Edward Tarte

Flexible and stretchable micro-electrodes for in vitro and in vivo neural interfaces

Microelectrode arrays (MEAs) are designed to monitor and/or stimulate extracellularly neuronal activity. However, the biomechanical and structural mismatch between current MEAs and neural tissues remains a challenge for neural interfaces. This article describes a material strategy to prepare neural electrodes with improved mechanical compliance that relies on thin metal film electrodes embedded in polymeric substrates. The electrode impedance of micro-electrodes on polymer is comparable to that of MEA on glass substrates. Furthermore, MEAs on plastic can be flexed and rolled offering improved structural interface with brain and nerves in vivo. MEAs on elastomer can be stretched reversibly and provide in vitro unique platforms to simultaneously investigate the electrophysiological of neural cells and tissues to mechanical stimulation. Adding mechanical compliance to MEAs is a promising vehicle for robust and reliable neural interfaces.

Long Micro-Channel Electrode Arrays: A Novel Type of Regenerative Peripheral Nerve Interface

We have demonstrated that micro-channel electrode arrays with 100 mum times 100 mum cross-section channels support axon regeneration well, and that micro-channels of similar calibre and up to 5 mm long can support axon regeneration and vascularisation. They may be microfabricated using silicon, silicone, or polyimide and thin metal films to form 3-D bundles of long micro-channels. Arrays of ldquomini-nerves,rdquo i.e., miniature nerve fascicles with their own blood vessels, successfully grew through implants 0.5-5 mm long. Furthermore, guiding the regenerating nerve fibres into the small insulating channels allows for a significant increase of the extracellular (recordable) amplitude of action potentials, which promises considerable improvement for in vivo electrophysiology.

Novel use of X-ray micro computed tomography to image rat sciatic nerve and integration into scaffold

This paper describes how specimens of nervous tissue can be prepared for successful imaging in X-ray Micro Computed Tomography (microCT), and how this method can be used to study the integration of nervous tissue into a polymeric scaffold. The sample preparation involves staining the biological tissue with osmium tetroxide to increase its X-ray attenuation, and a technique for maintaining the specimen in a moist environment during the experiment to prevent drying and shrinkage. Using this method it was possible to observe individual nerve fascicles and their relationship to the 3-D tissue structure. A scaffold supporting a regenerated sciatic nerve was similarly stained to distinguish the nervous tissue from the scaffold, and to observe how the nerve grew through a 2.5 mm long, 100 microm x 100 microm cross-section channel polyimide array. Furthermore, blood vessels could be identified in these images, and it was possible to monitor how a large proximal blood vessel split through the channel scaffold and proceeded down individual channels. This paper explains how microCT is a useful tool both for studying the location and extent of growth into a polymeric scaffold, and for determining whether the regenerated tissue has blood supply.

Design and fabrication of neural implant with thick microchannels based on flexible polymeric materials

Mechanical guidance can be used to provide a supporting structure through which and onto which regenerating axons can grow. The dimensions of the mechanical guide need to be suitable to support regenerated axon outgrowth and vascularisation. In this paper, we present the design and fabrication process of a three-dimensional (3D) device comprising a bundle of parallel (100µmx100µm) microchannels with embedded electrodes. This device can be used as a 3D electrode interface for peripheral nerve repair. The skeleton of the device is entirely made of flexible polyimide films. Gold microelectrodes and microchannels of photosensitive polyimide are patterned directly on polyimide substrates. After fabrication, the 2D electrode channel array is rolled into a 3D channel bundle that fits the anatomy of the peripheral nerve. Samples are rolled and inserted into 1.5mm inner diameter tube.

Chemically amplified fullerene resists, spin-on fullerene hardmasks and high aspect ratio etching

As resolution requirements increase there is a need for high performance ultra thin resists, which has led to significant interest in molecular resists. We have previously described a fullerene based resist whose electron beam lithography properties include sparse resolution of ~12 nm, half pitch ~20 nm, sub 5 nm linewidth roughness (LWR), sub 10 μC/cm2 sensitivity, and high etch durability. The material shows extremely wide process latitude and LWR <;2 nm in sparse features. Initial results of exposure via EUV lithography indicate a resolution capability of at least 30 nm half pitch. As resist films have become thinner to mitigate aspect ratio related pattern collapse, etching has become more challenging. We have studied the ICP plasma etching of high-resolution patterns in sub 40 nm thickness films of the fullerene resist. Silicon structures of 20 nm width and more than 100 nm height have been demonstrated. Additionally we have developed a fullerene based spin-on-carbon for use in a tri-layer etching scheme allowing aspect ratios greater than 19:1 to be achieved in room temperature ICP etching of sub 30 nm patterns. The same trilayer scheme has also been deployed for colloidal lithography fabrication of sub 100 nm silicon pillars with aspect ratios >;17:1.

Spiral peripheral nerve interface; updated fabrication process of the regenerative implant

The spiral peripheral nerve interface (SPNI) has been developed to record neural activity by utilizing the bodys own ability to regenerate axons after injury. The implantable device is capable of providing a chronic recording array for use with technology designed to compensate for a loss of motor function. The SPNI offers a good route to establishing an effective interface to the peripheral nervous system (PNS) as the signals are enclosed within an insulating array that amplifies the axon signals for the neural recording, and reduces the amount of current necessary for stimulation. This paper presents an updated fabrication process that addresses the problems of previous designs and allows for an easier integration to external electronics via a ball-bonding technique. The updated device has been tested electrically in vitro, to show that it is capable of providing a reliable electrical interface to the regenerated tissue.

On transmission line resonances in high TC dc SQUIDs

In this paper, we study transmission line resonances in high TC dc SQUIDs (superconducting quantum interference devices). These resonances are exhibited in the characteristics of SQUIDs which are fabricated on substrates with high dielectric constant, such as strontium titanate. The power balance equation is analytically derived both for symmetric and for asymmetric SQUIDs. Using this, we investigate SQUID current–voltage I(V), voltage–flux V (Φ) and voltage modulation ΔV characteristics.

Niobium-copper superconductor-normal metal-superconductor asymmetry modulated SQUIDs

We have developed a fabrication method using a focused ion beam microscope that allows us to produce SNS junctions in which thermally energetic electrons can enter the N region. We report on SQUIDs made with this technique which we are developing as proof of concept devices and prototype high energy resolution spectrometers. We discuss the various design parameters used for our devices and present results from our prototype SQUIDs. We present results for devices with a variety of N-electrode structures and discuss their suitability for our application.

Magnetophysiology of Brain Slices Using an HTS SQUID Magnetometer System

A high-transition-temperature superconducting quantum interference device (HTS SQUID) system has been developed and employed in neuromagnetic measurements of evoked fields from in vitro brain slices. Transverse hippocampal slices from rat were prepared and measured. The evoked neuronal activity produced neuromagnetic fields of ~5 pT.

The effect of UV-Vis to near-infrared light on the biological response of human dental pulp cells

Human dental pulp cells (DPCs) were isolated and cultured in phenol-red-free α-MEM/10%-FCS at 37ºC in 5% CO2. DPCs at passages 2-4 were seeded (150μL; 25,000 cell/ml) in black 96-microwell plates with transparent bases. 24h post-seeding, cultures were irradiated using a bespoke LED array consisting of 60 LEDs (3.5mW/cm2) of wavelengths from 400-900nm (10 wavelengths, n=6) for time intervals of up to 120s. Metabolic and mitochondrial activity was assessed via a modified MTT assay. Statistical differences were identified using multi-factorial analysis of variance and post-hoc Tukey tests (P=0.05). The biological responses were significantly dependent upon post-irradiation incubation period, wavelength and exposure time (P<0.05). At shorter wavelength irradiances (400nm), a reduction in mitochondrial activity was detected although not significant, whereas longer wavelength irradiances (at 633, 656, 781 and 799nm) significantly increased mitochondrial activity (P<0.05) in DPCs. At these wavelengths, mitochondrial activity was generally increased for exposures less than 90s with 30s exposures being most effective with 24h incubation. Increasing the post-irradiation incubation period increased the measured response and identified further significance (P<0.05). The biological responses of human DPCs were wavelength, exposure-time and incubation period dependent. The optimisation of irradiation parameters will be key to the successful application of LLLT in dentistry.