Sepsis is a devastating cause of morbidity and mortality in intensive care units (ICUs), with estimates of U.S. incidence ranging from 894,000 to 3.1 million cases annually. The heterogeneity of clinical presentation (etiology, patient history, severity, etc.) creates a major challenge for patient management and has significantly complicated development of new therapies, almost all of which have failed to show significant benefit. Because of its high incidence and high cost of treatment, sepsis imposes a heavy financial burden on the health care system. A prognostic test that stratifies diagnosed patients by baseline mortality risk would improve patient care and reduce expenditures by directing resources to those patients most at need. MBio Diagnostics is proposing a SBIR research program in collaboration with the Cincinnati Children's Hospital Medical Center (CCHMC) designed to translate the multi-biomarker pediatric sepsis mortality risk algorithm (PERSEVERE) to the MBio point-of-care platform. The MBio platform is unique in its ability to deliver a panel of quantitative immunoassay results from an easy-to-use, single-use cartridge and portable reader. Under this Phase I SBIR, MBio will establish feasibility of the point-of-care sepsis tool by developing the 5-plex immunoassay on the MBio platform and then validating on a set of clinical samples.
Specific aims are to (1) Deliver a multiplexed sandwich immunoassay on the MBio cartridge and reader platform that combines: heat shock protein 70 (HSPA1B), Matrix metalloproteinase-8 (MMP-8), Interleukin-8 (IL-8), C-C chemokine ligand 3 (CCL3), and Granzyme B (GZMB); (2) Combine the detection antibody combination from Aim 1 into an on-cartridge lyophilized formulation to establish feasibility of a single user interaction assay workflow; and (3) Validate the MBio 5-plex assay by evaluating a set of up to 200 clinical plasma samples sourced from the CCHMC sample repository. MBio has outstanding preliminary data showing that its platform delivers a unique and important assay solution in a format compatible with point-of- care implementation in the ICU. With clinical guidance and the characterized sample repository contributed by program collaborator Dr. Hector Wong, this Phase I research program is an important first step toward a high clinical need tool for sepsis patient management.
The outcome of the proposed research program will be a multi-biomarker assay system that provides rapid classification of mortality risk in pediatric sepsis patients. The same platform can be expanded to include biomarkers for adult sepsis classification. A successful research program will produce a product with broad applicability for acute disease management.
