Z. Stromberg, J. Hutchison, T. Alfaro and B. Hess
Pacific Northwest National Laboratory, Washington, United States
Keywords: biosensor, biomimetic, detection, label-free, toxin
Exposure to biological and chemical toxins can disrupt cellular signaling and pose significant threats to military personnel and to public health. Rapid, cost-effective platforms are needed to detect toxin activity and support timely response. Here, we developed a biosensor platform that incorporates membrane targets of interest into a biomimetic electronic device. The device is composed of cell-derived supported lipid bilayers deposited onto an electronic chip. It enables label-free monitoring of cell membrane integrity and target activity by measuring changes in impedance using electrochemical impedance spectroscopy (EIS). To demonstrate toxin detection, we engineered HEK293 cells to overexpress the sodium-potassium ATPase pump, the cellular target of palytoxin. Overexpression was confirmed using fluorescence-activated cell sorting. Following challenge with 3 µM of palytoxin, the biosensor detected impedance changes consistent with the known biological activity of the toxin, including changes associated with channel opening and plugging. These results demonstrate that the device can detect toxin-mediated effects in real time through EIS-based measurements. Overall, this biosensor provides a platform for assessing membrane-active toxins and other biological and chemical threats. Ongoing work has demonstrated proof-of-concept detection of additional agents, including other toxins (α-conotoxin, alpha-hemolysin), pathogens (Vibrio vulnificus, measles virus), and chemicals (fentanyl, verapamil).