US20110065590A1 - Method and Apparatus for Performing Microassays - Google Patents
Method and Apparatus for Performing Microassays Download PDFInfo
- Publication number
- US20110065590A1 US20110065590A1 US12/794,353 US79435310A US2011065590A1 US 20110065590 A1 US20110065590 A1 US 20110065590A1 US 79435310 A US79435310 A US 79435310A US 2011065590 A1 US2011065590 A1 US 2011065590A1
- Authority
- US
- United States
- Prior art keywords
- holes
- platen
- substances
- distinct
- liquid
- 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
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/302—Micromixers the materials to be mixed flowing in the form of droplets
- B01F33/3021—Micromixers the materials to be mixed 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/3035—Micromixers using surface tension to mix, move or hold the fluids
- B01F33/30351—Micromixers using surface tension to mix, move or hold the fluids using hydrophilic/hydrophobic surfaces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5025—Containers 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers 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
- B01L3/50857—Containers 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1002—Reagent dispensers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
- B01J2219/00315—Microtiter plates
- B01J2219/00317—Microwell devices, i.e. having large numbers of wells
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00533—Sheets essentially rectangular
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00536—Sheets in the shape of disks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/0054—Means for coding or tagging the apparatus or the reagents
- B01J2219/00547—Bar codes
- B01J2219/00549—2-dimensional
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00585—Parallel processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00599—Solution-phase processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0642—Filling fluids into wells by specific techniques
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00178—Special arrangements of analysers
- G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N35/00069—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
-
- Y—GENERAL 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
-
- Y—GENERAL 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
- Y10T436/112499—Automated chemical analysis with sample on test slide
-
- Y—GENERAL 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
Definitions
- 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.
- a method for selecting samples having specified properties from a library of samples has the steps of:
- 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 10.sup.8 per square meter.
- 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.
- a method 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 comprising:
- 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.
- a system for analyzing a plurality of liquid samples 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.
- 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
- FIG. 2A is top view of a portion of the platen of FIG. 1 in which the through-holes are configured on rectangular centers;
- 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;
- FIG. 3 is a top view of round sample wafer populated with through-holes in accordance with an embodiment of the present invention
- 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;
- 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;
- 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
- 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
- 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
- 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.
- 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.
- the volume of each well employed for the assay of a chemical or biochemical reaction is reduced typically to less than 100 nanoliters (10.sup.-10 m.sup.3).
- the packing density of wells may thereby be increased by several orders of magnitude over prior art technology.
- 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.
- plate 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.
- 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 .
- 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.
- 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 10.sup.7 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.
- 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.
- 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.
- libraries 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.
- 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.
- libraries may be composed of between 10.sup.3 and 10.sup.9 substances and combinations of substances.
- 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.mu.m.
- the volume of each through-hole 12 between surface 14 and surface 16 is on the order of .about.10.sup.-7 cm.sup.3 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.
- 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 .
- 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.
- platen 10 may be any solid or quasi-solid material into which through-holes 12 may be formed.
- platen 10 may be formed from metal, semiconductor, glass, quartz, ceramic or polymer materials, all given without limitation by way of example.
- 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.
- CD-ROM compact disk read-only-memory
- 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.
- 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.mu.m through-holes in glasses and polymers.
- Additional through-hole forming techniques include mechanical drilling, electrochemical methods, or selective chemical or charged-particle etching techniques.
- 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.
- 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 .
- 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.
- liquid may also be loaded through capillary action of liquid 32 along the walls of the through-holes.
- 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.
- 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.
- evaporation of the liquid 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.
- 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.
- a cross-section of a portion of platen 10 is shown to include through-hole microwell 12 .
- 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.
- the interior .about.160.mu.m 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.mu.m in length.
- 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.
- optical interrogation methods 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 .
- light returned by scattering in the original direction can be collected and analyzed using standard optical techniques.
- the beam shape and through-hole volume are preferably matched.
- 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.times.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.
- 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.
- wall 62 of through-hole 12 may be coated to prevent light leakage and cross-talk among the addressable sample volumes.
- 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.
- 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.
- 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 .
- 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.
- 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 .
- 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.
- 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 stiffing 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.
- 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.
- 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.
- 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.
- 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.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Plasma & Fusion (AREA)
- Optical Measuring Cells (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
- Sampling And Sample Adjustment (AREA)
- Devices For Use In Laboratory Experiments (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Electrical Discharge Machining, Electrochemical Machining, And Combined Machining (AREA)
- Apparatuses And Processes For Manufacturing Resistors (AREA)
- Pinball Game Machines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Executing Machine-Instructions (AREA)
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
- 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.
- 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.
- 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.
- 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.
- 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:
-
- a. providing a platen having two substantially parallel planar surfaces and a plurality of addressable through-holes disposed substantially perpendicularly to the planar surfaces;
- b. loading a first sample in liquid form into at least one of the through-holes;
- 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
- d. characterizing the reaction in the through-hole in terms of the specified properties.
- 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 10.sup.8 per square meter.
- 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.
- 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:
-
- a. providing a first perforated platen having through-holes and a second perforated platen having through-holes;
- b. loading a first set of samples in liquid form into the through-holes of the first perforated platen;
- c. loading a second set of samples in liquid form into the through-holes of the second perforated platen;
- d. registering the through-holes of the first perforated platen with the through-holes of the second perforated platen; and
- e. combining the first set of samples with the second set of samples.
- 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.
- 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.
- 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:
-
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; -
FIG. 2A is top view of a portion of the platen ofFIG. 1 in which the through-holes are configured on rectangular centers; -
FIG. 2B is top view of a portion of the platen ofFIG. 1 in which the through-holes are configured in a hexagonal close-packed array; -
FIG. 3 is a top view of round sample wafer populated with through-holes in accordance with an embodiment of the present invention; -
FIG. 4 is a side perspective view of an arrangement for loading a liquid sample into the platen ofFIG. 1 by employing capillary and inertial insertion forces; -
FIG. 5 is a cut-away view of a single through-hole in the platen ofFIG. 1 , showing the use of hydrophobic and hydrophilic layers for containment of an aqueous sample; -
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; -
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; -
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; -
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 -
FIG. 10 is a cross-sectional view of the portions of two platens ofFIG. 9 after the two platens have been brought into contact to facilitate mixing or dilution. - 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.sup.-10 m.sup.3). 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 aplaten 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 traverseplaten 10 from onesurface 14 to anopposing 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. - 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 aboveplanar surface 14 surrounding some or all of through-holes 12 whileindentations 6 may be fabricated rounding the edges of through-holes 12 atopposing surface 16.Flanges 8 andindentations 6 may advantageously provide for registration ofsuccessive platens 10, in the case where platens are stacked, and in processes of mixing or dilution, as discussed in detail below in reference toFIGS. 9-10 . - In accordance with an embodiment of the invention, through-
holes 12 are loaded with afirst 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. - 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 10.sup.7 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 ofplaten 10 may be populated with a single strain of cells. - 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. - 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 10.sup.3 and 10.sup.9 substances and combinations of substances.
- A
typical thickness 20 ofplaten 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.mu.m. Thus the volume of each through-hole 12 betweensurface 14 andsurface 16 is on the order of .about.10.sup.-7 cm.sup.3 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 inFIG. 2A , or in a close-packed hexagonal lattice, as shown inFIG. 2B . - 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 acircular sample wafer 300 having acentral hole 302 for purposes of centering with respect to handling equipment. - 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. -
Platen 10 may also advantageously be formed of a laminate of materials, with acentral layer 26 and outer “sandwiching” layers 28. Advantages of this construction for containment ofsample 18 will be discussed further below. - Through-
holes 12 may be formed inplaten 10 by means appropriate to the material ofplaten 10. Through-hole forming methods include, by way of example, laser ablation by means of an ultraviolet (UV) excimer laser which may form 100.mu.m 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. - 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 withsample fluid 18. Referring toFIG. 4 , two aspects of loading the through-hole wells are described with reference to asample 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 intoreservoir 34 viaport 33, may, as discussed above, contain cells or other particles in suspension. Liquid 32 may be forced into through-hole microwells 12 (shown inFIG. 1 ) by in-line impulsion as by drivingplaten 10 into liquid 32 by force applied alongdirection 36 transverse to the plane ofplaten 10. The transverse piston force may be applied viashaft 38 or in any other manner known in the mechanical arts. - 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 intoreservoir 34 and rotated, by torque applied throughshaft 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 immersingplaten 10 into liquid 32 and tilting the platen about an axis in the plane of the platen. - Stabilization with Respect to Capillary and Evaporative Liquid Loss
- 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.
- Referring to
FIG. 5 , a cross-section of a portion ofplaten 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 tosurfaces platen 10, has a hydrophobic wall surface in accordance with a preferred embodiment of the invention, while theinterior section 42 of the through-hole wall has a hydrophilic surface thereby preferentially attracting an aqueous liquid sample. Typically, the interior .about.160.mu.m 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.mu.m 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. - 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.
- 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 alight beam 50 into through-hole 12 ofplaten 10 and detecting light 52 emergent from the opposite aperture of through-hole 12 bydetectors 54constituting 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 collimatedbeam 50 is transformed byoptical element 58 into a beam having a diffraction limited focus at thecenter 60 of through-hole 12. The emergentoptical beam 52 is collected and focussed ontodetector array 56 byoptical 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 Detector array 56 may be a charge-coupled device (CCD) array, for example, and, in one embodiment of the invention, a 1000.times.1000 element format is employed, with each through-hole imaged onto threeelements 54 of the detector array. Awindow 62 may be disposed betweenplaten 10 anddetector 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 couplingelement 58 may be guided, in the manner of a guided wave through a waveguide, by thewalls 62 of through-hole 12 in order to provide efficient interrogation of the sampled volume within the through-hole. - In some cases, where the material of
platen 10 is not entirely opaque at the wavelengths of interrogatingoptical beam 50,wall 62 of through-hole 12 may be coated to prevent light leakage and cross-talk among the addressable sample volumes. -
FIG. 7 shows a preferred embodiment of the present invention in which platen 10 is configured in the CD-ROM format described above, with interrogatingoptical source 50 capable of travel inradial direction 68 whileplaten 10 rotates aboutcenter 66.Optical detector array 56 may translate in conjunction withsource 50, in accordance with an embodiment of the invention. - 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 adirection 70 past an optical interrogation system comprising anoptical source 72 and adetector 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 arow 76 is interrogated optically at the period during which a specified indication is expected. - Referring now to
FIG. 9 , a cross-sectional view is shown of portions of afirst platen 90 and asecond 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 ofplaten 90 are shown as having been loaded withliquid 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 orother targets 96 in solution within a solvent 98. - Through-
holes 12 ofsecond platen 92 is shown as having been loaded withliquid samples platen 92 may have been populated with a library of distinct compounds, each of which is to be exposed to target 96 ofplaten 90. -
FIG. 10 showsplatens 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 ofprotrusions 8 withindentations 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 oftargets 96 fromsamples 94 offirst platen 90 have migrated to the solvent ofsamples - The number of
platens FIGS. 9 and 10 by way of example only. Thus, the concentration oftargets 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 oftargets 96 throughout the liquid contained within the corresponding sample volumes of the stack. - 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.
- 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)
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. A method according to claim 1 , wherein the set of different substances includes a reagent.
3. A method according to claim 1 , wherein the set of different substances comprises a library of at least 1000 substances.
4. A method according to claim 1 , wherein the set of different substances include optical taggants.
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. 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. 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. A method according to claim 1 , wherein the step of characterizing contents of distinct through-holes includes characterizing by optical methods.
9. A method according to claim 8 , wherein the step of characterizing contents of distinct through-holes includes characterizing by fluorometric methods.
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. A platen according to claim 10 , wherein distinct substances of the set of distinct substances are coated on walls of the through-holes.
12. A platen according to claim 10 , wherein distinct substances of the set of distinct substances are retained within through-holes of the platen by surface tension.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/794,353 US20110065590A1 (en) | 1998-01-12 | 2010-06-04 | Method and Apparatus for Performing Microassays |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US7117998P | 1998-01-12 | 1998-01-12 | |
US09/225,583 US6387331B1 (en) | 1998-01-12 | 1999-01-05 | Method and apparatus for performing microassays |
US09/710,082 US6743633B1 (en) | 1998-01-12 | 2000-11-10 | Method for performing microassays |
US10/796,856 US20040171166A1 (en) | 1998-01-12 | 2004-03-09 | Method and apparatus for performing microassays |
US12/794,353 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 |
---|---|---|---|
US10/796,856 Continuation US20040171166A1 (en) | 1998-01-12 | 2004-03-09 | Method and apparatus for performing microassays |
Publications (1)
Publication Number | Publication Date |
---|---|
US20110065590A1 true US20110065590A1 (en) | 2011-03-17 |
Family
ID=22099761
Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/225,583 Expired - Lifetime US6387331B1 (en) | 1998-01-12 | 1999-01-05 | Method and apparatus for performing microassays |
US09/710,082 Expired - Lifetime US6743633B1 (en) | 1998-01-12 | 2000-11-10 | Method for performing microassays |
US10/796,856 Abandoned US20040171166A1 (en) | 1998-01-12 | 2004-03-09 | Method and apparatus for performing microassays |
US12/794,353 Abandoned US20110065590A1 (en) | 1998-01-12 | 2010-06-04 | Method and Apparatus for Performing Microassays |
US14/301,325 Abandoned US20150126412A1 (en) | 1998-01-12 | 2014-06-10 | Systems for filling a sample array by droplet dragging |
US14/582,122 Abandoned US20170028376A9 (en) | 1998-01-12 | 2014-12-23 | Systems for Filling a Sample Array by Droplet Dragging |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/225,583 Expired - Lifetime US6387331B1 (en) | 1998-01-12 | 1999-01-05 | Method and apparatus for performing microassays |
US09/710,082 Expired - Lifetime US6743633B1 (en) | 1998-01-12 | 2000-11-10 | Method for performing microassays |
US10/796,856 Abandoned US20040171166A1 (en) | 1998-01-12 | 2004-03-09 | Method and apparatus for performing microassays |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/301,325 Abandoned US20150126412A1 (en) | 1998-01-12 | 2014-06-10 | Systems for filling a sample array by droplet dragging |
US14/582,122 Abandoned US20170028376A9 (en) | 1998-01-12 | 2014-12-23 | Systems for Filling a Sample Array by Droplet Dragging |
Country Status (9)
Country | Link |
---|---|
US (6) | US6387331B1 (en) |
EP (3) | EP2286918B1 (en) |
JP (3) | JP4271371B2 (en) |
AT (2) | ATE322341T1 (en) |
AU (1) | AU2102699A (en) |
CA (1) | CA2316912C (en) |
DE (2) | DE69942697D1 (en) |
ES (1) | ES2350702T3 (en) |
WO (1) | WO1999034920A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080105549A1 (en) * | 2002-09-24 | 2008-05-08 | Pamela Vamsee K | Methods for performing microfluidic sampling |
US20080138815A1 (en) * | 1997-04-17 | 2008-06-12 | Cytonix | Method of loading sample into a microfluidic device |
US20090260988A1 (en) * | 2002-09-24 | 2009-10-22 | Duke University | Methods for Manipulating Droplets by Electrowetting-Based Techniques |
US8048628B2 (en) | 2002-09-24 | 2011-11-01 | Duke University | Methods for nucleic acid amplification on a printed circuit board |
US8268246B2 (en) | 2007-08-09 | 2012-09-18 | Advanced Liquid Logic Inc | PCB droplet actuator fabrication |
US20140322747A1 (en) * | 2011-12-19 | 2014-10-30 | Yamaha Hatsudoki Kabushiki Kaisha | Object selecting device and object selecting method |
US20150126412A1 (en) * | 1998-01-12 | 2015-05-07 | Massachusetts Institute Of Technology | Systems for filling a sample array by droplet dragging |
WO2021134014A1 (en) * | 2019-12-27 | 2021-07-01 | Sean Kelly | Analysis of a biological sample using tape-to-tape fluidic transfer |
Families Citing this family (163)
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 |
US6794127B1 (en) | 1997-06-16 | 2004-09-21 | Diversa Corporation | Capillary array-based sample screening |
US6972183B1 (en) | 1997-06-16 | 2005-12-06 | Diversa Corporation | Capillary array-based enzyme screening |
US6090251A (en) | 1997-06-06 | 2000-07-18 | Caliper Technologies, Inc. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7019827B2 (en) | 1997-06-16 | 2006-03-28 | Diversa Corporation | GigaMatrix holding tray having through-hole wells |
US6893877B2 (en) * | 1998-01-12 | 2005-05-17 | Massachusetts Institute Of Technology | Methods for screening substances in a microwell array |
US7282240B1 (en) * | 1998-04-21 | 2007-10-16 | President And Fellows Of Harvard College | Elastomeric mask and use in fabrication of devices |
AU762897B2 (en) * | 1999-02-16 | 2003-07-10 | Applera Corporation | Bead dispensing system |
US6296702B1 (en) | 1999-03-15 | 2001-10-02 | Pe Corporation (Ny) | Apparatus and method for spotting a substrate |
US6306578B1 (en) | 1999-03-19 | 2001-10-23 | Genencor International, Inc. | Multi-through hole testing plate for high throughput screening |
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 |
EP1214139A2 (en) * | 1999-09-17 | 2002-06-19 | Millipore Corporation | High throughput screening card |
DE19947495C2 (en) | 1999-10-01 | 2003-05-28 | Agilent Technologies Inc | Microfluidic microchip |
WO2001061054A2 (en) * | 2000-02-18 | 2001-08-23 | Board Of Trustees Of The Leland Stanford Junior University | Apparatus and methods for parallel processing of micro-volume liquid reactions |
US20020151040A1 (en) | 2000-02-18 | 2002-10-17 | Matthew O' Keefe | Apparatus and methods for parallel processing of microvolume liquid reactions |
KR20020097181A (en) * | 2000-02-22 | 2002-12-31 | 제노스펙트라 인코포레이티드 | Microarray fabrication techniques and apparatus |
US20040014102A1 (en) * | 2000-02-22 | 2004-01-22 | Shiping Chen | High density parallel printing of microarrays |
AU6291301A (en) | 2000-02-22 | 2001-09-03 | 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 |
CA2425476C (en) | 2000-10-10 | 2011-02-01 | Biotrove, Inc. | Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof |
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 |
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 |
US20020121443A1 (en) * | 2000-11-13 | 2002-09-05 | Genoptix | Methods for the combined electrical and optical identification, characterization and/or sorting of particles |
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 |
US6936811B2 (en) * | 2000-11-13 | 2005-08-30 | Genoptix, Inc. | Method for separating micro-particles |
US6965433B2 (en) * | 2000-11-16 | 2005-11-15 | Nagaoka & Co., Ltd. | Optical biodiscs with reflective layers |
WO2002044695A1 (en) * | 2000-11-16 | 2002-06-06 | Burstein Technologies, Inc. | Methods and apparatus for detecting and quantifying lymphocytes with optical biodiscs |
WO2002043866A2 (en) * | 2000-12-01 | 2002-06-06 | Burstein Technologies, Inc. | Apparatus and methods for separating components of particulate suspension |
EP1410026A2 (en) * | 2000-12-08 | 2004-04-21 | 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 |
FR2820058B1 (en) | 2001-01-29 | 2004-01-30 | Commissariat Energie Atomique | METHOD AND SYSTEM FOR MAKING A CONTINUOUS FLOW REALIZATION OF A BIOLOGICAL, CHEMICAL OR BIOCHEMICAL PROTOCOL |
US20020164824A1 (en) * | 2001-02-16 | 2002-11-07 | Jianming Xiao | Method and apparatus based on bundled capillaries for high throughput screening |
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 |
WO2003087827A2 (en) | 2001-04-11 | 2003-10-23 | Burstein Technologies, Inc. | Multi-parameter assays including analysis discs and methods relating thereto |
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 |
US20040023310A1 (en) * | 2001-04-27 | 2004-02-05 | Genoptix, Inc | Quantitative determination of protein kinase C activation using optophoretic analysis |
US20030194755A1 (en) * | 2001-04-27 | 2003-10-16 | Genoptix, Inc. | Early detection of apoptotic events and apoptosis using optophoretic analysis |
US20040009540A1 (en) * | 2001-04-27 | 2004-01-15 | Genoptix, Inc | Detection and evaluation of cancer cells using optophoretic analysis |
WO2002087760A1 (en) * | 2001-04-30 | 2002-11-07 | Epr Labautomation Ag | Method and device for storing and dosing small quantities of liquid |
WO2004010099A2 (en) * | 2001-05-16 | 2004-01-29 | Burstein Technologies, Inc. | Variable sampling for rendering pixelization of analysis results in optical bio-disc assembly |
US6685885B2 (en) * | 2001-06-22 | 2004-02-03 | Purdue Research Foundation | Bio-optical compact dist system |
US20040166593A1 (en) * | 2001-06-22 | 2004-08-26 | Nolte David D. | Adaptive interferometric multi-analyte high-speed biosensor |
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 |
US20030087309A1 (en) * | 2001-08-27 | 2003-05-08 | Shiping Chen | Desktop drug screening system |
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 |
US20030143637A1 (en) * | 2001-08-31 | 2003-07-31 | Selvan Gowri Pyapali | Capture layer assemblies for cellular assays including related optical analysis discs and methods |
JP2005502872A (en) * | 2001-09-07 | 2005-01-27 | バースタイン テクノロジーズ,インコーポレイティド | Identification and quantification of leukocyte types based on nuclear morphology using an optical biodisc system |
US20030124599A1 (en) * | 2001-11-14 | 2003-07-03 | Shiping Chen | Biochemical analysis system with combinatorial chemistry applications |
WO2003044481A2 (en) * | 2001-11-20 | 2003-05-30 | Burstein Technologies, Inc. | Optical bio-discs and microfluidic devices for analysis of cells |
WO2003055589A2 (en) * | 2001-12-31 | 2003-07-10 | Institut für Physikalische Hochtechnologie e.V. | Microtiter plate for parallel micro synthesis, especially at high temperatures |
US20040246252A1 (en) * | 2002-01-14 | 2004-12-09 | Morrow Jesse James | Method and apparatus for visualizing data |
CN1625779A (en) * | 2002-01-28 | 2005-06-08 | 长冈实业株式会社 | Methods and apparatus for logical triggering |
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 |
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 |
CN1625689A (en) * | 2002-01-31 | 2005-06-08 | 长冈实业株式会社 | Method for triggering through disc grooves and related optical analysis discs and system |
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 CARRYING A MOLECULE |
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 |
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 |
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 |
US20030211461A1 (en) * | 2002-05-01 | 2003-11-13 | Genoptix, Inc | Optophoretic detection of durgs exhibiting inhibitory effect on Bcr-Abl positive tumor cells |
US20030208936A1 (en) * | 2002-05-09 | 2003-11-13 | Lee Charles Hee | Method for manufacturing embroidery decorated cards and envelopes |
US8277753B2 (en) * | 2002-08-23 | 2012-10-02 | Life Technologies Corporation | Microfluidic transfer pin |
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 |
CA2521999A1 (en) | 2002-12-20 | 2004-09-02 | Biotrove, Inc. | Assay apparatus and method using microfluidic arrays |
US20060094108A1 (en) * | 2002-12-20 | 2006-05-04 | Karl Yoder | Thermal cycler for microfluidic array assays |
US20040129676A1 (en) * | 2003-01-07 | 2004-07-08 | Tan Roy H. | Apparatus for transfer of an array of liquids and methods for manufacturing same |
CA2518677A1 (en) * | 2003-03-03 | 2004-12-09 | Nagaoka & Co., Ltd. | Methods and apparatus for use in detection and quantitation of various cell types and use of optical bio-disc for performing same |
WO2004095034A1 (en) * | 2003-04-23 | 2004-11-04 | Nagaoka & Co., Ltd. | Optical bio-discs including spiral fluidic circuits for performing assays |
US7390464B2 (en) * | 2003-06-19 | 2008-06-24 | Burstein Technologies, Inc. | Fluidic circuits for sample preparation including bio-discs and methods relating thereto |
WO2004113871A2 (en) * | 2003-06-19 | 2004-12-29 | Nagaoka & Co., Ltd. | Fluidic circuits for sample preparation including bio-discs and methods relating thereto |
EP1644184A2 (en) * | 2003-06-27 | 2006-04-12 | Nagaoka & Co., Ltd. | Fluidic circuits, methods and apparatus for use of whole blood samples in colorimetric assays |
WO2005011830A2 (en) * | 2003-07-25 | 2005-02-10 | Nagaoka & Co., Ltd. | Fluidic circuits for sample preparation including bio-discs and methods relating thereto |
US7745221B2 (en) * | 2003-08-28 | 2010-06-29 | Celula, Inc. | Methods and apparatus for sorting cells using an optical switch in a microfluidic channel network |
US7063216B2 (en) | 2003-09-04 | 2006-06-20 | Millipore Corporation | Underdrain useful in the construction of a filtration device |
US20050225751A1 (en) * | 2003-09-19 | 2005-10-13 | Donald Sandell | Two-piece high density plate |
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 |
US20050226782A1 (en) * | 2003-09-19 | 2005-10-13 | Reed Mark T | High density plate filler |
US20050280811A1 (en) * | 2003-09-19 | 2005-12-22 | Donald Sandell | Grooved high density plate |
US8277760B2 (en) * | 2003-09-19 | 2012-10-02 | Applied Biosystems, Llc | High density plate filler |
US20050220675A1 (en) * | 2003-09-19 | 2005-10-06 | Reed Mark T | High density plate filler |
US9492820B2 (en) | 2003-09-19 | 2016-11-15 | Applied Biosystems, Llc | High density plate filler |
US20060233673A1 (en) * | 2003-09-19 | 2006-10-19 | Beard Nigel P | High density plate filler |
US7998435B2 (en) * | 2003-09-19 | 2011-08-16 | Life Technologies Corporation | High density plate filler |
US20060233671A1 (en) * | 2003-09-19 | 2006-10-19 | Beard Nigel P | High density plate filler |
US7407630B2 (en) * | 2003-09-19 | 2008-08-05 | Applera Corporation | High density plate filler |
US7695688B2 (en) * | 2003-09-19 | 2010-04-13 | Applied Biosystems, Llc | High density plate filler |
US20070017870A1 (en) | 2003-09-30 | 2007-01-25 | Belov Yuri P | Multicapillary device for sample preparation |
EP1677886A1 (en) * | 2003-09-30 | 2006-07-12 | Chromba, Inc. | Multicapillary column for chromatography and sample preparation |
US8753588B2 (en) | 2003-10-15 | 2014-06-17 | Emd Millipore Corporation | Support and stand-off ribs for underdrain for multi-well device |
WO2005081801A2 (en) * | 2004-02-09 | 2005-09-09 | Blueshift Biotechnologies, Inc. | Methods and apparatus for scanning small sample volumes |
CA2559171A1 (en) | 2004-03-12 | 2005-09-29 | Biotrove, Inc. | Nanoliter array loading |
JP2008504845A (en) * | 2004-06-07 | 2008-02-21 | バイオプロセッサーズ コーポレイション | Reactor environmental condition control |
US20060105453A1 (en) | 2004-09-09 | 2006-05-18 | Brenan Colin J | Coating process for microfluidic sample arrays |
US12070731B2 (en) | 2004-08-04 | 2024-08-27 | Life Technologies Corporation | Methods and systems for aligning dispensing arrays with microfluidic sample arrays |
DE102004041941B4 (en) * | 2004-08-30 | 2007-01-11 | P.A.L.M. Microlaser Technologies Ag | Method for obtaining biological objects with a recording unit |
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 |
TW200632314A (en) * | 2004-12-07 | 2006-09-16 | Honeywell Analytics Ag | Gas detection method and system |
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 |
US7663092B2 (en) | 2005-02-01 | 2010-02-16 | Purdue Research Foundation | Method and apparatus for phase contrast quadrature interferometric detection of an immunoassay |
JP4979941B2 (en) * | 2005-03-30 | 2012-07-18 | Hoya株式会社 | Manufacturing method of glass substrate for mask blanks, manufacturing method of mask blanks |
JP5011650B2 (en) * | 2005-04-01 | 2012-08-29 | パナソニック株式会社 | Light detection method |
KR20070120605A (en) * | 2005-04-14 | 2007-12-24 | 더 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 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 |
US7522282B2 (en) * | 2006-11-30 | 2009-04-21 | Purdue Research Foundation | Molecular interferometric imaging process and apparatus |
US20080230605A1 (en) * | 2006-11-30 | 2008-09-25 | Brian Weichel | Process and apparatus for maintaining data integrity |
US20080144899A1 (en) * | 2006-11-30 | 2008-06-19 | Manoj Varma | Process for extracting periodic features from images by template matching |
US7659968B2 (en) * | 2007-01-19 | 2010-02-09 | 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 |
JP5295733B2 (en) | 2007-11-30 | 2013-09-18 | キヤノン株式会社 | Living body holding method, living body testing method, living body growth method, living body holding sheet, and living body processing apparatus |
JP4518157B2 (en) * | 2008-01-31 | 2010-08-04 | カシオ計算機株式会社 | Imaging apparatus and program thereof |
WO2009121034A2 (en) * | 2008-03-28 | 2009-10-01 | Pelican Group Holdings, Inc. | Multicapillary sample preparation devices and methods for processing analytes |
CA2719877C (en) * | 2008-03-31 | 2016-08-09 | 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 | Method and apparatus for measuring volume of microdroplet |
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 |
CN102905987A (en) * | 2009-12-31 | 2013-01-30 | 巴斯夫欧洲公司 | Tampering detector and method |
GB2480596A (en) * | 2010-01-29 | 2011-11-30 | Kenneth John Cunningham | Disposable light scattering cuvette for liquid sample held by surface tension |
US9873118B2 (en) | 2010-12-30 | 2018-01-23 | Abbott Point Of Care, Inc. | Biologic fluid analysis cartridge with sample handling portion and analysis chamber portion |
US9267170B2 (en) * | 2011-09-30 | 2016-02-23 | Life Technologies Corporation | Systems and methods for biological analysis |
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 |
SG11201405785WA (en) * | 2012-03-16 | 2014-11-27 | Life Technologies Corp | Systems and methods for biological analysis |
JP2015515267A (en) | 2012-03-16 | 2015-05-28 | ライフ テクノロジーズ コーポレーション | System and method for evaluation of biological samples |
EP2856177B1 (en) | 2012-05-25 | 2020-11-18 | The University of North Carolina At Chapel Hill | Microfluidic devices, solid supports for reagents and related methods |
JP5483134B2 (en) * | 2012-10-09 | 2014-05-07 | 独立行政法人産業技術総合研究所 | Method and apparatus for measuring volume of microdroplet |
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 |
US11085067B2 (en) | 2013-06-10 | 2021-08-10 | President And Fellows Of Harvard College | Early developmental genomic assay for characterizing pluripotent stem cell utility and safety |
US20170080417A1 (en) * | 2014-05-14 | 2017-03-23 | University Of Limerick | Microfluidic devices that include channels that are slidable relative to each other and methods of use thereof |
WO2016004171A1 (en) | 2014-07-03 | 2016-01-07 | Centrillion Technology Holdings Corporation | Device for storage and dispensing of reagents |
US9702817B2 (en) * | 2015-01-06 | 2017-07-11 | Rolls-Royce Plc | Method and apparatus for testing of engine components |
CN106338418B (en) | 2015-07-02 | 2021-07-20 | 生捷科技控股公司 | System and method for dispensing and mixing reagents |
US11085039B2 (en) | 2016-12-12 | 2021-08-10 | xCella Biosciences, Inc. | Methods and systems for screening using microcapillary arrays |
CN110268108B (en) | 2016-12-12 | 2022-09-06 | 埃克切拉生物科学公司 | Methods and systems for screening using microcapillary arrays |
EP3562796B1 (en) | 2016-12-30 | 2023-04-19 | Xcella Biosciences, Inc. | Multi-stage sample recovery system |
WO2019035079A1 (en) | 2017-08-17 | 2019-02-21 | Abbott Point Of Care Inc. | Devices, systems, and methods for performing optical and electrochemical assays |
WO2020037194A1 (en) * | 2018-08-17 | 2020-02-20 | Sierra Biosystems, Inc. | Row-independent oligonucleotide synthesis |
WO2020043906A1 (en) * | 2018-08-31 | 2020-03-05 | Oerlikon Am Gmbh | Alloy development instrument for additive manufacturing (am) |
US20200316593A1 (en) | 2018-12-06 | 2020-10-08 | xCella Biosciences, Inc. | Lateral loading of microcapillary arrays |
TW202100247A (en) * | 2019-01-29 | 2021-01-01 | 美商伊路米納有限公司 | Flow cells |
ES2940487T3 (en) * | 2019-06-06 | 2023-05-08 | Siemens Healthcare Diagnostics Products Gmbh | Device for storing reagent containers on several levels |
FR3116008A1 (en) * | 2020-11-06 | 2022-05-13 | Preciphos | Production of biofunctionalized filter chips |
Citations (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3627431A (en) * | 1969-12-22 | 1971-12-14 | John Victor Komarniski | Densitometer |
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 |
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 |
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 |
US4394712A (en) * | 1981-03-18 | 1983-07-19 | General Electric Company | Alignment-enhancing feed-through conductors for stackable silicon-on-sapphire wafers |
US4407943A (en) * | 1976-12-16 | 1983-10-04 | Millipore Corporation | Immobilized antibody or antigen for immunoassay |
US4437109A (en) * | 1980-11-07 | 1984-03-13 | General Electric Company | Silicon-on-sapphire body with conductive paths therethrough |
US4473737A (en) * | 1981-09-28 | 1984-09-25 | General Electric Company | Reverse laser drilling |
US4527183A (en) * | 1981-07-10 | 1985-07-02 | General Electric Company | Drilled, diffused radiation detector |
US4547836A (en) * | 1984-02-01 | 1985-10-15 | General Electric Company | Insulating glass body with electrical feedthroughs and method of preparation |
US4562871A (en) * | 1984-03-16 | 1986-01-07 | Astle Thomas W | Rehydrator |
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 |
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 |
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 |
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 |
US5234666A (en) * | 1990-11-01 | 1993-08-10 | Mitsubishi Denki K.K. | Alcohol content detector |
US5290705A (en) * | 1992-01-13 | 1994-03-01 | R. E. Davis Chemical Corporation | Speciman support for optical analysis |
WO1995011755A1 (en) * | 1993-10-28 | 1995-05-04 | Houston Advanced Research Center | Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions |
US5515167A (en) * | 1994-09-13 | 1996-05-07 | Hughes Aircraft Company | Transparent optical chuck incorporating optical monitoring |
US5545531A (en) * | 1995-06-07 | 1996-08-13 | Affymax Technologies N.V. | Methods for making a device for concurrently processing multiple biological chip assays |
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 |
US5609828A (en) * | 1995-05-31 | 1997-03-11 | bio M erieux Vitek, Inc. | Sample card |
US5770860A (en) * | 1996-07-12 | 1998-06-23 | Franzen; Jochen | Method for loading sample supports for mass spectrometers |
US5788814A (en) * | 1996-04-09 | 1998-08-04 | David Sarnoff Research Center | Chucks and methods for positioning multiple objects on a substrate |
WO1998045406A1 (en) * | 1997-04-09 | 1998-10-15 | Minnesota Mining And Manufacturing Company | Method and devices for partitioning biological sample liquids into microvolumes |
US5840256A (en) * | 1996-04-09 | 1998-11-24 | David Sarnoff Research Center Inc. | Plate for reaction system |
US5854684A (en) * | 1996-09-26 | 1998-12-29 | Sarnoff Corporation | Massively parallel detection |
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 |
US6045753A (en) * | 1997-07-29 | 2000-04-04 | Sarnoff Corporation | Deposited reagents for chemical processes |
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 |
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 |
USH1919H (en) * | 1995-12-01 | 2000-11-07 | E. I. Du Pont De Nemours And Company | Agricultural product microscreen method and apparatus |
US6309890B1 (en) * | 1997-08-19 | 2001-10-30 | BIOMéRIEUX, INC. | Locking structure for securing a fluid transfer tube |
US6309828B1 (en) * | 1998-11-18 | 2001-10-30 | Agilent Technologies, Inc. | Method and apparatus for fabricating replicate arrays of nucleic acid molecules |
US6441973B1 (en) * | 1996-08-16 | 2002-08-27 | Imaging Research, Inc. | Digital imaging system for assays in well plates, gels and blots |
US7547556B2 (en) * | 1998-01-12 | 2009-06-16 | Massachusetts Institute Of Technology | Methods for filing a sample array by droplet dragging |
Family Cites Families (118)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2771398A (en) * | 1953-09-17 | 1956-11-20 | Thomas L Snyder | Method and apparatus for counting microorganisms |
US3260413A (en) * | 1964-08-31 | 1966-07-12 | Scientific Industries | Automatic chemical analyzer |
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 |
US3475128A (en) * | 1966-04-08 | 1969-10-28 | Bio Science Labor | Fluid processing apparatus and methods |
BE702970A (en) * | 1966-09-08 | 1968-02-23 | ||
US3508879A (en) * | 1966-12-15 | 1970-04-28 | Xerox Corp | Aliquotting device |
US3526480A (en) * | 1966-12-15 | 1970-09-01 | Xerox Corp | Automated chemical analyzer |
US3504376A (en) * | 1966-12-15 | 1970-03-31 | Xerox Corp | Automated chemical analyzer |
CH487401A (en) * | 1967-12-15 | 1970-03-15 | Hoffmann La Roche | Device for the automatic implementation of liquid analyzes |
US3554700A (en) * | 1968-05-06 | 1971-01-12 | Scientific Industries | Method for obtaining a known volume of liquid and absorption apparatus therefor |
FR2035058A1 (en) * | 1969-03-19 | 1970-12-18 | American Optical Corp | |
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 |
JPS5518906B1 (en) * | 1971-02-18 | 1980-05-22 | ||
GB1320426A (en) * | 1971-07-06 | 1973-06-13 | Pfizer | Multiple solution testing device |
US3979264A (en) * | 1975-03-31 | 1976-09-07 | Heinz Buerger | Band for carrying out microbiological examinations |
FR2353856A1 (en) * | 1976-06-02 | 1977-12-30 | Chateau Guy | TAPE INTENDED TO BE USED AS A SUPPORT FOR A REACTION FOR EXAMPLE CHEMICAL OR BIOCHEMICAL, AND ANALYSIS PROCESS IMPLEMENTING IT |
US4111754A (en) | 1976-11-29 | 1978-09-05 | Hydow Park | Immunological testing devices and methods |
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 |
US4500707A (en) * | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
US4327073A (en) * | 1980-04-07 | 1982-04-27 | Huang Henry V | Automated method for quantitative analysis of biological fluids |
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 |
JPS57175957A (en) | 1981-04-24 | 1982-10-29 | Chugai Pharmaceut Co Ltd | Measuring method and device for antigen- antibody reaction |
US4562045A (en) * | 1981-10-07 | 1985-12-31 | Murata Manufacturing Co. | Carrier for holding analytical samples |
US5310674A (en) | 1982-05-10 | 1994-05-10 | Bar-Ilan University | Apertured cell carrier |
CH655392B (en) * | 1982-06-05 | 1986-04-15 | ||
US4861448A (en) * | 1982-11-18 | 1989-08-29 | The Trustees Of Columbia University In The City Of New York | Electrophoretic methods employing gel inserts |
US4493815A (en) | 1983-07-28 | 1985-01-15 | Bio-Rad Laboratories, Inc. | Supporting and filtering biochemical test plate assembly |
FR2565350B1 (en) * | 1984-06-05 | 1986-10-10 | Paris Nord Universite | PROPER MEANS FOR ALLOWING AUTOMATIC CONTINUOUS SUPPORT, PROCESSING, STORAGE AND 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 |
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 |
US4685880A (en) * | 1985-06-18 | 1987-08-11 | American Hospital Supply Corporation | Cuvette belts and manufacture of same |
US5047215A (en) | 1985-06-18 | 1991-09-10 | Polyfiltronics, Inc. | Multiwell test plate |
JPS62144048A (en) * | 1985-12-18 | 1987-06-27 | Olympus Optical Co Ltd | Developer concentration measuring apparatus |
US5153319A (en) * | 1986-03-31 | 1992-10-06 | University Patents, Inc. | Process for preparing polynucleotides |
JPS63241359A (en) * | 1986-10-01 | 1988-10-06 | Olympus Optical Co Ltd | Micromodule solid phase method of reagent |
US5000921A (en) | 1986-10-24 | 1991-03-19 | Hanaway Richard W | Multiple pipette samples |
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 |
US4834946A (en) | 1987-02-05 | 1989-05-30 | Levin Andrew E | Apparatus for blot screening numerous, small volume, antibody solutions |
US5077085A (en) | 1987-03-06 | 1991-12-31 | Schnur Joel M | High resolution metal patterning of ultra-thin films on solid substrates |
US4828386A (en) | 1987-06-19 | 1989-05-09 | Pall Corporation | Multiwell plates containing membrane inserts |
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 |
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 |
FR2637687B1 (en) * | 1988-10-11 | 1991-01-11 | Inst Textile De France | SINGLE USE DEVICE FOR BIOLOGICAL TESTS |
DE69025969T2 (en) * | 1989-04-05 | 1996-08-08 | New York University, New York, N.Y. | Particle characterization method |
US5744101A (en) * | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
US5143854A (en) * | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
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 |
US5229163A (en) * | 1989-12-21 | 1993-07-20 | Hoffmann-La Roche Inc. | Process for preparing a microtiter tray for immunometric determinations |
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 |
JPH0678978B2 (en) * | 1990-05-25 | 1994-10-05 | スズキ株式会社 | Aggregation pattern detector |
JPH04250874A (en) * | 1991-01-09 | 1992-09-07 | Canon Inc | Liquid introducing device |
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 |
US5284753A (en) | 1991-03-20 | 1994-02-08 | Neuro Probe, Inc. | Multiple-site chemotactic test apparatus and method |
US5210021A (en) | 1991-03-20 | 1993-05-11 | Neuro Probe, Inc. | Multiple-site chemotactic test apparatus and method |
US5213766A (en) * | 1991-04-30 | 1993-05-25 | Apogee Designs, Ltd. | Liquid collecting apparatus for sample testing |
US5632957A (en) * | 1993-11-01 | 1997-05-27 | Nanogen | Molecular biological diagnostic systems including electrodes |
US5605662A (en) * | 1993-11-01 | 1997-02-25 | Nanogen, Inc. | Active programmable electronic devices for molecular biological analysis and diagnostics |
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 |
WO1995001559A2 (en) | 1993-07-02 | 1995-01-12 | Evotec Biosystems Gmbh | Sample holder and its use |
US5519218A (en) * | 1993-08-04 | 1996-05-21 | Chang; On Kok | Sample holder for spectroscopy |
FR2716263B1 (en) * | 1994-02-11 | 1997-01-17 | Pasteur Institut | Method for aligning macromolecules by passing a meniscus and applications in a method for highlighting, separating and / or assaying a macromolecule in a sample. |
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 |
DE19509094A1 (en) * | 1995-03-16 | 1996-09-26 | Boehringer Mannheim Gmbh | Quantitative transmission spectroscopy using sample carriers with networks |
JPH08254536A (en) * | 1995-03-17 | 1996-10-01 | Toshiba Corp | Automatic chemical analyzer |
US5560811A (en) | 1995-03-21 | 1996-10-01 | Seurat Analytical Systems Incorporated | Capillary electrophoresis apparatus and method |
CA2179364C (en) | 1995-06-27 | 1999-09-28 | Klaus W. Berndt | Method and apparatus for detecting microorganisms |
US5773238A (en) * | 1995-07-07 | 1998-06-30 | Shukla; Ashok K. | Droplet chemical reaction chamber |
AU722335B2 (en) * | 1995-07-31 | 2000-07-27 | Precision System Science Co., Ltd. | Container |
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 |
US5763263A (en) * | 1995-11-27 | 1998-06-09 | Dehlinger; Peter J. | Method and apparatus for producing position addressable combinatorial libraries |
CA2192262C (en) * | 1995-12-08 | 2011-03-15 | Yoshihide Hayashizaki | Method for purification and transfer to separation/detection systems of dna sequencing samples and plates used therefor |
US6660233B1 (en) * | 1996-01-16 | 2003-12-09 | Beckman Coulter, Inc. | Analytical biochemistry system with robotically carried bioarray |
US5849598A (en) * | 1996-03-15 | 1998-12-15 | Washington University | Method for transferring micro quantities of liquid samples to discrete locations |
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 |
US6103479A (en) * | 1996-05-30 | 2000-08-15 | Cellomics, Inc. | Miniaturized cell array methods and apparatus for cell-based screening |
US5795748A (en) * | 1996-09-26 | 1998-08-18 | Becton Dickinson And Company | DNA microwell device and method |
US6024925A (en) * | 1997-01-23 | 2000-02-15 | Sequenom, Inc. | Systems and methods for preparing low volume analyte array elements |
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 |
SE509274C2 (en) * | 1997-03-11 | 1999-01-11 | Gematron Medical Ab | Spectrophotometric analysis cuvette |
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 |
US5922604A (en) * | 1997-06-05 | 1999-07-13 | Gene Tec Corporation | Thin reaction chambers for containing and handling liquid microvolumes |
US6090251A (en) * | 1997-06-06 | 2000-07-18 | Caliper Technologies, Inc. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US6309600B1 (en) * | 1997-08-28 | 2001-10-30 | Biotrove, Inc. | Apparatus for droplet microchemistry |
US6660149B1 (en) * | 1997-10-24 | 2003-12-09 | Beckman Coulter, Inc. | 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 |
AU2102699A (en) * | 1998-01-12 | 1999-07-26 | Massachusetts Institute Of Technology | Method and apparatus for performing microassays |
WO1999039829A1 (en) | 1998-02-04 | 1999-08-12 | Merck & Co., Inc. | Virtual wells for use in high throughput screening assays |
JP3445501B2 (en) * | 1998-09-04 | 2003-09-08 | 日立ソフトウエアエンジニアリング株式会社 | Manufacturing method of sheet-like member laminate and sheet-like probe holder |
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 |
US6306578B1 (en) * | 1999-03-19 | 2001-10-23 | 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 |
WO2001061054A2 (en) * | 2000-02-18 | 2001-08-23 | Board Of Trustees Of The Leland Stanford Junior University | Apparatus and methods for parallel processing of micro-volume liquid reactions |
CA2425476C (en) * | 2000-10-10 | 2011-02-01 | Biotrove, Inc. | Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof |
-
1999
- 1999-01-05 AU AU21026/99A patent/AU2102699A/en not_active Abandoned
- 1999-01-05 DE DE69942697T patent/DE69942697D1/en not_active Expired - Lifetime
- 1999-01-05 EP EP20100008511 patent/EP2286918B1/en not_active Expired - Lifetime
- 1999-01-05 CA CA 2316912 patent/CA2316912C/en not_active Expired - Lifetime
- 1999-01-05 AT AT99901294T patent/ATE322341T1/en not_active IP Right Cessation
- 1999-01-05 WO PCT/US1999/000088 patent/WO1999034920A1/en active IP Right Grant
- 1999-01-05 EP EP19990901294 patent/EP1051259B1/en not_active Expired - Lifetime
- 1999-01-05 AT AT06075151T patent/ATE477850T1/en not_active IP Right Cessation
- 1999-01-05 JP JP2000527355A patent/JP4271371B2/en not_active Expired - Lifetime
- 1999-01-05 US US09/225,583 patent/US6387331B1/en not_active Expired - Lifetime
- 1999-01-05 ES ES06075151T patent/ES2350702T3/en not_active Expired - Lifetime
- 1999-01-05 DE DE1999630726 patent/DE69930726T2/en not_active Expired - Lifetime
- 1999-01-05 EP EP20060075151 patent/EP1714699B1/en not_active Expired - Lifetime
-
2000
- 2000-11-10 US US09/710,082 patent/US6743633B1/en not_active Expired - Lifetime
-
2004
- 2004-03-09 US US10/796,856 patent/US20040171166A1/en not_active Abandoned
-
2007
- 2007-12-19 JP JP2007326956A patent/JP4448166B2/en not_active Expired - Lifetime
-
2009
- 2009-06-15 JP JP2009141991A patent/JP4668334B2/en not_active Expired - Lifetime
-
2010
- 2010-06-04 US US12/794,353 patent/US20110065590A1/en not_active Abandoned
-
2014
- 2014-06-10 US US14/301,325 patent/US20150126412A1/en not_active Abandoned
- 2014-12-23 US US14/582,122 patent/US20170028376A9/en not_active Abandoned
Patent Citations (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3627431A (en) * | 1969-12-22 | 1971-12-14 | John Victor Komarniski | Densitometer |
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 |
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 |
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 |
US4387164A (en) * | 1980-11-05 | 1983-06-07 | Fmc Corporation | Method and apparatus for chemical analysis using reactive reagents dispersed in soluble film |
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 |
US4761378A (en) * | 1983-03-04 | 1988-08-02 | American Home Products Corp. (Del.) | Microbiological testing apparatus |
US4547836A (en) * | 1984-02-01 | 1985-10-15 | General Electric Company | Insulating glass body with electrical feedthroughs and method of preparation |
US4562871A (en) * | 1984-03-16 | 1986-01-07 | Astle Thomas W | Rehydrator |
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 |
US4806316A (en) * | 1987-03-17 | 1989-02-21 | Becton, Dickinson And Company | Disposable device for use in chemical, immunochemical and microorganism analysis |
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 |
US5183761A (en) * | 1989-07-21 | 1993-02-02 | Freeman Mary J | Method of making calibration solution for verifying calibration and linearity of vertical photometers |
US5234666A (en) * | 1990-11-01 | 1993-08-10 | Mitsubishi Denki K.K. | Alcohol content detector |
US5182082A (en) * | 1991-01-23 | 1993-01-26 | Becton, Dickinson And Company | Multiple aliquot device for distributing a liquid solution into a well |
US5290705A (en) * | 1992-01-13 | 1994-03-01 | R. E. Davis Chemical Corporation | Speciman support for optical analysis |
WO1995011755A1 (en) * | 1993-10-28 | 1995-05-04 | Houston Advanced Research Center | Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions |
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 |
US6121048A (en) * | 1994-10-18 | 2000-09-19 | Zaffaroni; Alejandro C. | Method of conducting a plurality of reactions |
US5609828A (en) * | 1995-05-31 | 1997-03-11 | bio M erieux Vitek, Inc. | Sample card |
US5545531A (en) * | 1995-06-07 | 1996-08-13 | Affymax Technologies N.V. | Methods for making a device for concurrently processing multiple biological chip assays |
USH1919H (en) * | 1995-12-01 | 2000-11-07 | E. I. Du Pont De Nemours And Company | Agricultural product microscreen method and apparatus |
US5840256A (en) * | 1996-04-09 | 1998-11-24 | David Sarnoff Research Center Inc. | Plate for reaction system |
US5788814A (en) * | 1996-04-09 | 1998-08-04 | David Sarnoff Research Center | Chucks and methods for positioning multiple objects on a substrate |
US5770860A (en) * | 1996-07-12 | 1998-06-23 | Franzen; Jochen | Method for loading sample supports for mass spectrometers |
US6441973B1 (en) * | 1996-08-16 | 2002-08-27 | Imaging Research, Inc. | Digital imaging system for assays in well plates, gels and blots |
US5854684A (en) * | 1996-09-26 | 1998-12-29 | Sarnoff Corporation | Massively parallel detection |
WO1998045406A1 (en) * | 1997-04-09 | 1998-10-15 | 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 |
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 |
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 |
US7547556B2 (en) * | 1998-01-12 | 2009-06-16 | Massachusetts Institute Of Technology | Methods for filing 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 |
US6309828B1 (en) * | 1998-11-18 | 2001-10-30 | Agilent Technologies, Inc. | Method and apparatus for fabricating replicate arrays of nucleic acid molecules |
Non-Patent Citations (2)
Title |
---|
Lehmann, V., Journal of the Electrochemical Society 1993, 140, 2836-2843. * |
Tonucci, R. J. et al, Science 1992, 258, 783-785. * |
Cited By (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090035759A1 (en) * | 1997-04-17 | 2009-02-05 | Cytonix | Method and device 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 |
US20080160525A1 (en) * | 1997-04-17 | 2008-07-03 | Cytonix | Method and device for detecting the presence of a single target nucleic acid in a sample |
US20080171325A1 (en) * | 1997-04-17 | 2008-07-17 | Cytonix | Method and device for detecting the presence of a single target nucleic acid in a sample |
US20080169184A1 (en) * | 1997-04-17 | 2008-07-17 | Cytonix | Device having regions of differing affinities to fluid, methods of making such devices, and methods of using such devices |
US20080213766A1 (en) * | 1997-04-17 | 2008-09-04 | Cytonix | Method and device for detecting the presence of a single target nucleic acid in samples |
US20080138815A1 (en) * | 1997-04-17 | 2008-06-12 | Cytonix | 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 |
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 |
US8067159B2 (en) | 1997-04-17 | 2011-11-29 | Applied Biosystems, Llc | Methods of detecting amplified product |
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 |
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 |
US8822183B2 (en) | 1997-04-17 | 2014-09-02 | Applied Biosystems, Llc | Device for amplifying target nucleic acid |
US20150126412A1 (en) * | 1998-01-12 | 2015-05-07 | Massachusetts Institute Of Technology | Systems for filling a sample array by droplet dragging |
US8394249B2 (en) | 2002-09-24 | 2013-03-12 | Duke University | Methods for manipulating droplets by electrowetting-based techniques |
US9110017B2 (en) | 2002-09-24 | 2015-08-18 | Duke University | Apparatuses and methods for manipulating droplets |
US20080105549A1 (en) * | 2002-09-24 | 2008-05-08 | Pamela Vamsee K | Methods for performing microfluidic sampling |
US8388909B2 (en) | 2002-09-24 | 2013-03-05 | Duke University | Apparatuses and methods for manipulating droplets |
US8349276B2 (en) | 2002-09-24 | 2013-01-08 | Duke University | Apparatuses and methods for manipulating droplets on a printed circuit board |
US9638662B2 (en) | 2002-09-24 | 2017-05-02 | Duke University | Apparatuses and methods for manipulating droplets |
US8871071B2 (en) | 2002-09-24 | 2014-10-28 | Duke University | Droplet manipulation device |
US20090260988A1 (en) * | 2002-09-24 | 2009-10-22 | Duke University | Methods for Manipulating Droplets by Electrowetting-Based Techniques |
US8906627B2 (en) | 2002-09-24 | 2014-12-09 | Duke University | Apparatuses and methods for manipulating droplets |
US8048628B2 (en) | 2002-09-24 | 2011-11-01 | Duke University | Methods for nucleic acid amplification on a printed circuit board |
US8524506B2 (en) | 2002-09-24 | 2013-09-03 | Duke University | Methods for sampling a liquid flow |
US9180450B2 (en) | 2002-09-24 | 2015-11-10 | Advanced Liquid Logic, Inc. | Droplet manipulation system and method |
US8268246B2 (en) | 2007-08-09 | 2012-09-18 | Advanced Liquid Logic Inc | PCB droplet actuator fabrication |
US9194865B2 (en) * | 2011-12-19 | 2015-11-24 | Yamaha Hatsudoki Kabushiki Kaisha | Object selecting device and object selecting method |
US20140322747A1 (en) * | 2011-12-19 | 2014-10-30 | Yamaha Hatsudoki Kabushiki Kaisha | Object selecting device and object selecting method |
WO2021134014A1 (en) * | 2019-12-27 | 2021-07-01 | Sean Kelly | Analysis of a biological sample using tape-to-tape fluidic transfer |
Also Published As
Publication number | Publication date |
---|---|
JP2008139319A (en) | 2008-06-19 |
US20150298089A1 (en) | 2015-10-22 |
DE69942697D1 (en) | 2010-09-30 |
JP4668334B2 (en) | 2011-04-13 |
AU2102699A (en) | 1999-07-26 |
US20150126412A1 (en) | 2015-05-07 |
EP1051259B1 (en) | 2006-04-05 |
JP4271371B2 (en) | 2009-06-03 |
DE69930726T2 (en) | 2007-01-25 |
EP2286918B1 (en) | 2014-10-01 |
US6387331B1 (en) | 2002-05-14 |
EP1714699B1 (en) | 2010-08-18 |
JP2009244271A (en) | 2009-10-22 |
DE69930726D1 (en) | 2006-05-18 |
JP2002500373A (en) | 2002-01-08 |
EP2286918A1 (en) | 2011-02-23 |
WO1999034920A1 (en) | 1999-07-15 |
EP1714699A1 (en) | 2006-10-25 |
JP4448166B2 (en) | 2010-04-07 |
EP1051259A1 (en) | 2000-11-15 |
US6743633B1 (en) | 2004-06-01 |
ATE322341T1 (en) | 2006-04-15 |
US20040171166A1 (en) | 2004-09-02 |
CA2316912A1 (en) | 1999-07-15 |
ES2350702T3 (en) | 2011-01-26 |
CA2316912C (en) | 2009-09-15 |
US20170028376A9 (en) | 2017-02-02 |
ATE477850T1 (en) | 2010-09-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6743633B1 (en) | Method for performing microassays | |
US6893877B2 (en) | Methods for screening substances in a microwell array | |
JP4387588B2 (en) | Virtual wells for high-throughput screening assays | |
US6306578B1 (en) | Multi-through hole testing plate for high throughput screening | |
US20020092767A1 (en) | Multiple array microfluidic device units | |
US20030180807A1 (en) | Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof | |
Kanigan et al. | Living chips for drug discovery |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |