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Objective: Closed-loop operation of neuro-electronic systems is desirable for both scientific and clinical (neuroprosthesis) applications. Integrating optical stimulation with recording capability further enhances the selectivity of neural stimulation. We have developed a system enabling the local delivery of optical stimuli and the simultaneous electrical measuring of the neural activities in a closed-loop approach., Approach: The signal analysis is performed online through the implementation of a template matching algorithm. The system performance is demonstrated with the recorded data and in awake rats., Main Results: Specifically, the neural activities are simultaneously recorded, detected, classified online (through spike sorting) from 32 channels, and used to trigger a light emitting diode light source using generated TTL signals., Significance: A total processing time of 8 ms is achieved, suitable for optogenetic studies of brain mechanisms online.

Simultaneous electrical stimulation and recording are used to gain insights into the function of neuronal circuitry. However, artifacts produced by the electrical stimulation pulses prevent the recording of neural responses during, and a short period after, the stimulation duration. In this work, we describe a mixed-signal recording topology with template subtraction for removing the artifact during the stimulation pulse. Emulated artifacts generated from a lumped electrical circuit model and experimental artifacts in cardiac cell cultures are used to evaluate the topology. The simulations show that delays between the emulated artifact and its estimated compensation template represent the largest error source of the analog template subtraction. The quantization error appears like random noise and determines the threshold level for the action potential detection. Simulations show that removal of the artifacts is possible, allowing the detection of action potentials during the stimulation pulsing period, even for high-amplitude saturating artifacts. Measurement results with artifacts elicited in cardiac cell cultures show feasible applications of this topology. The proposed topology therefore promisingly opens up a previously unavailable detection window for improving the analysis of the neuronal activity.

The investigation of single-neuron parameters is of great interest because many aspects in the behavior and communication of neuronal networks still remain unidentified. However, the present available techniques for single-cell measurements are slow and do not allow for a high-throughput approach. We present here a CMOS compatible microelectrode array with 84 electrodes (with diameters ranging from 1.2 to 4.2 μm) that are smaller than the size of cell, thereby supporting single-cell addressability. We show controllable electroporation of a single cell by an underlying electrode while monitoring changes in the intracellular membrane potential. Further, by applying a localized electrical field between two electrodes close to a neuron while recording changes in the intracellular calcium concentration, we demonstrate activation of a single cell (∼270%, DF/F(0)), followed by a network response of the neighboring cells. The technology can be easily scaled up to larger electrode arrays (theoretically up to 137,000 electrodes/mm(2)) with active CMOS electronics integration able to perform high-throughput measurements on single cells., (Copyright © 2010 Elsevier B.V. All rights reserved.)

In this paper, we describe the localized and selective electrical stimulation of single cells using a three-dimensional electrode array. The chip consisted of 84 nail-like electrodes with a stimulation surface of 0.8 microm(2) and interelectrode distances as small as 3 microm. N2A cells were used to compare bipolar stimulation between one electrode in- and one outside the cell on the one hand, and two electrodes in the same cell on the other hand. Selective and localized stimulation of primary embryonic cardiomyocytes showed the possibility to use this chip with excitable cells. The response of the cells to applied electrical fields was monitored using calcium imaging whereas assessment of electroporation was determined following influx of propidium iodide. Arrays of these three-dimensional electrodes could eventually be used as a tool to selectively electroporate the membrane of single cells for genetic manipulation or to obtain electrical access to the inner compartment of the cell.

In this paper, we demonstrate the feasibility of selective extracellular electrical stimulation at the (sub)cellular level in dissociated cultured cells. Using a CMOS-compatible process, we have fabricated an electrode array with sub-micrometer nail probes. Due to their particular configuration, the nails are strongly engulfed by the cellular membrane. By measuring the calcium signals, we found that electrical stimulation via the micronails activates the cell locally, in a dose-dependent manner, with very low applied currents. The results suggest the applicability of the device in pharmacological or signal propagation studies.