Method and apparatus for performing microassays

• US 20040171166A1
• Filed: 03/09/2004
• Published: 09/02/2004
• Est. Priority Date: 01/12/1998
• Status: Abandoned Application

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Hunter, Ian W.
• Application Number:
  US10/796,856
• Publication Number:
  US 20040171166A1
• Time in Patent Office: Days
• US Class Current: 436/164
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/30351 using hydrophilic/hydrophobic surfaces
• 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 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• 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 2219/00533 essentially rectangular
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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: C12Q 1/34 involving hydrolase
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 21/75 Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73
• CPC Class Codes: G01N 35/00069 : whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 : with sample on test slide
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

A method and apparatus for analyzing a plurality of substances. A platen is provided having two substantially parallel planar surfaces and a plurality of through-holes. An optical arrangement analyzes light emanating from the through-holes. The through-holes may be individually addressable, and may have volumes less than 100 nanoliters. Samples may be accurately dispensed, diluted and mixed in accordance with embodiments of the invention, and may be plated onto walls of the through-holes, and then subsequently resuspended prior to characterization, or, alternatively, retained in the through-holes by surface tension.

Claims

1. A method for analyzing specified properties of a set of substances, the method comprising:

a. providing a platen having two substantially parallel planar surfaces, an inner layer of hydrophilic material and two outer layers of hydrophobic material coupled to opposite sides of the inner layer, and a two-dimensional array of addressable through-holes having an areal density of at least 1.6 through-holes per square millimeter,

b. retaining a set of distinct substances in respective through-holes of the array in such a manner that a first through-hole contains a first substance distinct from a second substance contained in an adjacent through-hole to the first through-hole;

c. adding a liquid into at least one of the through-holes containing a substance for permitting a reaction between the liquid and the substance; and

d. characterizing contents of distinct through-holes in terms of the specified properties.

2. A method according to claim 1, wherein the set of different substances includes a reagent.

3. A method according to claim 1, wherein the set of different substances comprises a library of at least 1000 substances.

4. A method according to claim 1, wherein the set of different substances include optical taggants.

5. A method according to claim 1, wherein the step of retaining the set of distinct substances further includes:

loading the set of distinct substances in one of liquid solution and suspension; and

forming coatings of the distinct substances so as to retain the distinct substances on walls of the through-holes.

6. A method according to claim 1, wherein the step of adding a liquid includes adding a liquid substantially uniformly to the through-holes of the array.

7. A method according to claim 6, wherein the step of adding a liquid includes resuspending the distinct substances in liquid by means of wetting.

8. A method according to claim 1, wherein the step of characterizing contents of distinct through-holes includes characterizing by optical methods.

9. A method according to claim 8, wherein the step of characterizing contents of distinct through-holes includes characterizing by fluorometric methods.

10. A platen for retaining biological samples, the platen comprising:

a. an inner layer of hydrophilic material and two outer layers of hydrophobic material coupled to opposite sides of the inner layer;

b. a two-dimensional array of addressable through-holes having an areal density of at least 1.6 through-holes per square millimeter,

c. a set of distinct substances in respective through-holes of the array.

11. A platen according to claim 10, wherein distinct substances of the set of distinct substances are coated on walls of the through-holes.

12. A platen according to claim 10, wherein distinct substances of the the set of distinct substances are retained within through-holes of the platen by surface tension.