Optically transparent electrodes for ultrasensitive real-time detection of dopamine in brain-on-a-chip applications

Brain-on-a-chip models are rapidly being adopted in disease modeling and drug discovery, however characterization of the brain model condition often requires both the use of microscopy techniques and evaluation of neuronal activity. Although electrochemical techniques can offer the required selectivity between neuronal subtypes but also sensitivity in simple buffer solutions, a complete loss of electrode functionality is often observed when the brain model has been cultured directly on the electrode material or when recordings are performed in the culture medium. We prepared optically transparent sensors capable of accurately measuring dopamine at nanomolar concentrations in real-time. Furthermore, we displayed the recording of both spon- taneous and stimulated release of dopamine from primary mouse midbrain culture for the first time, as measured inside the culture medium with transparent electrodes. Due to excellent optical transparency, we were able to perform fluorescence microscopy but also live-cell Ca 2+ imaging through the electrodes. Lastly, biocompatibility of the sensors was validated by various different techniques and by using highly sensitive in vitro brain-on-a-chip cultures. • Ultrasensitive detection of dopamine was possible with 90 % transparent electrodes. • Fluorescence and live-cell Ca 2+ imaging were demonstrated through the electrodes. • Biocompatibility was evaluated with all the most-sensitive in vitro brain models. • Single-walled carbon nanotube electrodes were extremely biocompatible. • Dopamine was measured from the ultrasensitive brain-on-a-chip device in real-time.