Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof

• US 6,716,629 B2
• Filed: 10/10/2001
• Issued: 04/06/2004
• Est. Priority Date: 10/10/2000
• Status: Expired due to Term

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: BioTrove, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Brenan, Colin, Linton, John, Ozbal, Can, Kanigan, Tanya S., Hess, Robert A.
• Primary Examiner(s): Ponnaluri, Padmashri
• Assistant Examiner(s): TRAN, MY CHAU T
• Application Number:
  US09/975,496
• Publication Number:
  US 20020094533A1
• Time in Patent Office: 909 Days
• Field of Search: 435/410, 435/420, 435/286.1, 435/288.2, 435/283.1
• US Class Current: 435/420
• 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 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00319 the blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00587 High throughput 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 2219/00673 : Slice arrays
• CPC Class Codes: B01L 13/02 : for receptacle or instruments
• CPC Class Codes: B01L 2200/0657 : Pipetting powder
• CPC Class Codes: B01L 2300/0845 : Filaments, strings, fibres, i.e. not hollow
• CPC Class Codes: B01L 3/0244 : using pins
• CPC Class Codes: B01L 3/0262 : using touch-off at substrate or container
• CPC Class Codes: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50255 : Multi-well filtration
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2030/8417 : the store moving as a whole, e.g. moving wire
• CPC Class Codes: G01N 30/466 : with separation columns in parallel
• CPC Class Codes: G01N 30/6091 : Cartridges
• CPC Class Codes: G01N 30/6095 : Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: G01N 30/82 : Automatic means therefor
• CPC Class Codes: Y10T 29/301 : Method
• CPC Class Codes: Y10T 29/49938 : Radially expanding part in cavity, aperture, or hollow body

Abstract

The invention features methods of making devices, or “platens”, having a high-density array of through-holes, as well as methods of cleaning and refurbishing the surfaces of the platens. The invention further features methods of making high-density arrays of chemical, biochemical, and biological compounds, having many advantages over conventional, lower-density arrays. The invention includes methods by which many physical, chemical or biological transformations can be implemented in serial or in parallel within each addressable through-hole of the devices. Additionally, the invention includes methods of analyzing the contents of the array, including assaying of physical properties of the samples.

Claims

1. A method of maintaining the viability of a cell of an aerobic organism in a platen having a plurality of through-holes, the method comprising:

a) providing a cell of an aerobic organism in an aqueous medium;

b) loading the cell of the aerobic organism in the aqueous medium into at least some of the through-holes of the platen, wherein the aqueous medium is held in the through-holes by surface tension, and

c) submerging the platen into a gas permeable liquid, wherein the gas permeable liquid facilitates oxygen transport to the cell and wherein the gas permeable liquid is immiscible with the aqueous medium, thereby maintaining the viability of the cell.

2. The method of claim 1, further comprising assaying one or more physical properties of the cell of the aerobic organism.

3. The method of claim 1, wherein the gas permeable liquid is a fluorocarbon or a silicone polymer.

4. The method of claim 1, wherein the cell is attached to a wall of a through-hole.

5. The method of claim 1, wherein the aqueous media is held in the through-holes by capillary action.

6. The method of claim 1, wherein the cell is attached to or contained within a porous medium inside the through-hole.

7. The method of claim 1, wherein the aqueous medium is a cell culture medium.

8. The method of claim 1, wherein the cell is an embryo.

9. The method of claim 1, wherein the cell is a CaCo-2 cell.

10. The method of claim 3, wherein the gas permeable liquid is perfluorodecalin or perfluorooctylbromide.