The University of North Carolina at Chapel Hill

Laurent Menard

John Michael Ramsey

Michael Rubinstein

Sergey Panyukov

Jinsheng Zhou

Jean Pierre Alarie

Valeri Gorbounov

Michael A Tycon

Oscar A McCrate

Devices and methods generate an ordered restriction map of genomic DNA extracted from whole cells, nuclei, whole chromosomes, or other sources of long DNA molecules. The devices have a fluidic microchannel that merges into a reaction nanochannel that merges into a detection nanochannel at an interface where the nanochannel diameter decreases in size by between 50% to 99%. Intact molecules of DNA are transported to the reaction nanochannel and then fragmented in the reaction nanochannel using restriction endonuclease enzymes. The reaction nanochannel is sized and configured so that the fragments stay in an original order until they are injected into the detection nanochannel. Signal at one or more locations along the detection nanochannel is detected to map fragments in the order they occur along a long DNA molecule.

Nanofluidic devices for the rapid mapping of whole genomes and related systems and methods of analysis

Devices for controlling the capture, trapping, and transport of macromolecules include at least one fluidic transport nanochannel that intersects and is in fluid communication with at least one transverse nanochannel with (shallow) regions and/or with integrated transverse electrodes that enable fine control of molecule transport dynamics and facilitates analyses of interest, e.g., molecular identification, length determination, localized (probe) mapping and the like.

Nanofluidic devices with integrated components for the controlled capture, trapping, and transport of macromolecules and related methods of analysis

Devices and methods generate an ordered restriction map of genomic DNA extracted from whole cells. The devices have a fluidic microchannel that merges into a reaction nanochannel that merges into a detection nanochannel at an interface where the nanochannel diameter decreases in size by between 50% to 99%. Intact molecules of DNA are transported to the reaction nanochannel and then fragmented in the reaction nanochannel using restriction endonuclease enzymes. The reaction nanochannel is sized and configured so that the fragments stay in an original order until they are injected into the detection nanochannel. Signal at one or more locations along the detection nanochannel is detected to map fragments in the order they occur along a long DNA molecule.

Devices, such as chips for DNA analysis, have at least one fluid transport nanochannel with at least one intersecting (e.g., transverse) sensing nanochannel that can be monitored for change in ionic current to determine characteristics or parameters of interest, e.g., molecular identification, length determination, localized (probe) mapping and the like.

Devices with a fluid transport nanochannel intersected by a fluid sensing nanochannel and related methods

Methods of forming a chip with fluidic channels include forming (e.g., milling) at least one nanofunnel with a wide end and a narrow end into a planar substrate, the nanofunnel having a length, with width and depth dimensions that both vary over its length and forming (e.g., milling) at least one nanochannel into the planar substrate at an interface adjacent the narrow end of the nanofunnel.

Devices and systems with fluidic nanofunnels for processing single molecules

Fluidic devices with a primary transport nanochannel(s) intersected by at least one nanoscale manifold for active control of capture, manipulation and transport of analyte molecules. The at least one manifold can be an array or network of nanochannels, nanoslits or nanoelectrodes joined to a common voltage or pressure source. A respective nanoscale manifold can be configured to allow for precise and active control of driving forces applied to the primary transport nanochannel(s) to drive molecular transport through the various regions along the transport nanochannel(s). The at least one manifold can generate monotonic force gradients with a limited or reduced number of independent input potentials and/or pressures applied to the device.

Fluidic devices with nanoscale manifolds for molecular transport, related systems and methods of analysis

Devices with fluidic nanofunnels, associated methods, fabrication and analysis systems

Methods of forming at least one nanochannel include: (a) providing a substrate having a thick single or a thick multi-layer overlayer; (b) milling at least one channel through the overlayer into the substrate; then (c) removing the overlayer; and (d) forming at least one nanochannel in the substrate having an average width and depth dimension that is less than about 10 nm in response to the milling and removing steps.

Growing community of inventors

Cary, NC, United States of America

Laurent Menard