SPATIAL POSITIONING OF SPECTRALLY LABELED BEADS

• US 20100210472A1
• Filed: 11/17/2009
• Published: 08/19/2010
• Est. Priority Date: 04/06/2000
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: EMPEDOCLES, Stephen A., Watson, Andrew R., Jin, Jian
• Granted Patent: US 8,405,828 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00574 radioactive
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00578 electrophoric
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00743 Cells
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• CPC Class Codes: B01L 2400/0457 : passive flow or gravitation
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/545 : for laboratory containers
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2015/0092 : Monitoring flocculation or agglomeration
• CPC Class Codes: G01N 2015/1472 : with colour
• CPC Class Codes: G01N 2015/1497 : Particle shape
• CPC Class Codes: G01N 2021/6441 : with two or more labels
• CPC Class Codes: G01N 2021/6482 : Sample cells, cuvettes
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00742 : Type of codes
• CPC Class Codes: G01N 2035/00752 : bar codes
• CPC Class Codes: G01N 21/25 : Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/272 : for following a reaction, e.g. for determining photometrically a reaction rate (photometric cinetic analysis)
• CPC Class Codes: G01N 21/274 : Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/278 : Constitution of standards
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6456 : Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6486 : Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 21/6489 : Photoluminescence of semiconductors
• CPC Class Codes: G01N 2201/04 : Batch operation; multisample devices
• CPC Class Codes: G01N 2201/06113 : Coherent sources; lasers
• CPC Class Codes: G01N 2201/12 : Circuits of general importance; Signal processing
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

Devices, systems, kits, and methods for detecting and/or identifying a plurality of spectrally labeled bodies well-suited for performing multiplexed assays. By spectrally labeling the beads with materials which generate identifiable spectra, a plurality of beads may be identified within the fluid. Reading of the beads is facilitated by restraining the beads in arrays, and/or using a focused laser.

Claims

1. A spectral label identification method comprising:

spatially restraining a first spectrally labeled body at a site in an array of sites;

spatially restrained a plurality of labeled bodies behind the first body so as to define an array;

dispersing a plurality of spectra from the spatially restrained bodies simultaneously across the sensor surface; and

identifying the array of bodies from the spectrum, wherein the plurality of spectrally labeled bodies are simultaneously spatially restrained as an array when the first body is restrained.

2. The method of claim 1, wherein the array of bodies are restrained within an array of openings in a multi-well plate.

3. The method of claim 2, wherein the array of openings in the multi-well plate are spaced to avoid excessive overlap of the dispersed spectra such that each of the bodies can be identified from the associated spectrum.

4. The method in claim 2, wherein the array of openings in the multi-well plate are spaced in a staggered pattern so as to increase the array density while avoiding excessive overlap among the dispersed spectra.

5. The method of claim 2, wherein the array of openings in the multi-well plate are deep enough to contain a set of labeled bodies.

6. The method of claim 5, wherein the labeled bodies are moved into the array of openings in the multi-well plate by vacuum action.

7. The method of claim 1, wherein the labeled body is restrained by a restraining energy beam which is configured to restrain a single body.

8. A spectral label identification method comprising:

spatially restraining a first spectrally labeled body at a site in an array of sites;

spatially restraining a plurality of labeled bodies behind the first body so as to define an array.

sensing a first and second spectra with a scanning system by moving a sensing field between the bodies of the array; and

identifying the array of bodies from the spectrum, wherein the plurality of spectrally labeled bodies are simultaneously spatially restrained as an array when the first body is restrained.

9. The method of claim 8, wherein the array of bodies are restrained within the array of openings in a multi-well plate.

10. The method in claim 9, wherein the array of openings in the multi-well plate are spaced to avoid excessive overlap to dispersed spectra such that each of the bodies can be identified from the associated spectrum.

11. The method in claim 9, wherein the array of openings in the multi-well plate are spaced in a staggered pattern so as to increase the array density while avoiding excessive overlap among the dispersed spectra.

12. The method of claim 9, wherein the array of openings in a multi-well plate are deep enough to contain a set of labeled bodies.

13. The method of claim 12, wherein the labeled bodies are moved into the array of openings in a multi-well plate by vacuum action.

14. A spectral label identification method comprising:

spatially restraining a first spectrally labeled body at a site in an array of sites in an array of sites;

spatially restraining an array of bodies in the array by an array of discrete binding sites, the binding sites comprising material capable of binding bodies;

sensing a first and second spectra with a scanning system by moving a sensing field between the bodies of the array; and

identifying the array of bodies from the spectrum, wherein the plurality of spectrally labeled bodies are simultaneously spatially restrained as an array when the first body is restrained.

15. A spectral label identification method comprising:

spatially restraining a first spectrally labeled body at a site in an array of sites in an array of sites;

spatially restraining an array of bodies in the array by an array of discrete binding sites, the binding sites comprising material capable of binding bodies;

dispersing a plurality of spectra from the spatially restrained bodies simultaneously across the sensor surface; and

identifying the array of bodies from the spectrum, wherein the plurality of spectrally labeled bodies are simultaneously spatially restrained as an array when the first body is restrained.

16. A multiplex assay system comprising:

A plurality of bodies released in a fluid, the bodies having labels for generating identifiable spectra;

An energy transmitter coupled to the fluid so as to spatially restrain an array of bodies with a restraining energy beam; and

A sensor oriented to receive the spectrum which is simultaneously dispersed from the plurality of spatially restrained bodies across the sensor surface.