Optogenetically engineered cell-based graphene transistor for pharmacodynamic evaluation of anticancer drugs

Rapid and effective cell-based pharmacodynamic evaluation in vitro is crucial for providing an experimental basis for the effectiveness and safety of drugs, and the existing cell-based methods for pharmacodynamics evaluation are usually invasive, dependent on chemical reagents, and/or unable to monitor the process in real time. Here, an optogenetically engineered cell-based graphene transistor is presented as a biosensor for the pharmacodynamic evaluation of anticancer drugs. The biosensor consists of a bare graphene transistor and optogenetically engineered cells as the gate terminal. The photoresponse of engineered cells regulates the output of the transistor and the increment pattern in the transistor output current upon drug action can be used to evaluate the drug efficacy. The results show that the optogenetic engineering of cancer cells does not affect the killing effect of drugs on the cells, and validate the effectiveness of the biosensor. The patterns of photoinduced increments exhibit significant variation with drug action time within 4 h or drug concentration in a range of 1 nM to 1 mM, and can qualitatively characterize the drug efficacy. Furthermore, the drug efficacy can be quantitatively evaluated with an indicator by logarithmically fitting the photoinduced increment patterns. The result also shows that the drain–source voltage significantly affects the evaluation performance and it is necessary to calibrate the voltage value to enhance the performance of the biosensor. The proposed biosensor affords simple, non-destructive, and time-efficient pharmacodynamic evaluation in vitro and is significant to understand the effect and mechanism of drugs in its early development stage. An optogenetically engineered cell-based graphene transistor for real-time pharmacodynamic evaluation has been demonstrated. [Display omitted] •The engineered cell-based graphene transistor is effective for efficacy evaluation.•Optogenetic engineering does not affect the drug resistance of cancer cells.•The biosensor can monitor drug efficacy at different time or drug concentration.•The smaller the quantitative indicator, the more significant the drug effect.•An appropriate drain-source voltage can improve the performance of the biosensor.