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'.

Polyamorphism Mirrors Polymorphism in the Liquid-Liquid Transition of a Molecular Liquid.

Liquid-liquid transitions between two amorphous phases in a single-component liquid have courted controversy. All known examples of liquid-liquid transitions in molecular liquids have been observed in the supercooled state, suggesting an intimate connection with vitrification and locally favored structures inhibiting crystallization. However, there is precious little information about the local molecular packing in supercooled liquids, meaning that the order parameter of the transition is still unknown. Here, we investigate the liquid-liquid transition in triphenyl phosphite and show that it is caused by the competition between liquid structures that mirror two crystal polymorphs. The liquid-liquid transition is found to be between a geometrically frustrated liquid and a dynamically frustrated glass. These results indicate a general link between polymorphism and polyamorphism and will lead to a much greater understanding of the physical basis of liquid-liquid transitions and allow the systematic discovery of other examples.

Prediction of mosquito species and population age structure using mid-infrared spectroscopy and supervised machine learning.

Despite the global efforts made in the fight against malaria, the disease is resurging. One of the main causes is the resistance that Anopheles mosquitoes, vectors of the disease, have developed to insecticides. Anopheles must survive for at least 10 days to possibly transmit malaria. Therefore, to evaluate and improve malaria vector control interventions, it is imperative to monitor and accurately estimate the age distribution of mosquito populations as well as their population sizes. Here, we demonstrate a machine-learning based approach that uses mid-infrared spectra of mosquitoes to characterise simultaneously both age and species identity of females of the African malaria vector species Anopheles gambiae and An. arabiensis, using laboratory colonies. Mid-infrared spectroscopy-based prediction of mosquito age structures was statistically indistinguishable from true modelled distributions. The accuracy of classifying mosquitoes by species was 82.6%. The method has a negligible cost per mosquito, does not require highly trained personnel, is rapid, and so can be easily applied in both laboratory and field settings. Our results indicate this method is a promising alternative to current mosquito species and age-grading approaches, with further improvements to accuracy and expansion for use with wild mosquito vectors possible through collection of larger mid-infrared spectroscopy data sets.

Using optical tweezing to control phase separation and nucleation near a liquid-liquid critical point.

About 20 years ago, it was shown that lasers can nucleate crystals in super-saturated solutions and might even be able to select the polymorph that crystallises. However, no theoretical model was found explaining the results and progress was slowed down. Here we show that laser-induced nucleation may be understood in terms of the harnessing of concentration fluctuations near a liquid-liquid critical point using optical tweezing in a process called laser-induced phase separation (LIPS) and LIPS and nucleation (LIPSaN). A theoretical model is presented based on the regular solution model with an added term representing optical tweezing while the dynamics are modelled using a Kramers diffusion equation, and the roles of heat diffusion and thermophoresis are evaluated. LIPS and LIPSaN experiments were carried out on a range of liquid mixtures and the results compared to theory.

Control over phase separation and nucleation using a laser-tweezing potential.

Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is still a poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid-liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter.

Frustration of crystallisation by a liquid-crystal phase.

Frustration of crystallisation by locally favoured structures is critically important in linking the phenomena of supercooling, glass formation, and liquid-liquid transitions. Here we show that the putative liquid-liquid transition in n-butanol is in fact caused by geometric frustration associated with an isotropic to rippled lamellar liquid-crystal transition. Liquid-crystal phases are generally regarded as being "in between" the liquid and the crystalline state. In contrast, the liquid-crystal phase in supercooled n-butanol is found to inhibit transformation to the crystal. The observed frustrated phase is a template for similar ordering in other liquids and likely to play an important role in supercooling and liquid-liquid transitions in many other molecular liquids.