Dorothea Helmer

Three-dimensional printing of transparent fused silica glass

Glass is one of the most important high-performance materials used for scientific research, in industry and in society, mainly owing to its unmatched optical transparency, outstanding mechanical, chemical and thermal resistance as well as its thermal and electrical insulating properties. However, glasses and especially high-purity glasses such as fused silica glass are notoriously difficult to shape, requiring high-temperature melting and casting processes for macroscopic objects or hazardous chemicals for microscopic features. These drawbacks have made glasses inaccessible to modern manufacturing technologies such as three-dimensional printing (3D printing). Using a casting nanocomposite, here we create transparent fused silica glass components using stereolithography 3D printers at resolutions of a few tens of micrometres. The process uses a photocurable silica nanocomposite that is 3D printed and converted to high-quality fused silica glass via heat treatment. The printed fused silica glass is non-porous, with the optical transparency of commercial fused silica glass, and has a smooth surface with a roughness of a few nanometres. By doping with metal salts, coloured glasses can be created. This work widens the choice of materials for 3D printing, enabling the creation of arbitrary macro- and microstructures in fused silica glass for many applications in both industry and academia.

Liquid Glass: A Facile Soft Replication Method for Structuring Glass

Liquid glass is a photocurable amorphous silica nanocomposite that can be structured using soft replication molds and turned into glass via thermal debinding and sintering. Simple polymer bonding techniques allow the fabrication of complex microsystems in glass like microfluidic chips. Liquid glass is a step toward prototyping of glass microstructures at low cost without requiring cleanroom facilities or hazardous chemicals.

Rational design of a peptide capture agent for CXCL8 based on a model of the CXCL8:CXCR1 complex

Protein-capture agents are widely used for the detection, immobilization and isolation of proteins and are the foundation for the development of in vitro diagnostic chips. The chemokine CXCL8 is an interesting protein target due to its involvement in the human inflammatory response. We constructed a novel structural model of CXCL8 interaction with its G-protein coupled receptor CXCR1, taking into account previously reported experimental data. From this CXCL8:CXCR1 model complex, the interaction of CXCL8 with residues near the extracellular domains 3 and 4 of CXCR1 were used as a scaffold for the rational design of a peptide capture agent called ‘IL8RPLoops’. A molecular dynamics simulation of IL8RPLoops indicates a stable helical conformation consistent with the CXCR1 structure from which it was derived. CXCL8 capture in fluorescence-based assays on beads and on glass demonstrates that IL8RPLoops is an effective capture agent for CXCL8. Additionally, we found IL8RPLoops to be a potent inhibitor of CXCL8-induced neutrophil migration and CXCL8:CXCR1 association. A theoretical binding model for IL8RPLoops:CXCL8 is proposed, which shows the peptide predominantly interacting with CXCL8 via electrostatic contacts with the ELR motif at the CXCL8 N-terminus.

A haptotaxis assay for leukocytes based on surface-bound chemokine gradients

The migration of leukocytes in response to chemokine gradients is an important process in the homeostasis of the human immune system and inflammation. In vivo the migration takes place on the surface of the endothelium to which the chemokine gradient is immobilized via interaction with glycosaminoglycans. To study leukocyte migration in response to surface-bound chemokines, we generated chemokine gradients by a simple stamping method: agarose stamps were soaked with chemokine solution to form continuous chemokine gradients by diffusion. These gradients could be easily transferred to a petri dish surface by stamping. We show that neutrophil granulocytes recognize these gradients and migrate toward increasing chemokine concentrations dependent on the slope of the gradient. Single-cell responses were recorded, and statistical analyses of cell behavior and migration were performed. For analysis of chemotaxis/haptotaxis, we propose a chemotactic precision index that is broadly applicable, valid, and allows for a straightforward and rapid quantification of the precision by which cells follow the direction of a given gradient. The presented technique is very simple, cost-efficient, and can be broadly applied for generating defined and reproducible immobilized gradients of almost any protein on surfaces, and it is a valuable tool to study haptotaxis.

Functionalization of paper using photobleaching: A fast and convenient method for creating paper‐based assays with colorimetric and fluorescent readout

Lateral flow immunoassays (LFIA), where a protein–protein interaction can be monitored on a test strip by a color reaction, are of high interest in the field of point‐of‐care diagnostics due to their cost‐efficient production, portability, and ease of use. Despite their simple appearance, state‐of‐the‐art manufacturing of such test strips is not trivial since the strips comprise of several reaction zones: cellulose serves as hydrophilic support with excellent flow properties; and nitrocellulose is the membrane of choice for zones with immobilized biomolecules due to its hydrophobicity and thus preferable adhesion properties. These individual reaction zone membranes need to be joined together after fabrication. Variations in general membrane properties and production‐related lot‐to‐lot variations make it difficult to produce reliable tests with high reproducibility. In this paper, we present a facile and rapid method to immobilize antibodies directly onto cellulose by using maskless projection lithography. With this method it is possible to manufacture LFIA strips with individual reaction zones in a single material, i.e. cellulose.

Transparent, abrasion-insensitive superhydrophobic coatings for real-world applications

Superhydrophobic surfaces and surface coatings are of high interest for many applications in everyday life including non-wetting and low-friction coatings as well as functional clothing. Manufacturing of these surfaces is intricate since superhydrophobicity requires structuring of surfaces on a nano- to microscale. This delicate surface structuring makes most superhydrophobic surfaces very sensitive to abrasion and renders them impractical for real-life applications. In this paper we present a transparent fluorinated polymer foam that is synthesized by a simple one-step photoinitiated radical polymerization. We term this material “Fluoropor”. It possesses an inherent nano-/microstructure throughout the whole bulk material and is thus insensitive to abrasion as its superhydrophobic properties are not merely due to a thin-layer surface-effect. Due to its foam-like structure with pore sizes below the wavelength of visible light Fluoropor appears optically transparent. We determined contact angles, surface energy, wear resistance and Vickers hardness to highlight Fluoropor’s applicability for real-word applications.

Numerics made easy: solving the Navier–Stokes equation for arbitrary channel cross-sections using Microsoft Excel

The fluid mechanics of microfluidics is distinctively simpler than the fluid mechanics of macroscopic systems. In macroscopic systems effects such as non-laminar flow, convection, gravity etc. need to be accounted for all of which can usually be neglected in microfluidic systems. Still, there exists only a very limited selection of channel cross-sections for which the Navier–Stokes equation for pressure-driven Poiseuille flow can be solved analytically. From these equations, velocity profiles as well as flow rates can be calculated. However, whenever a cross-section is not highly symmetric (rectangular, elliptical or circular) the Navier–Stokes equation can usually not be solved analytically. In all of these cases, numerical methods are required. However, in many instances it is not necessary to turn to complex numerical solver packages for deriving, e.g., the velocity profile of a more complex microfluidic channel cross-section. In this paper, a simple spreadsheet analysis tool (here: Microsoft Excel) will be used to implement a simple numerical scheme which allows solving the Navier–Stokes equation for arbitrary channel cross-sections.

Glassomer-Processing Fused Silica Glass Like a Polymer

Fused silica glass is one of the most important high-performance materials for scientific research, industry, and society. However due to its high chemical and thermal resistance as well as high hardness, fused silica glass is notoriously difficult to structure. This work introduces Glassomer, a solid nanocomposite, which can be structured using polymer molding and subtractive technologies at submicrometer resolution. After polymer processing Glassomer is turned into optical grade fused silica glass during a final heat treatment. The resulting glass has the same optical transparency as commercial fused silica and a smooth surface with a roughness of a few nanometers. This work makes high-performance fused silica glass components accessible to high-throughput fabrication technologies and will enable numerous optical, photonic and medical applications in science and industry.

Suspended Liquid Subtractive Lithography: One-step generation of 3D channel geometries in viscous curable polymer matrices

The miniaturization of synthesis, analysis and screening experiments is an important step towards more environmentally friendly chemistry, statistically significant biology and fast and cost-effective medicinal assays. The facile generation of arbitrary 3D channel structures in polymers is pivotal to these techniques. Here we present a method for printing microchannels directly into viscous curable polymer matrices by injecting a surfactant into the uncured material via a steel capillary attached to a 3D printer. We demonstrate this technique using polydimethylsiloxane (PDMS) one of the most widely used polymers for the fabrication of, e. g. microfluidic chips. We show that this technique which we term Suspended Liquid Subtractive Lithography (SLSL) is well suited for printing actuators, T-junctions and complex three dimensional structures. The formation of truly arbitrary channels in 3D could revolutionize the fabrication of miniaturized chips and will find broad application in biology, chemistry and medicine.

Highly Fluorinated Methacrylates for Optical 3D Printing of Microfluidic Devices

Highly fluorinated perfluoropolyether (PFPE) methacrylates are of great interest for transparent and chemically resistant microfluidic chips. However, so far only a few examples of material formulations for three-dimensional (3D) printing of these polymers have been demonstrated. In this paper we show that microfluidic chips can be printed using these highly fluorinated polymers by 3D stereolithography printing. We developed photocurable resin formulations that can be printed in commercial benchtop stereolithography printers. We demonstrate that the developed formulations can be printed with minimal cross-sectional area of 600 µm for monolithic embedded microfluidic channels and 200 µm for open structures. The printed and polymerized PFPE methacrylates show a good transmittance above 70% at wavelengths between 520–900 nm and a high chemical resistance when being exposed to organic solvents. Microfluidic mixers were printed to demonstrate the great variability of different designs that can be printed using stereolithography.