Plasmonically Enhanced Point-of-care Detection of Cardiac Biomarkers by a Smart Phone

摘要 心脏病是美国的主要死因，导致超过63万人死亡 每年。心血管生物标志物在诊断、危险分层和治疗中起着重要作用 各种心血管疾病的症状目前有几种测试设备和技术， 量化心脏生物标志物的水平;然而，这些检测专为临床环境设计 并被设计用于检测个体生物标志物。该项目的目标是开发一个 喷墨打印、等离子体增强、单步、多重床旁检测，用于量化 心血管生物标志物，特别是NT-proBNP、cTnT和CRP。提出的生物标志物是核心， 诊断和管理广泛的心血管疾病，包括急性胸痛 和心肌梗死、急性和慢性心力衰竭以及一级和二级预防。的 该项目的技术创新源于两个最先进的平台的整合-1）单个 步骤：高灵敏度低背景噪声多路床旁蛋白质微阵列; 2）a 等离子体纳米结构显示出四个数量级的荧光增强， 在医院或家中使用基于手机的荧光成像设备从一滴血中进行检测 设置.在这个项目中，等离子体增强分析的所有组件都将被优化，智能手机- 兼容的多路芯片将被集成到一个被动的，毛细管驱动的微流体设备和它的数字- 使用存档患者样本评价的优效性。最后，我们将进行一项临床研究， 同时定量NTpro-BNP、cTnT和CRP的水平， 90名患者，使用我们的即时检测平台，将其与商业化的 免疫分析仪在杜克大学医院。拟议项目预计将导致 廉价的床旁心脏面板，这将对诊断和治疗产生重大影响， 心血管疾病，因为检测多种生物标志物可以更深入地了解潜在的 病理生理阶段，患者在家中进行自我检测，可以更密切地监测治疗 反应此外，该测定平台可以靶向抗体试剂可用的任何分析物， 使其广泛适用于临床医学中的大多数（如果不是全部）免疫测定靶。

ABSTRACT Heart disease is the leading cause of death in the United States, responsible for more than 630,000 deaths annually. Cardiovascular biomarkers play a fundamental role in the diagnosis, risk stratification, and treatment of a wide variety of cardiovascular disorders. Currently there are several testing devices and techniques to quantify the levels of cardiac biomarkers; however, these assays are designed exclusively for clinical settings and are engineered for the detection of individual biomarkers. The objective of this project is to develop an inkjet-printed, plasmonically enhanced, single-step, multiplex point-of-care test for the quantification of key cardiovascular biomarkers, specifically NT-proBNP, cTnT, and CRP. The proposed biomarkers are central to the diagnosis and management of a wide spectrum of cardiovascular conditions, including acute chest pain and myocardial infarction, acute and chronic heart failure, and primary and secondary prevention. The technological innovation of this project stems from the integration of two state-of-the-art platforms—1) a single step, multiplex point-of-care protein microarray with high sensitivity and low background noise and 2) a plasmonic nanostructure that has shown four orders of magnitude fluorescence enhancements—to enable testing from a drop of blood using a cellphone-based fluorescence imaging device in a hospital or home setting. In this project, all components of the plasmonically enhanced assay will be optimized, a smart phone- compatible multiplex chip will be integrated into a passive, capillarity-driven microfluidics device and its figures- of-merit evaluated using archival patient samples. Finally, we will conduct a clinical study where we will quantify the levels of NTpro-BNP, cTnT, and CRP simultaneously from a single drop of blood in approximately 90 patients, employing our point-of-care assay platform, which will be compared to results from commercial immunoassay analyzers at Duke University Hospital. The proposed project is expected to lead to an inexpensive point-of-care cardiac panel, which will have major impact on the diagnosis and treatment of cardiovascular disorders, as detection of multiple biomarkers provides deeper insight into the underlying pathophysiological stages, and self-testing by patients at home enables closer monitoring of treatment response. Moreover, this assay platform can target any analyte for which antibody reagents are available, making it broadly applicable to most, if not all, immunoassay targets in clinical medicine.