SBIR-STTR Award

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.

Public Health Relevance Statement:
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.

Project Terms:
Acute Disease; Adult; Algorithms; Antibodies; assay development; base; beta-Chemokines; Biological Assay; Biological Markers; biomarker discovery; biomarker panel; Childhood; Classification; Clinical; clinical application; Clinical Trials; Collaborations; Critical Care; Data; Data Set; design; Detection; Development; Diagnosis; Diagnostic; Direct Expenditure; Disease Management; Etiology; Formulation; Foundations; Freeze Drying; Funding; Grant; Granzyme; Healthcare Systems; Heat-Shock Proteins 70; Heterogeneity; Immunoassay; improved; Incidence; innovation; Intensive Care Units; interest; Interleukin-8; laboratory equipment; Ligands; Liquid substance; Medical center; Medicine; Modeling; Morbidity - disease rate; mortality; Neutrophil Collagenase; novel therapeutics; Outcome; Patient Care; Patient Selection; Patients; Pediatric Hospitals; Performance; Phase; Plasma; point of care; Population; portability; precision medicine; Probability; prognostic; prognostic assays; prognostic tool; programs; Reader; Reagent; Recombinant Proteins; Recording of previous events; Rehydrations; repository; Research; Resources; Risk; Sampling; Seeds; Sepsis; Septic Shock; Serum; Severities; Small Business Innovation Research Grant; Source; Stratification; System; Testing; Time; tool; Translating; Translations; Treatment Cost; Validation

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 to build on a successful Phase I SBIR research program. Working in collaboration with the Cincinnati Children's Hospital Medical Center (CCHMC), the program 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 II 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) Finalize the 5- plex PERSEVERE assay and establish the whole blood assay protocol, delivering 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) Build a analytical performance dataset establishing assay analytical sensitivity, precision, and linearity using CLSI guidelines; (3) Validate the MBio 5-plex assay by evaluating a set of up to 200 clinical serum samples sourced from the CCHMC sample repository; and (4) Run a prospective clinical sample evaluation including sepsis patients in an intended use setting at the CCHMC Pediatric Intensive Care Unit. MBio has outstanding Phase I 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 II research program is an important first step toward a high clinical need tool for sepsis patient management.

Public Health Relevance Statement:
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.

NIH Spending Category:
Bioengineering; Clinical Research; Health Services; Hematology; Infectious Diseases; Pediatric; Precision Medicine; Sepsis

Project Terms:
Acute Disease; Adult; Advocate; Algorithms; Archives; base; Benchmarking; beta-Chemokines; Biological Assay; Biological Markers; biomarker discovery; biomarker validation; Blood specimen; Blood Vessels; Childhood; Classification; Clinical; clinical application; clinical heterogeneity; Clinical Trials; Collaborations; Critical Care; Data; Data Set; design; Development; Diagnosis; Diagnostic; Direct Expenditure; Disease Management; Elements; Etiology; Evaluation; Financial Hardship; Funding; Granzyme; Guidelines; Healthcare Systems; Heat-Shock Proteins 70; Immunoassay; improved; Incidence; Intensive Care Units; interest; Interleukin-8; laboratory equipment; Ligands; Medical center; Medicine; meetings; Modeling; Morbidity - disease rate; mortality; mortality risk; Neutrophil Collagenase; novel therapeutics; Outcome; Paper; Patient Care; Patient Selection; Patients; Pediatric Hospitals; Pediatric Intensive Care Units; Performance; Phase; point of care; Population; portability; precision medicine; Probability; Procedures; prognostic; prognostic assays; prognostic tool; programs; prospective; Protocols documentation; Reader; Readiness; Recombinant Proteins; Recording of previous events; Recovery; repository; Research; Resources; Running; Sampling; Sampling Studies; Sepsis; septic patients; Septic Shock; Serum; Severities; Small Business Innovation Research Grant; Source; Stratification; System; Technology; Testing; Time; tool; Translating; Translations; Treatment Cost; Validation; Venipunctures; Whole Blood