Single-Molecule Sequencing Optics for Dense, Low-Background Detection

The patent integrates the excitation light source, waveguide, and sensor into a single integrated device structure. The waveguide is formed within the same substrate as the sequencing sites, and the sensor is positioned in direct proximity to detect fluorescent signals. This merging of components eliminates the need for separate optical elements and complex alignment mechanisms, enabling high-density sequencing sites (up to 1 million) while maintaining manageable device complexity.

The patent transitions from traditional lens-based optical paths to a planar waveguide structure that propagates light in a confined dimension within the substrate. The waveguide extends beneath multiple sequencing sites in the lateral dimension, allowing excitation light to reach and collect fluorescent signals from densely packed sites without requiring complex three-dimensional optical element arrangements.

The integrated device combines multiple functions (light generation, light guidance, sequencing reactions, and signal detection) into a single monolithic structure fabricated using planar processing techniques. This integration eliminates the need for assembling and aligning multiple separate optical components, significantly reducing manufacturing complexity and cost while enabling the production of devices with up to 1 million sequencing sites.

The patent replaces traditional mechanical optical systems (lenses, mirrors, beam splitters) with a planar waveguide structure that uses total internal reflection to guide light. This substitution eliminates complex mechanical alignment requirements and enables scalable fabrication using semiconductor-style planar processing, thereby reducing manufacturing costs for high-density sequencing devices.

The waveguide structure merges the excitation light delivery and fluorescent signal collection functions into a single integrated component. The evanescent field generated by the waveguide provides confined excitation precisely at the sequencing sites, while the same waveguide structure collects the emitted fluorescent signals. This eliminates the need for separate excitation and collection optical elements, achieving high measurement precision without increased device complexity.

The waveguide acts as an intermediary structure that generates an evanescent field to confine excitation to a narrow region near the sequencing sites. This evanescent field serves as the intermediate mechanism that provides precise spatial confinement of excitation without requiring complex optical elements, thereby improving measurement precision while maintaining simple device architecture.