Combination of Techniques

While HD-MEAs facilitate the study of network spiking dynamics at single-cell resolution, they currently do not allow for detection of small sub-threshold signals, such as postsynaptic potentials (PSPs). To overcome this limitation, HD-MEAs can be combined with whole-cell patch clamping, which provides the sensitivity to detect even small synaptically evoked currents or potentials.  Extracellular stimulation of neurons through HD-MEA electrodes and recording of evoked postsynaptic responses with a patch-clamp electrode can be used to infer the existence and strength of monosynaptic connections.

Simultaneous investigations of neural circuits by means of HD-MEAs and optical microscopy have also proven to be powerful. While both methods can be used to monitor and/or induce neural activity, they complement each other in terms of obtainable information. The quantitative optical readout of fluorescent reporters can provide estimates of concentrations of important ions (e.g., intracellular Ca²⁺) that are inaccessible to extracellular recordings alone.

Moreover, a growing body of evidence shows that neurons may be mechanosensitive cells, so that platforms that combine HD-MEAs with tools to deliver mechanical stimuli, such as an atomic force microscope (AFM) may provide new insights. Using a combined AFM/HD-MEA system provides subcellular resolution for both mechanical stimulation and electrical readout and enables to investigate mechanosensation of neurons in dependence of the stimulus characteristics.

Finally, we also work on combining technologies for use of the HD-MEA platform for in-vivo applications. The CMOS chip then serves as the base and provides all readout and stimulation functions to structures that are connected to the chip like metal-wire bundles, intended to penetrate living tissue, or large arrays of electrodes on a soft polymer substrate for high-density electrocorticography (ECoG)-like measurements. Arrays of penetrating electrodes also have been directly 3D-printed on our CMOS-chips.