Abstract: Disclosed herein are embodiments of single-molecule array sequencing (SMAS) devices and systems. Each sensor of an array of sensors of the SMAS device is capable of detecting labels attached to nucleotides incorporated into a single nucleic acid strand bound to a respective binding site. Each sensor can detect a single label (e.g., fluorescent, magnetic, organometallic, charged molecule, etc.) attached to the incorporated nucleotide. Also disclosed are methods of using SMAS devices and systems for highly-scalable nucleic acid (e.g., DNA) sequencing based on sequencing by synthesis (SBS) of multiple instances of clonally amplified DNA immobilized on such SMAS devices. Also disclosed are error correction methods that mitigate errors (e.g., errant label detections or non-detections) made in sequencing individual nucleic acid strands.

Abstract: 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.

Abstract: 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.

Abstract: Disclosed herein are apparatuses for nucleic acid sequencing using magnetic labels (e.g., magnetic particles) and magnetic sensors. Also disclosed are methods of making and using such apparatuses. An apparatus for nucleic acid sequencing comprises a plurality of magnetic sensors, a plurality of binding areas disposed above the plurality of magnetic sensors, each of the binding areas for holding fluid, and at least one line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor.

Abstract: 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.

Abstract: Disclosed herein are devices, systems, and methods for monitoring single-molecule biological processes using magnetic sensors and magnetic particles (MNP). A MNP is attached to a biopolymer (e.g., a nucleic acid, protein, etc.), and motion of the MNP is detected and/or monitored using a magnetic sensor. Because the MNP is small (e.g., its size is comparable to the size of the molecule being monitored) and is tethered to a biopolymer, changes in the volume of Brownian motion of the MNP in a solution can be monitored to monitor the movement of the MNP and, by inference, the tethered biopolymer. The magnetic sensor is small (e.g., nanoscale or having a size on the order of the sizes of the MNP and the biopolymer) and can be used to detect even small changes in the position of the MNP within the sensing region of the magnetic sensor.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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, and a fluid chamber adjacent to the magnetic sensor array, the fluid chamber having a proximal wall adjacent to the magnetic sensor array.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to a microfluidic device for extracting and isolating DNA from cells. The device includes a support having an inlet port for receiving a sample containing a cell, an outlet port for dispensing DNA isolated from the cell, and a microfluidic channel disposed within the support and extending from the inlet port to the outlet port. The microfluidic channel includes a micropillar array, an inflow channel disposed between the inlet port and the micropillar array, and an outflow channel disposed between the micropillar array and the outlet port. The micropillar array includes micropillars spatially configured to entrap, by size exclusion, the cell, to immobilize DNA released from the cell, and to maintain the immobilized DNA in elongated or non-elongated form when hydrodynamic force is applied to the microfluidic channel. Systems and methods of making and using the device are also provided herein.

Abstract: The present invention relates to a microfluidic device for extracting and isolating DNA from cells. The device includes a support having an inlet port for receiving a sample containing a cell, an outlet port for dispensing DNA isolated from the cell, and a microfluidic channel disposed within the support and extending from the inlet port to the outlet port. The microfluidic channel includes a micropillar array, an inflow channel disposed between the inlet port and the micropillar array, and an outflow channel disposed between the micropillar array and the outlet port. The micropillar array includes micropillars spatially configured to entrap, by size exclusion, the cell, to immobilize DNA released from the cell, and to maintain the immobilized DNA in elongated or non-elongated form when hydrodynamic force is applied to the microfluidic channel. Systems and methods of making and using the device are also provided herein.