Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00277—Apparatus
  • B01J2219/00351—Means for dispensing and evacuation of reagents
  • B01J2219/00364—Pipettes
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00277—Apparatus
  • B01J2219/00351—Means for dispensing and evacuation of reagents
  • B01J2219/00414—Means for dispensing and evacuation of reagents using suction
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00277—Apparatus
  • B01J2219/00497—Features relating to the solid phase supports
  • B01J2219/00527—Sheets
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
  • B01J2219/00608—DNA chips
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
  • B01J2219/00614—Delimitation of the attachment areas
  • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
  • B01J2219/00632—Introduction of reactive groups to the surface
  • B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00639—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium
  • B01J2219/00641—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium the porous medium being continuous, e.g. porous oxide substrates
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00639—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium
  • B01J2219/00644—Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium the porous medium being present in discrete locations, e.g. gel pads
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00583—Features relative to the processes being carried out
  • B01J2219/00603—Making arrays on substantially continuous surfaces
  • B01J2219/00659—Two-dimensional arrays
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
  • B01J2219/00718—Type of compounds synthesised
  • B01J2219/0072—Organic compounds
  • B01J2219/00722—Nucleotides
• • C—CHEMISTRY; METALLURGY
  • C40—COMBINATORIAL TECHNOLOGY
  • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
  • C40B40/00—Libraries per se, e.g. arrays, mixtures
  • C40B40/04—Libraries containing only organic compounds
  • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
• • C—CHEMISTRY; METALLURGY
  • C40—COMBINATORIAL TECHNOLOGY
  • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
  • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
  • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

• a first aspect of the invention provides a substrate-fixing device which fixes a substrate for detecting an organism-related substance in a state where it is mounted in a predetermined position on a mounting surface, the substrate being a porous substrate and having at least one probe region where a known specific binding substance can be immobilized, the substrate-fixing device including; a mounting stage having a through hole formed with an opening in the mounting surface in a non-probe region other than the probe region, and a holding device that holds a lower surface of the substrate via the through hole.
• the substrate-fixing device since a plurality of through holes are formed, the substrate can be stably fixed regardless of the number or shape of the probe region.
• the through hole in the mounting stage mounted on the base and the passage in the base are connected. If the air in the passage is sucked by operating the pressure device, for example, a suction pump, the through hole connected to the passage can be also sucked. That is, the lower surface of the substrate in the non-probe region can be sucked and held. In this manner, the substrate can be reliably fixed using suction force. Moreover, since the non-probe region is sucked, airborne dust is not sucked to the substrate via the porous probe region. Furthermore, since the air is simply sucked, the structure is simple, and there is little affect on the substrate because there is no heat generated.
• the pressure device for example, a suction pump
• the lid member by fixing the lid member to the mounting stage, the upper surface of the substrate can be covered, while covering the whole mounting surface.
• a ninth aspect of the invention provides a substrate-fixing device according to the seventh or eighth aspects, wherein the solution removal device comprises: a solution base on which the mounting stage is mounted, and which has a solution passage that is connectable to the solution through hole; a solution suction pump which is connected to the solution passage and which sucks the stored solution; and a solution storage device disposed between the solution suction pump and the solution base, which stores the solution sucked by the solution suction pump.
• the solution through hole in the mounting stage mounted on the solution base, and the solution passage in the solution base are connected.
• An eleventh aspect of the invention provides a substrate-fixing device according to any one of the first to tenth aspects, wherein the substrate is a membrane substrate.
• the probe discharge device discharges the specific binding substance in droplet form to the predetermined position on the probe region of the substrate to immobilize the specific binding substance into a solid phase thereon, to thereby enable a test piece such as a microarray to be manufactured.
• the specific binding substance can be immobilized into a sold phase on the substrate which is fixed by the substrate-fixing device, in a state where the adherence of dust thereto is prevented, higher quality test pieces can be manufactured. Consequently, there is no effect of noise, and the organism-related substance can be checked with higher accuracy.
• FIG. 8 shows a comparison between the time for the manufacturing steps per one substrate in the manufacturing method for a test piece of the present invention, and the time for the manufacturing steps per one substrate in a conventional manufacturing method.
• the membrane substrate A is formed overall from a porous member (for example, a flow-through type porous filter) B 5 and in a non-probe region T' which is the region other than the circular test site T, the upper surface and the lower surface of the membrane substrate A are coated with a holding member (resin laminate or the like) R for handling. That is, since the porous member B is exposed on the upper surface and the lower surface only in the region of the test site T, the test site T has a plurality of holes with openings in the upper surface and the lower surface.
• the test site T is not limited to a circular shape, and the number thereof is not limited to one.
• the probe P means a substance bindable specifically with the above organism-oriented substance, for example, including a ligand such as a hormone and the receptor thereof, an enzyme and the substrate thereof, a nucleic acid having a specific sequence and the nucleic acid having the complementary sequence thereof, and any substance having such a relation.
• the substrate-fixing device 2 as shown in FIG. 3, fixes a membrane substrate A for detecting the organism-related substance, in a state where it is mounted in a predetermined position on a mounting surface 10a.
• the mounting surface 10a is formed so as to mount a plurality of membrane substrates A.
• a total of twenty four membrane substrates A with four in the vertical direction (up and down direction with respect to the page) and six in the horizontal direction (horizontal direction with respect to the page), can be mounted adjacent to each other.
• mounting holes 10b for attaching fastening screws that fix the mounting stage 10 are formed respectively two on each side of the mounting surface 10a.
• the holding device 15 comprises: a base 21 on which the mounting stage 10 is mounted, having a passage 20 that is connectable to the respective through holes 11 ; and a vacuum pump (for example, DAl 5D made by Ul vac Techno Ltd.) (pressure device) 22 which is connected to the passage 20 and sucks the air inside the passage 20 to suck and hold a lower surface of the membrane substrate A in the non-probe region T' .
• a vacuum pump for example, DAl 5D made by Ul vac Techno Ltd.
• the solution dispensing nozzle 31 discharges, as the solution W, a solution to chemically treat the test site T into a predetermined condition, for example 10% poly-L-lysine (made by Sigma Corp.), or a cleaning solution to wash the test site T, for example PBS (phosphate-buffered salt solution) according to the condition.
• a solution to chemically treat the test site T into a predetermined condition, for example 10% poly-L-lysine (made by Sigma Corp.), or a cleaning solution to wash the test site T, for example PBS (phosphate-buffered salt solution) according to the condition.
• PBS phosphate-buffered salt solution
• the solution removal device 32 comprises: a solution base 34 on which the mounting stage 10 is mounted, and which has a solution passage 33 that is connectable to the solution through hole 12; the vacuum pump 22 (solution suction pump) which is connected to the solution passage 33 and sucks the stored solution W; and a discharge tank 35 (solution storage device) disposed between the vacuum pump 22 and the solution base 34, which stores the solution W sucked by the vacuum pump 22.
• the solution base 34 is set on a spotting apparatus (Bio chip arrayer made by
• the manufacturing method for a test piece of the present embodiment has: a treatment step for after mounting the membrane substrate A on the mounting surface 10a of the mounting stage 10, supplying the solution W to the test site T and letting it pass through the test site T, to chemically treat the test site T into a predetermined condition; a fixing step for, after the treatment step, sucking the lower surface of the membrane substrate A in the non-probe region T' other than the test site T, to hold and fix the membrane substrate A; a spotting step for, after the fixing step, discharging the probe P in droplet form to a predetermined position of the test site T to immobilize the probe P into a solid phase; a checking step for, after the spotting step, checking whether or not the probe P is discharged to the predetermined position; and a washing step for, after the checking step, supplying a cleaning solution to the test site T and letting it pass through the test site T to wash the test site T, so as to rinse out the probe P that is not completely immobilized into a solid phase
• the treatment step is performed after mounting the membrane substrate A.
• the mounting stage 10 on which the membrane substrate A is mounted is mounted on top of the solution base 34 with the rubber sheet 35 sandwiched therebetween, and the mounting stage 10 and the solution base 34 are fixed together. That is, the fastening screws 16 are inserted into the mounting holes 10b (counterbored holes) at the four corners of the mounting stage 10, and the fastening screws 16 are screwed into the threaded holes 34a in the solution base 34 to fix the mounting stage 10 to the solution base 34.
• the mounting stage 10 and the solution base 34 are fixed in a reliably sealed condition, so that leakage of air from any gaps between the mounting stage 10 and the solution base 34 can be prevented.
• the solution passage 33 in the solution base 34 is sucked by operating the vacuum pump 22, to thereby create a negative pressure.
• the stored solution passes through the porous test site T via a plurality of holes while infiltrating the test site T, and is then discharged to the discharge tank 35 through the solution through hole 12 and the solution passage 33.
• the test site T can be chemically treated into a predetermined condition.
• the solution W can be supplied to the test site T only, the contact state can be uniform and the chemical treatment can be even. As a result, variance in the analysis result can be reduced.
• the solution removal device 32 removes the solution W by simply using the suction force of air similarly to the holding device 15, the structure is simple, and the solution W can be reliably removed.
• the lid was opened and the membrane substrates were collected into a Petri dish by a pincette, then the lid was covered so as not to allow contamination with dust. After that, the Petri dish was placed into the vacuum dryer to dry the membrane substrates at room temperature for 60 minutes. After drying, the Petri dish was taken out from the vacuum dryer. Finally, the Petri dish was wrapped with aluminum foil so as to cover the whole membrane substrates, and the membrane substrates were placed into a refrigerator and stored in a temperature at 4 0 C.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Sampling And Sample Adjustment (AREA)
• Apparatus Associated With Microorganisms And Enzymes (AREA)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

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Cited By (1)

Citations (5)

• 2004
  • 2004-07-22 JP JP2004213988A patent/JP2006038460A/ja not_active Withdrawn
• 2005
  • 2005-07-19 WO PCT/JP2005/013538 patent/WO2006009273A1/en active Application Filing

Patent Citations (5)

Non-Patent Citations (1)

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