Roche Sequencing Solutions, Inc.

Illumina Corporation

Panazee

Sandisk Technologies Inc.

Roche Diagnostics Gmbh

F. Hoffmann-la Roche Ag

Juraj Topolancik

Yann A Astier

Cheng Frank Zhong

Dietrich A Dehlinger

Zsolt Majzik

Flint Mitchell

Yann Astier

Dieter Heindl

Frank Bergmann

Patrick Braganca

Hannes Kuchelmeister

Nikolaus Klaus-Peter Stengele

Nikolaus-Peter Stengele

Molecules may be analyzed (e.g., sequencing of nucleic acid molecules) by tunneling recognition at a tunneling junction. Embodiments of the present invention may allow detecting individual nucleotides and the sequencing of a nucleic acid molecule using a tunneling junction. By labeling a specific 5 nucleotide with a moiety, tunneling junctions may generate a signal with a suitable signal-to-noise ratio. An electric field may be applied to move the nucleic acid molecule and the moiety close to the tunneling junction so that a current may travel through the moiety. Because a single nucleotide can be detected with a signal with a suitable signal-to-noise ratio resulting from the tunneling current passing through 10 the moiety, embodiments of the present invention may allow for fast detection of nucleotides using a tunneling current.

Electric field-assisted junctions for sequencing

Embodiments of the present technology may allow for the analysis of molecules by tunneling recognition at a tunneling junction. A tunneling junction of the present technology can include an insulating layer between two electrodes. A voltage may be applied to the electrodes. When a molecule makes contact with both electrodes, the molecule allows current to tunnel through the molecule. The characteristics of the current may aid in identifying a portion of the molecule, for example, a particular nucleotide or base present in a nucleic acid molecule. Methods and systems for analysis of molecules are described.

Tunnel junctions in microfluidic arrays for molecular recognition

Disclosed herein are apparatuses for nucleic acid sequencing, and methods of making and using such apparatuses. In some embodiments, the apparatus comprises a magnetic sensor array comprising a plurality of magnetic sensors, each of the plurality of magnetic sensors coupled to at least one address line, at least one selector element, and a fluid chamber adjacent to the magnetic sensor array, the fluid chamber having a proximal wall adjacent to the magnetic sensor array. A method of manufacturing sequencing device comprises fabricating a first addressing line on a substrate, fabricating a plurality of magnetic sensors such that the bottom portion of each sensor is coupled to the first addressing line, depositing a dielectric material between the sensors, fabricating additional addressing lines coupled to the top portions of the sensors, and removing a portion of the dielectric material adjacent to the sensors to create a fluid chamber.

Nucleic acid sequencing by synthesis using magnetic sensor arrays

A microfluidic chip with an array of pillars for directing flow of beads is used to measure reaction kinetics. A stream may be continuously drawn from the reaction volume into the microfluidic chip. The bead is attached to a primary antibody. The reaction volume has an antigen. The primary antibody binds to the antigen. A secondary antibody with a label binds to the antigen, creating a sandwich of bead, antigen, and label. The binding reactions occur over time in the microfluidic chip. The beads may be imaged after traversing a laminar wash buffer, and the signal intensity is measured. Each bead provides a kinetic monitoring of the immunoassay over the reaction time at which the bead is removed from the reaction media. Methods and systems are described in this disclosure.

Multi-step kinetic immunoassay systems and methods

Embodiments of the present technology may allow for improved and more reliable tunneling junctions and methods of fabricating the tunneling junctions. Electrical shorting issues may be reduced by depositing electrodes without a sharp sidewall and corner but instead with a sloping or curved sidewall. Layers deposited on top of the electrode layer may then be able to adequately cover the underlying electrode layer and therefore reduce or prevent shorting. Additionally, two insulating materials may be used as the dielectric layer may reduce the possibility of incomplete coverage and the possibility of flaking. Furthermore, the electrodes may be tapered from the contact area to the junction area to provide a thin electrode where the hole is to be patterned, while the thicker contact area reduces sheet resistance. The electrode may also be patterned to be wider at the contact area and narrower at the junction area.

Fabrication of tunneling junctions with nanopores for molecular recognition

A microfluidic chip with an array of pillars for directing flow of beads is used to measure reaction kinetics. A stream may be continuously drawn from the reaction volume into the microfluidic chip. The bead is attached to a primary antibody. The reaction volume has an antigen and a second antibody with a label. The primary antibody binds to the antigen, and the secondary antibody binds to the antigen, creating a sandwich of bead, antigen, and label. The binding reactions occur over time in the reaction volume. The beads may be imaged after traversing a laminar wash buffer, and the signal intensity is measured. Each bead provides a kinetic monitoring of the immunoassay over the reaction time at which the bead is removed from the reaction media. Methods and systems are described in this disclosure.

Kinetic immunoassay systems and methods

Molecules may be analyzed (e.g., sequencing of nucleic acid molecules) by tunneling recognition at a tunneling junction. Embodiments of the present invention may allow detecting individual nucleotides and the sequencing of a nucleic acid molecule using a tunneling junction. By labeling a specific nucleotide with a moiety, tunneling junctions may generate a signal with a suitable signal-to-noise ratio. The tunneling recognition uses a tunneling current that is mostly through the moiety rather than mostly through the nucleotide or a portion of the molecule of interest. Because a single nucleotide can be detected with a signal with a suitable signal-to-noise ratio resulting from the tunneling current passing through the moiety, embodiments of the present invention may allow for fast detection of nucleotides using a tunneling current.

Tunneling junctions for sequencing

A device for luminescent imaging includes an array of imaging pixels, a photonic structure over the array of imaging pixels, and an array of features over the photonic structure. A first feature of the array of features is over a first pixel of the array of imaging pixels, and a second feature of the array of features is over the first pixel and spatially displaced from the first feature. A first luminophore is within or over the first feature, and a second luminophore is within or over the second feature. The device includes a radiation source to generate first photons having a first characteristic at a first time, and generate second photons having a second characteristic at a second time. The first pixel selectively receives luminescence emitted by the first and second luminophores responsive to the first photons at the first time and second photons at the second time, respectively.

Photonic structure-based devices and compositions for use in luminescent imaging of multiple sites within a pixel, and methods of using the same

Under one aspect, a device is provided for use in luminescent imaging. The device can include a photonic superlattice including a first material, the first material having a first refractive index. The first material can include first and second major surfaces and first and second pluralities of features defined through at least one of the first and second major surfaces, the features of the first plurality differing in at least one characteristic from the features of the second plurality. The photonic superlattice can support propagation of a first wavelength and a second wavelength approximately at a first angle out of the photonic superlattice, the first and second wavelengths being separated from one another by a first non-propagating wavelength that does not selectively propagate at the first angle out of the photonic superlattice.

Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same

Embodiments of the present technology include a system for analyzing a molecule. The system may include a device. The device includes a first conductive element, a second conductive element, and an insulating layer. The insulating layer may be tapered in a direction to reach a minimum thickness at a first end of the device. The insulating layer is disposed between the first conductive element and the second conductive element. The device may include a voltage source in electrical communication with the first conductive element and the second conductive element. The device may also include an electrical meter in electrical communication with the voltage source, the first conductive element, and the second conductive element.

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Redwood City, CA, United States of America

Juraj Topolancik