Direct-from-specimen characterization of bloodstream infections - PROJECT SUMMARY Septicemia, a systemic inflammatory response to bloodstream infections (BSIs), contributes to over 270,000 annual deaths in the US. Timely diagnosis and treatment are critical for improving patient outcomes and reducing hospitalization time. However, currently accepted diagnostic approaches still require primary blood cultures, which are not only slow (requiring ~1-3 days) but also demonstrate reduced sensitivity when antimicrobial treatment is administered. There is thus a pressing need for improved diagnostics that do not require blood cultures and provide faster, more accurate results. HelixBind has developed a novel sample-to-answer molecular assay incorporating a suite of proprietary technologies, from sample preparation to detection, capable of characterizing BSIs directly from whole-blood within ~4 hours. The assay utilizes synthetic, duplex DNA invading, nucleic acids for detection enabling (unlike ssDNA hybridization) single-bp specificity as required to reliably differentiate between closely related species while effectively eliminating false-positives due to random contaminations. We successfully completed a Direct-to-Phase II project, with all milestones met or exceeded, to provide for an exceptionally broad, yet detailed, test menu. During this project we developed the capability to perform dsDNA invasion in an array format. With this format, we created an assay providing coverage of >98% of potential BSIs, including key AMR genes, and demonstrated single CFUs/mL sensitivity for single and mixed infections, directly from human whole-blood. We then automated the entire sample-to-answer process onto a breadboard, bench-top, instrument which operates a disposable plastic consumable and incorporates a custom machine learning algorithm to provide unparalleled confidence in test results. In this Phase IIB project, we will advance the current breadboard to an alpha instrument suitable for reliable operation within a hospital setting. We will also transition the fabrication of the fluidic consumable developed in Phase II to scalable manufacturing processes. Finally, alpha instruments and fluidic consumables will be provided to a hospital partner for a clinical study to verify test performance using clinical specimens. To ensure success, we’ve assembled a seasoned team with expertise in assay development, instrumentation, consumables manufacturing, regulatory compliance, and clinical microbiology. This team boasts a successful track record of commercializing multiple FDA-cleared IVD platforms and assays. Upon successful project completion, we will be well positioned to finalize instrument design for manufacturability and ease-of-use as well as initiate studies for FDA clearance.
