Method for performing microassays

• US 6,743,633 B1
• Filed: 11/10/2000
• Issued: 06/01/2004
• Est. Priority Date: 01/12/1998
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Hunter, Ian W.
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US09/710,082
• Time in Patent Office: 1,299 Days
• Field of Search: 422/56, 422/58, 422/100, 422/82.05, 422/102, 422/82.09, 422/104, 436/164, 436/166, 436/171-172, 436/43, 436/46, 436/183, 356/244, 356/246
• US Class Current: 436/46
• 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 system and method for analyzing a plurality of liquid samples. The system has a platen having two substantially parallel planar surfaces and a plurality of through-holes dimensioned so as to maintain a liquid sample in each through-hole by means of surface tension. A source of optical radiation illuminates the through-holes, and an optical arrangement analyzes the light emanating from the through-holes. The through-holes may be individually addressable, and may have volumes less than 100 nanoliters. Samples may be drawn from a planar surface by capillary action and may be accurately dispensed, diluted and mixed in accordance with embodiments of the invention.

Claims

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

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

b. loading a first sample into a first set of through-holes of the two-dimensional array, the first sample being a liquid;

c. retaining the first sample in the first set of through-holes by surface tension;

d. adding a second sample into a specified subset of through-holes, the specified subset of through-holes having at least one adjacent through-hole containing a sample other than the second sample, the specified subset of through-holes further coinciding with one of the first set of at least one of the though-holes thereby permitting a reaction between the first sample and the second sample, wherein the layers of hydrophobic material prevent capillary outmigration of the samples; and

e. characterizing the reaction in the specified subset of through-holes in terms of the specified properties.

2. A method according to claim 1, wherein each through-hole is dimensioned so as to maintain a liquid sample therein by means of surface tension.

3. A method according to claim 1, wherein each through-hole has a volume less than 100 nanoliters.

4. A method according to claim 1, wherein the plurality of addressable through-holes has a density in excess of 10⁸ per square meter.

5. A method according to claim 1, wherein the first sample in liquid form includes at least one of a target in solution and a target in suspension.

6. A method according to claim 1, wherein at least one of a target in solution and a target in suspension includes a biological material.

7. A method according to claim 1, wherein the step of loading a first sample includes drawing the sample from a planar surface by capillary action.

8. A method according to claim 1, further including maintaining a humid atmosphere for preventing evaporation of the first sample.

9. A method according to claim 1, further including coating the liquid sample with a monolayer for preventing evaporation of the first sample.

10. A method according to claim 1, wherein the step of characterizing the reaction in the through-hole in terms of the specified properties includes optically analyzing the sample.

11. A method according to claim 1, the method further comprising:

f. illuminating a set of more than one of the plurality of through-holes with opitical radiation; and

g. seperately analyzing the optical radiation emanating from each through-hole of the set of more through-holes than one using an optical arrangement including a detector array.

12. A method in accordance with claim 11, wherein the step of analyzing includes spectrally characterizing the optical radiation emanating from each through-hole.