WO2002034944A1 - Agenceur de biopuces de haute precision et intelligent possedant une fonction de respotting - Google Patents

Agenceur de biopuces de haute precision et intelligent possedant une fonction de respotting Download PDF

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Publication number
WO2002034944A1
WO2002034944A1 PCT/KR2000/001200 KR0001200W WO0234944A1 WO 2002034944 A1 WO2002034944 A1 WO 2002034944A1 KR 0001200 W KR0001200 W KR 0001200W WO 0234944 A1 WO0234944 A1 WO 0234944A1
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WO
WIPO (PCT)
Prior art keywords
biochip
substrate
arrayer
spot
spots
Prior art date
Application number
PCT/KR2000/001200
Other languages
English (en)
Inventor
Heui Jae Pahk
Jung Hwan Kim
Original Assignee
Dia Chip Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dia Chip Limited filed Critical Dia Chip Limited
Priority to PCT/KR2000/001200 priority Critical patent/WO2002034944A1/fr
Priority to JP2002537913A priority patent/JP2004512514A/ja
Priority to AU2001210599A priority patent/AU2001210599A1/en
Publication of WO2002034944A1 publication Critical patent/WO2002034944A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, 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
    • 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
    • B01J2219/00387—Applications using probes
    • 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
    • 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
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B01J2219/00547—Bar codes
    • 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
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    • B01J2219/00547—Bar codes
    • B01J2219/00549—2-dimensional
    • 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
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    • B01J2219/00551—3-dimensional
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    • B01J2219/00583—Features relative to the processes being carried out
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    • 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
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    • B01J2219/0059—Sequential processes
    • 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
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    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • 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
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    • 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
    • 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
    • B01J2219/00659—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
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00689—Automatic using computers
    • 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
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00693—Means for quality control
    • 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
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00695—Synthesis control routines, e.g. using computer programs
    • 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
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00702—Processes involving means for analysing and characterising the products
    • 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
    • B01J2219/0074—Biological products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • 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
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Definitions

  • the present invention relates to a high precision and intellectual biochip arrayer
  • biochip substrate to its exact previous position, or an optical sensor for precisely
  • a biochip arrayer having a function of precise respotting, comprising an optical
  • a biological chip or a biochip is called a biological array.
  • a biochip has a substrate having biological material such as
  • a deoxyribonucleic acid (DNA) chip is one example of a well-known biochip.
  • the DNA chip has a substrate with DNA fixed thereon.
  • a protein chip is another
  • biochip has a substrate with protein formed thereon.
  • a biochip operates on the basis of the interaction between a target molecule and a
  • the DNA chip operates by means of a
  • a protein chip operates by means of the
  • the DNA chip means the substrate on
  • the DNA chip has many advantages. Enormous amounts of data can be obtained
  • the DNA chip can be widely applied to various fields such as
  • Pin micro-array Type wherein DNA is implanted at identical positions using a
  • the immunity diagnosis method of identifying diseases ranges from the utilization
  • the antigen-antibody in a sample (mainly, serum) obtained from an entity, the antigen-antibody
  • reaction is measured by using a secondary antigen composed of a radioactive indicator, an
  • the conventional method can measure only a
  • Protein chips comprises protein fixed onto a substrate while DNA chips has DNA
  • antigen proteins or peptides have various electrical properties
  • DNA spots while DNA has a minus charge and DNA spots range from 15 to 25 bases to about
  • proteins are fixed onto a substrate without interfering with, or deforming, the
  • the accurate position is chosen whereon to dot the sample in each reaction step.
  • the conventional biochip arrayer is disclosed as Genosensor Arrays manufactured
  • the conventional biochip arrayer may not cope with the
  • the conventional biochip arrayer often does not cope with deformations and
  • the conventional biochip arrayer may not overcome
  • the conventional biochip arrayer may not ensure a precise alignment
  • a protein chip should be precisely aligned while the DNA chip does not
  • the conventional biochip arrayer has a substrate retaining stand fixed onto the bed thereof, preventing the substrate retaining stand from being easily maintained or repaired.
  • the present invention is intended to overcome the above-described disadvantages.
  • biochip arrayer that can be
  • biochips such as a deoxyribonucleic acid chip or a protein chip by
  • a substrate retaining stand including a plurality of substrate retaining-grooves on which
  • aligning bosses are formed in order to set central positions and coordinates systems for a
  • an optical sensor for recognizing predetermined reference points previously indicated on a
  • biochip substrate so as to set a central position and a coordinate system for the biochip substrate.
  • a substrate retaining stand which can be formed separately, thereby facilitating ease of
  • a biochip arrayer comprising a substrate retaining stand
  • substrate retaining groove and a bed including at least one well plate retaining groove for
  • the substrate retaining groove comprises a first side for
  • biochip substrate wherein the biochip substrate supported by the two points means the
  • biochip' s substrate is supported by two retaining protuberances that corresponded to the
  • biochip substrate supported by the one point means the biochips substrate is supported by a
  • the first side is a first side
  • aligning boss is formed between the first side and the second side.
  • the substrate is formed of:
  • retaining groove further comprises push portions respectively formed on a third side and a
  • the push portions respectively support the biochip substrate so that the biochip substrate is
  • the push portions are springs or
  • the aligning boss has
  • central position is indicated by aligning a home position setting pin, a pin head and the
  • the bed comprises a
  • washing portion for washing a sample remaining on a probe or the container receiving the
  • dotting the second sample onto the second spot is performed by adjusting the size of a
  • the spot is smaller than the first spot when the first spot is an antigen and the second spot is an antibody.
  • biochip array comprising the step of recognizing a biochip identifier indicated on a biochip
  • biochip information includes at least one selected from the
  • spots the sizes of the spots, the intervals between the spots, the position of a reference spot
  • the biochip According to on preferred embodiment of the present invention, the biochip
  • identifier is recognized from a bar code attached to the biochip substrate.
  • the biochip substrate In this case, the
  • bar code is a first dimension bar code, a second dimension bar code or a third dimension
  • a biochip arrayer comprising an optical sensor
  • the optical sensor is an
  • a biochip arrayer comprising an optical sensor
  • FIG. 1 is a perspective view showing a biochip arrayer according to one preferred
  • FIG. 2 is a schematic view illustrating a configuration of a control system by using
  • FIG. 3 is an enlarged side view showing a portion of the biochip arrayer according
  • FIG. 4 is an exploded perspective view showing the bed in FIG. 3 according to one
  • FIG. 5 is a perspective view showing a substrate-retaining stand according to one
  • FIGS. 6A is a plane view illustrating a substrate-retaining groove according to one
  • FIG. 6B is a plane view illustrating a substrate-retaining groove according to
  • FIG. 6C is a plane view illustrating a substrate-retaining groove according to still another preferred embodiment of the present invention.
  • FIG. 6D is a plane view illustrating a substrate-retaining groove according to still
  • FIG. 6E is a side view illustrating a spring functioning as a push member in FIGS.
  • FIG. 6F is a side view illustrating an elastic member functioning as a push member
  • FIGS. 6B to 6D according to another preferred embodiment of the present invention.
  • FIG. 7 is a perspective view illustrating a method for setting a portion of an align
  • FIG. 8 is a perspective view illustrating a method for aligning a biochip substrate
  • FIG. 9 is a plane view for showing a biochip on which a reference point is
  • FIG. 10A is a flow chart illustrating a method for respotting a biochip arrayer by
  • FIG. 10B is a schematic plane view illustrating a reference representation according
  • FIG. 11 is a flow chart illustrating a method for manufacturing a biochip with high
  • FIG. 12 is a schematic view illustrating a database retrieving biochip information
  • FIG. 13 is a plane view illustrating a method for the calibration of a bed according
  • FIG. 14A is a cross-sectional view illustrating a method for adjusting the height of
  • FIG. 14B is a cross-sectional view illustrating a method for adjusting heights
  • FIG. 15 is a plane view illustrating a method for adjusting the y-axis direction of a
  • a biochip is representative of
  • a primary protein chip is formed by dotting an antigen onto a biochip arrayer
  • the primary protein chip is dried in a reaction apparatus
  • the primary protein chip can be identical or different. For example, a portion of the primary protein chip
  • HIV human immunodeficiency virus
  • the primary protein chip can hold a hepatitis B virus (HBV) antigen and the other portion
  • the primary protein chip can hold a hepatitis C virus (HCV) antigen.
  • HCV hepatitis C virus
  • the primary protein chip is provided to a consumer such as a hospital.
  • the secondary protein chip is
  • fluorescenin isothiocyanate a fluorescent material
  • the result of the reaction can be extracted using a biochip reader, thereby
  • FIG. 1 is a perspective view showing a biochip arrayer according to one preferred
  • the biochip arrayer comprises a transfer part 103 including a
  • probe mounting portion 103 whereon at least one probe is mounted, a transfer shaft 101 for
  • the transfer shaft 101 and the transfer part 103 can execute a multiple
  • a washing portion 117 for fixing several biochip substrates formed onto the bed 107 for fixing several biochip substrates formed onto the bed 107.
  • a washing portion 117 for fixing several biochip substrates formed onto the bed 107 for fixing several biochip substrates formed onto the bed 107.
  • washing the probe or a container for receiving samples is formed on the bed 107 and a
  • washing member 115 having a vacuum suction portion 119 and an ultrasonic washer 121 is
  • At least one well plate-retaining groove 113 having at least
  • the central control part having a controller (not shown), is in charge of a relative '
  • FIG. 2 is a schematic view illustrating a configuration of a control system using an
  • the central control part 201 receives a biochip identifier from
  • an optical sensor uses the identifier to recognize a chip 207 and receives a reference
  • optical sensor used for recognizing a reference
  • biochip identifier and the reference point position to an x-axis transfer driver 213, a y-axis
  • chip 207 can be composed of one optical sensor and the optical sensor for recognizing a
  • reference point 209 can also be composed of one optical sensor.
  • recognizing a chip 207 recognizes the biochip identifier from a bar code attached to the
  • the central control part 201 includes a standard personal computer 203 and the
  • the controller 205 generates the control signals after the controller 205
  • the controller 205 receives state information about each
  • driver 221 respectively control an x-axis motor 211, a y-axis motor 215 and a z-axis motor
  • the z-axis transfer driver 221 receive the control signal from the central
  • control part 201 controls the operation of the control part 201.
  • the ultrasonic driver 223 performs washing by generating ultrasonic waves in
  • the central control part 201 Furthermore, the vacuum valve driver 225 performs washing
  • FIG. 3 is an enlarged side view showing a portion of the biochip arrayer according
  • the biochip arrayer comprises a bed 107, a plurality of probes
  • the probe-mounting member 105 can rotate and move to the right or left.
  • probe-mounting member 105 can be established as a general robot arm.
  • the probe-mounting member 105 can be established as a general robot arm.
  • probe-mounting member 105 should be bound so that the probe 301 only moves in an
  • the probe 301 is shaped like a pin having thin and long dimensions so as to spot a
  • the sample onto a biochip substrate.
  • the sample is attached to an end of the probe 301 to be
  • the biochip substrate is that of a protein chip
  • the biochip substrate is a solid
  • the surface of the biochip is coated.
  • the solid plate can be composed of glass, deformed silicon, polymer or gel such as
  • the surface of the substrate is tetraflouroethylene, polystyrene or polypropylene.
  • the surface of the substrate is tetraflouroethylene, polystyrene or polypropylene.
  • the biochip substrate not only supports the samples but also provides the space
  • the size and the shape of the biochip substrate can be varied in accordance with the purpose
  • the position of the biochip substrate whereon the samples are fixed can be varied
  • the bed 107 has the biochip substrate affixed thereon and the samples are spotted
  • the bed 107 will described in detail with reference to FIG. 4.
  • FIG. 4 is an exploded perspective view showing the bed in FIG. 3 according to one
  • the bed 107 includes the substrate retaining stand 109 having a
  • the substrate-retaining stand 109 is separable from the bed 107.
  • the substrate-retaining stand 109 is separable from the bed 107.
  • retaining stand 109 can be tightly inserted into a groove formed on a portion of the bed 107
  • the substrate-retaining stand 109 can be combined with the bed 107 by means of a screw
  • the substrate-retaining stand 109 can be combined with the bed
  • the substrate retaining stand 109 alone can be separated and changed without it being
  • the substrate-retaining stand 109 can be easily maintained.
  • the number of biochip substrates to be mounted can be easily varied because the
  • substrate-retaining stand 109 can be separated from the bed 107 and the number of the
  • substrate-retaining groove 111 can be varied.
  • substrates can be changed from four to eight when the substrate-retaining stand 109 having
  • the substrate-retaining groove 111 will be explained with reference to FIGS. 6A to
  • the washing member 115 (see FIG. 1) washes the samples remaining on the probe
  • container washing portion 117 washes the remaining samples and the container with water.
  • the vacuum suction portion 119 washes the remaining samples and the container using the
  • the ultrasonic washer 121 washes the remaining samples and the
  • the well plate-retaining groove 113 retrieves the samples fixed onto the biochip
  • FIG. 5 is a perspective view showing a substrate-retaining stand according to one
  • four substrate-retaining grooves 111 are preferably formed on the substrate-retaining stand 109.
  • the substrate-retaining grooves 111 can be adjusted to
  • FIGS. 6A is a plane view illustrating a substrate-retaining groove according to one
  • the substrate-retaining groove 111 includes a retaining edge
  • biochip substrate 601 is supported at one point by the retaining protuberance 607 and is
  • retaining edge 603 and the retaining protuberance 607 are formed on the substrate retaining
  • the substrate-retainmg groove 111 corresponding to the retaining edge 603 is substantially
  • the aligning boss 605 has the shape of a circle so as to receive a corner of the
  • the aligning boss 605 performs the function of alignment.
  • the aligning boss 605 is aligned with the aligning boss 605
  • the biochip substrate 601 can have various shapes such as an ellipse, a triangle or a tetrahedron, thereby enabling the corner of the biochip substrate 601 to be received.
  • FIG. 6B is a plane view illustrating a substrate-retaining groove according to
  • substrate-retainmg groove 111 is substantially identical to that in FIG.
  • push members 609 are formed on the sides of the retaining edge 603 and the retaining
  • the push members 609 tightly hold the biochip substrate 601 when the biochip
  • the push members 609 are formed on the substrate-retaining groove 111, but the
  • push members 609 can be formed in such a way to enable them be separated from the
  • FIG. 6C is a plane view illustrating a substrate-retaining groove according to still
  • the substrate-retaining groove 111 is similar to that in
  • the substrate-retaining groove 111 includes two retaining protuberances 607
  • FIG. 6D is a plane view for illustrating a substrate-retaining groove according to
  • the substrate -retaining groove 111 is similar to that in
  • the retaining edge 603 is formed instead of the retaining protuberance 607.
  • the substrate-retaining groove 111 includes two retaining edges 603 respectively
  • FIG. 6E is a side view illustrating a spring as a push member in FIGS. 6B to 6D
  • the push member 609 can be composed of a plurality of springs 611. However,
  • the retaining protuberance 607 should be directed towards the retaining protuberance 607.
  • FIG. 6F is a side view illustrating an elastic member as a push member in FIGS.
  • the elastic member 613 generates a predetermined elastic force in one direction along the retaining edge 603 and the retaining protuberance 607 so
  • biochip substrate 601 is tightly held to the substrate-retaining groove 111 when the
  • biochip substrate 601 is inserted into the substrate-retaining groove 111.
  • the push member can be composed of a plurality of elastic members 613 similar
  • protuberance 607 should be directed toward the retaining protuberance 607.
  • the push member 609 is also fixed to the biochip substrate 601 at the same
  • biochip substrate 601 does not always have the
  • a plurality of substrate retaining grooves 111 are formed
  • substrate retaining grooves 111 is set as a central position and the positions of the other
  • substrate retaining grooves 111 are relatively set to the basis of the central position
  • position of the biochip substrate 601 may be difficult to discriminate due to transfer error or thermal deformation error.
  • positions of the biochip substrates 101 can be determined respectively as positions
  • FIG. 7 is a perspective view for illustrating a method for setting a portion of an
  • the biochip array dots the samples by using the central position and the coordinate
  • FIG. 8 is a perspective view illustrating a method for aligning a biochip substrate
  • the optical sensor 801 is attached to the probe mounting
  • the optical sensor 801 can be any optical sensor 801.
  • the optical sensor 801 can be any optical sensor 801.
  • the optical detector be an image detecting element or a position detecting element.
  • the optical detector be an image detecting element or a position detecting element.
  • the reference point can be any marks
  • the biochip array can dot the samples by using the established central position and
  • FIG. 9 is a plane view showing a biochip on which a reference point is indicated
  • optical sensor 801 especially the image detecting element, is indicated at a predetermined
  • the central reference point 803 is
  • reference point can be indicated by means of a sample dotted onto the biochip substrate.
  • the spot which functions as a reference spot can be set separately from the
  • the biochip arrayer can reset the
  • the central control part 201 (see FIG. 2) installed in the biochip arrayer for setting
  • FIG. 10A is a flow chart illustrating a method for respotting a biochip arrayer by
  • FIG. 10B is a schematic plane view illustrating a reference point according to one
  • the biochip substrate is recognized by means of the optical sensor (step 1001).
  • indication of the reference point can be accomplished by the method described in FIG. 10B.
  • the x-axis direction unit vector Ex and the y-axis direction unit vector Ey are identical to each other.
  • the reference point and the spot position X, Y can be configured into the
  • biochip arrayer for the manufacturer and the biochip arrayer for the user as previously
  • the pattern of the spot can be configured into the biochip arrayer for the
  • the pattern of the spot can be any pattern of the spot.
  • each pattern of each spot can be any pattern of each spot.
  • each motor is controlled in the step 1011 after each numerical control code is generated for controlling each motor in the step 1009.
  • FIG. 11 is a flow chart illustrating a method for manufacturing a high precision
  • the biochip can
  • the biochip identifier indicated on a portion of the biochip substrate is
  • the biochip identifier can be composed of bar codes.
  • the bar codes can include a one-dimensional bar code, a two-dimensional bar code or a
  • FIG. 12 is a schematic view illustrating a database retrieving biochip information
  • the database retrieves various pieces of information such as
  • the identifier 1201 the total number of spots 1203, the arrangement of the spots 1205, the contents of the spots 1207, the sizes of the spots 1209, the intervals between the spots 1211,
  • biochip information When the biochip identifier 1201 is recognized as '1', the biochip information
  • corresponding to '1' includes the total number of spots 1203 as 100, the arrangement of the
  • spots 1205 as HOR/ZIG the content of the spot 1207 as HTBC, the size of the spot 1209
  • the interval of the spots 1211 as 500 ⁇ m
  • the interval of the spots 1211 as lOOO ⁇ m
  • HOR/ZIG means the configuration of spots in
  • HTBC represents HIV/HANTA/Hepaditis B/
  • U represents the ultrasonic washing and V represents the vacuum suction.
  • FIG. 13 is a plane view illustrating a method for calibrating a bed according to one
  • the first supporting point 1303 and the second supporting point 1305 of the bed 107 adjust the height of the bed 107 and the y-axis direction.
  • each supporting point is
  • FIG. 14A is a cross-sectional view illustrating a method for adjusting the height of
  • the third supporting point 1307 adjusts the height of the bed
  • the screw adjusting part 1403 can
  • FIG. 14B is a cross-sectional view illustrating a method for adjusting the heights
  • the height of the bed 107 is adjusted at the first and the
  • the y-axis direction of the bed 107 is adjusted at the first and the second
  • first screw adjusting part 1403 precisely adjusts the inclined block with a screw.
  • the bed 107 is precisely calibrated according to the above-described method with
  • FIG. 15 is a plane view illustrating a method for adjusting the y-axis direction of a
  • the bed 107 is adjusted along the y-axis direction by
  • 1501 and 1503 are (125, 25), (25, 25) when the number of the substrate-retaining grooves
  • grooves are identified to adjust the bed in the y-axis direction when several substrate-
  • the diameter of the first spot can be different
  • the manufacturer a different size than the size of the probe of the biochip arrayer for the
  • the diameter of the first spot is larger than the diameter of the
  • the fluorescenin in the biochip reader including the CCD camera for detecting the result of reactions that have occurred in the biochip substrate, the fluorescenin
  • FITC isothiocynate
  • the first and the second spots respectively become the antigen and the antibody
  • the FITC is coated on the resultant antigen-antibody react, when the biochip substrate is
  • the biochip substrate is than
  • the biochip arrayer has a substrate-retaining
  • the biochip arrayer can cope with the
  • the biochip arrayer has an aligning boss
  • the biochip arrayer has a substrate-retaining
  • biochip substrates are biochip substrates, respectively.
  • the biochip arrayer has an optical sensor for
  • the biochip arrayer has the substrate-retaining
  • the biochip arrayer has different spots for
  • the biochip arrayer has the multiple spindle

Abstract

La présente invention concerne un agenceur de biopuces. Cet agenceur de biopuces comprend un support de retenue de substrat, qui peut être séparé de l'agenceur de biopuces et est pourvu d'une pluralité de rainures de retenue de substrat, chacune de ces rainures présentant un bord de retenue, une protubérance de retenue et un bossage d'alignement permettant d'insérer de façon ferme un substrat de biopuce. Grâce à l'utilisation d'un agenceur de biopuces selon l'invention, le substrat de biopuce peut subir un agencement chaque fois dans la même position. Le substrat de biopuces peut également être réagencé par un ajustement facile d'une position centrale et de coordonnées.
PCT/KR2000/001200 2000-10-23 2000-10-23 Agenceur de biopuces de haute precision et intelligent possedant une fonction de respotting WO2002034944A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/KR2000/001200 WO2002034944A1 (fr) 2000-10-23 2000-10-23 Agenceur de biopuces de haute precision et intelligent possedant une fonction de respotting
JP2002537913A JP2004512514A (ja) 2000-10-23 2000-10-23 再スポット機能を有する高精度知能型バイオチップアレイヤー
AU2001210599A AU2001210599A1 (en) 2000-10-23 2000-10-23 High precision and intellectual biochip arrayer having function of respotting

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2000/001200 WO2002034944A1 (fr) 2000-10-23 2000-10-23 Agenceur de biopuces de haute precision et intelligent possedant une fonction de respotting

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JP2009162773A (ja) * 2003-06-18 2009-07-23 Eppendorf Ag 試料液の定量システム
US7823535B2 (en) 2002-09-27 2010-11-02 Shimadzu Corporation Liquid portioning method and device
US8034194B2 (en) 2006-02-02 2011-10-11 Musashi Engineering, Inc. Pallet for fixing work and liquid applying apparatus provided with same
CN107478476A (zh) * 2017-07-31 2017-12-15 成都博奥晶芯生物科技有限公司 一种碟式芯片点样仪及其使用方法
US10533945B2 (en) 2013-11-17 2020-01-14 Quantum-Si Incorporated Optical system and assay chip for probing, detecting and analyzing molecules
US11377631B2 (en) 2016-10-13 2022-07-05 Sinfonia Technology Co., Ltd. Culture container linkage device, culture system, and method for washing needle
WO2023246645A1 (fr) * 2022-06-24 2023-12-28 深圳拜尔洛克生物技术有限公司 Appareil de déplacement de biopuce

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JP2015531486A (ja) 2012-09-28 2015-11-02 ヴィブラント ホールディングス リミテッド ライアビリティ カンパニー 生体分子解析のための方法、システム、およびアレイ
CN106226540B (zh) * 2016-08-31 2018-09-14 贵州金玖生物技术有限公司 全自动蛋白质芯片分析仪
KR102078567B1 (ko) * 2018-10-01 2020-02-19 주식회사 이바이오젠 이미지 인식 기술을 적용한 비접촉식 마이크로어레이어

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EP0998697A1 (fr) * 1997-07-25 2000-05-10 Affymetrix, Inc. (a California Corporation) Procede et systeme d'obtention d'une base de donnees de conception de puces a ensembles de sondes
WO2000051058A1 (fr) * 1999-02-26 2000-08-31 General Scanning, Inc. Imagerie automatique et analyse de biopuces d'ensembles de microechantillons

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EP0998697A1 (fr) * 1997-07-25 2000-05-10 Affymetrix, Inc. (a California Corporation) Procede et systeme d'obtention d'une base de donnees de conception de puces a ensembles de sondes
WO2000051058A1 (fr) * 1999-02-26 2000-08-31 General Scanning, Inc. Imagerie automatique et analyse de biopuces d'ensembles de microechantillons

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7823535B2 (en) 2002-09-27 2010-11-02 Shimadzu Corporation Liquid portioning method and device
JP2009162773A (ja) * 2003-06-18 2009-07-23 Eppendorf Ag 試料液の定量システム
US8034194B2 (en) 2006-02-02 2011-10-11 Musashi Engineering, Inc. Pallet for fixing work and liquid applying apparatus provided with same
US10533945B2 (en) 2013-11-17 2020-01-14 Quantum-Si Incorporated Optical system and assay chip for probing, detecting and analyzing molecules
US11287382B2 (en) 2013-11-17 2022-03-29 Quantum-Si Incorporated Optical system and assay chip for probing, detecting and analyzing molecules
US11377631B2 (en) 2016-10-13 2022-07-05 Sinfonia Technology Co., Ltd. Culture container linkage device, culture system, and method for washing needle
CN107478476A (zh) * 2017-07-31 2017-12-15 成都博奥晶芯生物科技有限公司 一种碟式芯片点样仪及其使用方法
WO2023246645A1 (fr) * 2022-06-24 2023-12-28 深圳拜尔洛克生物技术有限公司 Appareil de déplacement de biopuce

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