Rapid and accurate identification of highly infectious and pathogenic disease is extremely important for the early forecast of outbreak risk and the effective deployment of medical and administrative countermeasures. Unfortunately, current diagnostics for use at the point-of-care (POC) are largely immunological assays that often lack adequate sensitivity, specificity, and multiplex capacity for an accurate early diagnosis. Nucleic acid- based diagnostic products developed or under development requires a relatively expensive dedicated instrument that is often prohibitive to small clinics and resource-limited settings and unsuitable for pandemic high capacity demand. We propose to develop an instrumentation-free, self-contained, low cost (<$20/unit), disposable, rapid (<40 minute, sample-to-answer), nucleic acid POC diagnostic device (MTIDx) capable of detecting influenza A, influenza B, RSV and other relative respiratory diseases. The final MTIDx product is designed to be a FDA approved, CLIA-waived (Clinical Laboratory Improvement Amendments of 1988) nucleic acid (NA)-based diagnostic device for analyzing human nasal swab samples. MTIDx (Multiple Target Identification Diagnostic) will be a cell phone-sized, device that is easy to operate with minimal user- intervention and also has an option to be powered by a 9V battery for use in resource-limited/field settings. It will be suitable for high volume manufacturing allowing rapid production of millions of units to meet surge capacity during a pandemic outbreak. The diagnostic system is based on the integration of Mesa Tech's proprietary technologies of nucleic acid extraction, rapid amplification, lateral flow-based (LF-based) colorimetric detection components with simple fluid control and microheater solutions into one easily used, low cost, disposable device. In preliminary data, we have demonstrated the feasibility of integrated device approach through a laboratory prototype. Work in this Phase I SBIR proposal will focus on the optimization of system integration and the refinement of initial MTIDx laboratory prototype designs to facilitate the transition of laboratory prototypes to manufacture-ready designs. Existing prototype designs will be transitioned to injection- molded prototypes to enable short-run production for rigorous characterization and laboratory testing. We will also incorporate the development of lyophilized reagents for amplification and detection to confer ambient storage compatibility, development of stable buffer reagents and capsulation methods, design for manufacturing optimizations to facilitate future high volume production and initial testing to identify design refinements required to attain performance objectives. The primary Phase I deliverable is the demonstration of an integrated MTIDx DFM-prototype (Design For Manufacturing) that offers a sample-to-answer 4-plex diagnostic test (Flu A, B, RSV and RNaseP as a control) complete in <40 minutes. In a follow-on Phase 2 project, we will incorporate more disease targets, further optimize the manufacture-ready designs, produce injection-molded devices and validate performance on a large panel of well-characterized clinical samples.
To better protect the public from potentially deadly pandemic/epidemic outbreaks, we will develop an instrumentation-free, self-contained, easy-to-use, low cost (<$20/unit), disposable, rapid (<40 minute, sample-to-answer), nucleic acid-based POC diagnostic device (MTIDx) capable of detecting influenza A, influenza B, RSV and RNase P (as an internal control). The final MTIDx product is designed to be a FDA approved, CLIA-waived (Clinical Laboratory Improvement Amendments of 1988) nucleic acid (NA)-based diagnostic device for analyzing human nasal swab samples. This cell phone-sized, device will be compatible with high volume manufacturing and also an option to be powered by a 9V battery for use in resource- limited/field settings.
