Rapid Microfluidic-Based Point-of-Care Assessment of Epigenetic Marks for Diagnosis, Prognosis and Response to Therapy in Critical Illness

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Sepsis, whole body inflammation and organ failure triggered by an overwhelming andunbalanced response to infection, incurs enormous human and health care costs. Globally,over 30 million people are affected each year, at least a quarter of whom will die. Thesequelae include physical, mental, and psychological disability. Currently, no specifictreatments exist. For cancer patients, personalizing treatment on the basis of molecularcharacteristics of a tumor is simply good practice. There is an urgent need to do the same forsepsis. We have identified tags on DNA (DNA methylation marks) that can classify septic vs.non-septic patients, the likelihood of poor outcomes (death and organ failure) and response totherapy (blood pressure medications). In parallel, our partners have developed and patenteda point-of-care device that uses an innovative microfluidic approach to isolate DNA fromwhole blood. We propose to adapt this technology to develop a prototype able to performautomated measurements of DNA marks from patients using whole blood; to test our deviceon banked DNA and whole blood samples; to use predictive modeling to integrate clinical andmolecular data to validate outcome prediction and response to therapy in an independentcohort; and to test the performance of our prototype and precision marks prospectively in areal-world situation. Both the technology and biomarker detection approaches have neverbeen tried for sepsis before. This proposal brings together bioengineers, health researchscientists, bioinformaticians, physicians and clinical biochemists. Successful completion willprovide a Lab-on-chip technology employing low-cost industrially manufacturable polymermicrofluidic devices powered by an advanced patented centrifugal microfluidic technology thatpromises to be a disruptive innovation in the way to integrate and deploy genomic knowledgepractical devices that will impact clinical practices and the care of the critically ill.