A micropatterned multielectrode shell for 3D spatiotemporal recording from live cells

Microelectrode arrays (MEAs) have proved to be useful tools for characterizing electrically active cells such as cardiomyocytes and neurons. While there exist a number of integrated electronic chips for recording from small populations or even single cells, they rely primarily on the interface between the cells and 2D flat electrodes. Here, an approach that utilizes residual stress‐based self‐folding to create individually addressable multielectrode interfaces that wrap around the cell in 3D and function as an electrical shell‐like recording device is described. These devices are optically transparent, allowing for simultaneous fluorescence imaging. Cell viability is maintained during and after electrode wrapping around the cel and chemicals can diffuse into and out of the self‐folding devices. It is further shown that 3D spatiotemporal recordings are possible and that the action potentials recorded from cultured neonatal rat ventricular cardiomyocytes display significantly higher signal‐to‐noise ratios in comparison with signals recorded with planar extracellular electrodes. It is anticipated that this device can provide the foundation for the development of new‐generation MEAs where dynamic electrode–cell interfacing and recording substitutes the traditional method using static electrodes

Low loss CMOS-compatible PECVD silicon nitride waveguides and grating couplers for blue light optogenetic applications

This paper presents silicon nitride (SixNy) photonic integrated circuits (PICs) with high performance at a wavelength of 450 nm, which, therefore, is suitable for neuronal stimulation with optogenetics. These PICs consist of straight and bent waveguides, and grating couplers that are fabricated in a complementary metal-oxide-semiconductor (CMOS)-compatible plasma enhanced chemical vapor deposition SixNy platform. Their characterization shows propagation losses of 0.96 +/- 0.4 dB/cm on average for straight waveguides that are 1-5 mu m wide and bend insertion losses as low as 0.2 dB/90. for 1 mu m wide waveguides with a radius of 100 mu m. Additionally, the grating coupler characterization shows that they can deliver about 10 mu W of light in an area of 5 x 9 mu m(2) (240 mW/mm(2)), which is captured from an uncollimated laser diode (70 mW). Besides delivering sufficient power for optogenetic applications, the gratings have dimensions that are comparable to the size of a neuron, which would allow single cell interaction. These results demonstrate that, with this SixNy platform, high-density and large-scale implantable neural devices can be fabricated and readily integrated into existing CMOS-compatible neuro-electronic platforms

Ultra-thin biocompatible implantable chip for bidirectional communication with peripheral nerves

To realize optimal recording and stimulation of peripheral nerve cells, a CMOS chip is made with a multitude of electrodes which can be individually addressed in order to select after implantation the 16 best positioned electrodes. Since the Foreign Body Reaction should be minimal for optimum electrode-nerve contact, the CMOS chip is thinned down to 35um and fully packaged resulting in a 75um thin encapsulated chip. The chip is embedded in a biocompatible stack consisting of polymers and inorganic diffusion barriers deposited using atomic layer deposition (ALD). A biocompatible metallization is realized using gold and platinum sandwiched between polymers and ALD layers for flexible interconnects, and iridium oxide (IrOx) is selected as electrode material for optimal charge injection during stimulation. After this dedicated packaging based on the FITEP technology platform (Flexible Implantable Thin Electronic Package), the CMOS chip is still fully functional, which was tested dry (in air) as well as during submersion in saline. The form factor of the packaged chip is optimized for intra-fascicular implantation with minimum tissue damage. First acute in vivo stimulation tests proved that the stimulation capabilities of the IrOx electrodes are very good

Bioelectronic Interfacing: Electrical and Chemical Sensing of Biological Signals

In the search for mechanisms and pathways underlying disease processes, various techniques and strategies have been developed over the last deca des. In the field of cell physiology, the recording of electrical and ch emical activities of excitable cells is addressed using advanced optical techniques such as high-speed confocal microscopy of various fluorophor es and intracellular recording of electrical activity using patch clamp techniques. However, these techniques still suffer from limited throughp ut and low sensitivity, or need specialized intervention from the user. Innovative technologies are, therefore, needed to further elucidate the working principles underlying cellular processes. Biocompatible microfab ricated chips with integrated readout circuits will help to address thes e challenges because of their ability to increase the output by miniatur ization and automatization. The aim of this work was to develop and vali date methodologies for quantifying activities of excitable cells, at che mical and electrical level, using biocompatible and non-invasive microfa bricated transducers. The first part of this work has focused on the ass esment of a bioelectronic system for detection of glutamate release by h ippocampal neurons. The detection of neurotransmitter release is of grea t interest to neurophysiologists because a large number of disorders and pathologies are caused by an impairment of the chemical communication b etween neurons and their target cells such as is the case in Alzheimer's and Parkinson's diseases. The in vitro detection of neurotransmitter release is challenging because of the small amount o f molecules released in a large volume at the synapse and the fast disap pearance. Firstly, a glutamate-sensitive surface layer was developed and characterized for different sensor materials. Then, this surface chemis try was applied to a sensor system for the detection of glutamate. Glutamate detection with t his sensor proved to show good sensitivity and selectivity. The sensitiv y of the surface chemistry was further increased by the development of a patternable bienzymatic recycling system. Finally, the surface layers s howed to be compatible with neuronal cultures. In the second part of thi s work, we evaluated a commercially available system which is used for t he recording of extracellular field potentials of excitable cells and co mpared this system with conventional techniques for electrophysiology, i .e., whole-cell patch clamp technique. In addition, we evaluated the use of calcium imaging to relate the electrical activity. Because recorded signals from conventional systems still lack a good signal-to-noise rati o and the output is rather limited, we investigated a new approach to th at uses three-dimensional nail-shaped electrodes instead of at electrode s to enhance the cell-chip coupling. Morphological investigation of the cells on electrode surfaces showed tight coupling between cell and elect rode. Finally, electrical stimulation of cardiac cells was performed usi ng a passive nail electrode array. The cell response was monitored using calcium imaging. In this work, we presented bioelectronic devices for t he monitoring of electrical and chemical activity of excitable cells. They proved to be promising tools for future biomedical research applications.status: publishe

Amyloid beta oligomers induce neuronal elasticity changes in age-dependent manner: A force spectroscopy study on living hippocampal neurons

Small soluble species of amyloid-beta (Aβ) formed during early peptide aggregation stages are responsible for several neurotoxic mechanisms relevant to the pathology of Alzheimer's disease (AD), although their interaction with the neuronal membrane is not completely understood. This study quantifies the changes in the neuronal membrane elasticity induced by treatment with the two most common Aβ isoforms found in AD brains: Aβ40 and Aβ42. Using quantitative atomic force microscopy (AFM), we measured for the first time the static elastic modulus of living primary hippocampal neurons treated with pre-aggregated Aβ40 and Aβ42 soluble species. Our AFM results demonstrate changes in the elasticity of young, mature and aged neurons treated for a short time with the two Aβ species pre-aggregated for 2 hours. Neurons aging under stress conditions, showing aging hallmarks, are the most susceptible to amyloid binding and show the largest decrease in membrane stiffness upon Aβ treatment. Membrane stiffness defines the way in which cells respond to mechanical forces in their environment and has been shown to be important for processes such as gene expression, ion-channel gating and neurotransmitter vesicle transport. Thus, one can expect that changes in neuronal membrane elasticity might directly induce functional changes related to neurodegeneration.Hercules Foundation (Project HER/09/021)Peer Reviewe

Ultra-compact integrated electrical and optical silicone probe for recording and illumination in vivo

status: publishe