Point-of-Care Microfluidic Biochip for Biomarkers Monitoring for Contributing in Early Sepsis Diagnosis

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Principal Investigator/Program Director (Last, first, middle): Bashir, Rashid Project Summary: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis- 3 definition), is the leading cause of death and most expensive condition in hospitals. Annually, > 30 million people affected worldwide, with at least 1.7 million adults developing sepsis (nearly 270K die) at a cost of $24 billion per year in the U.S. Patients diagnosed with sepsis and no ongoing sign of organ failure have about a 15-30% chance of death. However, the mortality rate can increase up to 40-60% for severe sepsis or septic shock patients. One in three patients who die in a hospital have sepsis. One major factor in these rising mortality rates is the inability to accurately and quickly diagnose potentially septic patients. Likewise, sepsis is a leading cause of hospital readmission (higher proportion than hospitalizations for heart attack, heart failure, COPD, and pneumonia in the U.S.). EDs and ICUs rely on monitoring extremely non-specific parameters (e.g. fever, low blood pressure, increased heart rate) to initiate a clinical diagnosis and begin treatment. These crude indicators cause doctors to mistake early stage sepsis with several other diseases. A positive diagnose of early onset sepsis is critical because mortality increases with delays in treatment. Survival rates have been reported to drop by 7.6% every hour that the proper antibiotics are not administered, and these delays compound unnecessary hospital costs. Over the last 30 years, clinics have used different criteria such as SIRS, LODS and SOFA or qSOFA as screening tools to assess the severity of organ dysfunction in a potentially septic patient. Common factors among these criteria are non-specificity and very high false positive rates. For patients with positive criteria, the final diagnostic test is a blood culture that may take up to 5 day for a negative result. Likewise, blood culture has a very high false negative rate (> 60%) and does not work for fastidious pathogens such as Chlamydia pneumoniae. More importantly, blood culture cannot be a gold standard method for sepsis diagnosis. This technique only detects the presence of bacteria in the bloodstream (bacteremia), which does not necessarily indicate illness. Many non-bacteremic infections can also cause life-threatening sepsis. In order to improve the accuracy and sensitivity of sepsis diagnosis, the Sepsis-3 definition underscores the requirements for both pathogen detection and information about the personalized state of the immune system of the patient. Therefore, we propose to focus our efforts on monitoring selective biomarkers of this immune response. However, no single, or even a combination of biomarkers has been validated for the diagnosis of sepsis. Because no single biomarker is specific enough to predict sepsis, we propose to develop a point-of-care microfluidic biochip for measuring cell-surface and plasma-proteins biomarkers that will be used for contributing in early sepsis diagnosis. The microfluidic biochip will provide a complete white blood cell count (WBC), as well as quantification of CD64 expression on neutrophil (nCD64), procalcitonin (PCT), C-Reactive Protein (CRP) and Interleukin 6 (IL-6). Multiple studies have demonstrated the high sensitivity of these biomarkers to sepsis. The proposed device will combine for the first time the analysis of cell-surface proteins and plasma proteins biomarkers from the same sample of blood. Such a device, combined with the routinely test performed in the hospitals, could significantly accelerate the diagnosis of sepsis and as consequence the clinical decision, to provide the correct treatment to the patients.