A pH-sensitive field-effect transistor for monitoring of cancer cell external acid environment

The external acid environment of cancer cells is different from that of normal cells, making a profound impact on cancer progression. Here we report a simple poly-l-lysine-modified graphene field-effect transistor (PLL@G-FET) for in situ monitoring of extracellular acidosis around cancer cells. PLL is a well-known material with good biocompatibility and is rich in amino groups that are sensitive to hydrogen ions. After a simple drop-casting of PLL on the reduced graphene oxide (RGO) FET surface, the PLL@G-FET was able to realize the real-time monitoring of the localized pH change of cancer cells after the cancer cells were grown on the device. The PLL@G-FET sensor achieved a Nernstian value of 52.9 mV/pH in phosphate buffer saline from pH 4.0 to 8.0. In addition, the sensor exhibited excellent biocompatibility as well as good anti-interference ability in the cell culture medium. Furthermore, the device was used to real-time monitor the extracellular pH changes of MCF-7 cells under the intervention of different concentrations of drugs. This developed pH-sensitive FET provides a new method to study the extracellular acid environment in situ and helps us to enhance our understanding of cancer cell metabolism. The PLL@G-FET sensor was developed to real-time monitor the extracellular pH of cancer cells in situ. Cells are cultured on the surface of the chip. Cancer cells could change the extracellular pH through glycolysis, and the amino-rich PLL layer is sensitive to such hydrogen ion concentration change. Glucose and drug treatments modulate glycolysis thus altering the pH of the extracellular acid environment. The change of hydrogen ion concentration causes the changes in the surface charge of the graphene on the sensor due to electrostatic gating, resulting in a recordable signal. [Display omitted] •The PLL-functionalized graphene field-effect transistor sensor is established for pH sensing.•The sensor shows a rapid response and high sensitivity toward pH in a real-time manner.•Excellent biocompatibility and stability are realized for cell culture and detection.•The sensor is used to real-time monitor the extracellular pH changes of cancer cells.•The developed pH sensors will help understand the metabolism of cancer, clarify the mechanism of cancer development.