Method and apparatus for performing microassays

• US 6,387,331 B1
• Filed: 01/05/1999
• Issued: 05/14/2002
• 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:
  US09/225,583
• Time in Patent Office: 1,225 Days
• Field of Search: 356/244, 356/246, 422/56, 422/58, 422/82.05, 422/82.09, 422/100, 422/102, 422/104
• US Class Current: 422/82.05
• 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 perforated platen having substantially parallel planar surfaces for manipulating distinct liquid samples, each sample having a volume less than 1 microliter, the platen comprising:

a. an inner layer of hydrophilic material;

b. two outer layers of hydrophobic material coupled to opposite sides of the inner layer in such a manner as to isolate the distinct liquid samples from each other; and

c. a two-dimensional array of through-holes for retaining the distinct liquid samples, the through-holes each having a characteristic cross-sectional dimension of between 100 and 400 micrometers, the through-holes spaced on a two-dimensional grid with a center-to-center spacing between nearest neighbors of twice the characteristic cross-sectional dimension or less, each through-hole traversing the inner layer and the two outer layers in a direction substantially perpendicular to the planar surfaces of the platen,

wherein the platen has a substantially circular shape and includes a central aperture.

2. A system for analyzing a plurality of distinct liquid samples, the system comprising:

a. a platen having two substantially parallel planar surfaces and a two-dimensional array of through-holes, the platen having apertures and walls for retaining the distinct liquid samples in such a manner that the distinct liquid samples may not intermix, the through-holes each having a characteristic cross-sectional dimension of between 100 and 400 micrometers;

b. a source of optical radiation for illuminating a plurality of through-holes of the two-dimensional array; and

c. an optical arrangement including a detector array for separately analyzing light emanating from each of the plurality of illuminated through-holes.

3. A system according to claim 2, wherein the apertures of the plurality of through-holes are disposed on centers of a hexagonally close-packed lattice on the surface of the platen.

4. A system according to claim 2, wherein the apertures of the plurality of through-holes are disposed on centers of a rectangular lattice on the surface of the platen.

5. A system according to claim 2, wherein the through-holes have an aspect ratio of axial to transverse dimension of greater than 1.5.

6. A system according to claim 2, wherein the volume enclosed by the wall of each through-hole and the planes of the planar surfaces of the platen is less than 100 nanoliters.

7. A system according to claim 2, wherein the wall of each through-hole is in part hydrophilic and in part hydrophobic.

8. A system according to claim 2, wherein the wall of each through-hole comprises:

a. a central hydrophilic segment; and

b. two hydrophobic segments such that one hydrophobic segment extends from the central hydrophilic segment to each planar surface of the platen.

9. A system according to claim 2, wherein the platen is a laminate having a central hydrophilic layer and two outer hydrophobic layers disposed on opposite sides of the central hydrophilic layer.

10. A system according to claim 2, wherein the platen is a metal.

11. A system according to claim 2, wherein the platen is a material selected from the group consisting of amorphous materials, ceramic, glass, quartz, and glassy carbon.

12. A system according to claim 2, wherein the platen is a polymeric material.

13. A system according to claim 2, wherein the walls of the plurality of through-holes are coated for allowing emission of light from the through-holes only at the planar surfaces of the platen.

14. A system according to claim 2, further including an advancement mechanism for translating the platen in a direction perpendicular to the optical axis.