Lateral Flow Based Nanoelectronic Sensing Array for Detection of Chronic Cerebral Hypoperfusion Biomarkers

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Ability to understand and diagnose disease has experienced considerable progress over the past decades due to the advances in quantifications of molecular biomarkers. Commonly used methods for quantifying protein markers in a clinical setting are immunonephelometry or enzyme-linked immunosorbent assay. Both require a centralized lab to separate whole blood and to perform multiple strict washing steps over several hours. Also, proper infrastructure and a higher degree of training are required, and therefore expensive. This project aims to develop an enabling technology by integrating highly sensitive nanoelectronic immunoassay arrays and lateral flow devices for detecting protein biomarkers with improved diagnostic modalities, capable of using minimal amounts of blood and of returning rapid results. The results from this project can lead to the development of a generic platform for detecting a broad range of molecular biomarkers in assisting earlier disease diagnostics and assessment and monitoring treatment outcome. The applied technologies built from low-cost microfabrication and nanoelectronic detection would significantly reduce the costs for healthcare delivery, and be especially beneficial for regions with limited access to healthcare. Additionally, this project offers opportunities for integrating students' educational experience across interdisciplinary areas, stimulates students' interests in the fields of science, technology, engineering, and mathematics, encourages the participation of underrepresented groups, develops curriculum with new resources, and boosts the biomedical engineering program at West Virginia University.Chronic cerebral hypoperfusion has been considered a significant cause for vascular dementia and Alzheimer's disease associated with reduced blood supply and gradually damaged regions of the brain which are responsible for memory, cognition, and behavior. It is vital to diagnose chronic cerebral hypoperfusion as early as possible because the prompt institution of drugs for increasing cerebral blood flow improves outcomes and delays the onset of advanced dementia. The objective of the research is to develop an integrated multiplexed detection immunoassay for rapid-detecting chronic cerebral hypoperfusion biomarkers. Three research tasks have been proposed to accomplish the study. First, a nanoelectronic immunoassay array will be developed, fabricated, and optimized. The nanoelectronic immunoassay array will allow well regulation of matrix effects of electrolytes and statistical validation of measured results. Second, the nanoelectronic immunoassay array will be integrated with a lateral flow device to realize a portable and capillary driven platform with minimizing the need for off-chip equipment. The integrated device is capable of real-world sample pretreatment, fluid transport, and single biomarker detection. Third, multiplexed detection of biomarkers will be conducted and corroborated by a clinically relevant chronic cerebral hypoperfusion model to determine the most informative combinations of biomarkers. By accomplishing the proposed tasks, the integrated device will allow generation of more meaningful and conclusive information for clinical diagnosis. This project is jointly supported by the Electronics, Photonics and Magnetic Devices (EPMD) Program of the Electrical, Communications and Cyber Systems (ECCS) Division and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.