An analytical device including an optically opaque cladding, a sequencing layer including a substrate disposed below the cladding, and a waveguide assembly for receiving optical illumination and introducing illumination into the device. The illumination may be received from a top, a side edge, and a bottom of the device. The waveguide assembly may include a nanoscale aperture disposed in the substrate and extending through the cladding. The aperture defines a reaction cell for receiving a set of reactants. In various aspects, the device includes a sensor element and the illumination pathway is through the sensor element. Waveguides and illumination devices, such as plasmonic illumination devices, are also disclosed. Methods for forming and operating the devices are also disclosed.

Illumination of integrated analytical systems

Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor The apparatus also includes an instrument that interfaces with the assay chip The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells Each sensor may detect emission energy from a sample in a respective sample well The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors

Optical system and assay chip for probing, detecting and analyzing molecules

An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed.

Integrated analytical system and method

This disclosure describes systems and methods for a graphical interface including a graphical representation of medical data The graphical interface platform may receive medical data and provide medical safety reporting capabilities including reporting of history data and real-time visual monitoring data The graphical interface platform may be configured to identify potential problems and corrections to medical devices in operation while a reporting cycle is underway through visual representation of performance metrics

Systems and methods for a graphical interface including a graphical representation of medical data

The application relates to improved optical containment structures, methods of manufacture and use, and systems for employing same The optical containment structures generally comprise zero-mode waveguide structures having non-reflective walls The non-reflective walls allow the preparation of optical containment regions in which the optical containment dimensions can be decoupled from the solution containment dimensions The application also relates to methods for producing islands of functionality within nanoscale apertures

Zero-mode waveguides with non-reflecting walls

Apparatus, systems and methods for use in analyzing discrete reactions at ultra high multiplex with reduced optical noise, and increased system flexibility. Apparatus include substrates having integrated optical components that increase multiplex capability by one or more of increasing density of reaction regions, improving transmission of light to or collection of light from discrete reactions regions. Integrated optical components include reflective optical elements which re-direct illumination light and light emitted from the discrete regions to more efficiently collect emitted light. Particularly preferred applications include single molecule reaction analysis, such as polymerase mediated template dependent nucleic acid synthesis and sequence determination.

Ultra-high multiplex analytical systems and methods

This invention provides systems for analyzing substrates. Also provided by the invention are improved optical systems for enhanced multiplex illumination, optical systems with compact multi-wavelength illumination architectures, optical systems for enhanced detection of optical signals, and optical systems for reduced autofluorescence background noise.

Substrate analysis systems

High multiplex arrays and systems

Subwavelength metal apertures significantly enhance single molecule fluorescence signaling systems, but require
efficient illumination and collection optics. On-chip micromirror structures offer a way to markedly improve the
coupling efficiency between such subwavelength metal apertures and the external fluorescence illumination and
collection optics, which in turn greatly simplifies several aspects of instrument design including optics,
optomechanics, and thermal control. Modeling and experimental verification of the gains in illumination and
collection efficiency for subwavelength metal apertures leads to a micromirror design that is both highly efficient
yet also manufacturable. A combination of ray-based and finite-difference-time-domain models is used to optimize
conical micromirrors colocated with subwavelength metal apertures for the case where the illumination light
interacts strongly with the micromirror and the collection optics have modest numerical aperture (NA~0.5).
Experimental methods employing either freely diffusing or immobilized dye molecules are used to measure the
illumination and collection efficiencies of fabricated micromirror prototypes. An overall fluorescence gain of
~100x, comprising a 20x improvement with flood illumination efficiency together with a 5x improvement in
collection efficiency, are both predicted and experimentally verified.

Yanqiao Huang

Papers

Ultra-high multiplex analytical systems and methods

Substrate analysis systems

High multiplex arrays and systems

Enhancement of single molecule fluorescence using conical micromirrors