Abstract
Microelectrode arrays (MEAs) for stimulation and signal recording of in vitro cultured neurons are presented. Each MEA is composed of 60 independent electrodes with 59 working ones and one reference one. These electrodes are divided into 30 pairs. Through each pair of electrodes, four independent states can be realized to define the accessing modes of neurons cultured on the surface of the electrodes. A total MEA covers an area of 10 mm×10 mm. MEAs are fabricated in a silicon-based semiconductor process. An implemented MEA is bonded on a specially designed printed-circuit-board (PCB) and surrounded by a culture chamber. An impedance measurement has been made to verify the electrical characteristics of MEAs. The surface was modified to enhance the biocompatibility. A series of PC12 cells culture experiments validates the effectiveness of the modification. An extracellular signal recording experiment with acetylcholine (Ach) as a stimulant has been carried out, and the results show the feasibility of MEAs for extracellular action potential recording. Extracellular electrical stimulation and recording experiments have been carried out too. They indicate that MEAs can be used for extracellular stimulation, recording, simultaneous stimulation and recording, and isolation of PC12 cells network cultured in vitro.
Similar content being viewed by others
References
Hoag H, Neuroengineering: Remot control. Nature, 2003, 423: 796–798
Eversmann B, Jenkner M, Hofmann F, et al. A 128 × 128 CMOS biosensor array for extracellular recording of neural activity. IEEE J Solid State Circuit, 2003, 38: 2306–2317
Heer F, Hafizovic S, Franks W, et al. CMOS microelectrode array for bidirectional interaction with neuronal networks. IEEE J Solid State Circuits, 2006, 41: 1620–1629
Xiang G X, Pan L B, Huang L H, et al. Microelectrode array-based system for neuropharmacological applications with cortical neurons cultured in vitro. Biosens Bioelectron, 2007, 22: 2478–2484
Levitan I B, Kaczmarek L K. The neuron cell and molecular biology. New York: Oxford University Press, 1997. 168–169
Neher E, Sakmann B. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature, 1976, 260: 799–802
Cole K. Dynamic electrical characteristics of the squid axon membrane. Arch Sci Physiol, 1968, 3: 253–258
Thomas C A, Springer P A, Loeb G E, et al. A miniature microelectrode array to monitor the bioelectrical activity of cultured cells. Exp Cell Res, 1972, 74: 61–66
Gross G W, Rieske E, Kreutzberg G W, et al. A new fixedarray multi-microelectrode system designed for long-term monitoring of extracellular single unit neuronal activity in vitro. Neurosci Lett, 1977, 6: 101–105
Pine J. Recording action potentials from cultured neurons with extracellular microcircuit electrodes. J Neurosci Methods, 1980, 2: 19–31
Johnstone A F M, Gross G W, Weiss D G, et al. Microelectrode arrays: A physiologically based neurotoxicity testing platform for the 21st century. NeuroToxicology, 2010, 31: 331–350
Liu Q J, Ye W W, Xiao L D, et al. Extracellular potentials recording in intact olfactory epithelium by microelectrode array for a bioelectronic nose. Biosens Bioelectron, 2010, 25: 2212–2217
Hill A J, Jones N A, Williams C M, et al. Development of multi-electrode array screening for anticonvulsants in acute rat brain slices. J Neurosci Meth, 2010, 185: 246–256
Berdondini L, Massobrio P, Chiappalone M, et al. Extracellular recordings from locally dense microelectrode arrays coupled to dissociated cortical cultures. J Neurosci Meth, 2009, 177: 386–396
Gullo F, Maffezzoli A, Dossi E, et al. Short-latency cross- and autocorrelation identify clusters of interacting cortical neurons recorded from multi-electrode array. J Neurosci Meth, 2009, 181: 186–198
Heer F, Franks W, Blau A, et al. CMOS microelectrode array for the monitoring of electrogenic cells, Biosens Bioelectron, 2004, 20: 358–386
Frey U, Heer F, Pedron R, et al. An 11k-electrode 126-channel high-density microelectrode array to interact with electrogenic cells. In: IEEE International on Solid-State Circuits Conference, San Francisco, 2007, 158–160
Guillemaud R., Bêche J F, Billoint O, et al. A Multi-channel platform for recording and stimulation of large neuronal structures. IRBM, 2009, 30: 226–233
Pan H X, Lü X Y, Wang Z G, et al, Microelectrode array for detecting electrical activities of neuron assemble. J Southeast University (Natural Science Edition) (in Chinese), 2009, 39: 468–472
Chen C H, Yao D J, Tseng S H, et al. Micro-multi-probe electrode array to measure neural signals. Biosens Bioelectron, 2009, 24: 1911–1917
Xu G X, Ye X S, Qin L F, et al. Cell-based biosensors based on light-addressable potentiometric sensors for single cell monitoring. Biosens Bioelectron, 2005, 20: 1757–1763
Yao H, Ding F Z, Liu A S, et al. Detecting physiological parameters of hippocampal neurons cultured in vitro and the monitoring the effect of neurotransmitter. Chin J Appl Physiol, 1994, 10: 183–185
Lin J H, Wu X M, Huang P S, et al. Development of silicon-based microelectrode array, Sci China Ser E-Tech Sci, 2009, 25: 2391–2395
Norlin P, Kindlundh M, Mouroux A, et al. A 32-site neural recording probe fabricated by DRIE of SOI substrates. J Micromech Microeng, 2002, 12: 414–419
Yu H, Cai H, Zhang W, et al. A novel design of multifunctional integrated cell-based biosensors for simultaneously detecting cell acidification and extracellular potential. Biosens Bioelectron, 2009, 24: 1462–1468
Sprössler C, Denyer M, Britland S, et al. Electrical recordings from rat cardiac muscle cells using field-effect transistors, Phys Rev E, 1999, 60: 2171–2176
Yeung C K, Ingebrandt S, Krause M, et al. Validation of the use of field effect transistors for extracellular signal recording in pharmacyological bioassays. J Pharmacol Toxicol Methods, 2001, 45: 207–214
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Pan, H., Lü, X., Wang, Z. et al. Silicon-based microelectrode arrays for stimulation and signal recording of in vitro cultured neurons. Sci. China Inf. Sci. 54, 2199–2208 (2011). https://doi.org/10.1007/s11432-011-4384-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11432-011-4384-7