Publikationen

Electro-physiological sensing devices are becoming increasingly common in diverse applications. However, designing such sensors in compact form factors and for high-quality signal acquisition is a challenging task even for experts, is typically done using heuristics, and requires extensive training. Our work proposes a computational approach for designing multi-modal electro-physiological sensors. By employing an optimization-based approach alongside an integrated predictive model for multiple modalities, compact sensors can be created which offer an optimal trade-off between high signal quality and small device size. The task is assisted by a graphical tool that allows to easily specify design preferences and to visually analyze the generated designs in real-time, enabling designer-in-the-loop optimization. Experimental results show high quantitative agreement between the prediction of the optimizer and experimentally collected physiological data. They demonstrate that generated designs can achieve an optimal balance between the size of the sensor and its signal acquisition capability, outperforming expert generated solutions.

Ionic liquids are modern liquid materials with potential and actual implementation in many advanced technologies. They combine many favourable and modifiable properties but have a major inherent drawback compared to molecular liquids – slower dynamics. In previous studies we found that the dynamics of ionic liquids are significantly accelerated by the introduction of multiple ether side chains into the cations. However, the origin of the improved transport properties, whether as a result of the altered cation conformation or due to the absence of nanostructuring within the liquid as a result of the higher polarity of the ether chains, remained to be clarified. Therefore, we prepared two novel sets of methylammonium based ionic liquids; one set with three ether substituents and another set with three butyl side chains, in order to compare their dynamic properties and liquid structures. Using a range of anions, we show that the dynamics of the ether-substituted cations are systematically and distinctly accelerated. Liquefaction temperatures are lowered and fragilities increased, while at the same time cation–anion distances are slightly larger for the alkylated samples. Furthermore, pronounced liquid nanostructures were not observed. Molecular dynamics simulations demonstrate that the origin of the altered properties of the ether substituted ionic liquids is primarily due to a curled ether chain conformation, in contrast to the alkylated cations where the alkyl chains retain a linear conformation. Thus, the observed structure–property relations can be explained by changes in the geometric shape of the cations, rather than by the absence of a liquid nanostructure. Application of quantum chemical calculations to a simplified model system revealed that intramolecular hydrogen-bonding is responsible for approximately half of the stabilisation of the curled ether-cations, whereas the other half stems from non-specific long-range interactions. These findings give more detailed insights into the structure–property relations of ionic liquids and will guide the development of ionic liquids that do not suffer from slow dynamics.

Atom probe tomography (APT) provides sub-nm resolution in the analysis of complex industrial steels. It can resolve the carbonitride precipitates in Nb-Ti microalloyed high-strength low-alloy (HSLA) steels that strongly affect material performance and illuminate the complex precipitation sequence before and during the thermo-mechanical controlled process (TMCP). However, the precipitate concentration is low in HSLA steels during austenite conditioning, especially at temperatures > 850 °C, so that the probability of detecting precipitates via APT is below 5%. Here, we demonstrate two encapsulation-based approaches that increase the precipitate concentration in the APT sample volume sufficiently to enable the analysis of sparse precipitates. The first method is based on metallographic etching and direct targeting of precipitates in the steel. A focused ion beam was used to mark precipitation sites. Encapsulation with nickel-phosphorus (Ni-P) enabled localized APT and increased the yield by a factor of 10. The second method relies on the chemical extraction of precipitates and subsequent encapsulation in a silicon oxide (SiOx) network at a very high particle density. Analysis of tips cut from the encapsulated particles increased the yield by a factor of >15. We discuss and compare the spatial and chemical accuracy obtained in the analysis of pure Nb-, Ti- and mixed Nb-Ti carbonitrides.

The organization of plasmonic nanoparticles (NPs) determines the strength and polarization dependence of coupling of their surface plasmons. In this study, plasmon coupling of spherical Au NPs with an average diameter of 15 nm was investigated in shape-memory polymer films before and after mechanical stretching and then after thermally driving shape recovery. Clusters of Au NPs form when preparing the films that exhibit strong plasmon coupling. During stretching, a significant polarization-dependent response develops, where the optical extinction maximum corresponding to the surface plasmon resonance is redshifted by 19 nm and blueshifted by 7 nm for polarization parallel and perpendicular to the stretching direction, respectively. This result can be explained by non-uniform stretching on the nanoscale, where plasmon coupling increases parallel to the shear direction as Au NPs are pulled into each other during stretching. The polarization dependence vanishes after shape recovery, and structural characterization confirms the return of isotropy consistent with complete nanoscale recovery of the initial arrangement of Au NPs. Simulations of the polarized optical responses of Au NP dimers at different interparticle spacings establish a plasmon ruler for estimating the average interparticle spacings within the experimental samples. An investigation of the temperature-dependent recovery behavior demonstrates an application of these materials as optical thermal history sensors.

Metal-assisted chemical etching (MACE) affords porous silicon nanostructures control over size, shape, and porosity in a single step. Simplicity and flexibility are potential advantages over more traditional silicon bulk micromachining techniques. MACE-generated porous micro- and nanostructures are suitable as biomaterials through their length scales and biocompatibility. This work provides a comprehensive overview of the MACE reaction mechanism that yields biomedically relevant silicon nanostructures – from nanowires, nanopillars, to sub-micrometer holes and pores. We discuss their biomedical applications in biosensors, cell capture and transfection arrays, and drug delivery vectors. We assess the reported benefits of the various nanostructures and discuss whether MACE provides clear and distinct advantages over other techniques. The flexibility and simplicity of MACE comes at a cost. The reaction parameters are many and inter-related, and we lack a full model of the etching mechanism. While the cathode reaction is well understood, the anode reaction involving dissolution of the silicon remains controversial. Such uncertainties impede rational design of specific structures that address biomedical requirements. We summarize current understanding to provide design guidelines for structures used in biomedicine and review the effects of key parameters on the morphological attributes of the etched features.

Recently the use of microRNAs (miRNAs) as biomarkers for a multitude of diseases has gained substantial significance for clinical as well as point-of-care diagnostics. Amongst other challenges, however, it holds the central requirement that the concentration of a given miRNA must be evaluated within the context of other factors in order to unambiguously diagnose one specific disease. In terms of the development of diagnostic methods and devices, this implies an inevitable demand for multiplexing in order to be able to gauge the abundance of several components of interest in a patient's sample in parallel. In this study, we design and implement different multiplexed versions of our electrochemical microfluidic biosensor by dividing its channel into subsections, creating four novel chip designs for the amplification-free and simultaneous quantification of up to eight miRNAs on the CRISPR-Biosensor X (‘X’ highlighting the multiplexing aspect of the device). We then use a one-step model assay followed by amperometric readout in combination with a 2-min-stop-flow-protocol to explore the fluidic and mechanical characteristics and limitations of the different versions of the device. The sensor showing the best performance, is subsequently used for the Cas13a-powered proof-of-concept measurement of two miRNAs (miRNA-19b and miRNA-20a) from the miRNA-17–92 cluster, which is dysregulated in the blood of pediatric medulloblastoma patients. Quantification of the latter, alongside simultaneous negative control measurements are accomplished on the same device. We thereby confirm the applicability of our platform to the challenge of amplification-free, parallel detection of multiple nucleic acids. © 2020 Elsevier B.V.

Materials in nature have fascinating properties that serve as a continuous source of inspiration for materials scientists. Accordingly, bio-mimetic and bio-inspired approaches have yielded remarkable structural and functional materials for a plethora of applications. Despite these advances, many properties of natural materials remain challenging or yet impossible to incorporate into synthetic materials. Natural materials are produced by living cells, which sense and process environmental cues and conditions by means of signaling and genetic programs, thereby controlling the biosynthesis, remodeling, functionalization, or degradation of the natural material. In this context, synthetic biology offers unique opportunities in materials sciences by providing direct access to the rational engineering of how a cell senses and processes environmental information and translates them into the properties and functions of materials. Here, we identify and review two main directions by which synthetic biology can be harnessed to provide new impulses for the biologization of the materials sciences: first, the engineering of cells to produce precursors for the subsequent synthesis of materials. This includes materials that are otherwise produced from petrochemical resources, but also materials where the bio-produced substances contribute unique properties and functions not existing in traditional materials. Second, engineered living materials that are formed or assembled by cells or in which cells contribute specific functions while remaining an integral part of the living composite material. We finally provide a perspective of future scientific directions of this promising area of research and discuss science policy that would be required to support research and development in this field. © 2021 The Author(s)

Available methods for efficient gene transfer into user-selected or even single cells suffer from high invasiveness or the need for complicated equipment. Here, we present a technology for the light-guided transduction of native cell lines and primary cells by adeno-associated viral (AAV) vectors. We demonstrate the spatially resolved transduction of different cells with different genes within one culture and the selective transduction of single cells by local illumination. © 2021, Die Autoren.

Biological signals are sensed by their respective receptors and are transduced and pro-cessed by a sophisticated intracellular signaling network leading to a signal-specific cellular re-sponse. Thereby, the response to the signal depends on the strength, the frequency, and the duration of the stimulus as well as on the subcellular signal progression. Optogenetic tools are based on genetically encoded light-sensing proteins facilitating the precise spatiotemporal control of signal transduction pathways and cell fate decisions in the absence of natural ligands. In this review, we provide an overview of optogenetic approaches connecting light-regulated protein-protein interaction or caging/uncaging events with steering the function of signaling proteins. We briefly discuss the most common optogenetic switches and their mode of action. The main part deals with the engineering and application of optogenetic tools for the control of transmembrane receptors including receptor tyrosine kinases, the T cell receptor and integrins, and their effector proteins. We also ad-dress the hallmarks of optogenetics, the spatial and temporal control of signaling events. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.