Soft-Lithography of Polyacrylamide Hydrogels Using Microstructured Templates: Towards Controlled Cell Populations on Biointerfaces.

Polyacrylamide hydrogels are interesting materials for studying cells and cell-material interactions, thanks to the possibility of precisely adjusting their stiffness, shear modulus and porosity during synthesis, and to the feasibility of processing and manufacturing them towards structures and devices with controlled morphology and topography. In this study a novel approach, related to the processing of polyacrylamide hydrogels using soft-lithography and employing microstructured templates, is presented. The main novelty relies on the design and manufacturing processes used for achieving the microstructured templates, which are transferred by soft-lithography, with remarkable level of detail, to the polyacrylamide hydrogels. The conceived process is demonstrated by patterning polyacrylamide substrates with a set of vascular-like and parenchymal-like textures, for controlling cell populations. Final culture of amoeboid cells, whose dynamics is affected by the polyacrylamide patterns, provides a preliminary validation of the described strategy and helps to discuss its potentials.

Synergies between Surface Microstructuring and Molecular Nanopatterning for Controlling Cell Populations on Polymeric Biointerfaces.

Polymeric biointerfaces are already being used extensively in a wide set of biomedical devices and systems. The possibility of controlling cell populations on biointerfaces may be essential for connecting biological systems to synthetic materials and for researching relevant interactions between life and matter. In this study, we present and analyze synergies between an innovative approach for surface microstructuring and a molecular nanopatterning procedure of recent development. The combined set of techniques used may be instrumental for the development of a new generation of functional polymeric biointerfaces. Eukaryotic cell cultures placed upon the biointerfaces developed, both before and after molecular patterning, help to validate the proposal and to discuss the synergies between the surface microstructuring and molecular nanopatterning techniques described in the study. Their potential role in the production of versatile polymeric biointerfaces for lab- and organ-on-a-chip biodevices and towards more complex and biomimetic co-culture systems and cell cultivation set-ups are also examined.

Research on the Methods for the Mass Production of Multi-Scale Organs-On-Chips.

The success of labs- and organs-on-chips as transformative technologies in the biomedical arena relies on our capacity of solving some current challenges related to their design, modeling, manufacturability, and usability. Among present needs for the industrial scalability and impact promotion of these bio-devices, their sustainable mass production constitutes a breakthrough for reaching the desired level of repeatability in systematic testing procedures based on labs- and organs-on-chips. The use of adequate biomaterials for cell-culture processes and the achievement of the multi-scale features required, for in vitro modeling the physiological interactions among cells, tissues, and organoids, which prove to be demanding requirements in terms of production. This study presents an innovative synergistic combination of technologies, including: laser stereolithography, laser material processing on micro-scale, electroforming, and micro-injection molding, which enables the rapid creation of multi-scale mold cavities for the industrial production of labs- and organs-on-chips using thermoplastics apt for in vitro testing. The procedure is validated by the design, rapid prototyping, mass production, and preliminary testing with human mesenchymal stem cells of a conceptual multi-organ-on-chip platform, which is conceived for future studies linked to modeling cell-to-cell communication, understanding cell-material interactions, and studying metastatic processes.

Tailored surface-enhanced Raman nanopillar arrays fabricated by laser-assisted replication for biomolecular detection using organic semiconductor lasers.

Organic semiconductor distributed feedback (DFB) lasers are of interest as external or chip-integrated excitation sources in the visible spectral range for miniaturized Raman-on-chip biomolecular detection systems. However, the inherently limited excitation power of such lasers as well as oftentimes low analyte concentrations requires efficient Raman detection schemes. We present an approach using surface-enhanced Raman scattering (SERS) substrates, which has the potential to significantly improve the sensitivity of on-chip Raman detection systems. Instead of lithographically fabricated Au/Ag-coated periodic nanostructures on Si/SiO2 wafers, which can provide large SERS enhancements but are expensive and time-consuming to fabricate, we use low-cost and large-area SERS substrates made via laser-assisted nanoreplication. These substrates comprise gold-coated cyclic olefin copolymer (COC) nanopillar arrays, which show an estimated SERS enhancement factor of up to ∼ 10(7). The effect of the nanopillar diameter (60-260 nm) and interpillar spacing (10-190 nm) on the local electromagnetic field enhancement is studied by finite-difference-time-domain (FDTD) modeling. The favorable SERS detection capability of this setup is verified by using rhodamine 6G and adenosine as analytes and an organic semiconductor DFB laser with an emission wavelength of 631.4 nm as the external fiber-coupled excitation source.

Organic semiconductor distributed feedback laser pixels for lab-on-a-chip applications fabricated by laser-assisted replication.

The integration of organic semiconductor distributed feedback (DFB) laser sources into all-polymer chips is promising for biomedical or chemical analysis. However, the fabrication of DFB corrugations is often expensive and time-consuming. Here, we apply the method of laser-assisted replication using a near-infrared diode laser beam to efficiently fabricate inexpensive poly(methyl methacrylate) (PMMA) chips with spatially localized organic DFB laser pixels. This time-saving fabrication process enables a pre-defined positioning of nanoscale corrugations on the chip and a simultaneous generation of nanoscale gratings for organic edge-emitting laser pixels next to microscale waveguide structures. A single chip of size 30 mm × 30 mm can be processed within 5 min. Laser-assisted replication allows for the subsequent addition of further nanostructures without a negative impact on the existing photonic components. The minimum replication area can be defined as being as small as the diode laser beam focus spot size. To complete the fabrication process, we encapsulate the chip in PMMA using laser transmission welding.

Integrated microinterferometric sensor for in-plane displacement measurement.

We present an integrated sensor based on a grating interferometer (GI) for in-plane displacement measurement in microregions of large engineering structures. The system concept and design, based on a monolithic version of Czarnek's GI, is discussed in detail. The technology chain of the GI measurement head (MH), including the master fabrication and further replication by means of hot embossing, is described. The numerical analyses of the MH by means of geometric ray tracing and scalar wave propagation are provided. They allow us to determine geometrical tolerance values as well as refractive index homogeneity and nonflatness of MH working surfaces, which provide proper beam guiding. Finally the demonstrative measurement performed with a model of the sensor is presented.