Nanomonitors: Electrical Immunoassays for Protein Biomarker Profiling

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1106-PP03-02

Nanomonitors: Electrical Immunoassays for Protein Biomarker Profiling Manish Bothara1, Ravi K Reddy2, Thomas Barrett3, John Carruthers4, and Shalini Prasad2 1 Electrical and Computer Engineering, Portland State University, 1900 SW Fourth Avenue Bldg, Wilsonville, OR, 97201 2 Electrical and Computer Engineering, Portland State University, Portland, OR, 97201 3 Veteran Affairs, Oregon Health and Science University, Portland, OR, 97201 4 Physics Department, Portland State University, Portland, OR, 97201 ABSTRACT The objective of this research is to develop a “point-of-care” device for early disease diagnosis through protein biomarker characterization. Here we present label-free, high sensitivity detection of proteins with the use of electrical immunoassays that we call Nanomonitors. The basis of the detection principle lies in the formation of an electrical double layer and its perturbations caused by proteins trapped in a nanoporous alumina membrane over a microelectrode array platform. High sensitivity and rapid detection of two inflammatory biomarkers, C-reactive protein (CRP) and Myeloperoxidase (MPO) in pure and clinical samples through label-free electrical detection were achieved. The performance metrics achieved by this device makes it suitable as a “lab-on-a-chip” device for protein biomarker profiling and hence early disease diagnosis. INTRODUCTION Recent research in the field of proteomics has revealed that proteins can be utilized as biomarkers that facilitate disease diagnostics [1-4]. New trends have shown that a combination of biomarkers can significantly improve the reliability of disease detection [5-7]. Increased number of biomarkers for a disease can also give access to early detection capability. Fast and multiplexed protein detection techniques with high sensitivity and selectivity are imperative to realize the true potential of biomarkers in healthcare. Conventional immunoassay techniques, including enzyme linked immunosorbent assay (ELISA) have not been able to achieve this goal [6-10]. These techniques have several limitations such as the need for use of labels, time of detection in several hours, large volume of reagents, issues with concurrent multiple protein detection due to the associated expense and cross-reactivity [6-10]. Within the last two decades, label free techniques such as surface plasmon resonance, piezoelectric oscillators and electrochemical devices have been developed with higher speed of detection, lower cost and medium throughput [11-13]. The trend over the past few years is towards high throughput systems with device scaling approaching the molecular level to minimize the current limitations of low signal strength, signal variability due to cross reactivity and non-specific binding, which are not completely addressed by the existing label free techniques. Thus, in the last decade, nanotechnology has been applied to biomolecule detection as it provides the advantages of size matching with proteins thereby resulting in higher sensitivity due to increased signal