Nanogen, Inc.

Genoptix, Inc.

Gamida for Life B.v.

Siemens Aktiengesellschaft

James P O'Connell

Jing Cheng

Michael James Heller

Lei Wu

Eugene Tu

Ronald George Sosnowski

Mark Wang

Edward L Sheldon

William Frank Butler

Kristie L Lykstad

Jonathan M Diver

Dan Smolko

Shila Jalali

David Willoughby

Thomas R Jackson

Michael I Nerenberg

Ray R Radtkey

David Canter

Ling Wang

Robert David Juncosa

Ed Sheldon

Klaus Abraham-Fuchs

Norbert Windhab

Arne Hengerer

Kieran T Gallahue

Greg Gosch

Bill F Butler

Thomas J Macke

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

This application includes methods for detecting single nucleotide polymorphisms (SNPs) in a sample using an electronically addressable microchip having a plurality of test sites. A sample nucleic acid is electronically biased, concentrated at, and immobilized to a test site on the microchip. A mixture comprising a first labeled probe and a second labeled probe is electronically hybridized to the sample nucleic acid to form first or second hybridized complexes. The first labeled probe is perfectly complementary to the first sample nucleic acid and the second labeled probe is complementary to the sample nucleic acid and contains a nucleotide that forms a mismatch with the nucleotide at the site of the polymorphism. The first or second hybridized complexes are detected by determining a signal intensity of the label of the first or second probe.

Methods for determination of single nucleic acid polymorphisms using a bioelectronic microchip

In a method and a network for evaluating medical data in a clinical study, biochips containing patient samples with multiple biomolecular markers are tested in a number of point of care test devices respectively at point of care sites. Each test of each biochip sample produces a diagnostic result, which is entered into the electronic patient record for the patient who produced the sample. A follow-up examination is subsequently conducted for each patient, and the results of the follow-up examination are also entered into that patient's electronic patient record. The follow-up results indicate whether the diagnostic test result was a false positive, a false negative or correct. The follow-up data and the original diagnostic results from all point of care sites are electronically transmitted to a remote server, which has access to an expert system which uses the test results and the follow-up data to automatically devise a measurement protocol for a selected pathology.

Network for evaluating data obtained in a biochip measurement device

The present invention comprises devices and methods for performing channel-less separation of cell particles by dielectrophoresis, DC high voltage-pulsed electronic lysis of separated cells, separation of desired components from crude mixtures such as cell lysates, and/or enzymatic reaction of such lysates, all of which can be conducted on a single bioelectronic chip. A preferred embodiment of the present invention comprises a cartridge () including a microfabricated silicon chip () on a printed circuit board () and a flow cell () mounted to the chip () to form a flow chamber. The cartridge () also includes output pins () for electronically connecting the cartridge () to an electronic controller. The chip () % includes a plurality of circular microelectrodes () which are preferably coated with a protective permeation layer. Specific cells from various cell mixtures were separated, lysed, and enzymatically digested on the chip.

Channel-less separation of bioparticles on a bioelectronic chip by dielectrophoresis

A method for sorting a particle of interest from a plurality of particles includes the steps of determining an absorption maxima of the particle of interest, providing a light source for generating a beam of coherent light at a wavelength correlating to the absorption maxima, providing a plurality of particles on a support surface, and imparting relative motion between the beam of coherent light and the plurality of particles so as to cause differential movement between the particle of interest and the plurality of particles. The particle of interest is then collected.

Method for sorting particles

Apparatus and methods are provided for interacting light with particles, including but not limited to biological matter such as cells, in unique and highly useful ways. Optophoresis consists of subjecting particles to various optical forces, especially optical gradient forces, and more particularly moving optical gradient forces, so as to obtain useful results. In biology, this technology represents a practical approach to probing the inner workings of a living cell, preferably without any dyes, labels or other markers. In one aspect, a method is provided for separating particles by flowing the particles within a first constrained path, the first constrained path having an input and an output, and a sorting region, the sorting region coupling to a second constrained path, the second constrained path including an output, illuminating the sorting region with a moving optical gradient, characterized in that certain of the particles flow in a laminar manner between the first inlet and the output of the first constrained path, and selected particles are diverted from the first constrained path to the second constrained path under the force of the moving optical gradient.

Method for separation of particles

Apparatus and methods are provided for interacting light with particles, including but not limited to biological matter such as cells, in unique and highly useful ways. Optophoresis consists of subjecting particles to various optical forces, especially optical gradient forces, and more particularly moving optical gradient forces, so as to obtain useful results. In biology, this technology represents a practical approach to probing the inner workings of a living cell, preferably without any dyes, labels or other markers. In one aspect, a method is provided for interacting an optical gradient field in three dimensions with a particle by interfering two beams to generate a plurality of planar fronts, providing a plurality of particles in a medium, and moving the planar fronts relative to the particles, whereby the particles are separated at least in part based upon the dielectric constant of the particles.

Method of separating particles using an optical gradient

Apparatus and methods are provided for interacting light with particles, including but not limited to biological matter such as cells, in unique and highly useful ways. Optophoresis consists of subjecting particles to various optical forces, especially optical gradient forces, and more particularly moving optical gradient forces, so as to obtain useful results. In biology, this technology represents a practical approach to probing the inner workings of a living cell, preferably without any dyes, labels or other markers. The invention includes methods for separating particles in a medium where the particles having differing dielectric constants by providing a medium having a dielectric constant between the dielectric constants of the particles, subjecting the particles in the media to an optical gradient field, and separating the particles.

Methods of separating particles using an optical gradient

Methods are provided for the analysis and determination of the nature of single nucleic acid polymorphisms (SNPs) in a genetic target. In one method of this invention, the nature of the SNPs in the genetic target is determined by the steps of providing a plurality of hybridization complexes arrayed on a plurality of test sites on an electronically bioactive microchip, where the hybridization complex includes at least a nucleic acid target containing a SNP, a stabilizer probe having a sequence complementary to the target sequence and/or reporter probe, and a reporter probe having a selected sequence complementary to either the stabilizer or the same target sequence strand wherein a selected sequence of the reporter includes either a wild type nucleotide or a nucleotide corresponding to the SNP of the target. In accordance with the invention, the stabilizer, reporter and target amplicons are hybridized using electronic assistance of the microchip system such that base-stacking energies are utilized in discerning among other identifying indicators, the presence of wild type or polymorphism sequence. Applications include disease diagnostics, such as for the identification of polymorphisms in structural genes, regulatory regions, antibiotic or chemotherapeutic resistance conferring regions, or for SNPs associated with speciation or used for determination of genetic linkage.

Methods for determination of single nucleic acid polymorphisms using bioelectronic microchip

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 &ldquo;laboratory-on-a-chip&rdquo; system are presented which involves the selection of DNA probes, dyes, reagents and prototyping of the fully integrated portable instrument.

The present invention comprises devices and methods for performing channel-less separation of cell particles by dielectrophoresis, DC high voltage-pulsed electronic lysis of separated cells, separation of desired components from crude mixtures such as cell lysates, and/or enzymatic reaction of such lysates, all of which can be conducted on a single bioelectronic chip. A preferred embodiment of the present invention comprises a cartridge (,) including a microfabricated silicon chip (,) on a printed circuit board (,) and a flow cell (,) mounted to the chip (,) to form a flow chamber. The cartridge (,) also includes output pins (,) for electronically connecting the cartridge (,) to an electronic controller. The chip (,) includes a plurality of circular microelectrodes (,) which are preferably coated with a protective permeation layer which prevents direct contact between any electrode and a sample introduced into the flow chamber. The permeation layer also helps to reduce cell adhesion at field minima, and enables immobilization of specific antibodies for specific cell capture. Specific cells from various cell mixtures were separated, lysed, and enzymatically digested on the chip.

A system and method for processing, searching, and performing in-context searches on named annotated text string databases. The system and method provides users with a means for interactively refining database searches in order to account for differences in keywords used to describe similar phenomena. The system and method provides a means for performing searches for particular predefined target strings in context of particular predefined context strings. Data is represented using data types referred to as Hits and E-Hits. Hits data contains locations of search results and the E-Hits data contains text of search results. Hits lists are sorted and duplicate entries are discarded. Context search results are segregated from non-context search results by sorting the Hits lists. The Search module operates on a Hits list and selects those elements that match one or more search key(s). The output from a Search module is a Results Hits list. The Context Search module accepts two inputs in addition to the search key(s), a Context Hits list and a Target Hits list. The output of the Context Search module is a Hits list that contains matches found within the specified context. The Select module accepts a stream of Hits as input parameters and can be used to add or subtract annotations to the results of a search, remove base text sub-strings from the results of a search, or perform additional processing on Hits that may be useful for context searching. The Extract module is used to extract actual data from a Hits list, typically for display to a user and/or for converting results to keywords used for a subsequent search.

System and method for searching and processing databases comprising named annotated text strings

The present invention comprises devices and methods for performing channel-less separation of cell particles by dielectrophoresis, DC high voltage-pulsed electronic lysis of separated cells, separation of desired components from crude mixtures such as cell lysates, and/or enzymatic reaction of such lysates, all of which can be conducted on a single bioelectronic chip. A preferred embodiment of the present invention comprises a cartridge (10) including a microfabricated silicon chip (12) on a printed circuit board (14) and a flow cell (16) mounted to the chip (12) to form a flow chamber. The cartridge (10) also includes output pins (22) for electronically connecting the cartridge (10) to an electronic controller. The chip (12) includes a plurality of circular microelectrodes (24) which are preferably coated with a protective permeation layer which prevents direct contact between any electrode and a sample introduced into the flow chamber. The permeation layer also helps to reduce cell adhesion at field minima, and enables immobilization of specific antibodies for specific cell capture. Specific cells from various cell mixtures were separated, lysed, and enzymatically digested on the chip.

Growing community of inventors

Solana Beach, CA, United States of America

James P O'Connell