How additive manufacturing and microfabrication techniques could be complementary and applied to the development of the Galenic-on-chip concept?
Résumé
For many years, microfluidics has been considered as a technology which allows to transform the way research is performed in the biological and chemical fields1,2. Microfluidic devices have been used in several fields with applications including cell encapsulation3, DNA analysis4, drug development5, cell and droplet sorting and separation6, chemical synthesis1 and separations7, proteomics8 and diagnostic
technologies9, radiopharmaceuticals10 and nanomedicines11 production amongst others. Despite the diversity of these application areas and a growing interest during the last decade, microfluidics largely remains a high technologically advanced area, and especially manufacturing of microfluidic chips, which is expensive and not necessarily ease of access. Indeed, traditional microfluidic manufacturing methods, such as soft lithography and microetching, require skills and equipment that are not widespread in a standard research laboratory of biology, chemistry or pharmaceutics.
In this work, we demonstrate the applicability of two common additive manufacturing techniques, namely fused deposition modelling (FDM) and multi-jet modelling (MJM), to prototype customized microfluidic devices such as chips (in Poly Ether Ether Ketone, PEEK) for nanomedicines formulation and holders with connectors and an integrated waterblock system for the chip thermalization (in PEEK and/or acrylic resin). Hence, the prototyping of chips allows to achieve a rational development in terms of costs and designs of Si/Glass chips manufactured by DRIE technology (Deep Reactive Ion Etching). Note that these Si/Glass chips are compatible for in situ physicochemical investigations (microscopy, X-ray and dynamic light scattering techniques). The internal structures (size and shape of channels) of PEEK and Si/Glass chips have been fully characterized by confocal and scanning electronic microscopy, respectively. Lastly, these sets of development contribute to the conception of a home-made microfluidic pilot with customized chips dedicated to (i) the formulation of nanomedicines in Good Laboratory and Manufacturing Practices compliance (possibility to operate in aseptic conditions in a laminar flow isolator) and (ii) the integration of in situ characterization techniques in order to investigate the physicochemical pathways of our formulation processes.