Leland Stanford Junior University

Protogene Laboratories, Inc.

Other

Metrigen, Inc.

Thomas M Brennan

Albrecht W Frauendorf

Herbert L Heyneker

Mark S Berninger

John H Butler

Francois Chatelain

A polymer synthesis apparatus () for building a polymer chain including a head assembly () having an array of nozzles () with each nozzle coupled to a reservoir () of liquid reagent (), and a base assembly () having an array of reaction wells (). A transport mechanism () aligns the reaction wells () and selected nozzles () for deposition of the liquid reagent () into selected reaction wells (). A sliding seal () is positioned between the head assembly () and the base assembly () to form a common chamber () enclosing both the reaction well () and the nozzles () therein. A gas inlet () into the common chamber (), upstream from the nozzles (), and a gas outlet () out of the common chamber (), downstream from the nozzles (), sweeps the common chamber () of toxic fumes emitted by the reagents. Each reaction well () includes an orifice () extending into the well () which is of a size and dimension to form a capillary liquid seal to retain the reagent solution () in the well () for polymer chain growth therein. A pressure regulating device () is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well () and a second gas pressure exerted on an exit () of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution () is expelled from the well () through the orifice (). A method of synthesis of a polymer chain in a synthesis apparatus () is also included.

Apparatus and method for polymer synthesis using arrays

The invention concerns a polymer synthesis apparatus () for building a polymer chain including a head assembly () having an array of nozzles () with each nozzle coupled to a reservoir () of liquid reagent (), and a base assembly () having an array of reaction wells (). A transport mechanism () aligns the reaction wells () and selected nozzles () for deposition of the liquid reagent () into selected reaction wells (). A sliding seal () is positioned between the head assembly () and the base assembly () to form a common chamber () enclosing both the reaction well () and the nozzles () therein.

The invention provides apparatus and methods for determining the nucleotide sequence of target nucleic acids using hybridization to arrays of oligonucleotides. The invention further provides apparatus and methods for identifying the amino acid sequence of peptides that bind to biologically active macromolecules, by specifically binding biologically active macromolecules to arrays of peptides or peptide mimetics.

Method and apparatus for conducting an array of chemical reactions on a support surface

The present invention relates to a method and apparatus for performing a large number of reactions using array assembly. In particular, the present invention features a method and apparatus for performing a large number of chemical and biological reactions by bringing two arrays into close apposition and allowing reactants on the surfaces of two arrays to come into contact. The present invention is exemplified by performing a large number of polynucleotide amplification reactions using array assembly. In addition, the present invention features a method and apparatus for coupling the amplification of polynucleotides and the detection of sequence variations, expression levels, and functions thereof.

Method and apparatus for performing large numbers of reactions using array assembly with releasable primers

The present invention relates to methods for fabricating solid supports. More specifically, the present invention features methods for fabricating solid supports for in situ synthesis and for carrying out large numbers of reactions. The present invention also features solid supports with in situ synthesized long polynucleotides.

Method and apparatus for in situ synthesis on a solid support

A method for reducing evaporation of a liquid reagent solution during solid phase, micro-scale chemical synthesis of a molecule comprising sub-units on an open environment solid support surface. The method includes the steps of providing an open solid support surface including at least one binding site which is functionalized with a reactive chemical moiety; and depositing a substantially controlled and minute volume of liquid reagent solution onto the support surface, and in contact with the binding site. The reagent solution includes reactants contained in at least one relatively high boiling point solvent, in contrast to standard organic solvents for such reagents. Application of a high boiling point solvent substantially reduces evaporation of the reagent solution in the open environment during synthesis on the solid support while enabling the maintenance of a substantially high reaction yield.

Method and composition for chemical synthesis on an open environment support surface using high boiling point organic solvents to control evaporation

The invention provides apparatus and methods for making arrays of functionalized binding sites on a support surface. The invention further provides apparatus and methods for sequencing oligonucleotides and for identifying the amino acid sequence of peptides that bind to biologically active macromolecules, by specifically binding biologically active macromolecules to arrays of peptides or peptide mimetics.

Method and composition for chemical synthesis using high boiling point organic solvents to control evaporation

A chemical synthesis apparatus (20) for building chemical compounds includes a head assembly (21) having an array of nozzles (22) with each nozzle or plurality of nozzles coupled to a reservoir (23) of liquid reagent (24), and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) in a longitudinal X-direction for deposition of liquid reagent (24) into selected reaction wells (26). A plurality of independently controllable sliders (100) move nozzle columns (41) in a lateral Y-direction for deposition of liquid reagent (24) into selected reaction wells (26). A first sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A plurality of second sliding seals (120) is positioned between head assembly (21) and sliders (100). A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet (71) out of the common chamber (31), downstream from nozzles (22), sweeps the common chamber (31) of fumes emitted by the reagents.

Apparatus for diverse chemical synthesis using two-dimensional array

Method and apparatus for conducting an array of chemical reactions on a

A polymer synthesis apparatus (20) for building a polymer chain including a head assembly (21) having an array of nozzles (22) with each nozzle coupled to a reservoir (23) of liquid reagent (24), and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) for deposition of the liquid reagent (24) into selected reaction wells (26). A sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet: (71) out of the common chamber (31), downstream from the nozzles (22), sweeps the common chamber (31) of toxic fumes emitted by the reagents. Each reaction well (26) includes an orifice (74) extending into the well (26) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution (76) in the well (26) for polymer chain growth therein. A pressure regulating device (82) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well (26) and a second gas pressure exerted on an exit (80) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution (76) is expelled from the well (26) through the orifice (74). A method of synthesis of a polymer chain in a synthesis apparatus (20) is also included.

Method for polymer synthesis using arrays

A method of synthesis for building a polymer chain, oligonucleotides in particular, by sequentially adding monomer units to at least one solid support for growing and immobilizing a polymer chain thereon in a liquid reagent solution. The method includes the step of: A) depositing a liquid reagent in a reaction well (26) in contact with at least one solid support and at least one monomer unit of the polymer chain affixed to the solid support. The well (26) includes at least one orifice (74) extending into the well (26), and is of a size and dimension to form a capillary liquid seal to retain the reagent solution in the well (26) to enable polymer chain growth on the solid support. The method further includes the step of B) expelling the reagent solution from the well (26), while retaining the polymer chain therein. This is accomplished by applying a first gas pressure to the reaction well such that a pressure differential between the first gas pressure and a second gas pressure exerted on an exit (80) of the orifice (74) exceeds a predetermined amount sufficient to overcome the capillary liquid seal and expel the reagent solution from the well (26) through the orifice exit (80).

Method for polymer synthesis in a reaction well

A method for vertically aligning the color plate cylinders of a press, which prints a two-color image on paper, in order to eliminate the vertical misalignment of the colors in the image printed. The method requires the use of a cylinder positioner that is releasably mounted on the press and involves operating the press to initially print the image, detaching the cylinder positioner from the press, adjusting the position of a positioner stop on the cylinder positioner based on the amount of misalignment in the printed image, reattaching the cylinder positioner, decoupling a color plate cylinder from normal operation, rotating the press's blanket cylinder until it impacts the positioner stop on the cylinder positioner, recoupling the color plate cylinder and then operating the press to correctly print the image.

Cylinder positioning apparatus for offset presses and duplicators

A cylinder positioner apparatus for offset presses and duplicators which provides for rapid and efficient alignment of plate cylinders of single-color and multicolor presses. A detachable adjustment member is placed on printed images and a micrometer adjustment is used to accurately set the instrument for removing vertical misalignment or to change the vertical positioning of the plate cylinders of the press. The positioner can be used on two-color presses, single stations of multi-station color presses and single-color presses.

Cylinder positioning apparatus for offset presses and duplications

A polymer synthesis apparatus (20) for building a polymer chain including a head assembly (21) having an array of nozzles (22) with each nozzle coupled to a reservoir (23) of liquid reagent (24), and a base assembly (25) having an array of reaction wells (26). A transport mechanism (27) aligns the reaction wells (26) and selected nozzles (22) for deposition of the liquid reagent (24) into selected reaction wells (26). A sliding seal (30) is positioned between the head assembly (21) and the base assembly (25) to form a common chamber (31) enclosing both the reaction well (26) and the nozzles (22) therein. A gas inlet (70) into the common chamber (31), upstream from the nozzles (22), and a gas outlet (71) out of the common chamber (31), downstream from the nozzles (22), sweeps the common chamber (31) of toxic fumes emitted by the reagents. Each reaction well ( 26) includes an orifice (74) extending into the well (26) which is of a size and dimension to form a capillary liquid seal to retain the reagent solution (76) in the well (26) for polymer chain growth therein. A pressure regulating device (82 ) is provided for controlling a pressure differential, between a first gas pressure exerted on the reaction well (26) and a second gas pressure exerted on an exit (80) of the orifice, such that upon the pressure differential exceeding a predetermined amount, the reagent solution (76) is expelled from the well (26) through the orifice (74). A method of synthesis of a polymer chain in a synthesis apparatus (20) is also included.

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San Francisco, CA, United States of America

Thomas M Brennan