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

败血症，全身炎症和器官衰竭都是由压倒性的

Sepsis, whole body inflammation and organ failure triggered by an overwhelming and unbalanced 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. The sequelae include physical, mental, and psychological disability. Currently, no specific treatments exist. For cancer patients, personalizing treatment on the basis of molecular characteristics of a tumor is simply good practice. There is an urgent need to do the same for sepsis. 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 to therapy (blood pressure medications). In parallel, our partners have developed and patented a point-of-care device that uses an innovative microfluidic approach to isolate DNA from whole blood. We propose to adapt this technology to develop a prototype able to perform automated measurements of DNA marks from patients using whole blood; to test our device on banked DNA and whole blood samples; to use predictive modeling to integrate clinical and molecular data to validate outcome prediction and response to therapy in an independent cohort; and to test the performance of our prototype and precision marks prospectively in a real-world situation. Both the technology and biomarker detection approaches have never been tried for sepsis before. This proposal brings together bioengineers, health research scientists, bioinformaticians, physicians and clinical biochemists. Successful completion will provide a Lab-on-chip technology employing low-cost industrially manufacturable polymer microfluidic devices powered by an advanced patented centrifugal microfluidic technology that promises to be a disruptive innovation in the way to integrate and deploy genomic knowledge practical devices that will impact clinical practices and the care of the critically ill.