US20040171166A1 - Method and apparatus for performing microassays - Google Patents

Method and apparatus for performing microassays Download PDF

Info

Publication number
US20040171166A1
US20040171166A1 US10796856 US79685604A US2004171166A1 US 20040171166 A1 US20040171166 A1 US 20040171166A1 US 10796856 US10796856 US 10796856 US 79685604 A US79685604 A US 79685604A US 2004171166 A1 US2004171166 A1 US 2004171166A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
holes
platen
liquid
invention
hole
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10796856
Inventor
Ian Hunter
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Massachusetts Institute of Technology
Original Assignee
Massachusetts Institute of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING, DISPERSING
    • B01F13/00Other mixers; Mixing plant, including combinations of mixers, e.g. of dissimilar mixers
    • B01F13/0059Micromixers
    • B01F13/0069Micromixers the components flowing in the form of droplets
    • B01F13/0071Micromixers the components flowing in the form of droplets the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING, DISPERSING
    • B01F13/00Other mixers; Mixing plant, including combinations of mixers, e.g. of dissimilar mixers
    • B01F13/0059Micromixers
    • B01F13/0074Micromixers using mixing means not otherwise provided for
    • B01F13/0083Micromixers using mixing means not otherwise provided for using surface tension to mix, move or hold the fluids
    • B01F13/0084Micromixers using mixing means not otherwise provided for using surface tension to mix, move or hold the fluids using hydrophilic/hydrophobic surfaces
    • 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
    • B01L3/5025Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • 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
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • 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
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50857Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates using arrays or bundles of open capillaries for holding samples
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS 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
    • C12Q1/34Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • 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
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1002Reagent dispensers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00279Features relating to reactor vessels
    • B01J2219/00306Reactor vessels in a multiple arrangement
    • B01J2219/00313Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00279Features relating to reactor vessels
    • B01J2219/00306Reactor vessels in a multiple arrangement
    • B01J2219/00313Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315Microtiter plates
    • B01J2219/00317Microwell devices, i.e. having large numbers of wells
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00351Means for dispensing and evacuation of reagents
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00527Sheets
    • B01J2219/00533Sheets essentially rectangular
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00527Sheets
    • B01J2219/00536Sheets in the shape of disks
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/0054Means for coding or tagging the apparatus or the reagents
    • B01J2219/00547Bar codes
    • B01J2219/005492-dimensional
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00585Parallel processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00599Solution-phase processes
    • 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
    • B01L2200/0642Filling fluids into wells by specific techniques
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL CHEMISTRY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES, IN SILICO LIBRARIES
    • C40B60/00Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL CHEMISTRY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES, IN SILICO LIBRARIES
    • C40B70/00Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
    • 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
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00237Handling microquantities of analyte, e.g. microvalves, capillary networks
    • 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
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/112499Automated chemical analysis with sample on test slide
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation

Abstract

A method and apparatus for analyzing a plurality of substances. A platen is provided having two substantially parallel planar surfaces and a plurality of through-holes. An optical arrangement analyzes light emanating from the through-holes. The through-holes may be individually addressable, and may have volumes less than 100 nanoliters. Samples may be accurately dispensed, diluted and mixed in accordance with embodiments of the invention, and may be plated onto walls of the through-holes, and then subsequently resuspended prior to characterization, or, alternatively, retained in the through-holes by surface tension.

Description

  • [0001]
    This application is a divisional application of copending application U.S. Ser. No. 09/710,082, filed Nov. 10, 2000, a divisional application of U.S. Ser. No. 09/225,583, filed Jan. 5, 1999, claiming priority from U.S. Provisional Application No. 60/071,179, filed Jan. 12, 1998, from which application the present application also claims priority. All of the above applications are incorporated herein by reference.
  • TECHNICAL FIELD
  • [0002]
    The present invention pertains to an apparatus and method for manipulating, transporting, and analyzing a large number of microscopic samples of a liquid or of materials including cells currently or formerly in liquid suspension.
  • BACKGROUND OF THE INVENTION
  • [0003]
    Chemistry on the micro-scale, involving the reaction and subsequent analysis of quantities of reagents or analytes of order microliters or smaller, is an increasingly important aspect of the development of new substances in the pharmaceutical and other industries. Such reaction and analysis may accommodate vast libraries containing as many as a million compounds to be reacted and analyzed under various conditions. Significant problems associated with current technologies as applied to chemical analysis of vast numbers (potentially on the order of hundreds of thousands or millions per day) of compounds include the problem of handling vast numbers of compounds and reactions in parallel.
  • [0004]
    Existing technology relies on 96-, 384-, or 1536-well plates containing quantities between approximately 1 microliter and 1 milliliter of liquid compound per well, and, generally, involves chemical reactions and analysis in wells disposed with single openings on flat, two-dimensional surfaces such as silicon chips. It is not practical to apply existing technology in the art to form million-well disks. There is a need, therefore, for new approaches that permit the analysis of a million samples in a laboratory format.
  • SUMMARY OF THE INVENTION
  • [0005]
    In accordance with one aspect of the invention, in one of its embodiments, there is provided a method for selecting samples having specified properties from a library of samples. The method has the steps of:
  • [0006]
    a. providing a platen having two substantially parallel planar surfaces and a plurality of addressable through-holes disposed substantially perpendicularly to the planar surfaces;
  • [0007]
    b. loading a first sample in liquid form into at least one of the through-holes;
  • [0008]
    c. adding a second sample into the at least one of the through-holes for permitting a reaction between the first sample and the second sample; and
  • [0009]
    d. characterizing the reaction in the through-hole in terms of the specified properties.
  • [0010]
    In accordance with alternate embodiments of the invention, each through-hole may be dimensioned so as to maintain a liquid sample therein by means of surface tension, and may have a volume less than 100 nanoliters. The plurality of addressable through-holes may have a density in excess of 108 per square meter.
  • [0011]
    In accordance with further alternate embodiments of the invention, the step of loading a first sample may include drawing the sample from a planar surface by capillary action. The platen may be brought into contact with a reservoir of liquid and rotated about an axis perpendicular to the surface of the reservoir or about at least one of an axis perpendicular to the surface of the reservoir and an axis parallel to the surface of the reservoir. The method may include the further step of maintaining a humid atmosphere for preventing evaporation of the first sample or coating the liquid sample with a monolayer for preventing evaporation of the first sample.
  • [0012]
    In accordance with a further aspect of the present invention, a method is provided for preparing a plurality of combinations of members of a first set of samples in liquid form with members of a second set of samples in liquid form, the method comprising:
  • [0013]
    a. providing a first perforated platen having through-holes and a second perforated platen having through-holes;
  • [0014]
    b. loading a first set of samples in liquid form into the through-holes of the first perforated platen;
  • [0015]
    c. loading a second set of samples in liquid form into the through-holes of the second perforated platen;
  • [0016]
    d. registering the through-holes of the first perforated platen with the through-holes of the second perforated platen; and
  • [0017]
    e. combining the first set of samples with the second set of samples.
  • [0018]
    In accordance with yet further aspects of the present invention, there are provided methods for mixing and diluting liquid samples. The methods have steps of loading one set of liquid samples into through-holes of a first platen and loading another set of liquid samples into through-holes of a second platen, and then disposing a surface of the first platen in contact with a surface of the second platen in such a way as to register at least one through-hole of the first platten with at least one of through-hole of the second platten for permitting mixing of the liquid samples of the respective sets.
  • [0019]
    In accordance with another aspect of the present invention, there is provided a system for analyzing a plurality of liquid samples. The system has a platen having two substantially parallel planar surfaces and a plurality of through-holes having apertures and walls, a source of optical radiation for illuminating at least one through-hole along an optical axis, and an optical arrangement for analyzing light emanating from the at least one through-hole.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0020]
    The foregoing features of the invention will be more readily understood by reference to the following detailed description taken with the accompanying drawings in which:
  • [0021]
    [0021]FIG. 1 is a side view in cross-section of a portion of a laminated platen containing multiple through-holes for analysis of liquid samples in accordance with a preferred embodiment of the present invention;
  • [0022]
    [0022]FIG. 2A is top view of a portion of the platen of FIG. 1 in which the through-holes are configured on rectangular centers;
  • [0023]
    [0023]FIG. 2B is top view of a portion of the platen of FIG. 1 in which the through-holes are configured in a hexagonal close-packed array;
  • [0024]
    [0024]FIG. 3 is a top view of round sample wafer populated with through-holes in accordance with an embodiment of the present invention;
  • [0025]
    [0025]FIG. 4 is a side perspective view of an arrangement for loading a liquid sample into the platen of FIG. 1 by employing capillary and inertial insertion forces;
  • [0026]
    [0026]FIG. 5 is a cut-away view of a single through-hole in the platen of FIG. 1, showing the use of hydrophobic and hydrophilic layers for containment of an aqueous sample;
  • [0027]
    [0027]FIG. 6 is schematic diagram of a confocal optical arrangement for interrogation of a liquid sample in a through-hole in accordance with an embodiment of the present invention;
  • [0028]
    [0028]FIG. 7 is perspective view of a scanning arrangement for serially interrogating liquid samples retained in through-holes of a disk-type platen in accordance with an embodiment of the present invention;
  • [0029]
    [0029]FIG. 8 is schematic representation of a scanning arrangement for serially interrogating liquid samples retained in a continuous-process film-type platen, in accordance with an alternate embodiment of the present invention;
  • [0030]
    [0030]FIG. 9 is a cross-sectional view of portions of two platens brought into proximity with through-hole registration in anticipation of mixing or dilution in accordance with embodiments of the present invention; and
  • [0031]
    [0031]FIG. 10 is a cross-sectional view of the portions of two platens of FIG. 9 after the two platens have been brought into contact to facilitate mixing or dilution.
  • DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
  • [0032]
    Through-Hole Wells
  • [0033]
    In accordance with a preferred embodiment of the invention, the volume of each well employed for the assay of a chemical or biochemical reaction is reduced typically to less than 100 nanoliters (10−10 m3). The packing density of wells may thereby be increased by several orders of magnitude over prior art technology. Referring to FIG. 1, a side view is shown in cross section of a platen 10, otherwise referred to herein as a “substrate” or “sample wafer.” Platen 10 is the carrier of a large number of through-holes 12 which traverse platen 10 from one surface 14 to an opposing surface 16 of the platen and constitute assay wells (or “microwells”) in accordance with an embodiment of the invention. Through-holes 12 may be shaped as circular right cylinders, or, alternatively, may have rectangular cross-sections, however otherwise shaped through-holes are within the scope of the present invention. As used in the present description and in the appended claims, the term “platen” refers to a structure having substantially parallel plane surfaces and transverse dimensions substantially exceeding the thickness of the structure between the substantially parallel plane surfaces.
  • [0034]
    The apertures of through-holes 12 need not be square, and, in accordance with an alternate embodiment of the present invention, flanges 8 may extend above planar surface 14 surrounding some or all of through-holes 12 while indentations 6 may be fabricated rounding the edges of through-holes 12 at opposing surface 16. Flanges 8 and indentations 6 may advantageously provide for registration of successive platens 10, in the case where platens are stacked, and in processes of mixing or dilution, as discussed in detail below in reference to FIGS. 9-10.
  • [0035]
    In accordance with an embodiment of the invention, through-holes 12 are loaded with a first sample 18 in liquid form. Sample 18 is allowed to react with a second sample where the second sample may include a variety of test samples and by subsequent or concurrent analysis of the reaction products, using, for example, optical markers, a large number of reactions may be processed and analyzed in parallel.
  • [0036]
    As applied to biological assays, by way of example, first sample 18 may be a reagent, including, for example, cells in aqueous suspension, eukaryotic (animal, yeast) or prokaryotic (bacteria) cells, hybrid cells, and biological molecules including, for example, antibodies and enzymes, although application to other biological or non-biological assays is within the scope of the invention as claimed herein. All such reagents may also be referred to herein and in the appended claims as “targets.” Typical yeast cell concentrations of 107 cells per milliliter of solution yield on the order of 1000 cells per 100 nanoliter well. Typically, an entire chip or the subset of through-hole wells constituting a contiguous region of platen 10 may be populated with a single strain of cells.
  • [0037]
    A typical procedure assay procedure, such as may be employed in pharmaceutical research, entails the subsequent addressed introduction of a test sample including one or more analytes into the through-hole wells, with selected materials introduced into subsets of through-holes that may include one or more through-holes. The test sample addressably introduced into the subsets of through-holes may contain drug candidates or known drugs. The test sample may be comprised of multiple components, introduced at the same time or sequentially. Components of the test sample may include analytes, antagonists, reagents, solvents, or any other materials and may be introduced in liquid form or otherwise. In accordance with a preferred embodiment of the invention, test samples are introduced into the through-hole wells in liquid form in order to facilitate rapid reaction via diffusion with first sample 18 already resident in liquid form in the through-holes.
  • [0038]
    The set of substances from which the second sample addressed to a particular through-hole site is drawn is referred to in this description and in the appended claims as a “library” of substances. In typical applications, the library is of a substantial size and thus advantageously utilizes the capability of the present invention to facilitate parallel reaction and analysis of large numbers of substances. In pharmaceutical applications in particular, libraries may be composed of between 103 and 109 substances and combinations of substances.
  • [0039]
    A typical thickness 20 of platen 10 is on the order of 1-2 mm, while through-holes 12 have typical characteristic dimensions (such as diameters) 22 of on the order of 100-400 μm. Thus the volume of each through-hole 12 between surface 14 and surface 16 is on the order of ˜10−7 cm3 or greater. Through-holes 12 are spaced on centers typically on the order of twice the diameter of the holes, although all spacing configurations are within the scope of the invention and of the appended claims. In particular, through-holes 12 may be centered on a rectangular grid, as shown in FIG. 2A, or in a close-packed hexagonal lattice, as shown in FIG. 2B.
  • [0040]
    In accordance with an alternate embodiment of the present invention described with reference to FIG. 3, through-holes 12 may be disposed in an array within a circular sample wafer 300 having a central hole 302 for purposes of centering with respect to handling equipment.
  • [0041]
    Referring again to FIG. 1, platen 10 may be any solid or quasi-solid material into which through-holes 12 may be formed. In particular, in accordance with various embodiments of the invention, platen 10 may be formed from metal, semiconductor, glass, quartz, ceramic or polymer materials, all given without limitation by way of example. In accordance with a preferred embodiment of the invention, platen 10 is formed in a format associated with a compact disk read-only-memory (CD-ROM)-namely that of a polymer disk, approximately 1.2 mm in thickness, and approximately 100 mm in diameter.
  • [0042]
    Platen 10 may also advantageously be formed of a laminate of materials, with a central layer 26 and outer “sandwiching” layers 28. Advantages of this construction for containment of sample 18 will be discussed further below.
  • [0043]
    Through-holes 12 may be formed in platen 10 by means appropriate to the material of platen 10. Through-hole forming methods include, by way of example, laser ablation by means of an ultraviolet (UV) excimer laser which may form 100 μm through-holes in glasses and polymers. Additional through-hole forming techniques include mechanical drilling, electrochemical methods, or selective chemical or charged-particle etching techniques. Additionally, microcapillary bundles of glass fibers of varying compositions may be drawn from preform and sliced to form platens, and then selectively etched to form through-holes.
  • [0044]
    Loading the Through-Hole Microwells
  • [0045]
    On the size scale employed in accordance with embodiments of the invention, where through-holes 12 have aspect ratios of axial length to diameter greater than unity, viscous forces may dominate inertial forces in governing the fluid kinetics of material in the through-hole wells. Consequently, capillary action may be employed to populate through-holes 12 with sample fluid 18. Referring to FIG. 4, two aspects of loading the through-hole wells are described with reference to a sample insertion apparatus 30. Since through-hole microwells 12 are open at both sides, insertion of liquid into the wells does not require that the air displaced by the liquid on insertion flow through the entering fluid, as occurs in the prior art well structure having only a single aperture for influx of liquid and efflux of displaced air. Liquid 32, loaded into reservoir 34 via port 33, may, as discussed above, contain cells or other particles in suspension. Liquid 32 may be forced into through-hole microwells 12 (shown in FIG. 1) by in-line impulsion as by driving platen 10 into liquid 32 by force applied along direction 36 transverse to the plane of platen 10. The transverse piston force may be applied via shaft 38 or in any other manner known in the mechanical arts.
  • [0046]
    In accordance with another embodiment of the invention, liquid may also be loaded through capillary action of liquid 32 along the walls of the through-holes. To provide for wetting of the lower surface of platen 10, the platen is lowered into reservoir 34 and rotated, by torque applied through shaft 38, or otherwise, through an angle typically on the order of a quarter revolution. Alternatively, platen 10 may be wetted and liquid 32 drawn into the microwells by immersing platen 10 into liquid 32 and tilting the platen about an axis in the plane of the platen.
  • [0047]
    Stabilization with Respect to Capillary and Evaporative Liquid Loss
  • [0048]
    In order to maintain the sample in liquid form in the respective microwells, evaporation of the liquid must be avoided. One method of avoiding evaporation is to provide an ambient atmospheric environment of 100% humidity. Among other methods that may be practiced to suppress evaporation, in accordance with an embodiment of the invention, a high molecular-weight fluid, such as various alcohols, for example, may be introduced on each end of the microwells thereby forming molecular monolayers or other thin layers to prevent evaporation of the liquid sample.
  • [0049]
    Referring to FIG. 5, a cross-section of a portion of platen 10 is shown to include through-hole microwell 12. In order to enhance capillary loading of the microwell and to prevent capillary outmigration of the sample liquid, exterior sections 40 of the microwell, adjacent to surfaces 14 and 16 of platen 10, has a hydrophobic wall surface in accordance with a preferred embodiment of the invention, while the interior section 42 of the through-hole wall has a hydrophilic surface thereby preferentially attracting an aqueous liquid sample. Typically, the interior ˜160 μm segment of the microwell may have a hydrophilic wall surface, while the hydrophobic layers on either end of the well are on the order of 20 μm in length. On loading the sample liquid into the microwells, typically 10% of the well, on either end, is left unfilled, and subsequent test samples in liquid form will rapidly diffuse to hydrophilic center of microwell thereby mixing with the liquid already present.
  • [0050]
    Optical Interrogation
  • [0051]
    Depending upon the application to which the present invention is applied, the result of the reaction of the first sample in liquid form with subsequently added analytes may be read out in a wide variety of manners known to persons skilled in the biological or biochemical arts. Readout systems may employ taggants of various sorts allowing interrogation of the sample within the addressable microwell to determine whether a specified reaction has occurred. Some reactions may be interrogated optically, to include, without limitation, such optical methods as colorimetric or fluorometric methods, or resonant or non-resonant scattering methods, including Raman spectroscopic methods.
  • [0052]
    Referring now to FIG. 6, optical interrogation methods, of which the foregoing are but examples, may be implemented, in accordance with an embodiment of the invention by coupling a light beam 50 into through-hole 12 of platen 10 and detecting light 52 emergent from the opposite aperture of through-hole 12 by detectors 54 constituting detector array 56. Alternatively, light returned by scattering in the original direction can be collected and analyzed using standard optical techniques. In order to optimize the signal-to-noise of the optical signal, the beam shape and through-hole volume are preferably matched. In accordance with a preferred embodiment of the invention, optical matching to a through-hole of cylindrical cross-section and of aspect ratio greater than one is achieved through a confocal optical geometry in which an initially collimated beam 50 is transformed by optical element 58 into a beam having a diffraction limited focus at the center 60 of through-hole 12. The emergent optical beam 52 is collected and focussed onto detector array 56 by optical element 60. Superior optical sampling of the volume of the through-hole may be obtained if the through-hole has a rectangular cross-section, and if the optical radiation is guided by the walls of the through-hole in the manner of a waveguide. Optical element 58 and 60 may be lenses or mirrors or combinations thereof as well known to persons skilled in the optical arts. Detector array 56 may be a charge-coupled device (CCD) array, for example, and, in one embodiment of the invention, a 1000×1000 element format is employed, with each through-hole imaged onto three elements 54 of the detector array. A window 62 may be disposed between platen 10 and detector array 56 and may be dried using standard techniques if the assay is conducted in a humid ambient environment as discussed above. Alternatively, beam 50, coupled into through-hole 12 by coupling element 58 may be guided, in the manner of a guided wave through a waveguide, by the walls 62 of through-hole 12 in order to provide efficient interrogation of the sampled volume within the through-hole.
  • [0053]
    In some cases, where the material of platen 10 is not entirely opaque at the wavelengths of interrogating optical beam 50, wall 62 of through-hole 12 may be coated to prevent light leakage and cross-talk among the addressable sample volumes.
  • [0054]
    [0054]FIG. 7 shows a preferred embodiment of the present invention in which platen 10 is configured in the CD-ROM format described above, with interrogating optical source 50 capable of travel in radial direction 68 while platen 10 rotates about center 66. Optical detector array 56 may translate in conjunction with source 50, in accordance with an embodiment of the invention.
  • [0055]
    Continuous Process Analysis
  • [0056]
    Referring to FIG. 8, in accordance with an advantageous embodiment of the present invention, platen 10, which may be a flexible polymeric substance, for example, is conveyed in a direction 70 past an optical interrogation system comprising an optical source 72 and a detector array 74. Samples in liquid form may be loaded into through-holes 12 and advanced at a rate governed by the relevant reaction times so that a row 76 is interrogated optically at the period during which a specified indication is expected.
  • [0057]
    Mixing and Dilution
  • [0058]
    Referring now to FIG. 9, a cross-sectional view is shown of portions of a first platen 90 and a second platen 92 brought into proximity with each other in anticipation of processes performed in accordance with embodiments of the present invention for preparing, mixing, or diluting liquid samples. Through-holes 12 of platen 90 are shown as having been loaded with liquid samples 94 which may be identical across some specified subset of through-holes 12, or may be identical for the entire platen. Liquid sample 94, as shown schematically, may include cells or other targets 96 in solution within a solvent 98.
  • [0059]
    Through-holes 12 of second platen 92 is shown as having been loaded with liquid samples 100 and 102 shown comprising one or more solvents or other agents. In particular, platen 92 may have been populated with a library of distinct compounds, each of which is to be exposed to target 96 of platen 90.
  • [0060]
    [0060]FIG. 10 shows platens 90 and 92 of FIG. 9 having been brought into contact with one another, in such a manner as to allow through-holes of the respective platens to register on a one-to-one basis. The mating of protrusions 8 with indentations 6 of respective platens facilitates the registration of through-holes, and provides for the mixing of the liquid sample contents of the respective through-holes. Thus, as shown, half of targets 96 from samples 94 of first platen 90 have migrated to the solvent of samples 100 and 102. Mixing or dilution may be facilitated in this manner, either through ordinary statistical diffusion, or by any method employed to facilitate mixing. Mixing may be enhanced, for example, by the creation of thermal eddy currents and turbulence induced by laser irradiation. Mixing rates have been found to be enhanced in this way by more than an order of magnitude. Any other mixing techniques, including acoustic perturbation or stirring of the samples with micropipettes, for example, are within the scope of the present invention as described herein and as claimed in any appended claims.
  • [0061]
    The number of platens 90 and 92 that may be stacked, in accordance with the present invention, is not limited to two, as shown in FIGS. 9 and 10 by way of example only. Thus, the concentration of targets 96 in solvent 98 may be diluted to a specified degree by stacking a corresponding number of platens with registered through-holes and allowing migration of targets 96 throughout the liquid contained within the corresponding sample volumes of the stack.
  • [0062]
    Transportation of Biological Samples
  • [0063]
    The perforated platen described herein in accordance an embodiment of the present invention may be employed, for example, for shipping samples of a uniform strain of cells to laboratories. In this application, the cells or other biological sample may be introduced into the through-hole wells of the invention in aqueous or other liquid suspension. The liquid carrier is then evaporated, allowing the cells or other biological samples to form a coating, in the form of a chimney, of the walls of the plurality of through-hole wells. The samples may then subsequently be resuspended by wetting and further analytes may be introduced.
  • [0064]
    The described embodiments of the invention are intended to be merely exemplary and numerous variations and modifications will be apparent to those skilled in the art. All such variations and modifications are intended to be within the scope of the present invention as defined in the appended claims.

Claims (12)

    I claim:
  1. 1. A method for analyzing specified properties of a set of substances, the method comprising:
    a. providing a platen having two substantially parallel planar surfaces, an inner layer of hydrophilic material and two outer layers of hydrophobic material coupled to opposite sides of the inner layer, and a two-dimensional array of addressable through-holes having an areal density of at least 1.6 through-holes per square millimeter,
    b. retaining a set of distinct substances in respective through-holes of the array in such a manner that a first through-hole contains a first substance distinct from a second substance contained in an adjacent through-hole to the first through-hole;
    c. adding a liquid into at least one of the through-holes containing a substance for permitting a reaction between the liquid and the substance; and
    d. characterizing contents of distinct through-holes in terms of the specified properties.
  2. 2. A method according to claim 1, wherein the set of different substances includes a reagent.
  3. 3. A method according to claim 1, wherein the set of different substances comprises a library of at least 1000 substances.
  4. 4. A method according to claim 1, wherein the set of different substances include optical taggants.
  5. 5. A method according to claim 1, wherein the step of retaining the set of distinct substances further includes:
    loading the set of distinct substances in one of liquid solution and suspension; and
    forming coatings of the distinct substances so as to retain the distinct substances on walls of the through-holes.
  6. 6. A method according to claim 1, wherein the step of adding a liquid includes adding a liquid substantially uniformly to the through-holes of the array.
  7. 7. A method according to claim 6, wherein the step of adding a liquid includes resuspending the distinct substances in liquid by means of wetting.
  8. 8. A method according to claim 1, wherein the step of characterizing contents of distinct through-holes includes characterizing by optical methods.
  9. 9. A method according to claim 8, wherein the step of characterizing contents of distinct through-holes includes characterizing by fluorometric methods.
  10. 10. A platen for retaining biological samples, the platen comprising:
    a. an inner layer of hydrophilic material and two outer layers of hydrophobic material coupled to opposite sides of the inner layer;
    b. a two-dimensional array of addressable through-holes having an areal density of at least 1.6 through-holes per square millimeter,
    c. a set of distinct substances in respective through-holes of the array.
  11. 11. A platen according to claim 10, wherein distinct substances of the set of distinct substances are coated on walls of the through-holes.
  12. 12. A platen according to claim 10, wherein distinct substances of the the set of distinct substances are retained within through-holes of the platen by surface tension.
US10796856 1998-01-12 2004-03-09 Method and apparatus for performing microassays Abandoned US20040171166A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US7117998 true 1998-01-12 1998-01-12
US09225583 US6387331B1 (en) 1998-01-12 1999-01-05 Method and apparatus for performing microassays
US09710082 US6743633B1 (en) 1998-01-12 2000-11-10 Method for performing microassays
US10796856 US20040171166A1 (en) 1998-01-12 2004-03-09 Method and apparatus for performing microassays

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10796856 US20040171166A1 (en) 1998-01-12 2004-03-09 Method and apparatus for performing microassays
US12794353 US20110065590A1 (en) 1998-01-12 2010-06-04 Method and Apparatus for Performing Microassays

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09710082 Division US6743633B1 (en) 1998-01-12 2000-11-10 Method for performing microassays

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12794353 Continuation US20110065590A1 (en) 1998-01-12 2010-06-04 Method and Apparatus for Performing Microassays

Publications (1)

Publication Number Publication Date
US20040171166A1 true true US20040171166A1 (en) 2004-09-02

Family

ID=22099761

Family Applications (6)

Application Number Title Priority Date Filing Date
US09225583 Active 2019-01-17 US6387331B1 (en) 1998-01-12 1999-01-05 Method and apparatus for performing microassays
US09710082 Active US6743633B1 (en) 1998-01-12 2000-11-10 Method for performing microassays
US10796856 Abandoned US20040171166A1 (en) 1998-01-12 2004-03-09 Method and apparatus for performing microassays
US12794353 Abandoned US20110065590A1 (en) 1998-01-12 2010-06-04 Method and Apparatus for Performing Microassays
US14301325 Abandoned US20150126412A1 (en) 1998-01-12 2014-06-10 Systems for filling a sample array by droplet dragging
US14582122 Abandoned US20170028376A9 (en) 1998-01-12 2014-12-23 Systems for Filling a Sample Array by Droplet Dragging

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US09225583 Active 2019-01-17 US6387331B1 (en) 1998-01-12 1999-01-05 Method and apparatus for performing microassays
US09710082 Active US6743633B1 (en) 1998-01-12 2000-11-10 Method for performing microassays

Family Applications After (3)

Application Number Title Priority Date Filing Date
US12794353 Abandoned US20110065590A1 (en) 1998-01-12 2010-06-04 Method and Apparatus for Performing Microassays
US14301325 Abandoned US20150126412A1 (en) 1998-01-12 2014-06-10 Systems for filling a sample array by droplet dragging
US14582122 Abandoned US20170028376A9 (en) 1998-01-12 2014-12-23 Systems for Filling a Sample Array by Droplet Dragging

Country Status (7)

Country Link
US (6) US6387331B1 (en)
EP (3) EP2286918B1 (en)
JP (3) JP4271371B2 (en)
CA (1) CA2316912C (en)
DE (3) DE69930726T2 (en)
ES (1) ES2350702T3 (en)
WO (1) WO1999034920A1 (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040129676A1 (en) * 2003-01-07 2004-07-08 Tan Roy H. Apparatus for transfer of an array of liquids and methods for manufacturing same
US20070003448A1 (en) * 2004-03-12 2007-01-04 Kanigan Tanya S Nanoliter array loading
US20070017870A1 (en) * 2003-09-30 2007-01-25 Belov Yuri P Multicapillary device for sample preparation
US20070075007A1 (en) * 2003-09-30 2007-04-05 Belov Yuri P Multicapillary column for chromatography and sample preparation
US20080108112A1 (en) * 2000-02-18 2008-05-08 Biotrove, Inc. Apparatus and methods for parallel processing of micro-volume liquid reactions
US7666360B2 (en) 1999-03-19 2010-02-23 Biotrove, Inc. Multi-through hole testing plate for high throughput screening
US7682565B2 (en) 2002-12-20 2010-03-23 Biotrove, Inc. Assay apparatus and method using microfluidic arrays
US20110092686A1 (en) * 2008-03-28 2011-04-21 Pelican Group Holdings, Inc. Multicapillary sample preparation devices and methods for processing analytes
US7972778B2 (en) 1997-04-17 2011-07-05 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
US8029745B2 (en) 1998-01-12 2011-10-04 Massachusetts Institute Of Technology Systems for filling a sample array by droplet dragging
US8277753B2 (en) 2002-08-23 2012-10-02 Life Technologies Corporation Microfluidic transfer pin
US8906618B2 (en) 2000-02-18 2014-12-09 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for parallel processing of micro-volume liquid reactions
US20150044686A1 (en) * 2012-03-16 2015-02-12 Life Technologies Corporation Systems and Methods for Containing Biological Samples
US20150126412A1 (en) * 1998-01-12 2015-05-07 Massachusetts Institute Of Technology Systems for filling a sample array by droplet dragging
WO2017004502A1 (en) * 2015-07-02 2017-01-05 Centrillion Technology Holdings Corporation Systems and methods to dispense and mix reagents

Families Citing this family (138)

* 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
US7122338B2 (en) * 1995-11-14 2006-10-17 Biocontrol Systems, Inc. Method for quantification of biological material in a sample
US6090251A (en) 1997-06-06 2000-07-18 Caliper Technologies, Inc. Microfabricated structures for facilitating fluid introduction into microfluidic devices
US6794127B1 (en) * 1997-06-16 2004-09-21 Diversa Corporation Capillary array-based sample screening
US7019827B2 (en) 1997-06-16 2006-03-28 Diversa Corporation GigaMatrix holding tray having through-hole wells
US6972183B1 (en) 1997-06-16 2005-12-06 Diversa Corporation Capillary array-based enzyme screening
US7282240B1 (en) * 1998-04-21 2007-10-16 President And Fellows Of Harvard College Elastomeric mask and use in fabrication of devices
DE60031015T2 (en) 1999-02-16 2007-05-10 Applera Corp., Foster City Device for handling beads
US6296702B1 (en) 1999-03-15 2001-10-02 Pe Corporation (Ny) Apparatus and method for spotting a substrate
US6555389B1 (en) 1999-05-11 2003-04-29 Aclara Biosciences, Inc. Sample evaporative control
US6977145B2 (en) 1999-07-28 2005-12-20 Serono Genetics Institute S.A. Method for carrying out a biochemical protocol in continuous flow in a microreactor
WO2001019502A3 (en) * 1999-09-17 2001-08-09 Brian Foley High throughput screening card
DE19964337B4 (en) * 1999-10-01 2004-09-16 Agilent Technologies, Inc. (n.d.Ges.d.Staates Delaware), Palo Alto Microfluidic microchip with abbiegbarem intake
US20020164824A1 (en) * 2001-02-16 2002-11-07 Jianming Xiao Method and apparatus based on bundled capillaries for high throughput screening
US20040014102A1 (en) * 2000-02-22 2004-01-22 Shiping Chen High density parallel printing of microarrays
WO2001062377A3 (en) 2000-02-22 2002-03-14 Anthony C Chen Microarray fabrication techniques and apparatus
EP1257355A2 (en) 2000-02-22 2002-11-20 Genospectra, Inc. Microarray fabrication techniques and apparatus
US20020055111A1 (en) * 2000-08-25 2002-05-09 Shiping Chen Three-dimensional probe carriers
US20100261159A1 (en) 2000-10-10 2010-10-14 Robert Hess Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
JP4361271B2 (en) * 2000-10-10 2009-11-11 バイオトローブ・インコーポレイテツド Assay, synthesis, and instruments for storage, as well as methods of making, using, and operation
US6937323B2 (en) * 2000-11-08 2005-08-30 Burstein Technologies, Inc. Interactive system for analyzing biological samples and processing related information and the use thereof
US6936811B2 (en) * 2000-11-13 2005-08-30 Genoptix, Inc. Method for separating micro-particles
US20030194755A1 (en) * 2001-04-27 2003-10-16 Genoptix, Inc. Early detection of apoptotic events and apoptosis using optophoretic analysis
US20040023310A1 (en) * 2001-04-27 2004-02-05 Genoptix, Inc Quantitative determination of protein kinase C activation using optophoretic analysis
US20020121443A1 (en) * 2000-11-13 2002-09-05 Genoptix Methods for the combined electrical and optical identification, characterization and/or sorting of particles
US20030124516A1 (en) * 2001-04-27 2003-07-03 Genoptix, Inc. Method of using optical interrogation to determine a biological property of a cell or population of cells
US20020160470A1 (en) * 2000-11-13 2002-10-31 Genoptix Methods and apparatus for generating and utilizing linear moving optical gradients
US20020123112A1 (en) * 2000-11-13 2002-09-05 Genoptix Methods for increasing detection sensitivity in optical dielectric sorting systems
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
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
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
WO2002043866A3 (en) * 2000-12-01 2003-03-06 Burstein Technologies Inc Apparatus and methods for separating components of particulate suspension
US6995845B2 (en) * 2000-12-08 2006-02-07 Burstein Technologies, Inc. Methods for detecting analytes using optical discs and optical disc readers
US6760298B2 (en) * 2000-12-08 2004-07-06 Nagaoka & Co., Ltd. Multiple data layer optical discs for detecting analytes
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
FR2820058B1 (en) 2001-01-29 2004-01-30 Commissariat Energie Atomique Method and system for performing a streaming protocol biological, chemical or biochemical
US20030087309A1 (en) * 2001-08-27 2003-05-08 Shiping Chen Desktop drug screening system
WO2003087827A8 (en) 2001-04-11 2004-11-11 Burstein Technologies Inc Multi-parameter assays including analysis discs and methods relating thereto
US20040033539A1 (en) * 2002-05-01 2004-02-19 Genoptix, Inc Method of using optical interrogation to determine a biological property of a cell or population of cells
US20040009540A1 (en) * 2001-04-27 2004-01-15 Genoptix, Inc Detection and evaluation of cancer cells using optophoretic analysis
US20030007894A1 (en) * 2001-04-27 2003-01-09 Genoptix Methods and apparatus for use of optical forces for identification, characterization and/or sorting of particles
US20030211461A1 (en) * 2002-05-01 2003-11-13 Genoptix, Inc Optophoretic detection of durgs exhibiting inhibitory effect on Bcr-Abl positive tumor cells
WO2002087760A1 (en) * 2001-04-30 2002-11-07 Epr Labautomation Ag Method and device for storing and dosing small quantities of liquid
US20020171838A1 (en) * 2001-05-16 2002-11-21 Pal Andrew Attila Variable sampling control for rendering pixelization of analysis results in a bio-disc assembly and apparatus relating thereto
US20040166593A1 (en) * 2001-06-22 2004-08-26 Nolte David D. Adaptive interferometric multi-analyte high-speed biosensor
US6685885B2 (en) * 2001-06-22 2004-02-03 Purdue Research Foundation Bio-optical compact dist system
WO2003027723A2 (en) * 2001-07-24 2003-04-03 Burstein Technologies, Inc. Method and apparatus for bonded fluidic circuit for optical bio-disc
US20030032198A1 (en) * 2001-08-13 2003-02-13 Symyx Technologies, Inc. High throughput dispensing of fluids
GB0120131D0 (en) 2001-08-17 2001-10-10 Micromass Ltd Maldi target plate
US20030124599A1 (en) * 2001-11-14 2003-07-03 Shiping Chen Biochemical analysis system with combinatorial chemistry applications
WO2003055589A3 (en) * 2001-12-31 2003-11-06 Jens Albert Microtiter plate for parallel micro synthesis, especially at high temperatures
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
US20040241381A1 (en) * 2002-01-31 2004-12-02 Chen Yihfar Microfluidic structures with circumferential grooves for bonding adhesives and related optical analysis discs
WO2003064996A2 (en) * 2002-01-31 2003-08-07 Burstein Technologies, Inc. Bio-safe dispenser and optical analysis disc assembly
US7251210B2 (en) * 2002-01-31 2007-07-31 Burstein Technologies, Inc. Method for triggering through disc grooves and related optical analysis discs and system
US20050221048A1 (en) * 2002-01-31 2005-10-06 James Rodney Norton Manufacturing processes for making optical analysis discs including successive patterning operations and optical discs thereby manufactured
US20050023765A1 (en) * 2002-01-31 2005-02-03 Coombs James Howard Bio-safety features for optical analysis disc and disc system including same
FR2835614A1 (en) * 2002-02-07 2003-08-08 Antonios Vekris Device for analyzing molecules, useful for nucleic acid or protein interaction assays, comprises fluid-containing chamber in which binding carrier is rotated
FR2835615B1 (en) * 2002-02-07 2004-09-17 Antonios Vekris Device for analyzing a molecule by means of a fluid coming into contact with a support bearing a molecule
US6764818B2 (en) 2002-02-25 2004-07-20 Diversa Corporation Device for effecting heat transfer with a solution held in a through-hole well of a holding tray
US6918738B2 (en) 2002-03-11 2005-07-19 Diversa Corporation Stackable sample holding plate with robot removable lid
US6798520B2 (en) 2002-03-22 2004-09-28 Diversa Corporation Method for intensifying the optical detection of samples that are held in solution in the through-hole wells of a holding tray
US20030208936A1 (en) * 2002-05-09 2003-11-13 Lee Charles Hee Method for manufacturing embroidery decorated cards and envelopes
US8349276B2 (en) 2002-09-24 2013-01-08 Duke University Apparatuses and methods for manipulating droplets on a printed circuit board
US6911132B2 (en) * 2002-09-24 2005-06-28 Duke University Apparatus for manipulating droplets by electrowetting-based techniques
US7329545B2 (en) * 2002-09-24 2008-02-12 Duke University Methods for sampling a liquid flow
US20040121307A1 (en) * 2002-12-19 2004-06-24 Genoptix, Inc Early detection of cellular differentiation using optophoresis
US20040121474A1 (en) * 2002-12-19 2004-06-24 Genoptix, Inc Detection and evaluation of chemically-mediated and ligand-mediated t-cell activation using optophoretic analysis
US20060094108A1 (en) * 2002-12-20 2006-05-04 Karl Yoder Thermal cycler for microfluidic array assays
JP2007501407A (en) * 2003-03-03 2007-01-25 バースタイン テクノロジーズ,インコーポレイティド The use of optical bio-disc for performing the method, apparatus, and this is used in detection and quantification of diverse cell types
WO2004095034A1 (en) * 2003-04-23 2004-11-04 Nagaoka & Co., Ltd. Optical bio-discs including spiral fluidic circuits for performing assays
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
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
JP2007500351A (en) * 2003-07-25 2007-01-11 バースタイン テクノロジーズ,インコーポレイティド The method associated with the fluid circuit and its sample preparation having a bio-disc
CN1860363B (en) * 2003-08-28 2011-12-28 赛路拉公司 A method and apparatus for using an optical switch to the microfluidic channel network cell sorting
US7063216B2 (en) 2003-09-04 2006-06-20 Millipore Corporation Underdrain useful in the construction of a filtration device
US7407630B2 (en) * 2003-09-19 2008-08-05 Applera Corporation High density plate filler
US7998435B2 (en) * 2003-09-19 2011-08-16 Life Technologies Corporation High density plate filler
US20060233673A1 (en) * 2003-09-19 2006-10-19 Beard Nigel P High density plate filler
US20050280811A1 (en) * 2003-09-19 2005-12-22 Donald Sandell Grooved high density plate
US20050226782A1 (en) * 2003-09-19 2005-10-13 Reed Mark T High density plate filler
US9492820B2 (en) 2003-09-19 2016-11-15 Applied Biosystems, Llc High density plate filler
US20050232821A1 (en) * 2003-09-19 2005-10-20 Carrillo Albert L High density plate filler
US20060272738A1 (en) * 2003-09-19 2006-12-07 Gary Lim High density plate filler
US20050225751A1 (en) * 2003-09-19 2005-10-13 Donald Sandell Two-piece high density plate
US8277760B2 (en) * 2003-09-19 2012-10-02 Applied Biosystems, Llc High density plate filler
US20060233671A1 (en) * 2003-09-19 2006-10-19 Beard Nigel P High density plate filler
US20050220675A1 (en) * 2003-09-19 2005-10-06 Reed Mark T High density plate filler
US7695688B2 (en) * 2003-09-19 2010-04-13 Applied Biosystems, Llc High density plate filler
US8753588B2 (en) 2003-10-15 2014-06-17 Emd Millipore Corporation Support and stand-off ribs for underdrain for multi-well device
WO2005081801A3 (en) * 2004-02-09 2005-11-10 Blueshift Biotechnologies Inc Methods and apparatus for scanning small sample volumes
EP1761331A2 (en) * 2004-06-07 2007-03-14 Bioprocessors Corporation Control of reactor environmental conditions
DE102004041941B4 (en) * 2004-08-30 2007-01-11 P.A.L.M. Microlaser Technologies Ag A process for the recovery of biological objects with a receiving unit
US20060105453A1 (en) * 2004-09-09 2006-05-18 Brenan Colin J Coating process for microfluidic sample arrays
US20060229531A1 (en) * 2005-02-01 2006-10-12 Daniel Goldberger Blood monitoring system
US7608042B2 (en) * 2004-09-29 2009-10-27 Intellidx, Inc. Blood monitoring system
US20070191716A1 (en) * 2004-09-29 2007-08-16 Daniel Goldberger Blood monitoring system
US7981364B2 (en) * 2004-12-07 2011-07-19 Honeywell Analytics Ag Gas detection method and system
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
US20070023643A1 (en) * 2005-02-01 2007-02-01 Nolte David D Differentially encoded biological analyzer planar array apparatus and methods
JP5011650B2 (en) * 2005-04-01 2012-08-29 パナソニック株式会社 Light detection method
WO2006113492A3 (en) * 2005-04-14 2006-12-07 Harvard College Adjustable solubility in sacrificial layers for microfabrication
US20070047388A1 (en) * 2005-08-25 2007-03-01 Rockwell Scientific Licensing, Llc Fluidic mixing structure, method for fabricating same, and mixing method
WO2007054220A1 (en) * 2005-11-09 2007-05-18 Christian Schmidt Methods and devices for surface modification of micro-structured substrates
US20080200838A1 (en) * 2005-11-28 2008-08-21 Daniel Goldberger Wearable, programmable automated blood testing system
JP4861042B2 (en) * 2006-04-17 2012-01-25 株式会社日立ハイテクマニファクチャ&サービス Spectrophotometer
US20070259366A1 (en) * 2006-05-03 2007-11-08 Greg Lawrence Direct printing of patterned hydrophobic wells
US8092385B2 (en) * 2006-05-23 2012-01-10 Intellidx, Inc. Fluid access interface
WO2008046112A1 (en) * 2006-10-13 2008-04-17 Eliseev Alexey V Methods and microarrays compatible with dual functionality optical drives
US20080230605A1 (en) * 2006-11-30 2008-09-25 Brian Weichel Process and apparatus for maintaining data integrity
US7522282B2 (en) * 2006-11-30 2009-04-21 Purdue Research Foundation Molecular interferometric imaging process and apparatus
US20080144899A1 (en) * 2006-11-30 2008-06-19 Manoj Varma Process for extracting periodic features from images by template matching
WO2008089495A3 (en) * 2007-01-19 2008-10-09 Purdue Research Foundation System with extended range of molecular sensing through integrated multi-modal data acquisition
CA2681722A1 (en) * 2007-03-26 2008-10-02 Purdue Research Foundation Method and apparatus for conjugate quadrature interferometric detection of an immunoassay
WO2009021233A3 (en) 2007-08-09 2009-04-23 Advanced Liquid Logic Inc Pcb droplet actuator fabrication
JP5295733B2 (en) 2007-11-30 2013-09-18 キヤノン株式会社 Method of holding the living body, a method of testing a biological, growth method of a living body, living body holding sheet and the biological treatment device
JP4518157B2 (en) * 2008-01-31 2010-08-04 カシオ計算機株式会社 Imaging device and program
US8563326B2 (en) * 2008-03-31 2013-10-22 Qiagen Lake Constance Gmbh Sample holder and method of using the same
EP2395346A3 (en) * 2008-04-17 2013-10-16 QIAGEN Lake Constance GmbH Fluorescence standard and use of same
JP5283113B2 (en) * 2008-10-03 2013-09-04 独立行政法人産業技術総合研究所 Volumetric method and apparatus for trace droplet
US8753290B2 (en) * 2009-03-27 2014-06-17 Intellectual Inspiration, Llc Fluid transfer system and method
JP5550262B2 (en) * 2009-05-29 2014-07-16 キヤノン株式会社 Sample observation system and sample observation method
EP2519452A1 (en) * 2009-12-31 2012-11-07 Basf Se Tampering detector and method
GB201001487D0 (en) * 2010-01-29 2010-03-17 Cunningham Kenneth J Disposable light scattering cuvette
KR101660784B1 (en) * 2011-12-19 2016-09-28 야마하하쓰도키 가부시키가이샤 Object selecting device and object selecting method
KR101309129B1 (en) 2012-03-15 2013-09-16 주식회사 메카시스 Sample handler for analyzing a small quantity of sample, analyzing apparatus using the sample handler, and analyzing method
RU2014140835A (en) 2012-03-16 2016-05-10 Лайф Текнолоджис Корпорейшн Systems and methods for analyzing biological samples
JP5483134B2 (en) * 2012-10-09 2014-05-07 独立行政法人産業技術総合研究所 Volumetric method and apparatus for trace droplet
KR101387576B1 (en) 2012-11-08 2014-04-23 주식회사 신코 Micro-volume sample holder
US8711351B1 (en) 2013-01-29 2014-04-29 Hewlett-Packard Development Company, L.P. Scattering spectroscopy employing hotspot-aligned nanopores
CA2948976A1 (en) * 2014-05-14 2015-11-19 University Of Limerick Method for testing compounds on living cells
EP3043172A1 (en) * 2015-01-06 2016-07-13 Rolls-Royce plc Method and apparatus for testing of engine components

Citations (90)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6436632B1 (en) *
US2771398A (en) * 1953-09-17 1956-11-20 Thomas L Snyder Method and apparatus for counting microorganisms
US3645696A (en) * 1970-04-30 1972-02-29 Cities Service Oil Co Method for stabilizing chromogenic test reagent for aldehyde
US3768974A (en) * 1971-03-22 1973-10-30 Sterilizer Control Royalties Disposable colorimetric indicator device for measuring the concentration of chlorine in water
US3770383A (en) * 1971-04-05 1973-11-06 Akzona Inc Diagnostic test slide
US3873268A (en) * 1971-07-06 1975-03-25 Pfizer Multiple solution testing device
US3894512A (en) * 1971-02-18 1975-07-15 Ohno Res & Dev Lab Electrostatic developing apparatus
US3950133A (en) * 1971-10-20 1976-04-13 Mallinckrodt, Inc. Reagent formulations for assaying biological specimens and methods of preparing and using same
US3994594A (en) * 1975-08-27 1976-11-30 Technicon Instruments Corporation Cuvette and method of use
US4088448A (en) * 1975-09-29 1978-05-09 Lilja Jan Evert Apparatus for sampling, mixing the sample with a reagent and making particularly optical analyses
US4111754A (en) * 1976-11-29 1978-09-05 Hydow Park Immunological testing devices and methods
US4234316A (en) * 1979-04-02 1980-11-18 Fmc Corporation Device for delivering measured quantities of reagents into assay medium
US4387164A (en) * 1980-11-05 1983-06-07 Fmc Corporation Method and apparatus for chemical analysis using reactive reagents dispersed in soluble film
US4407943A (en) * 1976-12-16 1983-10-04 Millipore Corporation Immobilized antibody or antigen for immunoassay
US4415732A (en) * 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4446239A (en) * 1981-04-24 1984-05-01 Chugai Seiyaku Kabushiki Kaisha Light scattering immunoassay involving particles with selective frequency band apparatus
US4493815A (en) * 1983-07-28 1985-01-15 Bio-Rad Laboratories, Inc. Supporting and filtering biochemical test plate assembly
US4500707A (en) * 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4562045A (en) * 1981-10-07 1985-12-31 Murata Manufacturing Co. Carrier for holding analytical samples
US4562871A (en) * 1984-03-16 1986-01-07 Astle Thomas W Rehydrator
US4682891A (en) * 1985-05-31 1987-07-28 Health Research, Incorporated Microcircle system
US4682890A (en) * 1985-05-31 1987-07-28 Health Research, Incorporated Microsample holder and carrier therefor
US4761378A (en) * 1983-03-04 1988-08-02 American Home Products Corp. (Del.) Microbiological testing apparatus
US4806316A (en) * 1987-03-17 1989-02-21 Becton, Dickinson And Company Disposable device for use in chemical, immunochemical and microorganism analysis
US4828386A (en) * 1987-06-19 1989-05-09 Pall Corporation Multiwell plates containing membrane inserts
US4834946A (en) * 1987-02-05 1989-05-30 Levin Andrew E Apparatus for blot screening numerous, small volume, antibody solutions
US4861448A (en) * 1982-11-18 1989-08-29 The Trustees Of Columbia University In The City Of New York Electrophoretic methods employing gel inserts
US4973679A (en) * 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US5000921A (en) * 1986-10-24 1991-03-19 Hanaway Richard W Multiple pipette samples
US5047215A (en) * 1985-06-18 1991-09-10 Polyfiltronics, Inc. Multiwell test plate
US5108704A (en) * 1988-09-16 1992-04-28 W. R. Grace & Co.-Conn. Microfiltration apparatus with radially spaced nozzles
US5153319A (en) * 1986-03-31 1992-10-06 University Patents, Inc. Process for preparing polynucleotides
US5182082A (en) * 1991-01-23 1993-01-26 Becton, Dickinson And Company Multiple aliquot device for distributing a liquid solution into a well
US5183761A (en) * 1989-07-21 1993-02-02 Freeman Mary J Method of making calibration solution for verifying calibration and linearity of vertical photometers
US5210021A (en) * 1991-03-20 1993-05-11 Neuro Probe, Inc. Multiple-site chemotactic test apparatus and method
US5215593A (en) * 1991-01-09 1993-06-01 Canon Kabushiki Kaisha Method of introducing liquid into small-diameter hole
US5234666A (en) * 1990-11-01 1993-08-10 Mitsubishi Denki K.K. Alcohol content detector
US5262128A (en) * 1989-10-23 1993-11-16 The United States Of America As Represented By The Department Of Health And Human Services Array-type multiple cell injector
US5284753A (en) * 1991-03-20 1994-02-08 Neuro Probe, Inc. Multiple-site chemotactic test apparatus and method
US5290705A (en) * 1992-01-13 1994-03-01 R. E. Davis Chemical Corporation Speciman support for optical analysis
US5374525A (en) * 1992-09-30 1994-12-20 University Of Utah Research Foundation Methods to determine predisposition to hypertension and association of variant angiotensinogen gene and hypertension
US5453252A (en) * 1994-02-25 1995-09-26 Truett; William L. Screen cell for spectroscopy
US5455934A (en) * 1993-03-23 1995-10-03 Eclipse Technologies, Inc. Fault tolerant hard disk array controller
US5506141A (en) * 1982-05-10 1996-04-09 Bar-Ilan University Apertured cell carrier
US5508200A (en) * 1992-10-19 1996-04-16 Tiffany; Thomas Method and apparatus for conducting multiple chemical assays
US5510270A (en) * 1989-06-07 1996-04-23 Affymax Technologies N.V. Synthesis and screening of immobilized oligonucleotide arrays
US5519218A (en) * 1993-08-04 1996-05-21 Chang; On Kok Sample holder for spectroscopy
US5560811A (en) * 1995-03-21 1996-10-01 Seurat Analytical Systems Incorporated Capillary electrophoresis apparatus and method
US5599664A (en) * 1989-04-05 1997-02-04 New York University Method for characterizing polymer molecules or the like
US5605662A (en) * 1993-11-01 1997-02-25 Nanogen, Inc. Active programmable electronic devices for molecular biological analysis and diagnostics
US5609828A (en) * 1995-05-31 1997-03-11 bio M erieux Vitek, Inc. Sample card
US5621094A (en) * 1990-05-14 1997-04-15 Quadrant Holdings Cambridge Limited Method of preserving agarose gel structure during dehydration by adding a non-reducing glycoside of a straight-chain sugar alcohol
US5632957A (en) * 1993-11-01 1997-05-27 Nanogen Molecular biological diagnostic systems including electrodes
US5744101A (en) * 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US5763263A (en) * 1995-11-27 1998-06-09 Dehlinger; Peter J. Method and apparatus for producing position addressable combinatorial libraries
US5770860A (en) * 1996-07-12 1998-06-23 Franzen; Jochen Method for loading sample supports for mass spectrometers
US5770440A (en) * 1995-06-27 1998-06-23 Becton Dickinson And Company Apparatus for the early detection of microorganisms
US5773238A (en) * 1995-07-07 1998-06-30 Shukla; Ashok K. Droplet chemical reaction chamber
US5786226A (en) * 1995-03-16 1998-07-28 Boehringer Mannheim Gmbh Quantitative transmission spectroscopy using sample carriers with nets
US5795748A (en) * 1996-09-26 1998-08-18 Becton Dickinson And Company DNA microwell device and method
US5807522A (en) * 1994-06-17 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods for fabricating microarrays of biological samples
US5840862A (en) * 1994-02-11 1998-11-24 Institut Pasteur Process for aligning, adhering and stretching nucleic acid strands on a support surface by passage through a meniscus
US5843767A (en) * 1993-10-28 1998-12-01 Houston Advanced Research Center Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions
US5849598A (en) * 1996-03-15 1998-12-15 Washington University Method for transferring micro quantities of liquid samples to discrete locations
US5856100A (en) * 1995-12-08 1999-01-05 The Institute Of Physical And Chemical Research Method for purification and transfer to separation/detection systems of DNA sequencing samples and plates used therefor
US5888723A (en) * 1992-02-18 1999-03-30 Johnson & Johnson Clinical Diagnostics, Inc. Method for nucleic acid amplification and detection using adhered probes
US5910287A (en) * 1997-06-03 1999-06-08 Aurora Biosciences Corporation Low background multi-well plates with greater than 864 wells for fluorescence measurements of biological and biochemical samples
US5922604A (en) * 1997-06-05 1999-07-13 Gene Tec Corporation Thin reaction chambers for containing and handling liquid microvolumes
US5944652A (en) * 1996-12-27 1999-08-31 City Of Hope Method for breeding chickens
US5955377A (en) * 1991-02-11 1999-09-21 Biostar, Inc. Methods and kits for the amplification of thin film based assays
US5958345A (en) * 1997-03-14 1999-09-28 Moxtek, Inc. Thin film sample support
US5985214A (en) * 1997-05-16 1999-11-16 Aurora Biosciences Corporation Systems and methods for rapidly identifying useful chemicals in liquid samples
US6004744A (en) * 1991-03-05 1999-12-21 Molecular Tool, Inc. Method for determining nucleotide identity through extension of immobilized primer
US6027873A (en) * 1999-03-19 2000-02-22 Genencor International, Inc. Multi-through hole testing plate for high throughput screening
US6045753A (en) * 1997-07-29 2000-04-04 Sarnoff Corporation Deposited reagents for chemical processes
US6060240A (en) * 1996-12-13 2000-05-09 Arcaris, Inc. Methods for measuring relative amounts of nucleic acids in a complex mixture and retrieval of specific sequences therefrom
US6071702A (en) * 1998-09-04 2000-06-06 Hitachi Software Engineering Co., Ltd. Probe-bearing element and method for producing the same
US6071748A (en) * 1997-07-16 2000-06-06 Ljl Biosystems, Inc. Light detection device
US6121048A (en) * 1994-10-18 2000-09-19 Zaffaroni; Alejandro C. Method of conducting a plurality of reactions
USH1919H (en) * 1995-12-01 2000-11-07 E. I. Du Pont De Nemours And Company Agricultural product microscreen method and apparatus
US6147198A (en) * 1988-09-15 2000-11-14 New York University Methods and compositions for the manipulation and characterization of individual nucleic acid molecules
US6309600B1 (en) * 1997-08-28 2001-10-30 Biotrove, Inc. Apparatus for droplet microchemistry
US6309828B1 (en) * 1998-11-18 2001-10-30 Agilent Technologies, Inc. Method and apparatus for fabricating replicate arrays of nucleic acid molecules
US6309890B1 (en) * 1997-08-19 2001-10-30 BIOMéRIEUX, INC. Locking structure for securing a fluid transfer tube
US20020001546A1 (en) * 1998-01-12 2002-01-03 Massachusetts Institute Of Technology Methods for screening substances in a microwell array
US6387331B1 (en) * 1998-01-12 2002-05-14 Massachusetts Institute Of Technology Method and apparatus for performing microassays
US6436632B2 (en) * 1999-03-19 2002-08-20 Genencor International, Inc. Multi-through hole testing plate for high throughput screening
US6565813B1 (en) * 1998-02-04 2003-05-20 Merck & Co., Inc. Virtual wells for use in high throughput screening assays
US20030124716A1 (en) * 2000-10-10 2003-07-03 Biotrove, Inc., A Delaware Corporation Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
US6713309B1 (en) * 1999-07-30 2004-03-30 Large Scale Proteomics Corporation Microarrays and their manufacture

Family Cites Families (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3036893A (en) * 1960-03-14 1962-05-29 Scientific Industries Automatic chemical analyzer
US3098719A (en) * 1960-06-16 1963-07-23 Technicon Instr Fluid processing system with continuous filter apparatus
US3216804A (en) * 1962-01-31 1965-11-09 Scientific Industries Automatic chemical analyzer and sample dispenser
US3261668A (en) * 1962-08-14 1966-07-19 Scientific Industries Chemical analyzer tape
US3260413A (en) * 1964-08-31 1966-07-12 Scientific Industries Automatic chemical analyzer
US3475128A (en) * 1966-04-08 1969-10-28 Bio Science Labor Fluid processing apparatus and methods
BE702970A (en) * 1966-09-08 1968-02-23
US3526480A (en) * 1966-12-15 1970-09-01 Xerox Corp Automated chemical analyzer
US3497320A (en) * 1966-12-15 1970-02-24 Xerox Corp Automated chemical analyzer
US3508879A (en) * 1966-12-15 1970-04-28 Xerox Corp Aliquotting device
DE1811788A1 (en) * 1967-12-15 1969-08-21 Hoffmann La Roche Device for automatically carrying out Fluessigkeitsanalysen
US3554700A (en) * 1968-05-06 1971-01-12 Scientific Industries Method for obtaining a known volume of liquid and absorption apparatus therefor
DE2007405B2 (en) * 1969-03-19 1972-10-19 Apparatus for the colorimetric analysis of liquids serie
US3607079A (en) * 1969-06-02 1971-09-21 Scientific Industries Analysis arrangement for chemical analyzing apparatus
US3675488A (en) * 1969-09-11 1972-07-11 Res Foundation Of The Washingt Apparatus for transport and storage of liquid specimens for radio-immunoassay for insulin
US3607090A (en) * 1969-10-06 1971-09-21 Scientific Industries Analysis arrangment for multiple analyses of a single sample
US3627431A (en) * 1969-12-22 1971-12-14 John Victor Komarniski Densitometer
US3979264A (en) * 1975-03-31 1976-09-07 Heinz Buerger Band for carrying out microbiological examinations
FR2353856B1 (en) * 1976-06-02 1980-04-30 Chateau Guy
US4273877A (en) * 1978-06-13 1981-06-16 National Research Development Corporation Spiral plating apparatus
US4349510A (en) * 1979-07-24 1982-09-14 Seppo Kolehmainen Method and apparatus for measurement of samples by luminescence
US4263256A (en) * 1979-11-05 1981-04-21 Coulter Electronics, Inc. Cuvettes for automatic chemical apparatus
US4327073A (en) * 1980-04-07 1982-04-27 Huang Henry V Automated method for quantitative analysis of biological fluids
US4437109A (en) * 1980-11-07 1984-03-13 General Electric Company Silicon-on-sapphire body with conductive paths therethrough
US4394712A (en) * 1981-03-18 1983-07-19 General Electric Company Alignment-enhancing feed-through conductors for stackable silicon-on-sapphire wafers
US4527183A (en) * 1981-07-10 1985-07-02 General Electric Company Drilled, diffused radiation detector
US4473737A (en) * 1981-09-28 1984-09-25 General Electric Company Reverse laser drilling
US4568520A (en) * 1982-06-05 1986-02-04 Ismatec Sa Apparatus for the automated production of a series of samples for the analysis of mixtures
US4547836A (en) * 1984-02-01 1985-10-15 General Electric Company Insulating glass body with electrical feedthroughs and method of preparation
FR2565350B1 (en) * 1984-06-05 1986-10-10 Paris Nord Universite own to permit the support, treatment, storage and continuous automatic analysis of biological samples
US4863693A (en) * 1984-08-21 1989-09-05 E. I. Du Pont De Nemours And Company Analysis instrument having a blow molded reaction chamber
US4586546A (en) * 1984-10-23 1986-05-06 Cetus Corporation Liquid handling device and method
US4685880A (en) * 1985-06-18 1987-08-11 American Hospital Supply Corporation Cuvette belts and manufacture of same
JPS62144048A (en) * 1985-12-18 1987-06-27 Olympus Optical Co Ltd Developer concentration measuring apparatus
US4728591A (en) * 1986-03-07 1988-03-01 Trustees Of Boston University Self-assembled nanometer lithographic masks and templates and method for parallel fabrication of nanometer scale multi-device structures
JPS63241359A (en) * 1986-10-01 1988-10-06 Olympus Optical Co Ltd Micromodule solid phase method of reagent
US4777143A (en) * 1986-12-12 1988-10-11 Litmus Concepts Inc. Method of detecting carboxylic acids in a specimen
US4853059A (en) * 1986-12-24 1989-08-01 Baxter International Inc. Apparatus and process for manufacturing cuvetter belts
US5077085A (en) 1987-03-06 1991-12-31 Schnur Joel M High resolution metal patterning of ultra-thin films on solid substrates
US5077010A (en) * 1987-07-15 1991-12-31 Fuji Photo Film Co., Ltd. Long-test-film cassette for biochemical analysis, and system for loading the same
US4990459A (en) * 1988-04-25 1991-02-05 Kabushiki Kaisha Toshiba Impurity measuring method
US5009850A (en) * 1988-05-05 1991-04-23 Smiths Industries Medical Systems, Inc. Blood containment device
US4892409A (en) * 1988-07-14 1990-01-09 Smith Harry F Photometric apparatus for multiwell plates having a positionable lens assembly
WO1990002326A1 (en) * 1988-08-23 1990-03-08 Bio-Mediq (Australia) Pty. Ltd. Optical fluid analysis imaging and positioning
FR2637687B1 (en) * 1988-10-11 1991-01-11 Inst Textile De France Disposable device for biological tests
US5229163A (en) * 1989-12-21 1993-07-20 Hoffmann-La Roche Inc. Process for preparing a microtiter tray for immunometric determinations
JPH0678978B2 (en) * 1990-05-25 1994-10-05 スズキ株式会社 Agglutination pattern detecting device
US5213766A (en) * 1991-04-30 1993-05-25 Apogee Designs, Ltd. Liquid collecting apparatus for sample testing
WO1995001559A3 (en) * 1993-07-02 1995-02-16 Michael Doering Sample holder and its use
US5553616A (en) * 1993-11-30 1996-09-10 Florida Institute Of Technology Determination of concentrations of biological substances using raman spectroscopy and artificial neural network discriminator
US5578832A (en) * 1994-09-02 1996-11-26 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
US5515167A (en) * 1994-09-13 1996-05-07 Hughes Aircraft Company Transparent optical chuck incorporating optical monitoring
JPH08254536A (en) * 1995-03-17 1996-10-01 Toshiba Corp Automatic chemical analyzer
US5545531A (en) * 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
WO1997005492A1 (en) * 1995-07-31 1997-02-13 Precision System Science Co., Ltd Vessel
GB9521775D0 (en) 1995-10-24 1996-01-03 Pa Consulting Services Microwell plates
US5985594A (en) * 1995-11-14 1999-11-16 Idexx Laboratories, Inc. Method for quantification of biological material in a sample
US6660233B1 (en) * 1996-01-16 2003-12-09 Beckman Coulter, Inc. Analytical biochemistry system with robotically carried bioarray
GB9606367D0 (en) * 1996-03-26 1996-06-05 United Utilities Plc Optical instrument
US6001586A (en) * 1996-03-29 1999-12-14 Genencor International, Inc. Compartmentalization method for screening microorganisms
US5788814A (en) * 1996-04-09 1998-08-04 David Sarnoff Research Center Chucks and methods for positioning multiple objects on a substrate
US5840256A (en) * 1996-04-09 1998-11-24 David Sarnoff Research Center Inc. Plate for reaction system
US6103479A (en) * 1996-05-30 2000-08-15 Cellomics, Inc. Miniaturized cell array methods and apparatus for cell-based screening
WO1998007022A1 (en) * 1996-08-16 1998-02-19 Imaging Research, Inc. A digital imaging system for assays in well plates, gels and blots
US5854684A (en) * 1996-09-26 1998-12-29 Sarnoff Corporation Massively parallel detection
US6024925A (en) * 1997-01-23 2000-02-15 Sequenom, Inc. Systems and methods for preparing low volume analyte array elements
US6157456A (en) * 1997-03-11 2000-12-05 Hvass; Per Cuvette for spectrophotometrical analysis
EP0973863B1 (en) * 1997-04-09 2005-05-25 Minnesota Mining And Manufacturing Company Method and devices for partitioning biological sample liquids into microvolumes
US6143496A (en) * 1997-04-17 2000-11-07 Cytonix Corporation Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly
US6090251A (en) * 1997-06-06 2000-07-18 Caliper Technologies, Inc. Microfabricated structures for facilitating fluid introduction into microfluidic devices
WO1999022228A1 (en) * 1997-10-24 1999-05-06 Northeastern University A multichannel microscale system for high throughput preparative separation with comprehensive collection and analysis
US6878345B1 (en) * 1997-12-08 2005-04-12 Thomas W. Astle Ultra high throughput bioassay screening system
US6689323B2 (en) * 1998-10-30 2004-02-10 Agilent Technologies Method and apparatus for liquid transfer
US6296702B1 (en) * 1999-03-15 2001-10-02 Pe Corporation (Ny) Apparatus and method for spotting a substrate
WO2001061054A3 (en) * 2000-02-18 2002-02-28 Pamela K Foreman Apparatus and methods for parallel processing of micro-volume liquid reactions

Patent Citations (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6436632B1 (en) *
US2771398A (en) * 1953-09-17 1956-11-20 Thomas L Snyder Method and apparatus for counting microorganisms
US3645696A (en) * 1970-04-30 1972-02-29 Cities Service Oil Co Method for stabilizing chromogenic test reagent for aldehyde
US3894512A (en) * 1971-02-18 1975-07-15 Ohno Res & Dev Lab Electrostatic developing apparatus
US3768974A (en) * 1971-03-22 1973-10-30 Sterilizer Control Royalties Disposable colorimetric indicator device for measuring the concentration of chlorine in water
US3770383A (en) * 1971-04-05 1973-11-06 Akzona Inc Diagnostic test slide
US3873268A (en) * 1971-07-06 1975-03-25 Pfizer Multiple solution testing device
US3950133A (en) * 1971-10-20 1976-04-13 Mallinckrodt, Inc. Reagent formulations for assaying biological specimens and methods of preparing and using same
US3994594A (en) * 1975-08-27 1976-11-30 Technicon Instruments Corporation Cuvette and method of use
US4088448A (en) * 1975-09-29 1978-05-09 Lilja Jan Evert Apparatus for sampling, mixing the sample with a reagent and making particularly optical analyses
US4111754A (en) * 1976-11-29 1978-09-05 Hydow Park Immunological testing devices and methods
US4407943A (en) * 1976-12-16 1983-10-04 Millipore Corporation Immobilized antibody or antigen for immunoassay
US4234316A (en) * 1979-04-02 1980-11-18 Fmc Corporation Device for delivering measured quantities of reagents into assay medium
US4500707A (en) * 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4387164A (en) * 1980-11-05 1983-06-07 Fmc Corporation Method and apparatus for chemical analysis using reactive reagents dispersed in soluble film
US4415732A (en) * 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4973679A (en) * 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US4446239A (en) * 1981-04-24 1984-05-01 Chugai Seiyaku Kabushiki Kaisha Light scattering immunoassay involving particles with selective frequency band apparatus
US4562045A (en) * 1981-10-07 1985-12-31 Murata Manufacturing Co. Carrier for holding analytical samples
US5506141A (en) * 1982-05-10 1996-04-09 Bar-Ilan University Apertured cell carrier
US4861448A (en) * 1982-11-18 1989-08-29 The Trustees Of Columbia University In The City Of New York Electrophoretic methods employing gel inserts
US4761378A (en) * 1983-03-04 1988-08-02 American Home Products Corp. (Del.) Microbiological testing apparatus
US4493815A (en) * 1983-07-28 1985-01-15 Bio-Rad Laboratories, Inc. Supporting and filtering biochemical test plate assembly
US4562871A (en) * 1984-03-16 1986-01-07 Astle Thomas W Rehydrator
US4682890A (en) * 1985-05-31 1987-07-28 Health Research, Incorporated Microsample holder and carrier therefor
US4682891A (en) * 1985-05-31 1987-07-28 Health Research, Incorporated Microcircle system
US5047215A (en) * 1985-06-18 1991-09-10 Polyfiltronics, Inc. Multiwell test plate
US5153319A (en) * 1986-03-31 1992-10-06 University Patents, Inc. Process for preparing polynucleotides
US5000921A (en) * 1986-10-24 1991-03-19 Hanaway Richard W Multiple pipette samples
US4834946A (en) * 1987-02-05 1989-05-30 Levin Andrew E Apparatus for blot screening numerous, small volume, antibody solutions
US4806316A (en) * 1987-03-17 1989-02-21 Becton, Dickinson And Company Disposable device for use in chemical, immunochemical and microorganism analysis
US4828386A (en) * 1987-06-19 1989-05-09 Pall Corporation Multiwell plates containing membrane inserts
US6147198A (en) * 1988-09-15 2000-11-14 New York University Methods and compositions for the manipulation and characterization of individual nucleic acid molecules
US5108704A (en) * 1988-09-16 1992-04-28 W. R. Grace & Co.-Conn. Microfiltration apparatus with radially spaced nozzles
US5599664A (en) * 1989-04-05 1997-02-04 New York University Method for characterizing polymer molecules or the like
US5744101A (en) * 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US5510270A (en) * 1989-06-07 1996-04-23 Affymax Technologies N.V. Synthesis and screening of immobilized oligonucleotide arrays
US5183761A (en) * 1989-07-21 1993-02-02 Freeman Mary J Method of making calibration solution for verifying calibration and linearity of vertical photometers
US5262128A (en) * 1989-10-23 1993-11-16 The United States Of America As Represented By The Department Of Health And Human Services Array-type multiple cell injector
US5621094A (en) * 1990-05-14 1997-04-15 Quadrant Holdings Cambridge Limited Method of preserving agarose gel structure during dehydration by adding a non-reducing glycoside of a straight-chain sugar alcohol
US5234666A (en) * 1990-11-01 1993-08-10 Mitsubishi Denki K.K. Alcohol content detector
US5215593A (en) * 1991-01-09 1993-06-01 Canon Kabushiki Kaisha Method of introducing liquid into small-diameter hole
US5182082A (en) * 1991-01-23 1993-01-26 Becton, Dickinson And Company Multiple aliquot device for distributing a liquid solution into a well
US5955377A (en) * 1991-02-11 1999-09-21 Biostar, Inc. Methods and kits for the amplification of thin film based assays
US6004744A (en) * 1991-03-05 1999-12-21 Molecular Tool, Inc. Method for determining nucleotide identity through extension of immobilized primer
US5210021A (en) * 1991-03-20 1993-05-11 Neuro Probe, Inc. Multiple-site chemotactic test apparatus and method
US5284753A (en) * 1991-03-20 1994-02-08 Neuro Probe, Inc. Multiple-site chemotactic test apparatus and method
US5290705A (en) * 1992-01-13 1994-03-01 R. E. Davis Chemical Corporation Speciman support for optical analysis
US5888723A (en) * 1992-02-18 1999-03-30 Johnson & Johnson Clinical Diagnostics, Inc. Method for nucleic acid amplification and detection using adhered probes
US5374525A (en) * 1992-09-30 1994-12-20 University Of Utah Research Foundation Methods to determine predisposition to hypertension and association of variant angiotensinogen gene and hypertension
US5508200A (en) * 1992-10-19 1996-04-16 Tiffany; Thomas Method and apparatus for conducting multiple chemical assays
US5455934A (en) * 1993-03-23 1995-10-03 Eclipse Technologies, Inc. Fault tolerant hard disk array controller
US5519218A (en) * 1993-08-04 1996-05-21 Chang; On Kok Sample holder for spectroscopy
US5843767A (en) * 1993-10-28 1998-12-01 Houston Advanced Research Center Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions
US5605662A (en) * 1993-11-01 1997-02-25 Nanogen, Inc. Active programmable electronic devices for molecular biological analysis and diagnostics
US5929208A (en) * 1993-11-01 1999-07-27 Nanogen, Inc. Methods for electronic synthesis of polymers
US5632957A (en) * 1993-11-01 1997-05-27 Nanogen Molecular biological diagnostic systems including electrodes
US5840862A (en) * 1994-02-11 1998-11-24 Institut Pasteur Process for aligning, adhering and stretching nucleic acid strands on a support surface by passage through a meniscus
US5453252A (en) * 1994-02-25 1995-09-26 Truett; William L. Screen cell for spectroscopy
US5807522A (en) * 1994-06-17 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods for fabricating microarrays of biological samples
US6121048A (en) * 1994-10-18 2000-09-19 Zaffaroni; Alejandro C. Method of conducting a plurality of reactions
US5786226A (en) * 1995-03-16 1998-07-28 Boehringer Mannheim Gmbh Quantitative transmission spectroscopy using sample carriers with nets
US5560811A (en) * 1995-03-21 1996-10-01 Seurat Analytical Systems Incorporated Capillary electrophoresis apparatus and method
US5609828A (en) * 1995-05-31 1997-03-11 bio M erieux Vitek, Inc. Sample card
US5770440A (en) * 1995-06-27 1998-06-23 Becton Dickinson And Company Apparatus for the early detection of microorganisms
US5773238A (en) * 1995-07-07 1998-06-30 Shukla; Ashok K. Droplet chemical reaction chamber
US5763263A (en) * 1995-11-27 1998-06-09 Dehlinger; Peter J. Method and apparatus for producing position addressable combinatorial libraries
USH1919H (en) * 1995-12-01 2000-11-07 E. I. Du Pont De Nemours And Company Agricultural product microscreen method and apparatus
US5856100A (en) * 1995-12-08 1999-01-05 The Institute Of Physical And Chemical Research Method for purification and transfer to separation/detection systems of DNA sequencing samples and plates used therefor
US5849598A (en) * 1996-03-15 1998-12-15 Washington University Method for transferring micro quantities of liquid samples to discrete locations
US5770860A (en) * 1996-07-12 1998-06-23 Franzen; Jochen Method for loading sample supports for mass spectrometers
US5795748A (en) * 1996-09-26 1998-08-18 Becton Dickinson And Company DNA microwell device and method
US6060240A (en) * 1996-12-13 2000-05-09 Arcaris, Inc. Methods for measuring relative amounts of nucleic acids in a complex mixture and retrieval of specific sequences therefrom
US5944652A (en) * 1996-12-27 1999-08-31 City Of Hope Method for breeding chickens
US5958345A (en) * 1997-03-14 1999-09-28 Moxtek, Inc. Thin film sample support
US5985214A (en) * 1997-05-16 1999-11-16 Aurora Biosciences Corporation Systems and methods for rapidly identifying useful chemicals in liquid samples
US5910287A (en) * 1997-06-03 1999-06-08 Aurora Biosciences Corporation Low background multi-well plates with greater than 864 wells for fluorescence measurements of biological and biochemical samples
US5922604A (en) * 1997-06-05 1999-07-13 Gene Tec Corporation Thin reaction chambers for containing and handling liquid microvolumes
US6071748A (en) * 1997-07-16 2000-06-06 Ljl Biosystems, Inc. Light detection device
US6045753A (en) * 1997-07-29 2000-04-04 Sarnoff Corporation Deposited reagents for chemical processes
US6309890B1 (en) * 1997-08-19 2001-10-30 BIOMéRIEUX, INC. Locking structure for securing a fluid transfer tube
US6309600B1 (en) * 1997-08-28 2001-10-30 Biotrove, Inc. Apparatus for droplet microchemistry
US6387331B1 (en) * 1998-01-12 2002-05-14 Massachusetts Institute Of Technology Method and apparatus for performing microassays
US6743633B1 (en) * 1998-01-12 2004-06-01 Massachusetts Institute Of Technology Method for performing microassays
US20020001546A1 (en) * 1998-01-12 2002-01-03 Massachusetts Institute Of Technology Methods for screening substances in a microwell array
US6565813B1 (en) * 1998-02-04 2003-05-20 Merck & Co., Inc. Virtual wells for use in high throughput screening assays
US6071702A (en) * 1998-09-04 2000-06-06 Hitachi Software Engineering Co., Ltd. Probe-bearing element and method for producing the same
US6309828B1 (en) * 1998-11-18 2001-10-30 Agilent Technologies, Inc. Method and apparatus for fabricating replicate arrays of nucleic acid molecules
US6436632B2 (en) * 1999-03-19 2002-08-20 Genencor International, Inc. Multi-through hole testing plate for high throughput screening
US6027873A (en) * 1999-03-19 2000-02-22 Genencor International, Inc. Multi-through hole testing plate for high throughput screening
US6713309B1 (en) * 1999-07-30 2004-03-30 Large Scale Proteomics Corporation Microarrays and their manufacture
US20030124716A1 (en) * 2000-10-10 2003-07-03 Biotrove, Inc., A Delaware Corporation Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof

Cited By (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7972778B2 (en) 1997-04-17 2011-07-05 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
US8551698B2 (en) 1997-04-17 2013-10-08 Applied Biosystems, Llc Method of loading sample into a microfluidic device
US9506105B2 (en) 1997-04-17 2016-11-29 Applied Biosystems, Llc Device and method for amplifying target nucleic acid
US8278071B2 (en) 1997-04-17 2012-10-02 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
US8257925B2 (en) 1997-04-17 2012-09-04 Applied Biosystems, Llc Method for detecting the presence of a single target nucleic acid in a sample
US8822183B2 (en) 1997-04-17 2014-09-02 Applied Biosystems, Llc Device for amplifying target nucleic acid
US8067159B2 (en) 1997-04-17 2011-11-29 Applied Biosystems, Llc Methods of detecting amplified product
US8859204B2 (en) 1997-04-17 2014-10-14 Applied Biosystems, Llc Method for detecting the presence of a target nucleic acid sequence in a sample
US8563275B2 (en) 1997-04-17 2013-10-22 Applied Biosystems, Llc Method and device for detecting the presence of a single target nucleic acid in a sample
US20150126412A1 (en) * 1998-01-12 2015-05-07 Massachusetts Institute Of Technology Systems for filling a sample array by droplet dragging
US8029745B2 (en) 1998-01-12 2011-10-04 Massachusetts Institute Of Technology Systems for filling a sample array by droplet dragging
US7666360B2 (en) 1999-03-19 2010-02-23 Biotrove, Inc. Multi-through hole testing plate for high throughput screening
US8906618B2 (en) 2000-02-18 2014-12-09 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for parallel processing of micro-volume liquid reactions
US7833719B2 (en) 2000-02-18 2010-11-16 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for parallel processing of micro-volume liquid reactions
US9518299B2 (en) 2000-02-18 2016-12-13 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for parallel processing of micro-volume liquid reactions
US20080108112A1 (en) * 2000-02-18 2008-05-08 Biotrove, Inc. Apparatus and methods for parallel processing of micro-volume liquid reactions
US8277753B2 (en) 2002-08-23 2012-10-02 Life Technologies Corporation Microfluidic transfer pin
US8685340B2 (en) 2002-08-23 2014-04-01 Life Technologies Corporation Microfluidic transfer pin
US9428800B2 (en) 2002-12-20 2016-08-30 Life Technologies Corporation Thermal cycling apparatus and method
US8697452B2 (en) 2002-12-20 2014-04-15 Life Technologies Corporation Thermal cycling assay apparatus and method
US7682565B2 (en) 2002-12-20 2010-03-23 Biotrove, Inc. Assay apparatus and method using microfluidic arrays
US20040129676A1 (en) * 2003-01-07 2004-07-08 Tan Roy H. Apparatus for transfer of an array of liquids and methods for manufacturing same
US20110210057A1 (en) * 2003-09-30 2011-09-01 Belov Yuri P Multicapillary column for chromatography and sample preparation
US7964097B2 (en) 2003-09-30 2011-06-21 Belov Yuri P Multicapillary column for chromatography and sample preparation
US8980093B2 (en) 2003-09-30 2015-03-17 Yuri P. Belov Multicapillary device for sample preparation
US20070075007A1 (en) * 2003-09-30 2007-04-05 Belov Yuri P Multicapillary column for chromatography and sample preparation
US20070017870A1 (en) * 2003-09-30 2007-01-25 Belov Yuri P Multicapillary device for sample preparation
US8545772B2 (en) 2004-03-12 2013-10-01 Life Technologies Corporation Nanoliter array loading
US8105554B2 (en) 2004-03-12 2012-01-31 Life Technologies Corporation Nanoliter array loading
US20070003448A1 (en) * 2004-03-12 2007-01-04 Kanigan Tanya S Nanoliter array loading
US9266108B2 (en) 2004-03-12 2016-02-23 Life Technologies Corporation Nanoliter array loading
US20110092686A1 (en) * 2008-03-28 2011-04-21 Pelican Group Holdings, Inc. Multicapillary sample preparation devices and methods for processing analytes
US20150044686A1 (en) * 2012-03-16 2015-02-12 Life Technologies Corporation Systems and Methods for Containing Biological Samples
WO2017004502A1 (en) * 2015-07-02 2017-01-05 Centrillion Technology Holdings Corporation Systems and methods to dispense and mix reagents

Also Published As

Publication number Publication date Type
EP1051259B1 (en) 2006-04-05 grant
EP2286918A1 (en) 2011-02-23 application
US6387331B1 (en) 2002-05-14 grant
US20110065590A1 (en) 2011-03-17 application
CA2316912C (en) 2009-09-15 grant
US20170028376A9 (en) 2017-02-02 application
JP4271371B2 (en) 2009-06-03 grant
WO1999034920A1 (en) 1999-07-15 application
DE69942697D1 (en) 2010-09-30 grant
ES2350702T3 (en) 2011-01-26 grant
JP2002500373A (en) 2002-01-08 application
JP4448166B2 (en) 2010-04-07 grant
JP2009244271A (en) 2009-10-22 application
EP1714699A1 (en) 2006-10-25 application
EP1714699B1 (en) 2010-08-18 grant
US20150126412A1 (en) 2015-05-07 application
US6743633B1 (en) 2004-06-01 grant
EP1051259A1 (en) 2000-11-15 application
DE69930726D1 (en) 2006-05-18 grant
JP4668334B2 (en) 2011-04-13 grant
DE69930726T2 (en) 2007-01-25 grant
US20150298089A1 (en) 2015-10-22 application
CA2316912A1 (en) 1999-07-15 application
JP2008139319A (en) 2008-06-19 application
EP2286918B1 (en) 2014-10-01 grant

Similar Documents

Publication Publication Date Title
US6396995B1 (en) Method and apparatus for retaining and presenting at least one microsphere array to solutions and/or to optical imaging systems
US6677131B2 (en) Well frame including connectors for biological fluids
US4323536A (en) Multi-analyte test device
US5757482A (en) Module for optical detection in microscale fluidic analyses
US6734436B2 (en) Optical microfluidic devices and methods
US6818435B2 (en) Microfluidics devices and methods for performing cell based assays
Rose Microdispensing technologies in drug discovery
US6027695A (en) Apparatus for holding small volumes of liquids
US5560811A (en) Capillary electrophoresis apparatus and method
Weibel et al. Applications of microfluidics in chemical biology
US20120046203A1 (en) Imaging analyzer for testing analytes
Burbaum Miniaturization technologies in HTS: how fast, how small, how soon?
US5922617A (en) Rapid screening assay methods and devices
US6042789A (en) System for parallel synthesis of organic compounds
Kido et al. Disc-based immunoassay microarrays
US20090066936A1 (en) Three-dimensional (3d) hydrodynamic focusing using a microfluidic device
US20020164824A1 (en) Method and apparatus based on bundled capillaries for high throughput screening
US20030040129A1 (en) Binding assays using magnetically immobilized arrays
US20030190608A1 (en) Microfluidic devices comprising biochannels
US6284113B1 (en) Apparatus and method for transferring liquids
US20020164812A1 (en) Method for screening crystallization conditions in solution crystal growth
US20020187564A1 (en) Microfluidic library analysis
US6524456B1 (en) Microfluidic devices for the controlled manipulation of small volumes
US20050009101A1 (en) Microfluidic devices comprising biochannels
US7348183B2 (en) Self-contained microelectrochemical bioassay platforms and methods

Legal Events

Date Code Title Description
AS Assignment

Owner name: MASSACHUSETTS INSTITUTE OF TECHNOLOGY, MASSACHUSET

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:HUNTER, IAN W.;REEL/FRAME:015088/0906

Effective date: 20001219