Nanogen, Inc.

Gamida for Life B.v.

Other

Enterprise Partners Ii, L.p.

Michael James Heller

Eugene Tu

Ronald George Sosnowski

Carl Frederick Edman

James P O'Connell

Christian Gurtner

Thomas R Jackson

William Frank Butler

Rachel Formosa

Jing Cheng

Lei Wu

Edward L Sheldon

Michael I Nerenberg

Jonathan M Diver

Dan Smolko

Shila Jalali

Glen A Evans

David Willoughby

Paul David Swanson

Xiao Xu

Bradley S Scott

Lorelei P Westin

Ling Wang

Robert David Juncosa

Ed Sheldon

Brenda F Kahl

Elaine M Weidenhammer

Paul G Sutter

Sadik C Esener

Konrad Simeon Feldman

Michael K Krihak

John R Havens

Daniel E Raymond

Leonard Laufer

Nikolas Sulkowski

Charles H Greef

Patrick James Craig

Jeffrey M Cable

Methods are provided for the fabrication of microscale, including micron and sub-micron scale, including nanoscale, devices. Electronic transport of movable component devices is utilized through a fluidic medium to effect transport to a desired target location on a substrate or motherboard. Forces include electrophoretic force, electroosmotic force, electrostatic force and/or dielectrophoretic force. In the preferred embodiment, free field electroosmotic forces are utilized either alone, or in conjunction with, other forces. These forces may be used singly or in combination, as well as in conjunction with yet other forces, such as fluidic forces, mechanical forces or thermal convective forces. Transport may be effected through the use of driving electrodes so as to transport the component device to yet other connection electrodes. In certain embodiments, the component devices may be attached to the target device using a solder reflow step.

Methods for the electronic, homogeneous assembly and fabrication of devices

A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Method for the electronic analysis of a sample oligonucleotide sequence

Self-addressable self-assembling microelectronic systems and devices for molecular biological analysis and diagnostics

A method for electronically stabilizing hybridization of nucleic acids bound at a test site of a microelectronic device is described. First and second negatively charged nucleic acids are provided, the second nucleic acid being bound to the test site. A zwitterionic buffer having a conductance of less than 100 mS/cm is applied to the microelectronic device. A current is applied to the test site to positively bias the test site, such that the first negatively charged nucleic acid is transported to the positively biased test site having the bound the second negatively charged nucleic acid. At the test site, the first and second negatively charged nucleic acids hybridize. The zwitterionic buffer acquires a net positive charge under influence of the current, such that the positively charged zwitterionic buffer stabilizes the hybridization by reducing the repulsion between the first and second negatively charged nucleic acids.

Self-addressable self-assembling microelectronic integrated systems, component devices, mechanisms, methods, and procedures for molecular biological analysis and diagnostics

One embodiment of the present invention relates to a computer implemented method for transaction processing that includes: transacting for a first and a second transactions for at least one of: a purchase; and a cash advance; sending requests for authorization of the first and second transactions; declining, by a primary lender, the requests for authorization; evaluating the declined requests for authorization by a secondary lender; authorizing, by the secondary lender, the declined requests for authorization in the form of authorization approvals; communicating the authorization approvals by the primary lender; posting the transactions to a balance sheet of the secondary lender in the form of amounts due to the primary lender; funding the transactions by the primary lender; summing up one or more debits and one or more credits of the posted transactions of the secondary lender; and settling any amounts due between the primary and secondary lenders.

Systems and methods for transaction processing and balance transfer processing

A method for analyzing nucleic acid obtained from a cell sample on a platform is described. A platform having a cell selector, a nucleic acid selector, and an array of microlocations, wherein at least one microlocation has an associated capture sequence, is provided. The cell selector is contacted with a cell sample, wherein a portion of the cells remain associated with the cell selector. At least a portion of cells associated with the cell selector are lysed to release a nucleic acid sample. The nucleic acid selector is then contacted with the nucleic acid sample, such that a portion of the nucleic acid sample remains associated with the nucleic acid selector. The associated nucleic acid sample is then released from the nucleic acid selector and then is contacted with the array of microlocations, such that at least a portion of the released nucleic acid sample hybridizes with the capture sequence.

We have performed separation of bacterial and cancer cells from peripheral human blood in microfabricated electronic chips by dielectrophoresis. The isolated cells were examined by staining the nuclei with fluorescent dye followed by laser induced fluorescence imaging. We have also released DNA and RNA from the isolated cells electronically and detected specific marker sequences by DNA amplification followed by electronic hybridization to immobilized capture probes. Efforts towards the construction of a 'laboratory-on-a-chip' system are presented which involves the selection of DNA probes, dyes, reagents and prototyping of the fully integrated portable instrument.

Integrated portable biological detection system

A system for performing molecular biological diagnosis, analysis and multistep and multiplex reactions utilizes a selfaddressable, selfassembling microelectronic system for actively carrying out controlled reactions in microscopic formats. The device includes a power supply and waveform generator adapted to supply a DC bias and superimposed AC signal to the system through an interface to the array of microlocations.

Active programmable matrix devices

Method and apparatus for electronic synthesis of molecular structures

This invention pertains to the design, fabrication, and uses of an electronic system which can actively carry out and control multi-step and multiplex reactions in macroscopic or microscopic formats. In particular, these reactions include molecular biological reactions, such as nucleic acid hybridizations, nucleic acid amplification, sample preparation, antibody/antigen reactions, clinical diagnostics, combinatorial chemistry and selection, drug screening, oligonucleotide and nucleic acid synthesis, peptide synthesis, biopolymer synthesis, and catalytic reactions. A key feature of the present invention is the ability to control the localized concentration of two or more reaction-dependant molecules and their reaction environment in order to greatly enhance the rate and specificity of the molecular biological reaction.

Electronic systems and component devices for macroscopic and microscopic molecular biological reaction, analyses, and diagnostics

A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

Methods for electronically-controlled enzymatic reactions

A system for performing molecular biological diagnosis, analysis and multistep and multiplex reactions utilizes a selfaddressable, selfassembling microelectronic system for actively carrying out controlled reactions in microscopic formats. Preferably, a fluidic system flow a sample across an active area of the biochip, increasing diagnostic efficiency. Preferably, the fluidic system includes a flow cell having a window.

Apparatus for active programmable matrix devices

Methods and apparatus are provided for the fabrication of microscale, including micron and sub-micron scale, including nanoscale, devices. Electronic transport of movable component devices is utilized through a fluidic medium to effect transport to a desired target location on a substrate or motherboard. Forces include electrophoretic force, electroosmotic force, electrostatic force and/or dielectrophoretic force. In the preferred embodiment, free field electroosmotic forces are utilized either alone, or in conjunction with, other forces. These forces may be used singly or in combination, as well as in conjunction with yet other forces, such as fluidic forces, mechanical forces or thermal convective forces. Transport may be effected through the use of driving electrodes so as to transport the component device to yet other connection electrodes. In certain embodiments, the component devices may be attached to the target device using a solder reflow step.

The present invention contemplates monitoring the amplification of nucleic acid using chromophore-containing polynucleotides having at least two donor chromophores operatively linked to the polynucleotide by linker arms, such that the chromophores are positioned by linkage along the length of the polynucleotide at a donor-donor transfer distance, and at least one fluorescing acceptor chromophore operatively linked to the polynucleotide by a linker arm, such that the fluorescing acceptor chromophore is positioned by linkage at a donor-acceptor transfer distance from at least one of the donor chromophores, to form a photonic structure for collecting photonic energy and transferring the energy to an acceptor chromophore, and methods using the photonic structures.

Hybridization of polynucleotides conjugated with chromophores and fluorophores to generate donor-to-donor energy transfer system

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Encinitas, CA, United States of America

Michael James Heller