COSMOSID, INC. — Department of Defense SBIR Phase II: DHA201-001

Description

Diagnosis of bacterial resistance in military deployment settings is challenging, representing a current health gap. Culture-based resistance testing is laborious, time consuming, and difficult to provide in resource-limited settings. We propose development of a precision metagenomics-based diagnostic tool by taking advantage of the rapid sequencing speed and portability of the Oxford Nanopore MinION platform and the powerful genome database/algorithms of CosmosID. These curated databases and best-in-class bioinformatics can detect, identify, and characterize presence (or absence) of all microorganisms (bacteria, viruses, fungi, and protists), as well as resistome and virulome gene sequences, in individual isolate or complex (metagenomic) biological samples, directly on clinical samples without culture. The remaining gap is computational methods to identify the pathogens etc. rapidly, accurately, and actionably with a field device to allow improved and reliable patient decisions. The proposed efforts in this Phase II project will continue successful work on the prototype assay from Phase I and include field deployable capabilities and clinical/field validation. We have demonstrated proof-of-concept of the device and software platform to detect the ESKAPE(E) pathogens (Enterococcus spp., S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., and Escherichia coli), and will now rigorously test the limits of capabilities for the assay in its ability to detect bacterial pathogens and antibiotic susceptibility. The first objective will be to fully validate the platform as a CLIA laboratory developed test (LDT) using pathology samples that will be characterized using the developed platform and compared to current FDA approved clinical diagnostic methods. The second objective will be to optimize and finalize the fully field-deployable device, assay, and software suite required to conduct the assay in an offline, field hospital scenario. This will be accomplished through additional in vitro testing and equipment acquisition, and data/samples sequenced on this platform will assess the validated characteristics of the prototype (including stability) that can be used for FDA approval. The Milestones for this Phase II project will be met when the field deployed unit is capable of performing every step of the Phase I assay with no refrigeration and minimal equipment that can be fit in an approximate 5’x3’ footprint. This optimized prototype will not utilize any internet connectivity and will take approximately 8 hours from initiation to completion. This is a drastic reduction of current, culture-based methods, that can take several days to weeks, for diagnosis, and often require large facilities and highly capable personnel. We anticipate a reduced and easy to understand clinical report, an LDT, and an FDA data collection process and validation that can be used for future work, clients, and genomics research for pathogen identification.