Array cytometry

• US 7,056,746 B2
• Filed: 03/27/2002
• Issued: 06/06/2006
• Est. Priority Date: 04/25/1996
• Status: Expired due to Fees

• Current Assignee: BioArray Solutions Limited (Werfen SA)
• Original Assignee: BioArray Solutions Limited (Werfen SA)
• Inventors: Seul, Michael, Li, Alice Xiang
• Primary Examiner(s): Housel, James
• Assistant Examiner(s): Do, Pensee T.
• Application Number:
  US10/109,980
• Publication Number:
  US 20030022393A1
• Time in Patent Office: 1,532 Days
• Field of Search: 436/164, 436/538, 436/519, 436/806, 436/807, 422/57, 422/60, 422/63, 422/67, 422/68.1, 422/50, 435/4, 435/6, 435/7.1, 435/7.2, 435/7.21, 435/7.23, 435/7.94, 435/7.95, 435/7.92, 435/7.93, 427/2.12, 427/2.13, 427/483, 427/59, 427/77
• US Class Current: 436/164
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• 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 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• 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 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2563/155 : Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2565/501 : being an array of oligonucleotides
• CPC Class Codes: C12Q 2565/607 : being a sensor, e.g. electrode
• CPC Class Codes: C40B 40/00 : Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: G01N 15/14 : Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/149 : specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 30/0005 : Field flow fractionation
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/5438 : Electrodes
• CPC Class Codes: G02B 3/0012 : characterised by the manufacturing method
• CPC Class Codes: G02B 3/0056 : arranged along two different directions in a plane, e.g. honeycomb arrangement of lenses G02B3/0043 takes precedence; miniaturised objectives for electronic devices employing wafer level optics G02B13/0085
• CPC Class Codes: H05H 3/04 : Acceleration by electromagnetic wave pressure
• CPC Class Codes: Y10S 436/806 : Electrical property or magnetic property
• CPC Class Codes: Y10S 436/807 : Apparatus included in process claim, e.g. physical support structures

Abstract

A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations. In addition, the present invention provides a procedure for the creation of material surfaces with desired properties and for the fabrication of surface-mounted optical components. This invention is also for a method and apparatus to direct the lateral motion and induce the assembly into planar arrays of cells on semiconductor surfaces in response to temporally and spatially varying electric fields and to projected patterns of illumination.

Claims

1. A method of determining an interaction between different cell types, the method involving the assembly of cells comprising the following steps:

a) providing a first electrode positioned in a first plane and a second electrode positioned in a second plane different from the first plane;

b) providing a plurality of cells comprising at least two cell types suspended in an electrolyte solution, the cells and the electrolyte solution being located between the first and the second electrode, wherein the second electrode is either;

(i) a light-sensitive electrode, such that when an AC electric field is generated and the second electrode is illuminated with a predetermined light pattern, a planar assembly of cells forms in a designated area of the second electrode, said designated area being defined by the pattern of illumination, or

(ii) an electrode having a surface or an interior, the surface or interior having been modified to produce spatial modulation in properties of the second electrode that affects the local distribution of an AC electric field, such that a planar assembly of cells forms in a designated area of the second electrode when an AC electric field is generated, said designated area being defined by the spatial modulation in the properties of the second electrode;

c) forming a planar assembly of cells in a designated area of the second electrode by applying an AC electric field and, if the second electrode comprises a light sensitive electrode, by illuminating the second electrode with a predetermined light pattern, wherein the cells in the assembly comprise different types of cells, with the proximity of one cell type to another allowing an interaction between the different cell types to occur; and

d) detecting the interaction between different cell types wherein the interaction between the different cell types results in a morphological change of at least one cell type;

change in a surface marker of at least one cell type;

change in a gene expression of at least one cell type;

a change in the membrane permeability of at least one cell type;

or adhesion of the cells to form a cluster.

2. The method of claim 1, wherein step (d) comprises detecting the interaction between the cell types by ascertaining the formation of cell clusters.

3. The method of claim 1, wherein the assembly of the mixed cell types is prepared by the following steps:

forming an assembly of a first cell type in a designated area on the second electrode;

introducing cells of a second type to the electrolyte solution and moving said cells to the designated area on the second electrode in which the first cell type is located, thereby allowing the interaction between the two cell types to occur.

4. The method of claim 1, wherein the assembly of the mixed cell types is prepared by the following steps:

forming an assembly of a first cell type in a designated area on the second electrode;

forming an assembly of a second cell type in a second designated area on the second electrode; and

combining the assembly of the first and second cell type to allow the interaction between the different cell types to occur.