Advances in lithographic techniques for precision nanostructure fabrication in biomedical applications.

Nano-fabrication techniques have demonstrated their vital importance in technological innovation. However, low-throughput, high-cost and intrinsic resolution limits pose significant restrictions, it is, therefore, paramount to continue improving existing methods as well as developing new techniques to overcome these challenges. This is particularly applicable within the area of biomedical research, which focuses on sensing, increasingly at the point-of-care, as a way to improve patient outcomes. Within this context, this review focuses on the latest advances in the main emerging patterning methods including the two-photon, stereo, electrohydrodynamic, near-field electrospinning-assisted, magneto, magnetorheological drawing, nanoimprint, capillary force, nanosphere, edge, nano transfer printing and block copolymer lithographic technologies for micro- and nanofabrication. Emerging methods enabling structural and chemical nano fabrication are categorised along with prospective chemical and physical patterning techniques. Established lithographic techniques are briefly outlined and the novel lithographic technologies are compared to these, summarising the specific advantages and shortfalls alongside the current lateral resolution limits and the amenability to mass production, evaluated in terms of process scalability and cost. Particular attention is drawn to the potential breakthrough application areas, predominantly within biomedical studies, laying the platform for the tangible paths towards the adoption of alternative developing lithographic technologies or their combination with the established patterning techniques, which depends on the needs of the end-user including, for instance, tolerance of inherent limits, fidelity and reproducibility.

Microfluidic Fabrication of Hydrocortisone Nanocrystals Coated with Polymeric Stabilisers.

Hydrocortisone (HC) nanocrystals intended for parenteral administration of HC were produced by anti-solvent crystallisation within coaxial assemblies of pulled borosilicate glass capillaries using either co-current flow of aqueous and organic phases or counter-current flow focusing. The organic phase was composed of 7 mg/mL of HC in a 60:40 (v/v) mixture of ethanol and water and the anti-solvent was milli-Q water. The microfluidic mixers were fabricated with an orifice diameter of the inner capillary ranging from 50 µm to 400 µm and operated at the aqueous to organic phase flow rate ratio ranging from 5 to 25. The size of the nanocrystals decreased with increasing aqueous to organic flow rate ratio. The counter-current flow microfluidic mixers provided smaller nanocrystals than the co-current flow devices under the same conditions and for the same geometry, due to smaller diameter of the organic phase stream in the mixing zone. The Z-average particle size of the drug nanocrystals increased from 210⁻280 nm to 320⁻400 nm after coating the nanocrystals with 0.2 wt % aqueous solution of hydroxypropyl methylcellulose (HPMC) in a stirred vial. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analyses carried out on the dried nanocrystals stabilized with HPMC, polyvinyl pyrrolidone (PVP), and sodium lauryl sulfate (SLS) were investigated and reported. The degree of crystallinity for the processed sample was lowest for the sample stabilised with HPMC and the highest for the raw HC powder.