High-sensitivity multiplexed digital detection platform for DNA and RNA biomarkers at point-of-care

Overview

The Interferometric Reflectance Imaging Sensor (IRIS) is a single-molecule detection platform designed for ultrasensitive molecular analysis at the point of care. Unlike conventional ensemble measurements that average signals across many molecules, IRIS counts individual nanoparticles bound to a sensor surface, delivering sensitivity and resolution that exceed the limits of traditional assays. The technology uses gold nanorod labels combined with polarization-based imaging to enable digital detection on a compact, portable reader. The platform targets multiplexed detection of more than 10 DNA and RNA biomarkers in crude samples such as serum, whole blood, and plant extracts, with sensitivity below 10 fM. Potential applications span infectious disease diagnostics, cancer biomarker monitoring, agricultural pathogen detection, and any setting requiring highly sensitive nucleic acid measurement outside of a centralized laboratory.

Technical specifications

• Single-molecule digital readout: IRIS detects individual nanoparticle binding events through interference of light reflected from the sensor surface, enabling detection at attomolar concentrations.
• Gold nanorod labels with polarization imaging: Polarization-based discrimination allows specific identification of nanorod-labeled targets without moving parts, simplifying the optical architecture.
• Multiplexed microarray format: A 1 mm x 1 mm field-of-view supports imaging of more than 25 distinct probe spots, enabling 10X or greater multiplexing.
• Microfluidic cartridge integration: Disposable cartridges and automated multi-step binding assay control provide user-friendly operation suitable for non-expert users.
• Minimal sample preparation: Validated performance in serum, whole blood, and crude plant extracts reduces the need for complex nucleic acid extraction workflows.
• Kinetic, real-time assay capability: Dynamic tracking of single binding events allows measurement of analytes below reaction equilibrium limits.
• Portable instrument footprint: The IRIS reader has been reduced from benchtop to a field-deployable form factor.

Technology readiness level

IRIS has been developed over two decades with contributions from more than 20 PhD dissertations, establishing a strong foundation of validated performance. Digital detection of protein biomarkers has been demonstrated in serum and whole blood at 50 attomolar limits of detection, and virus detection has been shown at sensitivities below 50 PFU/ml. Kinetic assays on DNA and RNA biomarkers have exceeded reaction-limit sensitivities through single-molecule tracking, with microRNA detection demonstrated at approximately 10 attomolar. A stand-alone prototype instrument has been built. The current phase targets prototyping a polarization-based PD-IRIS instrument with no moving parts, integration with existing microfluidic cartridges, and validation using artificial DNA markers spiked into plant extracts in collaboration with an end-user partner. The first development stage is planned for completion within one year, with future work directed toward customer partnerships for assay customization and requirements definition.