US20060246576A1 - Fluidic system and method for processing biological microarrays in personal instrumentation - Google Patents

Fluidic system and method for processing biological microarrays in personal instrumentation Download PDF

Info

Publication number
US20060246576A1
US20060246576A1 US11388762 US38876206A US2006246576A1 US 20060246576 A1 US20060246576 A1 US 20060246576A1 US 11388762 US11388762 US 11388762 US 38876206 A US38876206 A US 38876206A US 2006246576 A1 US2006246576 A1 US 2006246576A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
sensor
fluidic
system
container
example
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11388762
Inventor
Mohsen Shirazi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Affymetrix Inc
Original Assignee
Affymetrix Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/52Supports for flat sample carrier, e.g. used for plates, slides, chips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/52Supports for flat sample carrier, e.g. used for plates, slides, chips
    • B01L9/523Supports for flat sample carrier, e.g. used for plates, slides, chips for multisample carriers, e.g. used for microtitration plates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30Staining; Impregnating Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31Apparatus therefor
    • G01N1/312Apparatus therefor for samples mounted on planar substrates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099Characterised by type of test elements
    • G01N2035/00158Elements containing microarrays, i.e. "biochip"
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346Heating or cooling arrangements
    • G01N2035/00356Holding samples at elevated temperature (incubation)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0401Sample carriers, cuvettes or reaction vessels
    • G01N2035/0418Plate elements with several rows of samples
    • G01N2035/0425Stacks, magazines or elevators for plates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0496Other details
    • G01N2035/0498Drawers used as storage or dispensing means for vessels or cuvettes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027General features of the devices
    • G01N2035/1048General features of the devices using the transfer device for another function

Abstract

A fluidic system and method for processing biological sensors. The fluidic system includes a fluidic component including at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the fluidic system includes a support component configured to support at least the first container and the second container. The first container and the second container are substantially stationary with respect to the support component. Moreover, the fluidic system includes a transport component configured to move a first sensor, with respect to the support component, into the first container and in contact with the first volume of the first fluid, and move a second sensor, with respect to the support component, into the second container and in contact with the second volume of the second fluid. The first sensor and the second sensor are moved substantially simultaneously.

Description

    CROSS-REFERENCES TO RELATED APPLICATIONS
  • [0001]
    This application claims priority to U.S. Provisional Application No. 60/669,130, filed Apr. 6, 2005, which is incorporated by reference herein.
  • STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
  • [0002]
    Not applicable.
  • REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED ON A COMPACT DISK.
  • [0003]
    Not applicable.
  • BACKGROUND OF THE INVENTION
  • [0004]
    The present invention relates in general to biological microarray techniques. More particularly, the invention provides a fluidic system and method for processing biological microarrays. Merely by way of example, the invention is described as it applies to personal instrumentation, but it should be recognized that the invention has a broader range of applicability.
  • [0005]
    A biological microarray often includes nucleic acid probes that are used to extract sequence information from nucleic acid samples. The nucleic acid samples are exposed to the nucleic acid probes under certain conditions that would allow hybridization. Afterwards, the biological microarray is processed and scanned to determine to which probes the nucleic acid samples have hybridized. Based on such determination, the sequence information is obtained by comparing patterns of hybridization and non-hybridization. As an example, the sequence information can be used for sequencing nucleic acids, or diagnostic screening for genetic diseases or for the presence of a particular pathogen or a strain of pathogen.
  • [0006]
    The processing of the biological microarray prior to scanning is often performed by a fluidic system. For example, the fluidic system includes a fluidic station. The fluidic station can wash and stain the microarray. With the advancement of the microarray design, the fluidic station often needs to be modified in order to improve automation and lower cost.
  • [0007]
    Hence it is highly desirable to improve fluidic techniques for processing microarrays.
  • BRIEF SUMMARY OF THE INVENTION
  • [0008]
    The present invention relates in general to biological microarray techniques. More particularly, the invention provides a fluidic system and method for processing biological microarrays. Merely by way of example, the invention is described as it applies to personal instrumentation, but it should be recognized that the invention has a broader range of applicability.
  • [0009]
    According to one embodiment of the present invention, a fluidic system for processing biological sensors includes a fluidic component including at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the fluidic system includes a support component configured to support at least the first container and the second container. The first container and the second container are substantially stationary with respect to the support component. Moreover, the fluidic system includes a transport component configured to move a first sensor, with respect to the support component, into the first container and in contact with the first volume of the first fluid, and move a second sensor, with respect to the support component, into the second container and in contact with the second volume of the second fluid. The first sensor and the second sensor are moved substantially simultaneously.
  • [0010]
    According to another embodiment, a fluidic system for processing biological sensors includes a fluidic component including at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the fluidic system includes a support component including a panel for supporting at least the first container and the second container. The first container and the second container are substantially stationary with respect to the panel. Moreover, the fluidic system includes a transport component including a gripper and at least one motor. The gripper is capable of gripping the first sensor and the second sensor substantially simultaneously and of releasing the first sensor and the second sensor substantially simultaneously. The at least one motor is configured to move the gripped first sensor, with respect to the panel, into the first container and in contact with the first volume of the first fluid. The at least one motor is further configured to move the gripped second sensor, with respect to the panel, into the second container and in contact with the second volume of the second fluid. The first sensor and the second sensor are moved substantially simultaneously.
  • [0011]
    According to another embodiment, a method for processing biological sensors includes performing a hybridization process on at least a first sensor and a second sensor, and after the hybridization process, transferring the first sensor and the second sensor into a fluidic system. The fluidic system includes at least a first container and a second container, the first container holds a first volume of a first fluid, and the second container holds a second volume of a second fluid. Additionally, the method includes moving the first sensor into the first container and in contact with the first volume of the first fluid, and moving the second sensor into the second container and in contact with the second volume of the second fluid. The moving the first sensor and the moving the second sensor are performed substantially simultaneously.
  • [0012]
    Many benefits are achieved by way of the present invention over conventional techniques. Certain embodiments of the present invention provide an automated fluidic system. Some embodiments of the present invention provide a low-cost fluidic system. Certain embodiments of the present invention can improve throughput of the fluidic system. For example, a plurality of biological sensors, such as microarrays, is processed in parallel. Some embodiments of the present invention can reduce cross-contamination between different processes performed on one or more biological sensors. For example, at a given process, different sensors are washed, stained, and/or held in different wells. In another example, a given sensor is washed, stained, and/or held in different wells for different processes respectively. In yet another example, each well is used for at most a single process for at most a single sensor, such as a microarray.
  • [0013]
    Depending upon embodiment, one or more of these benefits may be achieved. These benefits and various additional objects, features and advantages of the present invention can be fully appreciated with reference to the detailed description and accompanying drawings that follow.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0014]
    FIGS. 1-4 show a simplified fluidic system for processing biological sensors according to an embodiment of the present invention;
  • [0015]
    FIGS. 5(A) and (B) show a simplified well strip in fluidic system for processing biological sensors according to an embodiment of the present invention;
  • [0016]
    FIG. 6 is a simplified diagram showing temperature as function of time for well strip in fluidic system for processing biological sensors according to an embodiment of the present invention;
  • [0017]
    FIGS. 7(A) and (B) show a simplified gripper in fluidic system for processing biological sensors according to an embodiment of the present invention;
  • [0018]
    FIG. 8 shows a simplified fluidic system for processing biological sensors according to another embodiment of the present invention;
  • [0019]
    FIG. 9 shows a simplified fluidic method for processing biological sensors that is performed by fluidic system 100 or 800 according to an embodiment of the present invention;
  • [0020]
    FIGS. 10(A)-(V) are simplified diagrams showing movement of one or more sensors made by fluidic system 100 or 800 according to an embodiment of the present invention;
  • [0021]
    FIGS. 11(A) and (B) are simplified microarrays on pegs that can be processed by fluidic system 100 or 800 according to an embodiment of the present invention;
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0022]
    The present invention relates in general to biological microarray techniques. More particularly, the invention provides a fluidic system and method for processing biological microarrays. Merely by way of example, the invention is described as it applies to personal instrumentation, but it should be recognized that the invention has a broader range of applicability.
  • I. General Description
  • [0023]
    The present invention cites certain patents, applications and other references. When a patent, application, or other reference is cited or repeated below, it should be understood that it is incorporated by reference in its entirety for all purposes as well as for the proposition that is recited.
  • [0024]
    As used in this application, the singular form “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “an agent” includes a plurality of agents, including mixtures thereof.
  • [0025]
    An individual is not limited to a human being but may also be other organisms including but not limited to mammals, plants, bacteria, or cells derived from any of the above.
  • [0026]
    Throughout this disclosure, various aspects of this invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.
  • [0027]
    The practice of the present invention may employ, unless otherwise indicated, conventional techniques and descriptions of organic chemistry, polymer technology, molecular biology (including recombinant techniques), cell biology, biochemistry, and immunology, which are within the skill of the art. Such conventional techniques include polymer array synthesis, hybridization, ligation, and detection of hybridization using a label. Specific illustrations of suitable techniques can be had by reference to the example herein below. However, other equivalent conventional procedures can, of course, also be used. Such conventional techniques and descriptions can be found in standard laboratory manuals such as Genome Analysis: A Laboratory Manual Series (Vols. I-IV), Using Antibodies: A Laboratory Manual, Cells: A Laboratory Manual, PCR Primer: A Laboratory Manual, and Molecular Cloning: A Laboratory Manual (all from Cold Spring Harbor Laboratory Press), Stryer, L. (1995) Biochemistry (4th Ed.) Freeman, New York, Gait, “Oligonucleotide Synthesis: A Practical Approach” 1984, IRL Press, London, Nelson and Cox (2000), Lehninger, Principles of Biochemistry 3rd Ed., W.H. Freeman Pub., New York, N.Y. and Berg et al. (2002) Biochemistry, 5th Ed., W.H. Freeman Pub., New York, N.Y., all of which are herein incorporated in their entirety by reference for all purposes.
  • [0028]
    The present invention can employ solid substrates, including arrays in some preferred embodiments. Methods and techniques applicable to polymer (including protein) array synthesis have been described in U.S. Ser. No. 09/536,841, WO 00/58516, U.S. Pat. Nos. 5,143,854, 5,242,974, 5,252,743, 5,324,633, 5,384,261, 5,405,783, 5,424,186, 5,451,683, 5,482,867, 5,491,074, 5,527,681, 5,550,215, 5,571,639, 5,578,832, 5,593,839, 5,599,695, 5,624,711, 5,631,734, 5,795,716, 5,831,070, 5,837,832, 5,856,101, 5,858,659, 5,936,324, 5,968,740, 5,974,164, 5,981,185, 5,981,956, 6,025,601, 6,033,860, 6,040,193, 6,090,555, 6,136,269, 6,269,846 and 6,428,752, in PCT Applications Nos. PCT/US99/00730 (International Publication Number WO 99/36760) and PCT/US01/04285 (International Publication Number WO 01/58593), which are all incorporated herein by reference in their entirety for all purposes.
  • [0029]
    Patents that describe synthesis techniques in specific embodiments include U.S. Patent Nos. 5,412,087, 6,147,205, 6,262,216, 6,310,189, 5,889,165, and 5,959,098.
  • [0030]
    Nucleic acid arrays are described in many of the above patents, but the same techniques are applied to polypeptide arrays.
  • [0031]
    Nucleic acid arrays that are useful in the present invention include those that are commercially available from Affymetrix (Santa Clara, Calif.) under the brand name GeneChip®. Example arrays are shown on the website at affymetrix.com.
  • [0032]
    The present invention also contemplates many uses for polymers attached to solid substrates. These uses include gene expression monitoring, profiling, library screening, genotyping and diagnostics. Gene expression monitoring and profiling methods can be shown in U.S. Pat. Nos. 5,800,992, 6,013,449, 6,020,135, 6,033,860, 6,040,138, 6,177,248 and 6,309,822. Genotyping and uses therefore are shown in U.S. Ser. Nos. 15 10/442,021, 10/013,598 (U.S. Patent Application Publication 20030036069), and U.S. Pat. Nos. 5,856,092, 6,300,063, 5,858,659, 6,284,460, 6,361,947, 6,368,799 and 6,333,179. Other uses are embodied in U.S. Pat. Nos. 5,871,928, 5,902,723, 6,045,996, 5,541,061, and 6,197,506.
  • [0033]
    The present invention also contemplates sample preparation methods in certain preferred embodiments. Prior to or concurrent with genotyping, the genomic sample may be amplified by a variety of mechanisms, some of which may employ PCR. See, e.g., PCR Technology: Principles and Applications for DNA Amplification (Ed. H.A. Erlich, Freeman Press, NY, N.Y., 1992); PCR Protocols: A Guide to Methods and Applications (Eds. Innis, et al., Academic Press, San Diego, Calif., 1990); Mattila et al., Nucleic Acids Res. 19, 4967 (1991); Eckert et al., PCR Methods and Applications 1, 17 (1991); PCR (Eds. McPherson et al., IRL Press, Oxford); and U.S. Pat. Nos. 4,683,202, 4,683,195, 4,800,159 4,965,188, and 5,333,675, and each of which is incorporated herein by reference in their entireties for all purposes. The sample may be amplified on the array. See, for example, U.S. Pat. No. 6,300,070 and U.S. Ser. No. 09/513,300, which are incorporated herein by reference.
  • [0034]
    Other suitable amplification methods include the ligase chain reaction (LCR) (e.g., Wu and Wallace, Genomics 4, 560 (1989), Landegren et al., Science 241, 1077 (1988) and Barringer et al. Gene 89:117 (1990)), transcription amplification (Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989) and WO88/10315), self-sustained sequence replication (Guatelli et al., Proc. Nat. Acad. Sci. USA, 87, 1874 (1990) and WO90/06995), selective amplification of target polynucleotide sequences (U.S. Pat. No. 6,410,276), consensus sequence primed polymerase chain reaction (CP-PCR) (U.S. Pat. No. 4,437,975), arbitrarily primed polymerase chain reaction (AP-PCR) (U.S. Pat. Nos. 5,413,909, 5,861,245) and nucleic acid based sequence amplification (NABSA). (See, U.S. Pat. Nos. 5,409,818, 5,554,517, and 6,063,603, each of which is incorporated herein by reference). Other amplification methods that may be used are described in U.S. Pat. Nos. 5,242,794, 5,494,810, 4,988,617 and in U.S. Ser. No. 09/854,317, each of which is incorporated herein by reference.
  • [0035]
    Additional methods of sample preparation and techniques for reducing the complexity of a nucleic sample are described in Dong et al., Genome Research 11, 1418 (2001), in U.S. Pat. No. 6,361,947, 6,391,592 and U.S. Ser. Nos. 09/916,135, 09/920,491 (U.S. Patent Application Publication 20030096235), Ser. No. 09/910,292 (U.S. Patent Application Publication 20030082543), and Ser. No. 10/013,598.
  • [0036]
    Methods for conducting polynucleotide hybridization assays have been well developed in the art. Hybridization assay procedures and conditions will vary depending on the application and are selected in accordance with the general binding methods known including those referred to in: Maniatis et al. Molecular Cloning: A Laboratory Manual (2nd Ed. Cold Spring Harbor, N.Y., 1989); Berger and Kimmel Methods in Enzymology, Vol. 152, Guide to Molecular Cloning Techniques (Academic Press, Inc., San Diego, Calif., 1987); Young and Davism, P.N.A.S. 80: 1194 (1983). Methods and apparatus for carrying out repeated and controlled hybridization reactions have been described in U.S. Pat. Nos. 5,871,928, 5,874,219, 6,045,996 and 6,386,749, 6,391,623 each of which are incorporated herein by reference.
  • [0037]
    The present invention also contemplates signal detection of hybridization between ligands in certain preferred embodiments. See U.S. Pat. Nos. 5,143,854, 5,578,832; 5,631,734; 5,834,758; 5,936,324; 5,981,956; 6,025,601; 6,141,096; 6,185,030; 6,201,639; 6,218,803; and 6,225,625, in U.S. Ser. No. 10/389,194 and in PCT Application PCT/US99/06097 (published as WO99/47964), each of which also is hereby incorporated by reference in its entirety for all purposes.
  • [0038]
    Methods and apparatus for signal detection and processing of intensity data are disclosed in, for example, U.S. Pat. Nos. 5,143,854, 5,547,839, 5,578,832, 5,631,734, 5,800,992, 5,834,758; 5,856,092, 5,902,723, 5,936,324, 5,981,956, 6,025,601, 6,090,555, 6,141,096, 6,185,030, 6,201,639; 6,218,803; and 6,225,625, in U.S. Ser. Nos. 10/389,194, 60/493,495 and in PCT Application PCT/US99/06097 (published as WO99/47964), each of which also is hereby incorporated by reference in its entirety for all purposes.
  • [0039]
    The practice of the present invention may also employ conventional biology methods, software and systems. Computer software products of the invention typically include computer readable medium having computer-executable instructions for performing the logic steps of the method of the invention. Suitable computer readable medium include floppy disk, CD-ROM/DVD/DVD-ROM, hard-disk drive, flash memory, ROM/RAM, magnetic tapes and etc. The computer executable instructions may be written in a suitable computer language or combination of several languages. Basic computational biology methods are described in, e.g. Setubal and Meidanis et al., Introduction to Computational Biology Methods (PWS Publishing Company, Boston, 1997); Salzberg, Searles, Kasif, (Ed.), Computational Methods in Molecular Biology, (Elsevier, Amsterdam, 1998); Rashidi and Buehler, Bioinformatics Basics: Application in Biological Science and Medicine (CRC Press, London, 2000) and Ouelette and Bzevanis Bioinformatics: A Practical Guide for Analysis of Gene and Proteins (Wiley & Sons, Inc., 2nd ed., 2001). See U.S. Pat. No. 6,420,108.
  • [0040]
    The present invention may also make use of various computer program products and software for a variety of purposes, such as probe design, management of data, analysis, and instrument operation. See, U.S. Pat. Nos. 5,593,839, 5,795,716, 5,733,729, 5,974,164, 6,066,454, 6,090,555, 6,185,561, 6,188,783, 6,223,127, 6,229,911 and 6,308,170.
  • [0041]
    Additionally, the present invention may have preferred embodiments that include methods for providing genetic information over networks such as the Internet as shown in U.S. Ser. Nos. 10/197,621, 10/063,559 (United States Publication No. 20020183936), Ser. Nos. 10/065,856, 10/065,868, 10/328,818, 10/328,872, 10/423,403, and 60/482,389.
  • II. Definitions
  • [0042]
    An “array” is an intentionally created collection of molecules which can be prepared either synthetically or biosynthetically. The molecules in the array can be identical or different from each other. The array can assume a variety of formats, e.g., libraries of soluble molecules; libraries of compounds tethered to resin beads, silica chips, or other solid supports.
  • [0043]
    Nucleic acid library or array is an intentionally created collection of nucleic acids which can be prepared either synthetically or biosynthetically and screened for biological activity in a variety of different formats (e.g., libraries of soluble molecules; and libraries of oligos tethered to resin beads, silica chips, or other solid supports). Additionally, the term “array” is meant to include those libraries of nucleic acids which can be prepared by spotting nucleic acids of essentially any length (e.g., from 1 to about 1000 nucleotide monomers in length) onto a substrate. The term “nucleic acid” as used herein refers to a polymeric form of nucleotides of any length, either ribonucleotides, deoxyribonucleotides or peptide nucleic acids (PNAs), that comprise purine and pyrimidine bases, or other natural, chemically or biochemically modified, non-natural, or derivatized nucleotide bases. The backbone of the polynucleotide can comprise sugars and phosphate groups, as may typically be found in RNA or DNA, or modified or substituted sugar or phosphate groups. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interrupted by non-nucleotide components. Thus the terms nucleoside, nucleotide, deoxynucleoside and deoxynucleotide generally include analogs such as those described herein. These analogs are those molecules having some structural features in common with a naturally occurring nucleoside or nucleotide such that when incorporated into a nucleic acid or oligonucleoside sequence, they allow hybridization with a naturally occurring nucleic acid sequence in solution. Typically, these analogs are derived from naturally occurring nucleosides and nucleotides by replacing and/or modifying the base, the ribose or the phosphodiester moiety. The changes can be tailor made to stabilize or destabilize hybrid formation or enhance the specificity of hybridization with a complementary nucleic acid sequence as desired.
  • [0044]
    Biopolymer or biological polymer: is intended to mean repeating units of biological or chemical moieties. Representative biopolymers include, but are not limited to, nucleic acids, oligonucleotides, amino acids, proteins, peptides, hormones, oligosaccharides, lipids, glycolipids, lipopolysaccharides, phospholipids, synthetic analogues of the foregoing, including, but not limited to, inverted nucleotides, peptide nucleic acids, Meta-DNA, and combinations of the above. “Biopolymer synthesis” is intended to encompass the synthetic production, both organic and inorganic, of a biopolymer.
  • [0045]
    Related to a bioploymer is a “biomonomer” which is intended to mean a single unit of biopolymer, or a single unit which is not part of a biopolymer. Thus, for example, a nucleotide is a biomonomer within an oligonucleotide biopolymer, and an amino acid is a biomonomer within a protein or peptide biopolymer; avidin, biotin, antibodies, antibody fragments, etc., for example, are also biomonomers. initiation Biomonomer: or “initiator biomonomer” is meant to indicate the first biomonomer which is covalently attached via reactive nucleophiles to the surface of the polymer, or the first biomonomer which is attached to a linker or spacer arm attached to the polymer, the linker or spacer arm being attached to the polymer via reactive nucleophiles.
  • [0046]
    Complementary: Refers to the hybridization or base pairing between nucleotides or nucleic acids, such as, for instance, between the two strands of a double stranded DNA molecule or between an oligonucleotide primer and a primer binding site on a single stranded nucleic acid to be sequenced or amplified. Complementary nucleotides are, generally, A and T (or A and U), or C and G. Two single stranded RNA or DNA molecules are said to be complementary when the nucleotides of one strand, optimally aligned and compared and with appropriate nucleotide insertions or deletions, pair with at least about 80% of the nucleotides of the other strand, usually at least about 90% to 95%, and more preferably from about 98 to 100%. Alternatively, complementarity exists when an RNA or DNA strand will hybridize under selective hybridization conditions to its complement. Typically, selective hybridization will occur when there is at least about 65% complementary over a stretch of at least 14 to 25 nucleotides, preferably at least about 75%, more preferably at least about 90% complementary. See, M. Kanehisa Nucleic Acids Res. 12:203 (1984), incorporated herein by reference.
  • [0047]
    Combinatorial Synthesis Strategy: A combinatorial synthesis strategy is an ordered strategy for parallel synthesis of diverse polymer sequences by sequential addition of reagents which may be represented by a reactant matrix and a switch matrix, the product of which is a product matrix. A reactant matrix is a 1 column by m row matrix of the building blocks to be added. The switch matrix is all or a subset of the binary numbers, preferably ordered, between 1 and m arranged in columns. A “binary strategy” is one in which at least two successive steps illuminate a portion, often half, of a region of interest on the substrate. In a binary synthesis strategy, all possible compounds which can be formed from an ordered set of reactants are formed. In most preferred embodiments, binary synthesis refers to a synthesis strategy which also factors a previous addition step. For example, a strategy in which a switch matrix for a masking strategy halves regions that were previously illuminated, illuminating about half of the previously illuminated region and protecting the remaining half (while also protecting about half of previously protected regions and illuminating about half of previously protected regions). It will be recognized that binary rounds may be interspersed with non-binary rounds and that only a portion of a substrate may be subjected to a binary scheme. A combinatorial “masking” strategy is a synthesis which uses light or other spatially selective deprotecting or activating agents to remove protecting groups from materials for addition of other materials such as amino acids.
  • [0048]
    Effective amount refers to an amount sufficient to induce a desired result.
  • [0049]
    Genome is all the genetic material in the chromosomes of an organism. DNA derived from the genetic material in the chromosomes of a particular organism is genomic DNA.
  • [0050]
    A genomic library is a collection of clones made from a set of randomly generated overlapping DNA fragments representing the entire genome of an organism. Hybridization conditions will typically include salt concentrations of less than about 1M, more usually less than about 500 mM and preferably less than about 200 mM. Hybridization temperatures can be as low as 5.degree. C., but are typically greater than 22.degree. C., more typically greater than about 30.degree. C., and preferably in excess of about 37.degree. C. Longer fragments may require higher hybridization temperatures for specific hybridization. As other factors may affect the stringency of hybridization, including base composition and length of the complementary strands, presence of organic solvents and extent of base mismatching, the combination of parameters is more important than the absolute measure of any one alone.
  • [0051]
    Hybridizations, e.g., allele-specific probe hybridizations, are generally performed under stringent conditions. For example, conditions where the salt concentration is no more than about 1 Molar (M) and a temperature of at least 25 degrees Celsius (° C.), e.g., 750 mM NaCl, 50 mM NaPhosphate, 5 mM EDTA, pH 7.4 (5×SSPE) and a temperature of from about 25 to about 30° C.
  • [0052]
    Hybridizations are usually performed under stringent conditions, for example, at a salt concentration of no more than 1 M and a temperature of at least 25° C. For example, conditions of 5×SSPE (750 mM NaCl, 50 mM NaPhosphate, 5 mM EDTA, pH 7.4) and a temperature of 25-30° C. are suitable for allele-specific probe hybridizations. For stringent conditions, see, for example, Sambrook, Fritsche and Maniatis. “Molecular Cloning A laboratory Manual” 2nd Ed. Cold Spring Harbor Press (1989) which is hereby incorporated by reference in its entirety for all purposes above.
  • [0053]
    The term “hybridization” refers to the process in which two single-stranded polynucleotides bind non-covalently to form a stable double-stranded polynucleotide; triple-stranded hybridization is also theoretically possible. The resulting (usually) double-stranded polynucleotide is a “hybrid.” The proportion of the population of polynucleotides that forms stable hybrids is referred to herein as the “degree of hybridization.”
  • [0054]
    Hybridization probes are oligonucleotides capable of binding in a base-specific manner to a complementary strand of nucleic acid. Such probes include peptide nucleic acids, as described in Nielsen et al., Science 254, 1497-1500 (1991), and other nucleic acid analogs and nucleic acid mimetics.
  • [0055]
    Hybridizing specifically to: refers to the binding, duplexing, or hybridizing of a molecule only to a particular nucleotide sequence or sequences under stringent conditions when that sequence is present in a complex mixture (e.g., total cellular) DNA or RNA.
  • [0056]
    Isolated nucleic acid is an object species invention that is the predominant species present (i.e., on a molar basis it is more abundant than any other individual species in the composition). Preferably, an isolated nucleic acid comprises at least about 50, 80 or 90% (on a molar basis) of all macromolecular species present. Most preferably, the object species is purified to essential homogeneity (contaminant species cannot be detected in the composition by conventional detection methods).
  • [0057]
    Ligand: A ligand is a molecule that is recognized by a particular receptor. The agent bound by or reacting with a receptor is called a “ligand,” a term which is definitionally meaningful only in terms of its counterpart receptor. The term “ligand” does not imply any particular molecular size or other structural or compositional feature other than that the substance in question is capable of binding or otherwise interacting with the receptor. Also, a ligand may serve either as the natural ligand to which the receptor binds, or as a functional analogue that may act as an agonist or antagonist. Examples of ligands that can be investigated by this invention include, but are not restricted to, agonists and antagonists for cell membrane receptors, toxins and venoms, viral epitopes, hormones (e.g., opiates, steroids, etc.), hormone receptors, peptides, enzymes, enzyme substrates, substrate analogs, transition state analogs, cofactors, drugs, proteins, and antibodies. Linkage disequilibrium or allelic association means the preferential association of a particular allele or genetic marker with a specific allele, or genetic marker at a nearby chromosomal location more frequently than expected by chance for any particular allele frequency in the population. For example, if locus X has alleles a and b, which occur equally frequently, and linked locus Y has alleles c and d, which occur equally frequently, one would expect the combination ac to occur with a frequency of 0.25. If ac occurs more frequently, then alleles a and c are in linkage disequilibrium. Linkage disequilibrium may result from natural selection of certain combination of alleles or because an allele has been introduced into a population too recently to have reached equilibrium with linked alleles.
  • [0058]
    Mixed population or complex population: refers to any sample containing both desired and undesired nucleic acids. As a non-limiting example, a complex population of nucleic acids may be total genomic DNA, total genomic RNA or a combination thereof. Moreover, a complex population of nucleic acids may have been enriched for a given population but include other undesirable populations. For example, a complex population of nucleic acids may be a sample which has been enriched for desired messenger RNA (mRNA) sequences but still includes some undesired ribosomal RNA sequences (rRNA).
  • [0059]
    Monomer: refers to any member of the set of molecules that can be joined together to form an oligomer or polymer. The set of monomers useful in the present invention includes, but is not restricted to, for the example of (poly)peptide synthesis, the set of L-amino acids, D-amino acids, or synthetic amino acids. As used herein, “monomer” refers to any member of a basis set for synthesis of an oligomer. For example, dimers of L-amino acids form a basis set of 400 “monomers” for synthesis of polypeptides. Different basis sets of monomers may be used at successive steps in the synthesis of a polymer.
  • [0060]
    The term “monomer” also refers to a chemical subunit that can be combined with a different chemical subunit to form a compound larger than either subunit alone. mRNA or mRNA transcripts: as used herein, include, but not limited to pre-mRNA transcript(s), transcript processing intermediates, mature mRNA(s) ready for translation and transcripts of the gene or genes, or nucleic acids derived from the mRNA transcript(s). Transcript processing may include splicing, editing and degradation. As used herein, a nucleic acid derived from an mRNA transcript refers to a nucleic acid for whose synthesis the mRNA transcript or a subsequence thereof has ultimately served as a template. Thus, a cDNA reverse transcribed from an mRNA, an RNA transcribed from that cDNA, a DNA amplified from the cDNA, an RNA transcribed from the amplified DNA, etc., are all derived from the mRNA transcript and detection of such derived products is indicative of the presence and/or abundance of the original transcript in a sample. Thus, mRNA derived samples include, but are not limited to, mRNA transcripts of the gene or genes, cDNA reverse transcribed from the mRNA, cRNA transcribed from the cDNA, DNA amplified from the genes, RNA transcribed from amplified DNA, and the like.
  • [0061]
    Nucleic acid library or array is an intentionally created collection of nucleic acids which can be prepared either synthetically or biosynthetically and screened for biological activity in a variety of different formats (e.g., libraries of soluble molecules; and libraries of oligos tethered to resin beads, silica chips, or other solid supports). Additionally, the term “array” is meant to include those libraries of nucleic acids which can be prepared by spotting nucleic acids of essentially any length (e.g., from 1 to about 1000 nucleotide monomers in length) onto a substrate. The term “nucleic acid” as used herein refers to a polymeric form of nucleotides of any length, either ribonucleotides, deoxyribonucleotides or peptide nucleic acids (PNAs), that comprise purine and pyrimidine bases, or other natural, chemically or biochemically modified, non-natural, or derivatized nucleotide bases. The backbone of the polynucleotide can comprise sugars and phosphate groups, as may typically be found in RNA or DNA, or modified or substituted sugar or phosphate groups. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interrupted by non-nucleotide components. Thus the terms nucleoside, nucleotide, deoxynucleoside and deoxynucleotide generally include analogs such as those described herein. These analogs are those molecules having some structural features in common with a naturally occurring nucleoside or nucleotide such that when incorporated into a nucleic acid or oligonucleoside sequence, they allow hybridization with a naturally occurring nucleic acid sequence in solution. Typically, these analogs are derived from naturally occurring nucleosides and nucleotides by replacing and/or modifying the base, the ribose or the phosphodiester moiety. The changes can be tailor made to stabilize or destabilize hybrid formation or enhance the specificity of hybridization with a complementary nucleic acid sequence as desired.
  • [0062]
    Nucleic acids according to the present invention may include any polymer or oligomer of pyrimidine and purine bases, preferably cytosine, thymine, and uracil, and adenine and guanine, respectively. See Albert L. Lehninger, PRINCIPLES OF BIOCHEMISTRY, at 793-800 (Worth Pub. 1982). Indeed, the present invention contemplates any deoxyribonucleotide, ribonucleotide or peptide nucleic acid component, and any chemical variants thereof, such as methylated, hydroxymethylated or glucosylated forms of these bases, and the like. The polymers or oligomers may be heterogeneous or homogeneous in composition, and may be isolated from naturally-occurring sources or may be artificially or synthetically produced. In addition, the nucleic acids may be DNA or RNA, or a mixture thereof, and may exist permanently or transitionally in single-stranded or double-stranded form, including homoduplex, heteroduplex, and hybrid states.
  • [0063]
    An “oligonucleotide” or “polynucleotide” is a nucleic acid ranging from at least 2, preferable at least 8, and more preferably at least 20 nucleotides in length or a compound that specifically hybridizes to a polynucleotide. Polynucleotides of the present invention include sequences of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) which may be isolated from natural sources, recombinantly produced or artificially synthesized and mimetics thereof. A further example of a polynucleotide of the present invention may be peptide nucleic acid (PNA). The invention also encompasses situations in which there is a nontraditional base pairing such as Hoogsteen base pairing which has been identified in certain tRNA molecules and postulated to exist in a triple helix. “Polynucleotide” and “oligonucleotide” are used interchangeably in this application.
  • [0064]
    Probe: A probe is a surface-immobilized molecule that can be recognized by a particular target. See U.S. Pat. No. 6,582,908 for an example of arrays having all possible combinations of probes with 10, 12, and more bases. Examples of probes that can be investigated by this invention include, but are not restricted to, agonists and antagonists for cell membrane receptors, toxins and venoms, viral epitopes, hormones (e.g., opioid peptides, steroids, etc.), hormone receptors, peptides, enzymes, enzyme substrates, cofactors, drugs, lectins, sugars, oligonucleotides, nucleic acids, oligosaccharides, proteins, and monoclonal antibodies.
  • [0065]
    Primer is a single-stranded oligonucleotide capable of acting as a point of initiation for template-directed DNA synthesis under suitable conditions e.g., buffer and temperature, in the presence of four different nucleoside triphosphates and an agent for polymerization, such as, for example, DNA or RNA polymerase or reverse transcriptase. The length of the primer, in any given case, depends on, for example, the intended use of the primer, and generally ranges from 15 to 30 nucleotides. Short primer molecules generally require cooler temperatures to form sufficiently stable hybrid complexes with the template. A primer need not reflect the exact sequence of the template but must be sufficiently complementary to hybridize with such template. The primer site is the area of the template to which a primer hybridizes. The primer pair is a set of primers including a 5′ upstream primer that hybridizes with the 5′ end of the sequence to be amplified and a 3′ downstream primer that hybridizes with the complement of the 3′ end of the sequence to be amplified.
  • [0066]
    Polymorphism refers to the occurrence of two or more genetically determined alternative sequences or alleles in a population. A polymorphic marker or site is the locus at which divergence occurs. Preferred markers have at least two alleles, each occurring at frequency of greater than 1%, and more preferably greater than 10% or 20% of a selected population. A polymorphism may comprise one or more base changes, an insertion, a repeat, or a deletion. A polymorphic locus may be as small as one base pair. Polymorphic markers include restriction fragment length polymorphisms, variable number of tandem repeats (VNTR's), hypervariable regions, minisatellites, dinucleotide repeats, trinucleotide repeats, tetranucleotide repeats, simple sequence repeats, and insertion elements such as Alu. The first identified allelic form is arbitrarily designated as the reference form and other allelic forms are designated as alternative or variant alleles. The allelic form occurring most frequently in a selected population is sometimes referred to as the wildtype form. Diploid organisms may be homozygous or heterozygous for allelic forms. A diallelic polymorphism has two forms. A triallelic polymorphism has three forms. Single nucleotide polymorphisms (SNPs) are included in polymorphisms.
  • [0067]
    Receptor: A molecule that has an affinity for a given ligand. Receptors may be naturally-occurring or manmade molecules. Also, they can be employed in their unaltered state or as aggregates with other species. Receptors may be attached, covalently or noncovalently, to a binding member, either directly or via a specific binding substance. Examples of receptors which can be employed by this invention include, but are not restricted to, antibodies, cell membrane receptors, monoclonal antibodies and antisera reactive with specific antigenic determinants (such as on viruses, cells or other materials), drugs, polynucleotides, nucleic acids, peptides, cofactors, lectins, sugars, polysaccharides, cells, cellular membranes, and organelles. Receptors are sometimes referred to in the art as anti-ligands. As the term receptors is used herein, no difference in meaning is intended. A “Ligand Receptor Pair” is formed when two macromolecules have combined through molecular recognition to form a complex. Other examples of receptors which can be investigated by this invention include but are not restricted to those molecules shown in U.S. Pat. No. 5,143,854, which is hereby incorporated by reference in its entirety.
  • [0068]
    “Solid support”, “support”, and “substrate” are used interchangeably and refer to a material or group of materials having a rigid or semi-rigid surface or surfaces. In many embodiments, at least one surface of the solid support will be substantially flat, although in some embodiments it may be desirable to physically separate synthesis regions for different compounds with, for example, wells, raised regions, pins, etched trenches, or the like. According to other embodiments, the solid support(s) will take the form of beads, resins, gels, microspheres, or other geometric configurations. See U.S. Pat. No. 5,744,305 for exemplary substrates.
  • [0069]
    Target: A molecule that has an affinity for a given probe. Targets may be naturally occurring or man-made molecules. Also, they can be employed in their unaltered state or as aggregates with other species. Targets may be attached, covalently or noncovalently, to a binding member, either directly or via a specific binding substance. Examples of targets which can be employed by this invention include, but are not restricted to, antibodies, cell membrane receptors, monoclonal antibodies and antisera reactive with specific antigenic determinants (such as on viruses, cells or other materials), drugs, oligonucleotides, nucleic acids, peptides, cofactors, lectins, sugars, polysaccharides, cells, cellular membranes, and organelles. Targets are sometimes referred to in the art as anti-probes. As the term targets is used herein, no difference in meaning is intended. A “Probe Target Pair” is formed when two macromolecules have combined through molecular recognition to form a complex.
  • III. Specific Embodiments
  • [0070]
    FIGS. 1-4 show a simplified fluidic system for processing biological sensors according to an embodiment of the present invention. These diagrams are merely examples, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. The system 100 includes a fluidic component 110, a support component 120, and an electrical and mechanical component 130. Although the above has been shown using a selected group of components for the system 100, there can be many alternatives, modifications, and variations. For example, some of the components may be expanded and/or combined. Other components may be inserted to those noted above. Depending upon the embodiment, the arrangement of components may be interchanged with others replaced. Further details of these components are found throughout the present specification and more particularly below.
  • [0071]
    The fluidic component 110 includes at least some containers. Each of these containers includes one or more fluids for processing at least one biological sensor. For example, each container is a well. In another example, the wells are grouped into one or more plate and/or one or more strip. As shown in FIGS. 1-4, the wells are grouped into at least a well plate 112 and a well strip 114. In one embodiment, the well plate 112 includes 96 wells, and the well strip 114 includes 4 wells. In another embodiment, each well contains one or more fluids, and different wells contain the same or different fluids. In yet another embodiment, different wells have the same or different depths.
  • [0072]
    FIGS. 5(A) and (B) show a simplified well strip 114 in fluidic system 100 for processing biological sensors according to an embodiment of the present invention. These diagrams are merely examples, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. The well strip 114 includes a plurality of tubes 510, a heater 512, and a thermometer 514 such as a thermocouple. Although the above has been shown using a selected group of components for the well strip 114, there can be many alternatives, modifications, and variations. For example, some of the components may be expanded and/or combined. Other components may be inserted to those noted above. Depending upon the embodiment, the arrangement of components may be interchanged with others replaced. Further details of these components are found throughout the present specification and more particularly below.
  • [0073]
    The plurality of tubes 510 provides a plurality of wells for the one or more sensors. For example, each of the plurality of tubes 510 includes at least one fluid. The fluid is heated by the heater 512, and the temperature of the fluid is monitored, directly or indirectly, by the thermocouple 514. In response, the thermocouple 514 sends a signal to a temperature controller. In one embodiment, the temperature controller is also a component of the fluidic system 100. The temperature controller processes the received signal in light of a target temperature and adjusts the power of the heater 512 in order to achieve the targeted temperature for the fluid. As shown in FIG. 1, the targeted temperature is provided to the fluidic system 100 by the user through a temperature interface 140 according to an embodiment of the present invention. The temperature interface 140 is a component of the fluidic system 100.
  • [0074]
    FIG. 6 is a simplified diagram showing temperature as function of time for well strip 114 in fluidic system 100 for processing biological sensors according to an embodiment of the present invention. This diagram is merely an example, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. As shown in FIG. 6, a curve 610 represents the temperature measured by the thermometer 514 as a function of time. Curves 620 represent temperatures for fluids in the plurality of tubes 510, such as wells, as functions of time. The temperatures for fluids have been measured by other thermometers, such as thermocouples, in the plurality of tubes. Curves 620 show that at a given time the fluid temperatures in different tubes are close to each other, and the fluid temperatures stabilize at about 50° C. after a period of time.
  • [0075]
    As shown in FIGS. 1-4, the fluidic component 110 also includes holder strips 116 and 118. In one embodiment, the holder strip 116 is used to transport the one or more sensors to the fluidic system 100 after a hybridization process is performed. For example, the holder strip 116 is a hybridization tray. In another embodiment, the holder strip 118 is used to transport the one or more sensors out of the fluidic system 100. For example, the holder strip 118 includes at least a cuvette holder.
  • [0076]
    The support component 120 includes at least a panel 122. For example, the panel 122 is placed horizontally. As shown in FIGS. 1-4, the fluidic component 110 is placed on the panel 122. For example, the fluidic component 110 is fixed at a predetermined position, directly or indirectly, on the panel 122. In another example, the one or more wells of the fluidic component are substantially perpendicular to the panel 122.
  • [0077]
    As shown in FIGS. 1-4, the well plate 112 includes a plurality of wells arranged into a plurality of rows and a plurality of columns. For example, the number of rows is equal to or larger than the number of columns. In another example, each of the plurality of rows extends from a first side of the well plate to a second side of the well plate. In one embodiment, the well strip 114 and two holder strips 116 and 118 all are placed next to the first side of the well plate 112. In yet another example, the plurality of rows is perpendicular to the plurality of columns. Additionally, the well strip 114 includes a row of wells. The holder strips 116 and 118 each include a row of wells capable of holding the one or more sensors. In one embodiment, the plurality of rows is parallel to the rows of wells for the well strip 114 and the holder strips 116 and 118. In another embodiment, the plurality of columns is parallel to the rows of wells for the well strip 114 and the holder strips 116 and 118.
  • [0078]
    According to an embodiment, the well plate 112, the well strip 114, the holder strip 116, and/or the holder strip 118 include a plurality of wells. At least one of the plurality of wells contains one or more fluids. For example, the volume of the one or more fluids in each well is equal to or smaller than 3 ml or 5 ml. In one embodiment, the volume of the one or more fluids for low stringency wash or stain is about 1.9 ml, and for high stringency wash is about 3.7 ml. In another embodiment, different wells have the same or different depths.
  • [0079]
    The electrical and mechanical component 130 can move each of the one or more sensors from one position to another position. For example, the one or more sensors are not parts of the electrical and mechanical component 130. In another example, the electrical and mechanical component 130 is used as a transport component. In yet another example, the movement of the sensors can be made in one, two, or three dimensions. In yet another example, the movement of the sensors is made at various speed. As shown in FIGS. 1-4, the electrical and mechanical component 130 moves each of the one or more sensors from one well to another well of the fluidic component 110. Additionally, the electrical and mechanical component 130 can move each of the one or more sensors within a corresponding well of the fluidic component 110, and/or move each of the one or more sensors into and/or out of a corresponding well of the fluidic component 110.
  • [0080]
    According to an embodiment of the present invention, the electrical and mechanical component 130 includes at least a gripper 132, and motors 134, 136, and 138. Additionally, the motors 134, 136, and 138 each can move one or more sensors in two opposite directions of one dimension. For example, the motor 134 can move the one or more sensors in two opposite directions that are perpendicular to the panel 122. In another example, the motors 136 and 138 can move the one or more sensors in directions that are parallel to the panel 122. In one embodiment, the motor 136 can move the one or more sensors in directions that are parallel to the well strip 114. In another embodiment, the motor 138 can move the one or more sensors in directions that are perpendicular to the well strip 114.
  • [0081]
    Additionally, the electrical and mechanical component 130 includes other components. For example, the electrical and mechanical component 130 includes at least a high-voltage power supply and a low-voltage power supply. In one embodiment, the power suppliers are used to provide voltages at predetermined values and/or within predetermined ranges to, for example, the motors 134, 136, and 138. In another embodiment, the power suppliers receive 115-votage AC power from an external source.
  • [0082]
    FIGS. 7(A) and (B) show a simplified gripper 132 in fluidic system 100 for processing biological sensors according to an embodiment of the present invention. These diagrams are merely examples, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. The gripper 132 includes an actuator 710, and two arms 720 and 730. Although the above has been shown using a selected group of components for the gripper 132, there can be many alternatives, modifications, and variations. For example, some of the components may be expanded and/or combined. Other components may be inserted to those noted above. Depending upon the embodiment, the arrangement of components may be interchanged with others replaced. Further details of these components are found throughout the present specification and more particularly below.
  • [0083]
    The actuator 710 is used to move the arms 720 and 730. In one embodiment, the actuator 710 is an electrical actuator. In another embodiment, the actuator 710 is a pneumatic actuator. For example, the pneumatic actuator receives a gas at a first pressure from a gas regulator, and the gas regulator converts the gas at a second pressure to the gas at the first pressure. In another example, the gas is clean dry air. As shown in FIG. 1, the first pressure is monitored by a pressure meter 150, which is a component of the fluidic system 100. Additionally, the arm 720 includes a plurality of fingers, such as fingers 722, 724, 726, and 728, as shown in FIG. 7(A). Similarly, the arm 730 also includes a plurality of fingers. As shown in FIG. 7(B), the gripper 132 is used to grip the one or more sensors. For example, the one or more sensors are not parts of the system 100.
  • [0084]
    As discussed above and further emphasized here, FIGS. 1-4 are merely examples, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. For example, the well plate 112 can be replaced by a well strip with a single row or a single column. In another example, the strips 114, 116, and/or 118 can be replaced by a plate with a plurality of rows and a plurality of columns. In yet another example, one or more additional plates, and/or one or more additional strips can be included in the fluidic component 110.
  • [0085]
    FIG. 8 shows a simplified fluidic system for processing biological sensors according to another embodiment of the present invention. This diagram is merely an example, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. The system 800 includes a fluidic component, a support component, and an electrical and mechanical component. The fluidic component, the support component, and the electrical and mechanical component are either the same as or modified from the fluidic component 110, the support component 120, and the electrical and mechanical component 130 respectively.
  • [0086]
    For example, the fluidic component of the system 800 is either partially or completely enclosed by a cover 810. In another example, the fluidic component of the system 800 includes a well plate, a well strip, and two holder strips. The well plate includes a plurality of wells arranged into a plurality of rows and a plurality of columns. For example, the number of rows is equal to or larger than the number of columns. In another example, each of the plurality of columns extends from a first side of the well plate to a second side of the well plate. In one embodiment, the well strip and two holder strips all are placed next to the first side of the well plate. In yet another example, the plurality of rows is perpendicular to the plurality of columns. Additionally, the well strip includes a row of wells, and each of the holder strips includes a row of wells that are capable of holding the one or more sensors. In one embodiment, the plurality of rows is parallel to the rows of wells for the well strip and the holder strips. In another embodiment, the plurality of columns is parallel to the rows of wells for the well strip and the holder strips.
  • [0087]
    As discussed above and further emphasized here, a fluidic system for processing biological sensors according to certain embodiments of the present invention includes a fluidic component, a support component, and an electrical and mechanical component. For example, the fluidic system is the system 100 or 800. In another example, the electrical and mechanical component can move each of one or more sensors within a corresponding well of the fluidic component, and/or move each of the one or more sensors into and/or out of a corresponding well of the fluidic component. In another example, the fluidic component includes a well plate, a well strip, and two holder strips. In one embodiment, one holder strip is used to transport the one or more sensors to the fluidic system after a hybridization process is performed. In another embodiment, another holder strip is used to transport the one or more microarrays out of the fluidic system.
  • [0088]
    According to an embodiment of the present invention, the movement of the one or more sensors into, within, and/or out of the fluidic system 100 or 800 is controlled by instructions received by the electrical and mechanical component from a processing system. For example, the processing system is external to the fluidic system. In another example, the processing system is a component of the fluidic system. In one embodiment, the processing system includes a computer or a processor. For example, the computer or the processor is directed by a code. In another example, the computer or the processor is directed by instructions included by a computer-readable medium in a computer program product.
  • [0089]
    FIG. 9 shows a simplified fluidic method for processing biological sensors that is performed by fluidic system 100 or 800 according to an embodiment of the present invention. This diagram is merely an example, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. The method 900 includes a process 910 for low stringency wash, a process 920 for high stringency wash, a process 930 for Streptavidin Phycoerythrin (SAPE) stain, a process 940 for low stringency wash, a process 950 for antibody (AB) stain, a process 960 for low stringency wash, a process 970 for SAPE stain, and a process 980 for low stringency wash. Although the above has been shown using a selected sequence of processes, there can be many alternatives, modifications, and variations. For example, some of the processes may be expanded and/or combined. Other processes may be inserted to those noted above. Depending upon the embodiment, the specific sequence of processes may be interchanged with others replaced. Further details of these processes are found throughout the present specification and more particularly below.
  • [0090]
    At each of the processes 910, 940, and 960 for low stringency wash, each of the one or more sensors is washed in a plurality of wells at room temperature. For example, the plurality of wells includes two wells. In another example, the plurality of wells includes four wells. For each well, the corresponding sensor is mixed with the fluid in the well for a plurality of times. For example, the plurality of times includes 23 times within 3 minutes. In another example, the plurality of times includes 36 times within 2 minutes.
  • [0091]
    At the process 920 for high stringency wash, each of the one or more sensors is washed in at least one well. Within each well, the fluid is at an elevated temperature, and the corresponding sensor is mixed with the fluid for a period of time. For example, the elevated temperature is 48° C., and the period of time is 25 minutes. In another example, the elevated temperature is 41° C., and the period of time is also 25 minutes.
  • [0092]
    At each of the processes 930 and 970 for SAPE stain, each of the one or more sensors is stained in at least one well at room temperature. For each well, the corresponding sensor is mixed with the fluid for a period of time. As an example, example, the period of time is 10 minutes.
  • [0093]
    At the process 950 for AB stain, each of the one or more sensors is stained in at least one well at room temperature. For each well, the corresponding sensor is mixed with the fluid for a period of time. As an example, the period of time is 10 minutes.
  • [0094]
    As discussed above and further emphasized here, the processes 910, 920, 930, 940, 950, 960, 970, and 980 are all performed by the fluidic system 100 or 800 according to an embodiment of the present invention. Prior to the process 910, the one or more sensors are processed for hybridization. For example, the hybridization process is performed at 48° C. for 16 hours. Following the process 980, the one or more sensors are scanned.
  • [0095]
    FIGS. 10(A)-(V) are simplified diagrams showing movement of one or more sensors made by fluidic system 100 or 800 according to an embodiment of the present invention. This diagram is merely an example, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications.
  • [0096]
    According to one embodiment, each of FIGS. 10(A)-(V) shows the well plate 112, the well strip 114, and the holder strip 116 and 118. For example, the well plate includes 96 wells that are arranged into rows 1-12 and columns A-H. The row 1 is intended for SAPE stain, the row 3 is intended for AB stain, and rows 5-12 are intended for low stringency wash. In another example, the well strip 112 is intended for high stringency wash. In yet another example, the holder strip 116 is a hybridization tray that is intended to transport the one or more sensors to the fluidic system 100 after a hybridization process is performed. In yet another embodiment, the holder strip 118 includes a cuvette holder and is intended to transport the one or more microarrays out of the fluidic system 100.
  • [0097]
    In order to describe movement of the one or more sensors, when a well is being used or after a well has been used, the well is marked with a square with hatch pattern. As shown in FIG. 10(A), the one or more sensors are transported to the fluidic system 100 by the holder strip 116. Afterwards, the one or more sensors are processed with low stringency wash according to the process 910 as shown in FIGS. 10(B)-(E). Each sensor is washed in four wells in rows 12, 11, 10, and 9 respectively. At each well, the sensor is agitated substantially parallel to the well depth in order to achieve a plurality of times of mixture with the fluid within the well. After the process 920, the one or more sensors are moved to the well strip 114 and processed with high stringency wash as shown in FIG. 10(F).
  • [0098]
    FIG. 10(G) shows the one or more sensors are moved from the well strip 114 to the row 1 of the well plate 112. At the row 1, the one or more sensors are stained with SAPE according to the process 930. At the process 940, another low stringency wash is performed on the one or more sensors as shown in FIGS. 10(H)-(K). Each sensor is washed in four wells in rows 8, 7, 6, and 5 respectively. At each well, the sensor is agitated substantially parallel to the well depth in order to achieve a plurality of times of mixture with the fluid within the well.
  • [0099]
    Following the process 940, the one or more sensors are moved to the row 3 of the well plate 112 as shown in FIG. 10(L). At the row 3, the one or more sensors are stained with AB according to the process 950. Afterwards, the one or more sensors are processed with low stringency wash according to the process 960 as shown in FIGS. 10(M)-(P). Each sensor is washed in four wells in rows 12, 11, 10, and 9 respectively, and none of these four wells has been used at the process 910. At each well, the sensor is agitated substantially parallel to the well depth in order to achieve a plurality of times of mixture with the fluid within the well.
  • [0100]
    FIG. 10(Q) shows the one or more sensors are moved from the row 9 to the row 1 of the well plate 112. At the row 1, the one or more sensors are stained with SAPE according to the process 970. None of the wells used in the process 970 has been used in the process 930. At the process 980, another low stringency wash is performed on the one or more sensors as shown in FIGS. 10(R)-(U). Each sensor is washed in four wells in rows 8, 7, 6, and 5 respectively, and none of these four wells has been used at the process 940. At each well, the sensor is agitated substantially parallel to the well depth in order to achieve a plurality of times of mixture with the fluid within the well. After the process 980, the one or more sensors are placed into the holder strip 118 as shown in FIG. 10(V). These sensors can be transported from the fluidic system 100 to a scanner.
  • [0101]
    As discussed above and further emphasized here, the fluidic system 100 or 800 can be used to process biological sensors according to certain embodiments of the present invention. As an example, the processing is performed according to the method 900. In another example, the biological sensors can be various types. See U.S. patent application Ser. Nos. 10/826,577 filed Apr. 16, 2004 and Ser. No. 11/243,621 filed Oct. 4, 2005, each of which is incorporated by reference herein. In yet another example, each of the one or more biological sensors is a biological microarray. In one embodiment, the biological microarray has a sensor length, a sensor width, and a sensor thickness. For example, the sensor length is equal to or shorter than 10 mm, the sensor width is equal to or narrower than 10 mm, and the sensor thickness is equal to or thinner than 1000 μm. In another example, the sensor length is equal to about 6.3 mm, the sensor width is equal to about 6.3 mm, and the sensor thickness is equal to about 700 μm.
  • [0102]
    In one embodiment, each biological sensor is a biological microarray. In another embodiment, each biological sensor is attached to a support component. For example, the support component is a peg. FIGS. 11(A) and (B) are simplified microarrays on pegs that can be processed by fluidic system 100 or 800 according to an embodiment of the present invention. These diagrams are merely examples, which should not unduly limit the scope of the claims. One of ordinary skill in the art would recognize many variations, alternatives, and modifications. As shown in FIG. 11(A), a biological microarray is attached to one peg, and each biological microarray can be manipulated individually by the fluidic system 100 or 800. As shown in FIG. 11(B), a plurality of biological microarrays is attached to a plurality of pegs respectively, and the plurality of pegs is connected by a base component. For example, the plurality of pegs includes four pegs, and the plurality of biological microarrays includes four microarrays. In another example, the plurality of pegs includes eight pegs, and the plurality of biological microarrays includes eight microarrays. In yet another example, the plurality of microarrays is manipulated together by the fluidic system 100 or 800.
  • [0103]
    Also as discussed above and further emphasized here, the fluidic system 100 or 800 can be used to process biological sensors ready for scan according to certain embodiments of the present invention. In one embodiment, the processing is performed according to the method 900. In another embodiment, the scanner for scanning the processed biological sensors can be of various types. For example, the scanner is made by Axon. Alternatively, see U.S. Provisional Application Ser. Nos. 60/648,309 filed Jan. 27, 2005 and 60/673,969 filed Apr. 22, 2005, each of which is incorporated by reference herein.
  • [0104]
    According to another embodiment of the present invention, a fluidic system for processing biological sensors includes a fluidic component including at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the fluidic system includes a support component configured to support at least the first container and the second container. The first container and the second container are substantially stationary with respect to the support component. Moreover, the fluidic system includes a transport component configured to move a first sensor, with respect to the support component, into the first container and in contact with the first volume of the first fluid, and move a second sensor, with respect to the support component, into the second container and in contact with the second volume of the second fluid. The first sensor and the second sensor are moved substantially simultaneously. For example, the fluidic system is implemented according the system 100 and/or the system 800.
  • [0105]
    According to yet another embodiment, a fluidic system for processing biological sensors includes a fluidic component including at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the fluidic system includes a support component including a panel for supporting at least the first container and the second container. The first container and the second container are substantially stationary with respect to the panel. Moreover, the fluidic system includes a transport component including a gripper and at least one motor. The gripper is capable of gripping the first sensor and the second sensor substantially simultaneously and of releasing the first sensor and the second sensor substantially simultaneously. The at least one motor is configured to move the gripped first sensor, with respect to the panel, into the first container and in contact with the first volume of the first fluid. The at least one motor is further configured to move the gripped second sensor, with respect to the panel, into the second container and in contact with the second volume of the second fluid. The first sensor and the second sensor are moved substantially simultaneously. For example, the fluidic system is implemented according the system 100 and/or the system 800.
  • [0106]
    According to yet another embodiment, a method for processing biological sensors includes performing a hybridization process on at least a first sensor and a second sensor, and after the hybridization process, transferring the first sensor and the second sensor into a fluidic system. The fluidic system includes at least a first container and a second container, the first container holds a first volume of a first fluid, and the second container holds a second volume of a second fluid. Additionally, the method includes moving the first sensor into the first container and in contact with the first volume of the first fluid, and moving the second sensor into the second container and in contact with the second volume of the second fluid. The moving the first sensor and the moving the second sensor are performed substantially simultaneously. For example, the fluidic system is implemented according the system 100 and/or the system 800.
  • [0107]
    The present invention has various applications. For example, the fluidic system 100 or the fluidic system 800 is used as a fluidic station. In one embodiment, the fluidic station, as shown in FIG. 1, has a footprint of 19.5-inch width and 17.5-inch depth. Additionally, the fluidic station has a height of 15 inch. In another example, certain embodiments of the present invention are used for personal and portable instruments as well as methods for processing biological microarrays.
  • [0108]
    The present invention has various advantages. Certain embodiments of the present invention provide an automated fluidic system. Some embodiments of the present invention provide a low-cost fluidic system. Certain embodiments of the present invention can improve throughput of the fluidic system. For example, a plurality of biological sensors, such as microarrays, is processed in parallel. Some embodiments of the present invention can reduce cross-contamination between different processes performed on one or more biological sensors. For example, at a given process, different sensors are washed, stained, and/or held in different wells. In another example, a given sensor is washed, stained, and/or held in different wells for different processes respectively. In yet another example, each well is used for at most a single process for at most a single sensor, such as a microarray.
  • [0109]
    Although specific embodiments of the present invention have been described, it will be understood by those of skill in the art that there are other embodiments that are equivalent to the described embodiments. Accordingly, it is to be understood that the invention is not to be limited by the specific illustrated embodiments, but only by the scope of the appended claims.

Claims (55)

  1. 1. A fluidic system for processing biological sensors, the fluidic system comprising:
    a fluidic component including at least a first container and a second container, the first container capable of holding a first volume of a first fluid, the second container capable of holding a second volume of a second fluid;
    a support component configured to support at least the first container and the second container, the first container and the second container being substantially stationary with respect to the support component;
    a transport component configured to:
    move a first sensor, with respect to the support component, into the first container and in contact with the first volume of the first fluid;
    move a second sensor, with respect to the support component, into the second container and in contact with the second volume of the second fluid;
    wherein the first sensor and the second sensor are moved substantially simultaneously.
  2. 2. The fluidic system of claim 1 wherein the fluidic system is configured to process the first sensor and the second sensor so that the processed first sensor and the processed second sensor are ready for scan.
  3. 3. The fluidic system of claim 1 wherein:
    when the first sensor is inside the first container and in contact with the first volume of the first fluid, the first volume of the first fluid remains completely within the first container;
    when the second sensor is inside the second container and in contact with the second volume of the second fluid, the second volume of the second fluid remains completely within the second container.
  4. 4. The fluidic system of claim 1 wherein the first sensor is attached to a first support member.
  5. 5. The fluidic system of claim 4 wherein the first support member is a peg.
  6. 6. The fluidic system of claim 4 wherein the second sensor is attached to a second support member.
  7. 7. The fluidic system of claim 6 wherein each of the first support member and the second support member is a part of a plate.
  8. 8. The fluidic system of claim 1 wherein:
    the first sensor is associated with a sensor length, a sensor width, and a sensor thickness;
    the sensor length is equal to or shorter than 10 mm;
    the sensor width is equal to or narrower than 10 mm;
    the sensor thickness is equal to or thinner than 1000 μm.
  9. 9. The fluidic system of claim 1 wherein the first sensor is a biological sensor.
  10. 10. The fluidic system of claim 9 wherein the biological sensor includes a microarray.
  11. 11. The fluidic system of claim 1 wherein the first volume of the first fluid sensor is equal to or smaller than 5 ml.
  12. 12. The fluidic system of claim 1 wherein the support component is further configured to support, directly, at least the first container and the second container.
  13. 13. The fluidic system of claim 1 wherein the support component is further configured to support, indirectly through another object, at least the first container and the second container.
  14. 14. The fluidic system of claim 1 wherein the first fluid and the second fluid are the same or different in kind.
  15. 15. The fluidic system of claim 1 wherein the first volume and the second volume are the same or different in size.
  16. 16. The fluidic system of claim 1 wherein each of the first container and the second container is a well.
  17. 17. The fluidic system of claim 1 wherein the first container and the second container are two of a plurality of containers, the plurality of containers being attached, directly or indirectly, to a common component.
  18. 18. The fluidic system of claim 17 wherein the plurality of containers are arranged in one or more rows and one or more columns.
  19. 19. A fluidic system for processing biological sensors, the fluidic system comprising:
    a fluidic component including at least a first container and a second container, the first container capable of holding a first volume of a first fluid, the second container capable of holding a second volume of a second fluid;
    a support component including a panel for supporting at least the first container and the second container, the first container and the second container being substantially stationary with respect to the panel;
    a transport component including a gripper and at least one motor;
    wherein:
    the gripper is capable of gripping the first sensor and the second sensor substantially simultaneously and of releasing the first sensor and the second sensor substantially simultaneously;
    the at least one motor is configured to move the gripped first sensor, with respect to the panel, into the first container and in contact with the first volume of the first fluid;
    the at least one motor is further configured to move the gripped second sensor, with respect to the panel, into the second container and in contact with the second volume of the second fluid;
    wherein the first sensor and the second sensor are moved substantially simultaneously.
  20. 20. The fluidic system of claim 19 wherein the gripper includes an actuator.
  21. 21. The fluidic system of claim 20 wherein the actuator is a pneumatic actuator.
  22. 22. The fluidic system of claim 20 wherein the actuator is an electrical actuator.
  23. 23. The fluidic system of claim 19 wherein:
    the at least one motor is capable of moving the gripped first sensor in at lest six directions;
    each of the six directions is opposite to another direction of the six directions and is perpendicular to four directions of the six directions;
    the four directions of the six directions are different from the another direction.
  24. 24. The fluidic system of claim 19 wherein the fluidic component is at least partially enclosed by a cover.
  25. 25. The fluidic system of claim 19 wherein:
    the first container and the second container are attached to an object associated with a temperature;
    the object includes a heater configured to heat up the first volume of the first fluid and the second volume of the second fluid;
    the object further includes a thermometer configured to measure the temperature.
  26. 26. The fluidic system of claim 19, and further comprising a temperature controller coupled to the heater and the thermometer and configured to heat the temperature to a predetermined value.
  27. 27. The fluidic system of claim 19 wherein the transport component is coupled to a processing system, the processing system configured to provide instructions to the transport component for gripping, releasing, or moving the first sensor and the second sensor.
  28. 28. The fluidic system of claim 27 wherein the processing system includes a computer.
  29. 29. The fluidic system of claim 19 wherein the fluidic system is configured to process the first sensor and the second sensor so that the processed first sensor and the processed second sensor are ready for scan.
  30. 30. The fluidic system of claim 19 wherein:
    when the first sensor is inside the first container and in contact with the first volume of the first fluid, the first volume of the first fluid remains completely within the first container;
    when the second sensor is inside the second container and in contact with the second volume of the second fluid, the second volume of the second fluid remains completely within the second container.
  31. 31. The fluidic system of claim 19 wherein the first sensor is attached to a first support member.
  32. 32. The fluidic system of claim 31 wherein the first support member is a peg.
  33. 33. The fluidic system of claim 31 wherein the second sensor is attached to a second support member.
  34. 34. The fluidic system of claim 32 wherein each of the first support member and the second support member is a part of a plate.
  35. 35. The fluidic system of claim 19 wherein:
    the first sensor is associated with a sensor length, a sensor width, and a sensor thickness;
    the sensor length is equal to or shorter than 10 mm;
    the sensor width is equal to or narrower than 10 mm;
    the sensor thickness is equal to or thinner than 1000 μm.
  36. 36. The fluidic system of claim 19 wherein the first sensor is a biological sensor.
  37. 37. The fluidic system of claim 36 wherein the biological sensor includes a microarray.
  38. 38. The fluidic system of claim 19 wherein the first volume of the first fluid sensor is equal to or smaller than 5 ml.
  39. 39. The fluidic system of claim 19 wherein the support component is further configured to support, directly, at least the first container and the second container.
  40. 40. A method for processing biological sensors, the method comprising:
    performing a hybridization process on at least a first sensor and a second sensor;
    after the hybridization process, transferring the first sensor and the second sensor into a fluidic system, the fluidic system including at least a first container and a second container, the first container holding a first volume of a first fluid, the second container holding a second volume of a second fluid;
    moving the first sensor into the first container and in contact with the first volume of the first fluid;
    moving the second sensor into the second container and in contact with the second volume of the second fluid;
    wherein the moving the first sensor and the moving the second sensor are performed substantially simultaneously.
  41. 41. The method of claim 40 wherein:
    the fluidic system includes a support component configured to support at least the first container and the second container, the first container and the second container being substantially stationary with respect to the support component;
    the moving the first sensor includes moving the first sensor with respect to the support component;
    the moving the second sensor includes moving the second sensor with respect to the support component.
  42. 42. The method of claim 40, and further comprising after the moving the first sensor and the moving the second sensor, processing the first sensor and the second sensor so that the processed first sensor and the processed second sensor are ready for scan.
  43. 43. The method of claim 42 wherein the processing the first sensor and the second sensor includes performing at least a low stringency wash, at least a high stringency wash, and at least a stain process to the first sensor and the second sensor.
  44. 44. The method of claim 42, and further comprising:
    transferring the processed first sensor and the processed second sensor out of the fluidic system;
    performing a scanning process on the processed first sensor and the processed second sensor.
  45. 45. The method of claim 44 wherein between the transferring the first sensor and the second sensor-into a fluidic system and the transferring the processed first sensor and the processed second sensor out of the fluidic system:
    the first volume of the first fluid is not in contact with any sensor other than the first sensor;
    the second volume of the second fluid is not in contact with any sensor other than the second sensor.
  46. 46. The method of claim 44 wherein between the transferring the first sensor and the second sensor into a fluidic system and the transferring the processed first sensor and the processed second sensor out of the fluidic system:
    the first container is not provided with any volume of any fluid that is different from the first volume of the first fluid and is not provided by the first sensor;
    the second container is not provided with any volume of any fluid that is different from the second volume of the second fluid and is not provided by the second sensor.
  47. 47. The method of claim 40 wherein:
    the moving the first sensor includes when the first sensor is inside the first container and in contact with the first volume of the first fluid, keeping the first volume of the first fluid completely within the first container;
    the moving the second sensor includes when the second sensor is inside the second container and in contact with the second volume of the second fluid, keeping the second volume of the second fluid completely within the second container.
  48. 48. The method of claim 40 wherein the first sensor is attached to a first support member.
  49. 49. The method of claim 48 wherein the first support member is a peg.
  50. 50. The method of claim 48 wherein the second sensor is attached to a second support member.
  51. 51. The method of claim 50 wherein each of the first support member and the second support member is a part of a plate.
  52. 52. The method of claim 40 wherein the first sensor is a biological sensor.
  53. 53. The method of claim 52 wherein the biological sensor includes a microarray.
  54. 54. The method of claim 40 wherein the first fluid and the second fluid are the same or different.
  55. 55. The method of claim 40 wherein the first volume and the second volume are the same or different in size.
US11388762 2005-04-06 2006-03-23 Fluidic system and method for processing biological microarrays in personal instrumentation Abandoned US20060246576A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US66913005 true 2005-04-06 2005-04-06
US11388762 US20060246576A1 (en) 2005-04-06 2006-03-23 Fluidic system and method for processing biological microarrays in personal instrumentation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11388762 US20060246576A1 (en) 2005-04-06 2006-03-23 Fluidic system and method for processing biological microarrays in personal instrumentation
US12632429 US20100081583A1 (en) 2005-04-06 2009-12-07 Fludic system and method for processing biological microarrays in personal instrumentation

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12632429 Continuation US20100081583A1 (en) 2005-04-06 2009-12-07 Fludic system and method for processing biological microarrays in personal instrumentation

Publications (1)

Publication Number Publication Date
US20060246576A1 true true US20060246576A1 (en) 2006-11-02

Family

ID=37077485

Family Applications (4)

Application Number Title Priority Date Filing Date
US11388762 Abandoned US20060246576A1 (en) 2005-04-06 2006-03-23 Fluidic system and method for processing biological microarrays in personal instrumentation
US11389549 Abandoned US20060234371A1 (en) 2005-04-06 2006-03-24 System and method for processing large number of biological microarrays
US12481852 Active 2027-09-05 US8796186B2 (en) 2005-04-06 2009-06-10 System and method for processing large number of biological microarrays
US12632429 Abandoned US20100081583A1 (en) 2005-04-06 2009-12-07 Fludic system and method for processing biological microarrays in personal instrumentation

Family Applications After (3)

Application Number Title Priority Date Filing Date
US11389549 Abandoned US20060234371A1 (en) 2005-04-06 2006-03-24 System and method for processing large number of biological microarrays
US12481852 Active 2027-09-05 US8796186B2 (en) 2005-04-06 2009-06-10 System and method for processing large number of biological microarrays
US12632429 Abandoned US20100081583A1 (en) 2005-04-06 2009-12-07 Fludic system and method for processing biological microarrays in personal instrumentation

Country Status (2)

Country Link
US (4) US20060246576A1 (en)
CN (4) CN1847848B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060234371A1 (en) * 2005-04-06 2006-10-19 Affymetrix, Inc. System and method for processing large number of biological microarrays
US20100328732A1 (en) * 2006-11-21 2010-12-30 Illumina Inc. Hexagonal site line scanning method and system
US8351026B2 (en) 2005-04-22 2013-01-08 Affymetrix, Inc. Methods and devices for reading microarrays

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080003667A1 (en) * 2006-05-19 2008-01-03 Affymetrix, Inc. Consumable elements for use with fluid processing and detection systems
DE102010028769A1 (en) 2010-05-07 2011-11-10 Pvt Probenverteiltechnik Gmbh System for transporting containers between different stations and container carrier
EP2589968A1 (en) * 2011-11-04 2013-05-08 Roche Diagnostics GmbH Laboratory sample distribution system, laboratory system and method of operating
EP2589966A1 (en) 2011-11-04 2013-05-08 Roche Diagnostics GmbH Laboratory sample distribution system and corresponding method of operation
EP2589967A1 (en) 2011-11-04 2013-05-08 Roche Diagnostics GmbH Laboratory sample distribution system and corresponding method of operation
DE102014202838B3 (en) 2014-02-17 2014-11-06 Roche Pvt Gmbh Transport device, sample distribution system and Laborautomatierungssystem
DE102014202843B3 (en) 2014-02-17 2014-11-06 Roche Pvt Gmbh Transport device, sample distribution system and laboratory automation system
EP2927163B1 (en) 2014-03-31 2018-02-28 Roche Diagniostics GmbH Vertical conveyor, sample distribution system and laboratory automation system
EP2927167B1 (en) 2014-03-31 2018-04-18 F. Hoffmann-La Roche AG Dispatch device, sample distribution system and laboratory automation system
EP2927695A1 (en) 2014-03-31 2015-10-07 Roche Diagniostics GmbH Sample distribution system and laboratory automation system
EP2927168A1 (en) 2014-03-31 2015-10-07 Roche Diagniostics GmbH Transport device, sample distribution system and laboratory automation system
EP2957914B1 (en) 2014-06-17 2018-01-03 Roche Diagnostics GmbH Laboratory sample distribution system and laboratory automation system
EP2977766A1 (en) 2014-07-24 2016-01-27 Roche Diagniostics GmbH Laboratory sample distribution system and laboratory automation system
EP2995960A1 (en) 2014-09-09 2016-03-16 Roche Diagniostics GmbH Laboratory sample distribution system and method for calibrating magnetic sensors
US9952242B2 (en) 2014-09-12 2018-04-24 Roche Diagnostics Operations, Inc. Laboratory sample distribution system and laboratory automation system
EP3006943A1 (en) 2014-10-07 2016-04-13 Roche Diagniostics GmbH Module for a laboratory sample distribution system, laboratory sample distribution system and laboratory automation system
EP3016116A1 (en) 2014-11-03 2016-05-04 Roche Diagniostics GmbH Printed circuit board arrangement, coil for a laboratory sample distribution system, laboratory sample distribution system and laboratory automation system
KR20180044289A (en) * 2015-07-23 2018-05-02 메소 스케일 테크놀러지즈, 엘엘시 And it supplies the integrated data management system platform
EP3153867A1 (en) 2015-10-06 2017-04-12 Roche Diagniostics GmbH Method of configuring a laboratory automation system, laboratory sample distribution system and laboratory automation system

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4731335A (en) * 1985-09-13 1988-03-15 Fisher Scientific Company Method for treating thin samples on a surface employing capillary flow
US5601650A (en) * 1991-05-29 1997-02-11 Medite Gesellschaft Fur Medizintechnik Mbh Process and device for dyeing histological preparations arranged on microscope slides
US6361940B1 (en) * 1996-09-24 2002-03-26 Qiagen Genomics, Inc. Compositions and methods for enhancing hybridization and priming specificity
US20040185483A1 (en) * 1998-12-28 2004-09-23 Illumina, Inc. Composite arrays utilizing microspheres with a hybridization chamber
US20060234371A1 (en) * 2005-04-06 2006-10-19 Affymetrix, Inc. System and method for processing large number of biological microarrays

Family Cites Families (276)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US751084A (en) * 1904-02-02 Electric switch
US2371061A (en) * 1941-09-10 1945-03-06 Maryland Plastics Inc Method of making dies
US2610419A (en) * 1947-08-13 1952-09-16 Irvin Frey Marking garments for identification
US3281860A (en) 1964-11-09 1966-10-25 Dick Co Ab Ink jet nozzle
DE1617732C2 (en) 1966-03-01 1972-12-21 Promoveo Sobioda & Cie Apparatus for investigation of viable cells of microorganisms
US3802966A (en) 1969-08-22 1974-04-09 Ethyl Corp Apparatus for delivering a fluid suspension to a forming unit clear reactor power plant
BE793185A (en) 1971-12-23 1973-04-16 Atomic Energy Commission An apparatus for analyzing and sorting particles quickly such as biological cells
JPS6112373B2 (en) 1974-09-04 1986-04-08 Hitachi Ltd
US4121222A (en) 1977-09-06 1978-10-17 A. B. Dick Company Drop counter ink replenishing system
US4200110A (en) 1977-11-28 1980-04-29 United States Of America Fiber optic pH probe
US4204929A (en) 1978-04-18 1980-05-27 University Patents, Inc. Isoelectric focusing method
US4325910A (en) * 1979-07-11 1982-04-20 Technicraft, Inc. Automated multiple-purpose chemical-analysis apparatus
US4349510A (en) 1979-07-24 1982-09-14 Seppo Kolehmainen Method and apparatus for measurement of samples by luminescence
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4373071A (en) 1981-04-30 1983-02-08 City Of Hope Research Institute Solid-phase synthesis of polynucleotides
US4707454A (en) 1981-08-10 1987-11-17 Bio-Diagnostics, Inc. Fluorescent chlorophyll labeled assay reagents
US4499052A (en) 1982-08-30 1985-02-12 Becton, Dickinson And Company Apparatus for distinguishing multiple subpopulations of cells
EP0110610B1 (en) 1982-11-20 1988-07-27 The University Of Birmingham Dispensing device and recording apparatus
JPH063445B2 (en) 1983-03-08 1994-01-12 コモンウエルス セラム ラボラトリ−ズ コミツシヨン The method of determining the antigen active amino acid chain
US4672040A (en) 1983-05-12 1987-06-09 Advanced Magnetics, Inc. Magnetic particles for use in separations
CA1230552A (en) * 1983-11-07 1987-12-22 Howard M. Chandler Device and method for performing qualitative enzyme immunoassays
FI71768C (en) 1984-02-17 1987-02-09 Orion Yhtymae Oy Foerbaettrade nykleinsyrareagenser Science foerfarande Foer deras framstaellning.
DE3565986D1 (en) 1984-05-02 1988-12-08 Brendan James Hamill An apparatus for the chemical synthesis of oligonucleotides
GB8429212D0 (en) 1984-11-19 1984-12-27 Vincent Patents Ltd Exhaust systems for ic engines
JPH0823558B2 (en) 1984-11-27 1996-03-06 オ−ジエニクス リミテツド Test equipment
FR2583772B1 (en) 1985-06-20 1987-08-28 Roussel Uclaf New media, the preparation of these supports, the new intermediaries obtained, their application to the synthesis of oligonucleotides and new nucleosides and oligonucleotides subsequently assembled to the supports thus obtained
FR2584090B1 (en) 1985-06-27 1987-08-28 Roussel Uclaf New media, their preparation and intermediates obtained, their application to the synthesis of oligonucleotides and new nucleosides and subsequently assembled oligonucleotides to supports obtained
US4963498A (en) 1985-08-05 1990-10-16 Biotrack Capillary flow device
US5164598A (en) 1985-08-05 1992-11-17 Biotrack Capillary flow device
US4682895A (en) 1985-08-06 1987-07-28 Texas A&M University Fiber optic probe for quantification of colorimetric reactions
US5595908A (en) * 1985-09-26 1997-01-21 University Of Southern Mississipi Piezoelectric device for detection of polynucleotide hybridization
DE3684707D1 (en) * 1985-12-23 1992-05-07 Beckman Instruments Inc Method and apparatus for automatically analyzing for immunochemistry.
US4940670A (en) 1986-01-24 1990-07-10 Rhodes Buck A Method for compounding and testing patient specific monoclonal antibodies and monoclonal antibody fragments for in vivo use
US5256549A (en) 1986-03-28 1993-10-26 Chiron Corporation Purification of synthetic oligomers
US5153319A (en) 1986-03-31 1992-10-06 University Patents, Inc. Process for preparing polynucleotides
US4822746A (en) 1986-06-25 1989-04-18 Trustees Of Tufts College Radiative and non-radiative energy transfer and absorbance modulated fluorescence detection methods and sensors
US5114864A (en) 1986-06-25 1992-05-19 Trustees Of Tufts College Fiber optic sensors, apparatus, and detection methods using fluid erodible controlled release polymers for delivery of reagent formulations
US5252494A (en) 1986-06-25 1993-10-12 Trustees Of Tufts College Fiber optic sensors, apparatus, and detection methods using controlled release polymers and reagent formulations held within a polymeric reaction matrix
US5254477A (en) 1986-06-25 1993-10-19 Trustees Of Tufts College Flourescence intramolecular energy transfer conjugate compositions and detection methods
US5143853A (en) 1986-06-25 1992-09-01 Trustees Of Tufts College Absorbance modulated fluorescence detection methods and sensors
DE3782597D1 (en) 1986-09-18 1992-12-17 Pacific Biotech Inc Immunodiagnostic device.
US4764671A (en) * 1986-10-03 1988-08-16 Kollmorgen Corporation Fiber optic fluid sensor using coated sensor tip
US5021550A (en) 1986-10-07 1991-06-04 Thomas Jefferson University Method for preventing deletion sequences in solid phase synthesis
US4824789B1 (en) 1986-10-10 1996-08-13 Minnesota Mining & Mfg Gas sensor
US4798738A (en) 1986-10-10 1989-01-17 Cardiovascular Devices, Inc. Micro sensor
US5698450A (en) 1986-10-14 1997-12-16 Ringrose; Anthony Method for measuring antigens or antibodies in biological fluids
US4895706A (en) 1986-10-28 1990-01-23 Costar Corporation Multi-well filter strip and composite assemblies
US4877745A (en) 1986-11-17 1989-10-31 Abbott Laboratories Apparatus and process for reagent fluid dispensing and printing
US4922092A (en) 1986-11-26 1990-05-01 Image Research Limited High sensitivity optical imaging apparatus
EP0269764B1 (en) 1986-12-01 1991-08-28 Molecular Biosystems, Inc. Method for increasing the sensitivity of nucleic acid hybridization assays
JPH0750094B2 (en) 1987-01-28 1995-05-31 富士写真フイルム株式会社 The continuous process chemical analysis slide
US4859419A (en) * 1987-02-27 1989-08-22 American Bionetics, Inc. Diagnostic manifold apparatus
US4829010A (en) * 1987-03-13 1989-05-09 Tanox Biosystems, Inc. Immunoassay device enclosing matrixes of antibody spots for cell determinations
WO1988008973A1 (en) 1987-05-15 1988-11-17 Beckman Instruments, Inc. Improved flow cell
DE3870324D1 (en) 1987-06-16 1992-05-27 Wallac Oy Ligand-determination method for multiple analytes with labeled microsphere.
US5132242A (en) 1987-07-15 1992-07-21 Cheung Sau W Fluorescent microspheres and methods of using them
US5194300A (en) 1987-07-15 1993-03-16 Cheung Sau W Methods of making fluorescent microspheres
US5447837A (en) 1987-08-05 1995-09-05 Calypte, Inc. Multi-immunoassay diagnostic system for antigens or antibodies or both
US4785814A (en) 1987-08-11 1988-11-22 Cordis Corporation Optical probe for measuring pH and oxygen in blood and employing a composite membrane
US4853335A (en) 1987-09-28 1989-08-01 Olsen Duane A Colloidal gold particle concentration immunoassay
US5219712A (en) * 1987-11-28 1993-06-15 Thorn Emi Plc Method of forming a solid article
US5322799A (en) 1988-02-03 1994-06-21 The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University Observation cell and mixing chamber
US5100775A (en) 1988-03-16 1992-03-31 Smyczek Peter J Method for conducting nucleic acid hybridization in chamber with precise fluid delivery
US4988617A (en) 1988-03-25 1991-01-29 California Institute Of Technology Method of detecting a nucleotide change in nucleic acids
US4965725B1 (en) 1988-04-08 1996-05-07 Neuromedical Systems Inc Neural network based automated cytological specimen classification system and method
US5002867A (en) 1988-04-25 1991-03-26 Macevicz Stephen C Nucleic acid sequence determination by multiple mixed oligonucleotide probes
US5382511A (en) 1988-08-02 1995-01-17 Gene Tec Corporation Method for studying nucleic acids within immobilized specimens
US5281540A (en) 1988-08-02 1994-01-25 Abbott Laboratories Test array for performing assays
US5281516A (en) 1988-08-02 1994-01-25 Gene Tec Corporation Temperature control apparatus and method
US5346672A (en) 1989-11-17 1994-09-13 Gene Tec Corporation Devices for containing biological specimens for thermal processing
US5320808A (en) 1988-08-02 1994-06-14 Abbott Laboratories Reaction cartridge and carousel for biological sample analyzer
US5075077A (en) 1988-08-02 1991-12-24 Abbott Laboratories Test card for performing assays
US4992383A (en) 1988-08-05 1991-02-12 Porton Instruments, Inc. Method for protein and peptide sequencing using derivatized glass supports
US5104808A (en) * 1988-08-26 1992-04-14 Laska Paul F Method and apparatus for effecting a plurality of assays on a plurality of samples in an automatic analytical device
US5278048A (en) 1988-10-21 1994-01-11 Molecular Devices Corporation Methods for detecting the effect of cell affecting agents on living cells
US5683916A (en) * 1988-10-31 1997-11-04 Hemasure Inc. Membrane affinity apparatus and purification methods related thereto
US5200051A (en) 1988-11-14 1993-04-06 I-Stat Corporation Wholly microfabricated biosensors and process for the manufacture and use thereof
US5575849A (en) 1988-11-25 1996-11-19 Canon Kabushiki Kaisha Apparatus for producing a substrate having a surface with a plurality of spherical dimples for photoconductive members
US5047524A (en) 1988-12-21 1991-09-10 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
GB8829942D0 (en) 1988-12-22 1989-02-15 Isis Innovations Ltd Method
US5229297A (en) * 1989-02-03 1993-07-20 Eastman Kodak Company Containment cuvette for PCR and method of use
EP0417305A4 (en) 1989-03-07 1992-04-22 Idemitsu Petrochemical Co. Ltd. Analyzer of liquid sample and analyzing method of liquid sample using said analyzer
JPH02299598A (en) 1989-04-14 1990-12-11 Ro Inst For Molecular Genetics & Geneteic Res Determination of complete or partial content of very short sequence in sample of nucleic acids connected to discrete particle of microscopic size by hybridization with oligonucleotide probe
US5087820A (en) 1989-05-31 1992-02-11 Digital Diagnostic Corp. Radiometric analysis system for solid support samples
US5424186A (en) * 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
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
US5800992A (en) 1989-06-07 1998-09-01 Fodor; Stephen P.A. Method of detecting nucleic acids
US5176881A (en) 1989-08-11 1993-01-05 The University Of Tennessee Research Corporation Fiber optic-based regenerable biosensor
US5302509A (en) 1989-08-14 1994-04-12 Beckman Instruments, Inc. Method for sequencing polynucleotides
US5141813A (en) 1989-08-28 1992-08-25 Clontech Laboratories, Inc. Multifunctional controlled pore glass reagent for solid phase oligonucleotide synthesis
EP0416148A1 (en) 1989-09-07 1991-03-13 RSM ANALYTISCHE INSTRUMENTE GmbH Arrangement for simultaneously measuring particle or quantum radiation from multiple samples
US5188963A (en) 1989-11-17 1993-02-23 Gene Tec Corporation Device for processing biological specimens for analysis of nucleic acids
US5104792A (en) * 1989-12-21 1992-04-14 The United States Of America As Represented By The Department Of Health And Human Services Method for amplifying unknown nucleic acid sequences
US5073029A (en) 1990-02-16 1991-12-17 Eqm Research, Inc. Multisource device for photometric analysis and associated chromogens
EP0478753B1 (en) * 1990-04-06 1997-07-02 The Perkin-Elmer Corporation Automated molecular biology laboratory
US5204253A (en) 1990-05-29 1993-04-20 E. I. Du Pont De Nemours And Company Method and apparatus for introducing biological substances into living cells
JP3010057B2 (en) * 1990-08-24 2000-02-14 オリンパス光学工業株式会社 Cup cleaning device
EP0478319B1 (en) 1990-09-28 1997-04-02 Kabushiki Kaisha Toshiba Gene detection method
US5154888A (en) * 1990-10-25 1992-10-13 Eastman Kodak Company Automatic sealing closure means for closing off a passage in a flexible cuvette
US5105305A (en) 1991-01-10 1992-04-14 At&T Bell Laboratories Near-field scanning optical microscope using a fluorescent probe
US5320814A (en) 1991-01-25 1994-06-14 Trustees Of Tufts College Fiber optic array sensors, apparatus, and methods for concurrently visualizing and chemically detecting multiple analytes of interest in a fluid sample
US5244813A (en) 1991-01-25 1993-09-14 Trustees Of Tufts College Fiber optic sensor, apparatus, and methods for detecting an organic analyte in a fluid or vapor sample
US5250264A (en) 1991-01-25 1993-10-05 Trustees Of Tufts College Method of making imaging fiber optic sensors to concurrently detect multiple analytes of interest in a fluid sample
US5244636A (en) 1991-01-25 1993-09-14 Trustees Of Tufts College Imaging fiber optic array sensors, apparatus, and methods for concurrently detecting multiple analytes of interest in a fluid sample
US5230866A (en) * 1991-03-01 1993-07-27 Biotrack, Inc. Capillary stop-flow junction having improved stability against accidental fluid flow
US5133374A (en) * 1991-04-01 1992-07-28 Druding Kevin W Apparatus and method for purging medical instruments and disposing of infectious waste
US5170659A (en) 1991-04-08 1992-12-15 Kemp Development Corporation Apparatus and method for detecting fluid leakage
FR2678950B1 (en) * 1991-07-09 1993-11-05 Bertin Et Cie Cartridge, device and method of extraction of nucleic acids such as DNA from a blood sample or tissue cells.
US5726010A (en) * 1991-07-31 1998-03-10 Idexx Laboratories, Inc. Reversible flow chromatographic binding assay
US6165778A (en) 1993-11-02 2000-12-26 Affymax Technologies N.V. Reaction vessel agitation apparatus
US5639603A (en) 1991-09-18 1997-06-17 Affymax Technologies N.V. Synthesizing and screening molecular diversity
EP0612354B1 (en) 1991-10-04 1997-01-08 Orgenics Limited Method and apparatus for detection of nucleic acid sequences
DE69223980D1 (en) 1991-10-15 1998-02-12 Multilyte Ltd binding assay using a labeled reagent
US5215131A (en) * 1991-11-14 1993-06-01 Poy George L Automatic liquid delivery system
US5324633A (en) 1991-11-22 1994-06-28 Affymax Technologies N.V. Method and apparatus for measuring binding affinity
US5384261A (en) * 1991-11-22 1995-01-24 Affymax Technologies N.V. Very large scale immobilized polymer synthesis using mechanically directed flow paths
US5310469A (en) 1991-12-31 1994-05-10 Abbott Laboratories Biosensor with a membrane containing biologically active material
JP3007469B2 (en) * 1992-01-30 2000-02-07 パイオニア株式会社 Speaker magnetic circuit
US5888723A (en) 1992-02-18 1999-03-30 Johnson & Johnson Clinical Diagnostics, Inc. Method for nucleic acid amplification and detection using adhered probes
US5380489A (en) 1992-02-18 1995-01-10 Eastman Kodak Company Element and method for nucleic acid amplification and detection using adhered probes
WO1993017126A1 (en) 1992-02-19 1993-09-02 The Public Health Research Institute Of The City Of New York, Inc. Novel oligonucleotide arrays and their use for sorting, isolating, sequencing, and manipulating nucleic acids
US5445970A (en) 1992-03-20 1995-08-29 Abbott Laboratories Magnetically assisted binding assays using magnetically labeled binding members
US5376313A (en) 1992-03-27 1994-12-27 Abbott Laboratories Injection molding a plastic assay cuvette having low birefringence
US5258781A (en) * 1992-04-08 1993-11-02 Xerox Corporation One-step encapsulation, air gap sealing and structure bonding of thermal ink jet printhead
EP0565999A3 (en) 1992-04-16 1994-02-09 Siemens Ag
US5637469A (en) * 1992-05-01 1997-06-10 Trustees Of The University Of Pennsylvania Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems
US5587128A (en) 1992-05-01 1996-12-24 The Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification devices
US5486335A (en) * 1992-05-01 1996-01-23 Trustees Of The University Of Pennsylvania Analysis based on flow restriction
US5304487A (en) * 1992-05-01 1994-04-19 Trustees Of The University Of Pennsylvania Fluid handling in mesoscale analytical devices
US5326692B1 (en) 1992-05-13 1996-04-30 Molecular Probes Inc Fluorescent microparticles with controllable enhanced stokes shift
WO1994000597A1 (en) 1992-06-23 1994-01-06 Pharmacia Lkb Biotechnology Ab Method and system for molecular-biological diagnostics
JP3311752B2 (en) 1992-07-02 2002-08-05 ソイニ,エルッキ Biospecific multivariate assay
US5288514A (en) 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
EP0723146B1 (en) 1992-09-14 2004-05-06 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
US5674698A (en) 1992-09-14 1997-10-07 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
US5565324A (en) 1992-10-01 1996-10-15 The Trustees Of Columbia University In The City Of New York Complex combinatorial chemical libraries encoded with tags
US5288463A (en) * 1992-10-23 1994-02-22 Eastman Kodak Company Positive flow control in an unvented container
US5543329A (en) * 1992-11-03 1996-08-06 Intelligent Monitoring Systems And Advanced Global Technologies Sensor for antigen-antibody reactions
WO1994011529A1 (en) 1992-11-06 1994-05-26 Pharmacia Biotech Ab A method of processing nucleic acid samples
US5422271A (en) * 1992-11-20 1995-06-06 Eastman Kodak Company Nucleic acid material amplification and detection without washing
US5500187A (en) * 1992-12-08 1996-03-19 Westinghouse Electric Corporation Disposable optical agglutination assay device and method for use
US5314829A (en) 1992-12-18 1994-05-24 California Institute Of Technology Method for imaging informational biological molecules on a semiconductor substrate
US5298741A (en) 1993-01-13 1994-03-29 Trustees Of Tufts College Thin film fiber optic sensor array and apparatus for concurrent viewing and chemical sensing of a sample
JPH08506664A (en) * 1993-02-01 1996-07-16 セック,リミテッド The methods and apparatus of the Dna sequencing
US5364790A (en) * 1993-02-16 1994-11-15 The Perkin-Elmer Corporation In situ PCR amplification system
CA2102884A1 (en) 1993-03-04 1994-09-05 James J. Wynne Dental procedures and apparatus using ultraviolet radiation
US5279721A (en) * 1993-04-22 1994-01-18 Peter Schmid Apparatus and method for an automated electrophoresis system
US5395587A (en) * 1993-07-06 1995-03-07 Smithkline Beecham Corporation Surface plasmon resonance detector having collector for eluted ligate
JP3598123B2 (en) * 1993-07-15 2004-12-08 浜松ホトニクス株式会社 Modified detector nucleic acid
JP3302458B2 (en) 1993-08-31 2002-07-15 富士通株式会社 Integrated optical device and a manufacturing method
JP3106874B2 (en) * 1993-09-29 2000-11-06 松下電器産業株式会社 Disk recording and reproducing apparatus
US5374395A (en) 1993-10-14 1994-12-20 Amoco Corporation Diagnostics instrument
CA2174140C (en) 1993-10-28 2004-04-06 Kenneth L. Beattie Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions
US5494798A (en) 1993-12-09 1996-02-27 Gerdt; David W. Fiber optic evanscent wave sensor for immunoassay
US5496997A (en) 1994-01-03 1996-03-05 Pope; Edward J. A. Sensor incorporating an optical fiber and a solid porous inorganic microsphere
US5591384A (en) * 1994-03-31 1997-01-07 Modern Technologies Corp. Method for molding parts
EP0758405B1 (en) 1994-05-06 2001-07-18 APBiotech Aktiebolag Method of nucleic acid transfer
US5571639A (en) * 1994-05-24 1996-11-05 Affymax Technologies N.V. Computer-aided engineering system for design of sequence arrays and lithographic masks
US6287850B1 (en) 1995-06-07 2001-09-11 Affymetrix, Inc. Bioarray chip reaction apparatus and its manufacture
DE69527585T2 (en) * 1994-06-08 2003-04-03 Affymetrix Inc Method and apparatus for packaging chips
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
US5549974A (en) 1994-06-23 1996-08-27 Affymax Technologies Nv Methods for the solid phase synthesis of thiazolidinones, metathiazanones, and derivatives thereof
US5512490A (en) 1994-08-11 1996-04-30 Trustees Of Tufts College Optical sensor, optical sensing apparatus, and methods for detecting an analyte of interest using spectral recognition patterns
US5578832A (en) * 1994-09-02 1996-11-26 Affymetrix, Inc. Method and apparatus for imaging a sample on a device
US5627041A (en) * 1994-09-02 1997-05-06 Biometric Imaging, Inc. Disposable cartridge for an assay of a biological sample
US5695934A (en) 1994-10-13 1997-12-09 Lynx Therapeutics, Inc. Massively parallel sequencing of sorted polynucleotides
JPH08178926A (en) 1994-10-25 1996-07-12 Eiji Ishikawa Immunoassay plate and use thereof
US5585069A (en) * 1994-11-10 1996-12-17 David Sarnoff Research Center, Inc. Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis
US5866434A (en) * 1994-12-08 1999-02-02 Meso Scale Technology Graphitic nanotubes in luminescence assays
US5784152A (en) 1995-03-16 1998-07-21 Bio-Rad Laboratories Tunable excitation and/or tunable detection microplate reader
US5609826A (en) 1995-04-17 1997-03-11 Ontogen Corporation Methods and apparatus for the generation of chemical libraries
DE19514638C2 (en) * 1995-04-20 1998-06-04 Peter Dr Med Boekstegers An apparatus for venous pressure controlled selective extraction and retroinfusion a fluid from or in veins of the body
US6340588B1 (en) 1995-04-25 2002-01-22 Discovery Partners International, Inc. Matrices with memories
US5690894A (en) 1995-05-23 1997-11-25 The Regents Of The University Of California High density array fabrication and readout method for a fiber optic biosensor
US5628849A (en) * 1995-05-26 1997-05-13 International Business Machines Corporation Method for in-situ environment sensitive sealing and/or product controlling
US5545531A (en) 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US6074614A (en) 1995-06-07 2000-06-13 Molecular Devices Corporation Multi-assay plate cover for elimination of meniscus
US5856174A (en) 1995-06-29 1999-01-05 Affymetrix, Inc. Integrated nucleic acid diagnostic device
JP3561891B2 (en) 1995-08-25 2004-09-02 プレシジョン・システム・サイエンス株式会社 Microplate shielding means and luminometer
US5658802A (en) * 1995-09-07 1997-08-19 Microfab Technologies, Inc. Method and apparatus for making miniaturized diagnostic arrays
US5656241A (en) 1995-09-07 1997-08-12 Optical Sensors Incorporated Method for manufacturing fiber optic sensors
US6040138A (en) * 1995-09-15 2000-03-21 Affymetrix, Inc. Expression monitoring by hybridization to high density oligonucleotide arrays
US5981180A (en) 1995-10-11 1999-11-09 Luminex Corporation Multiplexed analysis of clinical specimens apparatus and methods
US5716825A (en) * 1995-11-01 1998-02-10 Hewlett Packard Company Integrated nucleic acid analysis system for MALDI-TOF MS
US5633972A (en) 1995-11-29 1997-05-27 Trustees Of Tufts College Superresolution imaging fiber for subwavelength light energy generation and near-field optical microscopy
US5814524A (en) 1995-12-14 1998-09-29 Trustees Of Tufts College Optical sensor apparatus for far-field viewing and making optical analytical measurements at remote locations
US6660233B1 (en) 1996-01-16 2003-12-09 Beckman Coulter, Inc. Analytical biochemistry system with robotically carried bioarray
US5837196A (en) 1996-01-26 1998-11-17 The Regents Of The University Of California High density array fabrication and readout method for a fiber optic biosensor
US5649576A (en) 1996-02-26 1997-07-22 Pharmacopeia, Inc. Partitioning device
US6114122A (en) * 1996-03-26 2000-09-05 Affymetrix, Inc. Fluidics station with a mounting system and method of using
US5840256A (en) 1996-04-09 1998-11-24 David Sarnoff Research Center Inc. Plate for reaction system
CA2255839A1 (en) * 1996-07-05 1998-01-15 Mark Gross Automated sample processing system
WO1998001744A1 (en) 1996-07-10 1998-01-15 Cambridge Imaging Limited Improved imaging system for fluorescence assays
GB2315131B (en) 1996-07-10 2000-11-29 Cambridge Imaging Ltd Improvements in and relating to imaging
US5854684A (en) 1996-09-26 1998-12-29 Sarnoff Corporation Massively parallel detection
US5900481A (en) 1996-11-06 1999-05-04 Sequenom, Inc. Bead linkers for immobilizing nucleic acids to solid supports
US5804384A (en) 1996-12-06 1998-09-08 Vysis, Inc. Devices and methods for detecting multiple analytes in samples
US6083763A (en) 1996-12-31 2000-07-04 Genometrix Inc. Multiplexed molecular analysis apparatus and method
US5837860A (en) 1997-03-05 1998-11-17 Molecular Tool, Inc. Covalent attachment of nucleic acid molecules onto solid-phases via disulfide bonds
US6023540A (en) 1997-03-14 2000-02-08 Trustees Of Tufts College Fiber optic sensor with encoded microspheres
US6327410B1 (en) 1997-03-14 2001-12-04 The Trustees Of Tufts College Target analyte sensors utilizing Microspheres
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
US6406845B1 (en) 1997-05-05 2002-06-18 Trustees Of Tuft College Fiber optic biosensor for selectively detecting oligonucleotide species in a mixed fluid sample
US5985214A (en) * 1997-05-16 1999-11-16 Aurora Biosciences Corporation Systems and methods for rapidly identifying useful chemicals in liquid samples
US5876946A (en) 1997-06-03 1999-03-02 Pharmacopeia, Inc. High-throughput assay
US5869004A (en) * 1997-06-09 1999-02-09 Caliper Technologies Corp. Methods and apparatus for in situ concentration and/or dilution of materials in microfluidic systems
US6071748A (en) 1997-07-16 2000-06-06 Ljl Biosystems, Inc. Light detection device
US6037186A (en) 1997-07-16 2000-03-14 Stimpson; Don Parallel production of high density arrays
US7115884B1 (en) 1997-10-06 2006-10-03 Trustees Of Tufts College Self-encoding fiber optic sensor
DE19745373A1 (en) 1997-10-14 1999-04-15 Bayer Ag Optical measuring system for detecting luminescence or fluorescence signals
US6090553A (en) * 1997-10-29 2000-07-18 Beckman Coulter, Inc. Use of uracil-DNA glycosylase in genetic analysis
US5922617A (en) 1997-11-12 1999-07-13 Functional Genetics, Inc. Rapid screening assay methods and devices
US6268131B1 (en) 1997-12-15 2001-07-31 Sequenom, Inc. Mass spectrometric methods for sequencing nucleic acids
US6458533B1 (en) 1997-12-19 2002-10-01 High Throughput Genomics, Inc. High throughput assay system for monitoring ESTs
US6232066B1 (en) 1997-12-19 2001-05-15 Neogen, Inc. High throughput assay system
US6887693B2 (en) * 1998-12-24 2005-05-03 Cepheid Device and method for lysing cells, spores, or microorganisms
US6269846B1 (en) 1998-01-13 2001-08-07 Genetic Microsystems, Inc. Depositing fluid specimens on substrates, resulting ordered arrays, techniques for deposition of arrays
US6210910B1 (en) 1998-03-02 2001-04-03 Trustees Of Tufts College Optical fiber biosensor array comprising cell populations confined to microcavities
US6519032B1 (en) 1998-04-03 2003-02-11 Symyx Technologies, Inc. Fiber optic apparatus and use thereof in combinatorial material science
JP3662850B2 (en) 1998-06-24 2005-06-22 イルミナ インコーポレイテッド Decoding array sensor having a microsphere
US6608671B2 (en) 1998-07-17 2003-08-19 Vertex Pharmaceuticals (San Diego) Llc Detector and screening device for ion channels
JP2002522065A (en) * 1998-08-10 2002-07-23 ジェノミック ソリューションズ インコーポレイテッド Nucleic acid hybridizing heat and fluid circulation device
US6132685A (en) 1998-08-10 2000-10-17 Caliper Technologies Corporation High throughput microfluidic systems and methods
US6050278A (en) * 1998-09-24 2000-04-18 Minntech Corporation Dialyzer precleaning system
US6100084A (en) * 1998-11-05 2000-08-08 The Regents Of The University Of California Micro-sonicator for spore lysis
WO2000029619A3 (en) * 1998-11-13 2000-08-10 T Christian Boles Multielement analytical device for assay of nucleic acid sequences and uses therefore
DE19852982C1 (en) * 1998-11-17 2000-03-16 Braun Melsungen Ag Cartridge holder for dialysis machine has lower cheek with outlet connection and upper cheek with inflow connection, with cartridge being insertable between cheeks
US6429027B1 (en) 1998-12-28 2002-08-06 Illumina, Inc. Composite arrays utilizing microspheres
US20020150909A1 (en) 1999-02-09 2002-10-17 Stuelpnagel John R. Automated information processing in randomly ordered arrays
EP1163369B1 (en) * 1999-02-23 2011-05-04 Caliper Life Sciences, Inc. Sequencing by incorporation
US6235479B1 (en) * 1999-04-13 2001-05-22 Bio Merieux, Inc. Methods and devices for performing analysis of a nucleic acid sample
US6355431B1 (en) 1999-04-20 2002-03-12 Illumina, Inc. Detection of nucleic acid amplification reactions using bead arrays
US20030108867A1 (en) 1999-04-20 2003-06-12 Chee Mark S Nucleic acid sequencing using microsphere arrays
US6261523B1 (en) 1999-04-27 2001-07-17 Agilent Technologies Inc. Adjustable volume sealed chemical-solution-confinement vessel
DE19923821A1 (en) * 1999-05-19 2000-11-23 Zeiss Carl Jena Gmbh Method and device for recording the position of a surface to be scanned with a laser scanner includes a microscope beam input directed through a microscope lens onto a lens with a biochip to pick up fluorescent samples.
US6544732B1 (en) 1999-05-20 2003-04-08 Illumina, Inc. Encoding and decoding of array sensors utilizing nanocrystals
WO2000075373A3 (en) 1999-05-20 2002-01-24 Illumina Inc Combinatorial decoding of random nucleic acid arrays
WO2000071992A1 (en) 1999-05-20 2000-11-30 Illumina, Inc. Method and apparatus for retaining and presenting at least one microsphere array to solutions and/or to optical imaging systems
JP4316050B2 (en) * 1999-05-31 2009-08-19 ボールセミコンダクター株式会社 Method of manufacturing a micromachine
US6170494B1 (en) * 1999-11-12 2001-01-09 Advanced Micro Devices, Inc. Method for automatically cleaning resist nozzle
US6663832B2 (en) 1999-12-13 2003-12-16 Illumina, Inc. Oligonucleotide synthesizer
US20010039014A1 (en) * 2000-01-11 2001-11-08 Maxygen, Inc. Integrated systems and methods for diversity generation and screening
US20020006617A1 (en) 2000-02-07 2002-01-17 Jian-Bing Fan Nucleic acid detection methods using universal priming
US6770441B2 (en) 2000-02-10 2004-08-03 Illumina, Inc. Array compositions and methods of making same
FR2806166B1 (en) * 2000-03-09 2002-11-15 Genomic Sa PLC for processing, signal acquisition and analysis of biochips
US6511277B1 (en) 2000-07-10 2003-01-28 Affymetrix, Inc. Cartridge loader and methods
US6422249B1 (en) * 2000-08-10 2002-07-23 Affymetrix Inc. Cartridge washing system and methods
US20030096239A1 (en) 2000-08-25 2003-05-22 Kevin Gunderson Probes and decoder oligonucleotides
WO2002021128A3 (en) 2000-09-05 2003-01-23 Illumina Inc Cellular arrays comprising encoded cells
JP4361271B2 (en) * 2000-10-10 2009-11-11 バイオトローブ・インコーポレイテツド Assay, synthesis, and instruments for storage, as well as methods of making, using, and operation
US7033761B2 (en) * 2000-11-14 2006-04-25 Shafer David A Expression miniarrays and uses thereof
US6905816B2 (en) * 2000-11-27 2005-06-14 Intelligent Medical Devices, Inc. Clinically intelligent diagnostic devices and methods
JP4583710B2 (en) * 2000-12-11 2010-11-17 プレジデント・アンド・フェローズ・オブ・ハーバード・カレッジ Nanosensors
US6869792B2 (en) * 2001-03-16 2005-03-22 Irm, Llc Method and apparatus for performing multiple processing steps on a sample in a single vessel
US7332127B2 (en) * 2001-07-11 2008-02-19 University Of Southern California DNA probe synthesis on chip on demand by MEMS ejector array
US7582420B2 (en) 2001-07-12 2009-09-01 Illumina, Inc. Multiplex nucleic acid reactions
EP1421365A1 (en) 2001-07-19 2004-05-26 Tufts University Optical array device and methods of use thereof for screening, analysis and manipulation of particles
US6998094B2 (en) * 2001-09-06 2006-02-14 Genetix Limited Apparatus for and methods of handling biological sample containers
CA2474530A1 (en) * 2002-02-07 2003-08-14 Eastern Virginia Medical School Of The Medical College Of Hampton Roads Diagnostic microarray and method of use thereof
US8048386B2 (en) * 2002-02-25 2011-11-01 Cepheid Fluid processing and control
EP1380337B1 (en) * 2002-07-12 2012-11-14 Tosoh Corporation Fine channel device and a chemically operating method for fluid using the device
US20040120861A1 (en) * 2002-10-11 2004-06-24 Affymetrix, Inc. System and method for high-throughput processing of biological probe arrays
US7402279B2 (en) * 2002-10-31 2008-07-22 Agilent Technologies, Inc. Device with integrated microfluidic and electronic components
US20040191807A1 (en) * 2002-12-13 2004-09-30 Affymetrix, Inc. Automated high-throughput microarray system
US7043939B2 (en) * 2003-08-14 2006-05-16 Imac Business Corporation Band-like ring
US7476360B2 (en) * 2003-12-09 2009-01-13 Genefluidics, Inc. Cartridge for use with electrochemical sensor
US20060034913A1 (en) 2004-08-13 2006-02-16 James Gaede Multiplex drug delivery device
US8075852B2 (en) 2005-11-02 2011-12-13 Affymetrix, Inc. System and method for bubble removal
US20080038714A1 (en) * 2005-11-02 2008-02-14 Affymetrix, Inc. Instrument to Pneumatically Control Lab Cards and Method Thereof
US8007267B2 (en) 2005-11-02 2011-08-30 Affymetrix, Inc. System and method for making lab card by embossing
US20070099288A1 (en) * 2005-11-02 2007-05-03 Affymetrix, Inc. Microfluidic Methods, Devices, and Systems for Fluid Handling
US20080311585A1 (en) 2005-11-02 2008-12-18 Affymetrix, Inc. System and method for multiplex liquid handling
KR100772893B1 (en) * 2006-05-02 2007-11-05 삼성전자주식회사 Oligomer probe array with improved signal to noise ratio and assay intensity and fabrication method thereof
US20080003667A1 (en) 2006-05-19 2008-01-03 Affymetrix, Inc. Consumable elements for use with fluid processing and detection systems

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4731335A (en) * 1985-09-13 1988-03-15 Fisher Scientific Company Method for treating thin samples on a surface employing capillary flow
US4731335B1 (en) * 1985-09-13 1991-07-09 Fisher Scientific Co
US5601650A (en) * 1991-05-29 1997-02-11 Medite Gesellschaft Fur Medizintechnik Mbh Process and device for dyeing histological preparations arranged on microscope slides
US6361940B1 (en) * 1996-09-24 2002-03-26 Qiagen Genomics, Inc. Compositions and methods for enhancing hybridization and priming specificity
US20040185483A1 (en) * 1998-12-28 2004-09-23 Illumina, Inc. Composite arrays utilizing microspheres with a hybridization chamber
US20060234371A1 (en) * 2005-04-06 2006-10-19 Affymetrix, Inc. System and method for processing large number of biological microarrays

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060234371A1 (en) * 2005-04-06 2006-10-19 Affymetrix, Inc. System and method for processing large number of biological microarrays
US8796186B2 (en) 2005-04-06 2014-08-05 Affymetrix, Inc. System and method for processing large number of biological microarrays
US8351026B2 (en) 2005-04-22 2013-01-08 Affymetrix, Inc. Methods and devices for reading microarrays
US20100328732A1 (en) * 2006-11-21 2010-12-30 Illumina Inc. Hexagonal site line scanning method and system
US8023162B2 (en) * 2006-11-21 2011-09-20 Illumina, Inc. Hexagonal site line scanning method and system

Also Published As

Publication number Publication date Type
CN1847848B (en) 2012-10-10 grant
CN1847848A (en) 2006-10-18 application
US20060234371A1 (en) 2006-10-19 application
CN201040757Y (en) 2008-03-26 grant
CN201006877Y (en) 2008-01-16 grant
US20100081583A1 (en) 2010-04-01 application
US20100069265A1 (en) 2010-03-18 application
US8796186B2 (en) 2014-08-05 grant
CN1876800A (en) 2006-12-13 application

Similar Documents

Publication Publication Date Title
US6280954B1 (en) Arrayed primer extension technique for nucleic acid analysis
US5919626A (en) Attachment of unmodified nucleic acids to silanized solid phase surfaces
US6248521B1 (en) Amplification and other enzymatic reactions performed on nucleic acid arrays
US7314750B2 (en) Addressable oligonucleotide array of the rat genome
US7250289B2 (en) Methods of genetic analysis of mouse
Bumgarner Overview of DNA microarrays: types, applications, and their future
Khrapko et al. An oligonucleotide hybridization approach to DNA sequencing
Graves Powerful tools for genetic analysis come of age
US20070238105A1 (en) High resolution chromosomal mapping
US6864097B1 (en) Arrays and their reading
US20090005259A1 (en) Random array DNA analysis by hybridization
US20020012926A1 (en) Combinatorial array for nucleic acid analysis
US20070059692A1 (en) Array oligomer synthesis and use
US20050196785A1 (en) Combinational array for nucleic acid analysis
US20030032035A1 (en) Microfluidic device for analyzing nucleic acids and/or proteins, methods of preparation and uses thereof
US6387631B1 (en) Polymer coated surfaces for microarray applications
Drmanac et al. Sequencing by hybridization (SBH): advantages, achievements, and opportunities
Jain Applications of biochip and microarray systems in pharmacogenomics
US20060057576A1 (en) Microcapillary hybridization chamber
US20060046251A1 (en) Element defined sequence complexity reduction
US20030143551A1 (en) Reading multiple chemical arrays
US7138506B2 (en) Universal microarray system
WO2003040410A1 (en) Detection of hybridization oligonucleotide microarray through covalently labeling microarray probe
US20050244851A1 (en) Methods of analysis of alternative splicing in human
WO2012148477A1 (en) Digital counting of individual molecules by stochastic attachment of diverse label-tags

Legal Events

Date Code Title Description
AS Assignment

Owner name: AFFYMETRIX, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SHIRAZI, MOHSEN;REEL/FRAME:018021/0789

Effective date: 20060605