Approaches for drug delivery with intracortical probes.

Intracortical microprobes allow the precise monitoring of electrical and chemical signaling and are widely used in neuroscience. Microelectromechanical system (MEMS) technologies have greatly enhanced the integration of multifunctional probes by facilitating the combination of multiple recording electrodes and drug delivery channels in a single probe. Depending on the neuroscientific application, various assembly strategies are required in addition to the microprobe fabrication itself. This paper summarizes recent advances in the fabrication and assembly of micromachined silicon probes for drug delivery achieved within the EU-funded research project NeuroProbes. The described fabrication process combines a two-wafer silicon bonding process with deep reactive ion etching, wafer grinding, and thin film patterning and offers a maximum in design flexibility. By applying this process, three general comb-like microprobe designs featuring up to four 8-mm-long shafts, cross sections from 150×200 to 250×250 µm², and different electrode and fluidic channel configurations are realized. Furthermore, we discuss the development and application of different probe assemblies for acute, semichronic, and chronic applications, including comb and array assemblies, floating microprobe arrays, as well as the complete drug delivery system NeuroMedicator for small animal research.

A modular diffusion barrier based on phase separation for localized delivery of discrete drug volumes in aqueous environments.

We present a new tool for the precisely controlled transfer of individual picoliter (pL) droplets in the range of 150-950 pL at user defined local positions within aqueous liquid environments while avoiding any leakage by diffusion. This is achieved by a low-cost, disposable and biocompatible cap that can be placed on top of any pL-dispenser and generates a phase-gap between dispensing agent and target liquid when the dispenser is dipped into the latter. We developed two different working modes: (i) the standard mode enables an instant injection (<< 1 ms) of the droplet into the liquid environment and (ii) the focus mode further increases the spatial resolution from 100 microm to 50 microm at the cost of slowing down the injection time. For the phase-gap we have proven an excellent long-term stability of more than 30 hours against capillary priming.