efficiency into account. The binding signal is preferably a method that can be monitored even if the sensor is inside the body, such as detecting the generation of ions or electrons due to enzymatic reaction as an electrical signal, but it is taken out of the body after a certain time and detected optically. This is not the case when such a method is available. Such a sensor is desirably used in combination with an infusion needle or a catheter (which may be configured on these devices) on the premise that the sensor is to be installed in the body for a long time. In particular, when a biomolecule such as an enzyme is used as a sensor, it is ideal to insert it into the body because it functions more easily in terms of environment such as temperature. Similarly, in the case of monitoring temperature and sound (vibration), the sensor unit and the detection target may be preferably in contact with each other.

Usually, the state detector of FIG. 17A has a size of several centimeters to several tens of centimeters, so the fixing member 176 may be a suction cup, a magnet, a magic tape, a double-sided tape, a screw, a clip, a pin, or the like. As a result, the casing 171 is fixed to a desired measurement location, and measurement is performed. The fixing member 176 and the housing 171 may be integrated when the application is limited, such as when monitoring a gel of an electrophoresis apparatus having a predetermined shape, but can be moved together by a screw or a hinge. If you are connected in such a state, the degree of freedom of the installation method will be higher.
If such a small configuration as a whole can be achieved, not only will the degree of freedom of installation of the detector be increased, but also the advantage that the devices can be closely arranged is born. For example, if it is a submarine type (horizontal type) electrophoresis apparatus, it can be used simultaneously by overlapping in the vertical direction by installing it on a shelf-like structure. Normally, if it is installed in this way, it will be impossible to observe other than the uppermost electrophoresis apparatus, so it is very difficult to use under different conditions, but at least one of the state detectors (corresponding to each electrophoresis apparatus). If the sensor part) is arranged, there is no problem because it is not necessary to observe. In the case of a vertical (vertical) electrophoresis apparatus, a plurality of devices can be installed in close contact with each other in the horizontal direction. In short, the experimental device can be arranged at a high density by eliminating the restriction that a space must be secured for the experimenter to observe.

  The purpose of use of this state detector is to detect by the sensor 172 that a specific state change has occurred in the detection target and notify the experimenter. From here, the flow of FIG. 16 will be described more specifically. First, regarding each setting method, the input switch 177 is normally used for each setting and determination. The input switch 177 performs numerical value input and character input as necessary, and the number thereof is also appropriately arranged. The input switch does not input numerical values or characters in this way, but may switch the setting condition itself. For example, sensor detection levels and detection items (wavelength components, etc.) are prepared in multiple stages in advance, and they can be switched each time an input switch is pressed, or multiple input switches correspond to those detection levels and detection items. It is a system like that. Note that an input switch is not required for a dedicated detector that has only one type of setting condition.

  First, it is desirable for the experimenter to correct the output of the light source 173. Specifically, using a standard sample that can be recognized as a reflectance of 100% (or the maximum value) such as a blank sheet or a mirror, detection is performed under the conditions of performing an experiment if possible, and this is the maximum value of the detection value. Or a setting for a specific detection value. This is a setting for correcting deterioration of the sensor or light source or characteristic changes due to experimental conditions, but if the desired detection state does not require strictness so far, or if it is performed automatically, This setting operation is omitted. As a standard sample other than the light measurement, a sample according to a state to be detected such as a standard voice or a standard temperature is used. Furthermore, even in the case of light measurement, when the sensor 172 is an image sensor, it is possible to detect a specific pattern or shape or a change thereof, so that a standard pattern or standard shape can be used for setting. It may be necessary. The advantage of using an image sensor is that, in addition to such pattern and shape recognition, the degree of freedom of the installation position of the detector is high, the detection area is wide, the two-dimensional distribution and displacement of the detection target and its speed. It can also be detected. In consideration of the fact that this state detector is mainly used for physics and chemistry experiments, it is assumed that the sensor part is clouded by the evaporated liquid. Therefore, a hydrophilic coating is applied to the sensor 172. It is necessary to add a device that does not change the sensitivity. However, this is not the case when the detection value is set in a cloudy state or is set on the premise that the detection value is clouded from the beginning.

Next, the experimenter must input (set) the state change to be detected to the state detector. For this purpose, it is desirable to detect and set the detection target that has actually reached the state to be detected, but even if a standard sample (such as a specific colored paper) that can obtain a detection signal equivalent to the desired detection state is used. Good. Alternatively, when the detected value in that state (absolute value or relative value with respect to the maximum value) is known, the value may be input as a numerical value. In any case, in the actual experiment, the set detection state (value) may be far exceeded, so the condition setting is not only a simple numerical value or standard sample detection, but the degree exceeds that condition. Usually, it is also necessary to specify a range such as notifying in the case of (below). For example, if a specific light emission is detected, notification is usually made when the specified detection level is exceeded. However, when a specific color density is detected, the intensity of reflected light is the color density. Therefore, it becomes necessary to notify the case where the detection level falls below the specified detection level. There are also cases where it is desired to know when the color density or light emission is lower than a certain level.

Furthermore, if you want to detect yellow and blue color development and do not want to detect green color development, if the sensor is simply configured to detect the intensity of the reflected light instead of identifying the color, the detection level If the range is not specified, correct notification will not be performed. That is, if the reflectance has a relationship of yellow> green> blue, after reading each density, the detection level (reflection intensity) should be in a certain range between yellow and green. If it is smaller than yellow or blue, it is possible to specify that blue is notified. For example, when using a dye containing three color dyes as a marker dye used in an electrophoresis experiment, such a use is notified when a yellow dye reaches the detection region, and further notified when a blue dye arrives. However, there are cases where other dyes are ignored. When a plurality of color components can be detected independently, such as when the sensor 172 includes a plurality of photodiodes each having a different color filter, a more accurate detection can be performed by designating a detection range for each color component. High detection can be performed.

Furthermore, in experiments such as electrophoresis, there is a case where it is desired to know only the timing when the second one arrives even if the same band arrives. Therefore, as a notification setting, it is desirable that even when the detection level is the same, it is possible to notify only when it reaches the designated number of times. Furthermore, even if the detection level is the same, it may be necessary to change the notification contents depending on how many times it is detected. In addition, the sensor 172 is a complex of a plurality of sensor units, and the light source 173 can emit light of a plurality of wavelengths. For example, the sensor 172 can detect a plurality of signals as well as high and low one-dimensional detection levels. In the notification setting, the accuracy can be improved by making it possible to select which signal to perform the sensing operation in the notification setting.

Obviously, if the above complicated setting becomes possible, it is possible to realize complicated detection with higher accuracy. However, from the viewpoint of ease of use, it is possible to simply use a changeover switch or the like to detect a plurality of detection levels (for example, signal levels). In some cases, it is better to use only strong, medium, weak, etc.). Further, when the detection level is set, if an input switch is used, digital signal processing is required, and the configuration of the detector may be complicated or the fine setting may not be supported. Therefore, the input switch 177 is not a digital processing switch. Instead, a dial type adjustment knob may be used, and a characteristic value of an element such as an internal resistor or a capacitor may be adjusted, and these may be appropriately selected. When the setting is not changed from the previous setting stored or when it is set from the beginning, the state setting is omitted. Note that the state that can be set is not necessarily one type, but a plurality of states can be set and stored.

  Next, the experimenter sets what notification signal is received when the desired detection state is reached. Most commonly, the sound notification is an electronic sound using a built-in sound source, but it is desirable that the experimenter himself can set the notification signal in cases such as when multiple states are detected and different notifications are desired. . Changing the electronic sound pattern is one means, but ideally it is desirable to be able to record sound. That is, for each state set in the above procedure (or set from the beginning), the experimenter himself / herself makes a voice input notification so that the characteristics of the state such as color, pattern, shape, and temperature are easy to understand. The sound is set. If such a setting is made possible, for example, when blue color development or movement is detected, not only is it simply notified that the color is “blue”, but also “dye XX is detected” “XX” It is possible to provide extremely specific notifications such as “The chemical reaction of“ has been completed ”or even when multiple detectors are used for the same experiment at the same time. It is also possible to distinguish between detectors. In particular, when there are many settings for the state that you want to detect, when you want to detect signals that humans cannot sense, such as invisible light, and when you want to conduct experiments under conditions that humans cannot access, such as high temperature conditions or pressurized conditions, The merit of using the voice notification means uniquely set by the experimenter increases. The voice notification may be converted to a combination of voices registered in this state detector, not the voice itself recorded by the experimenter. It can also be performed as text information. Of course, since the notification means may be not only voice but also light, video, text, etc., the fact that the experimenter can set them independently has a great merit.

The setting of the detection state and the setting of the notification method are not necessarily in order, and may be performed simultaneously. That is, it is only necessary to set notification contents such as voice while detecting a certain state or standard sample. Furthermore, if voice recognition is possible in addition to voice input, the experimenter can receive a notification of a certain state, and the experimenter can instruct the next operation of the present state detector in response thereto by voice. Become.

  In actual detection, even if the set value is reached, it may be better not to notify at that moment. For example, the detected value continues to change even when the set value is reached, and notification is desired when the peak value is reached. In order to deal with such a case, it is necessary to have a simple storage device in the detector and to be able to recognize the peak value by comparing the past detection value with the current value.

  Furthermore, the present state detector may have a configuration in which an external cable 178 used for transmission / reception of signals to / from the outside and power supply is connected or provided from the beginning. Therefore, each setting and each notification as described above may be performed by a device such as a computer through the external cable 178. By using such an external device, this state detector is realized with a very simple structure in which a light source, a sensor, a sound source, and the like are omitted. For example, if external light is used for detection, an external camera is used as a sensor, and a computer or mobile phone is used as the sound source, the function of this state detector can be realized by software alone, or the measured value can be obtained by using only the light source and sensor It can be transmitted to the outside, and determination and notification can be performed by an external device.

Furthermore, the setting conditions can be complicated, programmed, or algorithmized, and notification can be performed not only by voice but also by light, video, or text. Of course, if these advanced processes can be performed by the state detector itself, an external device is not necessary. In addition, when the state detector is equipped with wireless communication means, the external cable 178 is not necessary, and each setting and notification is received by a mobile phone, a personal digital assistant, an infrared remote controller, or a wireless signal. Since it can be performed through possible dedicated equipment, the experimenter can move to a place away from the state detector with peace of mind. The state detector itself does not necessarily have a wireless communication function, and a method of using these communication functions by connecting to a communication device such as a mobile phone or a personal digital assistant may be used. The notification is used not only by the experimenter but also for controlling the operation of external devices that are sent to the power supply to stop the experiment, or sent to the detection light source or camera to automatically detect and shoot. There is also a case.

Note that the sensor 172, the light source 173, and the power source for driving these processing circuits are preferably those that can be miniaturized, such as dry batteries, rechargeable batteries, solar cells, and fuel cells. The external cable 178 may be a USB cable that can supply power from the outside. In order to enable monitoring for a long time with a small configuration, it is preferable to intermittently supply power to the light source and sensor instead of continuously. For example, by using a timer IC, a microcomputer or the like, the light source is turned on at a high frequency or measured once every few seconds. Since the measurement interval varies depending on the detection target, it is desirable that this can also be set.

  The above basic configuration is summarized as a block diagram in FIG. This state detector basically irradiates a detection target with a light source and detects the reflected light with a sensor. Since a sensor often emits a weak output such as a photodiode or a phototransistor, an amplifying unit for the output is usually required. The amplification unit is an operational amplifier, a transistor, or the like, but may be incorporated in the sensor. If necessary, the detection condition (value) can be set by changing the amplification factor, the signal level, the output of the light source, and the like by an input switch. The input switch includes not only a setting prepared in advance or inputting a digital numerical value, but also an adjustment dial for changing the value of the variable resistor in an analog manner. For example, when a feedback circuit using an operational amplifier is applied for signal amplification, a resistance for controlling the amplification factor is made variable (adjustable). When using a sensor whose resistance value changes according to the amount of light, such as a cadmium sulfide element, it can be used as the resistance of the feedback circuit, or for measuring the output voltage of an operational amplifier. It may be used as a resistance. The detected (amplified) signal is compared with a set value (detection condition). If the set value is reached, a notification is sent from the notification unit to the experimenter by voice or the like. The light source may be an external light source, and it may be better not to incorporate the light source in the detector, for example, when performing transmission measurements rather than reflection measurements. If the set value is fixed from the beginning, no input switch is required.

In any case, this state detector can be used only for experimental purposes if it can detect and notify the specified color, pattern, shape, temperature, and changes in such a small configuration. Rather, it can be used in a wide range of applications, such as assisting human vision and hearing, detecting disasters such as fires and minimizing them, and detecting changes in places where humans are not normally accessible. Moreover, since it becomes possible to make an advanced detector combining these application examples, the usefulness is very large.

Further, FIG. 18 (a) shows an example in which the state detector of FIG. 17 (a) is advanced. The state detector in FIG. 18 (a) has sensors and light sources as in FIG. 17 (a), but a detection cord 1801 is connected to the housing 1800, and the sensor 1802, A light source 1803, a light source support 1804, and a screw 1805 are provided. In the state detector of FIG. 18 (a), the size of the device is increased by the increased functionality of the device, and the sensor part having such a flexible cord structure provides a fixing member to the sensor and / or light source. There are advantages such as the degree of freedom of the installation position obtained in this way and the versatility of being able to connect to the main body only when necessary while using only the sensor unit as an independent detector. Needless to say, the sensor 1802 and the light source 1803 may be directly installed in the housing 1800 as long as the environment in which the state detector can be used close to the detection target is assumed. Alternatively, the detection code 1801 may be a photoconductor such as an optical fiber, and may include only the light source 1803 and the sensor may be housed in the housing 1800 if necessary. Conversely, the housing 1800 does not have any sensors or light sources, and a state detector having at least a sensor as shown in FIG. 17A is connected to the housing 1800 (connection by communication using radio waves or light). The housing 1800 may simply start or stop energization or perform signal processing such as voice notification based on a signal obtained from the detector. In any case, the sensor 1802, the light source 1803, the light source support 1804, the screw 1805, the fixing member 1806, and the input switch 1807 have the same functions as those described in FIG. Omitted.

A display 1808 displays setting information, detection data, a message, an image acquired by the sensor 1802, and the like. Reference numeral 1809 denotes a vent hole array opened for voice output and voice input. Reference numeral 1810 denotes a power output terminal for obtaining AC power by plugging in an outlet of an external device. When the external device requires a DC output or a different voltage, control such as rectification or transformation is performed inside the state detector, and power suitable for the control is output. The state detector shown in FIG. 18 (a) also basically notifies the specific detection state by voice. However, when a terminal for outputting power is provided in this way, the predetermined state is displayed. When detected, it is possible to control the operation of an external device connected thereto by starting or stopping power output instead of voice notification. Normally, the signal detected by the sensor unit is processed by a built-in microcomputer or the like, but the electrical response of the sensor 1802 changes according to the sensed signal, such as a photocoupler or a phototransistor. In some cases, an operation such as shutting off the power supply can be performed without performing digital signal processing. In any case, the display 1808, the vent hole array 1809, and the power output terminal 1810 are not necessarily required. Reference numeral 1811 denotes an external cable. When the power output terminal 1810 is provided, the external cable 1811 needs to be capable of supplying power, such as a power cord. In addition, when a cable is used for information transmission, it is necessary to be able to transmit information such as a USB cable. Needless to say, there may be a plurality of these cables, and each of them may be detachable.

Note that the state detectors in FIGS. 17A and 18A not only fix the sensor unit, but also search for a location that has reached the target state while holding it in the hand, It is also possible to use the method of measuring the change due to the position of the intensity. In this case, since it is convenient to know the position of the sensor unit, it is desirable to attach a reflected light sensor such as an infrared ray so that the movement (displacement) of the sensor unit can be measured. When dealing with an object having a very low reflection intensity, it is preferable to have a sensor body such as a sphere inside and detect the displacement and movement of the sensor unit by the rotation and displacement of the sensor body. If the relationship between the signal intensity perceived by the sensor and the position can be recorded, it is possible to measure the light intensity distribution as described in the explanation of this software.

The above basic configuration is summarized in FIG. The difference from FIG. 17B is that external power is received by the output control unit, and the power supply state to the external experimental equipment is changed according to the detection state. Not only power supply but also control information such as a program may be supplied. By adding these functions, even if the experimenter is away, the experimental equipment is automatically controlled when the detection condition is reached. In addition, a display unit is provided to display setting values, detection conditions, detection values, etc., and it is also possible to input voice if the notification method is by voice. It is. When setting conditions while actually performing provisional measurement, it is more convenient to display the detected value. As described above, an external cable or the like is attached if necessary. Note that the configuration diagrams shown in FIG. 17B and FIG. 18B are merely examples, and may be configured such that these are combined or partially deleted, and details follow the above-described description. Shall.
Finally, the characteristics of this state detector are summarized: (1) detection of a change in the state of the experiment, (2) the detection level can be set, (3) notification content for detection can be set, (4 ) The main point is to have an output terminal for power or information and to control an external device by output according to the detection level.
The invention according to the fifth embodiment is made by Aoki who is the inventor.

The figure which shows the flame | frame of one Example of the biological sample detection apparatus of this invention. The figure which shows one Example of the irradiator of this invention The figure which shows one Example of the irradiator of this invention The figure which shows one Example of the biological sample detection apparatus of this invention The figure which shows one Example of the biological sample detection apparatus of this invention The figure which shows an example of the irradiation light quantity distribution of the biological sample detection apparatus of this invention The figure which shows one Example of the biological sample analysis method of this invention The figure which shows an example of the selection area | region by the biological sample analysis method of this invention The figure which shows one Example of the biological sample analysis method of this invention The figure which shows one Example of the biological sample analysis method of this invention The figure which shows one Example of the biological sample analysis method of this invention The figure which shows one Example of the biological sample analysis method of this invention The figure which shows the auxiliary instrument used for the biological sample detection apparatus of this invention The figure which shows the auxiliary instrument used for the biological sample detection apparatus of this invention The figure which shows the auxiliary instrument used for the biological sample detection apparatus of this invention The figure which shows the use procedure of the auxiliary tool used for the biological sample detection apparatus of this invention. The figure which shows the auxiliary instrument used for the biological sample detection apparatus of this invention The figure which shows the auxiliary instrument used for the biological sample detection apparatus of this invention

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Top plate 2 Lens 3 Lens housing 4 Upper fixing member 5 Light source 6 Upper frame 7 Lower frame 8 Adjustment screw 9 Lower fixing member 10 Power cord 1a Top plate 2a Lens 3a Lens housing 4a Filter 5a Filter housing 21 Transilluminator 22 Ultraviolet fluorescent tube 23 Filter 31 Light source 32 Light guide plate 33 Reflective member 41 Cover member 42 Fixing member 43 Light blocking member 44 Space 45 for hand 45 Hood 51 Light transmission plate 52 Light source 53 Detector 54 Detection target 61 Image 62 Detection target installation area 71 Whole image 72 Optical signal 73 Image area 81 Analysis target image 82 Rectangular designation 83 Ellipse (perfect circle) designation 84 Arbitrary shape 85 Analysis direction designation line 86 Area width 87 Label 91 Electrophoretic carrier 92 Sample separation pattern 93 Separation of electrophoretic marker Pattern 131 Plate-like part 132 Connection part 133 Groove 311 Channel 1312 Hall 1313 Reactor 1314 Connection uneven structure 1321 Container 1322 Lid 1323 Pack 1324 Gel 141 Support body 142 Processing tool 143 Image sensor 144 Cable 151 Cutting chip 152 Hollow part 171 Housing 172 Sensor 173 Light source 174 Support body 175 Screw 176 Fixed member 177 Input switch 178 External cable 1800 Case 1801 Detection code 1802 Sensor 1803 Light source 1804 Support 1805 Screw 1806 Fixed member 1807 Input switch 1808 Display 1809 Vent array 1810 Power output terminal 1811 External cable

Claims (14)

  An apparatus for detecting a biological sample which is covered with an external light from the periphery of the biological sample and at least a part of the side surface of which is formed of a flexible member.   The biological sample detection device according to claim 1, wherein the flexible member can be moved and / or opened and closed in a vertical direction or a horizontal direction. The biological sample detection device according to claim 1 or 2, wherein the biological sample is detected as a band separated by electrophoresis and / or a transcription of the band. 4. The biological sample detection apparatus according to claim 1, wherein the electrophoresis apparatus is installed in a space where external light is blocked.   Illuminating means for illuminating the biological sample, photographing means for photographing the illuminated carrier surface, and correcting means for two-dimensionally correcting the illumination light quantity of the illuminating means for an image photographed by the photographing means. The biological sample detection device according to claim 1, wherein:   The said two-dimensional correction is provided with the detection means which can detect the intensity | strength of the light quantity of the said illumination means two-dimensionally, The light quantity in each site | part obtained with the said detection means is used as a correction reference. A biological sample detection apparatus.   A biological sample analysis method comprising superposing images obtained by photographing biological samples with a plurality of light sources.   The biological sample analysis method according to claim 7, wherein the plurality of light sources have different wavelengths, and an image composed of a plurality of color components is obtained by superimposing images photographed at the respective wavelengths. .   It is arranged so as to monitor a predetermined position of the detection target, and a means for detecting a change in state at a specific part of the detection target is compared with detection information obtained by the detection means and predetermined information, A biological sample detection device comprising control means for performing control based on a compared value.   The state change in the specific part is a change in color density, a change in color component, a change in light amount, a change in emission wavelength, a change in absorbance, a change due to movement of a dye, a change in shape, a change in temperature, a change in volume, a displacement. The method for detecting a biological sample according to claim 9, which is one of changes in speed.   The biological sample detection method according to claim 9, wherein the detection unit detects a concentration of a specific color component.   The method for detecting a biological sample according to claim 9, wherein the detection means detects a concentration of a plurality of color components, and detects a color change based on a synthesis result of the color components. .   The biological sample detection method according to claim 9, wherein the control unit has a function of performing notification by at least one of light emission, sound generation, and communication.   The biological sample detection method according to claim 9, wherein the detection target is a dye and / or a biomolecule that moves in an electrophoresis carrier.

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