Incyte Pharmaceuticals, Inc.

California Institute of Technology

Thomas P Theriault

Ronald C Gamble

John D Baldeschwieler

Scott C Winder

A method and apparatus are provided for preparing a substrate upon which is located microdrop-sized loci at which chemical compounds are synthesized or diagnostic tests are conducted. The loci are formed by applying microdrops from a dispenser from which a microdrop is pulse fed onto the surface of the substrate.

Method and substrate for performing multiple sequential reactions on a

Devices and methods are provided for precise reduction of arrays of microspots. A pulse jetting device is employed having a capillary of micron dimensions, with a portion of the capillary proximal to the jetting orifice circumferentially surrounded by a piezoelectric transducer. By appropriate design of the capillary, orifice and piezoelectric transducer, droplets can be formed on a surface, separated by as little as 80 microns center-to-center, and having at least about a 15 micron spacing at the border. The subject substrate arrays can be used for providing miniaturized arrays of reagents, such as nucleic acids, for detecting the presence of homologous sequences in a sample.

Jet droplet device

An apparatus for the automated synthesis of molecular arrays. A jetting device is employed along with a reaction chamber to dispense reagents used in the synthesis onto the substrate. A positioning system moves the substrate from the jet to the reaction chamber. A controller controls the movement of the substrate and the application of the reagents so that the synthesis is carried out according to a pre-determined procedure. The apparatus will synthesize nucleotides in an array of micron-size spots according to a pattern selected by the operator immediately prior to synthesis.

Apparatus for the chemical synthesis of molecular arrays

Devices and methods are provided for precise production of arrays of microspots. A pulse jetting device is employed having a capillary of micron dimensions, with a portion of the capillary proximal to the jetting orifice circumferentially surrounded by a piezoelectric transducer. By appropriate design of the capillary, orifice and piezoelectric transducer, droplets can be formed on a surface, separated by as little as 80 microns center-to-center, and having at least about a 15 micron spacing at the border. The subject substrate arrays can be used for providing miniaturized arrays of reagents, such as nucleic acids, for detecting the presence of homologous sequences in a sample.

Solvent vehicles and methods of their use in the pulse jet delivery of reagents in automated oligonucleotide synthesis by the solid-phase phosphoramidite method are provided. For pulse jet delivery of the activated monomer, acetonitrile in combination with at least one stabilizer co-solvent is employed as the solvent vehicle, where the stabilizer co-solvent is an inert, organic solvent having a boiling point of at least 100.degree. C. For pulse jet delivery of the detritylation reagent, a mono- or disubstituted methane is employed as the solvent vehicle, where substituents have a molecular weight greater than 36 daltons. Use of the solvent vehicles according to the subject invention provides for reduced reagent precipitation in the pulse jet tubes and improved results.

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Manhattan Beach, CA, United States of America

Thomas P Theriault