WO2003080868A1 - Biodisque, appareil de biolecteur, et procede d'essai faisant appel a ceux-ci - Google Patents

Biodisque, appareil de biolecteur, et procede d'essai faisant appel a ceux-ci Download PDF

Info

Publication number
WO2003080868A1
WO2003080868A1 PCT/KR2003/000613 KR0300613W WO03080868A1 WO 2003080868 A1 WO2003080868 A1 WO 2003080868A1 KR 0300613 W KR0300613 W KR 0300613W WO 03080868 A1 WO03080868 A1 WO 03080868A1
Authority
WO
WIPO (PCT)
Prior art keywords
disc
bio
controller
optical
chamber
Prior art date
Application number
PCT/KR2003/000613
Other languages
English (en)
Inventor
Jae-Chern Yoo
Original Assignee
Jae-Chern Yoo
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 Jae-Chern Yoo filed Critical Jae-Chern Yoo
Priority to AU2003218806A priority Critical patent/AU2003218806A1/en
Publication of WO2003080868A1 publication Critical patent/WO2003080868A1/fr

Links

Classifications

    • G—PHYSICS
    • G11—INFORMATION STORAGE
    • G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
    • G11B7/00—Recording or reproducing by optical means, e.g. recording using a thermal beam of optical radiation by modifying optical properties or the physical structure, reproducing using an optical beam at lower power by sensing optical properties; Record carriers therefor
    • G11B7/24—Record carriers characterised by shape, structure or physical properties, or by the selection of the material
    • G11B7/26—Apparatus or processes specially adapted for the manufacture of record carriers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N35/00069—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
    • 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
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00871—Communications between instruments or with remote terminals
    • G—PHYSICS
    • G11—INFORMATION STORAGE
    • G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
    • G11B19/00—Driving, starting, stopping record carriers not specifically of filamentary or web form, or of supports therefor; Control thereof; Control of operating function ; Driving both disc and head
    • G11B19/02—Control of operating function, e.g. switching from recording to reproducing
    • G—PHYSICS
    • G11—INFORMATION STORAGE
    • G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
    • G11B23/00—Record carriers not specific to the method of recording or reproducing; Accessories, e.g. containers, specially adapted for co-operation with the recording or reproducing apparatus ; Intermediate mediums; Apparatus or processes specially adapted for their manufacture
    • G11B23/0014—Record carriers not specific to the method of recording or reproducing; Accessories, e.g. containers, specially adapted for co-operation with the recording or reproducing apparatus ; Intermediate mediums; Apparatus or processes specially adapted for their manufacture record carriers not specifically of filamentary or web form
    • G11B23/0021—Record carriers not specific to the method of recording or reproducing; Accessories, e.g. containers, specially adapted for co-operation with the recording or reproducing apparatus ; Intermediate mediums; Apparatus or processes specially adapted for their manufacture record carriers not specifically of filamentary or web form discs
    • G—PHYSICS
    • G11—INFORMATION STORAGE
    • G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
    • G11B7/00—Recording or reproducing by optical means, e.g. recording using a thermal beam of optical radiation by modifying optical properties or the physical structure, reproducing using an optical beam at lower power by sensing optical properties; Record carriers therefor
    • G11B7/24—Record carriers characterised by shape, structure or physical properties, or by the selection of the material
    • G11B7/241—Record carriers characterised by shape, structure or physical properties, or by the selection of the material characterised by the selection of the material
    • 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
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/023—Sending and receiving of information, e.g. using bluetooth
    • 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
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/024—Storing results with means integrated into the container
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • 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
    • B01L2300/0803—Disc shape
    • B01L2300/0806—Standardised forms, e.g. compact disc [CD] format
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • 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
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)
    • G01N2035/00366—Several different temperatures used
    • 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
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00732—Identification of carriers, materials or components in automatic analysers
    • G01N2035/00742—Type of codes
    • G01N2035/00782—Type of codes reprogrammmable code

Definitions

  • BIO-DISC BIO-DRIVER APPARATUS
  • BIO-DRIVER APPARATUS BIO-DRIVER APPARATUS
  • ASSAY METHOD USING THE SAME
  • the present invention relates to a non-optical bio-disc, a bio-disc device including the non-optical bio-disc and/or an optical disc, a bio-driver apparatus, and an assay method using the same. More particularly, the present invention relates to a bio-disc with a lab-on-a-chip for various diagnostic assays, nucleic acid hybridization assays, or immunoassays, a bio-driver apparatus integrated with a controller disc including a controller for the bio-disc, and an assay method using the same.
  • PCT/KR02/00126 and its priority Korean application are entitled "Nucleic acid hybridization assay method and device using cleavage technique responsive to complementary double strand or single strand of nucleic acids or oligonucleotides", and International Patent Application No. PCT/KR02/01035 and its priority Korean application are entitled "Micro valve apparatus using microbead and method for controlling the same".
  • the disclosures of the above previous applications are incorporated herein by reference in their entirety.
  • the nucleic acid hybridization assay method and device using a cleavage technique responsive to a complementary double strand or single strand of nucleic acids are applicable to diverse quantitative or qualitative assay devices.
  • the micro valve is an essential element to control the flow of fluid in a lab-on-a-chip.
  • the nucleic acid assay device may comprise a detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device to detect uncleaved or cleaved signal elements.
  • the detected results can be digitized as computer executable software and provided through an established communications network, such as the Internet, to a patient or a doctor.
  • an established communications network such as the Internet
  • a capacitance and impedance measurement for the detector may include interdigitated array electrodes with cleavable signal elements, as disclosed in the previous application.
  • the present invention relates to a non-optical bio-disc, a bio-disc device, a bio-driver apparatus, and an assay method using the same, which are applicable to various kinds of diagnostic assay devices, nucleic acid hybridization assay devices, and immunoassay devices.
  • Clinical laboratory analyzers of this type can accurately perform hundreds of assays using small quantities of samples and reagents in one hour automatically or semi-automatically.
  • these analyzers are expensive and only centralized laboratories and hospitals can afford them.
  • Such centralization necessitates sample transport to the laboratory or hospital and often precludes urgent or emergent analysis of time-critical samples.
  • the standard compact disk is formed from a 12-cm polycarbonate substrate, a reflective metal layer, and a protective lacquer coating.
  • DVD stands for digital video disk, a type of optical disk of the same size as the compact disk, but with significantly greater recording capacity.
  • the polycarbonate substrate is optical-quality clear polycarbonate.
  • the data layer is part of the polycarbonate substrate, and the data are impressed as a series of pits by a stamper during injection molding.
  • melted polycarbonate is injected into a mold under high pressure and cooled in a mirror image of the mold or stamper.
  • reverse pits of the stamper are formed on the polycarbonate disk surface during mastering as binary data.
  • the stamping master is typically glass.
  • U.S. Patent No. 5,580,696 discloses materials of a dye layer for optical discs using refractivity-based data detection. An optical disk using the dye layer is rotated about a rotary shaft and scanned by laser to read data from the dye layer.
  • a general optical pickup for the above-described optical discs includes both a light emitting unit and a light receiving unit in a single module.
  • its optical traveling path is relatively long, and there is a poor sensitivity problem of the light receiving unit.
  • laser scanning for information reading requires actuating the optical pickup to a predetermined location on an optical disc and rotating the optical disc. Furthermore, when such an optical disc read by laser scanning is applied to a bio-assay device, problems such as physical deformation of probes and inaccurate assay results occur.
  • CD-based assay devices Optical confocal compact scanning optical microscope based on compact disc technology" (Applied Optics, Vol. 30, No. 10, 1991 ), “Gradient-index objectives for CD applications” (Applied Optics,
  • Patents regarding CD-based assay devices include U.S. Patent No. 4,279,862 entitled “Centrifugal photometric analyzer” (published on
  • GB 1075800 discloses a device for flowing a sample fluid supplied via n inject hole of a disc over its surface by centrifugal force.
  • EP 3335946 discloses an apparatus for separating fluid samples injected via an inject hole of a disc by inducing flow of the samples through channels or chambers formed in the disc by centrifugal force.
  • U.S. Patent No. 4,311 ,039 discloses a disc type chemical assay device using centrifugal force and optical detection.
  • a bio-disc according to the present invention reads information using light transmission, capacitance and impedance measurements, or electrochemical detection, wherein the bio-disc includes chambers as fluid reservoirs and channels as flow paths.
  • a bio-disc according to the present invention is referred to as a "non-optical bio-disc", in contrast to the conventional "optical" bio-discs using the differential reflection of laser light scanned over the bio-disc.
  • the conventional ones could not detect information using light transmission due to their structure which includes a reflective metal layer and a dye layer.
  • non-optical bio-disc throughout the specification refers to a bio-disc which allows for selective detection of analytic sites using light transmission, capacitance and impedance measurements, or electrochemical detection, without need to rotate the bio-disc and scan it with laser light. Therefore, the "non-optical bio-disc” of the present invention could involve optical assay detectors.
  • optical bio-disc throughout the specification refers to a bio-disc using a common optical pickup scanning laser light over the bio-disc to read data from its differential reflectance.
  • Common polycarbonate substrates can be modified to suit to bio-discs, which are thin film type assay devices, for detecting a small quantity of an analyte in a fluid sample for the diagnostic purpose.
  • bio-discs instead of pits and a dye layer, channels as fluid flow paths and chambers as buffer reservoirs are formed in a surface of a polycarbonate substrate through injection molding.
  • micro valves for controlling fluid flow through the channel and flow rate and an electronic controlling method of the micro valves are needed.
  • channels as fluid flow paths and chambers as buffer reservoirs may be formed in a silicon wafer using semiconductor manufacturing processes.
  • Such a bio-disc according to the present invention includes an electronic circuit integrated into the silicon wafer to control fluid flow and flow rate.
  • the present invention provides a non-optical bio-disc, a bio-disc device using the non-optical bio-disc and/or an optical bio-disc, a bio-driver apparatus, and an assay method using the same, which are applicable for remote diagnosis, sample diagnosis, DNA assays, and immunoassays.
  • a bio-disc according to the present invention is controlled by a controller disc installed in a bio-driver apparatus.
  • the controller disc includes a controller to control the bio-disc with various control signals and is built in the bio-driver apparatus for the convenience of assays. In other words, it is enough to just load only one bio-disc into and eject it from the bio-driver apparatus according to the present invention.
  • the controller disc may be combined with a non-optical bio-disc or with both a non-optical bio-disc and a general optical disc, instead of be built in the bio-driver apparatus.
  • the controller disc detects whether a currently loaded disc is a common optical disc, such as an audio CD, a CD-RW, a game CD, or a DVD, or a bio-disc.
  • the controller disc operates in a common mode for optical discs if the currently loaded disc is determined to be a common optical disc and outputs various control signals to control a lab-on-a-chip integrated in a bio-chip if the currently loaded disc is determined to be a bio-disc.
  • the present invention also provides a controller-disc combined bio-disc device in which a bio-disc and a controller are combined, an optical disc-combined bio-disc device in which a bio-disc and a common optical disc are combined, and an assay method using the bio-disc devices.
  • the common optical disc of the bio-disc device is compatible with a bio-driver apparatus as well as general optical drivers for optical discs, such as CDs.
  • audio data, such as music, written to the optical disc of the bio-disc device can be read by means of the bio-driver apparatus or any general optical driver, such as a CD driver.
  • the present invention also provides a bio-disc for polymerase chain reaction (PCR) and a bio-disc for electrophoresis.
  • PCR polymerase chain reaction
  • a non-optical bio-disc comprising: a solid substrate in which channels as fluid flow paths, a chamber as a buffer reservoir, a hole connecting the channels, and an assay site with biomolecular arrays immobilized thereon are integrated; and a valve used to open and close the hole connecting the channels, wherein an analyte-specific signal from the assay site is detectable using a detector including a light transmission type device, an electrochemical device, or a capacitance and impedance measurement device.
  • analyte-specific signal includes an uncleaved signal element and a cleaved signal element.
  • the biomolecular arrays may be made from at least one selected from the group consisting of DNA, RNA, PNA, and protein probes.
  • the chamber of the non-optical bio-disc may comprise at least one selected from the group consisting of: a preparation chamber for preparing a DNA sample from blood, cells, or RNA; a PCR chamber for amplifying the DNA sample through polymerase chain reaction (PCR); a hybridization chamber in which assay and diagnostic probes are arrayed for hybridization with the amplified DNA from the PCR; and a trash chamber for collecting wastes generated from washing.
  • the preparation chamber may reserve a lysis buffer solution used to extract a DNA through lysis and ferroelectric beads having affinity to the extracted DNA.
  • the non-optical bio-disc according to the present invention may comprise a plurality of PCR chambers. In this case, each PCR chamber may reserve one type or several types of primer. Alternatively, all of the PCR chambers may reserve the same type of primer.
  • the chamber of the non-optical bio-disc may comprise at least one chamber selected from the group consisting of: at least one preparation chamber for preparing a serum sample, an antigen, or an antibody from blood or cells; at least one antigen-antibody reaction chamber in which immuno probes are arrayed for antigen-antibody reaction with the prepared antigen or antibody; and a trash chamber for collecting waste generated from washing.
  • the chamber may further comprise a filter at an outlet of the preparation chamber and a conjugate antibody chamber as a conjugate antibody reservoir.
  • the conjugate antibody chamber reserves conjugate antibodies labeled with colorimetric moiety selected from gold and latex.
  • the valve of the non-optical bio-disc according to the present invention may comprise: a microbead which plugs or opens the hole connecting channels; and electromagnets with an air core or a non-magnetic core, which are arranged above and below the microbead.
  • the microbead may be a film-like cylindrical permanent magnet.
  • the light transmission type device of the non-optical bio-disc may comprise: a laser device which emits a laser beam onto an uncleaved signal element and a cleaved signal element; and a photodetector which detects a differential light transmission signal between the uncleaved signal element and the cleaved signal element.
  • at least one photodetector may be arrayed along an outer perimeter region of the bio-disc to correspond to each assay site. A smaller distance between the photodetector and the corresponding assay site offers higher detection sensitivity.
  • At least one set of a laser device and a photodetector is arrayed along an outer perimeter region of the bio-disc to correspond to each assay site.
  • the analyte-specific signal can be detected from the assay site in a non-scanning manner without need to rotate the bio-disc.
  • the electrochemical device or the capacitance and impedance measurement device of the non-optical bio-disc according to the present invention may comprise: interdigitated array electrodes on the substrate of the assay site; and a horse radish peroxidase and/or a metal microsphere attached to the end of cleavable signal elements.
  • the electrochemical device or the capacitance and impedance measurement device using the interdigitated array electrodes may further comprise a multiplexer and/or a frequency generator.
  • the non-optical bio-disc further comprises a memory or an integrated circuit card storing a protocol of the bio-disc, assay interpretive algorithms, standard control values for analysis, positional information on analysis sites, bioinformatics information, self-diagnostics, bio-driver software, educational information for patients on clinical assays, a variety of web sites and links enabling a patient to communicate with a doctor or hospital at a remote location based on his/her diagnosis result, or encrypted personal information.
  • a bio-disc device comprising; the above-described non-optical bio-disc according to the present invention or an optical bio-disc; a controller disc including a controller which supplies power or a control signal to the bio-disc; and an interfacing zone for connecting the bio disc and the controller disc.
  • optical bio-disc refers to a bio-disc which can be read from a differential reflectance of laser light scanned over it using a general optical pickup.
  • the interfacing zone may comprise: a plurality of control signal nodes via which the control signal is supplied; and/or a power node via which power is supplied.
  • the interfacing zone may comprise: grooves formed in the bio-disc and coated with a conductive material; and conductive arms protruding from the controller disc and engaging the grooves.
  • power is supplied to the controller disc via fhctional contact between brushes connected to an external power supply and an annular electrode plate of the controller disc.
  • the controller disc comprises an integrated circuit in a printed circuit board or in a silicon wafer. Fluid flow in the bio-disc device is induced by the centrifugal force generated as the bio-disc engaged with the controller disc rotates and by the opening and closing of the valve.
  • the controller disc may further comprise a non-contact interface selected from among an infrared interface, an optical interface, and a wireless interface to transmit the result of a detection from the assay site by the detector to an external central control system, a storage unit, or an output unit via the non-contact interface.
  • a non-contact interface selected from among an infrared interface, an optical interface, and a wireless interface to transmit the result of a detection from the assay site by the detector to an external central control system, a storage unit, or an output unit via the non-contact interface.
  • the bio-disc and the controller disc may be integrated as a single body to form a controller disc-combined bio-disc.
  • the controller disc-combined bio-disc has a monolithic circuit structure integrated into a silicon wafer via photolithography and etching processes, the monolithic circuit structure including the controller, the integrated circuit card, a non-contact interface, an electrode plate or electromagnet for valve control, various circuit patterns, chambers, and channels.
  • the controller disc-combined bio-disc may be further combined with a general optical disc selected from among an audio CD, a CD-RW, a DVD-RW, a CD, and a DVD to form an optical disc-combined bio-disc.
  • a bio-driver apparatus comprising: a controller disc including a controller which outputs a power signal and/or a control signal to control power supply to and the operation of the above-described non-optical bio-disc according to the present invention and/or an optical bio-disc; a motor which drives the controller disc and the bio-disc to rotate; a power supply unit which supplies power to the controller of the controller disc; an interface via which the control signal and/or the power signal are transmitted from the controller to the bio-disc; and a body which supports the bio-driver apparatus.
  • a bio-driver apparatus may further comprise a detector including a light transmission type device to detect an analyte-specific signal from the assay site.
  • a bio-driver apparatus may further comprise a non-contact interface via which the result of a detection from the assay site is transmitted to a central control system, a storage unit, or an output unit and via which a command signal from the central control system is transmitted to the controller disc.
  • a bio-driver apparatus may further comprise a central control system and a storage or output unit installed on a printed circuit board connected as a base to the body, the central control system controlling the operation of the motor to rotate the bio-disc and the controller disc and stop their rotation and to push the controller disc and the bio-disc to be closer together so that the controller disc and the bio-disc mechanically and/or electrically combine together via their interfacing zones and rotate together.
  • the output unit may be a Universal Serial Bus or lEEE1394.
  • Another bio-disc device comprises: the above-described non-optical bio-disc according to the present invention or an optical bio-disc; a turntable on which the bio-disc or a general optical disc is loaded; and a controller disc including a controller which outputs a power or control signal to control the bio-disc, the controller disc being fixed to the turntable.
  • the controller disc may further comprise an electromagnet which controls the movement of a microbead in the bio-disc.
  • the bio-disc is loaded on the turntable with a gap of 0.1-5 mm, preferably, about 1 mm, from the controller disc fixed to the turntable.
  • the controller disc supplies to the bio-disc the power provided via frictional contact between a rotating annular electrode plate and blushes connected to an external power supply unit.
  • the controller disc comprises an integrated circuit in a printed circuit board or in a silicon wafer.
  • the controller disc may further comprise a non-contact interface selected from among an infrared interface, an optical interface, and a wireless interface to transmit the result of a detection from the assay site by the detector to an external central control system, a storage unit, or an output unit via the non-contact interface.
  • a non-contact interface selected from among an infrared interface, an optical interface, and a wireless interface to transmit the result of a detection from the assay site by the detector to an external central control system, a storage unit, or an output unit via the non-contact interface.
  • Another bio-driver apparatus comprise: a turntable on which the above-described non-optical bio-disc according to the present invention or a general optical disc is loaded; a controller disc fixed to the turntable and including a controller and an electromagnet, the controller controlling power supply to the bio-disc and the opening and closing of the valve installed in the bio-disc; a motor which drives the controller disc and the bio-disc to rotate; a power supply unit which supplies power to the controller of the controller disc; and a body which supports the bio-driver apparatus.
  • the power supply unit supplies a positive voltage via frictional contact between a rotating annular electrode and blushes and a negative voltage via electrical connection with the motor or its shaft, which are grounded, to the controller disc.
  • the bio-driver apparatus may further comprise a detector including a light transmission type device to detect an analyte-specific signal from the assay site.
  • the bio-driver apparatus may further comprise a non-contact interface via which the result of a detection from the assay site is transmitted to a central control system, a storage unit, or an output unit and via which a command signal from the central control system is transmitted to the controller disc.
  • the bio-driver apparatus may further comprise a central control system and a storage or output unit installed on a printed circuit board connected as a base to the body, the central control system controlling the operation of the motor to rotate the bio-disc and the control disc and stop their rotation.
  • the general optical disc is selected from among an audio CD, a CD-R, a game CD, and a DVD
  • the bio-driver apparatus further comprises an optical pickup to read information from the general optical disc.
  • the controller comprises a bio-disc detection unit determining whether a currently loaded disc is a bio-disc or a general optical disc selected from among an audio CD, a CD-R, a game CD, and a DVD.
  • the bio-disc detection unit measures a predetermined voltage across some or all resistors arranged in the bio-disc as a bio-disc detection signal and wirelessly transmits the bio-disc detection signal via a non-contact interface to a central control system to inform the central control system that the currently loaded disc is a bio-disc.
  • the bio-disc may have a groove pattern or a data pattern at a particular area on its surface for the optical pickup to be able to detect whether a currently loaded disc is a bio-disc from the groove pattern or the data pattern of the currently loaded disc and inform a central control system of the result of the detection.
  • a central control system may determine whether a currently loaded disc is a bio-disc or a general optical disc selected from among an audio CD, a CD-R, a game CD, and a DVD; transmit information read from the general optical disc using the optical pickup to a storage or output unit, transmit to the optical pickup information to be written, or output various read/write control signals if the currently loaded disc is determined to be a general optical disc; and transmit various control signals for the bio-disc via a non-contact interface to the controller if the currently loaded disc is determined to be a bio-disc.
  • the non-optical bio-disc according to the present invention loaded into the bio-driver apparatus further comprises a memory or an integrated circuit card storing a protocol of the bio-disc, assay interpretive algorithms, standard control values for analysis, positional information on analysis sites, bioinformatics information, self-diagnostics, bio-driver software, educational information for patients on clinical assays, a variety of web sites and links enabling a patient to communicate with a doctor or hospital at a remote location based on his/her diagnosis result, or encrypted personal information.
  • a signal indicative of bio-discs may be wirelessly transmitted to a central control system upon loading of a bio-disc, via a non-contact interface or an integrated circuit card of the bio-disc, to inform the central control system of the current loading of the bio-disc into the bio-driver apparatus.
  • a PCR bio-disc device for polymerase chain reaction comprising: a solid substrate in which channels as fluid flow paths, a chamber as a buffer reservoir, and a hole connecting the channels are integrated; and a valve used to open and close the hole connecting the channels, wherein the chamber comprises: at least one preparation chamber for preparing a DNA sample from blood, cells, or RNA; at least one PCR chamber reserving various enzymes, including a polymerase and a primer, required to amplify the DNA sample through polymerase chain reaction, in a buffer; and a plurality of out-chambers into which PCR products are discharged, the at least one preparation chamber, the at least one PCR chamber, and the plurality of out-chambers being sequentially connected with each other in the solid substrate.
  • the chamber comprises: at least one preparation chamber for preparing a DNA sample from blood, cells, or RNA; at least one PCR chamber reserving various enzymes, including a polymerase and a primer, required to amplify the DNA sample
  • the plurality of out-chambers have outlets via which the PCR products can be extracted by means of a pipette or a syringe.
  • a ladder marker reservoir, a positive control and negative control reservoir, and a stain reservoir are further integrated into the solid substrate.
  • the PCR bio-disc device may be combined with an electrophoresis bio-disc.
  • the electrophoresis bio-disc may comprise: gel plates made of agarose gel and/or polyacrylamide gel; and annular electrodes across which a voltage is applied to the gel plates.
  • the PCR bio-disc device may further comprise a UV radiator and a camera to identify, store, and transmit bands appearing on the gel plates.
  • a nucleic acid assay method using the above PCR bio-disc device comprising: preparing a DNA sample from blood, cells, or RNA; amplifying the prepared DNA sample through polymerase chain reaction; flowing PCR products into an out-chamber; moving the contents in the out-chamber into the electrophoresis bio-disc; incubating the electrophoresis bio-disc while applying a voltage across its annular electrodes; and identifying, storing, and transmitting bands appearing on the gel plates.
  • the present invention also provides a nucleic acid assay method using the bio-disc recited in claim 3, the method comprising: preparing a DNA sample from blood, cells, or RNA; amplifying the prepared DNA through polymerase chain reaction (PCR); hybridizing amplified DNA products from the PCR to the assay and diagnostic probe array immobilized on the assay site; and detecting a cleavable signal element remaining in the assay site using the detector including the light transmission type device, the electrochemical device, or the capacitance and impedance measurement device.
  • PCR polymerase chain reaction
  • preparing the DNA sample comprises: injecting blood via a sample inlet into the preparation chamber; incubating the preparation chamber to allow ferroelectric beads in the preparation chamber to attract DNA extracted through lysis; fixing the ferrroelectric beads and slowly rotating the bio-disc to wash out and flow the cell debris into the trash chamber; and separating the DNA from the ferroelectric beads or resuspending the DNA in a resuspension buffer.
  • Amplifying the prepared DNA sample through PCR comprises: slowly rotating the bio-disc to allow the prepared DNA sample to flow into the PCR chamber; and repeating a PCR cycle several times using a heater and a thermosensor installed in the PCR chamber to amplify the DNA sample.
  • the nucleic acid assay methods may further comprise, after amplifying the prepared DNA sample: slowly rotating the bio-disc and allowing a DNAse to flow into the PCR chamber; and heating the PCR chamber to deactivate the DNAse and obtain single-stranded DNA fragments.
  • each PCR chamber may comprise a heater which is controlled independently from the heaters of the other PCR chambers to give single-stranded DNA fragments which vary in lengths.
  • the assay site may comprise an immunoassay sector and a nucleic acid probe assay sector arranged in an angular or radial direction to enable an immunoassay and a nucleic acid probe assay to be performed concurrently.
  • the bio-driver apparatuses according to the present invention may send an eject message or a warning message to a user if a bio-disc into which a sample has not be injected yet is loaded.
  • an additional impedance measurement device may be installed in the preparation chamber so as to determine whether a sample has been injected into a bio-disc.
  • the additional impedance measurement device may comprise interdigitated array electrodes.
  • the bio-driver apparatuses according to the present invention may continue assay or diagnosis even when an unloading or a stop command is input, and optionally send a warding message or requesting a user's password, and stopping the assay or diagnosis or ejecting the bio-disc if a user enters the correct password.
  • the bio-driver apparatuses according to the present invention may further comprise a memory storing information on how many times a bio-disc has been used, its validation period, and kinds of diseases which it can diagnose, so as to provide a user with the stored information on the bio-disc or the availability of the bio-disc whenever the bio-disc is loaded.
  • the bio-driver apparatuses according to the present invention may comprise: a play and search button and a stop button for general optical discs; and a light emitting diode that indicates a bio-disc has been loaded.
  • Alternative indicative means instead of LEDs, can be used.
  • the bio-driver apparatuses according to the present invention comprises a liquid crystal display to display the status of progress in sample preparation, PCR, hybridization, and antigen-antibody reaction, which are main processes conducted in the bio-disc, in percentages or as a bar graph.
  • the bio-driver apparatuses according to the present invention are connected to a computer monitor to display the status of progress in sample preparation, PCR, hybridization, and antigen-antibody reaction, which are main processes conducted in the bio-disc, in percentages or as a bar or pie graph.
  • FIGS. 1A and 1 B are sectional views of a valve apparatus using microbeads, which is installed in a bio disc according to the present invention
  • FIG. 1 C illustrates an embodiment of a bio-disc, in which a lab-on-a-chip is integrated, and its controller disc;
  • FIG. 1 D is a sectional view illustrating an exemplary structure of a conductive arm
  • FIG. 1 E illustrates an exemplary spiral arrangement of grooves which allows spontaneous alignment and insertion of the conductive arm
  • FIG. 1 F illustrates an embodiment of a bio-driver apparatus according to the present invention in which a controller disc is installed
  • FIG. 1 G illustrates another example of a bio-disc with a lab-on-a-chip and its controller disc
  • FIGS. 1 H and 1 1 illustrate an example of an auxiliary substrate which supplies power to the controller disc via frictional contact between blushes and a rotary electrode shown in FIG. 1 G;
  • FIG. U illustrates another embodiment of a bio-driver apparatus according to the present invention in which a controller disc is installed
  • FIGS. 2A and 2B illustrate an embodiment of a controller disc-combined bio-disc device and a bio-driver apparatus according to the present invention according to the present invention
  • FIG. 2C illustrates an embodiment of an electrochemical device or a capacitance and impedance measurement device using interdigitated array electrodes
  • FIG. 2D illustrates an embodiment of an optical disc-combined bio-disc device according to the present invention
  • FIG. 3A illustrates an embodiment of how to determine whether a currently loaded disc is a non-optical bio-disc
  • FIG. 3B illustrates an embodiment of informing a central control system that a disc currently loaded into a bio-driver apparatus is a bio-disc
  • FIGS. 4A through 6D illustrate alternative embodiments of optical assay detectors
  • FIGS. 7A through 7G illustrate examples of electrochemical detectors or capacitance and impedance measurement devices
  • FIGS. 8A through 8F illustrate embodiments of bio-discs according to the present invention
  • FIGS. 9A and 9B illustrate alternative embodiments of bio-discs according to the present invention, in which sample preparation and PCR or further electrophoresis can be conducted in a single disc;
  • FIGS. 10A and FIG. 10B illustrate embodiments of assay devices according to the present invention that include an immunoassay sector and a nucleic acid probe hybridization sector for simultaneous immunoassays and DNA assays;
  • FIGS. 1 1A and 1 1 B illustrate exemplary appearances of bio-driver apparatuses according to the present invention.
  • a bio-disc according to the present invention includes a valve which controls fluid flow or the flow rate in a lab-on-a-chip integrated in the bio-disc.
  • the valve opens or closes a channel formed in the bio-disc using a microbead that is movable by the magnetic force generated by an electromagnet disposed on the top and/or bottom surface of the bio-disc.
  • International Patent Application No. PCT/KR02/01035 filed 31 May 2002 and its priority Korean Application No. 10-2001-0031284 filed 31 May 2002, which are entitled "Micro valve apparatus using microbead and method for controlling the same", can be referred to for the detailed structure of the valve.
  • the microbead may include, for example, a magnetic ball, ferroelectric particles, paramagnetic particles, diamagnetic particles, a stainless steel ball.
  • the microbead may be made of a solid metal, plastic, or glass bead.
  • the microbead is further coated with a metal.
  • Solid metals for the microbead may be metal alloys.
  • the microbead may be charged. In which case, instead of electromagnets, electrode plates are arranged on the top and bottom surfaces of the bio-disc.
  • the microbead is charged and moved in the direction in which a voltage is applied to the electrode plates, to open or close a hole connecting channels in the lab-on-a-chip.
  • the microbead has a diameter of 1 ⁇ m-1 mm, preferably, 100 ⁇ m-500 ⁇ m. When the diameter of the microbead is larger, the hole can be opened or plugged with higher reliability due to an increase in the contact area between the hole and the microbead.
  • the microbead may be a spherical permanent magnet or a film-like cylindrical or rectangular permanent magnet.
  • the microbead may be a wound wire having a diameter of, preferably, 0.01-0.1 mm, with an air core or a non-magnetic core.
  • FIGS. 1A and 1B are sectional views of a bio-disc showing a valve apparatus therein using a permanent magnetic microbead.
  • a bio-disc 100 includes an upper substrate 1 , an intermediate substrate 2, and a lower substrate 3. Channels as flow paths, chambers as buffer reservoirs, and holes connecting the channels are formed in each of the upper, intermediate, and lower substrates 1 , 2, and 3 by injection molding. Next, the upper, intermediate, and lower substrates 1 , 2, and 3 are bound together to form a body of the bio-disc 100.
  • FIG. 1A illustrates a state where a hole 10 is plugged by a permanent magnetic microbead 70a to block a channel 16a.
  • FIG. 1 B illustrates a state where the permanent magnetic microbead 70a is removed from the hole 10 to interconnect the channel 16a.
  • Preferred examples of the upper and lower electromagnets 4a and 5a include film-like electromagnets with an air core and bobbinless coils. Since the bio-disc 100 according to the present invention includes the channel 16a, which is relatively narrow, as a fluid path, a ventilating hole 12 is formed in the upper substrate 1 to reduce the air pressure and allow a fluid to smoothly flow through the channel 16a.
  • FIG. 1C illustrates a bio-disc 100 and a controller disc 200 for controlling the bio-disc 100, in which chambers as various assay buffer reservoirs and places for various reactions, channels as flow paths of a fluid sample and buffers, and valve apparatuses for controlling the opening and closing of the channels are integrated to form a lab-on-a-chip.
  • Suitable materials for the bio-disc 100 according to the present invention include plastics, polymethylmethacrylate (PMMA), glass, mica, silica, any material for semiconductor wafers, etc. However, among these materials, plastics are most preferred for economical reasons and the convenience of processing. Suitable examples of plastics include polypropylenes, polyacrylates, polyvinyl alcohols, polyethylenes, polymethylmethacrylates, and polycarbonates, with polypropylenes and polycarbonates being preferred and polycarbonates being more preferred.
  • the bio-disc 100 of FIG. 1C includes the upper substrate 1 , the intermediate substrate 2, and the lower substrate 3. Channels as flow paths, chambers as buffer reservoirs, and holes connecting the channels are formed in each of the upper, intermediate, and lower substrates 1 , 2, and 3 by injection molding. Next, the upper, intermediate, and lower substrates 1 , 2, and 3 are bound together to form a body of the bio-disc 100.
  • Suitable materials for the controller disc 200 include plastics, PMMA, glass, mica, silica, silicon, materials for printed circuit board (PCB), etc., in which PCB materials and any material for semiconductor wafers are preferred for their easy applicability in designing circuits.
  • the bio-disc 100 is built of the upper substrate 1 , the intermediate substrate 2, and the lower substrate 3 stacked upon one another. Permanent magnetic microbeads 70a, 70b, and 70c are individually moved up and down by the magnetic force generated by respective upper and lower electromagnet pairs 4a and 5a, 4b and 5b, and 4c and 5c to close and open holes connecting channels.
  • reference numeral 120 denotes a pipette or syringe for sample injection
  • reference numeral 121 denotes a sample inlet
  • reference numeral 170 denotes a disk hole.
  • Reference numeral 171a denotes an interfacing zone for electrical connection with the controller disc 200, which includes a plurality of control signal nodes 173 via which control signals are input to the bio-disc 100, and power nodes 33a for power supply.
  • the controls signal nodes 173 and the power nodes 33a are formed by coating grooves 33 with conductive materials.
  • reference numeral 130 denotes a preparation chamber for preparing a DNA sample directly from blood or cells or from RNA through reverse transcription (RT) or for preparing a serum sample from blood
  • reference numeral 131 denotes a PCR chamber for polymerase chain reaction (PCR)
  • reference numeral 132 denotes a chamber for hybridization or antigen-antibody reaction, which is an assay site with capture probes for analyzing and diagnosing amplified DNA products from the PCR or with immuno arrays immobilized thereon.
  • Reference numeral 133 denotes a trash chamber for collecting wastes generated during washing.
  • Reference numeral 140 denotes a chamber for reserving a buffer containing various enzymes, including polymerase, primer, etc., required for PCR, and reference numerals 141 , 142, and 143 denote chambers for reserving various enzymes required for hybridization.
  • Opening and closing of the valve apparatuses at the start and ending points of time of each of the processes are controlled by on/off control of the power supplied to the electromagnet pair 4a and 5a, 4b and 5b, or 4c and 5c arranged above and below each of the permanent magnetic microbeads 70a, 70b, and 70c.
  • Fluid flow in the bio-disc 100 is induced by the centrifugal force generated as it is rotated.
  • Power is supplied to a controller 63 of the controller disc 200 and a non-contact interface 107 serving as a wireless transmission and/or reception unit, through frictional contact with brushes 108 and 109.
  • Power and the control signals of the controller 63 are transmitted from the controller disc 200 to the bio-disc 100 via a plurality of conductive arms 13 fitted into the control signal nodes 173 and the power nodes 33a, actually the grooves 33 coated with a conductive material.
  • the conductive arms 13 and the grooves 33 act as connectors between the bio-disc 100 and the controller disc 200.
  • reference numeral 188 denotes an integrated circuit (IC) card storing a protocol of the lab-on-chip, assay interpretive algorithms, standard control values for analysis, positional information on analysis sites, bioinformatics information, self-diagnostics, and the like.
  • the IC card 188 may include bio-driver software, educational information for patients on clinical assays and may be adapted for users.
  • the IC card 188 may include a variety of web sites and links, for example, a web site enabling a patient to communicate with a doctor or hospital based on his/her diagnosis result, and encrypted personal information to prevent unauthorized user access.
  • a preferred example of the IC card 188 is a RAM or ROM embedded smart IC card.
  • the information stored in the IC card 188 may be wirelessly transmitted to a central control system to allow for remote analysis and diagnosis and encryption for personal information security.
  • FIG. 1 D is a sectional view illustrating the detailed structure of a conductive arm 13.
  • An end of the conductive arm 13 is fixed to the interfacing zone 171 b of the controller disc 200, and the other end of the conductive arm 13 is formed to protrude and be able to smoothly fit into each groove 33 of the bio-disc 100 when the controller disc 200 and the bio-disc 100 are rotated and become closer together.
  • a spring 13c is installed inside the body of the conductive arm 13. In FIG.
  • reference numeral 13a denotes the body of the conductive arm 13, whose one end is fixed to the interfacing zone 171 b of the controller disc 200
  • reference numeral 13b denotes the protruding end of the conductive arm 13 that is inserted into the groove 33 of the bio-disc 100
  • reference numeral 13d denotes a support plate which elastically supports the spring 13c and links the protruding end 13b to the body 13a of the conductive arm.
  • FIG. 1 E illustrates an exemplary spiral arrangement of grooves 33 in the bio-disc 100 that allows spontaneous insertion of the conductive arm 13 protruding from the interfacing zone 171 b of the controller disc 200 into each groove 33 upon rotation.
  • the conductive arm 12 fit into and is electrically connected to each groove 33.
  • reference numeral 170 denotes a disc hole of the bio-disc 100.
  • control signal nodes 173 and power nodes 33a which are formed by coating the grooves 33 with conductive materials, are arranged around the disc hole 170.
  • a circuit pattern 888 electrically connecting each groove 33 to a corresponding part, chamber or channel, of the bio-disc 100 to supply power or a control signal to that corresponding part is shown.
  • FIG. 1 F illustrates an embodiment of a bio-driver apparatus according to the present invention, which includes the controller disc 200 for controlling the operation of the bio-disc 100.
  • the bio-driver apparatus of FIG. 1 F includes a power supply unit 110 for supplying power to the controller 63 of the controller disc 200 via the blushes 108 and 109.
  • Reference numeral 300 denotes a body of the bio-driver apparatus.
  • a printed circuit board (PCB) 140 is connected to the body 300 of the bio-driver apparatus as a base.
  • a central control system 101 for controlling the bio-driver apparatus and a storage or output unit 111 are arranged on the PCB 140.
  • the central control system 101 controls a motor 102 to rotate the bio-disc 100 and the controller disc 200 or stop their rotation, and in particular, to push the controller disc 200 and the bio-disc 100 to be closer together such that the conductive arms 13 of the controller disc 200 spontaneously fit into the grooves 33 of the bio-disc 100.
  • the central control system 101 also controls the movement of an optical pickup 103.
  • the bio-driver apparatus includes a lower rotor 105 which rotates in contact with the bottom of the bio-disc 100 and an upper rotor 104 which rotates above the controller disc 200.
  • the upper rotor 104 has a plurality of connectors 143 extending to the controller disc 200 and a grooved circumference 111 ensuring free spinning without contacting the body 300 of the bio driver apparatus.
  • the central control system 101 determines whether a disc currently loaded into the bio-driver apparatus is a general optical disc, for example, an audio CD, a CD-R, a game CD, or a DVD, or a non-optical bio-disc. If the currently loaded disc is determined to be a general optical disc, the central control system 101 transmits information read from the optical disc using the optical pickup 103 to the storage or output unit 111 or transmits information to be written to the optical pickup 103 and controls the operation of the optical disc using read/write control signals.
  • a general optical disc for example, an audio CD, a CD-R, a game CD, or a DVD, or a non-optical bio-disc.
  • the central control system 101 sends various control signals for controlling a lab-on-a-chip of the bio-disc to the controller 63 of the controller disc 200 via non-contact interfaces 106 and 107 or the IC card 188 of the bio-disc 100.
  • the controller 63 of the controller disc 200 transmits the received control signals via the conductive arms 13 or the IC card 188 to the bio-disc 100.
  • the controller 63 transmits the result of a detection from the array chamber (assay site) 132 of the bio-disc 100 by a detector including an optical device, a non-optical device, an electrochemical device, or a capacitance and impedance measurement device, via the conductive arms 13 and the non-contact interfaces 106 and 107, which may be implemented with an infrared interface, optical interface, or wireless interface, to the central control system 101 or the storage or output unit 111.
  • the controller 36 transmits the result of a detection from the array chamber (assay site) 132 of the bio-disc 100 by a detector including an optical device, a non-optical device, an electrochemical device, or a capacitance and impedance measurement device, via the IC card 188 and a wireless transmission/reception unit (not shown), to the central control system 101 or the storage or output unit 111.
  • a detector including an optical device, a non-optical device, an electrochemical device, or a capacitance and impedance measurement device, via the IC card 188 and a wireless transmission/reception unit (not shown), to the central control system 101 or the storage or output unit 111.
  • the detector including such a transmission type device and used to detect information from the array chamber (assay site) 132 is discriminated from the optical pickup 103.
  • the detector is implemented with dedicated optical assay detectors 99a and 99b.
  • the optical pickup 103 is used to read information from a general optical disc
  • the optical assay detectors 99a and 99b are used to detect information from the assay site 132 of the non-optical bio-disc 100.
  • the non-contact interfaces 106 and 107 are reception and/or transmission units for non-contact interfacing.
  • the central control system 101 may transmit control commands via the non-contact interfaces 106 and 107 to the controller 63.
  • the non-contact interfaces 106 and 107 may be implemented with infrared sensors for infrared interfacing, photosensors for optical interfacing, or combinations of a stripe antenna and a modulator/demodulator for wireless interfacing.
  • the memory embedded IC card 188 of the bio-disc 100 stores a protocol of the lab-on-chip, assay interpretive algorithms, standard control values for analysis, positional information on analysis sites, bioinformatics information, self-diagnostics, and the like.
  • the IC card 188 may include bio-driver software, educational information for patients on clinical assays and may be adapted for users.
  • the IC card 188 may include a variety of web sites and links, for example, a web site enabling a patient to communicate with a doctor or hospital based on his/her diagnosis result, and encrypted personal information to prevent unauthorized user assess.
  • a preferred example of the IC card 188 is a RAM or ROM embedded smart IC card.
  • the information stored in the IC card 188 may be wirelessly transmitted to the central control system 101 to allow for remote analysis and diagnosis and encryption for personal information security.
  • a preferred example of the output unit 111 is a Universal Serial Bus (USB) or lEEE1394.
  • FIG. 1G illustrates another example of the bio-disc 100 and the controller disc 200 for controlling the bio-disc 100, in which chambers as various assay buffer reservoirs and places for various reactions, channels as flow paths of a fluid sample and buffers, and valve apparatuses for controlling the opening and closing of the channels are integrated to form a lab-on-a-chip.
  • the bio-disc 100 is built of the upper substrate 1 , the intermediate substrate 2, and the lower substrate 3 stacked upon one another.
  • Permanent magnetic microbeads 70a, 70b, and 70c are individually moved up and down by the magnetic force generated by respective electromagnets 4a, 4b, and 4c to close and open holes connecting channels.
  • reference numeral 120 denotes a pipette or syringe for sample injection
  • reference numeral 121 denotes a sample inlet
  • reference numeral 170 denotes a disk hole.
  • Reference numeral 130 denotes a preparation chamber for preparing a DNA sample directly from blood or cells or from RNA through reverse transcription (RT) or for preparing a serum sample from blood
  • reference numeral 131 denotes a PCR chamber for polymerase chain reaction (PCR)
  • reference numeral 132 denotes a chamber for hybridization or antigen-antibody reaction, which is an assay site with capture probes for analyzing and diagnosing amplified DNA products from the PCR or with immuno arrays immobilized thereon.
  • Reference numeral 133 denotes a trash chamber for collecting wastes generated during washing.
  • Reference numeral 140 denotes a chamber for reserving a buffer containing various enzymes, including polymerase, primer, etc., required for PCR, and reference numerals 141 , 142, and 143 denote chambers for reserving various enzymes required for hybridization.
  • Opening and closing of the valve apparatuses at the start and ending points of time of each of the processes are controlled by on/off control of the power supplied to the electromagnet 4a, 4b, or 4c arranged above and below each of the permanent magnetic microbeads 70a, 70b, and 70c. Fluid flow in the bio-disc 100 is induced by the centrifugal force generated as it is rotated.
  • reference numeral 55 denotes a rotary electrode coated with a conductive material and fixed to the motor 102.
  • Reference numeral 1 10 denotes a power supply unit which supplies a direct current (DC) voltage and has a grounded negative port connected to the motor 102 and a positive port connected via blushes 108 and 109 to the rotary electrode 55 and supplies a positive voltage to the rotary electrode 55.
  • DC direct current
  • a positive voltage is supplied to the controller 63 and the wireless transmission and/or reception unit 107 of the controller disc 200 by frictional contact between the rotary electrode 55 and the brushes 108 and 109, whereas a negative voltage is supplied to the controller disc 200 via a motor shaft 57 connected to the motor 102 and an auxiliary substrate 201.
  • Reference numerals 240 and 241 denote positive and negative power ports, respectively.
  • Reference numeral 181 denotes a turntable on which the bio-disc 100 or a general optical disc, such as an audio CD, a CD-R, a game CD, or a DVD, is loaded and which engages the disc hole 170 of the bio-disc 100 or a general optical disc.
  • the controller disc 200 is fixed to the turntable 181 , and the bio-disc 100 is loaded on the turntable 181 with a gap of about 1 mm from the controller disc 200.
  • the memory embedded IC card 188 of the bio-disc 100 stores a protocol of the lab-on-chip, assay interpretive algorithms, standard control values for analysis, positional information on analysis sites, bioinformatics information, self-diagnostics, and the like.
  • the IC card 188 may include bio-driver software, educational information for patients on clinical assays and may be adapted for users.
  • the IC card 188 may include a variety of web sites and links, for example, a web site enabling a patient to communicate with a doctor or hospital based on his/her diagnosis result, and encrypted personal information to prevent unauthorized user assess.
  • a preferred example of the IC card 188 is a RAM or ROM embedded smart IC card.
  • the information stored in the IC card 188 may be wirelessly transmitted to the central control system 101 to allow for remote analysis and diagnosis and encryption for personal information security.
  • Power nodes 240a and 241a of the bio-disc 100 are coated with a conductive material and are coupled with the respective power ports 240 and 241 of the controller disc 200, so that power is supplied to the bio-disc 100 from the controller disc 200.
  • FIGS. 1 H and 11 illustrate an example of the auxiliary substrate 201 which supplies the power generated by frictional contact between the blushes 108 and 109 and the rotary electrode 55, shown in FIG. 1G, to the controller disc 200.
  • a preferred auxiliary substrate is a double-sided PCB. Exemplary upper and lower surfaces of the auxiliary substrate 201 are shown in FIGS. 1 H and 11, respectively.
  • Reference numeral 91 denotes a grounded pattern, and reference numeral 92 denotes a positive voltage pattern.
  • the motor 102 is grounded, and the motor shaft 57 connected to the motor 102 is also grounded. Accordingly, as the motor shaft 57 is inserted into a through (via) hole 203 of the auxiliary substrate 201 , the grounded pattern 91 takes on a negative voltage.
  • a positive voltage supplied from the power supply unit 1 10 is transmitted to the rotary electrode 55 via the blushes 108 and 109, which frictionally contact the rotary electrode 55.
  • the positive voltage supplied to the rotary electrode 55 is transmitted via the positive voltage pattern 92 formed on the lower substrate of the auxiliary substrate 201. In other words, a positive voltage and a negative voltage are supplied via the positive voltage pattern 92 and the grounded pattern 91 , respectively, of the auxiliary substrate 201 to the controller disc 200.
  • FIG. U illustrates an embodiment of a bio-driver apparatus assembled from the bio-disc 100 and the controller disc 200 of FIG. 1 G, in which the controller disc 200 is fixed to the turntable 181 .
  • the bio-driver apparatus of FIG. U includes a power supply unit
  • Reference numeral 300 denotes a body of the bio-driver apparatus.
  • a printed circuit board (PCB) 140 is connected to the body 300 of the bio-driver apparatus as a base.
  • a central control system 101 for controlling the bio-driver apparatus and a storage or output unit 1 1 1 are arranged on the PCB 140.
  • the central control system 101 controls a motor 102 to rotate the bio-disc 100 and the controller disc 200 or stop their rotation and controls the movement of an optical pickup 103.
  • the central control system 101 determines whether a disc currently loaded into the bio-driver apparatus is a general optical disc, for example, an audio CD, a CD-R, a game CD, or a DVD, or a non-optical bio-disc. If the currently loaded disc is determined to be a general optical disc, the central control system 101 transmits information read from the optical disc using the optical pickup 103 to the storage or output unit 1 1 1 or transmits information to be written to the optical pickup 103 and controls the operation of the optical disc using read/write control signals.
  • a general optical disc for example, an audio CD, a CD-R, a game CD, or a DVD, or a non-optical bio-disc. If the currently loaded disc is determined to be a general optical disc, the central control system 101 transmits information read from the optical disc using the optical pickup 103 to the storage or output unit 1 1 1 or transmits information to be written to the optical pickup 103 and controls the operation of the optical disc using read/write control signals.
  • the central control system 101 sends various control signals for controlling the lab-on-a-chip of the bio-disc to the controller 63 of the controller disc 200 via non-contact interfaces 106 and 107 or the IC card 188 of the bio-disc 100.
  • the controller 63 of the controller disc 200 transmits the received control signals to the bio-disc 100 and controls the opening and closing of the valve apparatuses by on/off control of the power supplied to the electromagnet 4a, 4b, or 4c arranged on the controller disc 200.
  • the electromagnet 4a, 4b, and 4c of the controller disc 200 is arranged so close to the bio-disc 100 that the repulsive or attractive force of the permanent magnetic microbeads 70a, 70b, and 70c reaches the electromagnet 4a, 4b, and 4c.
  • the controller disc 200 fixed to the turntable 181 has a gap 182 of about 1 mm from the bio-disc 100 loaded on the turntable 181 .
  • the non-contact interfaces 106 and 107 are reception and/or transmission units for non-contact interfacing.
  • the controller 63 transmits the result of a detection from the array chamber (assay site) 132 of the bio-disc 100 by a detector including an optical device, a non-optical device, an electrochemical device, or a capacitance and impedance measurement device, via the non-contact interfaces 106 and 107, which may be implemented with an infrared interface, optical interface, or wireless interface, to the central control system 101 or the storage or output unit 111.
  • the controller 36 transmits the result of a detection from the array chamber (assay site) 132 of the bio-disc 100 by a detector including an optical device, a non-optical device, an electrochemical device, or a capacitance and impedance measurement device, via the IC card 188 and a wireless transmission/reception unit (not shown), to the central control system 101 or the storage or output unit 111.
  • a detector including an optical device, a non-optical device, an electrochemical device, or a capacitance and impedance measurement device, via the IC card 188 and a wireless transmission/reception unit (not shown), to the central control system 101 or the storage or output unit 111.
  • FIGS. 2A and 2B illustrate an example of a controller disc-combined bio-disc device 700 in which the controller disc 200 and the bio-disc 100 as described above are integrated as a single body.
  • reference numeral 700a denotes a bio-disc portion
  • reference numeral 700b denotes a controller disc portion. Any material for semiconductor wafers is preferable for the controller disc-combined bio-disc device 700.
  • a common silicon wafer is suitable to highly integrate a monolithic structure including, for example, the controller 63, the IC card 188, the non-contact interface 107, the electrode plates or electromagnets for valve control, and electronic circuit patterns, and is highly compatible with common photolithography and etching techniques applied to form chambers and channels of the bio-disc according to the present invention. Integrating circuits into a wafer using semiconductor manufacturing processes, and photolithography and etching processes are well known to one of skill in the art.
  • the bio-disc portion 700a is built of an upper substrate 1 , an intermediate substrate 2, and a lower substrate 3. Channels as fluid flow paths, chambers 130, 131 , 132, 133, 140, 141 , 142, and 143 as buffer reservoirs, and holes connecting the channels are formed in the upper, intermediate, and lower substrates 1 , 2, and 3 using photolithography and etching processes.
  • the blushes 108 and 109 for power supply and an annular electrode plate 223, which frictionally contacts the blushes 108 and 109, are formed in the controller disc portion 700b of the controller disc-combined bio-disc device 700.
  • Interfacing zones 171a and 171 b include a plurality of control signal nodes 173 via which the controller 63 of the controller disc portion 700b provides control signals to valve apparatuses and electronic circuits of the bio-disc portion 700a and power nodes 33a and 33b for power supply.
  • the control signal nodes 173 and the power nodes 33a and 33b are formed as via or through holes and are interconnected with one another in the interfacing zones 171 and 171 b.
  • the interfacing zones 171a and 171 b are illustrated as being around the disc hole, they may be formed at any position on the disc as far as they are interconnected with one another, for example, as via or through holes. How to form via or through holes are well known to one of skill in the art.
  • Reference numeral 555 denotes an optional opening filled with a transparent material, for example, glass, to enable a detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device to detect the assay site 132.
  • FIG. 2B illustrates an example of a bio-driver apparatus for driving the controller disc-combined bio-disc device 700.
  • the controller 63 transmits the result of a detection from the array chamber (assay site) 132 of the controller disc-combined bio-disc device 700 by a detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device, via the non-contact interfaces 106 and 107, which may be implemented with an infrared interface, optical interface, or wireless interface, to the central control system 101 or the storage or output unit 111.
  • the controller 36 transmits the result of a detection from the array chamber (assay site) 132 of the controller disc-combined bio-disc device 700 by a detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device, via the IC card 188 and a wireless transmission/reception unit (not shown), to the central control system 101 or the storage or output unit 1 1 1 .
  • the non-contact interfaces 106 and 107 are reception and/or transmission units for non-contact interfacing.
  • the central control system 101 may transmit control commands via the non-contact interfaces 106 and 107 or the IC card 188 to the controller
  • the non-contact interfaces 106 and 107 may be implemented with infrared sensors for infrared interfacing, photosensors for optical interfacing, or combinations of a stripe antenna and a modulator/demodulator for wireless interfacing.
  • the bio-driver apparatus of FIG. 2B includes a power supply unit 1 10 for supplying power to the controller 63 of the controller disc-combined bio-disc device 700 via the blushes 108 and 109.
  • Reference numeral 300 denotes a body of the bio-driver apparatus.
  • a printed circuit board (PCB) 140 is connected to the body 300 of the bio-driver apparatus as a base.
  • a central control system 101 for controlling the bio-driver apparatus and a storage or output unit 1 1 1 are arranged on the PCB 140.
  • the central control system 101 controls a motor 102 to rotate the controller disc-combined bio-disc device 700 or stop its rotation and controls the movement of an optical pickup 103.
  • the central control system 101 controls an upper rotor 104 and a lower rotor (turntable) 105 to become closer to the disc hole 170 of the controller disc-combined bio-disc device 700 when the controller disc-combined bio-disc device 700 starts to rotate.
  • the central control system 101 determines whether a disc currently loaded into the bio-driver apparatus is a general optical disc, for example, an audio CD, a CD-R, a game CD, or a DVD, or a combined bio-disc. If the currently loaded disc is determined to be a general optical disc, the central control system 101 transmits information read from the optical disc using the optical pickup 103 to the storage or output unit 111 or transmits information to be written to the optical pickup 103 and controls the operation of the optical disc using read/write control signals.
  • a general optical disc for example, an audio CD, a CD-R, a game CD, or a DVD, or a combined bio-disc.
  • the central control system 101 sends various control signals for controlling the lab-on-a-chip of the controller disc-combined bio-disc device 700 to the controller 63 via the non-contact interfaces 106 and 107 or the IC card 188 of the controller disc-combined bio-disc device 700.
  • a detector for detecting the assay site 132 of the controller disc-combined bio-disc device 700 which may include an optical device, is discriminated from the optical pickup 103 used to read information from a general optical disc and may be implemented, for example, with dedicated optical assay detectors 99a and 99b.
  • the optical pickup 103 is used to read information from a general optical disc
  • the optical assay detectors 99a and 99b are used to detect information from the assay site 132 of the non-optical, controller disc-combined bio-disc device 700.
  • the optical assay detectors 99a and 99b may be implemented as electrochemical detectors or capacitance and impedance measurement devices.
  • the IC card 188 of the controller disc-combined bio-disc device 700 stores a protocol of the lab-on-a-chip, assay interpretive algorithms, standard control values for analysis, positional information on analysis sites, bioinformatics information, self-diagnostics, and the like.
  • the IC card 188 may include bio-driver software, educational information for patients on clinical assays and may be adapted for users.
  • the IC card 188 may include a variety of web sites and links, for example, a web site enabling a patient to communicate with a doctor or hospital based on his/her diagnosis result, and encrypted personal information to prevent unauthorized user assess.
  • a preferred example of the IC card 188 is a RAM or ROM embedded IC card.
  • the information stored in the IC card 188 may be wirelessly transmitted to the central control system 101 to allow for remote analysis and diagnosis and encryption for personal information security.
  • FIG. 2C illustrates an embodiment of a detector used in the controller disc-combined bio-disc device 700 to detect analyte signals from the analyte site 312, the detector being implemented with an electrochemical device or a capacitance and impedance measurement device which use interdigitated array electrodes.
  • International Patent Application No. PCT/KR02/00126 filed 27 January 2002 and its priority Korean Patent Application No. 10-2001-0003956 filed 27 January 2001 , which are entitled "Nucleic acid hybridization assay method and device using cleavage technique responsive to complementary double strand or single strand of nucleic acids or oligonucleotides", can be referred to for the detailed structure of this type of detector.
  • reference numerals 371 , 372, 373, and 374 denote individual analyte sites on which cleavable signal elements or capture antibodies specific to analytes are immobilized and which are arrayed in the array chamber 132.
  • Reference numeral 271 denotes a frequency generator which applies an alternating current (AC) with a given bandwidth to the individual analyte sites.
  • AC signals detected from the individual analyte sites are input to input ports of the interdigitated array electrodes to measure their frequency response characteristics and measure the electrochemical properties or the capacitance and impedance of the analyte sites based on the frequency response characteristics.
  • AC alternating current
  • the frequency response characteristics of the analyte sites are provided to the controller 63 via a multiplexer 68, and the controller 63 measures the electrochemical properties or the capacitance and impedance of the analyte sites.
  • the multiplexer 68 is controlled by the controller 63, as indicated by reference numeral 64 in FIG. 2C.
  • the electrochemical device or the capacitance and impedance measurement device of FIG. 2C is integrated into the controller disc-combined bio-disc device 700 together with the controller 63.
  • the electrochemical device or the capacitance and impedance measurement device of FIG. 2C which serve as a detector with interdigitated array electrodes, can also be applied to such a bio-disc device as illustrated in FIGS. 1 C and 1 G.
  • the multiplexer 68 and the frequency generator 271 can be arranged in the bio-disc 100 and integrated with the IC card 188.
  • FIG. 2D illustrates an example of an optical disc-combined bio-disc device 1000 assembled from a general optical disc 900 and the controller disc-combined bio-disc device 700.
  • the optical disc 900 of the optical disc-combined bio-disc device 1000 stores assay interpretive algorithms, bioinformatics information, self-diagnostics, and the like.
  • the optical disc 900 may include software enabling remote assay information storage, bio-driver software, and educational information for patients on clinical assays and may be adapted for users.
  • the optical disc 900 may include a variety of web sites and links, for example, a web site enabling a patient to communicate with a doctor or hospital based on his/her diagnosis result.
  • the optical disc 900 may store various contents from, for example, audio CDs, game CDs, CD-Rs, DVDs, etc.
  • the optical pickup 103 is used to read information from the optical disc 900, whereas a dedicated assay detector including a transmissional optical device, an electrochemical device, or a capacitance and impedance measurement device is used to detect information from the assay site 132 of the controller disc-combined bio-disc device 700.
  • the optical disc 900 may be a recordable empty CD or DVD, such as CD-RW or DVD-RW.
  • the optical disc 900 and the controller disc-combined bio-disc device 700 can be read concurrently or at differing points in time by the optical pickup 103 and the dedicated assay detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device, respectively.
  • FIG. 3A illustrates an embodiment of how the controller 63 of the bio-driver apparatus of FIGS. 1 F and U determines whether a currently loaded disc is a general optical disc, such as an audio CD, a CD-R, a game CD, a DVD, etc., or a non-optical bio-disc 100.
  • a general optical disc such as an audio CD, a CD-R, a game CD, a DVD, etc., or a non-optical bio-disc 100.
  • the controller 63 of the controller disc 200 measures a predetermined voltage across one or both of resistors R1 and R2 arranged in the bio-disc 100 as a bio-disc detection signal, via the conductive arms 13 and the grooves 33, and determines a currently loaded disc to be a bio-disc.
  • a general optical disc does not include resistors R1 and R2, and no voltage is generated from the general optical disc.
  • the controller 63 wirelessly transmits the bio-disc detection signal to the central control system 101 via the non-contact interfaces 106 and 107 or the IC card 188 to inform the central control system 101 that the currently loaded disc is a bio-disc.
  • the controller 36 operates in a normal mode when a general optical disc is loaded. However, when a bio-disc 100 is loaded, the controller 63 transmits various control signals for controlling its lab-on-a-chip to the bio-disc 100.
  • FIG. 3B illustrates an embodiment of informing the central control system 101 that a disc currently loaded into a bio-driver apparatus is a bio-disc, which can be any one of the bio-disc 100, the controller disc-combined bio-disc device 700, and the optical disc-combined bio-disc 100.
  • the bio-disc wirelessly transmits a signal indicative of bio-discs to the central control system 101 via the non-contact interfaces 106 and 107 or the IC card 188.
  • the bio-disc 100, the controller disc-combined bio-disc device 700, and the optical disc-combined bio-disc 100 may have a groove pattern or data pattern at a particular area on their surface to enable a bio-disc driver to determine whether or not a currently loaded disc is a bio-disc from the groove pattern or data pattern and inform the central control system 100 of the loading of the bio-disc. In which case, the groove pattern or data pattern formed at a particular area on the surface of a disc is detected by the optical pickup 103.
  • a determination as to whether a disc currently loaded into a bio-driver is a general optical disc, such as an audio CD, a CD-R, a game CD, a DVD, etc., or a bio-disc, such as the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device, can be made.
  • a general optical disc such as an audio CD, a CD-R, a game CD, a DVD, etc.
  • a bio-disc such as the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device
  • a user may selectively load the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device 1000 that is appropriate for his/her assay or diagnostic purpose into a bio-driver.
  • FIGS. 4A through 6D illustrate various embodiments of the optical assay detectors 99a and 99b used to detect analyte-specific signals from the assay site 132 of a bio-disc according to the present invention.
  • FIG. 4A illustrates an embodiment of the optical assay detectors which detect analyte-specific signals from the assay site 132 using light transmission through metal microspheres. This light transmission method differs from conventional detection methods applied to general optical discs which are based on differential light reflection from indentation and flat areas formed on the surface of the disc, for example, a CD, due to its physical pits.
  • the left sectional view of FIG. 4A shows a state where numerous cleavable signal elements 557 are immobilized on the surface of an upper substrate 1 of the bio-disc 100, and the right sectional view of FIG. 4A shows a state where only a few cleavable signal elements 557 remain on the upper substrate 1 after cleavage reaction.
  • the optical assay detectors 99 and 99b are implemented with a laser device, which emits a laser beam onto the cleavable signal elements 557, and a photodetector, which detects a differential light transmission signal.
  • FIG. 4B illustrates another embodiment of the optical assay detectors which detect analyte-specific signals from the assay site 132 using light transmission through metal microspheres.
  • FIG. 4B shows a state where numerous cleavable signal elements 557 are immobilized on the surface of the upper substrate 1 of the bio-disc 100, and the right sectional view of FIG.
  • the optical array detectors 99a and 99a are identical in the embodiment of FIG. 4B.
  • a laser device which emits a laser beam onto the cleavable signal elements 557
  • a photodetector which detects a differential light transmission signal.
  • a transparent opening 555 is further formed for higher sensitivity of the photodetector 99b.
  • FIG. 5A illustrates a modification of the optical array detectors of FIG. 4B based on light transmission, in which the photodetector 99b is integrated into the upper substrate 1.
  • a plurality of photodetectors 99b are arrayed one-to-one corresponding to a plurality of assay sites.
  • This arrangement of the plurality of photodetectors 99b is distinguished from a modular light transmission and reception unit used in the general optical pickup 103, the modular light transmission and reception unit causing a low sensitivity problem at a receiving site due to its longer reflection path.
  • FIG. 5B illustrates an embodiment of a bio-disc with a plurality of photodetectors 99b arrayed along its outer perimeter region. As the bio-disc is rotated, individual analyte sites in the bio-disc are sequentially detected by the corresponding photodetectors 99b.
  • FIG. 6A illustrates another embodiment of a detector for detecting analyte sites using light transmission, in which both the laser device 99a and the photodetector 99b are integrated into a lower substrate 3.
  • FIG. 6C illustrate still another embodiment of a detector for detecting analytes sites using light transmission, in which the laser device 99a is integrated into the lower substrate 3, whereas the photodetector 99b is integrated into the upper substrate 1. In either case, the laser device 99a and the photodetector 99b may be arrayed one-to-one corresponding to a plurality of assay sites for higher detection sensitivity.
  • FIGS. 6A and 6C show a state where numerous cleavable signal elements 557 are immobilized on the surface of the upper substrate 1 of the bio-disc 100, and the right sectional views of FIG. 6A and 6C show a state where only a few cleavable signal elements 557 remain on the upper substrate 1 after cleavage reaction.
  • FIG. 6B illustrates an example of an array structure of the detector of FIG. 6A, in which the laser device 99a and the photodetector 99b are alternately arrayed along an outer perimeter region of the bio-disc 100.
  • FIG. 6D illustrates an example of an array structure of the detector of FIG. 6C, in which the laser device 99a and the photodetector 99b, which face each other, are arrayed along an outer perimeter region of the bio-disc 100.
  • an optical assay detector may include a combination of a laser device and a photodetector for each assay.
  • an optical assay detector for detecting assay sites of a bio-disc may be configured, based on the arrangement of FIG. 6B, such that at least two sets of a laser device and a photodetector are integrated for each assay site for higher detection sensitivity.
  • the optical array detectors of FIGS. 6A through 6D which detect assay sites using light transmission, allow for concurrent detections of assay sites 312 as well as direct detection without need to rotate the bio-disc. In other words, non-scanning detection of assay results using light transmission can be obtained with the structures of FIGS. 6A through 6D.
  • This assay detection method requires neither rotating the bio-disc to allow an optical pickup to access to individual assay sites nor predetermined site location information therefor, unlike laser scanning detection methods which use an optical pickup to read information from general optical discs.
  • FIGS. 7A through 7G illustrate examples of electrochemical detectors or capacitance and impedance measurement devices for detecting analyte-specific signals from the assay site 132 of the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device 1000.
  • Some of the electrochemical detectors or capacitance impedance measurement devices illustrated in FIGS. 7A through 7G are implemented with interdigitated array electrodes 702 and 703 arranged on a substrate 701 and a metal microsphere 40 or horse radish peroxidase (HRP) 41 attached as signal responsive moiety to each cleavable signal element immobilized as a probe on the substrate 701.
  • HRP horse radish peroxidase
  • Some of the electrochemical detectors or capacitance impedance measurement devices illustrated in FIGS. 7A through 7G are based on antigen-antibody reaction mainly used for immunochromatography.
  • FIG. 7A illustrates an example of an electrochemical detector or a capacitance and impedance measurement device with interdigitated array electrodes 702 and 703.
  • the controller 63 applies an AC signal having a given bandwidth to two input ports 704 and 705 of the respective interdigitated array electrodes 702 and 703 to measure the frequency response characteristics of assay sites and then the capacitance and impedance of the assay sites from the frequency response characteristics.
  • the controller 63 may be able to measure a voltage or a current induced as a result of the reduction/oxidation (REDOX) of analytes by HRP in H 0 2 solution, thereby enabling electrochemical detection of assay sites.
  • REDOX reduction/oxidation
  • FIGS. 7B and 7C illustrate an example of an electrochemical detector or a capacitance and impedance measurement device for detecting analyte-specific signals from the assay site 132 of the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device 1000.
  • 7B and 7C is implemented with the interdigitated array electrodes 702 and 703 arranged on the substrate 701 and HRP 41 attached as signal responsive moiety to each cleavable signal element immobilized as a probe on the substrate 701. Electrons are generated as a result of successive REDOX reactions by the HRP 41 and induce a current and a voltage across the interdigitated array electrodes 702 and 703.
  • the sensitivity of the interdigitated array electrodes 702 and 703 becomes higher with more digits.
  • the assay site 132 of the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device 1000 is manufactured by aminating the surface of the substrate 701 , forming a non-reactive monolayer, for example, of alkane chains (CH 2 ) n on the aminated surface of the substrate 701 , and immobilizing cleavable signal elements labeled with biotin 50, wherein the non-reactive layer is for preventing direct contact of the cleavable signal elements with the substrate 701.
  • a non-reactive monolayer for example, of alkane chains (CH 2 ) n
  • cleavable signal elements which are not hybridized with a sample remain as single strands are cleaved by a nuclease and removed through washing. Meanwhile, cleavable signal elements which are hybridized with the sample and form double strands 43 remain uncleaved after the cleavage and washing processes.
  • streptavidin-labeled HRP is injected to bind the streptavidin 51 to the biotin labeled to the uncleaved signal elements.
  • the controller 63 measures the voltage and the current across the interdigitated array electrodes 701 and 703. In this way, a differential electrochemical signal between the cleaved and uncleaved signal elements can be detected.
  • the left sectional view of FIG. 7C shows a state where cleavable signal elements remain uncleaved on the bio-disc 100, 700, or 1000, so that the uncleaved signal elements are highly likely to be oxidized and reduced by the HRP in H 2 O 2 solution.
  • the right sectional view of FIG. 7C shows a state where most cleavable signal elements are cleaved and removed through washing so that REDOX reaction is unlikely to occur. A differential electrochemical signal between the two states is detected.
  • FIGS. 7D and 7E illustrate another example of an electrochemical detector or a capacitance and impedance measurement device for detecting analyte-specific signals from the assay site 132 of the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device 1000.
  • the electrochemical detector or the capacitance and impedance measurement device of FIGS. 7D and 7E is implemented with the interdigitated array electrodes 702 and 703 arranged on the substrate 701 and HRP 41 and metal microspheres 40 attached as signal responsive moiety to cleavable signal elements immobilized as probes on the substrate 701 .
  • Electrons are generated as a result of successive REDOX reactions by the HRP 41 , contact the metal microspheres 40, and induce a current and a voltage across the interdigitated array electrodes 702 and 703.
  • the sensitivity of the detector is determined by the ratio of HRP-labeled probes and metal microsphere-labeled probes. More metal microspheres, which act as a carrier of electrons generated from a series of REDOX reactions by the HRP, lead to higher detection sensitivity.
  • cleavable signal elements which are hybridized with the sample and form double strands 43 remain uncleaved after the cleavage and washing processes.
  • streptavidin-labeled HRP and streptavidin-labeled metal microspheres 40 are provided to bind the streptavidin 51 to the biotin labeled to the uncleaved signal elements.
  • a series of REDOX reactions of the uncleaved signal elements are caused by the HRP in H 2 0 2 solution to induce a voltage and a current across the interdigitated array electrodes 701 and 703.
  • the controller 63 measures the voltage and the current across the interdigitated array electrodes 701 and 703. In this way, a differential electrochemical signal between the cleaved and uncleaved signal elements can be detected.
  • FIG. 7D illustrates the concept of REDOX reactions induced by the HRP.
  • the biotin 50 labeled to the end of the uncleaved signal elements prior to the hybridization and the HRP 41 and the metal microsphere 40 which are labeled with the streptavidin 51 appear.
  • the coupling of the streptavidin 51 of the HRP 41 and the metal microsphere 40 to the biotin 50 at the ends of the uncleaved signal elements, which is formed through simple contact, also appear.
  • the left sectional view of FIG. 7E shows a state where cleavable signal elements remain uncleaved on the bio-disc 100, 700, or 1000, so that the uncleaved signal elements are labeled with the HRP 41 and the metal microsphere 40 and are highly likely to be oxidized and reduced by the HRP 41 in H 2 0 2 solution.
  • the right sectional view of FIG. 7E shows a state where most cleavable signal elements are cleaved and removed through washing so that REDOX reaction is unlikely to occur. A differential electrochemical signal between the two states is detected.
  • FIGS. 7F and 7G illustrate another example of an electrochemical detector or a capacitance and impedance measurement device for detecting analyte-specific signals from the assay site 132 of the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device 1000.
  • the electrochemical detector or the capacitance and impedance measurement device of FIGS. 7F and 7G is implemented with the interdigitated array electrodes 702 and 703 arranged on the substrate 701 and a conjugate antibody 471 which forms a conjugate-antigen complex with a target sample (analyte or antigen) to be assayed.
  • the conjugate-antigen complex is applied to an assay site 312 in which capture antibodies 473 are immobilized on the substrate 701.
  • the electrochemical detector or the capacitance and impedance measurement device of FIGS. 7F and 7G are based on antigen-antibody reaction between the conjugate-antigen complex and the capture body 473.
  • the conjugate antibody 471 is labeled with colorimetric moiety 474 made of, preferably, gold or latex.
  • the conjugate-antigen complex reacts with the capture antibody 473
  • the antigen-antibody reaction product remains an uncleaved signal element after washing.
  • the capture antibody 473 which remains unreacted, serves as a cleaved signal element.
  • the capacitances and impedances of the uncleaved and cleaved signal elements are measured from their frequency response characteristics.
  • the left sectional view of FIG. 7G shows a state where the uncleaved signal elements labeled with gold or latex, which are products of antigen-antibody reactions in the bio-disc 100, 700, or 1000, remain on the substrate 701 after washing.
  • the right sectional view of FIG. 7G shows a state where no antigen-antibody reaction takes place and only the capture antibody remains unreacted after washing. A differential capacitance and impedance signal between the two states is detected.
  • FIGS. 8A through 8F Embodiments of bio-discs according to the present invention are illustrated in FIGS. 8A through 8F.
  • FIGS. 8A through 8C illustrate various examples of labs-on-a-chip which can be integrated into the bio-disc 100, the controller disc-combined bio-disc device 700, or the optical disc-combined bio-disc device 1000 according to the present invention.
  • reference numeral 170 denotes a disc hole
  • reference numeral 171 denotes an interfacing zone for electrical connection with the controller disc 200.
  • Reference numeral 130 denotes a preparation chamber for preparing a DNA sample or a serum sample from blood, cells, or RNA
  • reference numerals 131 and 131a denote PCR chambers for polymerase chain reaction (PCR), in which a buffer containing various enzymes, such as polymerase and primers, is reserved
  • reference numeral 132 denotes a chamber for hybridization or antigen-antibody reaction, which is an assay site with biotin-labeled capture probes for analyzing and diagnosing amplified DNA products from the PCR or with immuno arrays immobilized thereon
  • reference numeral 133 denotes a trash chamber for collecting wastes generated during washing.
  • the chambers for the main processes are arranged in a spiral formation from the center to the outer perimeter and are interconnected with each other, so as to induce natural fluid flow by centrifugal force to allow for sequential processes.
  • reagent reservoir chambers are arranged in a spiral formation near the corresponding reaction chambers.
  • Reference numeral 129 denotes a washing buffer reservoir; reference numeral 129a denotes a distilled water reservoir; reference numeral 144 denotes a hybridization buffer reservoir; reference numeral 136 denotes a reservoir of a DNAse used in DNA fragmentation into appropriate size; and reference numerals 141 , 142, and 143 denote reservoirs of various enzymes used in hybridization.
  • Reference numeral 141 denotes a reservoir of a nuclease used in single strand cleavage; reference numeral 142 denotes a reservoir of streptavidin-labeled metal microspheres; and reference numeral 143 denotes a reservoir of phosphate buffered saline (PBS).
  • PBS phosphate buffered saline
  • Reference numerals 150, 151 , 152, 153, 154, 155, 156, 157, 158, 160, 161 , and 162 denote valves. Fluid flow in the bio-discs 100, 700, and 1000 is controlled by the centrifugal force generated as the bio-disc is rotated and by opening and closing the valves.
  • Reference numeral 177 denotes an electromagnet embedded in the bio-disc 100, 700, or 1000, which may be disposed above or below the preparation chamber 130, instead of be embedded in the bio-disc 100, 700, or 1000.
  • Opening and closing of the valves at the start and ending points of time of each of the main processes, including sample preparation, PCR, hybridization, antigen-antibody reaction, and washing, are controlled by the controller 63 controlling the on/off of the power applied to the electromagnets arranged above and below each film-like cylindrical permanent magnet of the valves.
  • Reference numeral 128 denotes a distilled water reservoir
  • reference numeral 135 denotes a trash chamber.
  • FIG. 8A illustrates an embodiment of a bio-disc including one PCR chamber in its lab-on-a-chip.
  • FIG. 8B illustrates an embodiment of a bio-disc including a plurality of PCR chambers in its lab-on-a-chip.
  • each PCR chamber reserves one type of primer.
  • all of the PCR chambers reserves the same type of primer.
  • the amplified DNA products from each of the PCR chambers combine in a chamber 131 b.
  • FIG. 8C illustrates an embodiment of a lab-on-a-chip designed for antigen-antibody reaction, which can be integrated into the bio-disc 100, 700, or 1000.
  • reference numeral 130 denotes a preparation chamber for preparing a serum sample from blood injected via a sample inlet; cells, or RNA;
  • reference numeral 132 denotes a chamber for hybridization, which is an assay site with immuno arrays immobilized thereon so as to analyze and diagnose an antigen, i.e., sample or analyte; and reference numeral 133 denotes a trash chamber for collecting wastes generated during washing.
  • the chambers for the main processes are arranged in a spiral formation from the center to the outer perimeter of the disc and are interconnected with each other, so as to induce natural fluid flow by centrifugal force to allow for sequential processes.
  • reagent reservoir chambers are arranged in a spiral formation near the corresponding reaction chambers.
  • Reference numeral 129 denotes a washing buffer reservoir
  • reference numeral 142a denotes a conjugate antibody reservoir. Conjugate antibodies in reservoir 142a are labeled with colorimetric moiety made of, for example, gold or latex.
  • Reference numerals 150, 152, 153, and 156 denote valves. Fluid flow in the bio-discs 100, 700, and 1000 is controlled by the centrifugal force generated as the bio-disc is rotated and by opening and closing the valves.
  • Reference numeral 177a denotes a filter embedded in the bio-disc 100, 700, or 1000, which is used to filter a blood sample to extract serum.
  • FIGS. 8D and 8E are sectional views of the bio-discs of FIGS. 8A and 8B or 8C, illustrating the main assay processes conducted therein.
  • Permanent magnetic microbeads 150, 151 , 153, and 156 are individually moved up and down to close and open channels by the magnetic force generated by respective electromagnet pairs 4d and 5d, 4a and 5a, 4b and 5b, and 4c and 5c.
  • Reference numeral 121 denotes a sample inlet.
  • a DNA or serum sample is prepared from blood, cells, or RNA.
  • the preparation chamber 130 reserves a lysis buffer solution for DNA extraction through lysis and ferroelectric beads having affinity to extracted DNA.
  • the PCR chamber 131 contains various enzymes, including a polymerase and a primer such as dNTP, which are required for PCR, in a buffer.
  • capture probes for analyzing and diagnosing amplified DNA products from the PCR or immuno arrays are immobilized. Wastes from washing are collected in the trash chamber 133.
  • a blood sample injected via the sample inlet 121 is passed through the filter 177a to extract serum.
  • DNA is extracted from a sample in the preparation chamber 130 in the following way.
  • a heater 960 (refer to FIG. 8D) installed in the preparation chamber 130 is turned on to separate DNA from the electromagnetic beads or resuspend it in a resuspension buffer.
  • DNA amplification is conducted in the PCR chamber 131 (131a) in the following way.
  • the bio-disc is slowly rotated, the valve 152 is opened to allow the DNA separated from the electromagnetic beads in the preparation chamber 130 to flow into the PCR chamber 131.
  • Fragmentation which is optional, is conducted to cut the amplified DNA products from the PCR to proper size for hybridization.
  • the amplified DNA products may be fragmented as follows.
  • the bio-disc is slowly rotated, and the valve 158 is opened to allow a DNAse in the reservoir 136 to flow into the PCR chamber 131 (131 b) for fragmentation.
  • the heater 961 is turned on to deactivate the DNAse and stop the fragmentation. As a result, the DNA is denaturated into single strands.
  • the length of DNA fragments may be varied depending on the duration of incubation process 3).
  • the heaters are individually controlled during fragmentation to obtain DNA fragments which vary in length. It will be appreciated that the duration of the incubation can be varied in each PCR chamber 131 b.
  • Hybridization process Single-stranded DNA from the PCR, which has undergone high-temperature denaturation, optionally, has further undergone fragmentation into a proper size, is hybridized to biotin-labeled capture probes previously immobilized on the assay site 132 in the following way.
  • Hybridization reaction is controlled by varying the electric field strength of an external electrode pattern 962 and an electrode plate 963 and the amount of heat generated by a heater 962.
  • the electrode pattern 962 acts as a heater when operated alone but can also serve as an electrode plate generating a perpendicular electric field when operated in combination with the electrode plate 963.
  • the bio-disc is rotated, the valve 157 is opened to allow a hybridization buffer to flow into the assay site 132 for washing, with or without the application of an external electric field vertically through the bio-disc (first wash process).
  • the valve 157 is closed.
  • the valve 156 is opened during washing and closed after washing.
  • the bio-disc is slowly rotated, and the valve 154 is opened to allow a nuclease solution to enter and spread over the assay site 132.
  • the valve 154 is closed, and the bio-disc is incubated in a stationary state for 1-2 minutes to cleave single-stranded DNA (cleavage process).
  • the bio-disc is slowly rotated, and the valve 155 is opened to allow a streptavidin-labeled metal microsphere suspension to enter and spread over the assay site 132 ("uncleaved probe-label complex" formation).
  • the biotin-labeled capture probes are bound with the streptavidin-labeled metal microspheres 40, forming a biotin-streptavidin binding structure.
  • the valve 155 is closed. During this process, the reaction temperature and the electric field strength may be controlled using the external electrode pattern 962 and the electrode plate 963.
  • the electrode pattern 962 acts as a heater when operated alone but can also serve as an electrode plate generating a perpendicular electric field when operated in combination with the electrode plate 963. 7)
  • the bio-disc is rotated at a higher speed, and the valve 162 is opened to allow distilled water in the reservoir 128 to enter the assay site for washing, with or without the application of an electric field to the bio-disc (second wash process). During this wash process, the valve 156 is opened.
  • a detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device, which have the above-described structure, the detector being programmed to be able to selectively detect assay sites with cleavable signal elements.
  • the diagnostic data and a prescription based on the result of the detection are displayed on a computer monitor, and optionally automatically or manually transmitted through the Internet to a specialist at a remote location.
  • the patient waits for a prescription from the specialist.
  • FIG. 8D illustrates an embodiment of a bio-disc in which an electrochemical detector or a capacitance and impedance measurement device using the interdigitated array electrodes on the substrate 701 is installed as a detector in the assay site 132.
  • FIG. 8E illustrates an embodiment of a bio-disc in which a pair of optical assay detectors 99a and 99b are integrated into the same silicon wafer via semiconductor manufacturing processes to detect analyte-specific signals.
  • the optical assay detectors 99a and 99b of FIG. 8E may be any modification from the structures of FIGS. 5A, 5B, 6A, and 6B.
  • Serum is extracted from blood in the preparation chamber 130 in the following way. 1 ) 10 ⁇ L (EDTA, ACD Tube) of blood is injected via the sample inlet 121 into the preparation chamber 130 with the filter 177a at its outlet.
  • 10 ⁇ L (EDTA, ACD Tube) of blood is injected via the sample inlet 121 into the preparation chamber 130 with the filter 177a at its outlet.
  • valve 152 is opened, and the bio-disc is slowly rotated to allow the blood to flow out the preparation chamber 130 through the filter 177a and enter the conjugate antibody reservoir 142a.
  • the conjugate antibody reservoir 142a of FIG. 8C reserves conjugate antibodies labeled with colorimetric moiety, such as gold or latex, and the assay site 132 contains capture antibodies immobilized on a substrate.
  • Antigen-antibody reactions in a bio-disc according to the present invention involve binding an antigen in the serum extracted via the sample preparation to the labeled conjugate antibodies in the conjugate antibody reservoir 142a to form a conjugate-antigen complex and binding the conjugate-antigen complex to the capture antibodies in the assay site
  • conjugate reservoir chamber 142 After the serum enters the conjugate reservoir chamber 142, the conjugate reservoir chamber 142 is incubated for 1-2 minutes to induce a reaction between an antigen and conjugate antibodies to form a conjugate-antigen complex.
  • valve 153 is opened, the bio-disc is slowly rotated to allow the conjugate-antigen complex in the conjugate antibody reservoir 142a to flow into the assay site 132.
  • the bio-disc is incubated in a stationary state at room temperature for 3-5 minutes and left for a reaction between the conjugate-antigen antibody and the capture antibodies in the assay site 132.
  • the bio-disc is rotated, and the valves 150, 153, and 156 are opened to allow the washing buffer in the washing buffer reservoir 129 to enter and wash the assay site 132.
  • a detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device, which have the above-described structure, the detector being programmed to be able to selectively detect assay sites with cleavable signal elements.
  • the diagnostic data and a prescription based on the result of the detection are displayed on a computer monitor, and optionally automatically or manually transmitted through the Internet to a specialist at a remote location.
  • the patient waits for a prescription from the specialist.
  • FIG. 8F illustrates an embodiment of a heater and an electric field generation used in sample preparation, PCR, and hybridization.
  • the heaters 960, 961 , and 962 in FIGS. 8D and 8E are formed as an electrode pattern.
  • the electrode pattern 962 acts as a heater when operated alone but can also serve as an electrode plate generating a perpendicular electric field when operated in combination with the electrode plate 963.
  • the reaction temperature and the electric field strength are controlled by the controller 63.
  • the electrode pattern 962 as a heater have two input ports 962a and 962b. A voltage is applied across the input ports 962a and 962b to induce current flow in the electrode pattern 961 and enable the electrode pattern 961 to act as a resistive or thermal coil.
  • the controller 63 supplies a current to the electrode pattern 962 via its input ports 962a and 962b and controls the amount of current supplied to the electrode pattern 962 and its temperature using the temperatures of the electrode pattern 962 periodically measured by the thermosensor 520.
  • an equal voltage is applied across the two input ports 962a and 962b of the electrode pattern 962 to handle them as one port, while a voltage is applied to the electrode plate 962 as the other port.
  • the controller 63 applies an AC voltage across the electrode pattern 962 and the electrode plate 963 to generate an AC electric field. Since DNA has negative charges, the AC electric field strength between the electrode pattern 962 and the electrode plate 963 can be varied to control the stringency of DNA hybridization and for higher sensitivity in detecting single nucleotide polymorphism (SNP).
  • SNP single nucleotide polymorphism
  • thermosensor 520 of FIGS. 8D and 8E is described as being used for precise temperature control during PCR, it can be used in any process which requires thermal detection.
  • An assay automatically starts as soon as a bio-disc is loaded into a bio-driver apparatus.
  • the bio-driver apparatus sends an "eject" message or a warning message to a user.
  • an additional impedance measurement device may be installed in the preparation chamber 130. Whether a sample has been injected or not can be determined from different impedance characteristics between two states, one containing a sample and one without a sample.
  • Such an impedance measurement device for detecting the presence of a sample may be implemented with interdigitated array electrodes, like the capacitance and impedance measurement device installed in the assay site 132.
  • the bio-driver apparatus When an unloading or a stop command is input to the bio-driver apparatus during assay or diagnosis, the bio-driver apparatus sends a warning message or requests a user's password while continuing assay and diagnosis.
  • the bio-driver apparatus stops the assay or diagnosis and ejects the bio-disc.
  • the bio-driver apparatus ejects the bio-disc at the request of the user.
  • the bio-disc stores in its IC card 188 information on how many times it has been used, its validation period, and kinds of diseases which it can diagnose.
  • the bio-driver apparatus informs the user that the bio-disc is no longer valid.
  • FIGS. 9A and 9B illustrate alternative embodiments of bio-discs according to the present invention, in which sample preparation and PCR or further electrophoresis can be conducted in a single disc.
  • FIG. 9A illustrates an example of a PCR bio-disc capable of sample preparation and PCR therein.
  • reference numeral 170 denotes a disc hole
  • reference numeral 171 denotes an interfacing zone for electrical connection with its controller disc.
  • Reference numeral 130 denotes a preparation chamber for preparing a DNA sample or a serum sample from blood, cells, or RNA; reference numeral 131a denotes a PCR chamber in which a buffer containing various enzymes, such as polymerase and primers, is reserved; reference numeral 88a denotes an out-chamber into which PCR products are discharged; reference numeral 129 denotes a washing buffer reservoir; reference numeral 129a denotes a distilled water reservoir; reference numerals 144a and 88b denote a ladder marker reservoir and its out-chamber, respectively; reference numerals 141a and 88c denote a positive or negative control reservoir and its out-chamber, respectively; reference numerals 142a and 143a denote electrophoretic reagent reservoirs for storing various reagents used in electrophoresis, including strains; reference numerals 88d and 88e denote out-chambers of the respective electrophoretic reagent reservoirs 142a and 143
  • the out-chamber 88a may have an outlet via which PCR products can be extracted by means of a pipette or a syringe for manual electrophoresis.
  • FIG. 9B illustrates an example of an electrophoresis bio-disc device for automated electrophoresis that is assembled from an upper PCR bio-disc, which can be the PCR bio-disc of FIG. 9A, and a lower electrophoresis bio-disc.
  • the lower electrophoresis bio-disc includes gel plates 155 made of agarose gel and/or polyacrylamide gel and annular electrodes 555a and 555b across which a voltage is applied to the gel plates 155.
  • the PCR product out-chamber 88a, the ladder marker out-chamber 88b, the positive/negative control out-chamber 88c, and the strain out-chamber 88e are interconnected with respective in-chambers 99a, 99b, 99c, 99d, and 99e of the electrophoresis bio-disc.
  • electrophoresis starts with the application of a voltage across the electrodes 555a and 555b. After a predetermined amount of time, the voltage applied to the electrodes 555a and 555b is cut off to stop electrophoresis.
  • the controller 63 controls voltage level and the opening and closing of the valves.
  • the PCR bio-disc and the electrophoresis bio-disc are electrically connected via the interfacing zone 171 of their controller disc.
  • a bio-disc device including such an electrophoresis disc as described above may further include a UV radiator and a camera to identify, store, and transmit bands appearing on the gel plate 555c.
  • FIGS. 10A and FIG. 10B illustrate embodiments of assay devices according to the present invention, in which an immunoassay sector for antigen-antibody reaction and a nucleic acid probe hybridization sector are arranged in an angular or radial direction. An immunoassay and a DNA assay can be conducted simultaneously with the assay devices of FIGS. 10A and 10B. In addition, the number of assay sites can be reduced through proper combination, and diagnostic reliability is doubled.
  • FIGS. 11A and 11 B illustrate exemplary appearances of bio-driver apparatuses according to the present invention.
  • Reference numeral 751 denotes a case
  • reference numeral 750 denotes a bio-disc loading tray
  • reference numerals 745 and 746 denote a play/search button and a stop button, respectively, for general optical discs.
  • the bio-driver apparatus of FIG. 11A is an embodiment of indicating the status of proceeding with an assay using light emitting diodes (LEDs).
  • a LED 741 indicates that a currently loaded disc is a bio-disc
  • a LED 742 indicates the current status of proceeding with an assay
  • a LED 743 indicates that a general optical disc has been loaded.
  • Alternative indicative means instead of LEDs can be used for the same purpose.
  • the bio-driver apparatus of FIG. 11 B is an embodiment of indicating the status of proceeding with an assay through a liquid crystal display (LCD) 760.
  • the status of progress in each main process such as sample preparation, PCR, hybridization, and antigen-antibody reaction, can be expressed in percentages or as a bar graph.
  • the status of proceeding with an assay in the bio drive apparatus according to the present invention can be displayed through a computer monitor.
  • the status of progress in each main process such as sample preparation, PCR, hybridization, and antigen-antibody reaction, can be expressed in percentages or as a bar or pie graph.
  • a bio-disc device including an optical and/or non-optical disc, a bio-driver apparatus, and an assay method using the same according to the present invention are suitable for labs-on-a-chip for various diagnostic assay devices, nucleic acid hybridization assay devices, and immunoassays.
  • a particularly important feature of the present invention is that the bio-driver apparatus is compatible with general optical discs, including audio CDs, CD-Rs, game CDs, DVDs, etc., and the assay method is compatible with general optical disc drivers, including CD-ROMs, DVD players, etc.
  • the bio-driver apparatus can be readily and easily applied in connection with a computer for remote diagnosis via the Internet.

Abstract

L'invention concerne un biodisque non optique, un dispositif de biodisque comprenant le biodisque non optique et/ou un disque optique, un appareil de biolecteur dans lequel est installé un disque de dispositif de commande comprenant un dispositif de commande pour le biodisque, et un procédé d'essai faisant appel à ceux-ci, ces derniers étant appropriés à des laboratoires sur puce pour des essais diagnostiques variés, des essais d'hybridation d'acide nucléique, et des immunoessais. Cet appareil de biolecteur est compatible avec des disques optiques généraux, y compris des CD, des CD-R, des CD de jeu, des DVD etc., et ce procédé d'essai est compatible avec des lecteurs de disques optiques généraux, y compris des CD-ROM, des lecteurs de DVD, etc. Ainsi, l'appareil de biolecteur et le procédé d'essai constituent une alternative économique et pratique aux produits existants. En outre, cet appareil de biolecteur peut être facilement et rapidement appliqué à une connexion avec un ordinateur pour un diagnostic éloigné par l'Internet.
PCT/KR2003/000613 2002-03-27 2003-03-27 Biodisque, appareil de biolecteur, et procede d'essai faisant appel a ceux-ci WO2003080868A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003218806A AU2003218806A1 (en) 2002-03-27 2003-03-27 Bio-disc, bio-driver apparatus, and assay method using the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2002-0017558 2002-03-27
KR20020017558 2002-03-27

Publications (1)

Publication Number Publication Date
WO2003080868A1 true WO2003080868A1 (fr) 2003-10-02

Family

ID=28450108

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2003/000613 WO2003080868A1 (fr) 2002-03-27 2003-03-27 Biodisque, appareil de biolecteur, et procede d'essai faisant appel a ceux-ci

Country Status (3)

Country Link
KR (1) KR100830926B1 (fr)
AU (1) AU2003218806A1 (fr)
WO (1) WO2003080868A1 (fr)

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006042369A1 (fr) * 2004-10-22 2006-04-27 Fermiscan Australia Pty Limited Procede et appareil analytique
WO2006118420A1 (fr) * 2005-04-30 2006-11-09 Jae Chern Yoo Biodisque, appareil de biolecteur et procede d'essai faisant appel a ceux-ci
WO2006121266A1 (fr) * 2005-05-06 2006-11-16 Jae Chern Yoo Biodisque numerique (dbd), appareil de lecture de dbd, ainsi que procede d'analyse mettant en oeuvre ce biodisque
WO2007001160A1 (fr) * 2005-06-28 2007-01-04 Jae Chern Yoo DISPOSITIF DE BlOLECTURE ET PROCÉDÉ D’ESSAI L’UTILISANT
WO2007073107A1 (fr) 2005-12-21 2007-06-28 Jae Chern Yoo Disque a memoire biologique et appareil de lecture de disque a memoire biologique, et procede de dosage utilisant un tel appareil
WO2007079530A1 (fr) 2006-01-12 2007-07-19 Mycrolab Pty Ltd Nouveaux systèmes et procédés d'instrumentation
EP1883815A1 (fr) * 2005-05-20 2008-02-06 Rmit University Dispositif d'essai
WO2008016271A1 (fr) * 2006-08-02 2008-02-07 Jae Chern Yoo Appareil d'analyse de film mince et procédé d'analyse mettant en œuvre un tel appareil
WO2008051167A1 (fr) * 2006-10-25 2008-05-02 Nanyang Polytechnic Systèmes de laboratoire intégrés sur cd avec micro-soupapes de retenue actionnées magnétiquement et/ou immobilisation magnétique
DE102005059536B4 (de) * 2005-12-13 2008-08-28 Siemens Ag Verfahren und Biochip zur Untersuchung einer biologischen Probe
US7524464B2 (en) 2003-09-26 2009-04-28 Ahn Chong H Smart disposable plastic lab-on-a-chip for point-of-care testing
WO2010076337A1 (fr) * 2009-01-05 2010-07-08 Gottfried Wilhelm Leibniz Universität Hannover Microsystème électromagnétique pour la manipulation de microperles ou de nanoperles magnétiques
US7776553B2 (en) * 2005-09-16 2010-08-17 Presidents And Fellows Of Harvard College Screening assays and methods
US20100312574A1 (en) * 2008-02-14 2010-12-09 Jae Chern Yoo Bio-disc reading apparatus and assay method using same
CN101873885B (zh) * 2007-11-22 2013-07-31 三星电子株式会社 薄膜阀器件及其控制装置
CN101416048B (zh) * 2006-01-12 2013-10-02 迈克罗拉布诊断有限公司 新仪器系统和方法
CN103495440A (zh) * 2013-09-25 2014-01-08 中国科学院长春光学精密机械与物理研究所 离心式微流控芯片试剂预封装结构、制作方法及应用方法
WO2017085472A1 (fr) * 2015-11-16 2017-05-26 Mast Group Limited Appareil de réalisation d'essai
WO2018015931A1 (fr) * 2016-07-22 2018-01-25 Trustech S.R.L. Kit portatif pour dosages immunoenzymatiques automatisés
EP3046670B1 (fr) * 2013-09-19 2019-01-02 Dianax S.r.l. Dispositif de diagnostic, en particulier du type laboratoire-sur-puce
US10799862B2 (en) 2006-03-24 2020-10-13 Handylab, Inc. Integrated system for processing microfluidic samples, and method of using same
US10821446B1 (en) 2006-03-24 2020-11-03 Handylab, Inc. Fluorescence detector for microfluidic diagnostic system
US10844368B2 (en) 2007-07-13 2020-11-24 Handylab, Inc. Diagnostic apparatus to extract nucleic acids including a magnetic assembly and a heater assembly
US10865437B2 (en) 2003-07-31 2020-12-15 Handylab, Inc. Processing particle-containing samples
US10875022B2 (en) 2007-07-13 2020-12-29 Handylab, Inc. Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples
US10900066B2 (en) 2006-03-24 2021-01-26 Handylab, Inc. Microfluidic system for amplifying and detecting polynucleotides in parallel
US11060082B2 (en) 2007-07-13 2021-07-13 Handy Lab, Inc. Polynucleotide capture materials, and systems using same
US11142785B2 (en) 2006-03-24 2021-10-12 Handylab, Inc. Microfluidic system for amplifying and detecting polynucleotides in parallel
US11266987B2 (en) 2007-07-13 2022-03-08 Handylab, Inc. Microfluidic cartridge
US11441171B2 (en) 2004-05-03 2022-09-13 Handylab, Inc. Method for processing polynucleotide-containing samples
US11453906B2 (en) 2011-11-04 2022-09-27 Handylab, Inc. Multiplexed diagnostic detection apparatus and methods
US11549959B2 (en) 2007-07-13 2023-01-10 Handylab, Inc. Automated pipetting apparatus having a combined liquid pump and pipette head system
US11788127B2 (en) 2011-04-15 2023-10-17 Becton, Dickinson And Company Scanning real-time microfluidic thermocycler and methods for synchronized thermocycling and scanning optical detection
US11806718B2 (en) 2006-03-24 2023-11-07 Handylab, Inc. Fluorescence detector for microfluidic diagnostic system
US11959126B2 (en) 2021-10-07 2024-04-16 Handylab, Inc. Microfluidic system for amplifying and detecting polynucleotides in parallel

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100707171B1 (ko) * 2004-08-31 2007-04-13 삼성전자주식회사 Ｐｃｒ을 수행할 수 있는 잉크젯 방식의 ｄｎａ 어레이어및 이를 이용한 ｄｎａ 마이크로어레이의 제조방법
KR101255984B1 (ko) * 2006-01-16 2013-04-23 유재천 기록층을 포함하는 dbd 디스크를 이용한 질병 진단 데이터 저장 시스템 및 저장 방법
KR101250537B1 (ko) * 2006-01-16 2013-04-03 유재천 디비디 디스크상 진단 프로세스 점검 시스템 및 방법
KR101306341B1 (ko) * 2006-09-05 2013-09-09 삼성전자주식회사 원심력 기반의 핵산 추출용 미세유동 장치 및 상기미세유동 장치를 포함한 미세유동 시스템
KR100818274B1 (ko) * 2006-09-05 2008-04-01 삼성전자주식회사 미세유동 시스템 제어장치 및 그 방법, 및 미세유동 시스템
KR101433570B1 (ko) * 2007-04-23 2014-08-26 삼성전자주식회사 원격 의료 진단 시스템 및 방법
KR101307859B1 (ko) * 2007-07-19 2013-09-12 삼성전자주식회사 생화학 분석기 및 그 내부 온도 제어 방법
KR100806941B1 (ko) * 2007-08-09 2008-02-25 (주)와이즈앤블루 랩언어디스크 판독 장치
WO2009075513A2 (fr) * 2007-12-10 2009-06-18 Jae Chern Yoo Dispositif à valve biologique à film mince et son appareil de commande
KR20130099703A (ko) 2012-02-29 2013-09-06 삼성전자주식회사 옵티컬 헤드 및 이를 포함하는 시퀀싱 장치
KR101528433B1 (ko) * 2014-11-19 2015-06-11 고려대학교 산학협력단 질염테스트칩, 질염원인균검출장치 및 질염원인균검출방법

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10103558A (ja) * 1996-09-30 1998-04-21 Tokyo Gas Co Ltd マイクロバルブ
WO2000037163A1 (fr) * 1998-12-23 2000-06-29 Nanogen, Inc. Systeme de detection biologique integre portatif
WO2002018655A2 (fr) * 2000-09-01 2002-03-07 Board Of Regents, The University Of Texas System Compositions et procedes conçus pour generer des jeux ordonnes de microechantillons d'adnc simple brin a reference de quantification universelle exacte
WO2003021223A2 (fr) * 2001-08-30 2003-03-13 Burstein Technologies, Inc. Technique d'analyse qualitative et quantitative de cellules et systemes de disques optiques biologiques

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10103558A (ja) * 1996-09-30 1998-04-21 Tokyo Gas Co Ltd マイクロバルブ
WO2000037163A1 (fr) * 1998-12-23 2000-06-29 Nanogen, Inc. Systeme de detection biologique integre portatif
WO2002018655A2 (fr) * 2000-09-01 2002-03-07 Board Of Regents, The University Of Texas System Compositions et procedes conçus pour generer des jeux ordonnes de microechantillons d'adnc simple brin a reference de quantification universelle exacte
WO2003021223A2 (fr) * 2001-08-30 2003-03-13 Burstein Technologies, Inc. Technique d'analyse qualitative et quantitative de cellules et systemes de disques optiques biologiques

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LENIGK R. ET AL.: "Surface characterization of a silicon-chip-.based DNA microarray", LANGMUIR, vol. 17, no. 8, 2001, pages 2497 - 2501, XP001180968, DOI: doi:10.1021/la001355z *
NAGAI H. ET AL.: "High-troughput PCR in silicon based microchamber array", BIOSENSORS AND BIOELECTRONICS, vol. 16, no. 9-12, 2001, pages 1015 - 1019, XP001155197, DOI: doi:10.1016/S0956-5663(01)00248-2 *

Cited By (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11078523B2 (en) 2003-07-31 2021-08-03 Handylab, Inc. Processing particle-containing samples
US10865437B2 (en) 2003-07-31 2020-12-15 Handylab, Inc. Processing particle-containing samples
US7524464B2 (en) 2003-09-26 2009-04-28 Ahn Chong H Smart disposable plastic lab-on-a-chip for point-of-care testing
US11441171B2 (en) 2004-05-03 2022-09-13 Handylab, Inc. Method for processing polynucleotide-containing samples
WO2006042369A1 (fr) * 2004-10-22 2006-04-27 Fermiscan Australia Pty Limited Procede et appareil analytique
KR100941416B1 (ko) * 2005-04-30 2010-02-11 삼성전자주식회사 바이오 디스크 및 바이오 드라이버 장치 및 이들을 이용한분석방법
JP2008539419A (ja) * 2005-04-30 2008-11-13 シェーン ユウ、ジャエ バイオディスクおよびバイオドライバ装置、これを用いた分析方法
JP4819119B2 (ja) * 2005-04-30 2011-11-24 サムスン エレクトロニクス カンパニー リミテッド バイオディスクおよびバイオドライバ装置、これを用いた分析方法
EP1885883A1 (fr) * 2005-04-30 2008-02-13 Jae Chern Yoo Biodisque, appareil de biolecteur et procede d'essai faisant appel a ceux-ci
EP1885883A4 (fr) * 2005-04-30 2009-09-23 Jae Chern Yoo Biodisque, appareil de biolecteur et procede d'essai faisant appel a ceux-ci
CN101166834B (zh) * 2005-04-30 2011-09-14 三星电子股份有限公司 生物盘、生物驱动器装置和使用该盘和装置的化验方法
US8993487B2 (en) 2005-04-30 2015-03-31 Samsung Electronics Co., Ltd. Bio disc, bio-driver apparatus, and assay method using the same
WO2006118420A1 (fr) * 2005-04-30 2006-11-09 Jae Chern Yoo Biodisque, appareil de biolecteur et procede d'essai faisant appel a ceux-ci
EP2400039A3 (fr) * 2005-04-30 2012-11-07 Jae-Chern Yoo Biodisque, appareil de bio-commande et procédé d'analyse l'utilisant
US8263386B2 (en) 2005-05-06 2012-09-11 Samsung Electronics Co., Ltd. Digital bio disc (DBD), DBD driver apparatus, and assay method using the same
JP2008541043A (ja) * 2005-05-06 2008-11-20 シェーン ユウ、ジャエ デジタルバイオディスクおよびデジタルバイオディスクドライバ装置ならびに方法
JP4896127B2 (ja) * 2005-05-06 2012-03-14 サムスン エレクトロニクス カンパニー リミテッド デジタルバイオディスクおよびデジタルバイオディスクドライバ装置ならびに方法
WO2006121266A1 (fr) * 2005-05-06 2006-11-16 Jae Chern Yoo Biodisque numerique (dbd), appareil de lecture de dbd, ainsi que procede d'analyse mettant en oeuvre ce biodisque
EP1883815A4 (fr) * 2005-05-20 2008-10-22 Univ Rmit Dispositif d'essai
EP1883815A1 (fr) * 2005-05-20 2008-02-06 Rmit University Dispositif d'essai
JP2008544296A (ja) * 2005-06-28 2008-12-04 シェーン ユウ、ジャエ バイオドライブ装置およびそれを用いた分析方法
EP1917525A4 (fr) * 2005-06-28 2011-05-25 Samsung Electronics Co Ltd DISPOSITIF DE BlOLECTURE ET PROCÉDÉ D' ESSAI L' UTILISANT
EP1917525A1 (fr) * 2005-06-28 2008-05-07 Jae Chern Yoo DISPOSITIF DE BlOLECTURE ET PROCÉDÉ D' ESSAI L' UTILISANT
JP4940446B2 (ja) * 2005-06-28 2012-05-30 サムスン エレクトロニクス カンパニー リミテッド バイオドライブ装置およびそれを用いた分析方法
US9279818B2 (en) 2005-06-28 2016-03-08 Samsung Electronics Co., Ltd. Bio drive apparatus, and assay method using the same
WO2007001160A1 (fr) * 2005-06-28 2007-01-04 Jae Chern Yoo DISPOSITIF DE BlOLECTURE ET PROCÉDÉ D’ESSAI L’UTILISANT
US8835187B2 (en) 2005-09-16 2014-09-16 Presidents And Fellows Of Harvard College Screening assays and methods
US8865479B2 (en) 2005-09-16 2014-10-21 President And Fellows Of Harvard College Screening assays and methods
US10137426B2 (en) 2005-09-16 2018-11-27 President And Fellows Of Harvard College Screening assays and methods
US7776553B2 (en) * 2005-09-16 2010-08-17 Presidents And Fellows Of Harvard College Screening assays and methods
US11154833B2 (en) 2005-09-16 2021-10-26 President And Fellows Of Harvard College Screening assays and methods
US9463431B2 (en) 2005-09-16 2016-10-11 President And Fellows Of Harvard College Screening assays and methods
US8835188B2 (en) 2005-09-16 2014-09-16 Presidents And Fellows Of Harvard College Screening assays and methods
US8772049B2 (en) 2005-09-16 2014-07-08 President And Fellows Of Harvard College Screening assays and methods
DE102005059536B4 (de) * 2005-12-13 2008-08-28 Siemens Ag Verfahren und Biochip zur Untersuchung einer biologischen Probe
US8951779B2 (en) 2005-12-21 2015-02-10 Samsung Electronics Co., Ltd. Bio memory disc and bio memory disc drive apparatus, and assay method using the same
EP1971861A4 (fr) * 2005-12-21 2014-10-22 Samsung Electronics Co Ltd Disque a memoire biologique et appareil de lecture de disque a memoire biologique, et procede de dosage utilisant un tel appareil
JP2009520985A (ja) * 2005-12-21 2009-05-28 ジェ・チャーン・ユ バイオメモリディスク及びバイオメモリディスクドライブ装置及びそれを用いた分析方法
WO2007073107A1 (fr) 2005-12-21 2007-06-28 Jae Chern Yoo Disque a memoire biologique et appareil de lecture de disque a memoire biologique, et procede de dosage utilisant un tel appareil
EP1971861A1 (fr) * 2005-12-21 2008-09-24 Jae Chern Yoo Disque a memoire biologique et appareil de lecture de disque a memoire biologique, et procede de dosage utilisant un tel appareil
CN101416048B (zh) * 2006-01-12 2013-10-02 迈克罗拉布诊断有限公司 新仪器系统和方法
WO2007079530A1 (fr) 2006-01-12 2007-07-19 Mycrolab Pty Ltd Nouveaux systèmes et procédés d'instrumentation
EP1977223A4 (fr) * 2006-01-12 2011-01-19 Mycrolab Pty Ltd Nouveaux systèmes et procédés d'instrumentation
EP1977223A1 (fr) * 2006-01-12 2008-10-08 Mycrolab PTY LTD Nouveaux systèmes et procédés d'instrumentation
US10821446B1 (en) 2006-03-24 2020-11-03 Handylab, Inc. Fluorescence detector for microfluidic diagnostic system
US11142785B2 (en) 2006-03-24 2021-10-12 Handylab, Inc. Microfluidic system for amplifying and detecting polynucleotides in parallel
US11666903B2 (en) 2006-03-24 2023-06-06 Handylab, Inc. Integrated system for processing microfluidic samples, and method of using same
US10913061B2 (en) 2006-03-24 2021-02-09 Handylab, Inc. Integrated system for processing microfluidic samples, and method of using the same
US10857535B2 (en) 2006-03-24 2020-12-08 Handylab, Inc. Integrated system for processing microfluidic samples, and method of using same
US10821436B2 (en) 2006-03-24 2020-11-03 Handylab, Inc. Integrated system for processing microfluidic samples, and method of using the same
US10799862B2 (en) 2006-03-24 2020-10-13 Handylab, Inc. Integrated system for processing microfluidic samples, and method of using same
US11085069B2 (en) 2006-03-24 2021-08-10 Handylab, Inc. Microfluidic system for amplifying and detecting polynucleotides in parallel
US11141734B2 (en) 2006-03-24 2021-10-12 Handylab, Inc. Fluorescence detector for microfluidic diagnostic system
US10900066B2 (en) 2006-03-24 2021-01-26 Handylab, Inc. Microfluidic system for amplifying and detecting polynucleotides in parallel
US10843188B2 (en) 2006-03-24 2020-11-24 Handylab, Inc. Integrated system for processing microfluidic samples, and method of using the same
US11806718B2 (en) 2006-03-24 2023-11-07 Handylab, Inc. Fluorescence detector for microfluidic diagnostic system
KR101335920B1 (ko) 2006-08-02 2013-12-03 삼성전자주식회사 박막화학분석장치 및 이를 이용한 분석방법
WO2008016271A1 (fr) * 2006-08-02 2008-02-07 Jae Chern Yoo Appareil d'analyse de film mince et procédé d'analyse mettant en œuvre un tel appareil
US8097450B2 (en) * 2006-08-02 2012-01-17 Samsung Electronics Co., Ltd. Thin film chemical analysis apparatus and analysis method using the same
EP2046992A4 (fr) * 2006-08-02 2012-02-01 Electronics Co Ltd Samsung Appareil d'analyse de film mince et procédé d'analyse mettant en oeuvre un tel appareil
EP2046992A1 (fr) * 2006-08-02 2009-04-15 Jae Chern Yoo Appareil d'analyse de film mince et procédé d'analyse mettant en oeuvre un tel appareil
WO2008051167A1 (fr) * 2006-10-25 2008-05-02 Nanyang Polytechnic Systèmes de laboratoire intégrés sur cd avec micro-soupapes de retenue actionnées magnétiquement et/ou immobilisation magnétique
GB2455956A (en) * 2006-10-25 2009-07-01 Nanyang Polytechnic Lab-on-CD systems with magnetically actuated micro check valves and/or magnetic immobilization
US11845081B2 (en) 2007-07-13 2023-12-19 Handylab, Inc. Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples
US10844368B2 (en) 2007-07-13 2020-11-24 Handylab, Inc. Diagnostic apparatus to extract nucleic acids including a magnetic assembly and a heater assembly
US11466263B2 (en) 2007-07-13 2022-10-11 Handylab, Inc. Diagnostic apparatus to extract nucleic acids including a magnetic assembly and a heater assembly
US11254927B2 (en) 2007-07-13 2022-02-22 Handylab, Inc. Polynucleotide capture materials, and systems using same
US10875022B2 (en) 2007-07-13 2020-12-29 Handylab, Inc. Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples
US11266987B2 (en) 2007-07-13 2022-03-08 Handylab, Inc. Microfluidic cartridge
US11549959B2 (en) 2007-07-13 2023-01-10 Handylab, Inc. Automated pipetting apparatus having a combined liquid pump and pipette head system
US11060082B2 (en) 2007-07-13 2021-07-13 Handy Lab, Inc. Polynucleotide capture materials, and systems using same
US8658113B2 (en) 2007-11-22 2014-02-25 Samsung Electronics Co., Ltd. Thin film valve device and its controlling apparatus
CN101873885B (zh) * 2007-11-22 2013-07-31 三星电子株式会社 薄膜阀器件及其控制装置
US8609434B2 (en) * 2008-02-14 2013-12-17 Samsung Electronics Co., Ltd. Bio-disc reading apparatus and assay method using same
US20100312574A1 (en) * 2008-02-14 2010-12-09 Jae Chern Yoo Bio-disc reading apparatus and assay method using same
WO2010076337A1 (fr) * 2009-01-05 2010-07-08 Gottfried Wilhelm Leibniz Universität Hannover Microsystème électromagnétique pour la manipulation de microperles ou de nanoperles magnétiques
US11788127B2 (en) 2011-04-15 2023-10-17 Becton, Dickinson And Company Scanning real-time microfluidic thermocycler and methods for synchronized thermocycling and scanning optical detection
US11453906B2 (en) 2011-11-04 2022-09-27 Handylab, Inc. Multiplexed diagnostic detection apparatus and methods
EP3046670B1 (fr) * 2013-09-19 2019-01-02 Dianax S.r.l. Dispositif de diagnostic, en particulier du type laboratoire-sur-puce
CN103495440B (zh) * 2013-09-25 2015-04-22 中国科学院长春光学精密机械与物理研究所 离心式微流控芯片试剂预封装结构、制作方法及应用方法
CN103495440A (zh) * 2013-09-25 2014-01-08 中国科学院长春光学精密机械与物理研究所 离心式微流控芯片试剂预封装结构、制作方法及应用方法
WO2017085472A1 (fr) * 2015-11-16 2017-05-26 Mast Group Limited Appareil de réalisation d'essai
RU2732945C2 (ru) * 2015-11-16 2020-09-24 Маст Груп Лимитед Устройство для проведения анализа
CN108602068B (zh) * 2015-11-16 2021-11-05 马斯特集团有限公司 用于进行试验的设备
CN108602068A (zh) * 2015-11-16 2018-09-28 马斯特集团有限公司 用于进行试验的设备
JP2018533742A (ja) * 2015-11-16 2018-11-15 マスト グループ リミティド 分析を行うための装置
WO2018015931A1 (fr) * 2016-07-22 2018-01-25 Trustech S.R.L. Kit portatif pour dosages immunoenzymatiques automatisés
US11959126B2 (en) 2021-10-07 2024-04-16 Handylab, Inc. Microfluidic system for amplifying and detecting polynucleotides in parallel

Also Published As

Publication number Publication date
KR20050014797A (ko) 2005-02-07
KR100830926B1 (ko) 2008-05-22
AU2003218806A1 (en) 2003-10-08

Similar Documents

Publication Publication Date Title
WO2003080868A1 (fr) Biodisque, appareil de biolecteur, et procede d'essai faisant appel a ceux-ci
US8993487B2 (en) Bio disc, bio-driver apparatus, and assay method using the same
US8263386B2 (en) Digital bio disc (DBD), DBD driver apparatus, and assay method using the same
KR101292536B1 (ko) 바이오 메모리 디스크 및 바이오 메모리 디스크 드라이브장치 및 이를 이용한 분석 방법
KR100590902B1 (ko) 핵산 및 올리고뉴클레오티드의 상보적 이중가닥 또는단일가닥에 특이적으로 반응하는 절단 기법을 이용한 핵산혼성 분석 방법 및 장치
KR101335920B1 (ko) 박막화학분석장치 및 이를 이용한 분석방법
JP4591195B2 (ja) バイオアッセイ用の基板と装置、並びに基板の製造方法
KR100855996B1 (ko) Pcr 디스크 장치, pcr 디스크 드라이버 장치 및 그를 이용한 분석 방법
WO2002073605A2 (fr) Essai biologique a deux perles utilisant des espaceurs clivables et/ou la ligature pour ameliorer la specificite et la sensibilite, procedes et dispositifs associes

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 BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PH PL PT RO RU SC SD SE SG SK SL 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): GH GM KE LS MW MZ 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 IT LU MC NL 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
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1020047015027

Country of ref document: KR

WWP Wipo information: published in national office

Ref document number: 1020047015027

Country of ref document: KR

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP