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Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study., (Copyright © 2016 the American Physiological Society.)

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.

This paper presents multi-electrode arrays for in vivo neural recording applications incorporating the principle of electronic depth control (EDC), i.e., the electronic selection of recording sites along slender probe shafts independently for multiple channels. Two-dimensional (2D) arrays were realized using a commercial 0.5- μm complementary-metal-oxide-semiconductor (CMOS) process for the EDC circuits combined with post-CMOS micromachining to pattern the comb-like probes and the corresponding electrode metallization. A dedicated CMOS integrated front-end circuit was developed for pre-amplification and multiplexing of the neural signals recorded using these probes.

In this work, we propose the use of shape-memory polymer as an anchoring system for a bladder sensor. The anchoring system was designed from a biomedical biodegradable water-based poly(ester-urethane) produced in an aqueous environment by using isophorone diisocyanate/hydrazine (hard segment) and poly(caprolactone diol)/2,2-bis (hydroxymethyl) propionic acid (soft segment) as the main reagents. Tensile strength and elongation-at-break deterioration upon degradation in synthetic urine were investigated. In-body shape recovery was simulated and measured in synthetic urine. Results indicated that shape recovery can occur at body temperature and expulsion of the sensor by the body along with urine may occur through the combined effect of urine hydrolytic attack and compression exerted by the bladder walls., (Copyright © 2010 Wiley Periodicals, Inc.)

This paper reports on the high strength of high-aspect ratio (> 50) hollow, polymer microneedles fabricated out-of-plane using a fairly repeatable fabrication process. Further, these microneedle tips were sharpened by a molding principle, with a simple anisotropic etch of silicon wafer. Also, an enhanced elegant process was explored to incorporate the mounting of the microneedle onto a platform without using any additional material, such that the bore of the microneedle is continuous with the bore of the platform in order to facilitate microfluidic delivery through the hollow needles. The high aspect ratio microneedles undergo failure at the critical load of around 4 N, while the insertion force for such a needle into agar gel, which is a fairly good equivalent of the human skin due to its inherent visco-elastic properties, is 7 mN, which translates into a safety factor (ratio of critical loading force to the maximum applied force) of greater than 500 thus, making it adequately strong for skin penetration.

In this paper we present our investigations related to the optimization of hydrogels for the coating/packaging of biomedical devices. In order for hydrogels to be a viable interface/packaging material, a number of conditions must be met. We outline the tailoring of the mechanical properties of a HEMA based hydrogel by exploiting the influence of individual hydrogel components to achieve these requirements. The water sorption, the elasticity and the porosity of various hydrogel materials were tested and the effects of the different hydrogel components was determined. These components include gelatin (used as a pore generator or porogen), alginate (to influence mechanical properties) and collagen (to improve cell adhesion). We also report the results of in vitro fibroblast testing on various hydrogel types.

Tuning the electrode impedance through the DC biasing of iridium oxide is presented. Impedance reduction of up to two orders of magnitude was reproducibly observed in 20 microm diameter microelectrodes at a biasing of 1V.

This paper introduces the first experimental results of a new implantable slim-base three-dimensional (3D) probe array for cerebral applications. The probes are assembled perpendicularly into the slim-base readout platform where electrical and mechanical connections are achieved simultaneously. A new type of micromachined interconnect has been developed to establish electrical connection using extreme planarization techniques. Due to the modular approach of the platform, probe arrays of different dimensions and functionality can be assembled. The platform is only several hundred microns thick which is highly relevant for chronic experiments in which the probe array should be able to float on top of the brain. Preliminary tests were carried out with the implantation of a probe array into the auditory cortex of a rat.

The European project NeuroProbes has introduced a new methodology to allow the fine positioning of electrodes within an implantable probe with respect to individual neurons. In this approach, probes are built with a very large number of electrodes which are electronically selectable. This feature is implemented thanks to the modular approach adopted in NeuroProbes, which will allow the implementation of integrated electronics both along the probe shaft and on the array backbone.

Despite the significant progress in recent years in neural recording and stimulation using silicon-based probes, there is still a lack of suitable tools for the truly three-dimensional access to large ensembles of neurons over long periods of time. The objective of the NeuroProbes project is to address such needs and to extend probe capabilities by adopting a modular and scalable approach in which chemical sensing and drug delivery are also incorporated in the same probe system.

Biomolecular motors such as F1-adenosine triphosphate synthase (F1-ATPase) and myosin are similar in size, and they generate forces compatible with currently producible nanoengineered structures. We have engineered individual biomolecular motors and nanoscale inorganic systems, and we describe their integration in a hybrid nanomechanical device powered by a biomolecular motor. The device consisted of three components: an engineered substrate, an F1-ATPase biomolecular motor, and fabricated nanopropellers. Rotation of the nanopropeller was initiated with 2 mM adenosine triphosphate and inhibited by sodium azide.