Miniaturized cell array methods and apparatus for cell-based screening

• US 6,103,479 A
• Filed: 05/29/1997
• Issued: 08/15/2000
• Est. Priority Date: 05/30/1996
• Status: Expired due to Term

• Current Assignee: Cellomics Incorporated (Thermo Fisher Scientific Incorporated)
• Original Assignee: Cellomics Incorporated (Thermo Fisher Scientific Incorporated)
• Inventors: Taylor, D. Lansing
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Nguyen, Bao-Thuy L.
• Application Number:
  US08/865,341
• Time in Patent Office: 1,174 Days
• Field of Search: 422/57, 422/60, 422/63, 435/7.2, 435/34, 435/287.8, 435/287.9, 436/518, 436/524, 436/527, 427/466, 427/402, 216/2.11
• US Class Current: 506/14
• 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 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00743 : Cells
• CPC Class Codes: C12Q 1/68 : involving nucleic acids
• CPC Class Codes: C12Q 1/6813 : Hybridisation assays
• CPC Class Codes: C12Q 2525/179 : incorporating arbitrary or random nucleotide sequences
• CPC Class Codes: G01N 15/1433 : using image recognition
• CPC Class Codes: G01N 2015/1486 : Counting the particles
• CPC Class Codes: G01N 2015/1497 : Particle shape
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 33/5008 : for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/502 : for testing non-proliferative effects
• CPC Class Codes: G01N 33/5047 : Cells of the immune system
• CPC Class Codes: G01N 33/5058 : Neurological cells

Abstract

The present invention discloses devices and methods of performing high throughput screening of the physiological response of cells to biologically active compounds and methods of combining high-throughput with high-content spatial information at the cellular and subcellular level as well as temporal information about changes in physiological, biochemical and molecular activities. The present invention allows multiple types of cell interactions to be studied simultaneously by combining multicolor luminescence reading, microfluidic delivery, and environmental control of living cells in non-uniform micro-patterned arrays.

Claims

1. A method for producing a cassette for cell screening, comprising:

a) providing a base with a surface

b) preparing a micro-patterned chemical array;

c) modifying the micro-patterned chemical array to produce a modified micro-patterned chemical array comprising multiple different cell binding sites on the surface of the base, wherein the different cell binding sites interact with different cell types, wherein a cell binding site comprises a well;

d) binding cells to the modified micro-patterned chemical array to produce an ordered array of cell types seeded on the wells; and

e) providing a fluid delivery system for delivering a combinatorial of reagents to the ordered array of cell types;

wherein said fluid delivery system comprises a chamber that mates with the base containing the ordered array of cell types, wherein the chamber comprises;

(i) etched domains matching the wells on the surface of the base, and

(ii) microfluidic channels that supply fluid to the etched domains.

2. The method of claim 1, further comprising providing microfluidic channels to remove excess fluid from the etched domains.

3. The method of claim 1, wherein a single microfluidic channel supplies fluid to a single etched domain, to provide separate fluid flow to each etched domain, and wherein the etched domains are larger in diameter than the wells of the ordered array of cell types.

4. The method of claim 1, further comprising providing a plug between the end of the microfluidic channel and the etched domain.

5. The method of claim 1, wherein a microfluidic channel extends from each etched domain to the edge of the chamber.