Method and analytical system for rapid screening of combinatorial libraries

• US 6,558,624 B1
• Filed: 07/25/2000
• Issued: 05/06/2003
• Est. Priority Date: 07/25/2000
• Status: Expired due to Fees

• Current Assignee: General Electric Company
• Original Assignee: General Electric Company
• Inventors: Potyrailo, Radislav Alexandrovich, Lemmon, John Patrick
• Primary Examiner(s): Tung, T.
• Assistant Examiner(s): GAKH, YELENA G
• Application Number:
  US09/626,261
• Time in Patent Office: 1,015 Days
• Field of Search: 422/55, 422/63, 422/67, 422/69, 422/81, 422/82.05, 422/82.09, 436/173
• US Class Current: 422/69
• 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 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00587 High throughput processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00745 Inorganic compounds
• CPC Class Codes: B01J 2219/00747 Catalysts
• CPC Class Codes: C40B 30/08 by measuring catalytic activity
• CPC Class Codes: C40B 40/18 Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/64 : Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/65 : Raman scattering
• CPC Class Codes: Y10T 436/24 : Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Rapid, sensitive detection of analytes in small-scale samples is achieved with an analytical method in which samples are adsorbed on a sorbent material and probed spectroscopically. The method is suitable for monitoring the progress of reactions in combinatorial screening experiments.

Claims

1. An analytical system for high-throughput analysis of polycarbonate synthesis, comprising:

a plurality of analytical samples each comprising at least one analyte, wherein said analyte comprises at least one reagent, intermediate, or product of a polycarbonate synthesis reaction;

an analytical matrix comprising a plurality of spatially differentiated analytical sites, each site comprising at least one sorbent material, wherein said sorbent is selected from the group consisting of activated carbon, silica, alumina, diatomaceous earth, zeolite molecular sieves, carbon molecular sieves, graphitized carbon-based adsorbents, metallic particles, semiconductor particles, dielectric particles, polymeric sorbents, and mixtures thereof;

a sample loader capable of handling a plurality of samples for delivering a known amount of each analytical sample onto at least one analytical site;

a light source for irradiating the at least one analytical site on the matrix with a first wavelength range;

a detector for detecting a Raman spectroscopic characteristic of the analyte directly from the at least one analytical site on the matrix with a second wavelength range, wherein said Raman spectroscopic characteristic is specific to the analyte and not the sorbent; and

a computer for determining a concentration of the analyte at the at least one analytical site based on the spectroscopic characteristic.

2. The system of claim 1, wherein the computer is placed in communication with at least one item selected from the group consisting of the sample loader, the light source, and the detector such that the computer responsively controls said at least one item.

3. The system of claim 1, further comprising a heater in thermal communication with the at least one analytical site.

4. The system of claim 1, further comprising an evaporator in communication with the analytical matrix to subject the at least one analytical site to conditions of elevated temperature, reduced pressure, or both.

5. The system of claim 1, wherein said polymeric sorbent comprises a natural rubber or polymers formed at least in part from the polymerization of dienes, polyethylenes, polypropylenes, elastomeric polyesters, alkenyl aromatic resins, silicones, silicone polyimides, polyurethanes, and/or polyphenylene ethers.

6. The system of claim 1, wherein said sorbent comprises material selected from the group consisting of:

a poly(ethylene oxide) having a weight average molecular weight greater than 1,000,000;

a poly(2,6-diphenyl-p-phenylene ether);

a styrene divinyl benzene polymer;

an ethyl vinyl benzene polymer;

a divinyl benzene polymer;

a vinyl pyrrolidone polymer;

a vinyl pyridine polymer;

a cross-linked polystryene polymer;

a polyacrylonitrile polymer;

a cross-linked acrylic ester, or a diatomite-based sorbent.

7. The system of claim 1, wherein the sorbent comprises a polystyrene resin, a functionalized polystyrene resin, or a silica gel, wherein said silica gel comprises a mesh of greater than 200.

8. The system of claim 1, wherein the sorbent comprises at least one material selected from the group consisting of a porous polymer resin derived with dicyanoallyl, a porous divinylbenzene-ethylstyrene copolymer resin, a porous phenyl methyl derivatized polymer resin, a porous poly(cyanopropylphenyl siloxane) resin, a porous bis phenyl toluidine derivatized polymer resin, a porous ethylene succinate methyl silicone polymer resin, a porous phenyl-derivatized polystyrene resin, a silica gel derivatized with amine groups, and a phenyl-derivatized silica gel.

9. The system of claim 1, wherein the sorbents comprise particles that range in size from 1 nanometer to 1 millimeter.

10. The system of claim 1, wherein said analyte comprises a dialkyldialoxysilane or a tetralkoxysilane.

11. The system of claim 10, wherein said analyte comprises dimethyldimethoxysilane or tetramethoxysilane.

12. The system of claim 1, wherein said analyte comprises a bisphenol.

13. The system of claim 1, wherein said analyte comprises polycarbonate.

14. The system of claim 1, wherein said matrix comprises a catalyst of the polycarbonate synthesis reaction.

15. The system of claim 1, wherein said analyte comprises a volume ranging from 1 ml to 1 picoliter.