Neural microprobe modelling and microfabrication for improved implantation and mechanical failure mitigation.

Careful design and material selection are the most beneficial strategies to ensure successful implantation and mitigate the failure of a neural probe in the long term. In order to realize a fully flexible implantable system, the probe should be easily manipulated by neuroscientists, with the potential to bend up to 90°. This paper investigates the impact of material choice, probe geometry, and crucially, implantation angle on implantation success through finite-element method simulations in COMSOL Multiphysics followed by cleanroom microfabrication. The designs introduced in this paper were fabricated using two polyimides: (i) PI-2545 as a release layer and (ii) photodefinable HD-4110 as the probe substrate. Four different designs were microfabricated, and the implantation tests were compared between an agarose brain phantom and lamb brain samples. The probes were scanned in a 7 T PharmaScan MRI coil to investigate potential artefacts. From the simulation, a triangular base and 50 µm polymer thickness were identified as the optimum design, which produced a probe 57.7 µm thick when fabricated. The probes exhibit excellent flexibility, exemplified in three-point bending tests performed with a DAGE 4000Plus. Successful implantation is possible for a range of angles between 30° and 90°. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Cleanroom strategies for micro- and nano-fabricating flexible implantable neural electronics.

Implantable electronic neural interfaces typically take the form of probes and are made with rigid materials such as silicon and metals. These have advantages such as compatibility with integrated microchips, simple implantation and high-density nanofabrication but tend to be lacking in terms of biointegration, biocompatibility and durability due to their mechanical rigidity. This leads to damage to the device or, more importantly, the brain tissue surrounding the implant. Flexible polymer-based probes offer superior biocompatibility in terms of surface biochemistry and better matched mechanical properties. Research which aims to bring the fabrication of electronics on flexible polymer substrates to the nano-regime is remarkably sparse, despite the push for flexible consumer electronics in the last decade or so. Cleanroom-based nanofabrication techniques such as photolithography have been used as pattern transfer methods by the semiconductor industry to produce single nanometre scale devices and are now also used for making flexible circuit boards. There is still much scope for miniaturizing flexible electronics further using photolithography, bringing the possibility of nanoscale, non-invasive, high-density flexible neural interfacing. This work explores the fabrication challenges of using photolithography and complementary techniques in a cleanroom for producing flexible electronic neural probes with nanometre-scale features. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Nanotechnology Enables Novel Modalities for Neuromodulation.

Neuromodulation is of great importance both as a fundamental neuroscience research tool for analyzing and understanding the brain function, and as a therapeutic avenue for treating brain disorders. Here, an overview of conceptual and technical progress in developing neuromodulation strategies is provided, and it is suggested that recent advances in nanotechnology are enabling novel neuromodulation modalities with less invasiveness, improved biointerfaces, deeper penetration, and higher spatiotemporal precision. The use of nanotechnology and the employment of versatile nanomaterials and nanoscale devices with tailored physical properties have led to considerable research progress. To conclude, an outlook discussing current challenges and future directions for next-generation neuromodulation modalities is presented.

The Future of Neuroscience: Flexible and Wireless Implantable Neural Electronics.

Neurological diseases are a prevalent cause of global mortality and are of growing concern when considering an ageing global population. Traditional treatments are accompanied by serious side effects including repeated treatment sessions, invasive surgeries, or infections. For example, in the case of deep brain stimulation, large, stiff, and battery powered neural probes recruit thousands of neurons with each pulse, and can invoke a vigorous immune response. This paper presents challenges in engineering and neuroscience in developing miniaturized and biointegrated alternatives, in the form of microelectrode probes. Progress in design and topology of neural implants has shifted the goal post toward highly specific recording and stimulation, targeting small groups of neurons and reducing the foreign body response with biomimetic design principles. Implantable device design recommendations, fabrication techniques, and clinical evaluation of the impact flexible, integrated probes will have on the treatment of neurological disorders are provided in this report. The choice of biocompatible material dictates fabrication techniques as novel methods reduce the complexity of manufacture. Wireless power, the final hurdle to truly implantable neural interfaces, is discussed. These aspects are the driving force behind continued research: significant breakthroughs in any one of these areas will revolutionize the treatment of neurological disorders.