Pedestal High-Contrast Gratings for Biosensing.

High-contrast gratings (HCG) are an excellent candidate for label-free detection of various kinds of biomarkers because they exhibit sharp and sensitive optical resonances. In this work, we experimentally show the performance of pedestal HCG (PHCG), which is significantly enhanced in comparison with that of conventional HCG. PCHGs were found to provide a 11.2% improvement in bulk refractive index sensitivity, from 482 nm/RIU for the conventional design to 536 nm/RIU. The observed resonance was narrower, resulting in a higher Q-factor and figure of merit. By depositing Al2O3, HfO2, and TiO2 of different thicknesses as model analyte layers, surface sensitivity values were estimated to be 10.5% better for PHCG. To evaluate the operation of the sensor in solution, avidin was employed as a model analyte. For avidin detection, the surface of the HCG was first silanized and subsequently functionalized with biotin, which is well known for its ability to bind selectively to avidin. A consistent red shift was observed with the addition of each of the functional layers, and the analysis of the spectral shift for various concentrations of avidin made it possible to calculate the limit of detection (LoD) and limit of quantification (LoQ) for the structures. PHCG showed a LoD of 2.1 ng/mL and LoQ of 85 ng/mL, significantly better than the values 3.2 ng/mL and 213 ng/mL respectively, obtained with the conventional HCG. These results demonstrate that the proposed PHCG have great potential for biosensing applications, particularly for detecting and quantifying low analyte concentrations.

Bioinspired Microstructured Polymer Surfaces with Antireflective Properties.

Over the years, different approaches to obtaining antireflective surfaces have been explored, such as using index-matching, interference, or micro- and nanostructures. Structural super black colors are ubiquitous in nature, and biomimicry thus constitutes an interesting way to develop antireflective surfaces. Moth-eye nanostructures, for example, are well known and have been successfully replicated using micro- and nanofabrication. However, other animal species, such as birds of paradise and peacock spiders, have evolved to display larger structures with antireflective features. In peacock spiders, the antireflective properties of their super black patches arise from relatively simple microstructures with lens-like shapes organized in tightly packed hexagonal arrays, which makes them a good candidate for cheap mass replication techniques. In this paper, we present the fabrication and characterization of antireflective microarrays inspired by the peacock spider's super black structures encountered in nature. Firstly, different microarrays 3D models are generated from a surface equation. Secondly, the arrays are fabricated in a polyacrylate resin by super-resolution 3D printing using two-photon polymerization. Thirdly, the resulting structures are inspected using a scanning electron microscope. Finally, the reflectance and transmittance of the printed structures are characterized at normal incidence with a dedicated optical setup. The bioinspired microlens arrays display excellent antireflective properties, with a measured reflectance as low as 0.042 ± 0.004% for normal incidence, a wavelength of 550 nm, and a collection angle of 14.5°. These values were obtained using a tightly-packed array of slightly pyramidal lenses with a radius of 5 µm and a height of 10 µm.

Polarization-Dependent All-Dielectric Metasurface for Single-Shot Quantitative Phase Imaging.

Phase retrieval is a noninterferometric quantitative phase imaging technique that has become an essential tool in optical metrology and label-free microscopy. Phase retrieval techniques require multiple intensity measurements traditionally recorded by camera or sample translation, which limits their applicability mostly to static objects. In this work, we propose the use of a single polarization-dependent all-dielectric metasurface to facilitate the simultaneous recording of two images, which are utilized in phase calculation based on the transport-of-intensity equation. The metasurface acts as a multifunctional device that splits two orthogonal polarization components and adds a propagation phase shift onto one of them. As a proof-of-principle, we demonstrate the technique in the wavefront sensing of technical samples using a standard imaging setup. Our metasurface-based approach fosters a fast and compact configuration that can be integrated into commercial imaging systems.

Large plasmonic color metasurfaces fabricated by super resolution deep UV lithography.

In this paper, we demonstrate plasmonic color metasurfaces as large as ∼60 cm2 fabricated by deep UV projection lithography employing an innovative combination of resolution enhancement techniques. Briefly, in addition to the established off-axis dipole illumination, double- and cross-exposure resolution enhancement of lithography, we introduce a novel element, the inclusion of transparent assist features to the mask layout. With this approach, we demonstrate the fabrication of relief arrays having critical dimensions such as 159 nm nanopillars or 210 nm nanoholes with 300 nm pitches, which is near the theoretical resolution limit expressed by the Rayleigh criterion for the 248 nm lithography tool used in this work. The type of surface structure, i.e. nanopillar or nanohole, and their diameters can be tailored simply by changing the width of the assist features included in the mask layout. By coating the obtained nanopatterns with thin layers of either Au or Al, we observe color spectra originating from the phenomenon known as localized surface plasmon resonance (LSPR). We demonstrate the generation of color palettes representing a broad spectral range of colors, and we employ finite element modelling to corroborate the measured LSPR fingerprint spectra. Most importantly, the ∼60 cm2 nanostructure arrays can be written in only a few minutes, which is a tremendous improvement compared to the more established techniques employed for fabricating similar structures.

Recent Advances in Microswimmers for Biomedical Applications.

Microswimmers are a rapidly developing research area attracting enormous attention because of their many potential applications with high societal value. A particularly promising target for cleverly engineered microswimmers is the field of biomedical applications, where many interesting examples have already been reported for e.g., cargo transport and drug delivery, artificial insemination, sensing, indirect manipulation of cells and other microscopic objects, imaging, and microsurgery. Pioneered only two decades ago, research studies on the use of microswimmers in biomedical applications are currently progressing at an incredibly fast pace. Given the recent nature of the research, there are currently no clinically approved microswimmer uses, and it is likely that several years will yet pass before any clinical uses can become a reality. Nevertheless, current research is laying the foundation for clinical translation, as more and more studies explore various strategies for developing biocompatible and biodegradable microswimmers fueled by in vivo-friendly means. The aim of this review is to provide a summary of the reported biomedical applications of microswimmers, with focus on the most recent advances. Finally, the main considerations and challenges for clinical translation and commercialization are discussed.

Membrane interactions in drug delivery: Model cell membranes and orthogonal techniques.

To generate the desired effect in the human body, the active pharmaceutical ingredient usually needs to interact with a receptor located on the cell membrane or inside the cell. Thus, understanding membrane interactions is of great importance when it comes to the development and testing of new drug molecules or new drug delivery systems. Nowadays, there is a tremendous selection of both model cell membranes and of techniques that can be used to characterize interactions between selected model cell membranes and a drug molecule, an excipient, or a drug delivery system. Having such a wide selection of model cell membranes and techniques available makes it sometimes challenging to select the optimal combination for a specific study. Furthermore, it is difficult to compare results obtained using different model cell membranes and techniques, and not all in vitro studies translate as well to an estimation of the in vivo biological activity or understanding of mode of action. This review provides an overview of the available lipid bilayer-based model cell membranes and of the most widely employed techniques for studying membrane interactions. Finally, the need for employing complimentary characterization techniques in order to acquire more reliable and in-depth information is highlighted.

Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons.

In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic neurons derived from stem cells could restore dopamine levels without additional motor complications. However, the transplanted cells disperse in vivo and it is not possible to stimulate them on demand to modulate dopamine release to prevent dyskinesia. In order to address these issues, this paper presents a multifunctional leaky optoelectrical fiber for potential neuromodulation and as a cell substrate for application in combined optogenetic stem cell therapy. Pyrolytic carbon coated optical fibers are laser ablated to pattern micro-optical windows to permit light leakage over a large area. The pyrolytic carbon acts as an excellent electrode for the electrochemical detection of dopamine. Human neural stem cells are genetically modified to express the light sensitive opsin channelrhodopsin-2 and are differentiated into dopaminergic neurons on the leaky optoelectrical fiber. Finally, light leaking from the micro-optical windows is used to stimulate the dopaminergic neurons resulting in the release of dopamine that is detected in real-time using chronoamperometry.

Optical catapulting of microspheres in mucus models-toward overcoming the mucus biobarrier.

The generalized phase contrast method is employed as an efficient "phase-only" laser beam-shaping technique in an optical setup built for catapulting microspheres through simple mucus models. The influence of the laser power and mucin concentration on the motion of the microspheres is investigated in terms of instant and average velocities on a 250-µm trajectory, corresponding to the mucus thickness in the human gastrointestinal tract. Increasing the laser power leads to higher velocities in all the tested samples, while increasing the mucin concentration leads to significant velocity decrease for similar laser input power. However, velocities of up to 95 µm · s - 1 are demonstrated in a 5% mucin simple mucus model using our catapulting system. This study contributes to understanding and overcoming the challenges of optical manipulation in mucus models. This paves the way for efficient optical manipulation of three-dimensional-printed light-controlled microtools with the ability to penetrate the mucus biobarrier for in vitro drug-delivery studies.

Natural convection induced by an optically fabricated and actuated microtool with a thermoplasmonic disk.

Two-photon polymerization was employed for fabricating microtools amenable to optical trapping and manipulation. A disk feature was included as part of the microtools and further functionalized by electron-beam deposition. The nanostructured gold layer on the disk facilitates off-resonant plasmonic heating upon illumination with a laser beam. As a consequence, natural convection characterized by the typical toroidal shape resembling that of Rayleigh-Bénard flow can be observed. A velocity of several µm·s-1 is measured for 2 µm microspheres dispersed in the surroundings of the microtool. To the best of our knowledge, this is the first time that thermoplasmonic-induced natural convection is experimentally demonstrated using a mobile heat source.

Sensing based on the motion of enzyme-modified nanorods.

Asymmetric modification with an enzyme confers nanorods an enhanced diffusive motion that is dependent on the concentration of the enzyme substrate. In turn, such a motion opens the possibility of determining the concentration of the enzyme substrate by measuring the diffusion coefficient of nanorods modified with the appropriate enzyme. Nanorods, with a Pt and a polypyrrole (PPy) segment, were fabricated. The PPy segment of such nanorods was then modified with glucose oxidase (GOx), glutamate oxidase (GluOx), or xanthine oxidase (XOD). Calibration curves, linking the diffusion coefficient of the oxidase-modified nanorods to the concentration of the oxidase substrate, were subsequently built. The oxidase-modified nanorods and their calibration curves were finally used to determine substrate concentrations both in simple aqueous solutions and in complex samples such as horse serum and cell culture media. Based on the obtained results we are confident that our motion-based approach to sensing can be developed to the point where different nanorods in a mixture simultaneously report on the concentration of different compounds with good temporal and spatial resolution.

Modification with hemeproteins increases the diffusive movement of nanorods in dilute hydrogen peroxide solutions.

Nanorods were decorated with different hemeproteins that are able to convert hydrogen peroxide. When dispersed into hydrogen peroxide solutions, most of these nanorods are characterized by diffusion coefficients which increase with the concentration of hydrogen peroxide. Such a behaviour does not characterize unmodified nanorods.