Lab-on-a-chip (LOC) and organ-on-a-chip (OOC) devices are highly versatile platforms that enable miniaturization and advanced controlled laboratory functions (i.e., microfluidics, advanced optical or electrical recordings, high-throughput screening). The manufacturing advancements of LOCs/OOCs for biomedical applications and their current limitations are briefly discussed. Multiple studies have exploited the advantages of mimicking organs or tissues on a chip. Among these, we focused our attention on the brain-on-a-chip, blood–brain barrier (BBB)-on-a-chip, and neurovascular unit (NVU)-on-a-chip applications. Mainly, we review the latest developments of brain-on-a-chip, BBB-on-a-chip, and NVU-on-a-chip devices and their use as testing platforms for high-throughput pharmacological screening. In particular, we analyze the most important contributions of these studies in the field of neurodegenerative diseases and their relevance in translational personalized medicine.
Glass is an alternative solution to polymer for the fabrication of three-dimensional (3D) microfluidic biochips. Femtosecond (fs) lasers are nowadays the most promising tools for transparent glass processing. Specifically, the multiphoton process induced by fs pulses enables fabrication of embedded 3D channels with high precision. The subtractive fabrication process creating 3D hollow structures in glass, known as fs laser-assisted etching (FLAE), is based on selective removal of the laser-modified regions by successive chemical etching in diluted hydrofluoric acid solutions. In this work we demonstrate the possibility to generate embedded hollow channels in photosensitive Foturan glass volume by high repetition rate picosecond (ps) laser-assisted etching (PLAE). In particular, the influence of the critical irradiation doses and etching rates are discussed in comparison of two different wavelengths of ultraviolet (355 nm) and visible (532 nm) ranges. Fast and controlled fabrication of a basic structure composed of an embedded micro-channel connected with two open reservoirs, commonly used in the biochip design, are achieved inside glass. Distinct advantages such as good aspect-ratio, reduced processing time for large areas, and lower fabrication cost are evidenced.
Various material processing techniques have been proposed for fabrication of smart surfaces that can modulate cellular behavior and address specific clinical issues. Among them, laser-based technologies have attracted growing interest due to processing versatility. Latest development of ultrashort pulse lasers with pulse widths from several tens of femtoseconds (fs) to several picoseconds (ps) allows clean microfabrication of a variety of materials at micro- and nanoscale both at surface and in volume. In this study, we addressed the possibility of 3D microfabrication of photosensitive glass (PG) by high repetition rate ps laser-assisted etching (PLAE) to improve the fabrication efficiency for the development of useful tools to be used for specific biological applications. Microfluidic structures fabricated by PLAE should provide the flow aspects, 3D characteristics, and possibility of producing functional structures to achieve the biologically relevant microenvironments. Specifically, the microfluidic structures could induce cellular chemotaxis over extended periods in diffusion-based gradient media. More importantly, the 3D characteristics could reproduce capillaries for in vitro testing of relevant organ models. Single cell trapping and analysis by using the fabricated microfluidic structures are also essential for understanding individual cell behavior within the same population. To this end, this paper demonstrates: (1) generation of 3D structures in glass volume or on surface for fabrication of microfluidic channels, (2) subtractive 3D surface patterning to create patterned molds in a controlled manor for casting polydimethylsiloxane (PDMS) structures and developing single cell microchambers, and (3) designing glass photo-masks to be used for sequel additive patterning of biocompatible nanomaterials with controlled shapes, sizes, and periodicity. Mesenchymal stem cells grown on laser-processed glass surfaces revealed no sign of cytotoxicity, while a collagen thin coating improved cellular adhesion.
This study investigates the morphological changes induced by femtosecond (fs) laser pulses in arsenic trisulfide (As2S3) thin films and gold–arsenic trisulfide (Au\As2S3) heterostructures, grown by pulsed laser deposition (PLD). By means of a direct laser writing experimental setup, the films were systematically irradiated at various laser power and irradiation times to observe their effects on surface modifications. AFM was employed for morphological and topological characterization. Our results reveal a clear transition threshold between photoexpansion and photoevaporation phenomena under different femtosecond laser power regimes, occurring between 1 and 1.5 mW, irrespective of exposure time. Notably, the presence of a gold layer in the heterostructure minimally influenced this threshold. A maximum photoexpansion of 5.2% was obtained in As2S3 films, while the Au\As2S3 heterostructure exhibited a peak photoexpansion of 0.8%. The study also includes a comparative analysis of continuous-wave (cw) laser irradiation, confirming the efficiency of fs laser pulses in inducing photoexpansion effects.
Foturan glass is a photosensitive transparent material which has attracted much interest for microfluidic applications due to possibility of volume processing by ultrafast lasers. In this work, we have investigated the effect of picosecond laser on volume processing in Foturan glass when varying the beam diameter incident on a lens. To this end, specific laser focusing configurations have been designed using raytracing models and an analysis protocol has been developed in the lens focusing region in order to describe the focal point displacement occurring at the variation of the incident laser beam diameter. The numerically simulated results were explained in association with Rayleigh length and found to be in good agreement with the experimental data obtained at well-defined conditions. Specifically, it was found that the hollow microstructures developed by thermal treatment and chemical etching after laser irradiation were significantly displaced along the propagation direction when the incident beam diameter varied in the range of 1-3.5 times. This approach aims to bring an essential contribution to the field of ultrashort pulse lasers micro- and nanoprocessing in transparent materials proving that the laser beam focus position and its size can be precisely controlled with high precision by automated optics for the variation of incident laser beam diameter in predefined conditions. This approach has the potential for laser multi-beam processing at various volume depths using the same optics setup and may even be applicable to two-photon excitation microscopy. On the other hand, the processing protocol in Foturan glass may allow understanding transparent material modification by tailoring laser beam characteristics.