Nanotextured Material for Applications in CSF Sample Screening and Characterization
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Nanotextured Material for Applications in CSF Sample Screening and Characterization Krishna Vattipalli1, Savindra Brandigampala2, Claire McGraw3, Gaurav Chatterjee3, Srinath Kasturirangan3, Philip Schulz3, Michael Sierks3 and Shalini Prasad1,* 1
Department of Bioengineering, University of Texas at Dallas, Richardson, TX – 75080 Department of Electrical Engineering and Computer Science, Wichita State University, Wichita, KS – 67260 3 Department of Chemical Engineering, Arizona State University, Tempe, AZ - 85287 2
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Corresponding author
ABSTRACT Neurodegenerative disease is primarily characterized by protein misfolding and the resultant protein aggregation. Presence of soluble oligomeric aggregates of proteins including various Aβ and α-syn aggregate species can be correlated to the onset and progression of many neurodegenerative diseases. The ability to detect protein misfolding requires the design of a diagnostics assay the will enable molecular level probing. The use of nanoporous ceramic templates enables size based immobilization of the target proteins and by leveraging the principle of “macromolecular crowding” protein association can be mapped with a high degree of resolution. By tailoring the surface functionalization within nanoporous ceramic templates, macromolecular immobilization can be selectively controlled, which in turn significantly enhances the perturbation to the electrical double layer/. The changes to the electrical double layer are measured with a high degree of sensitivity through impedance spectroscopy. Pre symptomatic diagnosis and distinction between Alzheimer’s and Parkinson’s diseases can be achieved by the specific detection and quantification of levels of each of these different toxic protein species in cerebrospinal fluid (CSF). Detection using highly selective morphology specific reagents in conjunction with the ultrasensitive nanoporous electronic biosensor showed the presence of different protein morphologies in human CSF samples. Detection is primarily achieved by identifying the specific association of the protein with its receptor using electrochemical impedance spectroscopy. Furthermore, we show that these morphology specific reagents can readily classify between post-mortem CSF samples from AD, PD and cognitively normal sources. These studies suggest that detection of specific oligomeric aggregate species holds great promise as sensitive biomarkers for neurodegenerative disease. Key words: Neurodegenerative disease, rapid diagnostics, electrical immunoassay, ceramic nanoporous membranes INTRODUCTION A select subset of neurodegenerative disease namely Alzheimer’s Disease (AD) alone, over 5 million Americans currently are living with the disease with total yearly economic costs of over $170 billion [1]. Diagnosis of this disease along with other neurodegenerative diseases
like Parkinson’s (PD) is challenging as other neurodegenerative diseases such as Lewy are often classified as having Mild-Cognitive Impairment (MCI) [2]. Pathological changes associated with these different
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