Towards Novel Graphene-Enabled Diagnostic Assays with Improved Signal-to-Noise Ratio
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Towards Novel Graphene-Enabled Diagnostic Assays with Improved Signal-to-Noise Ratio Savannah J. Afsahi1, Lauren E. Locascio1, Deng Pan1, Yingning Gao1, Amy E. Walker1, Francie E. Barron1, Brett R. Goldsmith1, Mitchell B. Lerner1 1
Nanomedical Diagnostics Inc., 6185 Cornerstone Court East Suite #110, San Diego, CA 92121, U.S.A. ABSTRACT Large numbers of high quality graphene transistors were fabricated by chemical vapor deposition and packaged into a standard electronics assembly, enabling the readout of graphene properties on the benchtop. After chemical functionalization, these sensors demonstrate sensitivity into the pM range to inflammation (IL6) and Zika virus (ZIKV NS1) biomarkers. Signal-to-noise ratio (SNR) of graphene biosensors is over an order of magnitude greater than established diagnostic and biophysical assays, namely ELISA and BLI respectively. High precision measurements of protein kinetics captured using this technology, commercially available as the AGILE R100, are comparable to both clinical diagnostic and state-of-the-art biomolecule characterization tools. These results demonstrate that graphene-based platforms are highly attractive biological sensors for next generation diagnostics. INTRODUCTION Characterization of binding interactions is critical in all stages of clinical and research based disease intervention [1]. Accurate early stage diagnosis can significantly improve patient outcomes and reduce medical costs [2]. The current generation of antibody based diagnostic tools, such as enzyme-linked immunosorbent assays (ELISA), struggle in detecting disease biomarkers due to interfering compounds in biological fluids [3]. Characterization of binding kinetics is also a key metric in development of novel biotherapeutics. Current biophysical assays such as Bio-Layer Interferometry (BLI) are costly and labor intensive [4]. Both clinical and biophysical antibody binding assays demonstrate noise interference at ultralow concentrations, resulting in reduced sensitivity [5]. Noise interference lengthens the time to diagnosis in clinical assays and inhibits characterization of binding kinetics at physiological or therapeutic levels in biophysical analysis [6], thus complicating development of biotherapeutics [7]. Next-generation biosensors must increase their signal-to-noise ratio (SNR) to detect biomarkers in low levels and complex background to drive biotherapeutic advances in clinical and research applications [8,9]. Highly sensitive nanomaterials have been investigated as biosensors for decades. Graphene is a two-dimensional sheet of hexagonally arranged carbon atoms with the highest room temperature carrier mobility of any material and extremely low electronic noise [9]. Every atom in a graphene sheet is in direct contact with its environment, making it an ideal candidate for sensing applications [10]. Graphene has been incorporated into sensors of all varieties, including pressure [11], vapor [8,12], optical [13], and biomolecular sensors [14]. We have demonstrated a commercially mass-produced g
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