Development of a Piezoelectric Immunosensor to Rapidly Measure Prohibitin-1 as a Prognostic Biomarker for Sepsis and Other Serious Infectious Diseases

Sepsis is a life-threatening condition and the leading cause of mortality worldwide, particularly when an affected patient develops multiple organ dysfunction syndrome (MODS), a serious complication defined as progressive and potentially irreversible dysfunction in two or more organ systems. Clinical and experimental studies strongly suggest that patient outcomes with sepsis would improve if the risk for MODS and mortality could be identified in the first few hours after the onset of symptoms. We present an approach leveraging quartz crystal microbalance with dissipation monitoring (QCM-D) technology for rapid (∼30 min) detection of prohibitin-1 (PHB1), a protein with pleiotropic biological function that dramatically increases in blood during the acute phase of an infection. The feasibility of detection and reproducible quantification of recombinant PHB1 in physiological buffered conditions is described. Sensitivity and detection limit for the third overtone (12.19 Hz μg^-1 mL and 59.06 ng/mL, respectively) were determined to be within the physiological range, highlighting the QCM-D immunosensor's potential for applied use in plasma samples. Importantly, there was strong concordance between PHB1 concentration curves generated using the QCM-D immunosensor and those from enzyme-linked immunosorbent assay (ELISA), which typically requires 36 h. Our findings illustrate a feasible and reproducible method to detect a bloodborne protein using immunosensor technology that has the potential to improve patient outcomes in sepsis and other serious infectious diseases.