WO2006013832A1 - 検体の光情報認識装置およびその認識方法 - Google Patents
検体の光情報認識装置およびその認識方法 Download PDFInfo
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- WO2006013832A1 WO2006013832A1 PCT/JP2005/014057 JP2005014057W WO2006013832A1 WO 2006013832 A1 WO2006013832 A1 WO 2006013832A1 JP 2005014057 W JP2005014057 W JP 2005014057W WO 2006013832 A1 WO2006013832 A1 WO 2006013832A1
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- specimen
- sample
- optical information
- information recognition
- optical
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/251—Colorimeters; Construction thereof
- G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/08—Optical fibres; light guides
Definitions
- the present invention relates to an optical information recognition apparatus for a specimen and a recognition method thereof.
- the present invention relates to an optical information recognition apparatus for a specimen and a recognition method thereof.
- the present invention relates to an optical information recognition apparatus for a specimen and a recognition method thereof.
- FIG. 15 shows a conventional optical information recognition apparatus 101 for a specimen.
- a conventional optical information recognition apparatus for a specimen will be described with reference to FIG.
- a conventional optical information recognition apparatus 101 for a sample obtains optical information from a sample storage unit 105 that stores a sample 103 to be measured, a light source 107 that outputs light for observing the sample 103, and the sample 103.
- a sample measuring unit 111 including a light detecting unit 109 that performs light collection, a condensing unit 113 that condenses the sample 103 to irradiate the sample 103 with the light output from the light source 107 and propagated through the space.
- the specimen storage unit 105 has a plate reader 105a structure or a chip reader 105b structural force.
- the plate reader 105a has a structure in which a plurality of recesses are formed in the sample storage unit 105 at arbitrary intervals, and the sample 103 is stored in the recesses.
- the chip reader 105b has a structure in which the surface of the sample storage unit 105 is formed smoothly, and the sample 103 is arranged at an arbitrary interval on the surface.
- Patent Document 1 US Pat. No. 5,445,994
- Patent Document 2 US Pat. No. 5,744,305
- Patent Document 3 International Publication WO02Z063300
- the above-described conventional optical information recognition apparatus for specimens has the following problems.
- the sample storage unit in which the sample is stored, in the above chip reader, the sample storage unit is a measurement system having a planar structure, and the sample may be evaporated immediately after spotting. There is a problem.
- the sample concentration and the liquid surface position change due to evaporation it is difficult to use for the purpose of measuring the progress of the reaction in real time.
- the above-mentioned plate reader performs reaction and measurement using several tens to several hundreds of microliters of liquid per well. Therefore, the sensitivity to meet the need to minimize the amount of sample used. It is difficult to measure a small amount of sample due to problems such as lack of reaction and insufficient reaction. Further, in the plate reader as well as the chip reader, the means for obtaining the optical information obtained from the specimen is fixed, so the position of the specimen for obtaining the optical information is always the same position and one place. For this reason, if the position of the specimen is deviated from an arbitrary position, there is a problem that light information obtained from the specimen is reduced and measurement sensitivity is lowered.
- a conventional optical information recognition apparatus for a specimen has a configuration in which light output with light source power is propagated through the space and irradiated on the specimen. If there is a space (air layer) between the specimen and the optical measurement system (light source or light detection unit), optical noise due to Fresnel reflection occurs when light propagates, resulting in a decrease in measurement sensitivity. There was a problem. Furthermore, since the specimen is exposed to the space, there is a risk that contamination will be mixed in after the specimen is stored in the specimen storage section.
- the present invention has been made to solve the above-described conventional problems, and an object of the present invention is to provide an optical information recognition apparatus for a specimen that can measure a sample with high sensitivity, and a recognition method therefor. There is.
- one aspect of the present invention includes a sample storage unit that stores a sample to be measured, a sample measurement unit that includes a light detection unit that obtains optical information from the sample, the sample storage unit, and the sample measurement And an optical waveguide for propagating light between the two parts, and a specimen optical information recognition apparatus that recognizes specimen optical information from measured values obtained under at least two measurement conditions.
- a sample measurement unit including a sample storage unit that stores a sample to be measured, a light detection unit that obtains optical information from the sample, and the sample
- An optical information recognition apparatus for a sample comprising: an optical waveguide for propagating light between the storage unit and the sample measurement unit; and a measurement auxiliary liquid interposed between the tip of the optical waveguide and the sample is there.
- another aspect of the present invention includes a sample storage unit that stores a sample to be measured, a sample measurement unit that includes a light detection unit that obtains optical information from the sample, and the sample storage unit And an optical waveguide for propagating light between the specimen measuring section and the specimen measuring section, wherein the specimen accommodating section has at least the affinity between the specimen contacting the specimen and the specimen, and the other face and specimen
- a sample storage unit that stores a sample to be measured
- a sample measurement unit that includes a light detection unit that obtains optical information from the sample
- the sample storage unit And an optical waveguide for propagating light between the specimen measuring section and the specimen measuring section, wherein the specimen accommodating section has at least the affinity between the specimen contacting the specimen and the specimen, and the other face and specimen
- another aspect of the present invention includes an optical information recognition device for a specimen described above, a measurement device that obtains information on a specimen by operating the optical information recognition apparatus for the specimen,
- a sample measurement system equipped with a control / analysis device that analyzes information and controls the optical information recognition device for the sample.
- the sample storage unit determines the affinity between the surface other than the location where the sample is stored and the sample, and the surface of the storage location and the sample.
- contamination of specimens stored in other specimen storage units contamination
- the specimen storage section has a concave cross-sectional shape for accommodating a specimen, and the opening depth of the concave section is formed to be greater than the opening diameter.
- the specimen can be easily accommodated in this shape by keeping the hydrophilicity of the inner wall of the recess more than the other surface.
- the same effect can be obtained by making the specimen container a shape that prevents air accumulation such as a penetrating shape.
- the hole diameter is 1.5 mm or less, or less than the same area, and the specimen itself can be used even if it is a through-hole by appropriately selecting the hydrophilicity / hydrophobicity of the wall surface according to the hole shape
- the specimen is held by the wall surface or the bottom of the through hole without falling off due to the surface tension.
- the position of the specimen liquid surface can be stabilized by forming the opening at the top of the hole into a mortar shape.
- the specimen will go down the hole due to the weight of the specimen in this part, but as the volume of this part gradually decreases, Surface tension ⁇ Adsorption force with the wall surface is superior, and the sample stops descending and stops.
- the hole diameter is 1.5 mm or less or the same area or less
- the shape and physical properties of the sample container and the sample, and the affinity between them are dominant as the factors for determining the position of the upper surface of the sample. There is little contribution. Therefore, even if the supply amount of the sample fluctuates, the position of the stored sample surface can be managed almost constant.
- the measurement auxiliary liquid can be easily supplied by forming the opening at the top of the hole into a mortar shape.
- a very simple application such as a needle beside the optical waveguide tip structure.
- the specimen and the tip of the optical waveguide can be sufficiently brought close to each other.
- the volume of the mortar-shaped part is large, there is an advantage that even if the supply amount of the measurement auxiliary liquid varies, problems such as contamination do not occur if the measurement conditions change.
- the specimen position can be changed by making the lower part of the specimen a sealed structure and changing the volume or pressure of this part. Using the sensing function to detect the liquid level position, the specimen liquid level position can be accurately controlled.
- the specimen storage section is provided with temperature control means for controlling the temperature of the specimen, and is provided with vibration means for oscillating the specimen and promoting the reaction. For this reason, the sample can be stirred even at a volume level (nL) where the sample is difficult to stir by pipetting. Further, since the specimen can be agitated without using a means for agitating the specimen in contact with the specimen, contamination can be prevented from being mixed. Furthermore, by controlling the temperature of the specimen container, temperature control suitable for specimen observation or temperature control suitable for specimen agitation / reaction can be performed. For this reason, observation and measurement can be performed in an optimal state (observation temperature, reaction state) of the specimen.
- the measurement auxiliary liquid is interposed between the tip of the optical waveguide and the sample, so that the light irradiated to the sample does not propagate through the air layer.
- the optical information of the specimen force is coupled to the optical waveguide without passing through the air layer.
- Fresnel reflection can be reduced, enabling high-sensitivity measurement without bringing the tip of the optical waveguide into contact with the specimen, and even if another specimen is continuously measured, another specimen can be measured. It is possible to prevent contamination from entering.
- the specimen is sealed with the measurement auxiliary liquid without contacting the air layer, evaporation of the specimen can be prevented.
- the tip including the optical waveguide or the portion to which the optical waveguide is fixed is tapered, the tip of the optical waveguide can be brought closer to the specimen even when the amount of specimen is small.
- the tip including the optical waveguide or a portion to which the optical waveguide is fixed has a tapered shape, it can easily move not only outside the specimen container but also inside the specimen container. be able to.
- the optical waveguide has a movable structure in order to scan the specimen at its tip. Therefore, optical information from the specimen can be obtained at a plurality of places, for example, a plurality of places where the distance and angle of the specimen force are different. Furthermore, optical information from the specimen can be recognized based on measurement values obtained under a plurality of measurement conditions such as wavelength and light intensity. As a result, the measurement value does not vary regardless of the position of the sample in the sample container, and measurement with high sensitivity and high reproducibility is possible.
- the measurement auxiliary liquid is insoluble in water, it is not mixed with the specimen.
- the optical waveguide can be measured at a position closer to the specimen without passing through the air layer, and the specimen can be kept in an optimum state without being dried. High sensitivity can be measured.
- FIG. 1 (a) to FIG. 1 (c) are schematic configuration diagrams showing an embodiment of a sample optical information recognition apparatus of the present invention.
- FIGS. 2 (a) to 2 (d) are schematic views showing an embodiment of a sample storage unit used in the sample optical information recognition apparatus of the present invention.
- FIGS. 3 (a) to 3 (c) are schematic views showing an embodiment of an optical waveguide used in the optical information recognition apparatus for a specimen of the present invention.
- FIG. 4 (a) is a plan view showing an embodiment of an optical waveguide used in the optical information recognition apparatus for a specimen of the present invention
- FIG. 4 (b) is a cross-sectional view taken along line AA in FIG. 4 (a). It is.
- FIG. 5 is a schematic view showing an example of scan measurement using an optical waveguide of the optical information recognition device for a specimen of the present invention.
- Fig. 6 is a schematic view showing one embodiment of the sample measurement system of the present invention.
- FIG. 7 is a schematic configuration diagram showing an embodiment of a measuring apparatus of the sample measuring system of the present invention.
- FIG. 8 is a schematic view showing a measuring means of the measuring apparatus of the sample measuring system of the present invention.
- Fig. 9 is a schematic view showing a sample collecting means of the measuring apparatus of the sample measuring system of the present invention.
- Fig. 10 is an explanatory diagram in the case where the specimen storage portion includes a mortar-shaped opening.
- Fig. 11 is a diagram showing an example of the configuration of the specimen container of the present invention.
- FIG. 12 is a diagram showing an example of a liquid level control system according to the present invention.
- FIG. 13 is a cross-sectional view showing one relationship between a measurement auxiliary liquid, a sample, and a sample container.
- FIG. 14 is a cross-sectional view showing another structure of the specimen container.
- FIG. 15 is a schematic configuration diagram showing a conventional optical information recognition apparatus for a specimen.
- FIG. 16 is a schematic cross-sectional view showing a conventional specimen container.
- FIG. 17 is a schematic cross-sectional view showing another example of a conventional specimen container.
- FIG. 1 (a) to FIG. 1 (c) are main part configuration diagrams of an embodiment of an optical information recognition apparatus 10 for a specimen according to the present invention.
- the sample optical information recognition apparatus 10 of the present embodiment includes a sample storage unit 14 that stores a sample 12 to be measured, a light source 16 that outputs light for observing the sample 12, and A sample measurement unit 20 including a light detection unit 18 for obtaining optical information from the sample 12, and an optical waveguide 22 for propagating light between the sample storage unit 14 and the sample measurement unit 20.
- a measurement auxiliary liquid 24 is interposed between the optical waveguide 22 and the specimen 12.
- the specimen container 14 is generally a force that can be manufactured by cutting or molding a metal * waxen 'glass or the like and applying a desired coating to the surface as necessary. As shown in (a), it can also be configured by installing the accommodating portion 32 in which the fine hole shown in FIG. 2 (b) is formed on the substrate portion 30. The substrate part 30 is treated so that its surface has hydrophilicity by polymer coating. Further, the sliced storage portion 32 can be surface-treated so that the inner peripheral surface of the fine hole has hydrophilicity by polymer coating in the same manner as the substrate portion 30.
- the accommodating portion 32 can also be used by slicing a long glass body capable of propagating light such as an optical fiber.
- the part other than the inner peripheral surface of the fine hole has hydrophobicity due to the characteristics of the material.
- the inner peripheral surface of the fine hole of the accommodating portion 32 and the substrate portion 30 disposed on the bottom thereof can be surface-treated so as to have hydrophilicity by polymer coating. This treatment can prevent the sample from adhering to and aggregating on the inner surface of the sample container 14.
- the slice end surface of the storage portion 32 is hydrophobic due to the characteristics of the material, it is possible to prevent contamination from entering into other sample microholes.
- the container structure of the sample container 14 has a well shape with a depth larger than the opening diameter in Fig. 2 (d).
- the opening diameter of the specimen storage unit 14 is controlled by, for example, the design of a fine hole in the storage unit 32.
- the depth of the specimen container 14 is controlled by the number of stacked layers of the sliced container 32 as shown in FIG. 2 (c), for example.
- a well shape (diameter: 0.1 mm, depth: 0.3 mm) with a large opening diameter can be used. Efficient reaction is realized by reducing the contact area to prevent evaporation and ensuring the freedom of reaction of the sample. In addition, this shape enables high-sensitivity measurement because the measurement capacity per unit measurement area is increased.
- FIG. 11 shows an example of the configuration of the specimen storage unit of the present invention.
- a through hole is provided at the bottom of the opening on the mortar to accommodate the specimen.
- Lower force Since the air is released, the specimen supplied from the upper part descends by the weight of the specimen itself in the opening as shown in (b). Since it stops at a certain place, the liquid level can be managed constant. Note that the position of the specimen surface at this time is substantially constant regardless of the amount of specimen to be supplied (see (c)).
- FIG. 12 shows an example of a liquid level control system.
- a cylinder structure is provided under the through hole, and the liquid level can be raised and lowered by changing the pressure.
- the liquid level position can be accurately managed.
- the liquid surface position information from the sensor can also be used for optical waveguide position correction without being used for feedback to liquid surface position control. With either method, accurate analysis is possible by managing the distance between the optical waveguide tip and the sample liquid surface constant.
- the specimen storage unit 14 may further be a functional thin film in which a temperature control unit and a vibration unit are installed on the substrate unit 30. This is used when the sample amount of the specimen is very small and the reaction of the specimen is promoted. In general, if the amount of sample is large, the reaction can be promoted by stirring by pipetting. However, if the amount of sample is very small, when stirring by pipetting, it is difficult to agitate on a scale, and contamination will be mixed in other fine holes. For this reason, temperature control suitable for the reaction of the specimen is performed by the temperature control means, and the reaction of the specimen is promoted by the vibration means, so that a highly efficient reaction can be performed.
- the sample measurement unit 20 includes a light source 16 that outputs light for measuring the sample 12 and a light detection unit 18 that obtains optical information obtained from the sample 12.
- the light output from the light source 16 is transmitted through the specimen 12 by force, and the propagation direction of the light information obtained from the sample 12 is converted by 90 ° without passing through the light source 16 by force.
- a beam splitter 26 for propagating to the light detection unit 18 is installed.
- the beam splitter 26 may be installed as necessary. Also, depending on the location of the light source 16 and the light detector 18, the direction of propagation can be changed. The angle may be set arbitrarily. Furthermore, if the optical waveguide 22 described later has a two-core optical fiber structure, the beam splitter 26 need not be used.
- the optical waveguide 22 is provided with an optical fiber and a lens 28 for coupling the light output from the specimen measuring unit 20 to the optical fiber.
- the light output from the specimen measurement unit 20 is collected via the lens 28 and coupled to the optical fiber.
- the light coupled to the optical fiber propagates in the optical fiber, and is irradiated onto the specimen 12 through the measurement auxiliary liquid 24 from the end face of the optical fiber on the specimen 12 side.
- a plurality of optical fibers may be arranged as necessary.
- the installation structure and the number of optical fibers are not particularly limited, but a bundle like a bundle fiber is preferable because the accommodation space is narrow. In this way, by arranging a plurality of optical fibers, it is possible to measure a specimen in a wider range. In addition, optical information obtained from the specimen can be obtained without omission and high-sensitivity measurement is possible.
- the measurement auxiliary liquid 24 is interposed between the end surface of the optical waveguide 22 on the sample 12 side and the sample 12.
- the measurement auxiliary liquid 24 is preferably water-insoluble and low in volatility.
- silicone oil used as a refractive index matching agent is suitable.
- the measurement auxiliary solution 24 is stored in the sample storage unit 14 together with the sample 12 for the purpose of protecting the sample and assisting the measurement, and is not limited to the above-described components. Further, the measurement auxiliary liquid 24 is preferably liquid, but may be gel.
- the optical information recognition apparatus for the specimen 12 through which the measurement auxiliary liquid 24 is interposed and the recognition method thereof will be described in detail below.
- the well opening of the specimen container 14 is covered with a droplet of the measurement auxiliary liquid 24, and the measurement is performed with the tip core portion 22a of the optical waveguide 22 in contact with the droplet.
- the optical measurement system for example, the tip of the optical fiber
- the core portion 22a of the optical waveguide 22 and the measurement auxiliary liquid 24 have the same refractive index, the Fresnel reflection loss at the interface between them is reduced, and highly sensitive measurement is possible.
- the sample 12 is an aqueous solution, if an aqueous measurement auxiliary solution is used, it dissolves in the solution of the sample 12, and changes in the dilution rate, the tip of the optical waveguide There is a risk of contamination. Therefore, depending on the application, the risk of contamination adherence can be avoided by using a water-insoluble measurement auxiliary solution.
- the measurement head of the optical waveguide 22 as the end face of the optical fiber, it is possible to irradiate and receive light in a very small region, and realize high-sensitivity measurement compared to a conventional optical system using an objective lens. be able to. In both comparative experiments using a plate reader, it was possible to measure even ultra-small samples of 0. InL in a peptide reaction solution using an optical fiber.
- the optical fiber 40 shown in FIG. 4 is used as the optical waveguide 22.
- the optical fiber 40 supplies the measurement auxiliary liquid 24 from the droplet supply hole 23 and processes the tip into a trapezoidal shape to instantaneously form a droplet on the core portion 22a. Since this droplet covers the measurement well (specimen container 14), evaporation of the specimen 12 can be prevented.
- the tip shape of the optical waveguide 22 is not limited to the trapezoidal shape, or the tip shape including the adjacent member (for example, ferrule) to which the optical waveguide 22 is fixed is a cone or a pyramid. Or a wedge shape.
- the tip of the optical waveguide 22 can be disposed at every corner in the specimen container 14. Therefore, the measurement accuracy becomes higher.
- FIG. 3 (a) to FIG. 3 (c) show an example of the supply process of the measurement auxiliary liquid 24 and the sample 12 and the measurement start state.
- the sample 12 is injected into the sample container.
- the measurement auxiliary liquid 24 is supplied to the tip of the optical fiber from the hole 23 for supplying the measurement auxiliary liquid of the optical fiber 40 described above to form a droplet.
- the tip of the optical fiber 40 is brought close to the sample, and the sample and the measurement auxiliary liquid are brought into contact with each other.
- the supply process of measurement auxiliary liquid 24 and sample 12 After supplying the measurement auxiliary liquid 24, the optical fiber 40 is moved closer to contact with the measurement auxiliary liquid 24, or the optical fiber 40 is moved closer to the specimen 12 and the measurement auxiliary liquid 2 4 is placed in the gap between the two. Even the method of supplying
- the measurement of the specimen is performed at only one place, but the tip of the optical waveguide can be moved to a position where the distance and angle from the specimen are different.
- the structure can scan the specimen at a plurality of locations.
- the first time is performed by positioning the tip of the optical waveguide in the measurement auxiliary liquid
- the second time is when the tip of the optical waveguide is moved upward in FIG. Do not place it in the measurement auxiliary liquid!
- the optical information of these two measurement results can be recognized. Note that the number of measurements is not limited to two as described above, but is appropriately selected.
- the measurement at a plurality of locations is described by moving the optical waveguide.
- the measurement is performed under a plurality of measurement conditions such as changing the wavelength or light intensity for measuring the analyte force without moving the optical waveguide. Can also be performed. In this case, it is possible by controlling the light source and photodetector.
- the optical information of the specimen can be recognized from the measurement values obtained under at least two measurement conditions, the specimen with higher sensitivity can be measured.
- FIG. 13 is a cross-sectional view showing the relationship between the measurement auxiliary liquid, the sample, and the sample container.
- a through-hole is provided in the center of the specimen container 14.
- measurement auxiliary solutions 24 are arranged above and below the specimen 12.
- the measurement auxiliary liquid 24 positioned above the specimen 12 and the measurement auxiliary liquid 24 positioned below the specimen 12 may be the same auxiliary liquid or different auxiliary liquids.
- inject other liquids with different specific gravity in order.
- the same auxiliary liquid for example, mix in the mortar part of the specimen container and then inhale.
- FIG. 13 (b) only the upper side of the specimen 12
- the measurement auxiliary liquid 24 is arranged in
- FIG. 14 is a cross-sectional view showing another structure of the specimen container.
- the sample 12 in the cross-sectional shape, the sample 12 is arranged on the upper surface of the sample container 14 having a flat upper surface portion, and the measurement auxiliary liquid 24 is arranged so as to cover the entire sample. Is done.
- the specimen container 24 having a wedge-shaped portion on the upper surface is used in the cross-sectional shape.
- the sample 12 is arranged on the wedge-shaped portion, and the measurement auxiliary liquid 24 is arranged on the wedge 12 so as to cover the whole.
- a specimen container 14 having a semicircular portion on its upper surface in the cross-sectional shape is used.
- the sample 12 is disposed in the semicircular portion, and the measurement auxiliary liquid 24 is disposed thereon so as to cover the whole.
- the sample is arranged in a shape corresponding to each shape of the sample container.
- FIGS. 6 to 9 show a specimen optical information recognition measurement system 50 in which the reaction of the specimen and reagent, the optical information recognition apparatus shown in FIGS. 1 to 5 and the recognition method thereof are integrated.
- the optical information recognition measurement system 50 includes a measurement device 52, a measurement device 54, and a control / analysis device 56.
- this embodiment shows a fully automatic system. By automating each process, measurement can be quantified and contamination can be prevented. The outline of reaction and measurement operation is described below.
- the board surface of the measuring device 52 includes a three-dimensional rotary head 58, a reaction substrate 60, a sample / reagent tank 62, a cleaning tank 64, and a drying tank 66.
- the head portion 58 holds a pipette 68 for collecting a small amount of sample and a wedge fiber measuring portion 70.
- the head portion 58 has a structure capable of moving and rotating in accordance with each process. It has become.
- Sample • Reagent tank 62 contains the target sample (specimen) and the peptide library.
- the 3D rotary head 58 first cleans and dries the tip of the pipette 68, obtains the predetermined library, and then obtains the reaction substrate 60. Dispense to the designated wel.
- the tip of the pipette 68 is washed and dried to obtain a sample, which is then dispensed into the well where the library of the reaction substrate 60 has been dispensed.
- the sample reaction is a means of temperature control. Alternatively, it is performed under conditions optimized by vibration means (not shown).
- the three-dimensional rotary head 58 rotates and seals the well with the measurement auxiliary liquid from the tip of the wedge fiber measuring unit 70 to prevent the evaporation of the solution and stabilize the optimum reaction conditions.
- the number of axes per tool can be reduced, making it easy to make lightweight and small-sized moving parts.
- a precise positioning structure such as backlash can be easily realized.
- the tip of the wedge fiber measurement unit 70 is in contact with the measurement auxiliary liquid and is in a measurement standby state or a state in which observation over time is started, and measurement is performed until the reaction end time.
- the head 58 moves up, and thereafter, the entire process is executed by repeating the reaction and measurement.
- the wedge fiber measuring unit 70 is scanned in the well while being sealed with the measurement auxiliary liquid, and the maximum value is obtained.
- the fluorescent dye to be measured differs depending on the application, it is possible to support multi-color by preparing a wedge fiber head for each dye. In addition, more sensitive measurement can be performed by irradiating the sample with fluorescent light having the optimum characteristics.
- optical information recognition measurement system for specimens is a versatile system that can be widely applied by one system as well as analysis of peptide protein analysis and single cell ligand screening. Examples of applications include real-time analysis of stem cell sorting processes, analysis of highly specific SNPs, real-time analysis of cells based on drug effects, and high-sensitivity measurement of cells and proteins using nanophosphors. System.
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Abstract
Description
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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US11/659,132 US7999929B2 (en) | 2004-08-02 | 2005-08-01 | Specimen optical information recognizing device and its recognizing method |
JP2006531466A JPWO2006013832A1 (ja) | 2004-08-02 | 2005-08-01 | 検体の光情報認識装置およびその認識方法 |
EP05767144A EP1780532A4 (en) | 2004-08-02 | 2005-08-01 | DEVICE FOR RECOGNIZING OPTICAL INFORMATION OF A SAMPLE AND METHOD OF RECOGNIZING |
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JP2004226155 | 2004-08-02 | ||
JP2004-226155 | 2004-08-02 |
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EP (1) | EP1780532A4 (ja) |
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Cited By (2)
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JP2013181976A (ja) * | 2012-02-29 | 2013-09-12 | K-Mac | バイオリアクションデバイスチップ |
US9683927B2 (en) | 2011-12-02 | 2017-06-20 | Biochrom Limited | Device for receiving small volume liquid samples |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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US7957002B2 (en) * | 2009-03-13 | 2011-06-07 | The Furukawa Electric Co., Ltd. | Method for optical measurement and optical measurement apparatus |
FR3073940B1 (fr) * | 2017-11-20 | 2019-11-08 | Office National D'etudes Et De Recherches Aerospatiales | Dispositif optique autocalibrant pour la mesure sans contact du niveau d'un liquide |
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JP2013181976A (ja) * | 2012-02-29 | 2013-09-12 | K-Mac | バイオリアクションデバイスチップ |
Also Published As
Publication number | Publication date |
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JPWO2006013832A1 (ja) | 2008-05-01 |
US7999929B2 (en) | 2011-08-16 |
US20090021722A1 (en) | 2009-01-22 |
JP2011064702A (ja) | 2011-03-31 |
EP1780532A4 (en) | 2012-06-13 |
EP1780532A1 (en) | 2007-05-02 |
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