University of Illinois

Northeastern University

Cambridge Enterprise Limited

Johns Hopkins University

The University of North Carolina at Charlotte

Technische Universiteit Delft

Aleksei Aksimentiev

Meni Wanunu

Ulrich Keyser

Kirill Andreevich Afonin

Gregory L Timp

Winston Timp

Cornelis Dekker

Utkur Mirsaidov

Behzad Mehrafrooz

Luning Yu

Jeffrey Comer

The present invention provides compositions and methods for transferring phospholipids and other molecules between the leaflets of a cell membrane. The compositions comprise at least one nucleic acid or compound having a hydrophilic region, where the composition is able to form a nanostructure that forms a toroidal pore in a lipid membrane. The nucleic acid or hydrophilic region-containing compound further contains an attached molecule capable of inserting the nanostructure into the lipid membrane. The invention also provides methods for scrambling lipids and other molecules in a cell membrane, which can be used to alter the function of a selected cell or to facilitate the death of the cell. The scrambling activity of synthetic scramblases described herein outperforms previously known enzymatically active DNA nanostructures and naturally occurring scramblases, in some cases by several orders of magnitude.

Nucleic acid and other compositions and methods for the modulation of cell membranes

A method and system for performing single molecule proteomics utilizing a nanopore sensor to measure an electronic signature of protein or peptide being transported through the nanopore from a first chamber to a second chamber. The protein's electronic signature is a function of ionic current over time. The method and system utilizing an agent, such as guanidinium chloride, to bind to the nanopore's interior and provide an electroosmotic force within the nanopore. The electroosmotic force, in some embodiments, enables stretching and unfolding of the protein during transport through the nanopore. The agent may also or alternatively induce the unfolding of the protein before transport through the nanopore and/or provide force moving the protein through the nanopore.

Method and system for linearization and translocation of single protein molecules through nanopores

Aspects of the subject disclosure may include, for example, an apparatus comprising: a membrane, wherein the membrane has a first side and a second side, wherein the membrane has a first pore disposed therein, wherein the first pore extends through the membrane from the first side of the membrane to the second side of the membrane, wherein the membrane has a second pore disposed therein, and wherein the second pore extends through the membrane from the first side of the membrane to the second side of the membrane; a first channel disposed on the first side of the membrane, wherein the first channel is along a first longitudinal axis; a second channel disposed on the first side of the membrane, wherein the second channel is along a second longitudinal axis, and wherein the first channel and the second channel are disposed side by side adjacent to each other; a third channel disposed on the second side of the membrane, wherein the third channel is along a third longitudinal axis, wherein the third channel is in first fluid communication with the first channel via the first pore, and wherein the third channel is in second fluid communication with the second channel via the second pore; and one or more sensors disposed at one or more locations to facilitate sequencing of a molecule that extends from the first channel, through the first pore across at least a portion of the third channel, and through the second pore into the second channel. Additional embodiments are disclosed.

Systems and methods for high-fidelity capture, threading, and infinite-depth sequencing of single nucleic acid molecules

Aspects of the subject disclosure may include, for example, an apparatus comprising: a membrane having a first side and a second side, wherein the membrane has first and second pores disposed therein, a processing system; and a memory that stores executable instructions that, when executed by the processing system, facilitate performance of operations comprising: setting a first physical characteristic in a vicinity of the first pore to cause a first end of a molecule having the first end and a second end to be moved through the first pore; setting a second physical characteristic in a vicinity of the second pore to cause the second end of the molecule to be moved through the second pore; and adjusting the first physical characteristic to cause the molecule to be tightened, with a first given amount of force, between the first pore and the second pore. Additional embodiments are disclosed.

Nanopore-based system for trapping, controlled displacement, and sequencing of (bio)macromolecules

Provided is a highly multiplex approach to disease condition diagnostics that combines nanopore sensing and nucleic acid nanoparticle (NANP) design and synthesis to detect multiple biomarkers to diagnose diseases. The system works by taking a sample containing biomarkers that is mixed with a plurality of nucleic acid nanoparticle (NANP) populations, with each population designed and synthesized to be able to detect a particular biomarker. Upon incubation, the mixture is used with nanopore measurements, with recordings of the ionic current through the nanopore. The ionic current recordings are analyzed, which determines the presence and/or concentration of biomarkers in the sample.

Nucleic acid nanoparticles for analyte detection

A system that incorporates the subject disclosure may include, for example, a method for generating an electric or pressure difference force that induces a plurality of particles to flow through a through-hole. Independently adjustable heat source in a vicinity of the through-hole induces a thermodynamic force for modifying the flow of the plurality of particles through the through-hole. Additional embodiments are disclosed.

Method and apparatus for controlling a flow of particles by way of a through-hole

A system that incorporates the subject disclosure may include, for example, a method for selectively applying an electrical potential to a top surface of a membrane having a nanopore to repel or attract a molecular strand from the top surface of the membrane, applying a second electrical potential to a bottom surface of the membrane to repel or attract the molecular strand from the bottom surface of the membrane, applying a third electrical potential to an electrolyte solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the nanopore, arresting the section of the molecular strand in the nanopore by adjusting of the first electrical potential, the second electrical potential, the third electrical potential, or combinations thereof, and measuring a signal at the nanopore to identify the section of the molecular strand. Other embodiments are disclosed.

Method and apparatus for controlling materials through a through-hole

Methods of trapping a deformed portion of a double-stranded polynucleotide in a membrane nanopassage are provided. In an aspect, the membrane has a nanopassage that defines a confine region, wherein the membrane separates a first fluid compartment from a second fluid compartment, and the nanopassage is in fluid communication with the first and second compartments. A polynucleotide is provided to the first fluid compartment and optionally a threshold voltage for the membrane and the polynucleotide is determined. A driving voltage across the membrane that is greater than the threshold voltage is applied to force a portion of the polynucleotide sequence into the nanopassage confine region, and decreased to a holding voltage bias to trap the polynucleotide portion in the nanopassage confine region. In particular, at least one nucleotide base-pair is fixably positioned in the nanopassage confine volume. In further embodiments, any of the trapping methods are used to characterize or sequence double stranded DNA.

Growing community of inventors

Urbana, IL, United States of America

Aleksei Aksimentiev