Cardea Bio, Inc.

University of Pennsylvania

Nanomedical Diagnostics, Inc.

University of Illinois

Institute for Cancer Research

Ammr Joint Venture

Paragraf USA Inc.

Brett R Goldsmith

Mitchell Lerner

Paul Robert Hoffman

Alan T Johnson

Deng Pan

Bohdana Marie Discher

Kiana Aran

Alexander Kane

Ye Lu

Joseph J Mitala

Pieter Van Rooyen

Stephen G Sligar

Timothy H Bayburt

Nicholas J Kybert

Regis Peytavi

Savannah J Afsahi

Tatiana Pazina

Regis Paytavi

Dustin Brisson

Matthew W Robinson

Jennifer Dailey

Apparatuses, systems, and methods are disclosed for chemically differentiated sensor arrays and methods of manufacturing and using the same. In one or more examples. An integrated circuit chip includes a chemically differentiated array of graphene field effect transistors with one or more wells configured to receive a volume of biological sample liquid comprising a plurality of different types of biological substances to be distinguished using electrical measurements of output signals of the graphene field effect transistors. At least one electrode is configured to apply a changing gate bias voltage (Vs) that increases and decreases within a predetermined range to the sample liquid and at least one electrode is configured to monitor measurement vectors including slopes of drain current measurements relative to the voltage measurements and differences in slope of the measurement vectors distinguish different biological substances in the sample liquid. Systems and methods utilize the integrated circuit chip.

Chemically differentiated sensor array

A system and apparatus for direct or indirect target substance signal measurement include an integrated circuit with an array of 2D FETs with corresponding 2D transistor channels and a gate area for receiving a volume of liquid with one or more chemical or biological target substances, a conductive source electrically coupled to a first end of the 2D transistor channel, a conductive drain electrically coupled to a second end of the 2D transistor channel, a ceramic coating over the conductive source and the conductive drain and a thin film layer of synthetic biopolymer specific binding agents is adsorbed to the top surface of the 2D transistor channel. Methods for the system and apparatus and for selecting the synthetic biopolymer specific binding agents based on absorptivity are disclosed.

Integrated circuit with 2D FETs for direct and indirect target signal measurement

An apparatus may include a sensor chip fabricated on a semiconductor wafer, the sensor chip may include a graphene channel patterned in a graphene layer disposed on a dielectric substrate. The sensor chip may include a first electrode formed in electrode material so as to form one or more of an edge side contact or a top side contact in electrical contact with a first end of the graphene channel. The sensor chip may include a second electrode formed in electrode material so as to form one or more of an edge side contact or a top-side contact in electrical contact with a second end of the graphene channel. The sensor chip may include an insulation layer that is layered above at least of portion of the graphene layer and is selected from an inorganic oxide layer and an organic layer.

Chemically-sensitive field effect transistors, systems, and methods for manufacturing and using the same

An apparatus includes a biosensor integrated circuit (IC) chip with sensing zones and/or well structures configured to receive a liquid with biological analytes. The chip includes passivation and etch stop layers with an opening over a channel layer and an array of liquid gated field effect transistors with a 2D channel disposed on a dielectric oxide layer. A conductive drain and a conductive source form edge and/or top side contacts with opposite ends of the 2D channel. The chip further includes reference electrodes formed in a metal layer, configured to contact the liquid, and disposed at a horizontal distance apart from the graphene channels. The transistors are operable to enable a set of measurements to sense parameters of the biological analytes based on changes in a shape of Id-Vgs transconductance curves. A system and a method have similar structures and perform the functions of the apparatus.

An integrated circuit (IC) chip includes ROIC circuitry in a CMOS wafer with a top dielectric layer and at least one graphene field effect transistor (gFET) sensor array added above the CMOS wafer. The IC chip includes access transistors controlled by the ROIC circuitry and further includes sensing circuitry which includes the at least one gFET sensor array and a passivation opening that allows direct contact of a sample liquid with the graphene channels of the gFETs in the at least one gFET sensor array, such that a liquid gate is formed above the graphene channel upon receipt of the sample liquid. In some examples, the IC chip includes a process, memory controller, and memory. A system and a method have similar structures and perform the functions of the apparatus.

Ic with graphene fet sensor array patterned in layers above circuitry formed in a silicon based cmos wafer

An apparatus includes a biosensor integrated circuit (IC) chip having multiple well structures configured to receive a liquid comprising one or more biological analytes. The well structures include a passivation layer with an opening over one or more field effect transistors (gFETs) which include a layer of 2D channel material selected from molybdenum disulfide (MoS) and graphene; a drain electrode connected to a first end of the channel; a source electrode connected to a second end of the channel, wherein the individual gFETs are configured such that liquid received by the well structure is confined to form a liquid gate above a top surface of the channel. A system and method perform various functions of the apparatus.

Two-dimensional channel FET devices, systems, and methods of using the same for sequencing nucleic acids

For enhanced selection of efficient targeted genome manipulating agents, an apparatus includes first and second chip-based biosensors having one or more sensing surfaces configured to detect biomolecular binding interactions between a nucleic acid sample and a targeted genome manipulating agent functionalized to a capture surface within a sensing range of the one or more sensing surfaces. The first chip-based biosensor uses a nucleic acid sample incubated with a blocking agent that blocks on-target binding and the second chip-based biosensor holds a nucleic acid sample that omits the blocking agent. A measurement apparatus measures first and second sets of response signals produced in response to the biomolecular binding interactions occurring between the nucleic acid sample and the targeted genome manipulating agent. An analysis module determines the genome manipulating efficiency parameters of the targeted genome manipulating agent. A system and a method perform the functions of the apparatus.

Enhanced selection of efficient targeted genome manipulating agents

Apparatuses, systems, and methods are disclosed for target detection based on collateral cleavage of a reporter by an enzyme. A biologically gated transistor may include a channel and a reporter moiety immobilized to the channel. The state of the reporter moiety may affect one or more output signals from the biologically gated transistor when excitation conditions are applied to the biologically gated transistor and a sample fluid is applied in contact with the channel. A sample fluid may include an enzyme configured to activate in response to a target nucleic acid to cleave the reporter moiety. Excitation circuitry may apply the excitation conditions, and measurement circuitry may measure output signals from the biologically gated transistor. An analysis module may determine a parameter relating to presence of the target nucleic acid, based on the one or more measurements.

Electronic detection of a target based on enzymatic cleavage of a reporter moiety

An apparatus includes a biosensor integrated circuit (IC) chip with sensing zones and/or well structures configured to receive a liquid with biological analytes. The chip includes a passivation layer with an opening over a channel layer and an array of graphene field effect transistors (gFETs) individually having a 2D graphene channel disposed on a dielectric oxide layer, a conductive drain, and a conductive source. A liquid gate is formed above the top surface of the graphene channel. The chip further includes reference electrodes formed in a metal layer, configured to contact the liquid, and disposed at a horizontal distance apart from the graphene channels. The individual gFETs are operable to enable a set of measurements to sense parameters of the biological analytes based on changes in a shape of Id-Vgs transconductance curves. A system and a method have similar structures and perform the functions of the apparatus.

A DNA sequencing and blood chemistry analysis system and method are provided including one or more sensor chips and one or more sample wells, wherein each sample well is configured to form a seal with one of the sensors. The one or more sensor chips may comprise Graphene transistors, and each transistor having an associated sequencing probe. The sensor chips interact with a biological sample introduced into the sample well, wherein changes in the current, transconductance, and resistance of the Graphene transistors are indicative of a DNA binding process. Based on the associated sequencing probes, the DNA sequence present in a biological sample can be identified.

System and method for DNA sequencing and blood chemistry analysis

Provided are devices and methods featuring a nanoelectronic interface between graphene devices (for example, field effect transistors or FETs) and biomolecules such as proteins, which in turn provides a pathway for production of bioelectronic devices that combine functionalities of the biomolecular and inorganic components. In one exemplary application, one may functionalize graphene FETs with fluorescent proteins to yield hybrids that respond to light at wavelengths defined by the optical absorption spectrum of the protein. The devices may also include graphene in electronic communication with a biomolecule that preferentially binds to a particular analyte.

Graphene-biomolecule bioelectronic devices

A chemically differentiated sensor array system includes a plurality of environmentally-gated transistors and an environmental gate, wherein the environmental gate includes a liquid solution and each environmentally-gated transistor includes a drain, a source, and a Carbon-based substrate channel, the drain electrically couples to a first location on the substrate channel, the source electrically couples to a second location on the substrate channel separated by a gap from the first location on the substrate channel, the environmental gate covers and contacts the substrate channel, a first insulating layer covers and separates the drain from the environmental gate, and a second insulating layer covers and separates the source from the environmental gate.

Embodiments of the disclosed technology include patterning a graphene sheet for biosensor and electronic applications using lithographic patterning techniques. More specifically, the present disclosure is directed towards the method of patterning a graphene sheet with a hard mask metal layer. The hard mask metal layer may include an inert metal, which may protect the graphene sheet from being contaminated or damaged during the patterning process.

Providing a temporary protective layer on a graphene sheet

This invention concerns Chemically-sensitive Field Effect Transistors (ChemFETs) that are preferably fabricated using semiconductor fabrication methods on a semiconductor wafer, and in preferred embodiments, on top of an integrated circuit structure made using semiconductor fabrication methods. The instant ChemFETs typically comprise a conductive source, a conductive drain, and a channel composed of a one-dimensional (1D) or two-dimensional (2D) transistor nanomaterial, which channel extends from the source to the drain and is fabricated using semiconductor fabrication techniques on top of a wafer. The ChemFET also includes a gate, often the gate voltage is provided through a fluid or solution proximate the ChemFET. Such ChemFETs, preferably configured in independently addressable arrays, may be employed to detect a presence and/or concentration changes of various analyte types in chemical and/or biological samples, including nucleic acid hybridization and/or sequencing reactions.

Disclosed are devices that comprise a protein, such as an antibody, placed into electronic communication with a semiconductor material, such as a carbon nanotube. The devices are useful in assessing the presence or concentration of analytes contacted to the devices, including the presence of markers for prostate cancer and Lyme disease.

Growing community of inventors

San Diego, CA, United States of America

Brett R Goldsmith