A proton camera array technology for direct extracellular ion imaging

The study of cellular function and response is essential for basic research and for applications in the fields of biomedicine and biotechnology. We have developed the first 256-pixel proton camera array for imaging the hydrogen ion activity of cells grown in vitro. The proton camera is an integrated sensor array technology, designed and fabricated in a standard commercial 0.35 mum complementary metal oxide semiconductor (CMOS) process. Each pixel uses a hydrogen ion sensitive field-effect transistor (ISFET) and has an area of 12.8 mum times 12.8 mum, leading to a total on-chip sensing area of 200 mum times 200 mum. After electrical matching, it is found that each ISFET pixel has a threshold voltage of -1 V with a convergence accuracy of less than 10 mV and a measured sensitivity of 46 mV/pH. A cell bioassay is performed to demonstrate that the proton camera array can successfully image changes in extracellular pH.