POINT OF CARE ACUTE KIDNEY INJURY DETECTION USING MOLECULARLY IMPRINTED GOLD NANOCAGES

使用分子印迹金纳米笼进行护理点急性肾损伤检测

• 批准号: 8824216
• 负责人: Srikanth Singamaneni
• 金额: $ 20.56万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8824216
• 关键词: Accident and Emergency department; Acute Renal Failure with Renal Papillary Necrosis; Antibodies; Binding; Biological Assay; Biological Markers; Biosensor; Blood; Cessation of life; Chemicals; Chemistry; Chronic Kidney Failure; Clinical; Detection; Diagnosis; Dialysis procedure; Differential Diagnosis; Dimensions; Early Diagnosis; Elements; Enzyme-Linked Immunosorbent Assay; Excretory function; Fatty Acid-Binding Protein 1; Gelatinase A; Gold; Hand; Hospitals; Hydration status; Immune; Incidence; Intensive Care Units; Interleukin-18; Investigation; Kidney; Label; Length of Stay; Life; Link; Liquid substance; Marketing; Measurement; Measures; Metals; Methods; Molecular; Monitor; Nanosphere; Nanostructures; Paper; Patients; Physiological; Plasma; Procedures; Proteins; Refractive Indices; Refrigeration; Research; Resources; Risk; Sampling; Sensitivity and Specificity; Shapes; Specificity; Speed; Staging; Surface; Technology; Testing; Time; Translations; United States; Urine; Validation; base; biochip; cost; design; diagnostic accuracy; imprint; innovation; nanocage; nanorod; neutrophil; novel; outcome forecast; plasmonics; point of care; post gamma-globulins; public health relevance; rapid detection; rapid diagnosis; rat KIM-1 protein; screening; urinary

DESCRIPTION (provided by applicant): The primary objective of the project is to design and develop a novel point-of-care assay for rapid detection of three protein biomarkers, namely, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and fatty acid binding protein 1 (FABP1), for rapid diagnosis and prognosis of acute kidney injury (AKI). The incidence of dialysis-requiring AKI, which involves rapid loss of kidney's excretory function, has risen about 10% per year in the United States between 2000 and 2009. During the same time period, the number of deaths associated with dialysis-requiring AKI has more than doubled. In the United States, about 1.2 million patients are diagnosed with AKI and about 0.3 million die of AKI each year. The average length of stay in an ICU is increased by 3.5 days adding about 9 billion dollars in cost. Thus, the measurement of plasma and/or urine biomarker levels is of huge clinical importance. Various proteins such as NGAL, interleukin-18 (IL-18), KIM-1, cystatin C (CysC), and liver fatty acid-binding protein (FABP1) have been extensively studied as potential biomarkers for AKI. For example, during AKI, urinary NGAL levels are increased by several log-orders of magnitude while plasma levels increase 5 to10-fold. It has been recognized that plasma and urine levels of NGAL alone provide early detection and prognosis of patients at risk of developing AKI and support the differential diagnosis of established AKI. Current commercial assays are primarily immune-based and require clinical lab settings to measure protein biomarker concentration in physiological fluids, which not only makes the assay expensive but also results in significant delay. We propose to develop a novel point-of-care assay based on plasmonic nanotransducers and artificial antibodies for the detection of protein biomarkers at physiological and pathological concentrations. Specifically, we will investigate gold nanocages as plasmonic nanotransducers and molecularly imprinted artificial antibodies as recognition elements for selective capture of biomarkers and their quantification by simple hand-held vis-NIR spectrometer. Apart from significantly lowering the cost, the envisioned plasmonic biosensor based on artificial antibodies offers excellent chemical and temporal stability, obviating the need for special storage conditions (e.g., refrigeration, hydration) of and enabling point-of-care biomarker quantification even in resource-limited settings. Once this early, innovative and exploratory research is completed, we will have laid the groundwork and partially developed highly sensitive point-of-care plasmonic biosensor for the detection of protein biomarkers in urine and/or plasma, which enables rapid screening, early detection, diagnosis and prognosis of AKI. The stage would be set for the next steps, of developing plasmonic paper-based biochips for monitoring multiple biomarkers from urine, which enhances the accuracy of diagnosis and prognosis of various pathological conditions.

描述（由申请人提供）：该项目的主要目的是设计和开发一种新型床旁检测方法，用于快速检测三种蛋白质生物标志物，即中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肾损伤分子-1（KIM-1）和脂肪酸结合蛋白1（FABP 1），用于急性肾损伤（阿基）的快速诊断和预后。2000年至2009年，美国需要透析的阿基（涉及肾脏排泄功能的快速丧失）的发病率每年上升约10%。在同一时期，与需要透析的阿基相关的死亡人数增加了一倍多。在美国，每年约有120万患者被诊断患有阿基，约有30万人死于阿基。ICU的平均住院时间增加了3.5天，增加了约90亿美元的成本。因此，血浆和/或尿液生物标志物水平的测量具有巨大的临床重要性。已广泛研究了各种蛋白质，如NGAL、白细胞介素-18（IL-18）、KIM-1、胱抑素C（CysC）和肝脂肪酸结合蛋白（FABP 1）作为阿基的潜在生物标志物。例如，在阿基期间，尿NGAL水平增加几个对数数量级，而血浆水平增加5至10倍。已经认识到，单独的NGAL的血浆和尿液水平提供处于发展阿基的风险中的患者的早期检测和预后，并且支持已确定的阿基的鉴别诊断。目前的商业测定主要是基于免疫的，并且需要临床实验室设置来测量生理流体中的蛋白质生物标志物浓度，这不仅使得测定昂贵，而且导致显著延迟。我们建议开发一种基于等离子体纳米换能器和人工抗体的新型即时检测方法，用于检测生理和病理浓度的蛋白质生物标志物。具体而言，我们将研究金纳米笼作为等离子体纳米换能器和分子印迹人工抗体作为识别元素，用于选择性捕获生物标志物及其定量，通过简单的手持可见-近红外光谱仪。除了显著降低成本之外，设想的基于人工抗体的等离子体生物传感器提供了优异的化学和时间稳定性，避免了对特殊储存条件（例如，冷冻、水合），并且即使在资源有限的环境中也能够进行即时生物标志物定量。一旦这项早期的创新性和探索性研究完成，我们将奠定基础并部分开发出用于检测尿液和/或血浆中蛋白质生物标志物的高灵敏度床旁等离子体生物传感器，从而实现阿基的快速筛查，早期检测，诊断和预后。该阶段将为下一步做好准备，即开发用于监测尿液中多种生物标志物的等离子体纸基生物芯片，这将提高各种病理状况的诊断和预后的准确性。