Parallel recording of neurotransmitters release from chromaffin cells using a 10×10 CMOS IC potentiostat array with on-chip working electrodes.
Neurotransmitter release is modulated by many drugs and molecular manipulations. We present an active CMOS-based electrochemical biosensor array with high throughput capability (100 electrodes) for on-chip amperometric measurement of neurotransmitter release. The high-throughput of the biosensor array will accelerate the data collection needed to determine statistical significance of changes produced under varying conditions, from several weeks to a few hours. The biosensor is designed and fabricated using a combination of CMOS integrated circuit (IC) technology and a photolithography process to incorporate platinum working electrodes on-chip. We demonstrate the operation of an electrode array with integrated high-gain potentiostats and output time-division multiplexing with minimum dead time for readout. The on-chip working electrodes are patterned by conformal deposition of Pt and lift-off photolithography. The conformal deposition method protects the underlying electronic circuits from contact with the electrolyte that covers the electrode array during measurement. The biosensor was validated by simultaneous measurement of amperometric currents from 100 electrodes in response to dopamine injection, which revealed the time course of dopamine diffusion along the surface of the biosensor array. The biosensor simultaneously recorded neurotransmitter release successfully from multiple individual living chromaffin cells. The biosensor was capable of resolving small and fast amperometric spikes reporting release from individual vesicle secretions. We anticipate that this device will accelerate the characterization of the modulation of neurotransmitter secretion from neuronal and endocrine cells by pharmacological and molecular manipulations of the cells.
School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853, USA. bnk25@cornell.edu
Brian N
BN
Kim
Adam D
AD
Herbst
Sung J
SJ
Kim
Bradley A
BA
Minch
Manfred
M
Lindau
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D003217:Conductometry / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D046228:Microarray Analysis / Q000295:instrumentation*; D008839:Microelectrodes; D018377:Neurotransmitter Agents / Q000032:analysis / Q000096:biosynthesis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014173:Transistors, Electronic
D018377:Neurotransmitter Agents