Provided herein are systems, devices, and methods for improved optical waveguide transmission and alignment in an analytical system. Waveguides in optical analytical systems can exhibit variable and increasing back reflection of single-wavelength illumination over time, thus limiting their effectiveness and reliability. The systems are also subject to optical interference under conditions that have been used to overcome the back reflection. Novel systems and approaches using broadband illumination light with multiple longitudinal modes have been developed to improve optical transmission and analysis in these systems. Novel systems and approaches for the alignment of a target waveguide device and an optical source are also disclosed.

Arrays of integrated analytical devices and their methods for production are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices include an integrated diffractive beam shaping element that provides for the spatial separation of light emitted from the optical reactions.

An integrated device, comprising a substrate having a first surface; and at least one pixel formed on or in the substrate. The at least one pixel comprising a reaction chamber configured to receive a sample, and a sensor configured to detect emission light emitted from the reaction chamber and at least one nanostructure disposed in a plane between a waveguide and the sensor, wherein the optical nanostructure is configured to converge at least a portion of the emission light in a direction substantially perpendicular to the plane. The waveguide is configured to couple excitation light to each pixel.

Disclosed is an apparatus and method of forming, including a supporting structure, a sensor on the supporting structure, a pair of columns on the supporting structure at opposite sides of the sensor, the pair of columns having a column height relative to a top surface of the supporting structure, the column height being higher than a height of the active surface of the sensor relative to the top surface of the supporting structure, and a lidding layer on the pair of columns and over the active surface, the lidding layer being supported at opposite ends by the pair of columns. The active surface of the sensor, the lidding layer and the pair of columns form an opening above at least more than about half of the active surface of the sensor, and the supporting structure, the sensor, the lidding layer and the pair of columns together form a flow cell.

A “lab on a chip” includes an optofluidic sensor and components to analyze signals from the optofluidic sensor. The optofluidic sensor includes a substrate, a channel at least partially defined by a portion of a layer of first material on the substrate, input and output fluid reservoirs in fluid communication with the channel, at least a first radiation source coupled to the substrate adapted to generate radiation in a direction toward the channel, and at least one photodiode positioned adjacent and below the channel.

An example image sensor structure includes an image layer. The image layer includes an array of light detectors disposed therein. A device stack is disposed over the image layer. An array of light guides is disposed in the device stack. Each light guide is associated with at least one light detector of the array of light detectors. A passivation stack is disposed over the device stack. The passivation stack includes a bottom surface in direct contact with a top surface of the light guides. An array of nanowells is disposed in a top layer of the passivation stack. Each nanowell is associated with a light guide of the array of light guides. A crosstalk blocking metal structure is disposed in the passivation stack. The crosstalk blocking metal structure reduces crosstalk within the passivation stack.

A method includes obtaining, from one or more sequencing devices, raw data detected from luminescent labels associated with nucleotides during nucleotide incorporation events; and processing the raw data to perform a comparison of base calls produced by a learning enabled, automatic base calling module of the one or more sequencing devices with actual values associated with the raw data, wherein the base calls identify one or more individual nucleotides from the raw data. Based on the comparison, an update to the learning enabled, automatic base calling module is created using at least some of the obtained raw data, and the update is made available to the one or more sequencing devices.

The invention is a nanowire-comprising device for detecting at least one target biomolecule. The nanowires are placed between a substrate and a multilayer structure. The multilayer structure lies between the nanowires and a sample liable to contain a target biomolecule. The multilayer structure comprises a functionalization surface making contact with the sample. When light is emitted from the functionalization surface, fluorescence light for example, at least one nanowire allows the light to be detected. The fluorescence light may indicate the presence or absence of a target biomolecule on the functionalization surface.

Flow cells systems and corresponding methods are provided. The flow cells systems may include a socket comprising a base portion, a plurality of electrical contacts and a cover portion that includes a first port. The flow cells systems may also include a flow cell device secured within an enclosure of the socket. The flow cell device may comprise a frameless light detection device comprising a base wafer portion, a plurality of dielectric layers, a reaction structure, a plurality of light guides, a plurality of light sensors, and device circuitry electrically coupled to the light sensors. The flow cell device may also comprise a lid forming a flow channel over the reaction structure that includes a second port in communication with the flow channel and the first port of the socket. The device circuitry of the light detection device may be electrically coupled to the electrical contacts of the socket.

A detection chip, a using method for the same, and a reaction system. The detection chip includes a first substrate, a micro-cavity defining layer, and a heating electrode. The micro-cavity defining layer is on the first substrate and defines a plurality of micro-reaction chambers. The heating electrode is on the first substrate and is closer to the first substrate than the micro-cavity defining layer, and is configured to heat a plurality of micro-reaction chambers. The orthographic projection of the plurality of micro-reaction chambers on the first substrate is within the orthographic projection of the heating electrode on the first substrate.