Harvard College

California Institute of Technology

Brown University

Sri International

Massachusetts Institute of Technology

New York University

Children's Medical Center Corporation

University of Hawai'i

Korea University

Charles M Lieber

Yi Cui

Ping Xie

Hongkun Park

Xiangfeng Duan

Yu Huang

Qingqiao Wei

Bozhi Tian

Wenjie Liang

Ernesto Joselevich

Thomas Rueckes

André M DeHon

John E Savage

Kevin Kim

Ying Fang

Jia Liu

Fernando Patolsky

Andre DeHon

Ruixuan Gao

Thomas J Kempa

Xiaojie Duan

Gengfeng Zheng

Eric Rachlin

Robert Samuel Langer

Patrick Denis Lincoln

Jason H Hafner

Daniel S Kohane

Tal Dvir

Qihua Xiong

Ritesh Agarwal

Robert Day

Itzhaq Cohen-Karni

Quan Qing

Xiaocheng Jiang

Xuan Gao

Guihua Yu

Yue Wu

Hao Yan

Chin Li Cheung

Peidong Yang

David G Grier

Wei Lu

Max Nathan Mankin

Stanislaus S Wong

Philip Kim

Yael Roichman

Adam T Woolley

Hong-Gyu Park

Kosta Ladavac

Anyuan Cao

Steffen Strehle

Brian Timko

Sun-Kyung Kim

Hwan Sung Choe

Xueliang Liu

Jung-Ung Park

SungWoo Nam

Jeffrey J Urban

Qian Gu

Wan Soo Yun

Jie Xiang

Wenji Liang

Mark Gudiksen

Lincoln J Lauhon

Jianfang Wang

David C Smith

Deli Wang

Zhaohui Zhong

Michael J Wilson

Hongjie Dai

Yun Kim

Chunming Niu

Z John Zhang

Eric Wong

To sense the translocation of a molecule through a nanopore, there is directed to an inlet of the nanopore, having a nanopore fluidic resistance, R, a molecule disposed in a cis fluidic ionic solution having a cis fluidic access resistance, R. The molecule is caused to translocate through the nanopore from the inlet of the nanopore to an outlet of the nanopore and to a trans fluidic ionic solution having a trans fluidic access resistance, R. The trans fluidic access resistance, R, is of the same order of magnitude as the nanopore fluidic resistance, R, and both Rand Rare at least an order of magnitude greater than the cis fluidic access resistance, R. An indication of local electrical potential is produced at a site within the nanopore sensor that is on the trans fluidic ionic solution-side of the nanopore, to sense translocation of the molecule through the nanopore.

Method for nanopore sensing with local electrical potential measurement

There is provided a nanopore sensor including cis and trans fluidic reservoirs. A nanopore is provided in a support structure separating the cis and trans reservoirs. The nanopore has an inlet in fluidic connection with the cis fluidic reservoir and an outlet in fluidic connection with the trans fluidic reservoir. The cis fluidic reservoir has a fluidic access resistance, R, the trans fluidic reservoir has a fluidic access resistance, R, and the nanopore has a fluidic resistance, R. Ris of the same order of magnitude as Rand both Rand Rare at least an order of magnitude greater than R. An electrical transduction element is disposed at a nanopore sensor site that exposes the transduction element to the trans reservoir. An electrical circuit is connected to the electrical transduction element for producing an electrical signal indicative of changes in electrical potential local to the trans reservoir.

Nanopore sensing by local electrical potential measurement

There is provided a multi-channel nanopore sensor having a plurality of independent nanopore sensors. Each independent nanopore sensor includes a nanopore disposed in a support structure. A fluidic connection is between a first fluidic reservoir, common to all of the independent nanopore sensors, and an inlet to the nanopore, with a first ionic solution of a first ionic concentration disposed in the first fluidic reservoir. A fluidic connection is between a second fluidic reservoir, common to all of the independent nanopore sensors, and an outlet from the nanopore, with a second ionic solution of a second ionic concentration, different than the first ionic concentration, disposed in the second fluidic reservoir. An electrical transduction element, disposed in contact with that ionic solution having a lower ionic concentration, is arranged at a site that produces an electrical signal indicative of electrical potential local to that ionic solution having a lower ionic concentration.

Multi-channel nanopore sensing by local electrical potential measurement

The present invention generally relates to nanoscale wires, and to methods of producing nanoscale wires. In some aspects, the nanoscale wires are nanowires comprising a core which is continuous and a shell which may be continuous or discontinuous, and/or may have regions having different cross-sectional areas. In some embodiments, the shell regions are produced by passing the shell material (or a precursor thereof) over a core nanoscale wire under conditions in which Plateau-Raleigh crystal growth occurs, which can lead to non-homogenous deposition of the shell material on different regions of the core. The core and the shell each independently may comprise semiconductors, and/or non-semiconductor materials such as semiconductor oxides, metals, polymers, or the like. Other embodiments are generally directed to systems and methods of making or using such nanoscale wires, devices containing such nanoscale wires, or the like.

Controlled growth of nanoscale wires

There is provided a method for sensing the translocation of a molecule through a nanopore. In the method, there is directed to an inlet of a nanopore a molecule that is disposed in a first ionic solution of a first ionic concentration. The molecule is caused to translocate through the nanopore from the inlet of the nanopore to an outlet of the nanopore and into a second ionic solution of a second ionic concentration that is different than the first ionic concentration. An electrical potential, local to that ionic solution, of the first and second ionic solutions, which has a lower ionic concentration, is measured while the molecule is caused to translocate through the nanopore.

The present invention generally relates to nanoscale wires and tissue engineering. In various embodiments, cell scaffolds for growing cells or tissues can be formed that include nanoscale wires that can be connected to electronic circuits extending externally of the cell scaffold. The nanoscale wires may form an integral part of cells or tissues grown from the cell scaffold, and can even be determined or controlled, e.g., using various electronic circuits. This approach allows for the creation of fundamentally new types of functionalized cells and tissues, due to the high degree of electronic control offered by the nanoscale wires and electronic circuits. Accordingly, such cell scaffolds can be used to grow cells or tissues which can be determined and/or controlled at very high resolutions, due to the presence of the nanoscale wires, and such cell scaffolds will find use in a wide variety of novel applications, including applications in tissue engineering, prosthetics, pacemakers, implants, or the like.

Scaffolds comprising nanoelectronic components for cells, tissues, and other applications

The present invention generally relates to nanoscale wires and tissue engineering. Systems and methods are provided in various embodiments for preparing cell scaffolds that can be used for growing cells or tissues, where the cell scaffolds comprise nanoscale wires. In some cases, the nanoscale wires can be connected to electronic circuits extending externally of the cell scaffold. Such cell scaffolds can be used to grow cells or tissues which can be determined and/or controlled at very high resolutions, due to the presence of the nanoscale wires, and such cell scaffolds will find use in a wide variety of novel applications, including applications in tissue engineering, prosthetics, pacemakers, implants, or the like. This approach thus allows for the creation of fundamentally new types of functionalized cells and tissues, due to the high degree of electronic control offered by the nanoscale wires and electronic circuits.

Methods and systems for scaffolds comprising nanoelectronic components

A solid state molecular sensor having an aperture extending through a thickness of a sensing material is configured with a continuous electrically-conducting path extending in the sensing material around the aperture. A supply reservoir is connected to provide a molecular species, having a molecular length, from the supply reservoir to an input port of the aperture. A collection reservoir is connected to collect the molecular species from an output port of the aperture after translocation of the molecular species from the supply reservoir through the sensing aperture. The sensing aperture has a length between the input and output ports, in the sensing material, that is substantially no greater than the molecular length of the molecular species from the supply reservoir. An electrical connection to the sensing material measures a change in an electrical characteristic of the sensing material during the molecular species translocation through the aperture.

High-resolution molecular sensor

The present invention generally relates to nanoscale wires, including anisotropic deposition in nanoscale wires. In one set of embodiments, material may be deposited on certain portions of a nanoscale wire, e.g., anisotropically. For example, material may be deposited on a first facet of a crystalline nanoscale wire but not on a second facet. In some cases, additional materials may be deposited thereon, and/or the portions of the nanoscale wire may be removed, e.g., to produce vacant regions within the nanoscale wire, which may contain gas or other species. Other embodiments of the invention may be directed to articles made thereby, devices containing such nanoscale wires, kits involving such nanoscale wires, or the like.

Anisotropic deposition in nanoscale wires

The present invention generally relates to nanotechnology and sub-microelectronic circuitry, as well as associated methods and devices, for example, nanoscale wire devices and methods for use in determining nucleic acids or other analytes suspected to be present in a sample. For example, a nanoscale wire device can be used in some cases to detect single base mismatches within a nucleic acid. In one aspect, dynamical information such as a binding constant, an association rate, and/or a dissociation rate, can be determined between a nucleic acid or other analyte, and a binding partner immobilized relative to a nanoscale wire. In some cases, the nanoscale wire includes a first portion comprising a metal-semiconductor compound, and a second portion that does not include a metal-semiconductor compound. The binding partner, in some embodiments, is immobilized relative to at least the second portion of the nanoscale wire.

Nanosensors and related technologies

There is provided a nanopore disposed in a support structure, with a fluidic connection between a first fluidic reservoir and an inlet to the nanopore and a second fluidic connection between a second fluidic reservoir and an outlet from the nanopore. A first ionic solution of a first buffer concentration is disposed in the first reservoir and a second ionic solution of a second buffer concentration, different than the first concentration, is disposed in the second reservoir, with the nanopore providing the sole path of fluidic communication between the first and second reservoirs. An electrical connection is disposed at a location in the nanopore sensor that develops an electrical signal indicative of electrical potential local to at least one site in the nanopore sensor as an object translocates through the nanopore between the two reservoirs.

The present invention generally relates to nanoscale wires for use in sensors and other applications. In various embodiments, a probe comprising a nanotube (or other nanoscale wire) is provided that can be directly inserted into a cell to determine a property of the cell, e.g., an electrical property. In some cases, only the tip of the nanoscale wire is inserted into the cell; this tip may be very small relative to the cell, allowing for very precise study. In some aspects, the tip of the probe is held by a holding member positioned on a substrate, e.g., at an angle, which makes it easier for the probe to be inserted into the cell. The nanoscale wire may also be connected to electrodes and/or form part of a transistor, such that a property of the nanoscale wire, and thus of the cell, may be determined. Such probes may also be useful for studying other samples besides cells. Other aspects of the invention are generally directed to methods of making or using such probes, kits involving such probes, devices involving such probes, or the like.

Nanoscale sensors for intracellular and other applications

The present invention generally relates to nanotechnology, including field effect transistors and other devices used as sensors (for example, for electrophysiological studies), nanotube structures, and applications. Certain aspects of the present invention are generally directed to transistors such as field effect transistors, and other similar devices. In one set of embodiments, a field effect transistor is used where a nanoscale wire, for example, a silicon nanowire, acts as a transistor channel connecting a source electrode to a drain electrode. In some cases, a portion of the transistor channel is exposed to an environment that is to be determined, for example, the interior or cytosol of a cell. A nanotube or other suitable fluidic channel may be extended from the transistor channel into a suitable environment, such as a contained environment within a cell, so that the environment is in electrical communication with the transistor channel via the fluidic channel. In some embodiments, the rest of the transistor channel may be coated, e.g., so that the electrical properties of the transistor channel reflect the electrical behavior of the environment that the fluidic channel is in communication with. Other aspects of the invention are generally directed to methods of making such sensors, methods of using such sensors, kits involving such sensors, or the like.

Nanoscale wires, nanoscale wire FET devices, and nanotube-electronic hybrid devices for sensing and other applications

The present invention generally relates to nanoscale wires, including to nanoscale wires used as sensors. In some cases, the nanoscale wires may be used to directly determine analytes, even within relatively complicated environments such as blood, unlike many prior art techniques. In some aspects, the nanoscale wire form at least a portion of the gate of a field-effect transistor, and in certain aspects, different periodically-varying voltages or other electrical signals may be applied to the field-effect transistor. For example, in one set of embodiments, sinusoidally-varying voltages of different frequencies may be applied to the nanoscale wire and the source electrode of the field-effect transistor. The electrical conductance or other properties of the nanoscale wire in response to the periodically-varying voltages may then be determined and used to determine binding of the species.

Nanoscale field-effect transistors for biomolecular sensors and other applications

Growing community of inventors

Lexington, MA, United States of America

Charles M Lieber