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Laboratory in a disk

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Publication number
US20010048895A1
US20010048895A1 US09363929 US36392999A US2001048895A1 US 20010048895 A1 US20010048895 A1 US 20010048895A1 US 09363929 US09363929 US 09363929 US 36392999 A US36392999 A US 36392999A US 2001048895 A1 US2001048895 A1 US 2001048895A1
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Prior art keywords
assay
disk
sample
fig
analyte
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Abandoned
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US09363929
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Jorma Virtanen
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Nagaoka Co Ltd
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Burstein Technologies Inc
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502715Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
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    • B01L3/5027Containers 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
    • B01L3/50273Containers 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 the means or forces applied to move the fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
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    • B01L3/54Labware with identification means
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6816Hybridisation assays characterised by the means of detection
    • C12Q1/6825Nucleic acid detection involving sensors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6834Nucleic acid analysis involving immobilisation; Immobilisation characterised by the carrier or coupling agent
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay
    • G01N33/543Immunoassay; Biospecific binding assay with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54373Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029Automatic 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
    • G01N35/00069Automatic 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0605Metering of fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
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    • B01L2200/0673Handling of plugs of fluid surrounded by immiscible fluid
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    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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Abstract

An apparatus is described that includes an optical disk, adapted to be read by an optical reader, comprising a first sector having substantially self-contained assay means for localizing an analyte suspected of being in a sample to at least one, predetermined location in the first sector and a second sector containing control means for conducting the assay and analyte location information, with respect to one or more analytes suspected of being in a sample, accessible to the reader, wherein the presence or absence of the analyte at said location is determinable by the reader using the control means and the location information. Depending on the nature of the assay, the disk will include fluid storage means, fluid transfer means, such as one or more capillary ducts, valves, batteries, dialyzers, columns, filters, sources of electric fields, wires or other electrical conductive means such as metallic surface deposits and the like.

Description

    FIELD OF THE INVENTION
  • [0001]
    This invention relates generally to diagnostic assays and methodology therefor. In particular, it relates to diagnostic assay components configured on a compact optical disk and methodology for the use thereof
  • BACKGROUND
  • [0002]
    There is an enormous need to make clinical assays faster, cheaper and simpler to perform. Ideally patients should be able to test themselves, if so desired. One-way towards this goal has been through miniaturization and integration of various assay operations. Currently, a number of bio-chip assays (so-called because some are built using silicon chip photolithography techniques) are commercially available or under development. All of these approaches require a reading machine and a computer.
  • [0003]
    Disk-shaped cassettes used for clinical assays in conjunction with UV/Vis spectrometry are also commercially available. U.S. Pat. No. 15,122,284 describes a centrifugal rotor that contains a number of interconnected fluid chambers connected to a plurality of cuvettes. The rotor is adapted to be utilized with a conventional laboratory centrifuge, and is formed of materials that allow photometric detection of the results of assays that have been carried out in the reaction cuvettes. A large number of rotor configurations and related apparatus for the same or similar types of analysis have been described. See for example U.S. Pat. Nos. 5,472,603; 5,173,193; 5,061,381; 5,304,348; 5, 518,930; 5,457,053; 5,409,665; 5,160,702; 5,173,262; 5,409,665; 5,591,643; 5,186,844; 5,122,284; 5,242,606; and patents listed therein. Lyophilized reagents for use in such systems are described in U.S. Pat. No. 5,413,732.
  • [0004]
    The principles of a centrifugal analyzer have been adapted into a disk that can be used. in a CD-drive like instrument (Mian, et al., WO 97/21090 Application). Mian teaches a modified CD-drive with a dual function: 1. It is used to read information stored in the disk, and 2. It is used to rotate the disk. However, Mian does not teach utilization of the reading capability of a CD-drive for actual assay analysis.
  • [0005]
    Notwithstanding recent advances, there remains a need for a simpler assay configuration that performs assays quickly, efficiently, accurately and at low cost. The present invention combines diagnostic assays with computers and compact disk technology. In its most preferred embodiment, a computer with a compact disk reader is the only instrument needed. All chemistry is performed inside a compact disk that may be referred to as an integrated biocompact disk (IBCD). The same compact disk is also encoded with software, i.e., machine-readable instructional and control information, that provides instructions to a computer prior to, during and after the assay.
  • [0006]
    CDs or DVDs represent the most economical and in many ways best information storage media. It must be noted that CD and DVD are currently used acronyms that may change in the future even if the underlying technology stays basically the same. A CD- or DVD-drive is in several respects equivalent to a scanning confocal microscope. At the same time these instruments are comparable to good centrifuges, because in commercial drives the rotation frequency is between 200-12,000 rpm and can be adjusted within certain limits. Combining these three features into the same analytical system results into great simplification as compared with any other analytical technique. Yet, the performance is comparable or better than in most competing methods. Although this invention requires slightly modified CD-or DVD-drives, it is possible to incorporate these changes into commercial drives. This will enable Point-Of-Patient-Care (POPC) and home use of this invention. Use of CD- or DVD-drives will allow accurate digital analysis of any sample without any specific analytical instrumentation.
  • SUMMARY OF THE INVENTION
  • [0007]
    In one aspect, the invention is directed to an optical disk, adapted to be read by an optical reader, comprising a first sector having a substantially self-contained assay means for binding an analyte suspected of being in a sample to at least one predetermined location in the first sector and optionally a second sector containing control means for conducting the assay and analyte location information, with respect to one or more analytes suspected of being in a sample, accessible to a reader, wherein the presence or absence of the analyte at said location is determinable by the reader using the control means and the location information. Depending on the nature of the assay, the disk may include fluid storage means, fluid transfer means, such as one or more capillary ducts, valves, batteries, dialyzers, columns, filters, sources of electric fields, wires or other electrical conductive means such as metallic surface deposits and the like.
  • [0008]
    The disk may have one or more sample entry ports to deliver sample fluid to the assay sector. Such ports if present are preferably sealable so that after application of the sample to the disk, the sealed disk including the sample comprises a hermetically sealed device that may be conveniently disposed of by conventional means or other disposal mechanisms for dealing with biological waste. Also, the assay sector of the disk is conveniently divided into various subsections for sample preparation and analyte separation. A waste receptacle subsection may be conveniently provided as well. The assay sector may be divided into a multiplicity of subsectors that each receives a sample. Each such subsector may analyze for one or more analytes depending on the particular application at hand.
  • [0009]
    In another aspect the invention is directed to an apparatus for conducting an assay comprising an optical disk, a disk reader and an information processor, the disk comprising a first sector having substantially self-contained assay means for localizing an analyte suspected of being in a sample to at least one, predetermined location in the first sector and optionally a second sector containing control information for conducting the assay and analyte location information, with respect to one or more analytes suspected of being in the sample, accessible to the reader and processable by the information processor, wherein the disk is adapted to be read by the reader and the information processor is adapted to determine the presence or absence of the analyte at said location using the control information and the location information. The apparatus may include a reader having a CD-ROM or DVD reader and an information processor, such as a personal computer.
  • [0010]
    In still another aspect the invention is directed to an optical disk, adapted to be read by a CD-ROM or DVD reader, comprising a substantially self-contained assay means in the disk for localizing an analyte suspected of being in a sample to at least one, predetermined location on the disk and means at said location for detection of the absence or presence of the analyte by the CD-ROM or DVD reader.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0011]
    [0011]FIG. 1 is a schematic representation of a disk of this invention.
  • [0012]
    [0012]FIG. 2 A is a more detailed schematic representation of a sample preparation and assay sector of the disk, illustrating the overall layout of a typical assay sector.
  • [0013]
    [0013]FIG. 2 B is a schematic representation of an ubiquitous assay sector that is capable of performing immunoassays, DNA testing, cell counting, spectrophotometric assays and electrolyte analysis.
  • [0014]
    [0014]FIG. 3 is a schematic representation of a disk of this invention illustrating a multiplicity of assay sectors, each having an individual sample inlet port.
  • [0015]
    [0015]FIG. 4 is a more detailed schematic representation of one of the assay sectors illustrated in FIG. 3.
  • [0016]
    [0016]FIG. 5 is a schematic representation of a chemically actuated battery useful in the present invention.
  • [0017]
    [0017]FIG. 6 is a schematic representation of a structure to provide a dialysis function in the disk of this invention.
  • [0018]
    [0018]FIG. 7 is a schematic representation of a column that may be included in the disk of this invention.
  • [0019]
    [0019]FIG. 8 is a schematic representation of an electrically controlled valve useful in the present invention.
  • [0020]
    [0020]FIG. 9 is a schematic representation of a reagent train configured in joined capillary ducts that is useful in the present invention.
  • [0021]
    [0021]FIG. 10 is a schematic representation of an array of linear assay sites that are conveniently located in a flow channel in the assay sector of the disk of this invention.
  • [0022]
    [0022]FIG. 11 A-C is a schematic representation of a variation of an assay element that is particularly useful for the detection of viral and bacterial particles and cells using the general methodology of site specific localization of the substance to be detected.
  • [0023]
    [0023]FIG. 12 A-C is a schematic representation of a variation of the detection methodology in which opaque particles are utilized in the place of the reflective particles and bound to a reflective surface. Zig-zag lines represent oligonucleotides, but can be any recognition molecules, such antibodies. Particles are in this example plastic spheres, but can be liposomes, cells, etc.
  • [0024]
    [0024]FIG. 13 is a schematic representation of an assay element of the invention illustrating the spacer molecule, with component sidearms and cleavage site, bound to a disk surface at one end and to a reporter element (gold or latex sphere) at its other end.
  • [0025]
    [0025]FIG. 14 A is schematic representation of a first assay element of this invention, at an early stage during the assay procedure.
  • [0026]
    [0026]FIG. 14 B is schematic representation of a second assay element of this invention, at an early stage during the assay procedure.
  • [0027]
    [0027]FIG. 14 C is a schematic representation of the assay element in FIG. 14 A wherein analyte molecules have bound the sidearms forming a connective loop between the sides of the cleavage site.
  • [0028]
    [0028]FIG. 14 D is a schematic representation of the assay element in FIG. 14 B wherein analyte molecules have not bound to the sidearms and no connective loop has formed between the sides of the cleavage site.
  • [0029]
    [0029]FIG. 14 E is a schematic representation of the assay element in FIG. 14 C after the spacer molecules have been cleaved. The reporter element remains attached to the disk surface at a discrete site.
  • [0030]
    [0030]FIG. 14 F is a schematic representation of the assay element in FIG. 14 D after the spacer molecules have been cleaved. The reporter element is detached from the disk surface and free to be washed away from its discrete site.
  • [0031]
    [0031]FIG. 15 is a schematic representation of a cuvette assembly. Four cuvettes and their associated reagent and sample preparation chambers as well as light sources are shown in this example.
  • [0032]
    [0032]FIG. 16 is a schematic representation of a capillary array that can be used to perform isoelectric focusing.
  • [0033]
    [0033]FIG. 17 is a schematic representation of an apparatus for measuring exact volumes.
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0034]
    A schematic overall representation of an integrated bio-compact disk (IBCD) is set forth in FIG. 1. The disk (Bio-Compact Disk, BCD) may be virtually of any shape and size. For most practical applications it is circular having a diameter of 10-1000 mm, most advantageously 20-200 mm and a thickness of 0.1-20 mm, most advantageously 0.5-3 mm. The disk 10 contains two sectors: an assay sector 11 and a software sector 12. A central hole 13 is provided for location in a compact disk reader. Software for controlling the assay may be on a separate disk. However, it is preferred to have the software on the disk associated with an assay for a particular analyte or analytes to minimize the opportunity for human error when performing the assay. The possible components and unit operations of the IBCD are presented in the following description.
  • [0035]
    The disk rotates typically up to 16,000 rpm in conventional CD-ROM or DVD readers. In all CD-ROM and DVD readers the speed is adjustable within certain limits (200-16,000 rpm). However, for some operations it may be advantageous to utilize rotations at differing speeds, for example 1000-10,000 rpm, and most preferably 2000-5000 rpm. For any particular assay, the controlling software dictates the rotation regimen during the analysis. This regimen, the speeds and timing, including times in which perhaps no rotation occurs to allow for incubation, electrophoresis, isoelectric focusing, etc., is controlled to deliver reagents and sample to appropriate sites on the assay sector as dictated by the assay protocols. Available rotational speeds do allow for a significant centrifugal force that may be used to move liquids. Another energy source that may be easily used in the IBCD is chemical energy. A most suitable form of chemical energy is released by a battery in the form of electrical energy. Mechanical and chemical energy allow the operation of many kinds of components. Important components of a IBCD may include one or more of the following: capillaries, containers, filters, dialysis membranes, chromatographic columns, electrophoretic gels, valves, any micromechanical or electronic components including microprocessors, electrodes, especially enzyme electrodes, cuvettes, and assay elements. The possible unit operations carried out by the components include the following: centrifugation, filtering, transfer of liquids, mixing of liquids, dialysis, column separations, heating, cooling, electroconvection, electrophoresis, and analyte detection and signaling thereof.
  • [0036]
    The IBCD is conveniently made from two pieces comprising upper and lower halves. The lower half may contain almost all the components, while the upper half may be a flat cover containing only a few components, such as electrodes and wires. The number of layers in this invention may be more than two and many components may also be pre-made as modules. Especially reagent containers, cuvette assemblies, columns, micromechanical components, light sources, and microprocessors are advantageously assembled as modules. Various features may be printed onto the soft plastic. Various components may be glued, either by thermal or UV-curing, melted together, connected by complementary mechanical features, mechanically clamped or simply enclosed inside a larger component. Some areas may be treated, for instance, with ammonia plasma to render these areas hydrophilic. The surface may be further treated by various molecules that render the surface inert or alternatively give it specific adsorption properties. Silylation is a general method for the treatment of surfaces (Virtanen, J. A., Kinnunen, P. K. J. and Kulo, A., “Organosilanes and their hydrolytic polymers as surface treatment agents for use in chromatography and electronics,” U.S. Pat. No. 4,756,971). Covalent attachment of detergents will reduce the adsorption of proteins, such as albumin, and will also reduce the adsorption of soluble proteins. Metal electrodes and wires may be evaporated onto desired areas. Masks or resists may be used to localize the plasma treatment or metal deposition. Capillary ducts and fluid storage and retention compartments may be machined into the optical disks or formed by chemical means or in injection molding operations. As shown with reference to FIG. 2, the assay sector may contain a sample inlet port 14. The sample port is preferably sealable so that at the disk is effectively sealed, except for necessary venting to allow for fluid flow, to protect from any biological hazards. By various means, e.g. centrifugal force and like means that are well known in the art, a portion of the sample is metered to a sample preparation site 15, that may contain reagents and the like in order to conduct the assay. Alternatively, or in conjunction with reagents already in the sample preparation segment, a reagent train 16 may be provided to deliver, as needed, the necessary reagents in the proper order to the sample preparation segment. Additional details of the reagent train are shown in FIG. 9. It may be necessary to separate the analyte from the sample, at least partially, and this may be done in a sample separation segment designated generally as 17. A battery 18 is provided if electrical energy is required for the separation process. Additional details of the battery are shown in FIG. 5 and described below. The resultant sample is then transferred to the assay site 19. In a preferred embodiment of the invention, the assay site contains an assay element as described in greater detail below. The analyte binds to a predetermined location on the disk if it is present in the sample, and the presence of the analyte is detected by the reader from information that identifies the particular analyte with the location at which it is bound. A waste compartment is provided to collect overflow of reagents or sample that exceeds metered amounts for use in the assay and the various compartments and fluid transfer channels are vented appropriately to allow for fluid flow throughout the surface of the assay sector.
  • [0037]
    In one embodiment of the invention, a multiplicity of assay sectors 21, 22, 23, etc. as shown in FIG. 3 may be provided, each sector connected to an individual sample inlet port 24, 25, 26 respectively. The operation of each sector is substantially as described above although different assays may be conducted at the same time in individual sectors either for a multitude of analytes or a multitude of patients. The details of a particular sector are shown in greater detail in FIG. 4, where the various possible components are identified by the same numbers as used in the foregoing description.
  • Components
  • [0038]
    As shown in FIG. 5, a battery may be provided that consists simply of two metal layers, such as copper and zinc, which are in the lower and upper half, respectively. During storage they are separated by air. When the disk is rotated, the space between these two metals is filled by dilute mineral acid, depending on the nature of the metal electrodes. In the case of copper and zinc, this may be dilute sulfuric acid, containing copper ions and the battery is activated. This battery generates a voltage of 1.5 V for only about 1 hour. However, this is more than enough to complete the analysis. Longer lasting batteries may be made, if necessary, from other materials or thicker metal layers. Importantly, allowing water to flow into the space between the metal layers deactivates the battery. The activation and deactivation cycle may be repeated several times. Several batteries may be coupled in series to increase the potential, if necessary. Optionally, photodiodes may be included into the circuitry. In this case, the computer controlling the assay is provided with information about the active circuits. Also, a miniaturized, pre-fabricated battery may be utilized and activated by closing the electrical circuit with a salt, e.g. sodium chloride, solution.
  • [0039]
    Capillaries preferably are used to transfer liquid and air. Also, very small volumes of liquid may be stored in capillaries. Preferably, air capillaries are hydrophobic, while capillaries that come into contact with water are hydrophilic. As necessary, capillaries may have circular or rectangular cross-sections. Typical depths are between 10 μm and 500 μm, while widths are between 50 μm and 2 mm. Air capillaries utilize the larger dimensions to prevent any formation of a pressure gradient, unless otherwise desired. The velocity of the flow depends on the frequency of the rotation of the IBCD, the dimensions of the capillary and the viscosity and density of the liquid. Physical properties of the liquid are dictated by the assay and the frequency of rotation is limited to a certain extent by the CD-ROM or DVD reader. Thus, the dimensions of the capillary are used to adjust the speed of the liquid transfer. The capillary ducting may be provided with “bottlenecks,” i.e., restrictions in the cross-sectional areas of the capillary, to control the velocity of the liquid as necessary. Hydrophilicity and hydrophobicity may be used for the same purpose.
  • [0040]
    The exact dimensions of the capillary network and chambers may be designed by using the Navier-Stokes equation:
  • ρv=ρ−∇p+μ∇ 2 v
  • [0041]
    where ρ is the density, p is the pressure, v is the velocity, b is the body force field, μ is the viscosity and ∇is the differential operator del (Mase, Continuum Mechanics, McGraw-Hill, 1970). Pressure is a scalar field, while v and b are vector fields. Commercial computer software for solving of the Navier-Stokes equation in complicated geometries is available.
  • [0042]
    Containers or compartments formed in the disk are used for sample input, to store reagents, to perform reactions and to collect waste. Their depth is about 1-2000 μm, preferably about 10-800 μm and they may have any shape possible, although circular or rectangular cross-sections are preferred. Compartments are hydrophilic, except for one end of the waste container which has an air capillary that is hydrophobic. Reaction compartments may be formed with electrodes for heating, electroconvection of electrochemical purposes. Electrodes are preferably evaporated gold films. Compartments may also have valves that are operated by electricity or chemically as described below. Storage containers may be metal coated, preferably gold coated, to prevent the penetration of the water into the plastic. Reagents may also be prepacked into cassettes, which are virtually impermeable. These cassettes may be closed during storage and opened manually, by puncturing or by opening a valve or plug when the sample cassette is place in the disk. Opening of the cassette may also be facilitated by centrifugal force when the IBCD starts to rotate. In any case, proper liquid flow is maintained during the assay by computer control via CD or DVD-reader.
  • [0043]
    The liquid flow during the assay may be monitored by using a reflective element. The reflective element utilizes the laser that is in the CD or DVD-reader and the fact that even when the liquid is transparent its reflective index is significantly different from that of air. Thus the laser light is reflected back to the CD or DVD-reader in the presence of air and in some other direction in the presence of liquid, or vice versa. Another method of monitoring the liquid flow is to use an active light source, such as an LED or semiconductor laser. Such a light may be powered by the presence of an electrically conductive liquid, such as plasma or buffer, acting to close an electronic circuit.
  • [0044]
    A LC-display may be used to transmit information from the IBCD to the CD or DVD-drive and to the computer. LC-display may have a large number of pixels that reflect light when there is a potential over the LC-film. These pixels may be, for instance, linearly organized, so that in one end low potential is needed for the reflection of the light, while on the other end the potential must be much higher for the same result. A CD or DVD-drive is able to localize the reflective pixels and accordingly, the potential in the circuit can be measured. Potential change can be due to an electrochemical process in one of the electrochemical cells. For example, an electrode coated with cholesterol oxidase will generate hydrogen peroxide in the presence of cholesterol. Hydrogen peroxide will change the potential of the circuitry and cholesterol may be quantitated.
  • [0045]
    Filters may be used to remove large particles, such as cells, dust, etc. from the soluble sample. Accordingly, filters are most preferably included as part of the sample inlet compartment. Filters may be formed from porous plastic, glass, cross-linked cotton or cellulose, etc. These materials may be in the shape of rods or similar shapes depending on the particular use to which they are being put. Plastics, such as Teflon, may be used as films.
  • [0046]
    Since chaotropic agents are often used to denature oligonucleotides during sample preparation, it is advantageous to provide a means of dialysis in the disk to remove the salt prior to the assay being performed. As shown in FIG. 6, a dialysis unit is prepared by putting a dialysis membrane 27 on either one or both halves (top and bottom) of a compartment formed in the disk 10. Taking into account the small volumes, the buffer that is already inside the dialysis membrane is usually sufficient and typically no buffer is needed on the side of the membrane opposite the fluid layer.
  • [0047]
    A column may be prepared, such as shown in FIG. 7, by filling a compartment 28 with a desired gel, adsorbent or ion exchanger, e.g. silica gel, Sephadex, etc. (the particular material is chosen for the particular application for which it is used) and putting a filter 29 in the other end. Examples of potential uses, include separating smaller molecules from larger ones and fractionating hydrophilic and hydrophobic compounds. An ion exchange column is especially useful for the separation of nucleic acids from other biomolecules. The columns lend themselves to other uses that may be convenient or necessary for conducting any particular assay.
  • [0048]
    [0048]FIG. 8 illustrates a valve, designated generally as 30, that may be located in one end of a column or a reaction container, which has two outlet capillaries 31 and 32. In addition, there are two electrodes, 33 and 34, which are not charged initially at the position illustrated and a conductive, metallic foil 35 that is adapted to close one or the other of the capillaries depending on its position relative to each capillary. The metal foil is biased to close one of the capillaries when no current is flowing and operates to open the previously closed capillary and close the other capillary when current flows. As an example, the valve is made from a thin gold foil, which is mechanically pressed against the other outlet capillary and is electrically connected to the closest electrode. When the battery is activated the gold foil is repelled by the closest electrode and attracted by the other electrode. As a result the gold foil is pressed against the other outlet. Other conductive metallic foils may be used, but a metal that is conductive and non-corroding is preferred for most operations. The battery may be deactivated as explained earlier and the valve is then switched back to its original position.
  • [0049]
    The laser of CD-R or CD-RW-drives has power up to 10 mW that can heat objects to high temperatures, even to 600° C. The power is strong enough to puncture holes in several materials, including plastics. Plastic should contain a dye that absorbs the laser light. Thermal expansion may be used for reversible valving. For instance, the bending of bimetallic foils is extremely sensitive to the temperature.
  • [0050]
    Piezoelectric material may be used as a valve. Piezoelectricity may also be used for measuring extremely small volumes of liquids, for example nanoliters of the sample can be divided between different assays.
  • [0051]
    Valve-like operations may also be performed chemically by deposition from solution of a solid chemical compound and/or dissolution of a deposited, solid compound. The first outlet of such a valve is closed by deposition of a chemical compound inside the capillary. The compound may be, for example, silver chloride. The chloride ions may be in the main fluid stream while in separate side capillaries are pure water and silver nitrate in water. The side capillaries are configured such that first the water and then the silver nitrate are added to the main fluid stream containing the chloride. The moment the silver ions arrive at the intersection it is clogged, effectively acting as a closed valve. Alternatively, a capillary may be initially clogged by the solid form of a soluble compound, such as sodium chloride. Addition of any aqueous solution dissolves the sodium chloride clog and the capillary is opened.
  • [0052]
    The assay element is preferably utilized in the assay site of the present invention. Briefly, the assay element (FIG. 13) includes a cleavable spacer 61 covalently attached at one end 60 to the disk surface 59 and at the other end 62 to a reporter element 65. The preferred embodiments of the reporter element described herein include reflective gold spheres or opaque latex spheres. Also included are two recognition elements 63 a, 63 b, hereafter referred to as sidearms which are covalently attached to each spacer such that the one sidearm is connected to each side of the spacer's cleavage site 64. The preferred embodiments of the sidearms described herein include oligonucleotides, antibodies and oligonucleotide-antibody conjugates. The assay elements may be used to detect the presence of an analyte and create a signal thereof through either a positive or negative recognition event (FIG. 14). A positive recognition event (FIG. 14A, C and E) occurs when an analyte 66 binds to both sidearms 63 a, 63 b resulting in the completion of a connective loop 67 between the two sides the spacer bisected by the cleavage site 64. A negative recognition event (FIG. 14B, D and F) occurs when analyte 66 binds to only one or neither of the sidearms 68 a, 68 b and consequently no loop is made connecting the two sides of the spacer. When a positive recognition event is followed by cleavage of the spacers, an unbroken connection from disk to reporter element remains intact (FIG. 14E). On the other hand, cleavage of the spacers in an assay element following a negative recognition event results in the reporter elements being disconnected from the disk (FIG. 14F). Thus, negative recognition results in loose reporter elements that are easily washed away whereas positive recognition results in the reporter elements being retained in their discrete assay sectors. In either case, the results may be observed immediately by CD-ROM or DVD reader.
  • [0053]
    Further embodiments of the invention are described herein that utilize both reflective or opaque reporter molecules, and positive and/or negative recognition events to carry out a broad range of possible assays. For example, in some assays the sidearms may be connected before a sample is added and binding of the analyte acts to disconnect the sidearms. In this case, a positive recognition event results in the disappearance of the reporter element, while a negative recognition event results in the reporter element being retained.
  • [0054]
    Other possible embodiments of the assay element described herein do not include cleavable spacers with sidearms. In one such alternative scheme the surface of the IBCD is coated by metal, preferably by gold, and the analyte connects the opaque particles, such as latex beads, or dye loaded liposomes on the metal surface.
  • Opaque Spheres as Assay Elements
  • [0055]
    Previous assay elements are based on the binding of reflective particles to the transparent surface of the IBCD. The situation may be reversed so that opaque particles are bound to a reflective surface. This approach is especially advantageous when large cells are assayed and is illustrated generally in FIG. 12.
  • [0056]
    A metal film is deposited onto the plastic surface. Information may be coded into this metal layer as it is done in conventional CDs. This information may include spatial addresses or other information related to the assay. The metal layer is further covered by a plastic layer. This is then aminated, as described previously, and instead of gold spheres, large latex spheres 58 (10-50 μm diameter), which contain a dye, are attached to the substrate via spacer molecules as previously described. These latex spheres are partially coated with recognition molecules as described above for gold spheres. Cell recognition binds the latex spheres to the substrate even after the spacers are cleaved, and the dye in the spheres prevents the reflection of the laser light from the metal layer. Alternatively, if a proper fluorescent dye and wavelength of laser light are used, the fluorescent emission of the spheres may be used to monitor the assay. This requires a specialized instrument and will be facilitated by blue lasers when they become available for use in CD-ROM or DVD-readers.
  • [0057]
    In the simplest version of the cell detection assay, the latex spheres are not connected with the IBCD before the assay, but are added after the cells are bound to the IBCD. The latex sphere suspension is added, the recognition molecules on the spheres bind to the proper cells and these cells are immobilized. These latex spheres may then be observed by reduced reflectance using the CD-ROM or DVD-reader.
  • Complementary Binding of Spacers
  • [0058]
    One drawback of the covalent binding of spacers is that the disk is not easily regenerated after the spacers are cleaved. If the spacers are instead connected to the substrate with complementary oligonucleotides, the disk can be regenerated after an assay is completed. The spacers or their residues are removed by heating or by using chaotropic agents. The duplexes that bind spacers are denatured and the disk can be cleaned. The disk retains the oligonucleotides that were binding old spacers. All oligonucleotides on one assay site are identical. They may be different in different assay sites, or they may be identical on the whole IBCD. New spacers having oligonucleotides complementary to those on the IBCD are added. After incubation the complementary oligonucleotides of the spacer and the IBCD hybridize. The excess spacers are washed away. In this case the oligonucleotide sidearms may be attached to the spacers before the spacers are attached to the surface. Gold spheres are then added, they are bound by the thiol groups or disulfide bridges of the spacers, and the disk is ready to be used again.
  • [0059]
    A cuvette is used for UV/Vis spectrophotometric, fluorescence or chemiluminscence assays. A cuvette in the BCD is basically a capillary that is located between a light source and a photodetector. Light can be guided by mirrors and waveguides. The number of cuvettes in the BCD varies between 0-10,000 and most advantageously between 0-50 per assay sector. The sample arrives into the most cuvettes via a sample preparation chamber. These chambers may contain preloaded reagents or reagents are stored in separate chambers and are mixed with the sample while it arrives into the sample preparation chamber. Sample and reagents may be heated electrically by infrared radiation that is generated by a photodiode. After the incubation period the sample is transferred into the cuvette. The transmitted or emitted light is measured by a photodetector. In this invention the photodetector is most advantageously inside the CD or DVD drive.
  • [0060]
    Light sources for spectrophotometric assays are most advantageously photodiodes or semiconductor lasers. It is possible to use the light source of the CD or DVD drive. However, currently these instruments use only one wavelength that corresponds to infrared or red light. If an internal light source of the CD or DVD drive is used, the photodiode or laser in FIG. 15 is replaced by a mirror. Although several assays can be performed by using infrared or red light, it is advantageous for most applications to use additional light sources. For example, an array of photodiodes can be fabricated so that red, yellow, green and blue light can be generated. It is possible to design a photodiode for any given wavelength and accordingly, the number of photodiodes can be up to 300 to cover the whole UV/visible spectral range. Laser generate more power and are better focused than photodiodes and they are preferred. Especially microcavity and nanodot lasers are very small, and they can be fabricated to emit almost any wavelength. The light sources can be fabricated as a module that can be attached onto the disk before and removed after the use of the BCD.
  • Unit Operations
  • [0061]
    Next are described the unit operations: centrifugation, filtering, transfer of liquids, mixing of liquids, dialysis, column separations, heating, cooling, electroconvection and electrophoresis.
  • [0062]
    Centrifugal force is the main force used to transfer liquids in the IBCD. It may also be used for centrifugation, which is important when calls are separated from plasma. In this case, it is advantageous to include a filter with the sample intake container.
  • [0063]
    In the transfer of liquids, order and timing are important. In order to insure the proper sequence of arrival to a certain reaction site, liquid trains, such as illustrated in FIG. 9, may be created. In one embodiment, two main capillaries, 36 and 37, are provided that are in fluid communication with each other via connecting capillaries 38, 39 and 40. One of the main capillaries is an air channel to allow for fluid flow and typically is rendered hydrophobic. The other main channel carries the reagents in liquid form and typically is hydrophilic. The connecting capillaries and associated cavities may serve to store the reagents, generally designated 41, 42 and 43, and maintain their relative locations with respect to each other. The fluid compartment to which they are directed and their timing of delivery is controlled by their respective locations, the size of the capillaries, the density and viscosity of the fluids and the rotational speed of the disk. The liquids are separated by small air bubbles to prevent mixing, unless mixing is desired. To prevent pressure gradients air capillaries are connected upstream with all liquid capillaries. To further prevent the liquids from entering the air capillaries, these are hydrophobic.
  • [0064]
    Mixing of two solutions is performed by merging two capillaries in a Y-shaped formation. This alone provides good mixing. To guarantee more efficient mixing a capillary may have small periodic enlargements after the merge. It must be noted that rotation of the IBCD results in efficient mixing in the containers.
  • [0065]
    In dialysis the liquid is in contact with the membrane containing the buffer. The molecular weight cutoff of the membrane may be chosen to be between 300-500,000 Dalton. Because only a very thin layer of the liquid is in contact with the dialysis'membrane, the dialysis is very fast. However, the ratio of the liquid to buffer is only between 1:10 and 1:100 so that the dialysis is not quantitative. For most purposes it is sufficient.
  • [0066]
    Gel, adsorption and ion exchange chromatographies are all possible. The various molecular species are fractionated by the chromatographic media and exit the capillary separately as in conventional chromatography. Using a valve, certain fractions may be selected and guided into an assay element.
  • [0067]
    Heating is best done electrically. Upper and lower electrodes are separated by about 500 μm. If the solution contains ions, the system is virtually short circuited and heats up. Heating may be terminated by removing ions either from the battery or from the container. Constant temperature can be achieved by including a thermostat into the circuitry. A bimetallic element is a very simple thermostat that can close a circuit below a preset temperature and open it at higher temperature. Another heating mechanism is provided by the laser of the CD or DVD-drive. Especially, CD-R-drives have powerful lasers. Either the top or the bottom of the cavity can have a liquid crystalline film that is isolated by a transparent layer, if necessary. On the other side of the cavity is a reflective layer. When the temperature of the cavity is below the main transition temperature the liquid crystal will scatter the light and no reflection is observed. Above the main transition temperature the light is reflected back and the heating can be discontinued and it is less effective anyway. Cooling is preferably provided by endothermic dissolution, i.e., the absorption of heat by the presence of a dissolving substance. The cooling solution and the solution to be cooled should be separated by a thin aluminum, copper, silver or gold film. Cooling may also be produced by passive air cooling. This method cools only to ambient temperature, but for most purposes this is enough. Cooling and heating may also be alternated in a cyclical fashion, either in one cavity or in a serially alternating sequence of heating and cooling cavities. This allows PCR amplifications to be performed inside the IBCD.
  • [0068]
    Electroconvection, electrophoresis and isoelectric focusing may each be utilized in particular applications. In electroconvection the material is transferred without trying to separate it into components. In electrophoresis the separation is the main purpose. The separation is facilitated by the use of a gel that prevents convection. Because distances are very short, the available field strength is sufficient for proper electrophoresis. For the same reason the necessary time for separation is fairly short and may be on the order of 1-5 minutes, or even less than 1 minute. Useful electroconvection may be performed in few seconds. Isoelectric focusing is basically electrophoresis in a pH gradient. A pH gradient may be created by an array of parallel capillaries, each of which contains a different buffer so that the pH changes gradually. This is demonstrated in FIG. 16. A large part of the buffer will remain in the capillaries and this will guarantee the existence of the pH gradient during the isoelectric focusing. After the focusing is completed the components can be moved along the capillaries by centrifugal force or an orthogonal electrophoresis can be performed. This method allows almost complete fractionation of human plasma proteins (Anderson, Tracy and Anderson, “The Plasma Proteins,” 2nd Ed., Vol. 4, Academic Press, Inc., 1984).
  • [0069]
    A particularly advantageous configuration of an assay site is illustrated in FIG. 10. The assay element contains the spacer molecules and the reflective spheres as described previously but does so in a linear array that may be conveniently located in one or more of the capillary channels at the assay site of the disk. As has been described, analyte binds to the spacer molecules that have side arms receptive to or complementary to the analyte (as illustrated in A) and after washing the analyte that has bound is located at specific locations of the array (as illustrated in B). The presence of the bound analytes is determined by conventional address determination as with conventional compact disk readers and associated software as has been described.
  • EXAMPLE 1 Assay Sector for Oligonucleotide Analysis (FIG. 2, Assay Sector)
  • [0070]
    A sample that contains DNA is mixed with sodium dodecyl sulfate to lyse the cells. This solution is transferred into the container denoted “Sample in” and the disk is rotated. The sample is filtered and mixed with a mixture of complementary oligonucleotides. These oligonucleotides are complementary to those to be analyzed and also have a thiol group at one end. Hybridization is allowed to proceed in the container denoted “Sample prep.” Optionally, this container may be heated (not shown in Figure). After appropriate incubation, the disk is rotated. While the sample is transferred into the container denoted “Sample sep.” it is mixed with a nuclease S solution delivered from a side capillary. The mixture is allowed to incubate in the “Sample sep.” container which has two gold electrodes and a valve as has been illustrated in FIG. 8. The lower electrode is coated with spacers having isothiocyanate end groups. These bind to the thiol containing oligonucleotides several of which are hybridized with the sample. All unhybridized parts of DNA are digested and washed away. The battery then becomes operational. This is adjusted by the speed by which the acid and copper ions flow into the empty battery. The container heats up, the bound oligonucleotides are released and the valve is switched.
  • [0071]
    The oligonucleotides are flushed into the assay area. After suitable incubation the ligase arrives into the assay area and the two sidearms on the spacer molecule are connected, if the sample contains the proper oligonucleotide. The labile spacers are cut. If spacers contain siloxane groups the cutting is done by addition of fluoride ions.
  • [0072]
    The loose gold spheres are washed away by rotating the IBCD at high speed. Reading may be performed immediately.
  • EXAMPLE 2 Assay Element for the Detection of Cells and Viruses
  • [0073]
    Alternative embodiments of the assay element described elsewhere herein are useful for the detection of viral and bacterial particles, cells and other particles that are larger than the oligonucleotides, antibodies, antigens and the like that have been described previously. Viruses are typically nearly spherical particles having a diameter less than 0.5 μm. Bacteria are commonly either spherical or rod shaped. Their largest dimension is less than 2 μm excluding flagella and other similar external fibers. These pathogens are smaller or about the same size as the gold spheres used to detect them, and their interaction with two sidearms of the spacer may be limited. For this reason these sidearms are connected with the surface of the IBCD and the gold sphere instead of with the spacer as illustrated in FIG. 11. The gold sphere is attached to a spacer molecule 45 at one end of the spacer molecule and the other end of the spacer is attached to the surface of the substrate 46. The spacer molecule is provided with a typical cleavage site 47, for example a siloxane moiety, as has been previously described. In contrast to prior described embodiments where the side-arms are attached to the spacer molecule between the substrate and the cleavage site and the gold sphere and the cleavage site, side arms are attached to the gold sphere and to the surface of the substrate. For illustration purposes, in FIG. 11 oligonucleotides 48 and 49 are attached to the surface of the substrate and oligonucleotides 50 and 51 are attached to the surface of the gold sphere. Then complementary oligonucleotides are conjugated with members of a specific binding pair, designated as 52, 53, 54, and 55 are attached to the oligonucleotides on the substrate and the gold sphere as illustrated. This gives much more space for the cells to bind with the antibodies or other recognition molecules.
  • [0074]
    The spacers each still have at least one cleavage site. They are, in all respects identical to those described previously except that they have no attached sidearm molecules. When the cell for example arrives at the assay site, if it contains moieties that form specific binding pairs with their respective complementary members, a connective loop is formed between the gold sphere and the substrate. When the spacer molecule is cleaved, the gold sphere is retained on the substrate and the presence of the cell may be detected as previously described. However, if no specific binding pairs are formed, upon cleavage of the spacer, the gold sphere does not remain attached to the substrate and is removed.
  • [0075]
    Antibodies or other recognition molecules may be attached to the substrate in a manner similar to that with which the spacers are attached. All spacers on the IBCD are identical and are attached at the same time to the amino groups or analogous active groups on the surface. About half of the amino groups are used for the attachment of the spacers. The other half is used to couple recognition molecules to the substrate. If all recognition molecules on the surface of the IBCD are similar, they may be attached at the same time as spacers. Alternatively, if the recognition molecules are specific for each assay site, they may be dispensed locally by contact printing, ink-jet printing or microcapillary deposition.
  • [0076]
    After the gold spheres are attached to the thiol groups in the spacers, the other recognition molecules are attached, also via thiol groups, to the gold spheres. For this purpose these recognition molecules are first conjugated with a spacer containing a protected thiol or amino group. The amino group may be derivatized so that a thiol group is introduced. The various recognition molecules to be attached to the gold spheres are dispensed in a manner similar to that with which the other recognition molecules were attached with the surface of the IBCD.
  • [0077]
    The recognition molecules may be oligonucleotides. These oligonucleotides may be further hybridized with complementary oligonucleotide-biomolecule conjugates. This approach allows attachment of sensitive and reactive biomolecules, for example, proteins containing several amino or thiol groups.
  • [0078]
    The recognition molecules bound to the gold spheres are free to diffuse around the sphere although they are tightly bound. The cell that is recognized by both recognition molecules completes a connective loop that binds the gold sphere to the surface of the IBCD. After cleaving the spacer, the gold sphere is retained and detected by the CD-ROM or DVD reader.
  • [0079]
    A multiplicity of different recognition molecules in the same assay site may be used. The advantage of this approach is that all known mutants of a certain pathogen species may be detected on one assay site. The various mutants also may be characterized on different assay sites containing specific recognition molecules.
  • [0080]
    The IBCD is a universal analyzer. It is easy to use and in its most advanced form it contains all reagents and only the sample is added. It can be used in clinical laboratories, hospitals, doctors' offices, and in the home. In home use the information can be loaded into a doctor's office via the internet. The IBCD can be designed so that the genetic signature of each patient is measured every time. About 35 polymorphism points are enough to give every person a unique “bar-code” . This eliminates possible mistakes due to mixing of tubes or labels. Assays that can be performed include, but are not limited to immunoassays, DNA testing, cell counting and cell shape measurement, detection of cancerous cells in tissue samples, blood chemistry and electrolyte analysis. Other applications include mass screening of drug candidates, food and environmental safety analysis, and monitoring pathogens and toxins in a battlefield.
  • EXAMPLE 3
  • [0081]
    Turbidimetric Assay of Lipase Activity
  • [0082]
    The reagent cavity contains 15 μL of stabilized triolein (250 μM) emulsion that contains sodium deoxycholate (30 mM) and CaCl2 (100 μM) at pH 9.0 in TRIS buffer (25 mM). The sample preparation chamber contains lyophilized porcine colipase (0.5 μg). Two microliters of serum is taken into the sample preparation chamber (using apparatus as shown in FIG. 17) together with stabilized triolein and other reagents. Part of the mixture (5 μL) is further transferred into a cuvette. Because the exit capillary goes toward the center of the disk, the counterpressure will prevent further flow. Absorbance at 340 nm is read at one minute intervals. The ΔA/min is a measure of lipase activity.
  • [0083]
    While this invention has been described with respect to some specific embodiments, it is understood that modifications thereto and equivalents and variations thereof will be apparent to one skilled in the art and are intended to be and are included within the scope of the claims appended hereto.

Claims (16)

What is claimed is:
1. An optical disk, adapted to be read by an optical reader, comprising a first sector having a substantially self-contained assay means for binding or reacting an analyte suspected of being in a sample to at least one, predetermined location in the first sector and optionally a second sector containing a control means for conducting the assay and analyte location information with respect to one or more analytes suspected of being in a sample, accessible to a reader, and wherein the presence or absence of the analyte at said location is determinable by the reader using the control means and the location information.
2. The optical disk of
claim 1
which includes a sealable sample entry port in fluid communication with the assay means.
3. An apparatus for conducting an assay comprising an optical disk, a disk reader and an information processor, wherein the disk comprises a first sector having a substantially self-contained assay means for binding an analyte suspected of being in a sample to at least one, predetermined location in the first sector and optionally a second sector containing control information for conducting the assay and analyte location information with respect to one or more analytes suspected of being in the sample, accessible to the reader and processable by the information processor, wherein the disk is adapted to be read by the reader and the information processor is adapted to determine the presence or absence of the analyte at said location using the control information and the location information.
4. The apparatus of
claim 3
wherein the reader is a CD-ROM or a DVD reader and wherein the reader is adapted to be coupled to an information processor.
5. The apparatus of
claim 4
wherein the information processor is a personal computer.
6. The disk of
claim 1
wherein the assay means comprises a fluid storage means and a fluid transfer means formed in a disk surface.
7. The disk of
claim 6
wherein the fluid transfer means comprises a capillary duct.
8. The disk of
claim 7
wherein the fluid transfer means comprises a valve.
9. The disk of
claim 6
wherein the disk comprises an electrochemical energy means.
10. The disk of
claim 1
wherein the assay means comprises a sample port, a sample preparation sector, an analyte separation sector and an assay sector wherein the analyte is localized.
11. The disk of
claim 6
wherein the fluid transfer means is responsive to centrifugal force or an electric field.
12. The disk of
claim 1
wherein the disk comprises a multiplicity of first sectors adapted to analyze for a multiplicity of analytes.
13. The disk of
claim 1
further comprising a multiplicity of first sectors adapted to analyze for the same analyte or different analytes wherein each of said multiplicity of sectors is adapted for fluid communication to a sample port.
14. An assay element comprising a substrate, a first oligonucleotide bound to the substrate, a spacer molecule bound at a first end to the first oligonucleotide by a second oligonucleotide that is complementary to the first oligonucleotide, wherein the spacer molecule further comprises a means for binding to an analyte in a sample and having a second end that is detectable by a detection means, the spacer molecule further comprising a site intermediate the first and second ends that is cleavable, the binding means having a first moiety between the first end of the spacer molecule and the cleavage site for binding to a first part of the analyte and a second moiety between the second end of the spacer molecule and the cleavage site for binding to a second part of the analyte.
15. An assay component, adapted to be read by a CD-ROM or a DVD reader comprising an optical disk and a substantially self-contained assay means in the disk for binding an analyte suspected of being in a sample to at least one, predetermined location on the disk and means at said location for enabling detection of the absence or presence of the analyte by the CD-ROM or the DVD reader.
16. An optical disk, adapted to be read by a CD-ROM or a DVD reader comprising a substantially self-contained assay means for localizing an analyte suspected of being in a sample to at least one, predetermined location on the disk and a means at said location for detecting the absence or presence of the analyte by the CD-ROM or the DVD reader.
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005089910A1 (en) * 2004-03-17 2005-09-29 Ciphergen Biosystems, Inc. Multi-compartment filter and method of filtering using same
US20060063251A1 (en) * 2004-09-22 2006-03-23 Hsiao-Chung Tsai Immunoassay devices and methods of using same
WO2006042825A1 (en) * 2004-10-15 2006-04-27 Siemens Aktiengesellschaft Method for controlling valves during the thermocyclisation of a substance for the purpose of polymer chain reaction (pcr) and associated arrangement
US20080300148A1 (en) * 2007-06-04 2008-12-04 Samsung Electronics Co., Ltd. Microfluidic device for simultaneously conducting multiple analyses
WO2009003985A1 (en) * 2007-06-29 2009-01-08 Dublin City University Centrifugal device
US20100081213A1 (en) * 2008-10-01 2010-04-01 Samsung Electronics Co., Ltd. Centrifugal-based microfluidic apparatus, method of fabricating the same, and method of testing samples using the microfluidic apparatus
US9421541B2 (en) 2013-06-04 2016-08-23 Samsung Electronics Co., Ltd. Microfluidic apparatus with increased recovery rate of target material from a sample

Families Citing this family (281)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6327031B1 (en) 1998-09-18 2001-12-04 Burstein Technologies, Inc. Apparatus and semi-reflective optical system for carrying out analysis of samples
US6331275B1 (en) 1996-07-08 2001-12-18 Burstein Technologies, Inc. Spatially addressable, cleavable reflective signal elements, assay device and method
WO2002073605A3 (en) * 2001-03-14 2003-04-03 Burstein Technologies Inc Dual bead assays using cleavable spacers and/or ligation to improve specificity and sensitivity including related methods and apparatus
US20050069923A1 (en) * 1996-07-08 2005-03-31 Mullis Kary Banks Dual bead assays using cleavable spacers and/or ligation to improve specificity and sensitivity including related methods and apparatus
US20050214827A1 (en) * 1996-07-08 2005-09-29 Burstein Technologies, Inc. Assay device and method
US6342349B1 (en) 1996-07-08 2002-01-29 Burstein Technologies, Inc. Optical disk-based assay devices and methods
CA2260361A1 (en) * 1996-07-08 1998-01-15 Burstein Laboratories, Inc Cleavable signal element device and method
WO1998012559A1 (en) 1996-09-20 1998-03-26 Demers James P Spatially addressable combinatorial chemical arrays in cd-rom format
GB2337113B (en) * 1997-02-28 2001-03-21 Burstein Lab Inc Laboratory in a disk
US7622294B2 (en) 1997-03-14 2009-11-24 Trustees Of Tufts College Methods for detecting target analytes and enzymatic reactions
US6327410B1 (en) * 1997-03-14 2001-12-04 The Trustees Of Tufts College Target analyte sensors utilizing Microspheres
US20030027126A1 (en) * 1997-03-14 2003-02-06 Walt David R. Methods for detecting target analytes and enzymatic reactions
US6023540A (en) 1997-03-14 2000-02-08 Trustees Of Tufts College Fiber optic sensor with encoded microspheres
US7914994B2 (en) 1998-12-24 2011-03-29 Cepheid Method for separating an analyte from a sample
US6887693B2 (en) 1998-12-24 2005-05-03 Cepheid Device and method for lysing cells, spores, or microorganisms
CA2312102C (en) 1997-12-24 2007-09-04 Cepheid Integrated fluid manipulation cartridge
US20020177144A1 (en) * 1997-12-30 2002-11-28 Jose Remacle Detection and/or quantification method of a target molecule by a binding with a capture molecule fixed on the surface of a disc
JP3394181B2 (en) * 1998-03-30 2003-04-07 日立ソフトウエアエンジニアリング株式会社 Sample addition method and the sample addition device
JP2002521666A (en) * 1998-07-21 2002-07-16 バースタイン テクノロジーズ,インコーポレイティド Assay device and method for the optical disc based
US6196979B1 (en) * 1998-08-24 2001-03-06 Burstein Technologies, Inc. Cassette and applicator for biological and chemical sample collection
WO2001047638A3 (en) * 1999-12-23 2002-05-30 Per Andersson Integrated microfluidic disc
US20020019059A1 (en) * 1999-01-28 2002-02-14 Calvin Y.H. Chow Devices, systems and methods for time domain multiplexing of reagents
US6942771B1 (en) 1999-04-21 2005-09-13 Clinical Micro Sensors, Inc. Microfluidic systems in the electrochemical detection of target analytes
US7332326B1 (en) * 1999-05-14 2008-02-19 Tecan Trading Ag Centripetally-motivated microfluidics system for performing in vitro hybridization and amplification of nucleic acids
US20030096321A1 (en) * 1999-05-19 2003-05-22 Jose Remacle Method for the identification and/or the quantification of a target compound obtained from a biological sample upon chips
US8815521B2 (en) * 2000-05-30 2014-08-26 Cepheid Apparatus and method for cell disruption
US6818185B1 (en) 1999-05-28 2004-11-16 Cepheid Cartridge for conducting a chemical reaction
US9073053B2 (en) * 1999-05-28 2015-07-07 Cepheid Apparatus and method for cell disruption
DE60022025D1 (en) 1999-05-28 2005-09-22 Cepheid Sunnyvale Annex to the breaking of cells
US8264680B2 (en) 1999-05-28 2012-09-11 Yokogawa Electric Corporation Biochip reader and electrophoresis system
US6706519B1 (en) * 1999-06-22 2004-03-16 Tecan Trading Ag Devices and methods for the performance of miniaturized in vitro amplification assays
US6495104B1 (en) * 1999-08-19 2002-12-17 Caliper Technologies Corp. Indicator components for microfluidic systems
US7088650B1 (en) 1999-08-23 2006-08-08 Worthington Mark O Methods and apparatus for optical disc data acquisition using physical synchronization markers
US6888951B1 (en) 1999-08-23 2005-05-03 Nagaoka & Co., Ltd. Methods and apparatus for analyzing operational and analyte data acquired from optical disc
US6632400B1 (en) 2000-06-22 2003-10-14 Agilent Technologies, Inc. Integrated microfluidic and electronic components
US6734401B2 (en) 2000-06-28 2004-05-11 3M Innovative Properties Company Enhanced sample processing devices, systems and methods
US8097471B2 (en) * 2000-11-10 2012-01-17 3M Innovative Properties Company Sample processing devices
US6720187B2 (en) 2000-06-28 2004-04-13 3M Innovative Properties Company Multi-format sample processing devices
WO2004058405A1 (en) * 2001-05-02 2004-07-15 3M Innovative Properties Company Sample processing device with resealable process chamber
US6627159B1 (en) * 2000-06-28 2003-09-30 3M Innovative Properties Company Centrifugal filling of sample processing devices
US6890093B2 (en) * 2000-08-07 2005-05-10 Nanostream, Inc. Multi-stream microfludic mixers
US6877892B2 (en) * 2002-01-11 2005-04-12 Nanostream, Inc. Multi-stream microfluidic aperture mixers
EP1309404A2 (en) * 2000-08-07 2003-05-14 Nanostream, Inc. Fluidic mixer in microfluidic system
US20060014186A1 (en) * 2001-09-04 2006-01-19 Hodge Timothy A Methods for genotype screening of a strain disposed on an adsorbent carrier
US7011943B2 (en) * 2000-09-06 2006-03-14 Transnetyx, Inc. Method for detecting a designated genetic sequence in murine genomic DNA
US20050266494A1 (en) * 2000-09-06 2005-12-01 Hodge Timothy A System and method for computer network ordering of biological testing
US7494817B2 (en) * 2000-09-06 2009-02-24 Transnet Yx, Inc. Methods for genotype screening using magnetic particles
US20050239125A1 (en) * 2000-09-06 2005-10-27 Hodge Timothy A Methods for genotype screening
US20050272085A1 (en) * 2000-09-06 2005-12-08 Hodge Timothy A Methods for forensic and congenic screening
DE60024264T2 (en) * 2000-09-18 2006-08-17 The Regents Of The University Of California, Oakland Method and apparatus for the detection of molecular entities
US6855553B1 (en) 2000-10-02 2005-02-15 3M Innovative Properties Company Sample processing apparatus, methods and systems
US7200088B2 (en) * 2001-01-11 2007-04-03 Burstein Technologies, Inc. System and method of detecting investigational features related to a sample
US7221632B2 (en) 2001-07-12 2007-05-22 Burstein Technologies, Inc. Optical disc system and related detecting methods for analysis of microscopic structures
WO2002039446A3 (en) * 2000-11-09 2003-01-09 Burstein Technologies Inc Disc drive system and methods for use with bio-discs
US20080094974A1 (en) * 2001-11-09 2008-04-24 Burstein Technologies, Inc. Optical disc system and related detecting methods for analysis of microscopic structures
GB0027516D0 (en) * 2000-11-10 2000-12-27 Amersham Pharm Biotech Uk Ltd Support and method for cell based assays
CN1659439A (en) * 2001-09-07 2005-08-24 伯斯坦技术公司 Nuclear morphology based identification and quantitation of white blood cell types using optical bio-disc systems
US6965433B2 (en) * 2000-11-16 2005-11-15 Nagaoka & Co., Ltd. Optical biodiscs with reflective layers
US20030143637A1 (en) * 2001-08-31 2003-07-31 Selvan Gowri Pyapali Capture layer assemblies for cellular assays including related optical analysis discs and methods
US20030129665A1 (en) * 2001-08-30 2003-07-10 Selvan Gowri Pyapali Methods for qualitative and quantitative analysis of cells and related optical bio-disc systems
CA2468041A1 (en) * 2001-11-20 2003-05-30 Burstein Technologies, Inc. Optical bio-discs and microfluidic devices for analysis of cells
WO2002044695A1 (en) * 2000-11-16 2002-06-06 Burstein Technologies, Inc. Methods and apparatus for detecting and quantifying lymphocytes with optical biodiscs
US7026131B2 (en) * 2000-11-17 2006-04-11 Nagaoka & Co., Ltd. Methods and apparatus for blood typing with optical bio-discs
US7087203B2 (en) 2000-11-17 2006-08-08 Nagaoka & Co., Ltd. Methods and apparatus for blood typing with optical bio-disc
EP1410042A1 (en) * 2000-11-17 2004-04-21 Burstein Technologies, Inc. Methods and apparatus for blood typing with optical bio-discs
JP2005509865A (en) * 2001-11-19 2005-04-14 バースタイン テクノロジーズ,インコーポレイティド The methods and apparatus of the blood typing (bloodtyping) using optical bio-disc
WO2002042780A9 (en) * 2000-11-22 2004-03-04 Burstein Technologies Inc Apparatus and methods for separating agglutinants and disperse particles
WO2002068697A3 (en) * 2001-02-28 2003-10-30 Burstein Technologies Inc Methods for decreasing non-specific binding of beads in dual bead assays including related optical biodiscs and disc drive systems
WO2002042498A3 (en) * 2000-11-27 2003-07-31 Burstein Technologies Inc Dual bead assays including optical biodiscs and methods relating thereto
US20040248093A1 (en) * 2000-11-27 2004-12-09 Coombs James Howard Magneto-optical bio-discs and systems including related methods
US20030003464A1 (en) * 2000-11-27 2003-01-02 Phan Brigitte C. Dual bead assays including optical biodiscs and methods relating thereto
WO2002068696A3 (en) * 2001-02-27 2003-08-14 Burstein Technologies Inc Methods for dna conjugation onto solid phase including related optical biodiscs and disc drive systems
US20020172980A1 (en) * 2000-11-27 2002-11-21 Phan Brigitte Chau Methods for decreasing non-specific binding of beads in dual bead assays including related optical biodiscs and disc drive systems
WO2002043866A3 (en) * 2000-12-01 2003-03-06 Burstein Technologies Inc Apparatus and methods for separating components of particulate suspension
US7054258B2 (en) * 2000-12-08 2006-05-30 Nagaoka & Co., Ltd. Optical disc assemblies for performing assays
US6760298B2 (en) * 2000-12-08 2004-07-06 Nagaoka & Co., Ltd. Multiple data layer optical discs for detecting analytes
WO2002046721A8 (en) 2000-12-08 2003-03-06 Burstein Technologies Inc Optical discs for measuring analytes
EP1215613A1 (en) * 2000-12-15 2002-06-19 Clair James J. Dr. La A digital molecular integrator
US7091034B2 (en) 2000-12-15 2006-08-15 Burstein Technologies, Inc. Detection system for disk-based laboratory and improved optical bio-disc including same
WO2002051537A3 (en) * 2000-12-22 2003-04-24 Burstein Technologies Inc Optical bio-discs and methods relating thereto
US20020086294A1 (en) * 2000-12-29 2002-07-04 Ellson Richard N. Device and method for tracking conditions in an assay
US20020168663A1 (en) * 2001-02-27 2002-11-14 Phan Brigitte Chau Methods for DNA conjugation onto solid phase including related optical biodiscs and disc drive systems
WO2003007293A3 (en) * 2001-07-12 2009-06-18 Burstein Technologies Inc Optical disc system and related detecting methods for analysis of microscopic structures
US20020140940A1 (en) * 2001-02-28 2002-10-03 Bambot Shabbir B. System and method for measurement and analysis of a sample by absorption spectrophotometry
EP1483052B1 (en) * 2001-08-28 2010-12-22 Gyros Patent Ab Retaining microfluidic microcavity and other microfluidic structures
US6919058B2 (en) * 2001-08-28 2005-07-19 Gyros Ab Retaining microfluidic microcavity and other microfluidic structures
WO2002075312A1 (en) * 2001-03-19 2002-09-26 Gyros Ab Characterization of reaction variables
US6806088B2 (en) * 2001-04-09 2004-10-19 Matsushita Electric Industrial Co., Ltd. Method and apparatus for improving the performance of microanalytic and microsynthetic procedures
WO2003087827A8 (en) 2001-04-11 2004-11-11 Burstein Technologies Inc Multi-parameter assays including analysis discs and methods relating thereto
US20050019901A1 (en) * 2002-01-31 2005-01-27 Evgenia Matveeva Methods for synthesis of bio-active nanoparticles and nanocapsules for use in optical bio-disc assays and disc assembly including same
US7083920B2 (en) * 2001-05-18 2006-08-01 Nagaoka & Co. Ltd. Surface assembly for immobilizing DNA capture probes in genetic assays using enzymatic reactions to generate signal in optical bio-discs and methods relating thereto
US7635585B2 (en) 2001-05-31 2009-12-22 Jae Chern Yoo Micro valve apparatus using micro bead and method for controlling the same
US6811695B2 (en) * 2001-06-07 2004-11-02 Nanostream, Inc. Microfluidic filter
US6919046B2 (en) * 2001-06-07 2005-07-19 Nanostream, Inc. Microfluidic analytical devices and methods
WO2002103052B1 (en) * 2001-06-15 2004-03-04 Quiatech Ab Amplifiable probe
US20040166593A1 (en) * 2001-06-22 2004-08-26 Nolte David D. Adaptive interferometric multi-analyte high-speed biosensor
US20050003459A1 (en) * 2002-01-30 2005-01-06 Krutzik Siegfried Richard Multi-purpose optical analysis disc for conducting assays and related methods for attaching capture agents
US7141416B2 (en) * 2001-07-12 2006-11-28 Burstein Technologies, Inc. Multi-purpose optical analysis optical bio-disc for conducting assays and various reporting agents for use therewith
DE60215353D1 (en) * 2001-07-19 2006-11-23 Burstein Technologies Inc Transmissive optical disk for physical measurements
CN1556924A (en) * 2001-07-20 2004-12-22 伯斯坦技术公司 Optical analysis disc and related drive assembly for performing interactive centrifugation
DE10141691A1 (en) * 2001-08-25 2003-03-13 Friz Biochem Gmbh Displacement assay for the detection of ligate-ligand association events
JP2005502369A (en) * 2001-09-12 2005-01-27 バースタイン テクノロジーズ,インコーポレイティド Differential cell counting method and associated apparatus and software for performing it
US7127066B2 (en) 2001-10-03 2006-10-24 Now Showing Entertainment, Inc. Limited use DVD-video disc
CA2464476A1 (en) * 2001-10-24 2003-05-01 Burstein Technologies, Inc. Optical biological disk analyser
US20030082632A1 (en) * 2001-10-25 2003-05-01 Cytoprint, Inc. Assay method and apparatus
US7767437B2 (en) * 2001-11-02 2010-08-03 Genefluidics, Inc. System for detection of a component in a liquid
US6989891B2 (en) 2001-11-08 2006-01-24 Optiscan Biomedical Corporation Device and method for in vitro determination of analyte concentrations within body fluids
NL1019875C2 (en) * 2001-11-28 2003-06-02 Ibis Technologies B V A carrier for use in the determination of particles in a sample and a method for the manufacture of such a carrier, and a method for the determination of particles in a sample.
US20050158847A1 (en) * 2001-12-20 2005-07-21 Fosdick Stephen W. Centrifugal array processing device
US6889468B2 (en) * 2001-12-28 2005-05-10 3M Innovative Properties Company Modular systems and methods for using sample processing devices
WO2003060668A2 (en) * 2002-01-14 2003-07-24 Burstein Technologies, Inc. Method and apparatus for visualizing data
CA2471018A1 (en) * 2002-01-28 2003-08-07 Burstein Technologies, Inc. Methods and apparatus for logical triggering of an optical bio-disc
US20050002827A1 (en) * 2002-01-29 2005-01-06 Mcintyre Kevin Robert Optical discs including equi-radial and/or spiral analysis zones and related disc drive systems and methods
US20040241381A1 (en) * 2002-01-31 2004-12-02 Chen Yihfar Microfluidic structures with circumferential grooves for bonding adhesives and related optical analysis discs
US7251210B2 (en) 2002-01-31 2007-07-31 Burstein Technologies, Inc. Method for triggering through disc grooves and related optical analysis discs and system
US6869970B2 (en) * 2002-02-04 2005-03-22 Novartis Ag Crystalline salt forms of valsartan
US20050176858A1 (en) * 2002-02-15 2005-08-11 Bridgestone Corporation Rubber composition and pneumatic tire made therefrom
US7459127B2 (en) * 2002-02-26 2008-12-02 Siemens Healthcare Diagnostics Inc. Method and apparatus for precise transfer and manipulation of fluids by centrifugal and/or capillary forces
EP1490292A1 (en) * 2002-03-31 2004-12-29 Gyros AB Efficient mmicrofluidic devices
US7813938B2 (en) * 2002-04-17 2010-10-12 Shawn Kusterbeck Method and system for prescription distribution security
US7384602B2 (en) * 2002-05-08 2008-06-10 Hitachi High-Technologies Corporation Chemical analysis apparatus and genetic diagnostic apparatus
EP1532275A4 (en) * 2002-07-26 2005-09-14 Applera Corp Mg-mediated hot start biochemical reactions
US7619819B2 (en) * 2002-08-20 2009-11-17 Illumina, Inc. Method and apparatus for drug product tracking using encoded optical identification elements
US7164533B2 (en) * 2003-01-22 2007-01-16 Cyvera Corporation Hybrid random bead/chip based microarray
US7923260B2 (en) 2002-08-20 2011-04-12 Illumina, Inc. Method of reading encoded particles
US7900836B2 (en) * 2002-08-20 2011-03-08 Illumina, Inc. Optical reader system for substrates having an optically readable code
US7901630B2 (en) * 2002-08-20 2011-03-08 Illumina, Inc. Diffraction grating-based encoded microparticle assay stick
US20060057729A1 (en) * 2003-09-12 2006-03-16 Illumina, Inc. Diffraction grating-based encoded element having a substance disposed thereon
EP1575707A1 (en) * 2002-09-12 2005-09-21 Cyvera Corporation Method and apparatus for aligning elongated microbeads in order to interrogate the same
US7092160B2 (en) * 2002-09-12 2006-08-15 Illumina, Inc. Method of manufacturing of diffraction grating-based optical identification element
US7872804B2 (en) 2002-08-20 2011-01-18 Illumina, Inc. Encoded particle having a grating with variations in the refractive index
US20100255603A9 (en) * 2002-09-12 2010-10-07 Putnam Martin A Method and apparatus for aligning microbeads in order to interrogate the same
EP1552285B1 (en) * 2002-10-13 2010-04-14 Picosep A/S A two-dimensional microfluid biomolecule separation system
WO2004046689B1 (en) * 2002-11-15 2005-02-03 Richard Cote System and method for multiplexed biomolecular analysis
US7344678B2 (en) * 2002-11-15 2008-03-18 The Regents Of The University Of California Composite sensor membrane
WO2004050242A3 (en) 2002-12-04 2004-08-05 Spinx Inc Devices and methods for programmable microscale manipulation of fluids
US7507376B2 (en) * 2002-12-19 2009-03-24 3M Innovative Properties Company Integrated sample processing devices
US7094354B2 (en) * 2002-12-19 2006-08-22 Bayer Healthcare Llc Method and apparatus for separation of particles in a microfluidic device
US7125711B2 (en) * 2002-12-19 2006-10-24 Bayer Healthcare Llc Method and apparatus for splitting of specimens into multiple channels of a microfluidic device
US7332129B2 (en) * 2003-01-09 2008-02-19 3M Innovative Properties Company Sample processing device having process chambers with bypass slots
US20050014249A1 (en) * 2003-02-21 2005-01-20 Norbert Staimer Chromatographic analysis on optical bio-discs and methods relating thereto
US20040166551A1 (en) * 2003-02-24 2004-08-26 John Moulds Detection of agglutination of assays
US7706984B2 (en) * 2003-03-11 2010-04-27 The Regents Of The University Of California Method and device for identifying molecular species
EP1613946A4 (en) * 2003-03-20 2006-07-12 Univ Northeastern Ohio Self-contained assay device for rapid detection of biohazardous agents
US20060182329A1 (en) * 2003-03-24 2006-08-17 Ryosuke Yamada Analysis device and method for cell count in the analysis device
US7435381B2 (en) * 2003-05-29 2008-10-14 Siemens Healthcare Diagnostics Inc. Packaging of microfluidic devices
EP1656203A2 (en) * 2003-06-19 2006-05-17 Nagaoka & Co., Ltd., Fluidic circuits for sample preparation including bio-discs and methods relating thereto
US7390464B2 (en) * 2003-06-19 2008-06-24 Burstein Technologies, Inc. Fluidic circuits for sample preparation including bio-discs and methods relating thereto
US20040265171A1 (en) * 2003-06-27 2004-12-30 Pugia Michael J. Method for uniform application of fluid into a reactive reagent area
US20080257754A1 (en) * 2003-06-27 2008-10-23 Pugia Michael J Method and apparatus for entry of specimens into a microfluidic device
US20040265172A1 (en) * 2003-06-27 2004-12-30 Pugia Michael J. Method and apparatus for entry and storage of specimens into a microfluidic device
US20070166721A1 (en) * 2003-06-27 2007-07-19 Phan Brigitte C Fluidic circuits, methods and apparatus for use of whole blood samples in colorimetric assays
WO2005009581A3 (en) * 2003-07-15 2005-03-24 Nagaoka Kk Methods and apparatus for blood separation and analysis using membranes on an optical bio-disc
US20060210426A1 (en) * 2003-08-05 2006-09-21 Taiyo Yuden Co., Ltd. Sample analyzer and disk-like sample analyzing medium
US7347617B2 (en) * 2003-08-19 2008-03-25 Siemens Healthcare Diagnostics Inc. Mixing in microfluidic devices
EP1660870A2 (en) * 2003-08-26 2006-05-31 Blueshift Biotechnologies, Inc. Time dependent fluorescence measurements
JP5019088B2 (en) * 2003-09-17 2012-09-05 ソニー株式会社 Inspection system, the inspection apparatus and method, recording medium, program
US7476360B2 (en) 2003-12-09 2009-01-13 Genefluidics, Inc. Cartridge for use with electrochemical sensor
DE10359160A1 (en) * 2003-12-16 2005-07-21 Roche Diagnostics Gmbh Test element for analysis of sample material
US7485085B2 (en) 2004-01-23 2009-02-03 Applied Biosystems Inc. Heat transfer for thermal cycling
WO2005081801A3 (en) * 2004-02-09 2005-11-10 Blueshift Biotechnologies Inc Methods and apparatus for scanning small sample volumes
WO2005079544A9 (en) * 2004-02-19 2007-09-20 Cyvera Corp Multi-well plate with alignment grooves for encoded microparticles
US7433123B2 (en) 2004-02-19 2008-10-07 Illumina, Inc. Optical identification element having non-waveguide photosensitive substrate with diffraction grating therein
US20060160208A1 (en) * 2004-02-19 2006-07-20 Cyvera Corporation Multi-well plate with alignment grooves for encoded microparticles
JP2005257337A (en) * 2004-03-09 2005-09-22 Brother Ind Ltd Inspection object receiver, inspection device, and inspection method
JP2005309140A (en) * 2004-04-22 2005-11-04 Toshiba Corp Method for manufacturing photomask, method for determining position of photomask defect correction, and apparatus for determining position of photomask defect correction
JP4476050B2 (en) * 2004-06-30 2010-06-09 株式会社ニデック Perimeter
EP1774024A4 (en) 2004-07-02 2012-04-04 Blueshift Biotechnologies Inc Exploring fluorophore microenvironments
CN1985174B (en) 2004-07-12 2010-12-22 爱科来株式会社 Analyzer
US7932090B2 (en) * 2004-08-05 2011-04-26 3M Innovative Properties Company Sample processing device positioning apparatus and methods
WO2006038159A1 (en) 2004-10-06 2006-04-13 Koninklijke Philips Electronics N.V. Microfluidic testing system
US20060090800A1 (en) 2004-10-18 2006-05-04 Applera Corporation Fluid processing device including size-changing barrier
CN101116086A (en) 2004-11-16 2008-01-30 伊路敏纳公司 Methods and apparatus for reading for encoding microbeads
US7604173B2 (en) * 2004-11-16 2009-10-20 Illumina, Inc. Holographically encoded elements for microarray and other tagging labeling applications, and method and apparatus for making and reading the same
US7508608B2 (en) * 2004-11-17 2009-03-24 Illumina, Inc. Lithographically fabricated holographic optical identification element
US20060171288A1 (en) * 2005-01-04 2006-08-03 Children's Hospital Oakland Research Institute Optical disk assay device, system and method
WO2006080140A1 (en) 2005-01-28 2006-08-03 Matsushita Electric Industrial Co., Ltd. Blood treatment apparatus and blood supply method
US20070023643A1 (en) * 2005-02-01 2007-02-01 Nolte David D Differentially encoded biological analyzer planar array apparatus and methods
WO2006083917A3 (en) * 2005-02-01 2007-08-30 Purdue Research Foundation Laser scanning interferometric surface metrology
US7910356B2 (en) * 2005-02-01 2011-03-22 Purdue Research Foundation Multiplexed biological analyzer planar array apparatus and methods
US20060195058A1 (en) 2005-02-14 2006-08-31 Gable Jennifer H Methods and apparatus for extracting and analyzing a bodily fluid
JP2006242613A (en) * 2005-03-01 2006-09-14 Matsushita Electric Ind Co Ltd Sample analyzer
US7507575B2 (en) 2005-04-01 2009-03-24 3M Innovative Properties Company Multiplex fluorescence detection device having removable optical modules
US7709249B2 (en) 2005-04-01 2010-05-04 3M Innovative Properties Company Multiplex fluorescence detection device having fiber bundle coupling multiple optical modules to a common detector
US20070196820A1 (en) * 2005-04-05 2007-08-23 Ravi Kapur Devices and methods for enrichment and alteration of cells and other particles
CN101171346B (en) * 2005-05-06 2011-11-09 三星电子股份有限公司 Digital bio disc(DBD), DBD driver apparatus, and assay method using the same
US7596073B2 (en) 2005-05-09 2009-09-29 Searete Llc Method and system for fluid mediated disk activation and deactivation
US7519980B2 (en) * 2005-05-09 2009-04-14 Searete Llc Fluid mediated disk activation and deactivation mechanisms
US20110181981A1 (en) * 2005-05-09 2011-07-28 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Method and system for rotational control of data storage devices
US8264928B2 (en) * 2006-06-19 2012-09-11 The Invention Science Fund I, Llc Method and system for fluid mediated disk activation and deactivation
US8432777B2 (en) * 2006-06-19 2013-04-30 The Invention Science Fund I, Llc Method and system for fluid mediated disk activation and deactivation
US7668069B2 (en) * 2005-05-09 2010-02-23 Searete Llc Limited use memory device with associated information
US7748012B2 (en) 2005-05-09 2010-06-29 Searete Llc Method of manufacturing a limited use data storing device
US7907486B2 (en) * 2006-06-20 2011-03-15 The Invention Science Fund I, Llc Rotation responsive disk activation and deactivation mechanisms
US8462605B2 (en) 2005-05-09 2013-06-11 The Invention Science Fund I, Llc Method of manufacturing a limited use data storing device
US8220014B2 (en) * 2005-05-09 2012-07-10 The Invention Science Fund I, Llc Modifiable memory devices having limited expected lifetime
US8121016B2 (en) * 2005-05-09 2012-02-21 The Invention Science Fund I, Llc Rotation responsive disk activation and deactivation mechanisms
US7694316B2 (en) * 2005-05-09 2010-04-06 The Invention Science Fund I, Llc Fluid mediated disk activation and deactivation mechanisms
US7512959B2 (en) * 2005-05-09 2009-03-31 Searete Llc Rotation responsive disk activation and deactivation mechanisms
US8159925B2 (en) * 2005-08-05 2012-04-17 The Invention Science Fund I, Llc Limited use memory device with associated information
US8218262B2 (en) 2005-05-09 2012-07-10 The Invention Science Fund I, Llc Method of manufacturing a limited use data storing device including structured data and primary and secondary read-support information
US8099608B2 (en) 2005-05-09 2012-01-17 The Invention Science Fund I, Llc Limited use data storing device
US7916592B2 (en) * 2005-05-09 2011-03-29 The Invention Science Fund I, Llc Fluid mediated disk activation and deactivation mechanisms
WO2006122310A3 (en) * 2005-05-11 2009-06-04 William Abrams System for testing
US7916615B2 (en) * 2005-06-09 2011-03-29 The Invention Science Fund I, Llc Method and system for rotational control of data storage devices
US7668068B2 (en) * 2005-06-09 2010-02-23 Searete Llc Rotation responsive disk activation and deactivation mechanisms
US20060281192A1 (en) * 2005-06-13 2006-12-14 Harding Philip H Method for mixing fluids in microfluidic systems
US7935318B2 (en) * 2005-06-13 2011-05-03 Hewlett-Packard Development Company, L.P. Microfluidic centrifugation systems
US7437914B2 (en) * 2005-06-28 2008-10-21 Hewlett-Packard Development Company, L.P. Microfluidic test systems with gas bubble reduction
JP4940446B2 (en) * 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 Bio drive apparatus and analysis method using the same
US7323660B2 (en) * 2005-07-05 2008-01-29 3M Innovative Properties Company Modular sample processing apparatus kits and modules
US7754474B2 (en) 2005-07-05 2010-07-13 3M Innovative Properties Company Sample processing device compression systems and methods
US7763210B2 (en) * 2005-07-05 2010-07-27 3M Innovative Properties Company Compliant microfluidic sample processing disks
US7527763B2 (en) * 2005-07-05 2009-05-05 3M Innovative Properties Company Valve control system for a rotating multiplex fluorescence detection device
US9396752B2 (en) * 2005-08-05 2016-07-19 Searete Llc Memory device activation and deactivation
US7770028B2 (en) * 2005-09-09 2010-08-03 Invention Science Fund 1, Llc Limited use data storing device
US7565596B2 (en) * 2005-09-09 2009-07-21 Searete Llc Data recovery systems
US8140745B2 (en) * 2005-09-09 2012-03-20 The Invention Science Fund I, Llc Data retrieval methods
US20070059716A1 (en) * 2005-09-15 2007-03-15 Ulysses Balis Methods for detecting fetal abnormality
US20070059680A1 (en) * 2005-09-15 2007-03-15 Ravi Kapur System for cell enrichment
US20070059718A1 (en) * 2005-09-15 2007-03-15 Mehmet Toner Systems and methods for enrichment of analytes
US20070059781A1 (en) * 2005-09-15 2007-03-15 Ravi Kapur System for size based separation and analysis
US20070059719A1 (en) * 2005-09-15 2007-03-15 Michael Grisham Business methods for prenatal Diagnosis
US20070059774A1 (en) * 2005-09-15 2007-03-15 Michael Grisham Kits for Prenatal Testing
US7723120B2 (en) * 2005-10-26 2010-05-25 General Electric Company Optical sensor array system and method for parallel processing of chemical and biochemical information
US8133741B2 (en) 2005-10-26 2012-03-13 General Electric Company Methods and systems for delivery of fluidic samples to sensor arrays
WO2007050539A3 (en) * 2005-10-26 2007-08-30 Scott M Boyette Methods and systems for delivery of fluidic samples to sensor arrays
JP4331158B2 (en) * 2005-11-15 2009-09-16 シャープ株式会社 Blade cleaning jig
US20070113908A1 (en) * 2005-11-18 2007-05-24 The Ohio State University And Bioloc, Inc. Valve for microfluidic chips
US7623624B2 (en) * 2005-11-22 2009-11-24 Illumina, Inc. Method and apparatus for labeling using optical identification elements characterized by X-ray diffraction
CN101389956B (en) 2005-12-21 2013-01-02 三星电子株式会社 Bio memory disc and bio memory disc drive apparatus, and assay method using the same
US20070240178A1 (en) * 2006-04-07 2007-10-11 Kleker Richard G Apparatus and method for storing digital data
US7830575B2 (en) * 2006-04-10 2010-11-09 Illumina, Inc. Optical scanner with improved scan time
US20070259366A1 (en) * 2006-05-03 2007-11-08 Greg Lawrence Direct printing of patterned hydrophobic wells
US20080124721A1 (en) * 2006-06-14 2008-05-29 Martin Fuchs Analysis of rare cell-enriched samples
US8372584B2 (en) 2006-06-14 2013-02-12 The General Hospital Corporation Rare cell analysis using sample splitting and DNA tags
US8273310B2 (en) * 2006-09-05 2012-09-25 Samsung Electronics Co., Ltd. Centrifugal force-based microfluidic device for nucleic acid extraction and microfluidic system including the microfluidic device
US20100047130A1 (en) 2006-10-25 2010-02-25 Nanyang Polytechnic Lab-On-Cd Systems With Magnetically Actuated Micro Check Valves And/Or Magnetic Immobilization
EP2092301A1 (en) * 2006-11-09 2009-08-26 Biosurfit, S.A. Detection device based on surface plasmon resonance effect
US20080144899A1 (en) * 2006-11-30 2008-06-19 Manoj Varma Process for extracting periodic features from images by template matching
US7522282B2 (en) * 2006-11-30 2009-04-21 Purdue Research Foundation Molecular interferometric imaging process and apparatus
US20080230605A1 (en) * 2006-11-30 2008-09-25 Brian Weichel Process and apparatus for maintaining data integrity
US20080220442A1 (en) * 2006-12-06 2008-09-11 Proteinics Difference detection methods using isoelectric focusing chips
US8128893B2 (en) 2006-12-22 2012-03-06 3M Innovative Properties Company Thermal transfer methods and structures for microfluidic systems
CN101568384B (en) * 2006-12-22 2013-05-01 3M创新有限公司 Enhanced sample processing devices, systems and methods
WO2008089495A3 (en) * 2007-01-19 2008-10-09 Purdue Research Foundation System with extended range of molecular sensing through integrated multi-modal data acquisition
US9164111B2 (en) * 2007-03-12 2015-10-20 Resolved Technologies, Inc. Device for multiple tests from a single sample
CA2681722A1 (en) * 2007-03-26 2008-10-02 Purdue Research Foundation Method and apparatus for conjugate quadrature interferometric detection of an immunoassay
US7883898B2 (en) * 2007-05-07 2011-02-08 General Electric Company Method and apparatus for measuring pH of low alkalinity solutions
WO2008139697A1 (en) 2007-05-10 2008-11-20 Panasonic Corporation Substrate including channel part having chamber, and multistage liquid feed device comprising the same
KR101228308B1 (en) * 2007-05-23 2013-01-31 삼성전자주식회사 Disk type microfluidic device using microfluidic chip and disk type microfluidic device using biomolecule microarray chip
KR101335727B1 (en) * 2007-08-22 2013-12-04 삼성전자주식회사 Centrifugal force-based disk type microfluidic device for blood chemistry analysis
EP2062643B1 (en) 2007-11-24 2012-01-18 Roche Diagnostics GmbH Analysis system and method for analysing a bodily fluid sample on an analyte contained therein
US20090176312A1 (en) * 2007-12-04 2009-07-09 Selinfreund Richard H Biological and chemical test media and system
WO2009091187A3 (en) * 2008-01-15 2009-11-05 Lg Electronics Inc. Bio-disc
KR100934648B1 (en) * 2008-04-17 2009-12-31 연세대학교 산학협력단 Centrifugation device using Cd / dvdrom drive
KR20110008261A (en) 2008-04-24 2011-01-26 쓰리엠 이노베이티브 프로퍼티즈 컴파니 Analysis of nucleic acid amplification curves using wavelet transformation
GB0812680D0 (en) * 2008-07-10 2008-08-20 Sec Dep For Innovation Univers Fluid decontamination method and apparatus
EP2145682A1 (en) 2008-07-18 2010-01-20 Boehringer Mannheim Gmbh Test element for analysing a bodily fluid sample for an analyte contained therein, analysis system and method for controlling the movement of a fluid contained in a channel of a test element
US7947492B2 (en) * 2008-08-20 2011-05-24 Northeastern Ohio Universities College Of Medicine Device improving the detection of a ligand
US9554742B2 (en) 2009-07-20 2017-01-31 Optiscan Biomedical Corporation Fluid analysis system
US20110027905A1 (en) * 2009-08-03 2011-02-03 Henderson Douglas B Systems and Methods for Collection and Analysis of Analytes
USD638951S1 (en) 2009-11-13 2011-05-31 3M Innovative Properties Company Sample processing disk cover
USD667561S1 (en) 2009-11-13 2012-09-18 3M Innovative Properties Company Sample processing disk cover
US20110117607A1 (en) * 2009-11-13 2011-05-19 3M Innovative Properties Company Annular compression systems and methods for sample processing devices
US8834792B2 (en) 2009-11-13 2014-09-16 3M Innovative Properties Company Systems for processing sample processing devices
USD638550S1 (en) 2009-11-13 2011-05-24 3M Innovative Properties Company Sample processing disk cover
GB2476474B (en) 2009-12-22 2012-03-28 Biosurfit Sa Surface plasmon resonance detection system
EP2580589B1 (en) 2010-06-09 2016-08-31 Optiscan Biomedical Corporation Measuring analytes in a fluid sample drawn from a patient
JP6235462B2 (en) 2011-05-18 2017-11-22 スリーエム イノベイティブ プロパティズ カンパニー System and method for detecting the presence of a selected volume of the material in the sample processing device
EP2709761A1 (en) 2011-05-18 2014-03-26 3M Innovative Properties Company Systems and methods for volumetric metering on a sample processing device
USD672467S1 (en) 2011-05-18 2012-12-11 3M Innovative Properties Company Rotatable sample processing disk
JP2014517291A (en) 2011-05-18 2014-07-17 スリーエム イノベイティブ プロパティズ カンパニー System and method for valve operation of the sample processing device
WO2013006716A1 (en) 2011-07-06 2013-01-10 Optiscan Biomedical Corporation Sample cell for fluid analysis system
KR101257700B1 (en) * 2011-12-05 2013-04-24 삼성전자주식회사 Microfluidic device and microfluidic system including thereof
KR20130099703A (en) * 2012-02-29 2013-09-06 삼성전자주식회사 Optical head and sequencing apparatus including the same
US20140099703A1 (en) * 2012-10-05 2014-04-10 William P Parker Capillary Waveguide Cuvette
KR20140055528A (en) * 2012-10-31 2014-05-09 삼성전자주식회사 Microfluidic structure, microfluidic system and control method for microfluidic test device
WO2014078602A1 (en) * 2012-11-14 2014-05-22 University Of Utah Research Foundation Single step calibration curve through sample convection
US9810704B2 (en) 2013-02-18 2017-11-07 Theranos, Inc. Systems and methods for multi-analysis
DE102014019526B4 (en) * 2014-12-23 2016-10-27 Testo Ag Examination method, disk-shaped sample carrier, and use of a sample carrier

Citations (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6312901B1 (en) *
US1756971A (en) * 1927-07-08 1930-05-06 Harnischfeger Corp Trenching machine
US3798459A (en) * 1972-10-06 1974-03-19 Atomic Energy Commission Compact dynamic multistation photometer utilizing disposable cuvette rotor
US4284602A (en) * 1979-12-10 1981-08-18 Immutron, Inc. Integrated fluid manipulator
US4469793A (en) * 1981-04-14 1984-09-04 Jean Guigan Method and apparatus for dispensing a predetermined dose of a sample liquid into a receptor cell
US4870508A (en) * 1978-03-16 1989-09-26 U. S. Philips Corporation Record carrier body with an optical servo track and optical apparatus for writing and reading information from the carrier
US4917865A (en) * 1986-09-16 1990-04-17 E. I. Du Pont De Nemours And Company Analysis device
US4961916A (en) * 1988-06-02 1990-10-09 Irsst-Institut De Recherche En Sante Et En Securite Du Travail Du Quebec Sampling device
US5061381A (en) * 1990-06-04 1991-10-29 Abaxis, Inc. Apparatus and method for separating cells from biological fluids
US5119363A (en) * 1980-12-17 1992-06-02 Matsushita Electric Industrial Company, Ltd. Optical disk having an index mark
US5122284A (en) * 1990-06-04 1992-06-16 Abaxis, Inc. Apparatus and method for optically analyzing biological fluids
US5160702A (en) * 1989-01-17 1992-11-03 Molecular Devices Corporation Analyzer with improved rotor structure
US5173262A (en) * 1987-07-17 1992-12-22 Martin Marietta Energy Systems, Inc. Rotor assembly and method for automatically processing liquids
US5173193A (en) * 1991-04-01 1992-12-22 Schembri Carol T Centrifugal rotor having flow partition
US5186844A (en) * 1991-04-01 1993-02-16 Abaxis, Inc. Apparatus and method for continuous centrifugal blood cell separation
US5200314A (en) * 1990-03-23 1993-04-06 Chiron Corporation Polynucleotide capture assay employing in vitro amplification
US5242606A (en) * 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
US5304347A (en) * 1992-02-08 1994-04-19 Boehringer Mannheim Gmbh Liquid transfer device for an analysis unit
US5310523A (en) * 1990-06-15 1994-05-10 Chiron Corporation Self-contained assay assembly and apparatus
US5407554A (en) * 1993-05-10 1995-04-18 Asulab S.A. Electrochemical sensor with multiple zones on a disc and its application to the quantitative analysis of glucose
US5409665A (en) * 1993-09-01 1995-04-25 Abaxis, Inc. Simultaneous cuvette filling with means to isolate cuvettes
US5413732A (en) * 1991-08-19 1995-05-09 Abaxis, Inc. Reagent compositions for analytical testing
US5457053A (en) * 1992-02-11 1995-10-10 Abaxis, Inc. Reagent container for analytical rotor
US5472603A (en) * 1992-04-02 1995-12-05 Abaxis, Inc. Analytical rotor with dye mixing chamber
US5513169A (en) * 1993-10-06 1996-04-30 Sony Corporation CD-ROM with machine-readable i.d. code
US5543292A (en) * 1992-06-16 1996-08-06 Hitachi, Ltd. Process for the measurement of nucleic acids
US5585069A (en) * 1994-11-10 1996-12-17 David Sarnoff Research Center, Inc. Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis
US5591643A (en) * 1993-09-01 1997-01-07 Abaxis, Inc. Simplified inlet channels
US5598393A (en) * 1992-04-10 1997-01-28 Zen Research N.V. Method and apparatus for reading data
US5874214A (en) * 1995-04-25 1999-02-23 Irori Remotely programmable matrices with memories
US5874219A (en) * 1995-06-07 1999-02-23 Affymetrix, Inc. Methods for concurrently processing multiple biological chip assays
US5879774A (en) * 1997-12-03 1999-03-09 Eastman Kodak Company Multilayer laminate elements having an adhesive layer
US5882903A (en) * 1996-11-01 1999-03-16 Sarnoff Corporation Assay system and method for conducting assays
US5982577A (en) * 1995-03-31 1999-11-09 Brown; Paul Batteryless, spring-powered portable cassette player
US6030581A (en) * 1997-02-28 2000-02-29 Burstein Laboratories Laboratory in a disk
US6117630A (en) * 1997-10-30 2000-09-12 Motorola, Inc. Molecular detection apparatus and method
US6143247A (en) * 1996-12-20 2000-11-07 Gamera Bioscience Inc. Affinity binding-based system for detecting particulates in a fluid
US6277653B1 (en) * 1997-11-19 2001-08-21 Imation Corp. Optical assaying method and system having movable sensor with multiple sensing regions
US6312901B2 (en) * 1996-07-08 2001-11-06 Burstein Technologies, Inc. Spatially addressable, cleavable reflective signal elements, assay device and method
US6319469B1 (en) * 1995-12-18 2001-11-20 Silicon Valley Bank Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system
US6339473B1 (en) * 1994-09-21 2002-01-15 The University Court Of The University Of Glasgow Apparatus and method for carrying out analysis of samples
US6342349B1 (en) * 1996-07-08 2002-01-29 Burstein Technologies, Inc. Optical disk-based assay devices and methods
US20020047003A1 (en) * 2000-06-28 2002-04-25 William Bedingham Enhanced sample processing devices, systems and methods
US20020106661A1 (en) * 1996-07-08 2002-08-08 Burstein Laboratories, Inc. Optical disk-based assay devices and methods
US6709869B2 (en) * 1995-12-18 2004-03-23 Tecan Trading Ag Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI845161A0 (en) * 1984-12-28 1984-12-28 Ksv Chemicals Oy Ytbehandlingsmedel.
JP3276955B2 (en) * 1988-09-30 2002-04-22 ジーン−トラック・システムス Probe structure and methods of use thereof bonded to the terminal of the template of Rna
EP0417305A4 (en) * 1989-03-07 1992-04-22 Idemitsu Petrochemical Co. Ltd. Analyzer of liquid sample and analyzing method of liquid sample using said analyzer
GB9207381D0 (en) * 1992-04-03 1992-05-13 Ici Plc Synthesis of oligonucleotides
EP0637996B1 (en) * 1992-05-01 1997-07-23 The Trustees Of The University Of Pennsylvania Microfabricated detection structures
US6974666B1 (en) * 1994-10-21 2005-12-13 Appymetric, Inc. Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA
US5997861A (en) * 1994-10-31 1999-12-07 Burstein Laboratories, Inc. Antiviral supramolecules containing target-binding molecules and therapeutic molecules bound to spectrin
WO1996035940A1 (en) * 1995-05-12 1996-11-14 Novartis Ag Sensor platform and method for the parallel detection of a plurality of analytes using evanescently excited luminescence
JP2002503331A (en) * 1995-12-05 2002-01-29 ガメラ バイオサイエンス コーポレイション Apparatus and methods for using centripetal acceleration to propel liquid movement in ultratrace liquid element engineering system with information science mounted on board

Patent Citations (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6312901B1 (en) *
US1756971A (en) * 1927-07-08 1930-05-06 Harnischfeger Corp Trenching machine
US3798459A (en) * 1972-10-06 1974-03-19 Atomic Energy Commission Compact dynamic multistation photometer utilizing disposable cuvette rotor
US4870508A (en) * 1978-03-16 1989-09-26 U. S. Philips Corporation Record carrier body with an optical servo track and optical apparatus for writing and reading information from the carrier
US4284602A (en) * 1979-12-10 1981-08-18 Immutron, Inc. Integrated fluid manipulator
US5119363A (en) * 1980-12-17 1992-06-02 Matsushita Electric Industrial Company, Ltd. Optical disk having an index mark
US4469793A (en) * 1981-04-14 1984-09-04 Jean Guigan Method and apparatus for dispensing a predetermined dose of a sample liquid into a receptor cell
US4917865A (en) * 1986-09-16 1990-04-17 E. I. Du Pont De Nemours And Company Analysis device
US5173262A (en) * 1987-07-17 1992-12-22 Martin Marietta Energy Systems, Inc. Rotor assembly and method for automatically processing liquids
US4961916A (en) * 1988-06-02 1990-10-09 Irsst-Institut De Recherche En Sante Et En Securite Du Travail Du Quebec Sampling device
US5160702A (en) * 1989-01-17 1992-11-03 Molecular Devices Corporation Analyzer with improved rotor structure
US5200314A (en) * 1990-03-23 1993-04-06 Chiron Corporation Polynucleotide capture assay employing in vitro amplification
US5061381A (en) * 1990-06-04 1991-10-29 Abaxis, Inc. Apparatus and method for separating cells from biological fluids
US5122284A (en) * 1990-06-04 1992-06-16 Abaxis, Inc. Apparatus and method for optically analyzing biological fluids
US5242606A (en) * 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
US5310523A (en) * 1990-06-15 1994-05-10 Chiron Corporation Self-contained assay assembly and apparatus
US5173193A (en) * 1991-04-01 1992-12-22 Schembri Carol T Centrifugal rotor having flow partition
US5186844A (en) * 1991-04-01 1993-02-16 Abaxis, Inc. Apparatus and method for continuous centrifugal blood cell separation
US5413732A (en) * 1991-08-19 1995-05-09 Abaxis, Inc. Reagent compositions for analytical testing
US5304347A (en) * 1992-02-08 1994-04-19 Boehringer Mannheim Gmbh Liquid transfer device for an analysis unit
US5457053A (en) * 1992-02-11 1995-10-10 Abaxis, Inc. Reagent container for analytical rotor
US5472603A (en) * 1992-04-02 1995-12-05 Abaxis, Inc. Analytical rotor with dye mixing chamber
US5598393A (en) * 1992-04-10 1997-01-28 Zen Research N.V. Method and apparatus for reading data
US5543292A (en) * 1992-06-16 1996-08-06 Hitachi, Ltd. Process for the measurement of nucleic acids
US5407554A (en) * 1993-05-10 1995-04-18 Asulab S.A. Electrochemical sensor with multiple zones on a disc and its application to the quantitative analysis of glucose
US5409665A (en) * 1993-09-01 1995-04-25 Abaxis, Inc. Simultaneous cuvette filling with means to isolate cuvettes
US5518930A (en) * 1993-09-01 1996-05-21 Abaxis, Inc. Simultaneous cuvette filling with means to isolate cuvettes
US5591643A (en) * 1993-09-01 1997-01-07 Abaxis, Inc. Simplified inlet channels
US5513169A (en) * 1993-10-06 1996-04-30 Sony Corporation CD-ROM with machine-readable i.d. code
US6339473B1 (en) * 1994-09-21 2002-01-15 The University Court Of The University Of Glasgow Apparatus and method for carrying out analysis of samples
US5585069A (en) * 1994-11-10 1996-12-17 David Sarnoff Research Center, Inc. Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis
US5755942A (en) * 1994-11-10 1998-05-26 David Sarnoff Research Center, Inc. Partitioned microelectronic device array
US5863708A (en) * 1994-11-10 1999-01-26 Sarnoff Corporation Partitioned microelectronic device array
US5982577A (en) * 1995-03-31 1999-11-09 Brown; Paul Batteryless, spring-powered portable cassette player
US5874214A (en) * 1995-04-25 1999-02-23 Irori Remotely programmable matrices with memories
US5874219A (en) * 1995-06-07 1999-02-23 Affymetrix, Inc. Methods for concurrently processing multiple biological chip assays
US6319468B1 (en) * 1995-06-27 2001-11-20 Tecan Trading Ag Affinity binding-based system for detecting particulates in a fluid
US6319469B1 (en) * 1995-12-18 2001-11-20 Silicon Valley Bank Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system
US6709869B2 (en) * 1995-12-18 2004-03-23 Tecan Trading Ag Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system
US6312901B2 (en) * 1996-07-08 2001-11-06 Burstein Technologies, Inc. Spatially addressable, cleavable reflective signal elements, assay device and method
US6342349B1 (en) * 1996-07-08 2002-01-29 Burstein Technologies, Inc. Optical disk-based assay devices and methods
US20020106661A1 (en) * 1996-07-08 2002-08-08 Burstein Laboratories, Inc. Optical disk-based assay devices and methods
US5882903A (en) * 1996-11-01 1999-03-16 Sarnoff Corporation Assay system and method for conducting assays
US6143247A (en) * 1996-12-20 2000-11-07 Gamera Bioscience Inc. Affinity binding-based system for detecting particulates in a fluid
US6030581A (en) * 1997-02-28 2000-02-29 Burstein Laboratories Laboratory in a disk
US6117630A (en) * 1997-10-30 2000-09-12 Motorola, Inc. Molecular detection apparatus and method
US6277653B1 (en) * 1997-11-19 2001-08-21 Imation Corp. Optical assaying method and system having movable sensor with multiple sensing regions
US5879774A (en) * 1997-12-03 1999-03-09 Eastman Kodak Company Multilayer laminate elements having an adhesive layer
US20020047003A1 (en) * 2000-06-28 2002-04-25 William Bedingham Enhanced sample processing devices, systems and methods

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005089910A1 (en) * 2004-03-17 2005-09-29 Ciphergen Biosystems, Inc. Multi-compartment filter and method of filtering using same
US20060063251A1 (en) * 2004-09-22 2006-03-23 Hsiao-Chung Tsai Immunoassay devices and methods of using same
US7381374B2 (en) * 2004-09-22 2008-06-03 Hsiao-Chung Tsai Immunoassay devices and methods of using same
WO2006042825A1 (en) * 2004-10-15 2006-04-27 Siemens Aktiengesellschaft Method for controlling valves during the thermocyclisation of a substance for the purpose of polymer chain reaction (pcr) and associated arrangement
US20070265439A1 (en) * 2004-10-15 2007-11-15 Walter Gumbrecht Method for Controlling Valves During the Thermocyclisation of a Substance for the Purpose of Polymer Chain Reaction (Pcr) and Associated Arrangement
US9267616B2 (en) 2004-10-15 2016-02-23 Boehringer Ingelheim Vetmedica Gmbh Method for controlling valves during the thermocyclization of a substance for the purpose of polymer chain reaction (PCR) and associated arrangement
US20080300148A1 (en) * 2007-06-04 2008-12-04 Samsung Electronics Co., Ltd. Microfluidic device for simultaneously conducting multiple analyses
EP2002895A1 (en) * 2007-06-04 2008-12-17 Samsung Electronics Co., Ltd. Microfluidic device for simultaneously conducting multiple analyses
US9726685B2 (en) 2007-06-04 2017-08-08 Samsung Electronics Co., Ltd. Microfluidic device for simultaneously conducting multiple analyses
US20100245815A1 (en) * 2007-06-29 2010-09-30 Jens Ducree Centrifugal device
US8482734B2 (en) 2007-06-29 2013-07-09 Dublin City University Centrifugal device
WO2009003985A1 (en) * 2007-06-29 2009-01-08 Dublin City University Centrifugal device
US8367398B2 (en) * 2008-10-01 2013-02-05 Samsung Electronics Co., Ltd. Centrifugal-based microfluidic apparatus, method of fabricating the same, and method of testing samples using the microfluidic apparatus
US9616424B2 (en) 2008-10-01 2017-04-11 Samsung Electronics Co., Ltd. Centrifugal-based microfluidic apparatus, method of fabricating the same, and method of testing samples using the microfluidic apparatus
US20100081213A1 (en) * 2008-10-01 2010-04-01 Samsung Electronics Co., Ltd. Centrifugal-based microfluidic apparatus, method of fabricating the same, and method of testing samples using the microfluidic apparatus
US9421541B2 (en) 2013-06-04 2016-08-23 Samsung Electronics Co., Ltd. Microfluidic apparatus with increased recovery rate of target material from a sample

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