Graphene enabled low-noise surface chemistry for multiplexed sepsis biomarker detection in whole blood

Affinity-based electrochemical sensors offer a potentially valuable approach for point-of-care diagnostics applications, and for detection of diseases, such as sepsis, that require simultaneous detection of multiple biomarkers, but their development has been hampered due to biological fouling and electrochemical noise. Here we describe an electrochemical sensor platform that enables detection of multiple sepsis biomarkers simultaneously by incorporating a nanocomposite coating composed of crosslinked bovine serum albumin containing a network of reduced graphene oxide nanoparticles that prevents biofouling while maintaining electroconductivity. Using nanocomposite coated planar gold electrodes, a sensitive procalcitonin sensor was constructed and validated in undiluted serum, which produced an excellent correlation with a conventional ELISA (adjusted r2 = 0.95) using clinical samples. A single multiplexed platform containing sensors for three different sepsis biomarkers —procalcitonin, C-reactive protein, and pathogen-associated molecular patterns (PAMPs) — also was developed, which exhibited specific responses within the clinically significant range without any cross-reactivity. This platform enables sensitive simultaneous electrochemical detection of multiple analytes in human whole blood, and it can be applied to detect any target analyte with an appropriate antibody pair. Thus, this nanocomposite-enabled electrochemical sensor platform may offer a potentially valuable tool for development of a wide range of clinical point-of-care diagnostics.