A CMOS-based microelectrode array for interaction with neuronal cultures.
We report on the system integration of a CMOS chip that is capable of bidirectionally communicating (stimulation and recording) with electrogenic cells such as neurons or cardiomyocytes and that is targeted at investigating electrical signal propagation within cellular networks in vitro. The overall system consists of three major subunits: first, the core component is a 6.5 mm x 6.5 mm CMOS chip, on top of which the cells are cultured. It features 128 bidirectional electrodes, each equipped with dedicated analog filters and amplification stages and a stimulation buffer. The electrodes are sampled at 20 kHz with 8-bit resolution. The measured input-referred circuitry noise is 5.9 microV root mean square (10 Hz to 100 kHz), which allows to reliably detect the cell signals ranging from 1 mVpp down to 40 microVpp. Additionally, temperature sensors, a digital-to-analog converter for stimulation, and a digital interface for data transmission are integrated. Second, there is a reconfigurable logic device, which provides chip control, event detection, data buffering and an USB interface, capable of processing the 2.56 million samples per second. The third element includes software that is running on a standard PC performing data capturing, processing, and visualization. Experiments involving the stimulation of neurons with two different spatio-temporal patterns and the recording of the triggered spiking activity have been carried out. The response patterns have been successfully classified (83% correct) with respect to the different stimulation patterns. The advantages over current microelectrode arrays, as has been demonstrated in the experiments, include the capability to stimulate (voltage stimulation, 8 bit, 60 kHz) spatio-temporal patterns on arbitrary sets of electrodes and the fast stimulation reset mechanism that allows to record neuronal signals on a stimulating electrode 5 ms after stimulation (instantaneously on all other electrodes). Other advantages of the overall system include the small number of needed electrical connections due to the digital interface and the short latency time that allows to initiate a stimulation less than 2 ms after the detection of an action potential in closed-loop configurations.
Hafizovic
S
S
Physical Electronics Laboratory, ETH Zurich, Wolfgang-Pauli Str. 16, 8093 Zurich, Switzerland. sadik.hafizovic@ethz.ch
Heer
F
F
Ugniwenko
T
T
Frey
U
U
Blau
A
A
Ziegler
C
C
Hierlemann
A
A
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D004582:Electronics, Medical / Q000295:instrumentation* / Q000379:methods; D004594:Electrophysiology / Q000295:instrumentation* / Q000379:methods; D008839:Microelectrodes / Q000592:standards / Q000639:trends; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009482:Neurophysiology / Q000295:instrumentation* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation; D012984:Software