Development of A Novel Nanoparticle Biosensor for Rapid, Point-of-Care Sepsis Diagnosis and Risk Assessment

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Abstract. In the United States, about 1.7 million adults affected by sepsis annually, which leads to more than 270,000 deaths per year. If sepsis cannot be diagnosed and treated early, it not only causes high morbidity and mortality rates, but also poses a major burden to the healthcare system since septic patients are generally hospitalized for extended stay and rarely discharged from ICU before 2-3 weeks. In response to this health problem, NaMi Diagnostics collaborates with Texas Tech University to develop a nanoparticle-based electrochemical testing kit to pinpoint early sign of sepsis before it progresses systemic inflammatory response syndrome (SIRS) and other serious complications. Our technology features include high sensitivity, fast turnaround results, multiplexing capability, quantitative measurement, cost-efficiency, and portability. The proposed study design is adapted from a prototype sensor architecture that has been previously applied to detect food pathogens such as E. coli O157:H7 and Salmonella yet utilizes sepsis-specific cell markers validated in a microfluidic platform by our project collaborator. Specifically, the key component of our testing platform includes functionalized magnetic particles for isolation of target immune cells specific to sepsis and employs different types of modified metal sulfide nanoparticles for identification and detection, producing nearly real-time diagnostic answers, enabling prompt medical intervention, and allowing long-term monitoring of sepsis survivors to prevent the recurrence of sepsis. The proposed workflow is simple, requiring minimal infrastructure and labor, and can be readily implemented in point-of-care and resource-limited settings. The goal of upcoming Phase I project at NaMi Diagnostics will be demonstrating the feasibility for sensitive and simultaneous detection of leukocytes with upregulated CD64 and CD69 expression as proof-of-concept for early and accurate sepsis diagnosis. To validate the prognostic value for severe disease, correlation between testing result and clinical outcome in sepsis patients will be also explored in this study.