Abstract:
Provided herein are cartridges, packaged devices, and systems for improved nucleic acid sequencing. The cartridges, devices, and systems include a highly multiplexed optical chip comprising a plurality of nanoscale reaction regions that is configured to perform and report nucleic acid sequencing reactions. The chips are, in some embodiments, packaged for use in analytical nucleic acid sequencing reactions. The chips may be attached to a printed circuit board, may be surrounded by a protective enclosure, may include a flow cell, and may include optical features to minimize or block photobleaching of the sequencing reagents and background fluorescent signals. Also provided are analytical systems for nucleic acid sequencing that comprise the disclosed cartridges and packaged devices. The systems comprise an analytical instrument with electronic, optical, mechanical, fluidic, and/or thermal connectors designed to interact with the corresponding connectors on an associated cartridge or packaged device in a highly precise but reversible manner.
Abstract:
Apparatus, systems and methods for use in analyzing discrete reactions are provided. The analytical devices of the invention use an array of nanoscale regions (a chip) that has discrete patches of nanoscale regions. The chip mates with a collection device comprising an array of compact lens trains (CLTs) where each of the CLTs corresponds to a single patch of nanoscale regions. Each CLT collects the emitted light from a patch on the chip, collimates the light, performs color separation on the collimated emitted light, and focuses the separated light onto a portion of pixels on the detector below the CLT. Such systems are useful for monitoring many analytical reactions at one time including single molecule sequencing reactions.
Abstract:
Integrated target waveguide devices and optical analytical systems comprising such devices are provided. The target devices include an optical coupler that is optically coupled to an integrated waveguide and that is configured to receive optical input from an optical source through free space, particularly through a low numerical aperture interface. The devices and systems 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 provide for the efficient and reliable coupling of optical excitation energy from an optical source to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination. The devices and systems are well suited for miniaturization and high throughput.
Abstract:
Optical delivery devices and integrated analytical systems comprising the optical delivery devices are provided. The optical delivery devices include optical inputs, optical outputs, and integrated optical waveguides that are configured for coupling of optical energy to a target waveguide device through free space. The integrated analytical systems include the optical delivery devices in combination with the target waveguide device. The devices and systems 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 provide for the efficient coupling of optical excitation energy from an optical source to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination. The devices and systems are well suited for miniaturization and high throughput.
Abstract:
Provided herein are highly multiplexed optical analytical systems for improved nucleic acid sequencing. The systems include a plurality of highly multiplexed optical chips, at least one optical source, and a plurality of optical delivery devices for illuminating an array of nanoscale rection regions on each of the optical chips. In use, the reaction regions contain fluorescent nucleic acid sequencing reagents and are arranged to report nucleic acid sequence information to optical detectors associated with the multiplexed optical chips in real time. The systems enable a massive increase in the scale of nucleic acid sequencing reactions capable of being performed within a single instrument without a corresponding increase in size, complexity, or cost of the instrument.
Abstract:
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.