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

通过智能手机对心脏生物标志物进行等离子体增强即时检测

• 批准号: 10570910
• 负责人: Maiken Mikkelsen
• 金额: $ 66.58万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570910
• 关键词: Acute; Adsorption; Antibodies; Architecture; Biological Assay; Biological Markers; Blood; Capillarity; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cellular Phone; Cessation of life; Chest Pain; Chickens; Clinical; Clinical Medicine; Clinical Research; Congestive Heart Failure; Custom; Detection; Development; Devices; Diagnosis; Drops; Electromagnetic Fields; Electrons; Engineering; Enzyme-Linked Immunosorbent Assay; Film; Fluorescence; Generations; Geometry; Heart Diseases; Home; Hospitals; Human; Image; Imaging Device; Immunoassay; Individual; Infrastructure; Inpatients; Laboratories; Metals; Microfluidic Microchips; Microfluidics; Monitor; Myocardial Infarction; Nanostructures; Noise; Output; Patients; Performance; Play; Primary Prevention; Printing; Protein Microchips; Proteins; Reader; Reagent; Refrigeration; Research; Role; Sampling; Secondary Prevention; Serum; Signal Transduction; Silver; Spottings; Surface; Techniques; Telephone; Testing; Thick; United States; University Hospitals; Variant; absorption; antibody detection; clinical decision-making; cost effective; cross reactivity; design; detection limit; detector; expectation; fabrication; fetal bovine serum; fluorescence imaging; fluorophore; innovation; insight; nano; nanoscale; novel; plasmonics; point of care; point of care testing; point-of-care detection; portability; pro-brain natriuretic peptide (1-76); risk stratification; self testing; stem; technological innovation; treatment response; user-friendly; virtual; wireless transmission

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.

抽象的 心脏病是美国死亡的主要原因，造成超过630,000人死亡 心血管生物标志物在诊断，风险分层和治疗中起着基本作用 各种各样的心血管疾病。目前有几种测试设备和技术 量化心脏生物标志物的水平；但是，这些测定专门针对临床环境设计 并设计用于检测单个生物标志物。该项目的目的是开发 喷墨印刷，塑料增强的单步，多重护理测试，以定量键 心血管生物标志物，特别是NT-Probnp，CTNT和CRP。拟议的生物标志物是 多种心血管疾病的诊断和管理，包括急性胸痛 以及心肌梗死，急性和慢性心力衰竭以及原发性和次要预防。 该项目的技术创新从两个最先进平台的集成（1）。 步骤，多路复用点蛋白微阵列具有高灵敏度和低背景噪声和2） 等离子体纳米结构显示了四个数量级荧光增强功能 - 以实现 使用基于手机的荧光成像设备在医院或家庭中的荧光成像从一滴血液中进行测试 环境。在这个项目中，将优化塑料增强测定的所有组件，这是一种智能手机 - 兼容的多重芯片将集成到被动的，毛细管驱动的微流体设备及其数字 - 使用档案患者样品评估了候选物。最后，我们将进行一项临床研究 仅从一滴血液中量化NTPRO-BNP，CTNT和CRP的水平 90名患者采用了我们的护理点测定平台，将与商业的结果进行比较 杜克大学医院的免疫测定分析仪。预计拟议的项目将导致 廉价的护理点心脏面板将对诊断和治疗产生重大影响 心血管疾病，因为对多种生物标志物的检测提供了对基础的更深入的见解 病理生理阶段和家里患者进行自我测试，可以更仔细地监测治疗 回复。此外，该测定平台可以针对可用于可用抗体试剂的任何分析物， 使其广泛适用于大多数（如果不是全部）临床医学中的免疫测定目标。