NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons.

: Cochlear implants (CI) restore functional hearing in the majority of deaf patients. Despite the tremendous success of these devices, some limitations remain. The bottleneck for optimal electrical stimulation with CI is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear. As a consequence, current devices are limited through 1) low frequency resolution, hence sub-optimal sound quality and 2), large stimulation currents, hence high energy consumption (responsible for significant battery costs and for impeding the development of fully implantable systems). A recently completed, multinational and interdisciplinary project called NANOCI aimed at overcoming current limitations by creating a gapless interface between auditory nerve fibers and the cochlear implant electrode array. This ambitious goal was achieved in vivo by neurotrophin-induced attraction of neurites through an intracochlear gel-nanomatrix onto a modified nanoCI electrode array located in the scala tympani of deafened guinea pigs. Functionally, the gapless interface led to lower stimulation thresholds and a larger dynamic range in vivo, and to reduced stimulation energy requirement (up to fivefold) in an in vitro model using auditory neurons cultured on multi-electrode arrays. In conclusion, the NANOCI project yielded proof of concept that a gapless interface between auditory neurons and cochlear implant electrode arrays is feasible. These findings may be of relevance for the development of future CI systems with better sound quality and performance and lower energy consumption. The present overview/review paper summarizes the NANOCI project history and highlights achievements of the individual work packages.

Red blood cell phase separation in symmetric and asymmetric microchannel networks: effect of capillary dilation and inflow velocity.

The non-uniform partitioning or phase separation of red blood cells (RBCs) at a diverging bifurcation of a microvascular network is responsible for RBC heterogeneity within the network. The mechanisms controlling RBC heterogeneity are not yet fully understood and there is a need to improve the basic understanding of the phase separation phenomenon. In this context, in vitro experiments can fill the gap between existing in vivo and in silico models as they provide better controllability than in vivo experiments without mathematical idealizations or simplifications inherent to in silico models. In this study, we fabricated simple models of symmetric/asymmetric microvascular networks; we provided quantitative data on the RBC velocity, line density and flux in the daughter branches. In general our results confirmed the tendency of RBCs to enter the daughter branch with higher flow rate (Zweifach-Fung effect); in some cases even inversion of the Zweifach-Fung effect was observed. We showed for the first time a reduction of the Zweifach-Fung effect with increasing flow rate. Moreover capillary dilation was shown to cause an increase of RBC line density and RBC residence time within the dilated capillary underlining the possible role of pericytes in regulating the oxygen supply.

Mid-infrared spectroscopy for gases and liquids based on quantum cascade technologies.

In this paper we present two compact, quantum cascade laser absorption spectroscopy based, sensors developed for trace substance detection in gases and liquids. The gas sensor, in its most integrated version, represents the first system combining a quantum cascade laser and a quantum cascade detector. Furthermore, it uses a toroidal mirror cell with a volume of only 40 cm(3) for a path length of up to 4 m. The analytical performance is assessed by the measurements of isotope ratios of CO2 at ambient abundance. For the (13)CO2/(12)CO2 isotope ratio, a measurement precision of 0.2‰ is demonstrated after an integration time of 600 s. For the liquid sensor, a microfluidic system is used to extract cocaine from saliva into a solvent (PCE) transparent in the mid-infrared. This system is bonded on top of a Si/Ge waveguide and the concentration of cocaine in PCE is measured through the interaction of the evanescent part of the waveguide optical mode and the solvent flowing on top. A detection limit of <100 µg mL(-1) was achieved with this system and down to 10 µg mL(-1) with a simplified, but improved system.

Microfluidic droplet-based liquid-liquid extraction and on-chip IR spectroscopy detection of cocaine in human saliva.

We present a portable microsystem to quantitatively detect cocaine in human saliva. In this system, we combine a microfluidic-based multiphase liquid-liquid extraction method to transfer cocaine continuously from IR-light-absorbing saliva to an IR-transparent solvent (tetrachloroethylene) with waveguide IR spectroscopy (QC-laser, waveguide, detector) to detect the cocaine on-chip. For the fabrication of the low-cost polymer microfluidic chips a simple rapid prototyping technique based on Scotch-tape masters was further developed and applied. To perform the droplet-based liquid-liquid extraction, we designed and integrated a simple and robust droplet generation method based on the capillary focusing effect within the device. Compared to well-characterized and commonly used microfluidic H-filters, our system showed at least two times higher extraction efficiencies with potential for further improvements. The current liquid-liquid extraction method alone can efficiently extract cocaine and pre-concentrate the analytes in a new solvent. Our fully integrated optofluidic system successfully detected cocaine in real saliva samples spiked with the drug (500 µg/mL) and allowed real time measurements, which makes this approach suitable for point-of-care applications.

Cocaine detection by a mid-infrared waveguide integrated with a microfluidic chip.

A germanium (Ge) strip waveguide on a silicon (Si) substrate is integrated with a microfluidic chip to detect cocaine in tetrachloroethylene (PCE) solutions. In the evanescent field of the waveguide, cocaine absorbs the light near 5.8 µm, which is emitted from a quantum cascade laser. This device is ideal for (bio-)chemical sensing applications.

Development and validation of a low cost blood filtration element separating plasma from undiluted whole blood.

Clinical point of care testing often needs plasma instead of whole blood. As centrifugation is labor intensive and not always accessible, filtration is a more appropriate separation technique. The complexity of whole blood is such that there is still no commercially available filtration system capable of separating small sample volumes (10-100 µl) at the point of care. The microfluidics research in blood filtration is very active but to date nobody has validated a low cost device that simultaneously filtrates small samples of whole blood and reproducibly recovers clinically relevant biomarkers, and all this in a limited amount of time with undiluted raw samples. In this paper, we show first that plasma filtration from undiluted whole blood is feasible and reproducible in a low-cost microfluidic device. This novel microfluidic blood filtration element (BFE) extracts 12 µl of plasma from 100 µl of whole blood in less than 10 min. Then, we demonstrate that our device is valid for clinical studies by measuring the adsorption of interleukins through our system. This adsorption is reproducible for interleukins IL6, IL8, and IL10 but not for TNFα. Hence, our BFE is valid for clinical diagnostics with simple calibration prior to performing any measurement.

Microfluidic biochip for chemiluminescent detection of allergen-specific antibodies.

Protein microarrays for allergen-specific antibodies detection were integrated in microfluidic chips, with imaging chemiluminescence as the analytical technique. This paper demonstrates the feasibility of miniaturized chemiluminescent ELISA by presenting rapid, reproducible and sensitive detection of protein antibodies using microfluidics. Three different proteins, beta-lactoglobulin, peanut lectin and human IgG were immobilized via a "macromolecules to polydimethylsiloxane elastomer (PDMS) transfer" protocol and used as capturing agent for the detection of specific antibodies. A convenient and reversible procedure was used to bond the PDMS microarray substrate to complimentary SU-8/glass microfluidic reaction chambers. The hydrodynamic behaviours of the three proteins interactions within the micro-chambers were investigated to select the most efficient flowing parameters (come to terms with the assay time and performances). The use of optimized conditions led to the concomitant detection of three specific antibodies at pM level in 300 microL and using 6 min sample incubation time. Finally, sera from allergic patients were assayed using the microfluidic device modified with apple hazelnut and pollen allergen. The results obtained compared favourably with those obtained with the classical Pharmacia CAP system.

A high current density DC magnetohydrodynamic (MHD) micropump.

This paper describes the working principle of a DC magnetohydrodynamic (MHD) micropump that can be operated at high DC current densities (J) in 75-microm-deep microfluidic channels without introducing gas bubbles into the pumping channel. The main design feature for current generation is a micromachined frit-like structure that connects the pumping channel to side reservoirs, where platinum electrodes are located. Current densities up to 4000 A m(-2) could be obtained without noticeable Joule heating in the system. The pump performance was studied as a function of current density and magnetic field intensity, as well as buffer ionic strength and pH. Bead velocities of up to 1 mm s(-1) (0.5 microL min(-1)) were observed in buffered solutions using a 0.4 T NdFeB permanent magnet, at an applied current density of 4000 A m(-2). This pump is intended for transport of electrolyte solutions having a relatively high ionic strength (0.5-1 M) in a DC magnetic field environment. The application of this pump for the study of biological samples in a miniaturized total analysis system (microTAS) with integrated NMR detection is foreseen. In the 7 T NMR environment, a minimum 16-fold increase in volumetric flow rate for a given applied current density is expected.