SBIR-STTR Award

Direct to Phase II

Septicemia, induced by an invasive microbial bloodstream infection (BSI), is a significant healthcare burden,accounting for over 1.7M cases annually just in the US. Characterized by high mortality rates (~20%), prognosisfor septic patients deteriorates hourly in the absence of appropriate treatment. Timely and accurate pathogenidentification is critical to match treatment to the infection. Unfortunately, current diagnostic approaches forBSIs rely on blood culture, which is slow (1-3 days) and unreliable in the presence of prior antimicrobialtreatment. In the meantime, physicians must rely on broad-spectrum treatment, which often misses the infection,leads to complications, and drives antimicrobial resistance. New diagnostic approaches are needed which canquickly detect and identify the infectious agent directly from blood, without cultures To address this unmet need, HelixBind has developed a sample to answer process which can identifybacterial and fungal BSIs directly from blood in 3 hours. Utilizing a proprietary detection approach leveragingsynthetic, duplex DNA invading, nucleic acids, the assay provides species level detail at single CFUs/mlsensitivity. dsDNA invasion-based detection (rather than ssDNA hybridization) affords single-bp specificity andthe ability to reliably differentiate between closely related species and reduce false-positives due to randomcontaminations. To date, though, invasion has never been demonstrated in a format appropriate for massivelyparallel detection. In this proposal, HelixBind will develop, for the first time, a DNA invasion array which candetect and identify hundreds of pathogens simultaneously. This array will be incorporated into a sample-to-answer fluidic cassette operated on a benchtop instrument. The resulting test will provide clinicians withcomprehensive coverage of essentially all pathogens associated with BSIs and unequivocal identification of aninfection within hours of patient presentation, enabling early application of appropriate antimicrobials,improving care and saving countless lives. HelixBind has previously established the capability of fluid-based invasion to identify BSIs from clinicalsamples and in this application, we present preliminary data for solid-phase array-based invasion, allowingmassively multiplexed detection. In this proposal we will address the biophysical challenges associated withcreating a highly multiplexed dsDNA invasion array and the technical hurdles associated with integrating thisarray into a sample-to-answer fluidic device. Specific Aims, each with quantifiable deliverables, serve to addressthe key risks and progressive steps in the development process. Upon completion of this Phase II project, wewill have a fully functional assay and a product appropriate for manufacturing scale up and clinical testing. Wewill also have developed a new, highly multiplexed assay format, with single-bp resolution, which can beadapted for a wide range of applications requiring sensitive and specific differentiation among closely relatedtargets.

Public Health Relevance Statement:
PROJECT NARRATIVE Timely determination of the appropriate antimicrobial intervention for bloodstream infections (BSIs) is recognized as among the most urgent clinical needs. Unfortunately, available techniques for identifying BSIs require days to provide results. Since a key driver of mortality is time to appropriate treatment, this leads to over 270,000 deaths annually in the US. HelixBind has previously demonstrated the ability of its proprietary suite of assay technologies to identify BSIs direct from blood in a few hours. In this proposal we will expand the capabilities of the technology to identify hundreds of organisms, complete development of an assay covering essentially all (>99%) BSIs simultaneously, and integrate this assay into a sample-to-answer device. Upon completion of this project, we will have a fully functional assay and a product appropriate for manufacturing scale up and clinical testing.

Project Terms: