Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients.

A challenge in current stem cell therapies for Parkinson's disease (PD) is controlling neuronal outgrowth from the substantia nigra towards the targeted area where connectivity is required in the striatum. Here we present progress towards controlling directional neurite extensions through the application of iron-oxide magnetic nanoparticles (MNPs) labelled neuronal cells combined with a magnetic array generating large spatially variant field gradients (greater than 20 T m-1). We investigated the viability of this approach in both two-dimensional and organotypic brain slice models and validated the observed changes in neurite directionality using mathematical models. Results showed that MNP-labelled cells exhibited a shift in directional neurite outgrowth when cultured in a magnetic field gradient, which broadly agreed with mathematical modelling of the magnetic force gradients and predicted MNP force direction. We translated our approach to an ex vivo rat brain slice where we observed directional neurite outgrowth of transplanted MNP-labelled cells from the substantia nigra towards the striatum. The improved directionality highlights the viability of this approach as a remote-control methodology for the control and manipulation of cellular growth for regenerative medicine applications. This study presents a new tool to overcome challenges faced in the development of new therapies for PD.

Electrochemical DNA biosensors based on long-range electron transfer: investigating the efficiency of a fluidic channel microelectrode compared to an ultramicroelectrode in a two-electrode setup.

Here, we describe the transposition of an ultramicroelectrode (UME) setup into a microfluidic chip configuration for DNA biosensors. The hydrodynamic properties of the fluidic channel microelectrode were screened with an [Fe(iii)(CN)6]3-/[Fe(ii)(CN)6]4- redox couple by cyclic voltammetry to provide a basis for further biological processes. A 23-base DNA probe was self-assembled into a monolayer on gold microelectrodes both in classical configuration and integrated in a microfluidic setup. Special interest was focused on the DNA target mimicking the liver-specific micro-ribonucleic acid 122 (miRNA122). Long-range electron transfer was chosen for transducing the hybridization. This direct transduction was indeed significantly enhanced after hybridization due to DNA-duplex π-stacking and the use of redox methylene blue as a DNA intercalator. Quantification of the target was deduced from the resulting electrical signal characterized by cyclic voltammetry. The limit of detection for DNA hybridization was 0.1 fM in stopped flow experiments, where it can reach 1 aM over a 0.5 µL s-1 flow rate, a value 104-fold lower than the one measured with a conventional UME dipped into an electrolyte droplet under the same analytical conditions. An explanation was that forced convection drives more biomolecules to the area of detection even if a balance between the speed of collection and the number of biomolecules collected has been found. The latter point is discussed here along with an attempt to explain why the sensor has reached such an unexpected value for the limit of detection.