Nanomonitors: A Proteomics Platform for early and rapid disease diagnostics

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Title: Nanomonitors: A Proteomics Platform for Early and Rapid Disease Diagnostics

Authors: Gaurav Chatterjee and Shalini Prasad,
School of Electrical, Computer and Energy Engineering, Arizona State University

Abstract:  Recent proteomics research has elucidated many new biomarkers that have the potential to greatly improve disease diagnosis. Combination of multiple biomarkers has been determined to provide the information necessary for robust diagnosis of a disease in any person within a population. In addition, detection of biomarkers associated with different stages of disease pathogenesis could further facilitate early detection. The current analytical tools for the protein biomarker detection need expensive instrumentation, advanced expertise, is time consuming and therefore not practical for routine screening from human samples in a non-clinical setting. We have developed a novel ultrasensitive diagnostic platform called ‘NanoMonitor’ to enable rapid, label-free detection of protein biomarkers which can be applied to both clinical as well as non-clinical settings. The technology is based on electrochemical impedance spectroscopy where capacitance changes are measured at the electrical double layer interface as a result of binding of protein molecules on to the diagnostics platform.

The NanoMonitor leverages multi scale design and integrates nanoporous membranes on to microelectronic platform to generate a miniaturized multi-well plate similar to the ELISA plate. The miniaturized NanoMonitor platform leverages the biological principle of macromolecular crowding towards achieving signal enhancement in detecting ultra-low concentrations of biomolecules from clinically relevant samples. The NanoMonitor diagnostics platform comprises of a printed circuit board with array of electrodes forming multiple sensor spots. Each sensor spot is overlaid with a nanoporous alumina membrane that forms a high density of nanowells. Protein receptors are immobilized in to the nanowells using robust linker chemistries. When specific antigens from a test sample bind to proteins in the nanowells; it produces a perturbation to the electrical double layer at the solid/liquid interface at the base of each nanowell. This perturbation results in a change in the impedance of the double layer which is dominated by the capacitance changes within the electrical double layer and the interaction of the antigens from the test samples. We have incorporated the techniques of miniaturization, automation, packaging and assembly in producing hand-held NanoMonitor diagnostics platforms. We have successfully used this platform in detecting changes in protein glycosylation that are biomarkers for the early diagnosis of cancer and other diseases. We have demonstrated lower pg/ml sensitivity in detection with specificity comparable to ELISA and microarray techniques. We have also used this platform in detecting early diagnostic markers for Alzheimer’s disease.