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

• US 9,314,764 B2
• Filed: 07/21/2011
• Issued: 04/19/2016
• Est. Priority Date: 10/10/2000
• Status: Expired due to Fees

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Hess, Robert, Linton, John, Kanigan, Tanya S., Brenan, Colin, Ozbal, Can
• Primary Examiner(s): Gross, Christopher M
• Application Number:
  US13/188,337
• Publication Number:
  US 20120021951A1
• Time in Patent Office: 1,734 Days
• Field of Search: None
• US Class Current: 1/1
• 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: B01L 3/50857 : using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: C12M 23/12 : Well or multiwell plates C12M25/04 takes precedence
• 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

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 loading a platen having opposing surfaces and a plurality of through-holes extending between the surfaces, the method comprising:

a) dipping the platen into a first liquid comprising a sample to be loaded into the through-holes, thereby loading at least some of the through-holes with the sample and leaving a portion of the first liquid on at least one surface of the opposing surfaces; and

b) retaining at least some of the loaded sample within at least one of the through-holes while contacting the platen with a second liquid that has an affinity for the at least one surface but is immiscible with the first liquid, thereby cleaning the portion of the first liquid from the at least one surface.

3. The method of claim 1, wherein the volume of the solution in at least some of the thorough-holes is less than about 25 nl.

4. The method of claim 1, wherein the first liquid loaded into at least some of the through-holes comprises a biological compound.

5. The method of claim 1, wherein the first liquid loaded into at least some of the through-holes comprises a nucleic acid molecule.

6. The method of claim 1, wherein the first liquid loaded into at least some of the through-holes comprises a fluorophore.

7. The method of claim 1, wherein the first liquid loaded into at least some of the through-holes comprises a fetal serum.

8. The method of claim 1, further comprising performing a biological assay or biological alteration on the first liquid in at least some of the through-holes.

9. The method of claim 1, further comprising performing a PCR alteration on the first liquid in at least some of the through-holes.

10. The method of claim 1, further comprising performing a real time PCR alteration on the first liquid in at least some of the through-holes.

11. The method of claim 1, further comprising performing a gene expression alteration on the first liquid in at least some of the through-holes.

12. The method of claim 1, further comprising performing a biological assay or detecting a cell alteration in the first liquid in at least some of the through-holes.

13. The method of claim 1, further comprising detecting a PCR alteration on the first liquid in at least some of the through-holes.

14. The method of claim 1, further comprising detecting a real time PCR alteration on the first liquid in at least some of the through-holes.

15. The method of claim 1, further comprising detecting a gene expression alteration on the first liquid in at least some of the through-holes.

2. A method of loading a platen having opposing surfaces and a plurality of through-holes extending between the surfaces, the method comprising:

(a) providing a sample mixture to be loaded into the through-holes;

(b) dipping the platen into the mixture, thereby loading at least some of the through-holes with the sample and leaving a portion of the mixture on at least one surface of the opposing surfaces; and

(c) retaining at least some of the loaded sample in (b) within at least one of the through-holes while passing the platen through a fluid that has an affinity for the at least one surface but that is immiscible with the mixture, thereby wiping the portion of the mixture from the at least one surface.

18. The method of claim 2, further comprising detecting a biological alteration on the sample fluid in at least some of the through-holes.

16. A method of loading a platen having opposing surfaces and a plurality of through-holes extending between the surfaces, the method comprising:

a) providing a liquid comprising a sample to be loaded into the through-holes;

b) dipping the platen into the liquid, thereby loading at least some of the through-holes with the sample and leaving a portion of the liquid on at least one surface of the platen; and

c) subsequent to dipping the platen, passing the platen through a wiping fluid to wipe at least some of the portion of the liquid from the at least one surface of the opposing surfaces.

17. The method of claim 16, further comprising detecting a biological alteration on the sample fluid in at least some of the through-holes.