Array cytometry

• US 6,958,245 B2
• Filed: 11/28/2001
• Issued: 10/25/2005
• 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: Li, Alice X., Seul, Michael
• Primary Examiner(s): Chin, Christopher L.
• Assistant Examiner(s): Do, Pensee T.
• Application Number:
  US09/995,894
• Publication Number:
  US 20020123078A1
• Time in Patent Office: 1,427 Days
• Field of Search: 436/534, 436/518, 436/524, 436/526, 436/528, 436/531, 436/535, 436/63, 436/164, 436/165, 436/166, 436/169, 436/172, 436/175, 435/6, 435/90, 435/91.2, 435/91.5, 435/91.51, 435/173.1, 435/174, 435/176, 435/177, 435/283.1, 435/285, 204/403, 204414-416, 204/417, 422/50, 422/54, 422/55
• US Class Current: 436/534
• 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 2219/00713 Electrochemical synthesis
• 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 2300/0877 Flow chambers
• 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 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• 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: 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 15/1433 : using image recognition
• CPC Class Codes: G01N 15/149 : specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• 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: Y10T 436/25125 : Digestion or removing interfering materials

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 elektrokinetic 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 manipulating cells suspended adjacent to a surface of an electrode in a polarizable liquid medium, the method comprising the following steps:

providing a plurality of cells suspended adjacent to a surface of a light-sensitive electrode in a polarizable liquid medium;

generating an electric field; and

illuminating the electrode with a predetermined light pattern to control the movement of and to manipulate the cells in accordance with the predetermined light pattern and the properties of the electrode.

2. The method or claim 1, further comprising an additional electrode, the additional electrode and the light-sensitive electrode being substantially planar and aligned to one another and separated by a gap, wherein the additional electrode comprises an optically transparent electrode and wherein the suspended cells reside in the gap.

3. The method of claim 1 wherein the electric filed is generated by applying an AC voltage.

4. The method of claim 3 wherein the AC voltage is between 1 and 10V (peak-to-peak), and between 500 Hz and 10 kHz.

5. The method of claim 3 further including applying DC potential between the light-sensitive electrode and the additional electrode.

6. The method of claim 1, wherein the light-sensitive electrode has a surface or an interior, the surface or interior having been modified to produce spatial modulations in properties of the electrode, said properties affecting the local distribution of the electric field.

7. The method of claim 6 wherein the surface or interior have been modified by spatially modulated oxide growth, surface chemical patterning or surface profiling.

8. The method of claim 1, further comprising the step of spatially or temporally varying the light pattern to affect the manipulation and movement of cells.

9. The method of claim 1, further comprising the step of varying the frequency or the voltage of the electric field to affect the manipulation and movement of cells.

10. The method of claim 1, in which the plurality of cells comprises more than one type of cells, the method further comprising the step of fractionating one type of cells from another.

11. The method of claim 1, further comprising the step of adjusting the electric field and the predetermined light pattern to maintain the cells in a particular configuration following movement and manipulation.

12. The method of claim 10, further comprising immobilizing the cells by chemical or physical means.

13. The method of claim 11, in which the cells are immobilized on the electrode by chemically linking a cells or physically confining the cells.

14. The method of claim 1 wherein the polarizable liquid medium is a mannitol solution.