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

摘要 心脏病是美国的头号死因，造成超过63万人死亡 每年一次。心血管生物标志物在诊断、风险分层和治疗中起着基础性作用 各种各样的心血管疾病。目前有几种测试设备和技术可用于 量化心脏生物标志物的水平；然而，这些分析是专门为临床环境设计的 并被设计用于检测单个生物标记物。这个项目的目标是开发一种 用于密钥量化的喷墨打印、等离子增强、单步、多路护理点测试 心血管生物标志物，特别是NT-proBNP、cTnT和CRP。拟议的生物标记物是 包括急性胸痛在内的多种心血管疾病的诊断和治疗 以及心肌梗死、急性和慢性心力衰竭，以及一级和二级预防。这个 该项目的技术创新源于两个最先进的平台的集成-1)单个 步骤、高灵敏度、低背景噪声多重护理点蛋白质微阵列和2)a 等离子体纳米结构已显示出四个数量级的荧光增强-使 在医院或家中使用基于手机的荧光成像设备对一滴血进行检测 布景。在这个项目中，等离子体增强检测的所有组件都将得到优化，一款智能手机- 兼容的多路芯片将被集成到一种无源、毛细管驱动的微流体设备中，其数字- 使用存档的患者样本进行优秀性评估。最后，我们将进行一项临床研究，我们将 从一滴血中同时定量NTpro-BNP、cTnT和CRP水平 90名患者，使用我们的护理点分析平台，将其与商业结果进行比较 杜克大学医院的免疫分析仪器。拟议中的项目预计将导致 廉价的护理点心脏面板，这将对诊断和治疗 心血管疾病，因为检测多个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情况 回应。此外，该分析平台可以针对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)免疫分析靶标。

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.