JP2016223919A - Chip for chromatographic processing, chromatographic processing device, and chromatographic processing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a chip for chromatographic processing, a chromatographic processing device, and a chromatographic processing method such that chromatographic processing is performed speedily and efficiently with high reliability.SOLUTION: The present invention relates to a chip for chromatographic processing that has: a dispensing chip with light transmissivity which has, at a lower end, a mouth part inserted into a container to suck and discharge a liquid and also has a thin pipe communicating with the mouth part and a thick pipe communicating with the thin pipe and provided, on a lower side, with a reservoir part for reserving the sucked liquid, and a porous stationary phase carrier which is provided in the thick pipe of the dispensing chip and provided with a substance stationary plane for inspection where a substance for inspection enabling a target substance in a sucked moving phase solvent to be adsorbed, captured, separated, or combined is fixed in a predetermined region by a predetermined amount. The porous stationary phase carrier is sealed such that an optical state of the substance stationary plane for inspection can be measured from outside a side face of the dispensing chip, and a lower end of the porous stationary phase carrier is provided in the reservoir part.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a chromatography chip, a chromatography apparatus, and a chromatography method.

  Conventionally, as a method for diagnosing an infectious disease, there has been a method for diagnosing an infectious disease by amplifying a nucleic acid extracted from a specimen by a PCR method and specifying its base sequence. Although this method has high detection sensitivity, it has a problem that it is complicated in operation and requires several hours for measurement.

  On the other hand, there has been a method of diagnosing infectious diseases using a chromatographic method. In this method, a nitrocellulose membrane is used as a substrate, and a sample pad to which a sample is dropped is provided at the end with a conjugate pad for labeling interposed therebetween. An absorption pad is provided at the other end of the substrate, and a test line and a control line are spaced between the conjugate pad and the absorption pad on the substrate so as to partition gas into the conjugate pad side and the absorption pad side. Is provided. The conjugate pad is coated with a colloidal gold-labeled antibody capable of specifically binding to the target antigen, the immobilized antibody capable of specifically binding to the target antigen is fixed to the test line, and the control line is fixed to the control line. The immobilized antibody capable of specifically binding to the labeled antibody is immobilized. When a sample is dropped on the sample pad, the sample flows to the conjugate pad, and the target antigen bound to the gold colloid-labeled antibody is released from the conjugate pad onto the substrate, and labeled with gold colloid by capillary action. If there is an antigen, it will be captured by the test line and colored red. Furthermore, the gold colloid-labeled antibody that is not bound to the target antigen further moves the substrate by capillary action to give a control line.

  By the way, the above-described immunochromatographic diagnosis method is performed by dropping the sample onto the sample pad by a method, and since the coloration is measured by visual observation, the user mistakenly takes the sample. There was a risk of contact with the solution or exposure to the splashes.

  In addition, this method has a problem that it is difficult to make a judgment on quantitativeness because it qualitatively measures whether or not coloration occurs. In addition, since the treatment and measurement are performed by the conventional method, there is a risk of contact with the stationary phase carrier used in the extraction or contamination of nucleic acids other than the target nucleic acid in the extraction step, amplification step or measurement step of the target nucleic acid. There was a problem that there was a possibility that highly reliable measurement could not be performed.

  Further, when processing a plurality of samples, it is necessary to perform processing for each user one by one, which has a problem that the processing efficiency may be low.

Japanese Patent No. 5218235 “Current Status and Future Prospects of Immunochromatography Technology” (December Nanotech Business Matching Forum) (http://www.nbci.jp/file/051227-4.pdf#search)

  Accordingly, a first object of the present invention is to provide a chromatographic processing chip, a chromatographic processing device, and a chromatographic method capable of highly accurate measurement that can ensure quantitativeness for chromatography utilizing capillary action. The purpose is to provide a processing method.

  A second object of the present invention is to provide a chromatography chip, a chromatography apparatus, and a chromatography method capable of performing a highly reliable process by preventing cross-contamination for chromatography utilizing capillary action. It was made for the purpose.

  A third object is a highly versatile chromatography chip, a chromatography apparatus, and a chromatography apparatus that can perform not only immunological tests but also tests on nucleic acids extracted from a sample for chromatography using capillary action. The object is to provide a chromatography method.

  The fourth purpose is a chromatography chip, a chromatography chip that facilitates the consistent automation of the process from the reaction to measurement of chromatography using capillary action, and further including the extraction and amplification of the target substance from the specimen. The present invention has been made for the purpose of providing a chromatography processing apparatus and a chromatography processing method.

  According to a first aspect of the present invention, there is provided at the lower end a mouth portion which is inserted into a container and performs suction and discharge of liquid, and has a narrow tube communicating with the mouth portion and a storage portion for storing the fluid sucked through the narrow tube. A translucent dispensing tip having a thick tube provided on the side, and a target substance in the aspirated mobile phase solution that is provided in the thick tube of the dispensing tip is adsorbed, captured, and separated. Or a porous stationary phase carrier provided with a testing substance immobilizing surface in which a predetermined amount of a testing substance that can be bound is immobilized in a predetermined region, and the porous stationary phase carrier is An optical state of the test substance fixing surface is enclosed in the thick tube of the injection tip so that it can be measured from the outside of the side surface of the dispensing tip, and the lower end of the porous stationary phase carrier is provided in the reservoir. It is the obtained chip for chromatography processing.

Here, the “dispensing tip” is an instrument capable of sucking and discharging a liquid, for example, a nozzle having a mounting opening that is mounted on a nozzle communicating with a suction / discharge mechanism that performs suction / discharge of gas. A mounting type dispensing tip or a deformable type dispensing tip having a deformable element that can be deformed by a movable member as a suction / discharge mechanism or having a deformed wall. The mounting opening is provided on the upper side of the thick tube. The size of the dispensing tip is, for example, about 2 to 30 cm in total length.
“Chromatography” means that substances are bound, separated, and extracted in the process of passing a substance called a mobile phase through the surface or inside of a substance called a stationary phase (or carrier).
“Porous stationary phase carrier” is a carrier in which a mobile phase solvent (or a developing solution) can move by capillarity, for example, filter paper, cotton yarn, glass fiber, pulp, nonwoven fabric, synthetic fiber, More specifically, it is formed of nitrocellulose, regenerated cellulose, nylon, polyvinylidene fluoride, polycarbonate, cellulose acetate, and the like, for example, a thin film (paper, membrane), strip, thin plate, or rod. The thickness of the porous stationary phase carrier is, for example, about 1 mm or less, preferably about 0.1 mm to 0.8 mm, and the size of the porous stationary phase carrier is a size that can be enclosed in the thick tube of the dispensing tip. The length in the vertical direction is, for example, about 1 cm to 20 cm, and the width is, for example, about 1 mm to 20 mm. “Test substances” include chemical substances such as nucleic acids such as nucleic acids that bind to target chemical substances (including biological substances) to be tested, proteins such as antigens and antibodies, chemistry such as sugars, sugar chains, and peptides. Substance (including biological substance).

  The “predetermined area” is, for example, a fixed area (an area where one or more kinds of test substances are fixed) between a mobile phase storage line and a positive control line, which will be described later, and is bonded to a target substance. One or more kinds of test substances having the property are fixed in a straight line so as to partition the region into an upper side and a lower side, for example, along a direction orthogonal to the suction and discharge direction. The part where each test substance is fixed is called "fixed part". These one or two or more fixing parts are arranged at predetermined positions with a predetermined interval therebetween.

The “predetermined amount” is a predetermined quantitative value, and it is possible to measure the quantitative property by measuring the optical state. The “optical state” is a state caused by the target chemical substance or the like labeled in the mobile phase solution, and the target chemical substance or the like is labeled with the target chemical substance or the like and a fluorescent substance as the labeling substance. Chemiluminescent substance, color substance, photochromic substance, or a combination with or reaction with a color change substance, and includes luminescence, color, light change, and color change due to fluorescence or chemiluminescence.
It is preferable that an absorption pad is provided in contact with the upper end of the porous stationary phase carrier. As a result, the amount of liquid that can be impregnated by the porous stationary phase carrier is increased, the saturation state where the capillary phenomenon stops is delayed, the movement distance in the fixed region of the solution due to the capillary phenomenon is increased, and Cleaning in the fixed area becomes possible. The absorbent pad is formed of the same material as the porous stationary phase carrier or a water absorbent such as a sponge or a super absorbent polymer.

  A second aspect of the invention is a chromatography chip in which the test substance fixing surface of the porous stationary phase carrier is arranged in parallel to the liquid suction and discharge direction.

  Here, the test substance fixing surface is preferably a flat surface having a maximum area formed on the porous stationary phase carrier. The thick tube of the dispensing tip is preferably formed in a rectangular tube shape, and is a thin rectangular tube in which the area of the side surface of the rectangular tube corresponding to the test substance fixing surface is maximized. Thereby, the optical state inside the dispensing tip can be reliably obtained from the outside of the side surface of the dispensing tip without suffering distortion due to the lens effect. The “suction / discharge direction” is the vertical direction when in use, and in the case of a nozzle-mounted dispensing tip, is the direction connecting the mouth and the mounting opening, or the axial direction of the dispensing tip.

  According to a third aspect of the present invention, there is provided an enclosing portion for enclosing the porous stationary phase carrier in a predetermined arrangement position in the dispensing tip so as to be in contact with the mobile phase solvent that has flowed into the dispensing tip. This is a chromatographic chip provided on the tip.

  As the enclosing portion, for example, it has a thin plate-like plate to which the porous stationary phase carrier is attached and supported, and the thin plate-like plate is inserted into the thick tube from the opening for mounting and the inner wall of the thick tube. It is preferable to attach using a frictional force between them or a step or an inclined surface of a transition portion between a thin tube and a thick tube. The predetermined arrangement position means, for example, that the plate is arranged in parallel with the liquid suction / discharge direction.

  According to a fourth aspect of the present invention, there is provided a mobile phase storage line drawn in a direction perpendicular to the suction / discharge direction at an interval in the suction / discharge direction on the test substance fixing surface of the porous stationary phase carrier, This is a chromatographic processing chip in which a predetermined area, a positive control line, and a negative control line are provided in order from the lower side to the upper side.

  Here, the “mobile phase storage line” is a portion indicating the liquid level of the liquid to be stored in the storage section necessary for bringing the mobile phase solvent moving along the test substance fixing surface into contact with the lower end thereof. It is. The “positive control line” is a part where a substance that is colored, luminescent, or discolored is fixed whenever the mobile phase solvent moves to this position. The “negative control line” is the part where the mobile phase solvent is Even if it moves to a position, it is a site where a substance that does not normally color (emission, discoloration, etc.) is fixed.

  According to a fifth aspect of the present invention, there is provided a processing head to which one or more dispensing tips capable of sucking and discharging a liquid by a suction and discharging mechanism can be mounted, and the processing head is mounted on the processing head. A suction / discharge mechanism for sucking and discharging liquid to the dispensing tip, one or more tip accommodating portions for accommodating one or more dispensing tips so as to be attachable to the processing head, and A container group having one or two or more liquid storage portions capable of storing or storing various liquids; and a moving means for moving the processing head relative to the container group; The tip is filled with a porous stationary phase carrier with a test substance immobilization surface on which a test substance that can adsorb, capture, or bind the target substance in the mobile phase solvent is provided. Was A chromatographic processing chip, the amount, time or position of suction or discharge of the suction / discharge mechanism, the structure of the chromatographic chip mounted on the processing head, the substance present in the mobile phase solution And at least one substance condition selected from the coordinate position including the type, concentration, amount of the mobile phase solution, the temperature of the mobile phase solution or porous stationary phase carrier, and the location of the mobile phase solution, and the treatment It is a chromatography processing apparatus which further has a control part controlled based on the contents.

  The liquid storage unit includes at least a sample storage unit that stores a sample, a liquid storage unit that stores a solution of a labeling substance such as a fluorescent substance and a gold colloid, or a mobile phase that moves these relative to a porous stationary phase carrier. It has a mobile phase solvent (developing liquid) storage section for storing a solvent and a developing liquid, a mobile phase solution storage section for storing a mobile phase solution obtained by mixing these, a liquid storage section for storing a cleaning liquid, and the like. .

6th invention is a chromatography processing apparatus which has a measurement part which optically measures the optical state in the said test substance fixed surface of the said porous stationary phase support | carrier enclosed with the said chip | tip for chromatography processing. .
As a premise, the porous stationary phase carrier is sealed so that the optical state of the test substance fixing surface can be measured from the outside of the side surface of the dispensing tip.

  According to a seventh aspect of the present invention, the light intensity of the fluorescent substance or the chemiluminescent substance labeled with the target substance bonded to the test substance fixed on the test substance fixing surface is measured based on the optical state on the test substance fixing face. It is a chromatography processing apparatus.

  Labeling with a fluorescent substance is performed by, for example, adding a fluorescent substance that can be chemically bonded to an amino group, SH group, aldehyde group, carboxyl group, hydroxyl group, or the like of a target substance, or a chemiluminescent compound such as an acridinium ester derivative. In some cases, the antibody or antigen is directly labeled.

  According to an eighth aspect of the present invention, the measuring unit is provided corresponding to the chromatography processing chip, and has a measuring end provided so as to be close to each of the test substance fixing surfaces. A plurality of light guides provided so that light obtained based on an optical state that can be generated by coupling on the substance fixing surface can be guided to a connection end, and the measurement ends of the plurality of light guides are Measurement provided to be movable relative to each of the test substance fixing surfaces so as to reach a predetermined measurement position of each corresponding test substance fixing surface of each chromatography processing chip at a predetermined scanning period. The plurality of light guides are sequentially selected and selected at a predetermined selection period while each measurement end is moved to the predetermined measurement position or stopped at the position by the measurement head and the measurement head. The connection end of the light guide A light guide path selection unit having a light guide region capable of emitting light incidentally connected thereto, a light receiving unit that sequentially receives and photoelectrically converts the light emitted from the light guide region, and the light receiving unit. A chromatographic processing apparatus comprising: a digital data conversion unit for converting the obtained image area data at the predetermined selection period to obtain digital data sequentially; and storage means for sequentially storing the digital data.

Here, “contact” includes close contact, close contact, or connection.
The “light receiving unit” refers to a sensor having one, a plurality, or a large number of light receiving elements. An example of a highly sensitive light-receiving element is the APD (avalanche photodiode) array made by Hamamatsu Photonics. As a special case where the arrangement density of the light receiving elements is high, for example, an “imaging sensor” such as a CCD image sensor or a CMOS image sensor is included. For example, the bit run BU-50LM (ICX415AL) is 6.4 × 4.8 mm and 772 × 580 pixels. By processing the image area data (analog signal) obtained by the light receiving element belonging to the light receiving unit, corresponding digital data can be obtained. These are formed by an integrated circuit (IC). “Image area data” is a set of data obtained from the light receiving unit in consideration of the arrangement of the light receiving elements, and when there is only one light receiving element in the light receiving unit, the pixel data If there are a large number of light receiving elements such as a plurality or about the above-mentioned number (772 × 580 pixels), it corresponds to image data.

  The “light receiving element” is an electronic element using a photoelectric effect, such as a photodiode or a phototransistor. Further, it includes a photon counting sensor having a multiplication effect such as the APD, a PMT, and the like.

  The “predetermined measurement position” is a position provided so as to correspond to the test substance fixing surface of each chromatography processing chip, and the measurement end performs a measurement on the test substance fixing surface, and at least each At least one or two or more are set for each fixed part so as to approach or come into contact with the fixed part (or measurement line) to which the test substance is fixed. Each fixed portion has a finite size, and the measurement end also has a finite size, and preferably has a size, shape, or predetermined measurement position that enables measurement of only one fixed portion. preferable. When a plurality of the predetermined measurement positions are set for one fixed part, the mutual distances between the adjacent predetermined measurement positions are set to be equal, as is the mutual distance between each of the adjacent fixed parts. It is preferable to do. For example, this is a case where the predetermined measurement positions are set every 0.1 mm when the fixed parts are arranged in a line at intervals of 1 mm. In this case, ten measurement values are set for one fixed part. As the number of the predetermined measurement positions is larger, more accurate measurement can be performed, but the time required for measurement is extended.

The “predetermined scanning period (ts)” is a time for the measurement end to move between adjacent predetermined measurement positions in the same chromatography chip and to perform measurement.
On the other hand, the “predetermined selection period” (tc) is for the light guide path selection unit to sequentially select each light guide path so that all of the plurality of light guide paths can be selected during the predetermined scanning period ts. Is the time. Accordingly, the predetermined selection period TC and the predetermined scanning period ts are correlated with each other, and the longest and therefore the best predetermined selection period TC is determined based on the predetermined scanning period ts and the number n of the chromatography processing chips. = Ts / n. That is, since the predetermined selection period is shorter than the predetermined scanning period, it is sufficient to photoelectrically convert the light received by the light receiving unit during the predetermined selection period and output the necessary area data. This is because it is preferable to set tc to be the longest length in order to ensure a sufficient length. Then, when the measurement end moves continuously for each chromatography processing chip, all light guide paths are selected while the measurement end moves to the next predetermined measurement position, and the measurement end Is moved intermittently to the predetermined measurement position, it is preferable that all light guides are selected while the measurement end is stopped at the predetermined measurement position.

  The predetermined scanning period and the predetermined selection period are the contents of the optical state to be measured, the coloration, the type of light emission (for example, the type of fluorescent material, the type of chemiluminescent material), the reagent used for coloration and light emission (reagents). (Including type and amount of reagent), number of measurement positions per chromatographic chip, mode of light emission (for example, instantaneous light emission, plateau light emission, light emission lifetime, stable light reception time, etc.), measurement Movement mode from the position to the next measurement position (when the measurement end scans the test substance fixing surface of the chromatography chip, intermittent operation, continuous operation, scanning speed, moving distance, moving time, stop time, Movement path, etc.), size of the fixed part, arrangement of the fixed part or number in the test substance fixing surface, etc., the number of chromatography processing chips, the size of the light guide part, the distance between the fixed parts, the light receiving part Characteristics, determined exposure time, and depending on the light measurement mode comprising one or more elements selected from the group, such as reaction time in the fixation site. In addition, data transfer or data read time (when CCD is used) may be considered. For example, when the amount of light is large as in the case of fluorescence, the predetermined scanning cycle is short, and the predetermined scanning cycle is lengthened as the amount of light decreases.

  For example, in the case of plateau-shaped chemiluminescence, the stable light reception time (T) during which the plateau is maintained, the number of fixed sites (m) (m is a natural number), the number of predetermined measurement positions per fixed site (light reception) (Number of times) (ν) (ν is a natural number), and the predetermined scanning period (ts) is T / (m · ν). Within this period, from the predetermined measurement position to the next predetermined measurement position in each chromatography chip. And the time for the digital conversion at the predetermined measurement position.

  Then, as the longest “predetermined selection period” (tc), since all the light guide paths are selected once, the predetermined scan period ts is ts / n divided by the number of light guide paths (n). Each light guide is selected in a cycle. Therefore, when the predetermined scanning cycle is ts = T / (m · ν), the predetermined selection cycle tc is T / (m · ν · n), and all the light guide paths are performed once in the predetermined selection cycle. Will be selected. Therefore, the number of times of light reception is ν · n times for each fixed part. When sufficient light receiving time can be taken, it is preferable that selection is performed a plurality of times for each fixed part.

  More specifically, for example, the processing head has 16 (= n) chromatographic chips, and each chromatographic chip has a 50 mm (= m) test length in the vertical direction. When there is a substance fixing surface and each fixed part is 1 mm in the vertical direction, when five predetermined measurement positions are set every 0.2 mm for each fixed part (ν = 5) If the scanning is continuously performed and the light reception stabilization time T is 200 seconds, the predetermined scanning period ts is ts = 200 / (50 × 5) = 0.8 seconds. Then, the predetermined selection period tc is tc = ts / 16 = 50 msec. This time needs to be a time when the light receiving unit receives light and can perform photoelectric conversion. As a result, the 800 mm test substance fixed surface as a whole can be accurately and optically measured in about 3 minutes.

  For example, in the case of a CCD image sensor, the “digital data conversion unit” includes a shift register, an amplifier, and an AD converter that can be controlled by a gate, depending on the intensity or luminance of light received by the light receiving element. In the case of a PMT photon counting sensor that generates a predetermined number of photons or a photon counting sensor using a semiconductor, it has a pulse counter capable of gate control as a photon counter, and is formed of an IC circuit in the same manner as a light receiving element array. The These operate at a predetermined scanning cycle obtained based on the light measurement mode in accordance with an instruction from a measurement control unit described later.

  The generated digital data is stored in a storage unit of a semiconductor storage element such as a DRAM, and digital data obtained by converting image area data of one or more light receiving elements corresponding to the light receiving unit at a predetermined selection cycle by arithmetic processing. Based on this, the temporal change in the brightness of the optical state is derived and analyzed. The “predetermined selection cycle” is, for example, an instruction signal such as a pulse signal output by an instruction of a measurement control unit provided in an information processing unit having a drive unit or a CPU, a program, and a memory that generates a pulse signal in the cycle. Set based on.

  The “light receiving part” has at least one light receiving element. In the case where at least three light receiving elements are provided, color light reception can be made based on light received through the color filter (RGB) for each light receiving element. The number and type of the light receiving elements are the size or sensitivity of the light receiving elements, the size and shape of the connection end of the light guide, the interval of the connection time, the interval between the emission end and the light receiving surface, which will be described later, Depends on the shape or aspect of the optical state.

  The “digital data” is data that can be processed by an information processing apparatus such as a CPU, for example, and represents numerical values. For example, when there are many light receiving elements in the light receiving unit, the data can be stored in the storage means by compression, thinning out image area data, or the like. The storage means is a memory for recording data, and is a semiconductor memory, a hard disk, a CD, a DVD, an SSD, a Blu-ray disc, or the like.

  The “light guide” includes, for example, a cavity, an optical system element such as a lens, an optical fiber, and the like. The optical fiber is, for example, a plastic optical fiber that can handle visible light having an outer diameter of 500 μm. The optical fiber also includes an optical fiber bundle in which a plurality of optical fibers are bundled. At least a part of the light guide path is preferably flexible.

  When the optical state is “fluorescence”, it is a light guide for irradiating the fixed part with excitation light, and is close to or in contact with one of the chromatography processing chips provided in the processing head. It is preferable to have a second light guide path having an irradiation end provided so as to be close to or in contact with, and a connection end provided so as to be close to or in contact with the light source surface of the excitation light source. Further, when the optical state is “coloration”, the optical path is a light guide for irradiating each of the fixed parts with visible light, and is close to the chromatographic processing chip of the processing head 1 or It is preferable to have a third light guide path having an irradiation end that is in contact with or close to or in contact with, and a connection end that is in proximity to or in contact with the light source surface of the visible light source. In these cases, it is preferable that the measurement end is bundled with the irradiation end and the tip aligned and handled as the measurement end.

  The “light receiving surface” is a surface formed by arranging light receiving portions of the light receiving elements, and is fine in the case of an image sensor and rough in the case of an ADP array. The stored digital data is read and analyzed by the analysis means of the information processing unit such as a CPU, and the target chemical substance is inspected.

  The light guide path selection unit further includes a light absorption area that can absorb light from an unselected light guide path other than the selected light guide path, and the light guide area is connected to the selected light guide path. It is preferable that the light absorption region is provided so as to be optically connected to each connection end of the light guide path that is not selected when optically connected to the end.

  Here, the “light-absorbing region” is a region in which reflection and scattering of light can be prevented or reduced by allowing light from the light guide path to be absorbed. The light absorption region is surrounded by a boundary line or a wall surface so that the light guide region exists, does not penetrate or intersect, and has a light shielding property from the outside except for a flat portion or an opening optically connected to the connection end. It is preferable that the region is partitioned. For example, a planar region having a shape and an area including the connection end coated with a black dye, or an opening having a shape and an area including the connection end and extending in a direction opposite to the connection end. A formed depression, recess, groove, tube or cavity. A portion other than the connection end of the connection end array plate is formed with a light shielding surface having a light shielding property, and the planar region and the opening are connected to a portion other than the connection end and the light shield surface of the connection end array plate. There is no connection. The wall surface in the recess, recess, groove, tube, or cavity is formed of a light-shielding material such as metal or resin, and a black fibrous material, such as carbonized cotton, coated with black dye or carbonized inside. It is preferable to be accommodated in

  With this configuration, the selected light guide path reliably guides the light emitted from the connection end to the light receiving surface of the light receiving unit, while the light guide paths that are not selected are simply shielded. In addition, by absorbing light from the light guide path, it is possible to reliably prevent the intrusion of the miscellaneous light generated based on reflection and scattering of the light into the light receiving unit, and to perform highly reliable measurement. .

  According to a ninth aspect of the present invention, there is provided a magnetic mechanism capable of applying and removing a magnetic force in a dispensing tip attached to the processing head and / or the dispensing tip or chromatographic processing attached to the processing head. The chromatography processing apparatus is provided with a temperature raising / lowering body that is provided so as to approach or be accessible to the outside of the chip and raises and lowers the temperature by an external signal, and is controlled by the control unit.

  According to a tenth aspect of the present invention, there is provided a thin tube having a mouth portion at the lower end thereof, which is inserted into a container and in which liquid is sucked and discharged, and a thick tube provided with a storage portion for storing the sucked liquid in communication with the thin tube. A test substance capable of adsorbing, capturing, separating, or binding the target substance in the aspirated mobile phase solution is placed in a predetermined region within the thick tube of the translucent dispensing tip having Mounted on a processing head equipped with a suction / discharge mechanism that enables suction and discharge of liquid to a chromatographic processing chip enclosing a porous stationary phase carrier provided with a fixed fixed substance for testing. , The amount, time or position of suction or discharge of the suction / discharge mechanism, the structure of the chromatographic chip mounted on the processing head, the type, concentration, and movement of the substance present in the mobile phase solution Compatible By controlling the amount of the mobile phase solution or the temperature of the porous stationary phase carrier and at least one substance condition selected from the coordinate positions including the storage position of the mobile phase solution, and the processing content The chromatography chip is moved relatively to at least the liquid storage part in which the mobile phase solution is stored, and the porous stationary phase carrier and at least the mobile phase solution are brought into contact with each other for chromatography. A chromatographic processing method for performing a graphic processing. The mobile phase solution is labeled with a target chemical substance or the like contained in the mobile phase solution before the chromatography step. Therefore, it is not necessary to prepare a labeling substance in advance on the porous stationary phase carrier so that it can bind to the target chemical substance in the mobile phase solution.

  In an eleventh aspect of the present invention, in the execution step of the chromatography method, the mobile phase solution is sucked to a predetermined position of the reservoir portion of the chromatography chip by the suction / discharge mechanism. A certain amount of liquid is brought into contact with the lower end of the carrier to move the mobile phase solution along the test substance immobilizing surface, and the residual liquid of the mobile phase solution is discharged from the chromatography chip, and the chromatography treatment is performed. The chip is moved to the liquid storage part in which the developing liquid and / or the cleaning liquid is stored by the moving means, and the porous liquid is fixed by sucking the developing liquid and / or the cleaning liquid to the storage part by the suction / discharge mechanism. A chromatograph in which a constant liquid amount is brought into contact with the lower end of the phase carrier, and the developing solution and / or the washing solution is brought into contact with the test substance fixing surface. It is over processing method.

  Here, by bringing the “developing solution” or mobile phase solvent into contact with the porous stationary phase carrier, the mobile phase solution can be further moved to the extent that it passes through the entire stationary region, and the mobile phase solution It is possible to reliably bind the target substance in the test substance to the test substance, and to perform processing with high quantitativeness. Similarly, by bringing the “washing solution” into contact with the porous stationary phase carrier, the labeling substance that is not bound to the test substance can be excluded from the immobilization region, and a highly quantitative measurement can be performed. Will be able to do.

A twelfth aspect of the invention is a chromatography processing method for optically measuring the test substance immobilization surface of a porous stationary phase carrier enclosed in the chromatography chip after the chromatography processing execution step. .
As a premise, the porous stationary phase carrier is sealed so that the optical state of the test substance fixing surface can be measured from the outside of the side surface of the dispensing tip.

  According to a thirteenth aspect of the present invention, the optical state on the test substance fixing surface is bonded to a test substance fixed on the test substance fixing face among target substances labeled with a fluorescent substance or a chemiluminescent substance. The chromatographic treatment method is the emission intensity of the fluorescent substance or chemiluminescent substance labeled with the target substance.

  According to the present invention, precise and quantitative measurement is possible by allowing the measurement of luminescence in the chromatographic process.

  In a fourteenth aspect of the invention, in the measurement step, light based on an optical state generated by a reaction in each chromatography processing chip is transmitted to a plurality of light guides provided corresponding to each chromatography processing chip. Scanning in which each measurement end is moved relative to the test substance fixing surface of the porous stationary phase carrier so as to arrive at a predetermined measurement position corresponding to each test substance fixing surface at a predetermined scan period. And while the measurement end is moved to or stopped at the measurement position of the detection substance fixing surface of each chromatography processing chip, all of the plurality of light guide paths are all moved to the predetermined position. A light guide path selection step that sequentially selects at a selection cycle, and allows light from the connection end of the selected light guide path to be emitted to the light receiving surface of the light receiving unit; and light emitted from the selected light guide path sequentially. Receiving A chromatographic processing method comprising: a light receiving process in which the light is received and photoelectrically converted by the unit; and a digital data conversion process in which the image area data obtained from the light receiving unit is sequentially converted into digital data at the predetermined selection period and sequentially stored. .

  According to a fifteenth aspect of the present invention, there is provided a step of applying a magnetic force to a dispensing tip attached to the processing head by a magnetic force mechanism to remove, or the dispensing tip or chromatography processing tip attached to the processing head. It is the chromatography processing method which further has the process of making the temperature raising / lowering body which raises / lowers temperature with the signal from the outside with respect to the outer side of this.

  According to the first invention, the fifth invention, and the tenth invention, the mobile phase solvent is sucked and discharged to the porous stationary phase carrier by enclosing the porous stationary phase carrier in the dispensing tip. By making contact possible in the dispensing tip, it is possible to reduce the burden on the user and prevent cross-contamination due to a contact accident to the stationary phase or the mobile phase by the user and perform highly reliable processing. .

  Furthermore, it is possible to perform a plurality of processes in parallel and perform them at the same time, thereby performing highly efficient processes. Therefore, processing time can be shortened and processing can be performed quickly.

  According to the present invention, it is possible to consistently and automatically perform from the attachment of the chromatography chip to the processing head to the chromatography process and measurement without touching the dispensing chip itself, Therefore, highly reliable processing can be performed.

  According to the second invention, by disposing the test substance fixing surface in parallel with the suction and discharge direction, suction and discharge is not hindered by the test substance fixing surface, and from the outside through the side surface of the dispensing tip. The optical state generated on the test substance fixing surface can be reliably measured.

  According to the third invention, the porous stationary phase carrier is encapsulated in the dispensing tip by using the enclosing portion, so that even a thin plate or flexible porous stationary phase carrier can be reliably obtained. Can be enclosed in a dispensing tip.

  According to the fourth invention, it is possible to easily set the mobile phase solvent so that a predetermined amount that reaches the mobile phase storage line can be set, and a highly reliable and highly quantitative process can be performed. Will be able to do.

  According to the sixth invention or the twelfth invention, the porous stationary phase carrier is enclosed in the dispensing tip, and the mobile phase solvent in an amount determined by the suction / discharge mechanism can be supplied to the stationary phase carrier. In addition, by labeling the target substance in the mobile phase solvent and performing a predetermined washing treatment, etc., by measuring the optical state such as coloration of the test substance fixing surface, not only qualitative measurement results The quantitative measurement result can also be obtained. As a result, the number of liquid storage units, the work area, and the processing procedure can be reduced.

  According to the seventh invention or the thirteenth invention, the target substance labeled with the fluorescent substance or the chemiluminescent substance in the chromatography chip can be combined with the test substance, so that the optical state is obtained. By measuring the emission intensity, precise and reliable measurement can be performed, so that quantitative measurement can be performed beyond qualitative measurement.

  According to the eighth invention or the fourteenth invention, for each of the plurality of chromatographic processing chips, the light guides provided corresponding to the respective chromatographic processing chips are sequentially selected, and each chromatographic process is selected. The light based on the optical state generated by the chip for use is guided to the one light receiving part to be guided and received, so that the reactions simultaneously performed by a large number of chromatographic processing chips can be converted into digital data using the one light receiving part. It can be analyzed by converting to. Therefore, since the spatial and temporal changes in the optical state of each of the plurality of chromatography processing chips are received by one light receiving unit, it can be temporally and spatially integrated and measured. In addition to suppressing expansion, highly reliable processing can be performed quickly and efficiently.

  Reduces the number of expensive light receiving units by receiving light with one light receiving unit by switching between chromatographic processing chips as well as moving or scanning between fixed sites in each chromatographic processing chip Thus, an inexpensive device can be provided.

  Since each chromatography chip can be processed and measured independently and in parallel, the chromatographic chips are physically separated from each other as compared to the case where the entire fixed part is handled collectively, or By shielding light between each chromatographic chip, it eliminates the optical effects between adjacent chromatographic chips and performs more reliable processing. Simultaneous and parallel processing allows efficient and quick processing. It can be carried out.

  A large number of fixed sites are divided into each chromatography processing chip, a predetermined measurement position is set for the corresponding fixed site belonging to each chromatography processing chip, and the measurement end is moved at a predetermined scanning period. Since the light guide corresponding to the chromatographic processing chip is sequentially switched and optically connected to one light receiving unit at a predetermined selection period associated with the predetermined scanning period, it is possible to measure a large number of fixed parts. In spite of the fact, from scanning to digital data conversion is performed in an orderly manner using one light receiving unit. Therefore, the change in the number of chromatography processing chips and the number of fixed parts can be easily dealt with by changing the predetermined scanning period and the predetermined selection period, and the flexibility and versatility are high.

  According to the ninth or fifteenth invention, the temperature is controlled by bringing the temperature raising and lowering body closer in the dispensing tip, so that the target substance in the mobile phase solvent and the porous stationary phase carrier are fixed. The reaction with the test substance can be promoted, so that the reaction time can be shortened and highly efficient processing can be performed. In addition, by providing a magnetic mechanism, by separating the target substance from the sample using magnetic particles, it is possible to consistently process from extraction to measurement with one apparatus, so that the efficiency is high.

  According to the eleventh aspect of the present invention, the developing solution and / or the cleaning solution can be automatically and easily brought into contact with the porous stationary phase carrier, so that the target substance in the mobile phase solution can be reliably transferred to the test substance. In addition to being able to move and bind, a labeled substance that is not bound to the test substance can be excluded from the fixed region, and a precise and highly quantitative measurement can be performed.

It is a block diagram which shows the chromatography processing apparatus which concerns on embodiment of this invention. It is a block diagram which shows the chromatography processing apparatus which concerns on the 1st Example of embodiment of this invention. It is an external appearance perspective view which shows the example which actualized the chromatography processing apparatus shown in FIG. 2 more. It is a perspective view which expands and shows the chip | tip for a chromatography process shown in the chromatography apparatus shown in FIG. It is a perspective view which shows the principal part of the chromatography processing apparatus shown in FIG. It is operation | movement explanatory drawing of the chromatography processing apparatus shown in FIG. It is operation | movement explanatory drawing in the extraction process of the chromatography processing apparatus shown in FIG. It is operation | movement explanatory drawing at the time of temperature control of the chromatography processing apparatus shown in FIG. It is a perspective view of the principal part which shows the other example of the chromatography processing apparatus shown in FIG. It is operation | movement explanatory drawing of the chromatography processing apparatus shown in FIG. It is operation | movement explanatory drawing at the time of temperature control of the chromatography processing apparatus shown in FIG. It is a block diagram which shows the chromatography processing apparatus which concerns on the 2nd Example of embodiment of this invention. It is a side view which shows more specifically the measurement part of the chromatography processing apparatus shown in FIG.

  Next, the chromatography apparatus 10 according to the first embodiment of the present invention will be described with reference to FIGS.

FIG. 1 is a block diagram showing the chromatography apparatus 10.
The chromatographic processing apparatus 10 is roughly classified into samples such as serum, plasma, whole blood, stool, urine and the like collected from a subject, gold colloid, platinum = gold colloid, fluorescent substance, chemiluminescent substance and other labeled substances. , A plurality of solutions containing various solutions such as a physiological saline solution and a buffer solution as a solvent, a cleaning solution and a developing solution, and various dispensing tips 4 ₁ to 4 _n and chromatographic processing tips 8 ₁ to 8 _n. The container group 3 having the accommodating part groups 3 _{1 to} 3 _{n in} which the parts 3a to 3c are arranged in n rows on the stage along the Y-axis direction, and a horizontal direction with respect to the container group 3, for example, the Y-axis direction A plurality of (n in this example) translucent tips 4 ₁ to 4 _n are provided so as to be relatively movable along the X axis and capable of sucking and discharging liquid by the suction and discharging mechanism 43. Previously mounted to be aligned in the direction A processing head 7 in which a mouth portion at the front end can be inserted into each housing portion, and a processing head that is relatively movable between the processing head 7 and the container group 3 at least along the Y-axis direction. The head moving mechanism 52 and the chromatographic chips 8 ₁ to 8 _n are enclosed in the thick pipes to adsorb, capture, separate, or bind the target substance in the sucked mobile phase solvent. Porous stationary phase carriers 2 ₁ to 2 _n formed of, for example, a nitrocellulose membrane, a CPU + program + memory 9 as a so-called information processing unit that performs information processing for various controls, and the CPU + program + And an operation panel 14 for performing operations such as user instructions for the memory 9.

The processing head 7 optically measures the porous stationary phase carriers 2 ₁ to 2 _n enclosed in the chromatography processing chips 8 ₁ to 8 _n provided and attached to the processing head 7. Measuring part 6 or a part thereof. The measuring unit 6 includes one measuring end, a measuring device having a light receiving element such as one PMT optically connected to the measuring end, and the X-axis direction and the Z-axis direction or the X-axis direction only. A measuring instrument moving mechanism provided so as to be sequentially accessible to each of the chromatography chips 8 ₁ to 8 _n arranged by moving the measuring instrument (first embodiment). Alternatively, as another example, a measurement end support provided with a plurality of measurement ends for each of the chromatography chips 8 ₁ to 8 _n and the measurement end support are moved closer to or away from each other by moving in the Z-axis direction. And a measurement end moving mechanism that enables the measurement end to move in the Z-axis direction so as to be sequentially and simultaneously close to the encapsulated porous stationary phase carrier (second embodiment) ). Furthermore, it is conceivable to provide not only the measurement end but also a light receiving part such as PMT for each of the chromatography chips 8 ₁ to 8 _n .

As described above, the processing head 7 has a suction / discharge mechanism 43 that performs suction / discharge of liquid to the dispensing tips 4 ₁ to 4 _n and the chromatography processing chips 8 ₁ to 8 _n , The dispensing tips and the chromatography chips are arranged and supported on the dispensing tip support member 45 at intervals according to the arrangement of the container group 3 along the X-axis direction. In the dispensing tip support member 45, for example, each nozzle communicating with the suction / discharge mechanism 43 is arranged, and the dispensing tips 4 ₁ to 4 _n and the chromatography chips 8 ₁ to 8 _n are It is attached to and supported by the lower end of the nozzle. The suction / discharge mechanism includes a desorption mechanism (42, see FIG. 5) for desorbing the dispensing tip and the chromatographic treatment tip from the nozzle.

  As another example, when a modified dispensing tip and a modified chromatography chip are used for the dispensing tip, the modified dispensing tip and the modified chromatograph are used to suck and discharge liquid. It has a movable mechanism including a deformable element of the chip for graphic processing, a vertically movable rod for deforming the deformable wall, a motor for moving the arm, and the like. In this case, the deformable dispensing tip and the modified chromatographic processing tip are detachably attached to these indicating members.

Further, the processing head 7 is provided for moving the dispensing tips 4 ₁ to 4 _n or the chromatography tips 8 ₁ to 8 _n supported by the dispensing tips 4 ₁ to 4 _n all at once in the Z-axis direction. The injection tip Z-axis moving mechanism 53 and the liquid sucked into the dispensing tips 4 ₁ to 4 _n or the porous stationary phase carriers 2 ₁ to 2 enclosed in the chromatography chips 8 ₁ to 8 _n a temperature elevating body 48 for controlling the temperature of _{n, and} the temperature elevating body 48 is moved forward or backward to bring the temperature elevating body 48 close to or in contact with each of the chromatography chips 8 ₁ to 8 _n. a temperature controller 48a for controlling the raising and lowering of the temperature of the lifting body forward and backward driving mechanism 48b, and the temperature raising and lowering body 48 for causing, for applying a force to said dispensing tip 4 within _one to 4 _n And a magnetic force mechanism 44 of the eye. The processing head moving mechanism 52 and the dispensing tip Z-axis moving mechanism 53 constitute moving means 5 for the dispensing tips 4 ₁ to 4 _n and the chromatography processing chips 8 ₁ to 8 _n .

  In the CPU + program + memory 9, the temperature controller 48a, the lifting / lowering body advancing / retracting drive mechanism 48b, the suction / discharge mechanism 43 (including the detaching mechanism 42), the moving means 5 and the magnetic force mechanism 44 are instructed to perform extraction or reaction. The extraction / reaction control unit 91 for performing the measurement, the measurement unit 6, the moving unit 5, the storage unit 93, and the measurement control unit 92 for instructing the analysis unit 94 to perform measurement, and the data from the measurement unit are stored. Storage means 93 and analysis means 94 for analyzing the measurement by calculation based on digital data stored in the storage means 93 are provided.

  Next, a chromatography processing apparatus 100 in which the measurement unit 6 is more specific to the chromatography processing apparatus 10 according to the embodiment of the present invention described in FIG. 1 will be described with reference to FIGS.

In the chromatography apparatus 100, the measuring unit 6 includes a measuring instrument support 6b connected to the dispensing tip support member 45, and a measuring instrument 6a supported slidably on the measuring instrument support 6b. And a measuring instrument moving mechanism for moving the measuring end of the measuring instrument 6a slidably supported by the measuring instrument support 6b to the chromatographic processing chips 8 ₁ to 8 _n along the X-axis direction. 6c. Whether the measurement end includes only the light receiving end or the irradiation end depending on the state of the optical state generated on the test substance fixing surface of the porous stationary phase carrier of the chromatography chips 8 ₁ to 8 _n . The type of light to be irradiated by the irradiation end is determined. That is, when the optical state is colored, predetermined visible light is irradiated, and in the case of light emission by fluorescence, the corresponding excitation light is irradiated. In the case of chemiluminescence, only the light receiving end is assumed.

  Subsequently, based on FIGS. 3 to 8, the chromatography processing apparatuses 101 and 102 that further embody the chromatography processing apparatus 100 according to the first embodiment described in FIG. 2 will be described.

FIG. 3 shows the appearance of the chromatography processing apparatus 101.
The apparatus 101 is incorporated in the housing 11. The casing 11 includes a main body 12 in which a processing head 71 and a container group 31 which are main parts of the apparatus 101 are incorporated, and a lid 13 provided on the upper side so as to be openable and closable. Indicates a touch panel tablet wirelessly connected to the main body as an operation panel. Reference numeral 81 ₄ denotes a chromatography chip mounted on the processing head 71.

  FIG. 4 shows the chromatographic processing chip 81 of the chromatography processing apparatus 101 in detail.

  As shown in FIG. 4, the chromatography chip 81 is obtained by enclosing a porous stationary phase carrier 21 in a dispensing chip 41. The dispensing tip 41 is a tapered cylindrical thin tube 41a, a thick tube 41b communicating with the thin tube 41a via a transition portion 41e, a tip provided at the tip of the thin tube 41a, and can be inserted into a container. Nozzle communicating with a suction / discharge mechanism provided for suction / discharge of gas and a suction / discharge mechanism provided in a cylindrical mounting tube 41h formed thicker than the thick tube 41b above the thick tube 41b. (43a, see FIG. 6) a plurality of mounting openings 41c provided along the outer periphery of the outer surface of the mounting pipe 41h on the upper side of the thick pipe 41b provided with the mounting opening 41c. It has a protrusion 41d extending in the vertical direction of the book, and a pyramidal transition portion 41e provided between the narrow tube 41a and the thick tube 41b.

  The portion excluding the mounting tube 41h on the upper side of the thick tube 41b is formed in a thin prismatic shape, and the porous stationary phase carrier 21 is enclosed inside. Thus, the test substance fixing surface 21a of the porous stationary phase carrier 21 enclosed in the thick tube 41b can be reliably measured from the outside of the thick tube 41b without distortion based on the lens effect. .

  The lower end of the porous stationary phase carrier 21 is inserted into a storage part 41g provided on the lower side of the thick tube 41b, and can come into contact with the liquid sucked into the storage part 41g. On the test substance fixing surface 21a, a mobile phase storage line 21b, a positive control line 21d, and a negative control line 21e indicating the level of liquid to be sucked into the storage portion 41g are provided from the lower side to the upper side. In order, each is drawn horizontally. Furthermore, between the mobile phase storage line 21b and the positive control line 21d, one or more test substances are fixed to any one of a plurality of fixed parts set in advance at intervals ( In this example, 3) fixed portions 21c are drawn in the horizontal direction. The upper side of the porous stationary phase carrier 21 is in contact with or connected to the absorption pad 21f, and the upper side of the absorption pad 21f is provided with a filter 21g through which only gas can pass. The whole of the porous stationary phase carrier 21 is supported on the lower surface of the transition portion 41e as the enclosing portion, and supported on the upper surface by the inclined surface between the thick tube 41b and the mounting tube 41h. The thin plate-like plastic plate 21h is pasted and supported.

  FIG. 5 shows the chromatographic processing apparatus 101 shown in FIG.

The chromatographic processing apparatus 101 generally includes a cartridge container 31 in which a plurality of storage portions arranged in a row so as to extend along the Y-axis direction are arranged in a plurality of rows (in this example, four rows) in the X-axis direction. _{1 to 3-4} , a plurality of container groups 31 and a plurality of container groups 31 that can be moved relative to the container group 31 in the horizontal direction, for example, in the Y-axis direction, and can suck and discharge liquid by the suction and discharge mechanism 431. number nozzles of the suction and discharge mechanism 431 as the dispensing tip ₄₁ 1-41 ₄ or chromatography chip ₈₁ 1-81 ₄ having translucency (in this four in the example) are arranged in the X-axis direction 43a, each of which is attached to each of the accommodating portions and has a mouth at the tip of which can be inserted, and a space between the processing head 71 and the container group 31 is at least along the Y-axis direction. A timing belt and mechanism of the pulley such as a processing head moving mechanism 52 to be movable pairs manner, the chromatography chip 81 sealed in the _{1-81 4} thick tube 41b, aspirated mobile phase solution the target substance adsorbed in, captured, and separate porous stationary phase carriers 21 ₁ to 21 ₄ or formed by nitrocellulose membrane or the like that enables binding, provided on the processing head 71 , having a measuring unit 61 for measuring a porous stationary phase carrier ₂₁ 1 to 21 ₄ which has been sealed in the chromatography chip ₈₁ 1-81 ₄ mounted on the processing head 71 optically.

Serum each cartridge container 31 _{1-31 4} of the container group 31, as also shown in FIG. 6, in order to identify the bacterial or viral infection the subject has been ill, taken from a subject , A sample storage unit 31g for storing samples such as plasma, whole blood, body fluid, etc. (first liquid storage unit, the order is in the liquid storage unit group 31b), and a magnetic particle suspension used for collecting bacteria, etc. Part (second liquid storage part), storage part (third liquid storage part) containing 40 μL of protein-denaturing enzyme solution (Lysis 1) for crushing bacteria and cells, and proteolytic enzyme solution (Lysis 2) A storage part (fourth liquid storage part) for storing 200 μL, a storage part (fifth liquid storage part, sixth liquid storage part) for storing 500 μL of the separated extract (binding buffer solution, NaCl, SDS, isopropanol), Container (seventh liquid) for storing 700μL of cleaning liquid (water, isopropanol) A container, an eighth liquid storage part), a dissociation liquid (tenth liquid storage part), a temperature-controllable reaction vessel 31f (a ninth liquid storage part), and a mobile phase solvent (developing liquid, washing liquid). 10 mL storage part storage part (11th liquid storage part, 12th liquid storage part), liquid storage part group 31b consisting of PCR solution storage part (13th liquid storage part), and said chromatography processing chip 81 _{1 to} 81 ₄ , dispensing tips 41 _{1 to} 41 ₄ , perforating tips 46 are accommodated or can be accommodated such that the mounting openings of the respective chips are on the upper side, and extracted nucleic acids a PCR reaction vessel for 31c for amplifying a, a lid housing portion 31e for accommodating a sealing lid for sealing the opening of the temperature-controllable PCR container 31c, a cross by splashing between the cartridge container ₃₁ 1-31 ₄ adjacent Contamination Each cartridge container 31 _{1-31 4} more lines in parallel to the X-axis direction (four columns in this example) arranged containers group 31 on the stage extending in series form in the Y-axis direction, each having a partition wall 31d for preventing Or it has in the main-body part 12. FIG.

The suction / discharge mechanism 431 of the processing head 71 includes a cylinder 43b in which a plunger is slidable, and the dispensing tips 41 _{1 to} 41 ₄ and a chromatography processing tip provided at the lower end of the cylinder 43b. 81 _1-81 fitting opening and the nozzle 43a can be mounted in _4, wherein the has an inner diameter larger than the nozzle 43a of the dispensing tip ₄₁ 1-41 ₄ and chromatographed chip ₈₁ 1-81 ₄ A desorption mechanism 42 having a notch portion 42a having an inner diameter smaller than the outer diameter of the mounting tube 41h on the upper side of the thick tube 41b and a demounting member 42b provided with the notch portion 42a, the cylinder 43b and the inside of the cylinder 43b A dispensing tip support member 451 for supporting a cylinder driving mechanism for reciprocating a plunger sliding on the The dispensing chip supporting member 451 and a dispensing tip Z-axis driving mechanism 531 to be movable along the Z-axis direction.

When the plunger is pushed down by the cylinder driving mechanism to a range exceeding the suction / discharge range of the plunger, the upper end of the detaching member 42b is also pushed down by the cylinder driving mechanism. 41 _{1-41 4} or desorbing chromatographed chip ₈₁ 1-81 _4.

Wherein the processing head 71, the porous further measuring unit 61 is enclosed in the chip supporting member 451 to the support by being attached to the processing head 71 has been chromatographed chip 81 _{1-81 4} normal substance for detection fixed surface 21a of the stationary phase carriers ₂₁ 1 to 21 ₄ is mounted to face the Y-axis direction. The measurement unit 61, the irradiation light to the light receiving end and the detection substance fixing surface 21a for receiving the optical state caused by the detection substance fixing surface 21a of the chromatography chip 81 _{1-81 4} A measurement end 61a composed of an irradiation end for irradiation and a light guide path for supporting the measurement end 61a, guiding the irradiation light to the irradiation end, and guiding the light from the light receiving end to the light receiving portion are provided inside. It has a measuring end support arm 61b as a measuring instrument support 6b, and a slide mechanism 61c as a measuring instrument moving mechanism 6c that slides the measuring end support arm 61b along the X-axis direction. Here, the “irradiation light” is, for example, excitation light when the optical state is fluorescence, and visible light when the optical state is color.

Further, the processing head 71 is provided with a magnetic force mechanism 44 for exerting a magnetic force in the dispensing tips 41 _{1 to} 41 ₄ attached to the nozzles. The magnetic mechanism 44 supports, for example, n (in this example, four) permanent magnets 441 arranged at intervals corresponding to the arrangement of the dispensing tips 41 _{1 to} 41 ₄ and the n permanent magnets. A magnet array member 442 to be moved, and the magnet array member 442 are provided along the X-axis direction along the Y-axis direction for performing a forward / backward movement with respect to the dispensing tip, and one end is pivotally supported by the magnet array member. A ball screw whose other end is pivotally supported by a ball screw shaft support plate, and a motor that rotationally drives a nut portion that engages with the ball screw, and is supported by the processing head 71, and the ball screw is And at least an actuator 443 that moves in the front-rear direction along the axial direction (see FIG. 7). Further, the processing head 71 has a liquid sucked into the dispensing tips 4 ₁ to 4 _n or a porous stationary phase carrier 2 ₁ to 2 sealed in the chromatography chips 8 ₁ to 8 _n. 2 _n for controlling the temperature of _n, the temperature elevating body 481 is moved forward to bring the temperature elevating body 481 close to or in contact with each of the chromatographic chips 8 ₁ to 8 _n etc. Or it has the raising / lowering body advancing / retreating drive mechanism for making it reverse, and the temperature controller for controlling the temperature rise / fall of the temperature raising / lowering body 481 (refer FIG. 8).

Next, the operation of the chromatography processing apparatus 101 will be described with reference to FIGS. Here, a test is performed to determine whether or not there is a bacterium that causes a predetermined infectious disease from the subject's sample. Steps S1 to S9 correspond to a nucleic acid extraction step.
In step S1, the start of the infectious disease inspection process is instructed by operating the touch panel of the operation panel 14 or the like.

In step S2, the extraction / reaction control unit 91 provided in the CPU + program + memory 9 of the chromatography processing apparatus 101 instructs the processing head moving mechanism 52 to move the processing head 71 in the Y-axis direction. along moved, the cartridge container 31 _{1-31 4} of the by driving the pipette tip Z-axis moving mechanism 531 after position above the chip accommodation portion group 31a to be accommodated drilling tip 46 nozzle 43a The drilling tip 46 is mounted and lifted, and the punching tip 46 is moved by the processing head moving mechanism 52 to above the second liquid storage portion of the liquid storage portion group 31b of the container group 31. Is positioned and lowered by the dispensing tip Z-axis moving mechanism 53 to perforate a film covering the opening of the liquid container, and in the same manner, The de 71 is moved in the Y-axis direction sequentially drilling the other liquid storage portion and the reaction vessel of the liquid accommodating portion 31b.

In step S3, the piercing tip 46 is detached from the original tip accommodating portion 31a using the detaching member 42, and then the processing head 71 is moved along the Y-axis direction to the dispensing tips 41 _{1 to} 41. ₄ is moved to the tip accommodating portion group 31a in which the nozzle ₄ is accommodated, and the nozzle 43a is lowered by the dispensing tip Z-axis moving mechanism 531, whereby the dispensing tips 41 _{1 to} 41 ₄ are used for processing through the nozzle 43a. Mount on the head 71. Next, after being raised by the dispensing tip Z-axis moving mechanism 531, the dispensing tips 41 _{1 to} 41 ₄ are moved along the Y-axis by the processing head moving mechanism 52, and the parent sample is accommodated. after moving to the in which the sample accommodating portion 31 g (first liquid storage portion), dispensing with chip Z-axis moving mechanism 531, and lowered by inserting the mouth of the dispensing tips 41 _{1-41 4,} The sample liquid accommodated in the sample container 31g is lifted and lowered by the suction / discharge mechanism 431, and then the sample liquid is suspended in the liquid by repeating the suction / discharge. dispense aspirated into tip ₄₁ 1-41 _4. The sample liquid is moved along the Y-axis direction by the processing head 71 while being sucked into the dispensing tips 41 _{1 to} 41 ₄ , and Lysis 1 (enzyme) as a separated extract is accommodated. Aspiration discharge for moving to the third liquid container 31b and inserting the thin tubes 41a of the dispensing tips 41 _{1 to} 41 ₄ through the holes of the perforated film to stir the sample liquid and the Lysis 1 repeat.

In step S4, the total amount of the agitated liquid is sucked by the dispensing tips 41 _{1 to} 41 _{4 and} is composed of a reaction tube held in the accommodation hole set to 55 ° C. by the constant temperature controller 48c. Incubation is performed in 31f (9th liquid storage unit). Thereby, the protein contained in the sample is denatured. After a predetermined time, leaving the reaction mixture to the reaction vessel 31f, a fourth liquid storage of the cartridge container ₃₁ 1-31 ₄ the dispensing tip ₄₁ 1-41 ₄ by the processing head moving mechanism 52 And the suction tip discharge mechanism 431 is used to suck the entire amount of Lysis 2 stored in the fourth liquid storage unit, and the processing head moving mechanism 52 By using the dispensing tips 41 _{1 to} 41 ₄ , penetrating the holes of the film into the fifth liquid storage part, inserting the thin tubes 41 a and discharging the liquid, thereby reducing the molecular weight of the protein. To do.

  In step S5, the binding buffer solution as the separation / extraction solution housed in the fifth solution housing section and the reaction solution are stirred to further dehydrate the solubilized protein, and the nucleic acid or fragment thereof is solution Disperse in.

In step S6, the dispensing tips 41 _{1 to} 41 ₄ are used to insert the thin tubes through the holes of the film into the fifth liquid container, and the entire amount is sucked to dispose the dispensing tips Z-axis moving mechanism 531. The dispensing tips 41 _{1 to} 41 ₄ are raised by the above, the reaction container is transferred to the second liquid container, and the magnetic particle suspension accommodated in the second liquid container and the reaction Stir the solution. A cation structure is formed in which Na + ions are bonded to hydroxyl groups formed on the surface of silica or the like covering the magnetic particles contained in the magnetic particle suspension. Therefore, negatively charged DNA is captured by the magnetic particles.

In step S7, as shown in FIG. 7, the inner wall of the pipette tip ₄₁ 1-41該分by the _fourth capillary be brought close to the magnet 441 of the magnetic force mechanism 44 dispensing tips ₄₁ 1-41 ₄ capillaries 41a The magnetic particles are adsorbed. The magnetic particles are lifted by the dispensing tip Z-axis moving mechanism 531 in a state where the magnetic particles are adsorbed to the thin tubes 41 a of the dispensing tips 41 _{1 to} 41 ₄ , and the dispensing tips are moved by using the processing head moving mechanism 52. 41 _{1-41 4} through the hole of the film is moved from the liquid accommodating portion of the fourth to the fifth liquid storage portion for insertion of the capillary.

The magnet 441 of the magnetic force mechanism 44 is housed in the sixth liquid housing portion in a state in which the magnetic force into the thin tube is removed by separating the magnet 441 from the thin tubes 41a of the dispensing tips 41 _{1 to} 41 ₄ . The cleaning liquid 1 (NaCl, SDS, isopropanol) is repeatedly aspirated and discharged to separate the magnetic particles from the inner wall, and the cleaning liquid 1 is stirred to be cleaned. Thereafter, the dispensing tip 41 _{1 to} 41 ₄ is brought into a state where the magnetic particles are adsorbed on the inner wall of the thin tube by bringing the magnet of the magnetic mechanism 44 again to the thin tube 41 a of the dispensing tip 41 _{1 to} 41 _4. Is moved by the processing head moving mechanism 52 from the sixth liquid container to the seventh liquid container by the dispensing tip Z-axis moving mechanism 531.

In step S8, inserted through the hole of the film using the pipette tip 41 _1-41 min ₄ capillary pipette tip Z-axis moving mechanism 531. The cleaning liquid 2 (stored in the seventh liquid storage part) in a state in which the magnetic force into the capillary is removed by separating the magnet of the magnetic mechanism 44 from the capillary of the dispensing tips 41 _{1 to} 41 ₄ . By repeating suction and discharge for isopropanol), the magnetic particles are stirred in the liquid to remove NaCl and SDS and wash. Thereafter, while adsorbing the magnetic particles to the inner wall of the tubules be brought close to the magnet again the pipette tip 41 _{1-41 4} capillaries of the magnetic mechanism 44, the dispensing tip 41 _{1-41 4} Then, after being moved up by the dispensing tip Z-axis moving mechanism 531, the processing head moving mechanism 52 moves the seventh liquid container from the seventh liquid container to the eighth liquid container containing distilled water. .

In step S9, the dispensing tips Z-axis moving mechanism 531 lowers the thin tubes of the dispensing tips 41 _{1 to} 41 ₄ through the holes, and the magnetic force is reduced to the thin tubes 41a of the dispensing tips 41 _{1 to} 41 ₄ . By repeatedly sucking and discharging the distilled water at a slow flow rate while being applied to the inside, the cleaning liquid 2 (isopropanol) is replaced with water and removed. Thereafter, the magnetic particles are stored in the tenth liquid storage section as the dissociation liquid in a state where the magnet of the magnetic mechanism 44 is separated from the thin tubes of the dispensing tips 41 _{1 to} 41 ₄ and the magnetic force is removed. By stirring and discharging repeatedly in distilled water, the nucleic acid or fragments thereof held by the magnetic particles are dissociated (eluted) into the liquid from the magnetic particles. Thereafter, the magnet 441 is brought close to the thin tubes 41a of the dispensing tips 41 _{1 to} 41 ₄ to apply a magnetic field in the thin tubes to adsorb magnetic particles on the inner wall, and the extracted nucleic acid or the like in the tenth liquid container The solution containing is left. It moves to the 8th liquid storage part in which the washing | cleaning liquid 3 is hold | maintained by the processing head moving mechanism 52, and with the washing | cleaning liquid 3 in the state which resuspended the magnetic particle by repeating aspiration / discharge by removing the magnetic field. The dispensing tip is washed by discharging.

Hereinafter, Steps S10 to S15 correspond to nucleic acid amplification and measurement processes.
In step S10, the processing head 71 is moved by the processing head moving mechanism 52, the solution containing the nucleic acid or the like stored in the tenth liquid storage unit is sucked, and the amplification solution is stored in advance. The sample is transferred to the PCR container 31c, discharged, and introduced into the container. The PCR container 31c contains in advance a primer labeled with a fluorescent substance for amplifying the characteristic base sequence portion of the target bacterium or target virus of the infectious disease to be detected. Etc., the base sequence portion is amplified. The processing head moving mechanism 52 returns to the tip accommodating portion 31a, removes the dispensing tips 41 _{1 to} 41 ₄ attached by the detachable member 42b, and again above the sealing lid accommodating portion 31e. Until the nozzle 43a is moved. The dispensing tip Z-axis moving mechanism 531 is used to lower the nozzle 43a so as to be fitted to the lower end of the nozzle 43a by being lowered. The dispensing tip Z-axis moving mechanism 531 lowers the sealing lid so that it is fitted into the opening of the wide-mouthed tube portion of the PCR container 31c and sealed.

In step S11, when amplification of the nucleic acid extracted by performing temperature control based on the PCR method is completed, the sealing lid is punctured by the puncturing tip 46, and the processing head 92 is instructed by the measurement control unit 92. The moving mechanism 52 is instructed to move the processing head 71 to mount the dispensing tips 41 _{1 to} 41 ₄ and to be positioned above the eleventh liquid storage portion, and to lower the dispensing tip As a result, for example, several hundred μL to several mL of a developing solution, for example, physiological saline or buffer solution, is sucked, and the dispensing tips 41 _{1 to} 41 ₄ are moved in the Y-axis direction by the processing head moving mechanism 52. As a result, the PCR product is transferred to the PCR container 31c and the amplification product and the developing solution contained in the PCR container 31c are mixed.

In Step S12, the processing head moving mechanism 52 moves the dispensing tips 41 _{1 to} 41 ₄ in the Y-axis direction to above the tip accommodating portion 31a and is detached by the detaching member 42b. is moved in the axial direction and located above the chromatography chip 81 _{1-81 4,} the dispensing by lowering the chip Z-axis moving mechanism 531, the chromatography chip ₈₁₁ to the nozzle 43a to 81 ₄ is mounted by the later rise dispensing tip Z-axis moving mechanism 531, it moves the chromatography chip ₈₁₁ to 81 ₄ to above the PCR container 31c. By the dispensing tip Z-axis moving mechanism 531, the by chromatography chip 81 _{1-81 4} is lowered and inserted into the PCR container 31c, as shown in FIG. 6, wherein the solution suction discharge mechanism 431 by aspirating up the mobile phase reservoir line of the chromatography chip 81 _{1-81 4,} after a predetermined time (e.g., after a few seconds) by discharging a residual liquid sucked in, the porous stationary phase carriers 21 The amount of liquid in contact with is fixed (for example, several 100 μL). A base sequence complementary to the base sequence of the characteristic part of the target bacterium or virus to be detected is fixed in advance on the test substance fixing surface 21a of the porous stationary phase carrier 21 as the test substance. Yes.

In step S13, the chromatographed chip 81 _{1-81 4} is raised by the dispensing tip Z-axis moving mechanism 531, the washing liquid 12 of the liquid housing part (the a developing solution same) is accommodated The washing solution is aspirated to, for example, several 100 μL to several mL, and is brought into contact with the porous stationary phase carrier 21, so that it is labeled without being hybridized with the target base sequence as the test substance. The base sequence is moved to the absorption pad. At this time, as shown in FIG. 8, the temperature raising and lowering body 481 is that to approach the chromatography chip 81 _{1-81 4,} it is preferable to accelerate the reaction provides temperature control.

In step S14, in accordance with an instruction from the measurement control unit 92, the measurement device moving mechanism 6c of the measurement unit 61 is connected to the dispensing tip support member 45 and is movably supported by the measurement end support arm 61b. by moving the end 61a in the X-axis direction to perform sequential measurements for each chromatographed chip ₈₁ 1-81 _4. That is, by irradiating the excitation light for each chromatographed chip 81 _{1-81 4} from the measurement end 61a of the measuring unit 61, when there is interest bacteria or viruses, the fluorescence generated the measuring end The light intensity can be measured by sequentially receiving light from the light receiving end provided on the surface. Then, the treatment progress of the patient is monitored by measuring and comparing the fluorescence intensity at the position where the test substance is fixed using the quantitative nucleic acid amplification solution and the developing solution with respect to the sample solution of the predetermined concentration. Will be able to.

  Next, a chromatography processing apparatus 102 according to another example in which the chromatography processing apparatus 100 according to the first embodiment shown in FIG. 2 is more specific will be described with reference to FIGS.

  FIG. 9 shows the chromatography apparatus 102 taken out of the housing and shown in more detail.

Unlike the chromatography apparatus 101 according to the above example, the chromatography apparatus 102 includes a plurality of storage units arranged in a line so as to extend along the Y-axis direction. 4 columns) are those having a container group 32 consisting of the cartridge container ₃₂₁ to 323 ₄ which are arranged.

  The chromatographic processing apparatus 102 according to this example performs specific food allergen detection for items selected from seven items (egg, milk, wheat, buckwheat, peanut, shrimp, crab) for four types of food. The case will be described. As shown also in FIG. 10, each cartridge container 321 to 324 of the container group 32 has a sample storage part 32g (first liquid storage part) containing 100 μL of a food extract extracted from the test food. , The order is in the liquid storage unit group 32b), the liquid storage unit (second liquid storage unit) that stores the colloidal gold labeled antibody solution, the liquid storage unit (third liquid storage unit, (Fourth liquid storage part), a liquid storage part (fifth liquid storage part) for storing the cleaning liquid, an empty liquid storage part (sixth liquid storage part), and an empty liquid storage part (seventh liquid storage part) Part).

Wherein the chip housing portion 32a, the piercing tip 46, the dispensing chip ₄₁ 1-41 _4, chromatographed chip ₈₂ 1-82 ₄ is previously housed in the top fitting opening. The The chromatography chip ₈₂ 1-82 _4, the porous stationary phase carriers ₂₂ 1 to 22 ₄ is sealed. The porous stationary phase carrier 22 has a test substance fixing surface 22a. From the lower side, the test substance fixing surface 22a has a mobile phase storage line 22b, a fixing part 22c displayed by measurement, and a positive It has a control line 22d and a negative control line 22e.

  As the fixing site 22c, antibodies (for example, anti-wheat antibody and anti-egg antibody) capable of capturing two types of allergens are formed at predetermined height positions at intervals in a horizontal straight line.

  The negative control line 22e is a part that is blocked so that antigens and antibodies do not bind, and the positive control line 22d is a part that is always colored.

The operation | movement which performs the specific food allergen detection about 2 selected items about 4 types of foods is demonstrated below.
In step S21, the processing head 71 is moved in the Y-axis direction by the processing head moving mechanism 52, and is positioned above the tip accommodating portion 32a in which the dispensing tips 41 _{1 to} 41 ₄ are accommodated. The dispensing tips Z-axis moving mechanism 531 causes the nozzles 43a provided in the processing head 71 to descend, so that the dispensing tips 41 _{1 to} 41 ₄ are mounted and raised again, and the dispensing tips are When the lower end of the chip reaches above the chip accommodating part 32a, it relatively moves in the Y-axis direction.

In step S22, the dispensing tip 41 is lowered by being positioned above the sample storage portion 32g (first liquid storage portion) in which the food extract as the sample is stored in the liquid storage portion 32b. _{1-41 4} tip is inserted into the liquid accommodating portion, with the suction and discharge mechanism 431 aspirates the food extract, it is moved in the Y-axis direction by the processing head moving mechanism 52 and the sixth A sample is discharged into the sixth liquid container by being positioned and lowered above the liquid container. Subsequently, the processing head moving mechanism 52 moves the dispensing tips 41 _{1 to} 41 ₄ to the second liquid storage unit in which the gold colloid labeled antibody solution is stored, and lowers the dispensing tips 41 _{1 to} 41 ₄ to the labeled antibody. Is sucked and discharged into the sixth liquid container, and suction and discharge are repeated to react the allergen in the sample with the colloidal gold labeled antibody. Moving the pipette tip 41 _{1-41 4} until the third liquid storage portion, transferring the developing liquid contained in the third liquid receiving part by a predetermined amount sucked to the liquid storage portion of said 7 Then, a predetermined amount of the allergen contained in the sixth liquid storage unit labeled with gold colloid is sucked and transferred to the seventh liquid storage unit, and the agitation is repeated by repeating the suction and discharge. Let

In step S23, the processing head 71 is moved by the processing head moving mechanism 52 in the Y-axis direction, and the mounted dispensing tips 41 _{1 to} 41 ₄ are detached by the detachable member 42b and moved in the Y-axis direction. is lowered by the pipette tip Z-axis moving mechanism 531 is newly attached chromatographed chip ₈₂ 1-82 _4. As shown in FIG. 10, after the ascending, the labeled sample liquid is moved in the Y-axis direction by the processing head moving mechanism 52 to be positioned above the seventh liquid container and then lowered. Is sucked up to the mobile phase storage line, and the liquid is discharged after a predetermined time (for example, several seconds). The residual liquid sucked after a predetermined time has elapsed (for example, several seconds later) is discharged, and the amount of liquid that contacts the porous stationary phase carrier 21 is made constant. An antibody corresponding to a food allergen to be detected is immobilized in advance as a test substance on the test substance fixing surface of the porous stationary phase carrier 22. At this time, as shown in FIG. 11, the temperature elevating body 481 is brought close to the chromatography chip 82, whereby the reaction can be promoted by controlling the temperature.

In step S24, the chromatographed chip 82 _{1-82 4} is raised by the dispensing tip Z-axis moving mechanism 531, the cleaning solution (the developing solvent and the same) the fifth liquid storage portion which is accommodated Go to the, in contact with the porous stationary phase carrier 22 _{1-22 4} by sucking the washing solution, a labeled antigen or the like is not specifically bind to said antibody as the test substance Move to the absorbent pad.

In step S25, in response to an instruction from the measurement control unit 92, the measuring device moving mechanism 6c of the measuring unit 61 connects the dispensing tip support member 45 to the measuring end support arm 61b as the measuring device support. operably supported measuring portion 61a is moved in the X-axis direction to perform sequential measurements for each chromatographed chip 82 _{1-82 4.} That is, the irradiation for light from the measuring portion 61a of the measurement section 61 by irradiating each chromatographed chip 82 _{1-82 4,} when there is a food allergen of interest, based on the resulting color Light can be sequentially received from the light receiving end provided at the measurement end, and the degree of coloration can be measured. Then, it is possible to specify the degree of food allergy by measuring and comparing the degree of coloration at a position where the test substance is fixed using a constant amount of developing solution with respect to the sample liquid having a predetermined concentration. It will be possible.

  Next, the chromatography apparatus 103 according to the second embodiment based on FIGS. 12 and 13 will be described.

The chromatography processing apparatus 103 is different from the chromatography processing apparatus 101 according to the first embodiment in the measurement unit 6. The measuring unit 6 is provided with a light receiving processing unit 66 that performs a light receiving process on the light guided from the respective chromatography processing chips 8 ₁ to 8 _n by the light guide paths 6 _{1 to} 6 _n . The light guides 6 _{1 to} 6 _n can approach or be in contact with the thick tubes of the chromatography chips 8 ₁ to 8 _n , respectively. Therefore, the sealed porous stationary phase carriers 2 ₁ to 2 _n are in contact with each other. It has _n measurement ends 62 _{1 to} 62 _n provided so as to be close to each other, and light obtained based on an optical state that can be generated by a reaction on the test substance fixing surface is transmitted to the connection ends 64 ₁ to 64 _n . and n of the light guide ₆ 1 to 6 _n to the optical guide to the measuring portion ₆₂ 1 through 62 _n of the light guide ₆ 1 to 6 _n of the plurality of the said test substance of each chromatography chip Measuring heads (62 _{1 to} 62 _n , movably provided relative to the chromatographic processing chip so as to arrive at predetermined measuring positions corresponding to the fixed surface all at a predetermined scanning period (ts). 63, 65) Have.

The light receiving processing unit 66 sequentially sets the plurality of light guide paths sequentially while the measurement ends 62 _{1 to} 62 _n are moved to the predetermined measurement position or stopped at the position by the measurement head. select the selection period (tc), light guiding path having a light guide region that allows emitting light incident connect connection end 64 ₁ to 64 _n and optically selected light guiding path 6 ₁ to 6 _n The selection unit 73, the light receiving unit 67 that sequentially receives and photoelectrically converts the light emitted from the light guide region of the light guide path selection unit 73, and the image area data obtained from the light receiving unit 67 is the predetermined selection period. And a digital data converter 75 for sequentially obtaining digital data.

The measurement head includes a measurement end support 63 that supports a plurality of the measurement ends 62 _{1 to} 62 _n arranged at intervals according to the arrangement of the chromatography chips 8 ₁ to 8 _n , and the measurement end support 63. The measurement end support 63 can be moved closer to or away from the dispensing tips 4 ₁ to 4 _n by moving in the Y-axis direction, and each test substance is fixed to the enclosed porous stationary phase carriers 2 ₁ to 2 _n. A measuring end moving mechanism 65 that enables the measuring ends 62 _{1 to} 62 _n to move in the Z-axis direction so as to sequentially approach the surface all at once; The measurement ends 62 _{1 to} 62 _n are arranged at the ends corresponding to the end points of the movement paths of the dispensing tips in the accommodating unit groups 3 _{1 to} 3 _n , and the dispensing tips 4 ₁ at the positions thereof. When the tip of ˜4 _n is a reaction container 3c that can be inserted and the dispensing tips 4 ₁ to 4 _n are in that position, the dispensing tip 4 ₁ to 4 _n is moved to the measuring end moving mechanism 65. When the container group 3 is moved in the Y-axis direction and the dispensing tips 4 ₁ to 4 _n are immovable in the Y-axis direction, the dispensing tips 4 _{1 are provided.} It is preferable that the measuring end moving mechanism 65 is arranged at a position that can be approached and separated with respect to ˜4 _n .

FIG. 13 shows the light receiving processing unit 66 in more detail.
Wherein the light receiving portion 671, as the light guide path selecting section 731, a plurality of (e.g., the four in the example) a predetermined central angle of each connection end of the light guide 61 _{1-61 4} along the circumference of, In this example, the connection end array plate 73b is supported by being arranged at an equal angle of 90 degrees, and the light guide region is provided in a dark box and has a rotation axis concentric with the circumference of the connection end array plate 73b. And a motor 76a as a rotation drive mechanism 76 capable of continuously or intermittently driving the selection rotator at the predetermined selection cycle.

  A case where a CCD image sensor is used as the light receiving portion 671 will be described. As a CCD image sensor, for example, a light receiving surface of 6.4 mm × 4.8 mm is arranged and 772 × 580 light receiving elements are arranged. In this case, the digital data converter 75 includes a shift register that sequentially transfers charges by gate control, an amplifier that performs voltage amplification, and an AD converter that converts the amount of charges into digital data. The predetermined selection cycle can be determined based on, for example, a time interval specified by an instruction from the operation panel 14 or an instruction from the CPU + program + memory 9 measurement control unit. As described above, the predetermined selection period is the predetermined scanning period, the number of types of test substances, the number of chips for each chromatography process, the type of optical state, the reagent, the aspect of the optical state, the characteristics of the light receiving unit It is determined on the basis of the movement time of the mobile phase on the test substance immobilization surface, the reaction time, the optical state, or the lifetime or the time during which light can be stably received. Therefore, the measurement end moving mechanism 65 determines the scanning speed of the test substance fixing surface, a predetermined scanning cycle, the size, shape, or movement mode of the test substance fixing face in accordance with the light measurement mode. . For example, measurement is performed so as to scan along the Z-axis direction using an optical fiber having a diameter of 1 mm provided at the measurement end. In that case, the measurement end is relatively positioned, for example, the distance from the light receiving position to the next light receiving position is 0.1 mm, and the light receiving time (the stop time required for photon counting is taken into account) ) And intermittently moving while stopping for 10 msec so that the measurement is performed a plurality of times (10 times in this example) for one fixed part. This takes into consideration the uncertainty based on the fact that the position of the fixed part is not necessarily an exact straight line, the size of the optical fiber, and the like. As a result, Gaussian function-type luminance of light emission can be obtained with respect to one fixed part, and thus precise measurement of light emission and the like can be performed. For this purpose, the measurement control unit 92 causes the dispensing tip Z-axis moving mechanism 53 and the storage means 93 to generate a pulse signal of such timing. Then, for the entire fixed area of 50 mm, light reception or digital data conversion is performed 500 times in about 30 seconds to about 50 seconds (including the chemiluminescence plateau state) including the movement time.

As shown in FIG. 13, the container group 3 further includes measurement ends provided so as to be in contact with the thick tubes of the chromatography processing chips, and the connection end array plate of the light guide path selection unit 731. (in this example four) plurality each having a support connection end to have a light guide path 61 _{1-61 4.} The measurement ends are arranged and supported on the measurement end support 631 along the X-axis direction at intervals corresponding to the arrangement of the chromatography processing chips.

  In addition, the container group 31 has the measurement end support 631 and, therefore, a plurality (four in this example) of the measurement ends movable along the Z-axis direction that is the axial direction of the dispensing tip. Thus, the processing head 71 is provided with a measurement end moving mechanism 65 capable of scanning the test substance fixing surface of each chromatography processing chip. In this example, the processing head is provided in the housing 12 so as to be stationary in the Y-axis direction, so that the measurement head is also provided so as to be stationary with respect to the container group 31. However, it is provided so as to be movable by the measurement end moving mechanism 65 only in the Y-axis direction for approaching and separating from the chromatography processing chip.

The measurement end, when moving the container group so that the chromatography chip 81 _{1-81 4} comes above the reaction vessel 31c provided at the rear side along the Y-axis direction of the container group In addition, the measurement process is performed.

The measuring portion moving mechanism 65 includes an arm member connected to the measuring end support 631, the arm member slidably retained, the chromatography chip 81 _{1-81 4} along the Y-axis direction An arm holding base provided with an elastic member that is always elastically urged so as to move forward, and screwing with the ball screw in order to move the ball screw up and down along the Z-axis direction. A motor that rotationally drives the nut portion to be rotated, a base portion that is provided with a hole through which the motor is mounted and through which the ball screw passes and is fixed to the bottom, and a nut portion that is rotationally driven by the motor, and is screwed into the upper and lower sides. And a ball screw whose tip is pivotally supported on the lower side of the arm holding base, and a lower end is provided at the base, passes through the arm holding base, and its upper end is attached to a fixture. It has a guide column and, a fixture attached to the housing.

Then, the container group 3 moves while processing the Y-axis direction and finally the chromatography chip 81 _{1-81 4} reaches the reaction vessel 31c as the liquid storage portion, the dispensing Each thin tube of the tip presses the measuring end and receives an elastic repulsion to come into contact.

Therefore, by the measuring end support 631 is moved in the Z axis direction, the chromatography chip ₈₁ 1-81 ₄ SEQ measuring portion ₆₂ 1-62 ₄ arranged in accordance with of the porous stationary It moves in the Z-axis direction with respect to the phase carriers 21 _{1 to} 21 ₄ , and moves relative to the fixed part of the test substance fixing surface belonging to the porous stationary phase carriers 21 _{1 to} 21 ₄ of the chromatography chips. Scan simultaneously and sequentially close and spaced apart. In this case, the measurement end support 631 is provided with a plurality of (5 in this example) predetermined measurements provided for each 0.2 mm corresponding to each fixing portion (particle having a diameter of 1 mm) of each chromatography processing chip. The position is a predetermined scanning period (ts, 0.8 seconds in this example).

FIGS. 13A, 13B, and 13C show the light guide path selection unit 731 in detail.
As shown in FIG. 13 (c), the light guide path selecting section 731, a plurality of predetermined central angle along the circumference of the connection end of the light guide 61 _{1-61 4} (the four in the example) (In this example, 22.5 degrees) A connection end array plate 73b that is arranged and supported at an equal angle and a switching light guide path 74 as the light guide region are provided and concentric with the circumference of the connection end array plate 73b. And a rotation drive mechanism 76 capable of continuously or intermittently rotating the selection rotation body 73a at the predetermined selection period tc. The light guide region, the light receiving of the light guide 61 _{1-61 4} connecting the predetermined sequentially and continuously in the selected period or intermittently incident end provided to be optically coupled 74a and the light receiving portion to the end 671 At least a switching light guide 74 having an exit end 74b optically connected to the surface is provided.

FIG. 13A shows the connection end array plate 73b viewed from the direction of the arrow of the AA line in FIG. The incident end 74a is arranged on the incident end arrangement surface 73e, which is determined so as to approach the connection end arrangement plate 73b in parallel, and the circumference in which the connection ends 64 ₁ to 64 _{16 of the} connection end arrangement plate 73b are arranged. The light emitting end 74b is disposed on a light emitting end arrangement point 73c defined on the rotation axis 73d.

  The selection rotating body 73a has a rotation shaft 73f provided along the rotation axis 73d, and both ends thereof are pivotally supported by a shaft support portion 76d via bearings 76e. The rotating shaft 73f is rotatably connected to the shaft 76b of the motor 76a through a coupling 76c.

  FIG. 13B shows the inside of the selection rotating body 73a viewed from the direction of the arrow of the BB line in FIG. 13C. The selection rotating body 73a is a solid cylindrical body, and a groove 74d is provided along a radius of the circumference 73g of the connection end array plate 73b in the portion where the switching light guide path 74 is provided. The light absorption region 77 is recessed so as to extend along the radial direction from the rotation axis 73d, and the groove 77a has an arc-shaped opening along the circumference 73g without intersecting the groove 74d, and is deep. Is recessed so as to have a depth (for example, 90% of the length) shorter than the length in the axial direction of the selection rotating body 73a. . The back of the groove 77a is filled with, for example, carbonized cotton or black fiber.

  Subsequently, whether or not the chromatographic processing apparatus 103 according to the second example is used by examining specific SNPs related to the effect of a predetermined drug on the genomes of four subjects. The operation when checking the validity of is described.

Chromatographic processing chips 81 _{1 to} 81 _{4 in which} extraction chip, PCR dispensing chip, perforation chip and porous stationary phase carriers 21 _{1 to} 21 ₁₆ are enclosed in the chip housing portion group 31a. Is accommodated in advance with the mounting opening facing up. In each liquid storage part of the liquid storage part group 31b, samples such as oral mucosa collected from the subject in advance, genome extraction reagent, magnetic particle suspension, primer-containing liquid as a PCR reagent Mineral oil and cleaning liquid, such as restriction enzyme solution, are accommodated, and some of the accommodating parts are empty. Moreover, it has reaction containers, such as a PCR container which can control temperature. Wherein the chromatography chip 81 _{1-81 4} is fixed to the polymorphic each fixed site while probes appropriate intervals having the nucleotide sequence of each two kinds of SNP in a plurality of locations associated with the drug It shall be. Each fixing part is, for example, linear, and the line width is, for example, 1 mm.

  In step S31, the processing head 71 is moved in the Y-axis direction by the processing head moving mechanism 52, and the first chip storage of the chip storage portion group 31a in which unused dispensing tips are stored. It is located above the part. By lowering the 16 nozzles provided in the processing head 71 by the dispensing tip Z-axis moving mechanism 421, the extraction dispensing tips are mounted and raised again to lower the lower end of the dispensing tip. Moves to the upper side of the chip accommodating portion, it moves in the Y-axis direction.

  In step S32, the processing head 71 is moved to the position of one liquid storage section belonging to the liquid storage section group 31b for storing the genome extraction reagent, and lowered to move the tip of the dispensing tip to the position. The extraction reagent is inserted into the liquid container and the relevant extraction reagents are simultaneously aspirated using the suction / discharge mechanism 431. The dispensing chip is transferred to one liquid container of the liquid container group 31b in which the sample solution is stored, and the lower end of the dispensing chip is inserted into the liquid container and discharged. Further, similarly, a magnetic particle suspension that is stored in one liquid storage section of the liquid storage section group 31b and for extracting each subject's DNA as a target substance is sucked into the dispensing tip. Then, the sample solution is transported and discharged to the liquid storage part in which the sample solution is stored, and agitation is performed by repeating suction and discharge, thereby binding the DNA of each subject as the target substance to the magnetic particles. If necessary, suction and discharge are further repeated with the cleaning liquid in order to remove impurities.

  In step S33, using the actuator of the magnetic force mechanism, the magnet arrangement member is brought close to the dispensing tip for extraction, and the magnet is brought close to the thin tube of the dispensing tip to exert a magnetic field in the capillary tube, The magnetic particles to which the subject's DNA is bound are adsorbed on the inner wall of the capillary tube and separated. The separated magnetic particles are transported to the next one liquid storage part in which the detachment liquid of the liquid storage part group 31b is stored by the processing head 71 while being adsorbed on the inner wall, and by a magnetic mechanism. In a state where the magnet array member is separated from the extraction dispensing tip, the DNA of each subject of the target substance is suspended in the separation solution by repeating suction and discharge of the separation solution, and the magnetic mechanism While the magnetic particles are again adsorbed on the inner wall, the processing head 71 is moved, and in the chip accommodating part group 31a, the dispensing dispensing chip is detached from the nozzle by lowering the chip detaching plate 43e and discarded. To do.

  In step S 34, the unused PCR dispensing tip accommodated in one tip accommodating portion of the tip accommodating portion group 31 a is lowered by the dispensing tip Z-axis moving mechanism 421 of the processing head 71. Then, the nozzle is fitted and mounted in the mounting opening of the dispensing tip, and the processing head 71 is moved up in the Y-axis direction and stored in the liquid storage section of the liquid storage section group 31b. The aforesaid DNA solution is aspirated by the aspiration / discharge mechanism 431, and the dispensing tip is lifted by the dispensing tip Z-axis moving mechanism 421, and a liquid storage portion for PCR provided in the liquid storage portion group 31b And the DNA solution is discharged. Similarly, a reagent solution such as a primer having a corresponding base sequence for amplifying the base sequence containing each SNP is discharged into the PCR reaction vessel, and the relevant temperature control cycle based on the PCR method is applied. A DNA fragment having a base sequence containing each SNP is amplified and generated.

  In step S35, the generated DNA fragment solution containing various SNPs is a chemiluminescent substance solution connected to an adapter having a base sequence complementary to a base sequence unique to each DNA fragment by the PCR dispensing chip. The liquid SNP is dispensed and stirred in one liquid storage section provided in the liquid storage section group 31b to be stored, and the various SNPs are labeled with a chemiluminescent substance. Here, an enzyme, horseradish peroxidase (HRP) is used as the chemiluminescent substance, and luminol / hydrogen peroxide is used as the substrate, and detection is performed by the CLEIA method.

  In step S36, the processing head 71 is returned to the chip accommodating part group 31a again, and the PCR dispensing chip mounted in the empty chip accommodating part is detached by the chip detaching plate 43e and discarded.

In step S37, the processing head 71 is raised and then moved again in the Y-axis direction to be one chip housing portion in the chip housing portion group 31a, which is the porous stationary phase carrier 21 _{1 to} 21. ₄ is placed above the tip accommodating portion in which the dispensing tips 41 _{1 to} 41 ₄ in which ₄ is enclosed are accommodated. The nozzles are lowered by the dispensing tip Z-axis moving mechanism 421 so that the nozzles are fitted into the mounting openings and the dispensing tips 41 _{1 to} 41 ₄ are attached to the nozzles.

In step S38, the dispensing tip ₄₁ 1-41 ₄ is moved in the Y-axis direction, the said labeled various SNP cartridge container ₃₁ fragment is contained 1-31 ₄ of the liquid accommodating portion group 31b The tip of the dispensing tips 41 _{1 to} 41 ₄ is inserted into the liquid containing portion using the dispensing tip Z-axis moving mechanism 421 and is sucked by the suction / discharge mechanism 431. By repeating the discharge, the porous stationary phase carriers 21 _{1 to} 21 ₄ having the fixed part are brought into contact with the solution. At that time, the temperature raising / lowering body 48 is advanced to the dispensing tips 41 _{1 to} 41 ₄ by the motor as the raising / lowering body advancing / retreating drive mechanism 48b according to the instruction of the extraction / reaction control unit 91, and is closely contacted. to maintain the _{1-41 4} at a predetermined temperature.

In step S39, the dispensing tips 41 _{1 to} 41 ₄ are moved in the Y-axis direction by using the processing head moving mechanism 55, so that one liquid container in which the cleaning liquid in the liquid container group 31b is stored. In the state where the temperature raising and lowering body 48 is separated from the dispensing tips 41 _{1 to} 41 ₄ , washing and discharging are repeated.

In step S40, the dispensing tips 41 _{1 to} 41 ₄ are moved to the reaction vessel 31c containing the chemiluminescent substrate, and the tip is inserted into the reaction vessel 31c. At that time, moves in the Y axis direction so that the state of contact with the measuring portion ₆₂ 1-62 ₄ by the measuring portion moving mechanism 65 in the dispensing tips ₄₁ 1-41 ₄ tubules. Also, to maintain the dispensing tip _{41 1-41 16} temperature raising and lowering body 48 is in close contact with advanced to the dispensing tip ₄₁ 1-41 ₄ by the motor as the elevating member reciprocating drive mechanism 82 to a predetermined temperature.

In step S41, the solution in the reaction vessel 31c is sucked by the dispensing tips 41 _{1 to} 41 ₄ . Then, the sucked substrate, will react with these dispensing tips 41 _1-41 porous stationary phase enclosed in the ₄ carrier 21 ₁ to 21 ₄ of the enzyme emission.

Then, by the measuring portion moving mechanism 65, the measurement end support 63 by moving along the Z-axis direction, a fixing portion corresponding are respectively arranged on the porous stationary phase carrier 21 ₁ to 21 ₄ simultaneous sequential from the measuring portion ₆₂ 1-62 ₄ until the connection ends ₆₄ 1 to 64 ₄ to will be guided to the porous stationary phase carrier ₂₁ 1 to 21 ₄ through the light guide path ₆₁ 1-61 _4.

Step S42 sequentially receiving accordance optical state corresponding to 50 each movement in the Z axis direction of the measuring portion 62 _{1-62 4} by the measuring portion moving mechanism 65. Then, the measuring end 62 _{1-62 16} relative movement, for example, 0.2 mm wherein the predetermined measure the distance between the position 800msec movement and stop times of: moving (ts predetermined scanning cycle), such as intermittently repeated By performing the above, it is possible to receive light five times at the predetermined measurement position with respect to one 1 mm fixed portion. During the predetermined scanning cycle (ts), said the light guide path selecting section 731, the four total light guiding channel ₆₁ 1-61 _4, by sequentially selected in a predetermined selection period (tc), 1 of the light receiving portion Reference numeral 671 makes it possible to sequentially receive light from each fixed portion of the entire chromatography chip. In this case, the selection rotating body 73a of the light guide path selection unit 731 rotates intermittently while stopping at a predetermined selection period (tc), 800 msec / 4 = 200 msec. That is, the scanning speed in the Z-axis direction of the measurement end is an intermittent movement of 1 mm per second, and the rotational speed of the selection rotating body is an intermittent rotation of 60 revolutions per minute synchronized with the movement of the measurement end. .

  At that time, according to an instruction from the measurement control unit 92, the digital data conversion unit 75 converts the intensity or luminance of the light received by the light receiving unit 671 into the corresponding digital data at the predetermined selection period, and The target biological material to be inspected can be inspected by being sequentially stored in the storage means 93, read out by the analysis means 94, and subjected to arithmetic analysis. Here, the “predetermined scanning cycle” (ts) is, for example, a movement time required for relative movement between adjacent measurement positions of measurement ends by the measurement end moving mechanism (for example, between adjacent predetermined positions, 800 msec), the number of times of light reception for each chromatography chip (for example, 5 times), the number of fixed sites (for example, 50), and the stable light reception time for which chemiluminescence can be received stably (light emission) Is determined based on a light measurement mode consisting of a time during which the plateau state is maintained (for example, 200 seconds), and thereby a stop time for light reception (digital data conversion) with respect to the fixed portion is determined to be, for example, 800 msec. This is instructed by the measurement control unit 92. On the other hand, the “predetermined selection period” is determined based on the predetermined scanning period (ts) and the number of chromatography processing chips (n), for example.

  Each of the embodiments described above is specifically described for better understanding of the present invention, and does not limit other embodiments. Therefore, changes can be made without changing the gist of the invention. For example, in the above examples, only chemiluminescence, fluorescence, and color have been described as optical states. However, other optical states, for example, even when the light is changed, can be performed by receiving the light generated thereby. it can. The chemiluminescent reagent is not limited to the acridinium ester derivatives, horseradish peroxidase (HRP) and the like described above.

  In the above example, only the case where the measurement end is combined with the processing head has been described. However, the case where the measurement end is not provided in the processing head is also possible. In addition, the devices described in the embodiments of the present invention, the components forming these devices, or the devices and reagents forming these components can be appropriately selected and combined with each other with appropriate changes. . For example, chemiluminescent materials, chromatographic chips, porous stationary phase carriers, immobilization sites, container groups, light receiving element arrays, light receiving elements, light guides, light guides, light guides selection units, digital data converters, dispensing A chip or a measurement control unit.

  In this application, “X axis”, “Y axis”, “Z axis”, “upward”, “downward”, “internal”, “external”, “upper and lower”, “row”, “column”, etc. Such spatial representations are for illustration only and are not limited to a particular spatial orientation or arrangement of the structure.

  The numerical values, the number of times, the shape, the number, the amount, etc. used in the above description are not limited to these cases. For example, the number of chromatography chips is not limited to four, and it goes without saying that the number of fixed sites belonging to each chromatography chip is not limited to that shown in the drawings.

  The present invention relates to a chromatography chip, a chromatography apparatus and a chromatography method, and relates to food allergens, pregnancy-related, myocardial infarction-related, renal function, drugs (cocaine, marijuana, etc.) collected from foods and patients. ), Testing for and measuring infectious diseases, etc., fields that require the handling of biopolymers such as genes, immune systems, amino acids, proteins, sugars, and biomolecules, such as biochemistry, It can be used in various fields such as the industrial field, the agricultural field such as food, agriculture, and fish processing, the pharmaceutical field, and the medical field such as hygiene, health, immunity, disease, and genetics.

10,100,101～104 chromatographed apparatus _{2 1 ~2 n, 21 1 ~21} n, 22 1 ~22 n porous stationary phase carrier 3, 31, 32 container group 4 ₁ ~4 _{n, 41 1} ~41 _n Dispensing tips 43, 431 Suction / discharge mechanism 44 (441, 442, 443) Magnetic mechanism 48, 481 Temperature raising / lowering body 5 (52, 53, 531) Moving means (processing head moving mechanism, dispensing tip Z-axis moving mechanism) )
6 Measurement unit 7,71 Processing head 8 ₁ to 8 _n , 81 _{1 to} 81 _n , 82 _{1 to} 82 _n Chromatographic processing chip 9 CPU + program + memory

Claims (15)

  A thick tube is provided at the lower end with a mouth portion that is inserted into the container where liquid is sucked and discharged, and a thin tube that communicates with the mouth portion and a reservoir portion that communicates with the thin tube and stores the sucked liquid. A translucent dispensing tip having a tube, and a target substance in the aspirated mobile phase solvent, which is provided in the thick tube of the dispensing tip, adsorbs, captures, separates, or binds And a porous stationary phase carrier provided with a testing substance immobilizing surface in which a predetermined amount of the inspecting substance is fixed in a predetermined region, and the porous stationary phase carrier is an optical component of the inspection substance immobilizing surface. A chromatographic processing chip in which a target state is sealed so as to be measurable from the outside of the side surface of the dispensing chip, and the lower end of the porous stationary phase carrier is provided in the reservoir.   The chromatography processing chip according to claim 1, wherein the test substance fixing surface is arranged in parallel with a liquid suction / discharge direction.   Claims wherein the dispensing tip is provided with an enclosing portion that encloses the porous stationary phase carrier in a predetermined arrangement position in the dispensing tip so as to be in contact with the mobile phase solution flowing into the dispensing tip. The chromatography chip according to claim 1 or 2.   On the test substance fixing surface of the porous stationary phase carrier, a mobile phase storage line drawn in a direction perpendicular to the suction / discharge direction at an interval in the suction / discharge direction, the predetermined region, a positive control line, The chromatography chip according to claim 1, wherein negative control lines are provided in order from the lower side to the upper side. A processing head capable of mounting one or more dispensing tips capable of sucking and discharging a liquid by a suction and discharging mechanism;
A suction / discharge mechanism that is provided in the processing head and sucks / discharges a liquid to the dispensing tip attached to the processing head;
From one or two or more tip accommodating portions that accommodate one or two or more dispensing tips so as to be attachable to the processing head, and one or two or more liquid accommodating portions that can accommodate or accommodate various liquids. A container group,
Moving means for moving the processing head relative to the container group,
At least one of the dispensing tips is provided with a test substance fixing surface on which a predetermined amount of a test substance that can adsorb, capture, separate, or bind a target substance in a mobile phase solution is fixed in a predetermined region. A chromatographic processing chip in which a solid stationary phase carrier is enclosed in a dispensing chip,
The suction, discharge amount, time or position of the suction / discharge mechanism is determined according to the structure of the chromatography chip mounted on the processing head, the type of substance present in the mobile phase solution, the concentration, and the mobile phase. Control is performed based on the amount of the solution, the temperature of the mobile phase solution or the porous stationary phase carrier, and the material condition consisting of at least one selected from the coordinate positions including the storage position of the mobile phase solution, and the processing content The chromatography processing apparatus which further has a control part.   The chromatography processing apparatus according to claim 5, further comprising a measurement unit that optically measures an optical state of the porous stationary phase carrier sealed in the chromatography processing chip on the test substance fixing surface.   The optical state of the test substance fixing surface is defined as the emission intensity of a fluorescent substance or a chemiluminescent substance labeled with a target substance bound to the test substance fixed to the test substance fixing surface. The chromatography apparatus as described. The measurement unit is provided corresponding to the chromatography processing chip, has a measurement end provided so as to be close to each of the test substance fixing surfaces, and is coupled to each of the test substance fixing surfaces. A plurality of light guides provided so as to be able to guide the light obtained based on the optical state that can be generated to the connection end;
Each of the test substance fixing surfaces so that the measurement ends of the plurality of light guide paths simultaneously reach a predetermined measurement position of each of the corresponding test substance fixing surfaces of the chromatography processing chips at a predetermined scanning period. A measuring head provided so as to be relatively movable with respect to
While the measurement ends are moved to the predetermined measurement position by the measurement head or stopped at the predetermined measurement position, the plurality of light guide paths are sequentially selected at a predetermined selection period, and the selected light guide paths A light guide path selection unit having a light guide region that is optically connected to the connection end of the light source and allows incident light to be emitted;
A light receiving unit that sequentially receives and photoelectrically converts the light emitted from the light guide region; and a digital data conversion unit that sequentially converts the image area data obtained from the light receiving unit at the predetermined selection period to obtain digital data. ,
The chromatography processing apparatus according to claim 6, further comprising storage means for sequentially storing the digital data.   A magnetic force mechanism capable of applying and removing a magnetic force in a dispensing tip attached to the processing head and / or an outside of the dispensing tip or the chromatography processing tip attached to the processing head. 6. The chromatography apparatus according to claim 5, wherein a temperature elevating body that is provided so as to approach or be accessible and raises or lowers a temperature by an external signal is controlled by the control unit. A thin tube having a mouth portion at the lower end for suction and discharge of liquid that is inserted into the container and a thick tube provided on the lower side with a reservoir portion for storing the suctioned liquid communicating with the narrow tube, and having translucency A test substance in which a predetermined amount of a test substance capable of adsorbing, capturing, separating, or binding the target substance in the aspirated mobile phase solution is fixed in a predetermined area in the thick tube of the dispensing tip. Attached to a processing head provided with a suction / discharge mechanism that enables suction / discharge of liquid to a chromatographic processing chip enclosing a porous stationary phase carrier provided with a substance fixing surface,
The amount, time or position of suction or discharge of the suction / discharge mechanism is determined according to the structure of the chromatography chip mounted on the processing head, the type of substance present in the mobile phase solution, the concentration, and the mobile phase. Control based on the amount of the solution, the temperature of the mobile phase solution or the porous stationary phase carrier, and at least one substance condition selected from coordinate positions including the storage position of the mobile phase solution, and the processing content The chromatographic treatment chip is moved relatively to the liquid container containing the mobile phase solution, and the porous stationary phase carrier and at least the mobile phase solution are brought into contact with each other. A chromatographic processing method for performing chromatographic processing. In the execution step of the chromatography method, the mobile phase solution is sucked to a predetermined position of the reservoir portion of the chromatography chip by the suction / discharge mechanism, and a constant liquid is applied to the lower end of the porous stationary phase carrier. Moving the mobile phase solution along the test substance immobilization surface by contacting the amount,
The residual liquid of the mobile phase solution is discharged from the chromatography chip, and the chromatography chip is moved to a liquid storage part in which a developing solution and / or a cleaning solution is stored by a moving means,
The developing liquid and / or the cleaning liquid is sucked up to the reservoir by the suction / discharge mechanism, and a fixed liquid amount is brought into contact with the lower end of the porous stationary phase carrier so that the developing liquid and / or the cleaning liquid is brought into contact with the test substance fixing surface. The chromatographic processing method according to claim 9, wherein the chromatographic processing method is moved along the line.   12. The chromatography method according to claim 11, wherein after the chromatography process execution step, the test substance immobilization surface of the porous stationary phase carrier enclosed in the chromatography chip is optically measured.   The optical state on the test substance fixing surface is labeled with a target substance bound to the test substance fixed on the test substance fixing surface, among fluorescent substances or target substances labeled with chemiluminescence. The chromatographic treatment method according to claim 11, which is a fluorescent substance or chemiluminescence emission intensity. In the measurement step, the light based on the optical state generated by the reaction in each chromatography processing chip, the measurement ends of a plurality of light guides provided corresponding to the chromatography processing chips, A scanning step of moving relative to the test substance fixing surface of the porous stationary phase carrier and simultaneously reaching a predetermined measurement position corresponding to each of the test substance fixing surfaces in a predetermined scan cycle;
While the measurement end moves to or stops at the measurement position of the detection substance fixing surface in each chromatography processing chip, all of the plurality of light guide paths are moved at the predetermined selection period. A light guide path selection step that sequentially selects and allows light from the connection end of the selected light guide path to be emitted to the light receiving surface of the light receiving unit;
A light receiving step in which the light receiving unit sequentially receives light emitted from the selected light guide path and performs photoelectric conversion;
The chromatographic processing method according to claim 12, further comprising: a digital data conversion step of sequentially converting the image area data obtained from the light receiving unit into digital data at the predetermined selection period and sequentially storing the digital data.   A step of applying and removing a magnetic force in a dispensing tip attached to the processing head by a magnetic mechanism, or external to the outside of the dispensing tip or chromatographic processing tip attached to the processing head The chromatography processing method according to claim 9, further comprising a step of bringing a temperature raising / lowering body that raises or lowers the temperature in accordance with a signal from.

Images