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

脓毒症，全身炎症和器官衰竭， 对感染的反应不平衡，造成巨大的人力和保健费用。在全球范围内， 每年有3 000多万人受到影响，其中至少四分之一的人将死亡。的 后遗症包括身体、精神和心理残疾。目前，没有具体的 治疗是存在的。对于癌症患者，基于分子生物学的个性化治疗 肿瘤的特征是一个很好的实践。迫切需要对以下方面采取同样的行动： 败血症我们已经确定了DNA上的标签（DNA甲基化标记），可以将脓毒症与 非脓毒症患者，不良结局（死亡和器官衰竭）的可能性和对 治疗（血压药物）。与此同时，我们的合作伙伴开发了 这是一种即时检测设备，它使用创新的微流体方法从 全血。我们建议采用这种技术来开发一种原型， 使用全血自动测量患者的DNA标记;测试我们的设备 库DNA和全血样本;使用预测建模来整合临床和 分子数据，以验证结果预测和对治疗的反应， 队列;并在一个前瞻性的测试我们的原型和精密标记的性能 现实世界的情况。技术和生物标志物检测方法都从未 曾因败血症接受过治疗这项提案汇集了生物工程师，健康研究， 科学家、生物信息学家、医生和临床生物化学家。成功完成将 提供一种采用低成本工业可制造聚合物的芯片实验室技术 微流控设备由先进的专利离心微流控技术提供动力， 有望成为整合和部署基因组知识的颠覆性创新 将影响临床实践和危重病人护理的实用设备。

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.