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

抽象的。在美国，每年约有170万成年人感染败血症，导致超过 每年有27万人死亡。如果脓毒症不能及早诊断和治疗，不仅会导致高发病率 和死亡率，但也构成了医疗保健系统的主要负担，因为败血症患者通常 因延长住院时间住院，很少在2-3周前出院。为了应对这种健康 问题是，NAMI诊断公司与德克萨斯理工大学合作开发了一种基于纳米颗粒的 电化学检测试剂盒可在全身炎症反应进展之前确定脓毒症的早期迹象 综合征(SIRS)和其他严重并发症。我们的技术特点包括高灵敏度、快速 周转结果、多路传输能力、定量测量、成本效益和可移植性。这个 建议的研究设计改编自以前应用于 检测食品病原体，如大肠杆菌O157：H7和沙门氏菌，但使用败血症特异性细胞标记物 我们的项目合作者在微流控平台上进行了验证。具体来说，我们测试的关键组件 平台包括功能化磁性颗粒，用于分离针对脓毒症和 采用不同类型的修饰金属硫化物纳米颗粒进行鉴定和检测，产生了近 实时诊断答案，支持及时的医疗干预，并允许长期监控 脓毒症幸存者防止脓毒症复发。建议的工作流程很简单，只需要最少的工作 基础设施和劳动力，并且可以很容易地在护理点和资源有限的环境中实施。这个 NAMI诊断公司即将进行的第一阶段项目的目标将是展示敏感和 同时检测上调CD64和CD69表达的白细胞作为概念验证 早期准确的脓毒症诊断。为了验证严重疾病的预后价值， 本研究还将探讨脓毒症患者的检测结果和临床结果。

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.