WO2005111572A1 - 試料調製装置及び方法 - Google Patents
試料調製装置及び方法 Download PDFInfo
- Publication number
- WO2005111572A1 WO2005111572A1 PCT/JP2005/008945 JP2005008945W WO2005111572A1 WO 2005111572 A1 WO2005111572 A1 WO 2005111572A1 JP 2005008945 W JP2005008945 W JP 2005008945W WO 2005111572 A1 WO2005111572 A1 WO 2005111572A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- container
- solution
- shaking
- sample
- sample preparation
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1065—Multiple transfer devices
- G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00524—Mixing by agitating sample carrier
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
- G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
Definitions
- the present invention relates to an apparatus and a method for preparing a specimen from a substance such as a carrier containing a biomolecule.
- proteome analysis has attracted attention as an important research in the post-genome era.
- proteome analysis exhaustive analysis of proteins contained in cells constituting living organisms is performed.
- protein separation by gel electrophoresis represented by two-dimensional electrophoresis and protein profiling using mass spectrometry have been performed. Rings are frequent.
- a typical analysis procedure first, a biological sample prepared for electrophoresis is separated on a polyacrylamide gel, stained, image analyzed, and spots of each protein are cut out based on the results. .
- a sample containing a digested peptide fragment as a sample sample for mass spectrometry is recovered using a solution reagent or the like. Then, mass spectrometry of the peptide fragment was performed, and the theoretical mass spectrum of the peptide fragment predicted from the database was compared with the measured mass spectrum pattern using a protein identification search engine, and digestion was performed. Identify the previous protein.
- Non-Patent Document 1 discloses a gel in which a gel plug containing a protein recovered from a two-dimensional electrophoresis gel is enzymatically digested in a plate, and then a process of automatically dispensing a peptide to another plate is performed.
- An enzymatic digestion apparatus product name: Ettan Digester
- Non-Patent Document 2 describes a series of procedures such as sampling, dispensing, dilution, and plate washing.
- a laboratory automation system product name: BIOMEK (registered trademark) 2000 in which the work of the above is automated is described.
- Non-Patent Document 3 discloses a mass spectrometry pretreatment automation device (product name) that automates in-gel enzymatic digestion, desalting 'concentration, and spotting of a protein isolated by electrophoresis on a target plate of a mass spectrometer. : MultiPROBE II).
- Non-Patent Document 4 discloses an in-gel protein digestion automation system (product name: Investigator ProGest) that automatically performs in-gel digestion of proteins separated by electrophoresis, and a sample preparation device for mass spectrometry (product name: Investigator ProMS), sample preparation automation system (product name: Investigator ProPrep), etc.
- Non-Patent Document 1 Amersham Bioscience Co., Ltd. “Spot Picking & Enzyme Treatment Gel Enzyme Digestion Equipment” pamphlet
- Non-patent document 2 Beckman Coulter, Inc. BIOMEK (registered trademark) 2000 Laboratory Automation System
- Non-patent document 3 PerkinElmer Japan Co., Ltd., “Life Science Budget Application Catalog 2003 ⁇ 2004” pamphlet, page 26, lower part (Mass Spectrometry Preprocessing Automation System)
- Non-Patent Document 4 Nippon Technolactas Co., Ltd. “Automated Protein Digestion System in Gel Investigator ProGest TM Protein Digestion Station” Nomfret
- the present invention has been made in view of powerful circumstances, and can cope with various protocols, sufficiently suppress strong variations, improve reproducibility, and improve reliability. It is an object of the present invention to provide a sample preparation device and a method capable of obtaining a high analysis result.
- a sample preparation device provides a material including a biomolecule.
- a biomolecule-containing substance Force A first container for preparing a test sample, in which the biomolecule-containing substance is stored, and a second container in which a solution to be injected into the first container is stored.
- Dispensing means for injecting the solution contained in the second container into the first container; moving and holding means for movably holding the first container; and Shaking means for stirring the biomolecule-containing substance and the solution, and a collecting means for discharging the shaken solution onto the first container and collecting the test sample in the third container.
- the biomolecule-containing substance is stored in the first container.
- the second container contains an appropriate solution to be injected into the first container. This solution is injected from the second solution into the first container by the dispensing means. The first container is moved to a desired position by the moving and holding means, and is held in that state.
- the first container moved and held at an appropriate position is shaken by shaking means, whereby the substance containing the biomolecule and the solution in the first container are stirred.
- the first container may be shaken via the moving and holding means.
- the biomolecules contained in the biomolecule-containing substance and the solution are sufficiently mixed. Therefore, the frequency of contact between the biomolecules in the biomolecule-containing substance and the solution is increased, compared to the case where the solution is simply injected into the biomolecule-containing substance and incubation or other treatment is performed in a stationary state. Non-uniform progress of the reaction or chemical operation is suppressed.
- various salts that hinder mass spectrometry can be efficiently removed by washing.
- the solution after the shaking treatment is discharged from the first container, and the solution that has interacted with the biomolecule in the biomolecule-containing substance is used as a subject for another processing operation. Collected in a third container as a sample.
- a collection process can be performed by, for example, moving the first container to an appropriate desired place by the moving and holding means, so that it becomes easy to equip a mechanism, a device, and the like for the collection.
- the second container individually accommodates a plurality of solutions of different types.
- various solutions eg, chemical reagents, digestive enzymes, etc.
- the interaction between each solution and the biomolecule-containing substance can be suitably performed using the moving and holding means and the shaking means. .
- the shaking means is such that the stirring speed is adjusted according to the type of the solution. Suitable conditions for mixing each solution with the biomolecule-containing substance differ depending on their interaction. Therefore, in the sample preparation device according to the present invention, the interaction between the biomolecule in the biomolecule-containing substance and the solution is sufficiently controlled by adjusting the stirring speed of the shaking means to a constant value according to each solution. It is performed with good reproducibility.
- a region where the first container is placed and a region where the second container is placed are provided continuously, and the region where the shaking is performed and the specimen sample are collected. It is more preferable that the region to be set is provided in parallel with the region where the first container is placed and the region where the second container is placed. In this way, it is possible to separate the area (area) where the dispensing operation into the first container is performed, which is a so-called static processing, from the area where the shaking operation and the like which are the dynamic processing are performed. Therefore, it is preferable in process management.
- a pressurizing means for supplying gas into the first container containing the solution after being shaken to pressurize the inside of the first container.
- the pressurizing means is more efficient It is preferable to provide a sealing means (for example, an elastic body such as silicon rubber or the like) at the time of pressurization in order to apply pressure.
- the sample preparation method according to the present invention is a method that is effectively performed using the sample preparation device according to the present invention, and is a method for preparing a sample from a biomolecule-containing substance.
- the solution accommodating step it is useful to use, as the second container, one in which a plurality of solutions of different types are individually accommodated.
- a sealing means for example, an elastic body such as silicon rubber or the like
- the solution is also supplied to the biomolecule-containing substance contained in the first container by the second container force, and then the first container is moved by the moving and holding means.
- the first container is kept, and is sufficiently stirred by shaking the first container under desired conditions. Then, since the solution is collected as a sample, the extraction and separation of the target component from the biomolecule-containing substance can be performed with high efficiency, and the reproducibility of the processing operation can be extremely enhanced. Therefore, it is possible to realize a process corresponding to various protocols, sufficiently suppress the variation in the analysis process in which the sample is provided, and improve the reproducibility to obtain a highly reliable analysis result. It is possible to obtain.
- FIG. 1 is a front view schematically showing a preferred embodiment of a sample preparation device according to the present invention.
- FIG. 2 is a cross-sectional plan view taken along line II-II in FIG.
- FIG. 3 is a right side view of the sample preparation device shown in FIG.
- the processing device 100 is a pretreatment device for preparing an analyte sample to be subjected to mass spectrometry, for example, a peptide mass fingerprinting (PMF) method utilizing enzymatic digestion in a gel, which will be described later.
- PMF peptide mass fingerprinting
- This is a pretreatment device for preparing an analyte sample to be subjected to mass spectrometry for identifying protein spots separated by electrophoresis.
- a chip disposal unit 3 a chip stage 4, and reagent reservoirs 5 and 6 (both are second containers) are arranged in a row on a base 2 in a housing 1, and a chip It is equipped with a temperature controller 7, vacuum holders 8 and 9.
- the chip stage 4 has a chip holder 41 on which a plurality of chips 42 are arranged in an array, for example.
- the chip 42 is formed in a slender, substantially cylindrical shape, and the number of chips placed on the chip holder 41 is not particularly limited.
- a chip having a capacity of 200 L has 8 columns ⁇ 12 rows (of the processing device 100).
- the direction orthogonal to the depth direction is referred to as the “row” direction.
- the reagent reservoir 5 (second container) has a concave portion 51 having a large depth and a small width in a horizontal cross section, and a proper reagent (solution) is accommodated in the concave portion 51.
- the reagent reservoir 5 functions as a constant temperature bath that holds the reagent contained in the concave portion 51 at a constant temperature, for example, a normal temperature.
- the reagent reservoir 6 (second container) is provided with a plurality (10 in the illustrated example) of recesses 61 having the same shape as the recesses 51 in the longitudinal direction of the processing apparatus 100. 61 is configured to store appropriate reagent solutions (solutions) different from each other. Still further, the reagent reservoir 6 functions as a thermostat that holds the reagent contained in the recesses 61,... At a low temperature of, for example, 4 ° C. (4 ° C. incubation).
- a dispensing head 10 (dispensing means) is provided vertically above the chip disposal section 3, the chip stage 4, and the reagent reservoirs 5, 6 arranged in a line.
- the dispensing head 10 includes a dispensing syringe probe 11 arranged in parallel in the depth direction with the same number of chips 42,... (Eight in the illustrated example).
- the dispensing head 10 itself is driven in the force train direction (arrow X direction in the figure) and the depth direction (arrow Y direction in the figure).
- the valve 11 is driven in the vertical direction (the direction indicated by the arrow Z in the figure).
- the method of driving the dispensing head 10 is not particularly limited, and for example, a one-way stage having a known guide rail provided above the dispensing head 10 or an XY stage can be used.
- the method of driving the syringe probe 11 in the vertical direction is not particularly limited, and a known motor device may be used, or an XYZ stage movable with the dispensing head 10 may be used.
- a gripping and shaking unit 15 is provided adjacent to the rear of the chip temperature control unit 7 and the vacuum marshalls 8 and 9.
- the gripping and shaking unit 15 has an arm-shaped stage 151 which can be gripped on the filter plate 81 (holding tool) and driven in the depth direction (Y direction in the drawing) on a stage 151 driven in the row direction (X direction in the drawing).
- Robot No. 152 (holding means) is attached.
- the gripping and shaking unit 15 has a PZT element 153 that comes into contact with the robot hand 152. Accordingly, the filter plate 81 held by the robot 152 is shaken at a predetermined shaking speed.
- the grip and shake unit 15 serves both as the movement holding means and the shake means of the present invention.
- the holding and shaking unit 15 is provided with a light-shielding cover (not shown) that can be opened and closed so as to cover the entire upper portion of the filter plate 81 held by the robot hand 152. With this cover closed, the filter plate 81 is sealed and shielded from light, and is sealed by nitrogen gas supplied from a nitrogen gas source (not shown) connected to the nitrogen gas supply port 21. The space is purged with nitrogen.
- a nitrogen gas source not shown
- the filter plate 81 for example, a filter plate in which a plurality of wells 82 (first containers) are arranged may be mentioned.
- the number of the plurality of wells 82 is not particularly limited, and, for example, there is a case where 96 pieces are arranged in 8 columns ⁇ 12 rows.
- the well 82 has a filter 83 on the bottom surface.
- the filter 83 include a PVDF membrane.
- the chip temperature control unit 7 is for mounting the filter plate 81 moved by the gripping and shaking unit 15, and for mounting the filter 82 on the filter plate 81.
- ... functions as a thermostat that holds the contents of (first container) at a temperature of, for example, 37 ° C (37 ° C incubation).
- the vacuum holder 9 is connected to an exhaust port 20 to which a decompression exhaust system (not shown) is connected.
- the contents of each well 82 on the filter plate 81 transferred by the filter 15 are recovered from the well 82 by so-called vacuuming.
- the vacuum manifold 8 is also connected to an exhaust port 20 to which a depressurizing exhaust system (not shown) is connected, and discharges residual liquid in the well 82 and performs depressurizing cleaning.
- the housing 1 is provided with a front door la on which a rod-shaped handle H is installed. With the front door la pushed upward, the space above the base 2 is opened, and the front door la is opened. With the door la pushed down, the space above the base 2 is shut off by external force. Further, a glass window W1 is provided on the front door la, and a glass window W2 is further provided on the side wall of the housing 1, so that the inside can be visually recognized.
- the front panel 30 below the front door la is inclined so as to protrude downward, and is provided with an emergency stop button 31, a tatchin nonel 32, a decompression monitor 33 in the vacuum manifolds 8, 9, and the like. Have been. Further, a nitrogen gas pressure gauge 35, an exhaust heat source 36, a temperature controller 37 of the chip temperature controller 7, and a temperature controller 38 of the reagent reservoir 6 are provided on a side surface 34 communicating with the front panel 30. RU
- peptides are extracted from protein spots separated by two-dimensional electrophoresis by the PMF method using enzyme elimination in a gel, and an analyte sample for mass spectrometry is prepared.
- a gel fragment of a protein spot is cut out and washed as a biomolecule-containing substance.
- a plurality of protein spots having a relatively high content and a relatively high content of isoelectric points or molecular weights on the polyacrylamide gel subjected to two-dimensional electrophoresis are selected by image processing or the like.
- a gel piece containing the selected protein spot is cut out.
- each gel piece (an example of a biomolecule-containing substance) is accommodated in each well 82 of the filter plate 81 (accommodation step).
- the filter plate 81 is placed on the vacuum holder 8.
- the following reagents are prepared and stored in recesses 51, 61,... At appropriate positions of the reagent reservoirs 5, 6 (solution storage step; hereinafter, stored in the reagent reservoir 6). It will be explained as something.)
- destaining is performed prior to in-gel digestion. Specifically, first, the dispensing head 10 is moved so that the syringe probes 11,... Of the dispensing head 10 are positioned on the tip 42 placed on the tip holder 41. Further, the syringe probes 11,... Are moved downward, and the tips 42 are attached to the respective syringe probes 11. Next, the dispensing head 10 is moved from the initial position so that the syringe probes 11,... Of the dispensing head 10 are positioned at the destaining solution contained in the reagent reservoir 6. Next, the plurality of syringe probes 11,...
- the syringe probes 11 are moved downward until the tip of the tip 42 is immersed in the destaining solution and stopped, and then, after inhaling an appropriate amount (for example, 200), the syringe probes 11,. Move it upward so that it comes to the initial position in the vertical direction.
- the dispensing head 10 is moved so that the syringe probes 11,... Of the dispensing head 10 are located on each of the wells 82 of the filter plate 81 placed on the vacuum holder 8. Further, the syringe probes 11,... Are moved downward, and the destaining solution sucked and held inside the chip 42 is injected into the well 82 (dispensing step). This dispensing operation is the same even if the solution is different, and the detailed description is omitted in the following description.
- the gripping shaking unit 15 After shaking, the gripping shaking unit 15 is driven, the filter plate 81 is transferred to the vacuum holder 8, and the vacuum exhaust system is operated to absorb the destaining solution remaining in the bottle 82. Discharge. Then, the gripping and shaking unit 15 is driven, and the filter plate 81 is transferred to the chip temperature controller 7 or the vacuum holder 8.
- a reducing solution is dispensed in place of the destaining solution, and the mixture is stirred at a high speed at room temperature for 30 minutes, and the remaining solution is suctioned and discharged.
- the alkylation solution is dispensed, and the mixture is stirred at a high speed for 30 minutes at room temperature.
- acetonitrile is dispensed, and the mixture is stirred at a high speed for 5 minutes, and then the remaining liquid is suctioned and discharged to dehydrate the gel pieces. Then, trypsin is dispensed, for example, at a rate of about 0.5 to 3 / z L and allowed to stand for about 5 to 10 minutes to swell the gel pieces.
- an ammonium bicarbonate is dispensed, for example, in an amount of about 10 to 20 ⁇ L and kept at 37 ° C. for about 5 to 12 hours, and then mixed with acetonitrile ZO.
- 1% TFA aqueous solution 1: 1.
- the liquid is dispensed, for example, at 100 / z L and stirred at a high speed for 15 minutes.
- the gripping and shaking unit 15 is driven, the filter plate 81 is transferred to the vacuum holder 9, and the vacuum exhaust system is operated.
- the solution (test sample) in the level 82 is collected by suction into the level 92 (third container) on the recovery plate 91 (recovery step).
- these collected liquids collected from the processing apparatus 100 as the test sample are combined, and centrifuged and concentrated, for example, to about 1 to 5 L. Further, after it is completely dried, it is separately prepared and dissolved in a mixed solution of 5% acetonitrile ZO. 1% TFA (for example, about 5 ⁇ L) to obtain a sample for mass spectrometry. The unnecessary chip 42 is discarded to the chip discarding unit 3.
- the gel pieces contained in the plurality of wells 82 According to the processing apparatus 100 configured as described above and the sample preparation method of the present invention using the same, the gel pieces contained in the plurality of wells 82,.
- the reagent solution is dispensed and transferred to the chip temperature control unit 7 together with the filter plate 81 by the holding and shaking unit 15. Then, shaking 'stirring is performed at an appropriate stirring speed.
- shaking 'stirring is performed at an appropriate stirring speed.
- the protein solution contained in the gel piece and the reagent solution are sufficiently mixed in a series of automated processes.
- the filter plate 81 is held at the distal end of the arm-shaped robot hand 152 of the gripping and shaking unit 15, that is, in a state where the distance is larger than the base of the gripping and shaking unit 15. As a result, the contents in the filter plate 81 are more easily stirred vigorously. Therefore, the protein molecules contained in the gel piece and the reagent solution are mixed better, and the extraction efficiency can be further improved.
- the filter plate 81 is moved by the vacuum shaping unit 15 by the gripping shaking unit 15. It is possible to transfer the liquid to the pipes 8 and 9 as needed, and to perform the suction and discharge of the remaining liquid in the well 82 and the suction and recovery of the sample on the spot. Recovers the solution.
- the layout design margin of the mechanism for Z discharge cleaning can be increased.
- the processing performance (throughput) when executing a protocol requiring various reagent solutions for each process can be improved.
- the agitation speed can be adjusted with good reproducibility according to the type of reagent solution by the gripping and shaking unit 15, so that the recovery efficiency (chemical yield) of the final recovered sample and the reproducibility of the recovered amount can be further improved. Can be enhanced.
- a chip disposal section 3, a chip stage 4, and reagent reservoirs 5 and 6 are arranged in a row on a base 2 in a housing 1, and the chip temperature is controlled.
- Part 7, Vacuum Holders 8, 9 are provided, so the filter plate 81 is settled and the area for dispensing operation, which is static processing, is shaken. This can be separated from the area for performing operations, which is a so-called dynamic process, which is preferable for process management.
- a shaking operation can be performed under an inert atmosphere, thereby suppressing an undesired reaction such as oxygen oxidation in the air. And the reproducibility of the concentration of the extracted components in the recovered sample can be more reliably maintained.
- the vacuum holders 8, 9 can be located directly below the filter plate 81, and as a result, the filter plate The reagent solution in the well 82 can be more easily collected than when the 81 is supported from below.
- FIG. 4 is a right side sectional view schematically showing a main part of another preferred embodiment of the sample preparation device according to the present invention.
- the processing apparatus 200 (sample preparation apparatus) is configured similarly to the processing apparatus 100 except that the processing apparatus 200 includes a nitrogen gas pressurizing head 70 (pressurizing means).
- the nitrogen gas pressurizing head 70 includes nozzles 71 arranged in parallel in the depth direction (the Y direction in the drawing) as many as the nozzles 82 (some are omitted in the illustrated example, but eight in number). Be prepared.
- the nitrogen gas pressurizing head 70 itself is driven in a row direction (arrow X direction in FIG. 2) and a depth direction (arrow Y direction in FIG. 2), and the nozzle 71 is moved in a vertical direction (arrow Z direction in FIG. 2).
- the driving method of the nitrogen gas pressurizing head 70 is not particularly limited as in the case of the dispensing head 10.
- a one-way stage having a known guide rail provided above the nitrogen gas pressurizing head 70 or an XY stage Etc. can be used.
- the method of driving the nozzle 71 in the vertical direction is not particularly limited, and a known motor device may be used, or an XYZ stage that moves together with the nitrogen gas pressurizing head 70 may be used.
- annular groove R is formed at the tip (the lower end in the figure) of the nozzle 71, and the annular groove R has an annular ring 72 (sealing means) made of an elastic material such as silicon rubber. ) Is fitted. Further, the nozzle 71 has a taper formed at a tip end portion of the annular ring 72, and the tip end is inserted into a well 82 juxtaposed to the filter plate 81. Further, a nitrogen gas supply pipe 73 connected to the nitrogen gas supply port 21 (see FIG. 2) is connected to the other end (the upper end in the figure) of the nozzle 71 via a joint 74.
- the robot hand 152 holds the filter plate 81 including the gel 82 containing the gel piece G and the reagent solution L and subjected to the shaking operation.
- the nitrogen gas pressurizing head 70 is moved to the vacuum holder 9 so that the nozzles 71,. Move to the upper predetermined position.
- the nozzles 71,... Are moved downward, the tip of the nozzle 71 is inserted into the well 82, and the annular ring 72 is brought into contact with the upper peripheral edge of the well 82, and the upper open end of the well 82 is sealed with the annular ring 72. Stop.
- the tip of the nozzle 71 including the annular ring 72 is urged in advance with an elastic body such as a panel, and the annular ring 72 is brought into contact with the upper edge of the well 82 while the annular ring 72 is in contact with the upper edge of the well 82. It is preferable to press against the well 82 with a predetermined pressing pressure, because the adhesion between the well 82 and the annular ring 72 and, further, the tightness inside the well 82 are further enhanced.
- a nitrogen gas (N 2) is supplied from a nitrogen gas source (not shown) through a nitrogen gas supply pipe 73.
- each nozzle 71 is supplied to each nozzle 71 at a predetermined pressure.
- the nitrogen gas Ng flowing through the internal space K of the nozzle 71 is sent out from the tip of the nozzle 71 into the column 82.
- the inside of the well 82 is pressurized by the nitrogen gas Ng, and the sample solution L is pushed downward from the lower open end 82a of the well 82.
- the sample solution L passes through the filter 83 and is collected in the vacuum holder 9 in the well 92 of the collection plate 91 (collection step).
- the processing apparatus 200 including the nitrogen gas pressurizing head 70 is particularly useful for proteome analysis (proteomics) in which sample collection efficiency is particularly important.
- processing device 200 has the same operation and effect as the processing device 100 described above, the detailed description is omitted here to avoid redundant description.
- the present invention is not limited to the above-described embodiment, and various modifications can be made without departing from the spirit and scope of the invention.
- the samples processed by the processing apparatuses 100 and 200 are not limited to gel pieces, but may be solid (body) or liquid (body) samples other than gel pieces.
- the processing devices 100 and 200 are not limited to only the processing operation involving in-gel digestion, and can be applied to various pretreatments of other carriers including biological samples.
- the number of the wells 82 held in the filter plate 81 and the wells 92 of the collection plate 91, the number of the concave portions 61 provided in the reagent reservoir 6, the layout on the base 2, and the like are not limited to those illustrated.
- the syringe 11 and the nozzle 71 may be provided integrally and integrally, or may be provided separately from each other.
- the sample preparation device and the method according to the present invention provide a moving holding means for holding a first container in a moving position, and a method for shaking the moving holding means to produce a sample in a first container. Since it is equipped with a shaking means for stirring the body molecule-containing substance and the solution, it is possible to cope with various protocols and sufficiently suppress the variation that has been a problem in the conventional sample pretreatment. In addition, it is possible to improve the reproducibility and obtain a highly reliable analysis result. Therefore, it can be widely used for analysis of substances containing biomolecules and sample preparation therefor.
- FIG. 1 is a front view schematically showing a preferred embodiment of a sample preparation device according to the present invention.
- FIG. 2 is a cross-sectional plan view taken along the line II-II in FIG. 1.
- FIG. 3 is a right side view of the sample preparation device shown in FIG. 1.
- FIG. 4 is a right side sectional view schematically showing a main part of another preferred embodiment of the sample preparation device according to the present invention.
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006513603A JPWO2005111572A1 (ja) | 2004-05-18 | 2005-05-17 | 試料調製装置及び方法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004-148371 | 2004-05-18 | ||
JP2004148371 | 2004-05-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005111572A1 true WO2005111572A1 (ja) | 2005-11-24 |
Family
ID=35394269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2005/008945 WO2005111572A1 (ja) | 2004-05-18 | 2005-05-17 | 試料調製装置及び方法 |
Country Status (2)
Country | Link |
---|---|
JP (1) | JPWO2005111572A1 (ja) |
WO (1) | WO2005111572A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109991049A (zh) * | 2017-12-29 | 2019-07-09 | 同方威视技术股份有限公司 | 用于食品安全检测的前处理装置以及前处理方法 |
WO2020017022A1 (ja) * | 2018-07-20 | 2020-01-23 | 株式会社島津製作所 | 振とう装置および分析方法 |
CN113432958A (zh) * | 2021-05-27 | 2021-09-24 | 浙江好搭档农业开发有限公司 | 一种用于农药残留检测中前处理的提取装置 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02187110A (ja) * | 1988-09-16 | 1990-07-23 | W R Grace & Co | マイクロフィルトレーション装置とその方法 |
JPH09304251A (ja) * | 1996-05-14 | 1997-11-28 | Aloka Co Ltd | 生物組織の処理装置及び処理容器 |
JPH10197534A (ja) * | 1996-12-18 | 1998-07-31 | Stiftung Fuer Diagnostische Forsch | 凝集により試験液中の分析物を検出するための方法及び試薬キット、固定リガンド分子を担持する合成粒子並びにその使用 |
JPH10332707A (ja) * | 1997-03-31 | 1998-12-18 | Japan Tobacco Inc | 自動分析システム |
US20020108857A1 (en) * | 2000-12-18 | 2002-08-15 | Michael Paschetto | Automated laboratory system and method |
JP2002286726A (ja) * | 1995-05-29 | 2002-10-03 | Hitachi Ltd | デイスポーザブルな反応容器を用いる分析装置 |
WO2003020426A1 (en) * | 2001-09-05 | 2003-03-13 | Irm, Llc | Parallel reaction devices |
JP2003532117A (ja) * | 2000-04-13 | 2003-10-28 | サーモ フィニガン リミテッド ライアビリティ カンパニー | 並列質量分析によるプロテオミクス解析 |
JP2004004078A (ja) * | 2002-05-24 | 2004-01-08 | Millipore Corp | 閉塞防止装置及びそのゲル内消化への適用方法 |
WO2004040313A1 (ja) * | 2002-11-01 | 2004-05-13 | Tss Biotech Inc. | 尿路上皮癌腫瘍マーカー |
-
2005
- 2005-05-17 WO PCT/JP2005/008945 patent/WO2005111572A1/ja active Application Filing
- 2005-05-17 JP JP2006513603A patent/JPWO2005111572A1/ja active Pending
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02187110A (ja) * | 1988-09-16 | 1990-07-23 | W R Grace & Co | マイクロフィルトレーション装置とその方法 |
JP2002286726A (ja) * | 1995-05-29 | 2002-10-03 | Hitachi Ltd | デイスポーザブルな反応容器を用いる分析装置 |
JPH09304251A (ja) * | 1996-05-14 | 1997-11-28 | Aloka Co Ltd | 生物組織の処理装置及び処理容器 |
JPH10197534A (ja) * | 1996-12-18 | 1998-07-31 | Stiftung Fuer Diagnostische Forsch | 凝集により試験液中の分析物を検出するための方法及び試薬キット、固定リガンド分子を担持する合成粒子並びにその使用 |
JPH10332707A (ja) * | 1997-03-31 | 1998-12-18 | Japan Tobacco Inc | 自動分析システム |
JP2003532117A (ja) * | 2000-04-13 | 2003-10-28 | サーモ フィニガン リミテッド ライアビリティ カンパニー | 並列質量分析によるプロテオミクス解析 |
US20020108857A1 (en) * | 2000-12-18 | 2002-08-15 | Michael Paschetto | Automated laboratory system and method |
WO2003020426A1 (en) * | 2001-09-05 | 2003-03-13 | Irm, Llc | Parallel reaction devices |
JP2004004078A (ja) * | 2002-05-24 | 2004-01-08 | Millipore Corp | 閉塞防止装置及びそのゲル内消化への適用方法 |
WO2004040313A1 (ja) * | 2002-11-01 | 2004-05-13 | Tss Biotech Inc. | 尿路上皮癌腫瘍マーカー |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109991049A (zh) * | 2017-12-29 | 2019-07-09 | 同方威视技术股份有限公司 | 用于食品安全检测的前处理装置以及前处理方法 |
CN109991049B (zh) * | 2017-12-29 | 2024-03-01 | 同方威视技术股份有限公司 | 用于食品安全检测的前处理装置以及前处理方法 |
WO2020017022A1 (ja) * | 2018-07-20 | 2020-01-23 | 株式会社島津製作所 | 振とう装置および分析方法 |
CN112437875A (zh) * | 2018-07-20 | 2021-03-02 | 株式会社岛津制作所 | 振动装置和分析方法 |
JPWO2020017022A1 (ja) * | 2018-07-20 | 2021-07-15 | 株式会社島津製作所 | 振とう装置および分析方法 |
CN113432958A (zh) * | 2021-05-27 | 2021-09-24 | 浙江好搭档农业开发有限公司 | 一种用于农药残留检测中前处理的提取装置 |
Also Published As
Publication number | Publication date |
---|---|
JPWO2005111572A1 (ja) | 2008-03-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4149736B2 (ja) | 核酸サンプル、タンパク質、および組織断片の雑種を作るための交雑室、処理装置、およびシステムを提供する装置 | |
KR102610239B1 (ko) | 식별 및 항생제 감수성 시험용 미생물 샘플을 수득 및 준비하기 위한 자동화된 방법 및 시스템 | |
CN102492603B (zh) | 一种用于提取核酸和质谱点样的自动化仪器 | |
US20080026472A1 (en) | Instrument For Efficient Treatment Of Analytical Devices | |
CN1965223A (zh) | 用于生物学着色仪的试剂传送系统、释放设备和容器 | |
JP2003505711A (ja) | 低容量の化学反応および生化学反応システム | |
EP3000896B1 (en) | Device and method for pretreating sequencer | |
KR100632893B1 (ko) | 시료처리장치 및 시료처리방법 | |
WO2005111572A1 (ja) | 試料調製装置及び方法 | |
WO2006106597A1 (ja) | 複数試料自動処理システム及び複数試料自動処理方法 | |
US7365847B2 (en) | Method and apparatus for automated excision of samples from two-dimensional electrophoresis gels | |
JP3413418B2 (ja) | 動物細胞等の注入排液装置 | |
JP4328787B2 (ja) | 核酸試料検査装置 | |
JP4328788B2 (ja) | 核酸試料検査装置 | |
WO2000049397A1 (en) | Method and apparatus for automated excision of samples from two-dimensional electrophoresis gels | |
CN105723202B (zh) | 用于固相和液相之间的反应的改进的设备和方法 | |
US20050170512A1 (en) | Method for cleaning reaction vessels in place | |
JP2000083650A (ja) | 酵素反応試験用の自動試験装置 | |
US20080141930A1 (en) | Instrument for forming solid phase of protein, protein solid phase forming device, and protein expression amount and activity value measuring device | |
JP7505010B2 (ja) | 前処理機構一体型核酸分析装置 | |
JP2010523942A (ja) | マイクロ流路洗浄方法 | |
JP4378821B2 (ja) | ゲルからのサンプル分取方法 | |
JP2002365177A (ja) | 質量分析用試料の前処理装置 | |
CN117511722A (zh) | 分子诊断分析仪和分子诊断方法 | |
CN117511728A (zh) | 分子诊断分析仪 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2006513603 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: DE |
|
122 | Ep: pct application non-entry in european phase |