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.

[1]  D. Cumming,et al.  Design of a single-chip pH sensor using a conventional 0.6-/spl mu/m CMOS process , 2004, IEEE Sensors Journal.

[2]  P Bergveld,et al.  Development of an ion-sensitive solid-state device for neurophysiological measurements. , 1970, IEEE transactions on bio-medical engineering.

[3]  B Wolf,et al.  Non-invasive measurement of cell membrane associated proton gradients by ion-sensitive field effect transistor arrays for microphysiological and bioelectronical applications. , 2000, Biosensors & bioelectronics.

[4]  Andreas Hierlemann,et al.  An 11k-Electrode 126-Channel High-Density Microelectrode Array to Interact with Electrogenic Cells , 2007, 2007 IEEE International Solid-State Circuits Conference. Digest of Technical Papers.

[5]  V. Rocher,et al.  An Oxynitride ISFET Modified for Working in a Differential Mode for pH Detection , 1994 .

[6]  J. Meindl,et al.  Ion-sensing devices with silicon nitride and borosilicate glass insulators , 1987, IEEE Transactions on Electron Devices.

[7]  D. Cumming,et al.  Design of a Single-Chip pH Sensor Using a Conventional 0 . 6-m CMOS Process , 2004 .

[8]  K. Wise,et al.  An Integrated Field-Effect Electrode for Biopotential Recording , 1974 .

[9]  Yael Nemirovsky,et al.  Ion-sensitive field-effect transistors in standard CMOS fabricated by post processing , 2002 .

[10]  J. W. Parce,et al.  Biosensors based on the energy metabolism of living cells: the physical chemistry and cell biology of extracellular acidification. , 1992, Biosensors & bioelectronics.

[11]  Phillip E Allen,et al.  CMOS Analog Circuit Design , 1987 .

[12]  Y. Nemirovsky,et al.  1/f noise in ion sensitive field effect transistors from subthreshold to saturation , 1999 .

[13]  D. Schmitt-Landsiedel,et al.  A 128 /spl times/ 128 CMOS bio-sensor array for extracellular recording of neural activity , 2003, 2003 IEEE International Solid-State Circuits Conference, 2003. Digest of Technical Papers. ISSCC..

[14]  R. Ferretti,et al.  pH sensor based on differential measurements on one pH-FET chip , 1991 .

[15]  B. Eversmann,et al.  A 128 × 128 CMOS bio-sensor array for extracellular recording of neural activity , 2003 .

[16]  A. Errachid,et al.  ION-SENSITIVE FIELD-EFFECT TRANSISTORS FABRICATED IN A COMMERCIAL CMOS TECHNOLOGY , 1999 .