Fabrication of multilevel metalenses using multiphoton lithography: from design to evaluation.

We present a procedure for the design of multilevel metalenses and their fabrication with multiphoton-based direct laser writing. This work pushes this fast and versatile fabrication technique to its limits in terms of achievable feature size dimensions for the creation of compact high-numerical aperture metalenses on flat substrates and optical fiber tips. We demonstrate the design of metalenses with various numerical apertures up to 0.96, and optimize the fabrication process towards nanostructure shape reproducibility. We perform optical characterization of the metalenses towards spot size, focusing efficiency, and optical functionality with a fiber beam collimation design, and compare their performance with refractive and diffractive counterparts fabricated with the same technology.

Increasing the Microfabrication Performance of Synthetic Hydrogel Precursors through Molecular Design.

Implementation of hydrogel precursors in two-photon polymerization (2PP) technology provides promising opportunities in the tissue engineering field thanks to their soft characteristics and similarity to extracellular matrix. Most of the hydrogels, however, are prone to post-fabrication deformations, leading to a mismatch between the computer-aided design and the printed structure. In the present work, we have developed novel synthetic hydrogel precursors to overcome the limitations associated with 2PP processing of conventional hydrogel precursors such as post-processing deformations and a narrow processing window. The precursors are based on a poly(ethylene glycol) backbone containing urethane linkers and are, on average, functionalized with six acrylate terminal groups (three on each terminal group). As a benchmark material, we exploited a precursor with an identical backbone and urethane linkers, albeit functionalized with two acrylate groups, that were reported as state-of-the-art. An in-depth characterization of the hexafunctional precursors revealed a reduced swelling ratio (<0.7) and higher stiffness (>36 MPa Young's modulus) compared to their difunctional analogs. The superior physical properties of the newly developed hydrogels lead to 2PP-based fabrication of stable microstructures with excellent shape fidelity at laser scanning speeds up to at least 90 mm s-1, in contrast with the distorted structures of conventional difunctional precursors. The hydrogel films and microscaffolds revealed a good cell interactivity after functionalization of their surface with a gelatin methacrylamide-based coating. The proposed synthesis strategy provides a one-pot and scalable synthesis of hydrogel building blocks that can overcome the current limitations associated with 2PP fabrication of hydrogel microstructures.

3D direct laser writing of microstructured optical fiber tapers on single-mode fibers for mode-field conversion.

We present a design and fabrication approach for 3D printed polymer microstructured optical fiber tapers on standard single-mode glass fibers for efficient and compact mode-field conversion. This paves the way towards complex functionalized fiber tips for various applications, like sensors and beam shaping components, currently limited by the mode-field size and distribution of standard optical fibers. In this paper, we demonstrate the potential of mode-field converting tapers for relaxing the misalignment tolerance in fiber-to-fiber connections and maximizing the coupling efficiency in fiber-to-chip connections. We demonstrate a mode-field diameter expansion ratio of 1.7 and reduction ratio of 3 and show that our microstructured tapers achieve a comparable performance in coupling efficiency as their step-index counterparts, while providing greater robustness.

Technological advancements for the development of stem cell-based models for hepatotoxicity testing.

Stem cells are characterized by their self-renewal capacity and their ability to differentiate into multiple cell types of the human body. Using directed differentiation strategies, stem cells can now be converted into hepatocyte-like cells (HLCs) and therefore, represent a unique cell source for toxicological applications in vitro. However, the acquired hepatic functionality of stem cell-derived HLCs is still significantly inferior to primary human hepatocytes. One of the main reasons for this is that most in vitro models use traditional two-dimensional (2D) setups where the flat substrata cannot properly mimic the physiology of the human liver. Therefore, 2D-setups are progressively being replaced by more advanced culture systems, which attempt to replicate the natural liver microenvironment, in which stem cells can better differentiate towards HLCs. This review highlights the most recent cell culture systems, including scaffold-free and scaffold-based three-dimensional (3D) technologies and microfluidics that can be employed for culture and hepatic differentiation of stem cells intended for hepatotoxicity testing. These methodologies have shown to improve in vitro liver cell functionality according to the in vivo liver physiology and allow to establish stem cell-based hepatic in vitro platforms for the accurate evaluation of xenobiotics.

On the potential use of two-photon polymerization to 3D print chromatographic packed bed supports.

The continuous quest for chromatographic supports offering kinetic performance properties superior to that of the packed bed of spheres has pushed the field to consider alternative formats such as for example monolithic and pillar array columns. This quest seems bound to culminate in the use of 3D printing technology, as this intrinsically offers the possibility to produce supports with a perfect uniformity and with a size and shape that is fully optimized for the chromatographic separation process. However, to be competitive with the current state-of-the-art, structures with sub-micron feature sizes are required. The present contribution therefore investigates the use of the 3D printing technology with the highest possible resolution available today, i.e., two-photon polymerization (2PP). It is shown that 2PP printing is capable of achieving the required ≤ 1 µm printing resolution. Depending on the laser scan speed, the lower limit through-pore size for a tetrahedral skeleton monolith with a theoretical 80% external porosity was found to be at 800 nm, when printing at a scan speed of 50 mm/s with a laser power of 10%. For a scan speed of 10 mm/s, the minimal through-pore size dropped to 500 nm. However, this very high resolution comes at the cost of excessively long printing times. The total printing time for a column volume equivalent to that of a typical nano-LC column (75 µm i.d. cylindrical tube with length L = 15 cm) has been determined to correspond to 330 and 470 h for the 50 mm/s and the 10 mm/s scan speed respectively. Other issues remaining to be solved are the need to clad the printed skeleton with a suitable mesoporous layer for chromatographic retention and the need to add a top-wall to the printed channels after the removal of the non-polymerized resin. It is therefore concluded that 2PP printing is not ready yet to replace the existing column fabrication methods.

SERS using two-photon polymerized nanostructures for mycotoxin detection.

Improved chemical- and bio-sensing with Surface Enhanced Raman Spectroscopy (SERS) requires nanostuctures that can be flexibly designed and fabricated with different physical and optical properties. Here, we present nano-pillar arrays ranging from 200 nm to 600 nm as SERS substrates for mycotoxin detection that are fabricated by means of two-photon polymerization. We built a nominal shape and a voxel-based model for simulating the enhancement of the electric field of the nano-pillar arrays using the Finite-Difference Time-Domain (FDTD) method. A new model was built based on the Atomic Force Microscopy (AFM) data obtained from the fabricated nanostructures and introduced into a FDTD model. We demonstrated the enhancement behavior by measuring the Raman spectrum of Rhodamine B solutions. Both the simulations and experimental results suggest that the 200 nm nano-pillar array has the highest Enhancement Factor (EF). Besides, we determined the limit of detection of the 200 nm pillar array by performing Raman measurements on Rhodamine B solutions with different concentrations. The detection limit of our 200 nm nano-pillar array is 0.55 µM. Finally we discriminated 1 ppm deoxynivalenol and 1.25 ppm fumonisin b1 in acetonitrile solutions by our SERS substrate in combination with principal component analysis. This versatile approach for SERS substrates fabrication gives new opportunities for material characterization in chemical and biological applications.