Robert Boschgmbh

Nadezda Fomina

Christopher Johnson

Habib Ahmad

Christoph Lang

Sam Kavusi

Young Shik Shin

Autumn Maruniak

Ashwin Raghunathan

Patrick A Staley

Franz Laermer

Armin Darvish

Aldrich Lau

Piyush Verma

Efthymios Papageorgiou

Rajan Gangadharan

Gary Yama

Nathan P Craig

Karim Gadelrab

Jochen Hoffmann

Juergen Steigert

Habibullah Ahmad

Giovanna Bucci

Murat Deliomeroglu

Provided is a method for monitoring a change of ion strength in a sample solution by a closed-loop device that provides continuous cycling of electrochemical pH modulation between pre-defined pH values. In particular, the change of ion strength may be induced by a chemical reaction and may ultimately alter the electrical control parameters of the closed-loop device. By measuring such electrical control parameters, the degree and progress of the underlying chemical reaction may be monitored.

Measuring ion strength using closed-loop electrochemical ph modulation

Device for use in a biosensor comprising a multisite array of test sites, the device being useful for modulating the binding interactions between a (biomolecular) probe or detection agent and an analyte of interest from a biological by modulating the pH or ionic gradient near the electrodes in such biosensor. The device provides a biosensor which is more accurate, reliable and the results of which are more reproducible. Analytic methods for more accurately measuring an analyte of interest in a biological sample are also provided.

Smart glass slide for microarrays

Device and methods for controlling pH or ionic gradient comprising a multisite array of feedback electrode sets comprising electrodes and pH sensing elements. The electrodes can include a reference electrode, counter electrode, and a working electrode. The device and methods iteratively select an amount of current and/or voltage to be applied to each working electrode, apply the selected amount of current and/or voltage to each working electrode to change pH of a solution close to the working electrode, and measure the signal output of the sensing element. The multisite array can include feedback and non-feedback electrode sets.

Electronic control of the pH of a solution close to an electrode surface

The present disclosure relates to systems, devices, and methods for nucleic acid sequencing including polynucleotide strands having a nucleotide(s) modified with a redox label(s) attached thereto or capable of receiving the modified nucleotide(s) with a redox label(s) attached thereto. The systems, devices, and methods include a dielectric member with an attached translocating protein positioned between oxidizing and reducing electrodes. The oxidizing and reducing electrodes generate an electrical field extending to a reaction area where the translocation of the polynucleotide strand through the protein occurs such the modified nucleotide(s) with redox label(s) attached thereto are identified by changes in current flow in the oxidizing and reducing electrodes, wherein the changes identify electron transfer from the reducing electrode, to redox label, and to oxidizing electrode when the modified nucleotide with a redox label covalently bonded to the nucleoside base of the modified nucleotide of the polynucleotide strand is at the reaction area.

Edge sequencing with an immobilized translocator

Closed-loop systems and methods for controlling pH. The system includes a working electrode, a counter electrode, a reference electrode, a first ion-sensitive field-effect transistor (ISFET), a second ISFET, and an electronic controller. The working electrode, the counter electrode, the reference electrode, and a first sensing terminal of the first ISFET are immersible in an active solution. A second sensing terminal of the second ISFET is immersible in a reference solution. The electronic controller is configured to apply a first amount of current or voltage to the working electrode and determine a differential voltage between the first ISFET and the second ISFET. The electronic controller is also configured to set a second amount of current or voltage to reduce a difference between the differential voltage and a target voltage. The electronic controller is further configured to apply the second amount of current or voltage to the working electrode.

Closed-loop PH control with differential sensor

Device and methods for use in a biosensor comprising a multisite array of test sites, the device and methods being useful for modulating the binding interactions between a (biomolecular) probe or detection agent and an analyte of interest by modulating the pH or ionic gradient near the electrodes in such biosensor. An electrochemically active agent that is suitable for use in biological buffers for changing the pH of the biological buffers. Method for changing the pH of biological buffers using the electrochemically active agents. The methods of modulating the binding interactions provided in a biosensor, analytic methods for more accurately controlling and measuring the pH or ionic gradient near the electrodes in such biosensor, and analytic methods for more accurately measuring an analyte of interest in a biological sample.

A device to electrochemically sequence DNA that includes a redox species includes at least one edge electrode, at least one stack of insulator material, and a pair of DNA translocation electrodes including a DNA translocation working electrode and a DNA translocation counter electrode, where the thickness of the at least one edge electrode is about 0.5 nanometers, and the thickness of the at least one stack of insulator material is about 10 nanometers. Methods of electrochemically sequencing a strand of DNA are also provided.

Electrochemical sequencing of DNA using an edge electrode

A sensor and a corresponding method measure the pH of a solution without using an external reference electrode. The pH sensor has at least one functionalized electrode with an attached first redox active molecule and an attached second redox active molecule that are differently sensitive to pH and oxidize/reduce at different voltages, and a difference in peaks of a response of the two molecules to applied electrical parameter is measured and correlated to a particular pH.

PH sensing method based upon the potential difference between two electrochemical waves

A method of fabricating a nanoscale topography system for inducing unfolding of a DNA molecule for sequencing includes providing a substrate and creating trench walls on the substrate which define a trench therebetween. The method further includes depositing a layer of a block copolymer (BCP) in the trench and forming cylindrical domains by self-assembly of the BCP between the trench walls, removing a first portion of the cylindrical domains to create a vacant region in the trench, and depositing a subsequent layer of the BCP in the vacant region and forming spherical domains by self-assembly of the BCP between the trench walls adjacent a second portion of the cylindrical domains. The spherical domains form staggered post structures for unfolding the DNA molecule and the cylindrical domains form parallel channel structures for entry of the DNA molecule for sequencing.

Nanoscale topography system for use in DNA sequencing and method for fabrication thereof

An apparatus to detect more than one analyte in a solution comprising at least one electrode in contact with the solution, at least two dyes including a first dye and a second dye, and an electrochemically active agent, where the solution has a pH, the electrode is configured to modulate the pH of the solution by oxidizing or reducing the electrochemically active agent, the first dye and the second dye fluoresce at different pH levels, fluorescence of the first dye is used to indicate the presence of a first analyte, and fluorescence of the second dye is used to indicate the presence of a second analyte. Methods of detecting multiple analytes in a solution are also provided.

Fluorophore multiplexing via PH modulation

Electrochemically active agents for pH modulation in biological buffers

At least one electrode is integrated on a lab on a chip cartridge in a sample preparation chamber of the cartridge, a DNA hybridization chamber of the cartridge, a protein assay chamber of the cartridge, and/or a detection chamber of the cartridge, for example, where the electrode is used to generate pH electrochemically in order to activate, deactivate, or intermediately attenuate an enzyme's activity on demand, in order to increase the fidelity of analyte detection, for cell lysis, for protein extraction, for DNA dehybridization, for primer hybridization control, for sample pre concentration, and/or for washing to remove non target species.

Integration of electrochemical pH modulation with lab on a chip technologies

A method for detecting a presence and/or a concentration of a target substance in a reagent solution using enzyme-linked immunosorbent assay (ELISA) includes binding the target substance directly or indirectly to an electrode, and binding a detection agent directly or indirectly to the bound target substance. The method further includes modulating a pH of only a portion of the reagent solution in which the bound target substance and the bound detection agent are located using the electrode, the modulated pH of the portion of the reagent solution causing the bound detection agent to undergo a change, and detecting the change in the bound detection agent. The detected change corresponds to the presence of the target substance in the reagent solution and/or the concentration of the target substance in the reagent solution.

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Fremont, CA, United States of America

Nadezda Fomina