US5874219A — Methods for concurrently processing multiple biol…

Claim 1

Independent Claim 141 words

A method for concurrently processing multiple biological chip assays comprising the steps of: (a) providing a biological chip plate comprising a contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays and, surrounding the probe arrays, material resistant to the flow of liquid thereby forming a plurality of test wells, each test well defining a space for the introduction of a sample; (b) manipulating the biological chip plate with a fluid handling device that automatically performs steps to carry out reactions between target molecules in a test sample and probes in a plurality of the test wells; and (c) interrogating the probe arrays of the biological chip plate with a biological chip plate reader to detect reactions between target molecules and probes in a plurality of the test wells to generate assay results.

Claim 2

Independent Claim 141 words

A method for concurrently processing multiple biological chip assays comprising the steps of: (a) providing a biological chip plate comprising a contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays and, surrounding the probe arrays, material resistant to the flow of liquid thereby forming a plurality of test wells, each test well defining a space for the introduction of a sample; (b) manipulating the biological chip plate with a fluid handling device that automatically performs steps to carry out reactions between target molecules in a test sample and probes in a plurality of the test wells; and (c) interrogating the probe arrays of the biological chip plate with a biological chip plate reader to detect reactions between target molecules and probes in a plurality of the test wells to generate assay results.

Claim 3

Dependent Claim 16 words

The method of claim 1 further comprising the step of processing the results with a computer.

Claim 4

Dependent Claim 32 words

The method of claim 2 wherein the results are processed into an image with the intensity in each region of the image varying according to the binding affinity between targets and probes.

Claim 5

Dependent Claim 13 words

The method of claim 1 wherein the probes are DNA or RNA molecules.

Claim 6

Dependent Claim 30 words

The method of claim 4 wherein (a) the reactions are hybridization of target molecules to probes; and (b) the results provide information regarding the nucleotide sequence of the target molecule.

Claim 7

Dependent Claim 17 words

The method of claim 5 wherein the assay is the detection or identification of a pathogenic organism.

Claim 8

Dependent Claim 11 words

The method of claim 6 wherein the pathogenic organism is HIV.

Claim 9

Dependent Claim 18 words

The method of claim 5 wherein the assay is the detection or identification of a human nucleic acid.

Claim 10

Dependent Claim 16 words

The method of claim 8 wherein the assay is the detection of a human gene variant.

Claim 11

Dependent Claim 24 words

The method of claim 8 wherein the human gene variant indicates the existence of, or predisposition to cystic fibrosis, diabetes, muscular dystrophy or cancer.

Claim 12

Dependent Claim 36 words

The method of claim 1 wherein the assay is the identification of a probe in a library that binds to a receptor and the reaction is the binding of a target molecule to a peptide probe.

Claim 13

Dependent Claim 20 words

The method of claim 1 wherein the reaction is the catalytic transformation of a probe molecule by a target catalyst.

Claim 14

Dependent Claim 29 words

The method of claim 1 further comprising controlling the temperature of the samples in the test wells and adding or removing fluids from the test wells at predetermined times.

Claim 15

Dependent Claim 26 words

The method of claim 1 wherein the target molecule is tagged with a fluorescent marker, a chemiluminescent marker, a light scattering marker or a radioactive marker.

Claim 16

Dependent Claim 22 words

The method of claim 14 wherein the marker is a fluorescent marker selected from the group consisting of fluorescein, rhodamine, or cyanine.

Claim 17

Dependent Claim 75 words

The method of claim 1 wherein the fluid handling device and the biological chip plate reader comprise (a) a confocal detection device having a monochromatic or polychromatic light source; (b) optics for directing an excitation light from the light source at the substrate; (c) a temperature controller for controlling temperature of the substrate during a reaction; and (d) a detector for detecting fluorescence emitted by a fluorescently labelled molecule in response to the excitation light.

Claim 18

Dependent Claim 25 words

The method of claim 1 wherein the manipulating step comprises robotically controlling pipets for adding or removing fluids from the test wells at predetermined times.

Claim 19

Dependent Claim 12 words

The method of claim 16 wherein the detector comprises a photomultiplier tube.

Claim 20

Dependent Claim 29 words

The method of claim 16 wherein the interrogating step comprises focusing the excitation light to a point on the plate and determining the region from which the fluorescence originated.

Claim 21

Dependent Claim 24 words

The method of claim 16 wherein the target is tagged with a fluorescent marker and the biological chip plate reader comprises a CCD array.

Claim 22

Dependent Claim 16 words

The method of claim 1 wherein the probe arrays each have at least about 2500 features.

Claim 23

Dependent Claim 16 words

The method of claim 1 wherein the probe arrays each have at least about 50,000 features.

Claim 24

Dependent Claim 14 words

The method of claim 1 wherein each test well comprises an individual probe array.

Claim 25

Dependent Claim 25 words

The method of claim 1 wherein said chip plate is made by the steps of mating a wafer to an array of open ended wells.

Claim 26

Dependent Claim 14 words

The method of claim 5, wherein the samples are from a plurality of patients.

Claim 27

Dependent Claim 27 words

The method of claim 25 further comprising the step of using information from the results to determine which of the patients exhibit a genetic disease or characteristic.

Claim 28

Dependent Claim 34 words

The method of claim 1 wherein the interrogating step comprises the steps of: (a) directing excitation light through a bottom surface of said plate; and (b) detecting where targets bound on said probe arrays.

Claim 29

Dependent Claim 15 words

The method of claim 1 wherein the probe arrays are produced by light-directed probe synthesis.

Claim 30

Dependent Claim 25 words

The method of claim 1 wherein the interrogating step comprises determining the on- or off-rates of binding between target molecules in a sample and probes.

Claim 31

Independent Claim 126 words

A system for concurrently processing multiple biological chip assays comprising: (a) a biological chip plate comprising a contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays and, surrounding the probe arrays, material resistant to the flow of liquid thereby forming a plurality of test wells, each test well defining a space for the introduction of a sample; (b) a fluid handling device that automatically performs steps to carry out reactions between target molecules in the samples and probes in a plurality of the test wells; and (c) a biological chip plate reader that interrogates the probe arrays to detect any reactions between target molecules and probes in a plurality of the test wells to produce assay results.

Claim 32

Independent Claim 126 words

A system for concurrently processing multiple biological chip assays comprising: (a) a biological chip plate comprising a contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays and, surrounding the probe arrays, material resistant to the flow of liquid thereby forming a plurality of test wells, each test well defining a space for the introduction of a sample; (b) a fluid handling device that automatically performs steps to carry out reactions between target molecules in the samples and probes in a plurality of the test wells; and (c) a biological chip plate reader that interrogates the probe arrays to detect any reactions between target molecules and probes in a plurality of the test wells to produce assay results.

Claim 33

Dependent Claim 17 words

The system of claim 30 further comprising a computer comprising a program for processing the assay results.

Claim 34

Dependent Claim 13 words

The system of claim 30 wherein the probes are DNA or RNA molecules.

Claim 35

Dependent Claim 71 words

The system of claim 30 wherein the fluid handling device and the biological chip plate reader comprise (a) a confocal detection device having a monochromatic or polychromatic light source; (b) means for directing an excitation light from the light. source at the substrate; (c) means for controlling temperature of the substrate during a reaction; and (d) means for detecting fluorescence emitted by fluorescently labelled molecules in response to the excitation light.

Claim 36

Dependent Claim 93 words

The system of claim 33 wherein the fluid handling device comprises robotically controlled pipets for adding or removing fluids from the test wells at predetermined times; and wherein (a) the means for detecting the fluorescent emissions from the substrate comprise a photomultiplier tube; (b) the means for focusing the excitation light to a point on the substrate and determining the region from which the fluorescence originated comprise an x-y-z translation table; and (c) wherein translation of the x-y-z translation table, temperature control and data collection are managed and recorded by a digital computer.

Claim 37

Dependent Claim 33 words

The system of claim 33 wherein the means for directing excitation light and means for detecting are arranged to illuminate and read the test wells through a bottom side of the test wells.

Claim 38

Dependent Claim 15 words

The system of claim 30 wherein the biological chip plate reader comprises a line scanner.

Claim 39

Dependent Claim 15 words

The system of claim 30 wherein the biological chip plate reader comprises a CCD array.

Claim 40

Dependent Claim 15 words

The system of claim 30 wherein each probe array has at least about 2500 features.

Claim 41

Dependent Claim 15 words

The system of claim 30 wherein each probe array has at least about 50,000 features.

Claim 42

Dependent Claim 15 words

The system of claim 30 wherein the biological chip plate comprises about 96 test wells.

Claim 43

Dependent Claim 49 words

A biological chip plate comprising a contiguous substrate that comprises on its surface a plurality of probe arrays and, surrounding the probe arrays, material resistant to the flow of liquid thereby forming a plurality of test wells, each test well defining a space for the introduction of a sample.

Claim 44

Dependent Claim 49 words

A biological chip plate comprising a contiguous substrate that comprises on its surface a plurality of probe arrays and, surrounding the probe arrays, material resistant to the flow of liquid thereby forming a plurality of test wells, each test well defining a space for the introduction of a sample.

Claim 45

Dependent Claim 28 words

The biological chip plate of claim 41 wherein the substrate comprises functionalized glass or silica comprising Si, Ge, GaAs, GaP, SiO 2 , SiN 4 or modified silicon.

Claim 46

Dependent Claim 35 words

The biological chip plate of claim 41 wherein the surface comprises polymers, plastics, resins, polysaccharides, silica or silica-based materials, carbon, metals, inorganic glasses, membranes, polymerized Langmuir Blodgett film, functionalized glass, (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polystyrene or polycarbonate.

Claim 47

Dependent Claim 22 words

The biological chip plate of claim 41 comprising a body having test wells, wherein each test well comprises an individual probe array.

Claim 48

Dependent Claim 19 words

The biological chip plate of claim 44 wherein the body comprises (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polypropylene, polystyrene, polycarbonate, or combinations thereof.

Claim 49

Dependent Claim 69 words

The biological chip plate of claim 41 comprising a wafer and a body, the wafer comprising a plurality of probe arrays and the body comprising a plurality of channels, wherein the body is attached to the surface of the wafer so that a plurality of the channels each cover a probe array and the wafer closes one end of a plurality of the channels, thereby forming the test wells.

Claim 50

Dependent Claim 19 words

The biological chip plate of claim 46 wherein the body comprises (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polypropylene, polystyrene, polycarbonate, or combinations thereof.

Claim 51

Dependent Claim 32 words

The biological chip plate of claim 41 comprising a wafer having a plurality of probe arrays and a material resistant to the flow of a liquid sample that surrounds each probe array.

Claim 52

Dependent Claim 14 words

The biological chip plate of claim 48 wherein the material is a hydrophobic material.

Claim 53

Dependent Claim 17 words

The biological chip plate of claim 41 comprising 96 wells arranged in 8 rows and 12 columns.

Claim 54

Dependent Claim 15 words

The biological chip plate of claim 41 wherein the probes are DNA or RNA molecules.

Claim 55

Dependent Claim 19 words

The biological chip plate of claim 51 wherein the DNA or RNA molecules comprise sequences directed to pathogenic organisms.

Claim 56

Dependent Claim 13 words

The biological chip plate of claim 52 wherein the pathogenic organism is HIV.

Claim 57

Dependent Claim 19 words

The biological chip plate of claim 51 wherein the DNA or RNA molecules comprise sequences directed to human DNA.

Claim 58

Dependent Claim 28 words

The biological chip plate of claim 52 wherein the sequences are directed to a human gene variant that indicates the existence of or predisposition to a genetic disease.

Claim 59

Dependent Claim 18 words

The biological chip plate of claim 55 wherein the disease is cystic fibrosis, diabetes, muscular dystrophy or cancer.

Claim 60

Dependent Claim 19 words

The biological chip plate of claim 41 wherein the probe arrays each of the test wells are the same.

Claim 61

Dependent Claim 32 words

The biological chip plate of claim 41 wherein the test wells are arranged in rows and columns and the rows contain the same probe array and the columns contain different probe arrays.

Claim 62

Dependent Claim 16 words

The biological chip plate of claim 41 wherein the probe arrays comprise at least 1000 features.

Claim 63

Dependent Claim 16 words

The biological chip plate of claim 41 wherein the probe arrays comprise at least 10,000 features.

Claim 64

Dependent Claim 16 words

The biological chip plate of claim 41 wherein the probe arrays comprise at least 100,000 features.

Claim 65

Dependent Claim 16 words

The biological chip plate of claim 41 wherein the probe arrays comprise at least 1,000,000 features.

Claim 66

Independent Claim 91 words

A method for making a biological chip plate comprising the steps of providing a contiguous substrate and a body, the contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays, and the body comprising a plurality of channels; and attaching the body to the surface of the contiguous substrate whereby a plurality of the channels each cover a probe array and the surface of the substrate closes one end of the plurality of channels, thereby forming test wells defining spaces for receiving samples.

Claim 67

Independent Claim 91 words

A method for making a biological chip plate comprising the steps of providing a contiguous substrate and a body, the contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays, and the body comprising a plurality of channels; and attaching the body to the surface of the contiguous substrate whereby a plurality of the channels each cover a probe array and the surface of the substrate closes one end of the plurality of channels, thereby forming test wells defining spaces for receiving samples.

Claim 68

Dependent Claim 13 words

The method of claim 63 wherein the probes are DNA or RNA molecules.

Claim 69

Dependent Claim 55 words

A wafer comprising a contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays, wherein the probe arrays are arranged on the wafer surface in rows and columns, wherein the probe arrays in each row are the same and the probe arrays in each column are different.

Claim 70

Dependent Claim 55 words

A wafer comprising a contiguous substrate that comprises a contiguous surface and, attached to the contiguous surface, a plurality of probe arrays, wherein the probe arrays are arranged on the wafer surface in rows and columns, wherein the probe arrays in each row are the same and the probe arrays in each column are different.

Claim 71

Dependent Claim 13 words

The wafer of claim 65 wherein the probes are DNA or RNA molecules.

Claim 72

Dependent Claim 15 words

The wafer of claim 66 wherein the DNA or RNA molecules comprise sequences of HIV.

Claim 73

Dependent Claim 21 words

The wafer of claim 66 wherein the probe arrays in the columns comprise sequences for screening a plurality of genetic diseases.

Claim 74

Dependent Claim 17 words

The wafer of claim 68 wherein the genetic diseases comprise cystic fibrosis, diabetes, muscular dystrophy or cancer.

Claim 75

Dependent Claim 37 words

The method of claim 28 wherein said arrays of probes are made by repeating the steps of: (a) selectively directing light at said surface to remove photoremovable protecting groups; and (b) selectively coupling monomers to said surface.

Claim 76

Dependent Claim 15 words

The system of claim 30 wherein the probe arrays are produced by light-directed probe synthesis.

Claim 77

Dependent Claim 17 words

The biological chip plate of claim 41 wherein the probe arrays are produced by light-directed probe synthesis.

Claim 78

Dependent Claim 15 words

The method of claim 63 wherein the probe arrays are produced by light-directed probe synthesis.

Claim 79

Dependent Claim 15 words

The wafer of claim 69 wherein the probe arrays are produced by light-directed probe synthesis.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2002-02-22	2002-08-24	2003-02-23	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2006-02-22	2006-08-24	2007-02-23	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2010-02-22	2010-08-24	2011-02-23	$7700.00	Window Closed / Lapsed

Methods for concurrently processing multiple biological chip assays

Abstract

Inventors

Bibliographic Details

Claims Analysis

References Cited (Backward Citations)

USPTO Annuity & Maintenance Windows

Assigned Categories & Tags

Assign Category Tag