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.
We propose to develop a novel point-of-care assay for rapid detection of proteins such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1) and fatty acid binding protein 1 (FABP1), potential biomarkers for AKI. The envisioned novel plasmonic biosensor based on artificial antibodies will be a life-saving technology in that it eliminates the significant time lapse associated with current immune-based technologies, which require clinical settings to quantitatively measure protein biomarker levels in physiological fluids (e.g., urine and plasma), thus enabling clinical practitioners to make critica decisions immediately.
