Combinatorial synthesis on arrays

a technology of arrays and synthesis, applied in the field of combinatorial synthesis on arrays, can solve the problems of inadequate application of "dot-blot" procedures

Inactive Publication Date: 2003-06-19
STRATHMANN MICHAEL PAUL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

"Dot-blot" procedures are therefore inadequate for applications in which many thousand samples must be determined.
This method employs elaborate synthetic schemes, and is generally limited to relatively short nucleic acid sample, e.g., less than 20 bases.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

6.1 Example 1

[0025] The following example demonstrates the synthesis of three different dinucleotides (AC, AG, TT) on an array (at positions 1, 2 & 3, respectively).

[0026] An array of four electrodes is made by insertion of four platinum wires (diameter 0.6 mm) into a glass cylinder (diameter 5 mm.times.height 10 mm). One electrode serves as a counter electrode. The array is inserted into a reaction chamber with a reference electrode (see Teoule, R. et al., U.S. Pat. No. 5,837,859 for details). The three working electrodes are functionalized with a polypyrrole film that contains dimethoxytrityl (DMT) protected hydroxyl groups according to the method taught by Teoule (ibid, Example 4). Briefly, pyrrole and aminoethylpyrrole are copolymerized in the presence of 0.1M LiClO.sub.4. The incorporated amine functional groups are coupled to an activated nucleoside. Secondary alcohol groups and unreacted amine functions are blocked with acetic / anhydride / N-methylimidazole in pyridine.

[0027] To...

example 2

6.2 Example 2

[0035] A dinucleotide array is synthesized as described in Example 1, except whenever the barrier is removed from one position, it is redeposited at the position (or positions) that just underwent coupling. This step is accomplished by replacing the Reducing Solution with the Barrier Solution. Now, in addition to reducing the poly(SNS) barrier at a selected electrode, the SNS monomer is simultaneously oxidized at another electrode to redeposit the poly(SNS) barrier. Following Example 1, just after "C" is deposited at position 1, the array is washed with acetonitrile. The barrier at position 2 is removed by reducing the poly(SNS) film in the Barrier Solution at constant current (-0.2 mA cm.sup.-2) while the barrier is electrodeposited by oxidizing the SNS monomer at electrode 1 at constant current (0.5 mA cm.sup.-2). Now, when the array is exposed to the "G" Coupling Solution, only position 2 is exposed. In this way, if any hydroxyls at position 1 did not couple to "C" d...

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Abstract

The present invention provides methods for synthesizing arrays of polymers. A barrier to a reaction is applied to select features of the array thereby limiting the reaction to the remaining features.

Description

1. RELATED APPLICATION DATA[0001] This application claims priority to U.S. Provisional Patent Application Serial No. 60 / 341,648, filed Dec. 17, 2001.2. FIELD OF THE INVENTION[0002] The present invention is directed to the synthesis and placement of materials at select locations on a substrate. In particular, the present invention is directed to a method for providing separate sequences of chemical monomers at select locations on a substrate.3. BACKGROUND[0003] A variety of methods are currently available for making arrays of biological macromolecules, such as arrays of nucleic acid molecules or proteins. One method for making ordered arrays of DNA on a porous membrane is a "dot blot" approach. In this method, a vacuum manifold transfers a plurality, e.g., 96, aqueous samples of DNA from 3 millimeter diameter wells to a porous membrane. A common variant of this procedure is a "slot-blot" method in which the wells have highly-elongated oval shapes. The DNA is immobilized on the porous...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): B01J19/00G01N35/00
CPCB01J19/0046B01J2219/00443B01J2219/00608B01J2219/00612B01J2219/00617G01N2035/00158B01J2219/00653B01J2219/00659B01J2219/00713B01J2219/00722B01J2219/00626
Inventor STRATHMANN, MICHAEL PAUL
Owner STRATHMANN MICHAEL PAUL
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