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Abstract Pharmaceutical formulations are increasingly based on drug nanoparticles or carrier nanoparticles encapsulating drugs or mRNA molecules. Sizes and monodispersity of the nanoparticles regulate bioavailability, pharmacokinetics and pharmacology. Microfluidic mixers promise unique conditions for their continuous preparation. A novel microfluidic antisolvent precipitation device was realized by two-photon-polymerization with a mixing channel in which the organic phase formed a sheet with a homogeneous thickness of down to 7 μm completely wrapped in the aqueous phase. Homogeneous diffusion through the sheet accelerates mixing. Optical access was implemented to allow in-situ dynamic light scattering. By centering the thin sheet in the microchannel cross-section, two important requirements are met. On the one hand, the organic phase never reaches the channel walls, avoiding fouling and unstable flow conditions. On the other hand, in the sheet positioned at the maximum of the parabolic flow profile the nanoparticle velocities are homogenized which enables flow-compensated Dynamic Light Scattering (flowDLS). These unique features allowed in-situ particle size determination for the first time. Monitoring of lipid nanoparticle precipitation was demonstrated for different rates of solvent and antisolvent flows. This breakthrough innovation will not only enable feedback control of nanoparticle production but also will provide new insights into the dynamics of nanoparticle precipitation.

Filamentous microorganisms exhibit a complex macro-morphology constituted of branched and cross-linked hyphae. Fully resolved mechanical models of such mycelial compounds rely heavily on accurate input data for mechanical properties of individual hyphae. Due to their irregular shape and high adaptability to environmental factors, the measurement of these intrinsic properties remains challenging. To overcome previous shortcomings of microfluidic bending tests, a novel system for the precise measurement of the individual bending stiffness of fungal hyphae is presented in this study. Utilizing two-photon polymerization, microfluidic molds were fabricated with a multi-material approach, enabling the creation of 3D cell traps for spore immobilization. Unlike previous works applying the methodology of microfluidic bending tests, the hyphae were deflected in the vertical center of the microfluidic channel, eliminating the adverse influence of nearby walls on measurements. This lead to a significant increase in measurement yield compared to the conventional design. The accuracy and reproducibility of bending tests was ensured through validation of the measurement flow using micro-particle image velocimetry. Our results revealed that the bending stiffness of hyphae of Aspergillus niger is approximately three to four times higher than that reported for Candida albicans hyphae. At the same time, the derived longitudinal Young’s Modulus of the hyphal cell wall yields a comparable value for both organisms. The methodology established in this study provides a powerful tool for studying the effects of cultivation conditions on the intrinsic mechanical properties of single hyphae. Applying the results to resolved numerical models of mycelial compounds promises to shed light on their response to hydrodynamic stresses in biotechnological cultivation, which influences their expressed macro-morphology and in turn, product yields.

Abstract Blue-green infrastructure (BGI), combining semi-natural and engineered elements, offers multifaceted benefits like stormwater management, water purification, heat mitigation, and habitat provision. However, current BGI designs prioritize engineering goals, overlooking its ecological potential. Here we advocate for integrating engineering and ecological objectives into BGI design to enhance performance and biodiversity. Through an interdisciplinary literature review, we emphasize the importance of species diversity, abundance, and ecological processes, to improve engineering performance and resilience, and lower management costs. We emphasize the importance of interdisciplinary collaboration to navigate trade-offs between engineering and ecological objectives, ultimately enabling us to engineer both for and with biodiversity.

Flexible sensor arrays with multilevel circuits typically require complex production cycles leading to high costs and reliability issues. For establishing flexible arrays of strain sensors in Wheatstone bridge configurations structures on different levels within flexible films have to be connected by robust μ-via technology. Usually, dry etching is used to establish via-holes and direct current (DC) electrodeposition is used to fill them with copper. However, dry etching can lead to damages in the underlying electrode or incomplete removal of polymeric material, as inhomogeneities of polymeric foil thicknesses cannot completely be eliminated. This affects the quality of the plating and the reliability of the μ-via connections. It is aggravated by the fact that DC electroplated copper is often weakened by various defects, such as small voids. This article describes a reliable and less complex fabrication process for a Wheatstone bridge sandwich structure consisting of five polymer interlayers separating four metal layers. The femtosecond-laser μ-via drilling proved to be fast, material selective and therefore tolerant to inhomogeneities of polymeric foil thicknesses. Moreover, pulsed current (PC) electrodeposition significantly improved the quality of the copper filling. No voids were found using electron microscopy. Finally, the respiration monitoring sensors produced using this method were subjected to repetitive cycles of bending and relaxation. At a frequency of five cycles per second, reproducible cycles of signal changes were obtained, indicating the usefulness for detecting respiratory cycles of premature infants.

Microbioreactors increase information output in biopharmaceutical screening applications because they can be operated in parallel without consuming large quantities of the pharmaceutical formulations being tested. A capillary wave microbioreactor (cwMBR) has recently been reported, allowing cost-efficient parallelization in an array that can be activated for mixing as a whole. Although impedance spectroscopy can directly distinguish between dead and viable cells, the monitoring of cells in suspension within bioreactors is challenging because the signal is influenced by the potentially varying properties of the culture medium. In order to address this challenge, an impedance sensor consisting of two sets of microelectrodes in a cwMBR is presented. Only one set of electrodes was covered by a two-photon cross-linked hydrogel to become insensitive to the influence of cells while remaining sensitive to the culture medium. With this impedance sensor, the biomass of Saccharomyces cerevisiae could be measured in a range from 1 to 20 g L−1. In addition, the sensor can compensate for a change in the conductivity of the suspension of 5 to 15 mS cm−1. Moreover, the two-photon cross-linking of hydroxyethyl starch methacrylate hydrogel, which has been studied in detail, recommends itself for even much broader sensing applications in miniaturized bioreactors and biosensors.

Future industrial applications of microparticle fractionation with deterministic lateral displacement (DLD) devices are hindered by exceedingly low throughput rates. To enable the necessary high-volume flows, high flow velocities as well as high aspect ratios in DLD devices have to be investigated. However, no experimental studies have yet been conducted on the fractionation of bi-disperse suspensions containing particles below 10 µm with DLD at a Reynolds number (Re) above 60. Furthermore, devices with an aspect ratio of more than 4:1, which require advanced microfabrication, are not known in the DLD literature. Therefore, we developed a suitable process with deep reactive ion etching of silicon and anodic bonding of a glass lid to create pressure-resistant arrays. With a depth of 120 µm and a gap of 23 µm between posts, a high aspect ratio of 6:1 was realized, and devices were investigated using simulations and fractionation experiments. With the two-segmented array of 3° and 7° row shifts, critical diameters of 8 µm and 12 µm were calculated for low Re conditions, but it was already known that vortices behind the posts can shift these values to lower critical diameters. Suspensions with polystyrene particles in different combinations were injected with an overall flow rate of up to 15 mL/min, corresponding to Re values of up to 90. Suspensions containing particle combinations of 2 µm with 10 µm as well as 5 µm with 10 µm were successfully fractionated, even at the highest flow rate. Under these conditions, a slight widening of the displacement position was observed, but there was no further reduction in the critical size as it was for Re = 60. With an unprecedented fractionation throughput of nearly 1 L per hour, entirely new applications are being developed for chemical, pharmaceutical, and recycling technologies.

This paper describes the design, fabrication, integration, characterization, and demonstration of a novel flexible double-sided curvature sensor array for use in soft robotics. The paper explores the performance and potential applications of a piezoresistive sensor array consisting of four gold strain gauges on a flexible polyimide (PI) substrate arranged in a Wheatstone bridge configuration. Multiple sensor strips were arranged like the fingers of a hand. Integrating Shape Memory Alloy (SMA) foils alongside the fingers was explored to mimic a human hand-gripping motion controlled with temperature, while curvature sensor array strips measure the resulting finger shapes. Moreover, object sensing in a flexible granular material gripper was demonstrated. The sensors were embedded within Polydimethylsiloxane (PDMS) to enhance their tactile feel and adhesive properties. The findings of this study are promising for future applications, particularly in robotics and prosthetics, as the ability to accurately mimic human hand movements and reconstruct sensor surfaces paves the way for robotic hand functionality.

The nasal mucosa, being accessible and highly vascularized, opens up new opportunities for the systemic administration of drugs. However, there are several protective functions like the mucociliary clearance, a physiological barrier which represents is a difficult obstacle for drug candidates to overcome. For this reason, effective testing procedures are required in the preclinical phase of pharmaceutical development. Based on a recently reported immortalized porcine nasal epithelial cell line, we developed a test platform based on a tissue-compatible microfluidic chip. In this study, a biomimetic glass chip, which was equipped with a controlled bidirectional airflow to induce a physiologically relevant wall shear stress on the epithelial cell layer, was microfabricated. By developing a membrane transfer technique, the epithelial cell layer could be pre-cultivated in a static holder prior to cultivation in a microfluidic environment. The dynamic cultivation within the chip showed a homogenous distribution of the mucus film on top of the cell layer and a significant increase in cilia formation compared to the static cultivation condition. In addition, the recording of the ciliary transport mechanism by microparticle image velocimetry was successful. Using FITC-dextran 4000 as an example, it was shown that this nasal mucosa on a chip is suitable for permeation studies. The obtained permeation coefficient was in the range of values determined by means of other established in vitro and in vivo models. This novel nasal mucosa on chip could, in future, be automated and used as a substitute for animal testing.

Embedded porous membranes are a key element of various organ-on-chip systems. The widely used commercial polymer membranes impose limits with regard to chip integration and thinness. We report a microfluidic chip platform with the key element of a monolithically integrated, ultra-thin (700 nm) nanoporous membrane made of ultra-low-stress (

In recent years, there has been a significant increase in the registration of drugs for nasal application with systemic effects. Previous preclinical in vitro test systems for transmucosal drug absorption studies have mostly been based on primary cells or on tumor cell lines such as RPMI 2650, but both approaches have disadvantages. Therefore, the aim of this study was to establish and characterize a novel immortalized nasal epithelial cell line as the basis for an improved 3D cell culture model of the nasal mucosa. First, porcine primary cells were isolated and transfected. The P1 cell line obtained from this process was characterized in terms of its expression of tissue-specific properties, namely, mucus expression, cilia formation, and epithelial barrier formation. Using air–liquid interface cultivation, it was possible to achieve both high mucus formation and the development of functional cilia. Epithelial integrity was expressed as both transepithelial electrical resistance and mucosal permeability, which was determined for sodium fluorescein, rhodamine B, and FITC-dextran 4000. We noted a high comparability of the novel cell culture model with native excised nasal mucosa in terms of these measures. Thus, this novel cell line seems to offer a promising approach for developing 3D nasal mucosa tissues that exhibit favorable characteristics to be used as an in vitro system for testing drug delivery systems.

Observing the curing reaction of epoxy resins is a key to quality assurance in fibre composite production. The evaluation of electrical impedance spectra is an established monitoring method. Such impedance spectra contain the physical effects of dipole relaxation, ionic conduction and electrode polarisation, which shift to lower frequencies as curing progresses. In the early stage of the curing reaction, ionic conductivity and electrode polarisation dominate, and in the later stage of the curing reaction, dipole relaxation dominates. Due to the shift of the effects over several frequency decades, it makes sense to evaluate electrical impedance spectra not exclusively at one frequency but over an entire available frequency spectrum. The measured spectral raw data cannot be easily interpreted by a control algorithm and have to be mapped to simpler key indicators. For this purpose, a frequency-dependent model is proposed to address the aforementioned physical effects. With only five free parameters, measured spectra can be described with a relative error of only 2.3%. The shift of the occurring effects to lower frequencies necessitates switching the key indicator used in the progression of the cure reaction.

Electrical impedance spectroscopy (EIS) is widely recognized as a powerful tool in biomedical research. For example, it allows detection and monitoring of diseases, measuring of cell density in bioreactors, and characterizing the permeability of tight junctions in barrier-forming tissue models. However, with single-channel measurement systems, only integral information is obtained without spatial resolution. Here we present a low-cost multichannel impedance measurement set-up capable of mapping cell distributions in a fluidic environment by using a microelectrode array (MEA) realized in 4-level printed circuit board (PCB) technology including layers for shielding, interconnections, and microelectrodes. The array of 8 × 8 gold microelectrode pairs was connected to home-built electric circuitry consisting of commercial components such as programmable multiplexers and an analog front-end module which allows the acquisition and processing of electrical impedances. For a proof-of-concept, the MEA was wetted in a 3D printed reservoir into which yeast cells were locally injected. Impedance maps were recorded at 200 kHz which correlate well with the optical images showing the yeast cell distribution in the reservoir. Blurring from parasitic currents slightly disturbing the impedance maps could be eliminated by deconvolution using an experimentally determined point spread function. The MEA of the impedance camera can in future be further miniaturized and integrated into cell cultivation and perfusion systems such as organ on chip devices to augment or even replace light microscopic monitoring of cell monolayer confluence and integrity during the cultivation in incubation chambers.

Numerous synthetic techniques for the fabrication of porous metal electrodes were developed in recent decades. A very promising and facile route is the 3D printing of structures, which can be designed directly on the computer first. However, the current techniques allow structures to be printed with a resolution down to 20 µm, which is still quite rough regarding tuning the pore distribution and diameter of electrode materials for potential applications. For the first time, a laser-induced forward transfer (LIFT) process was used to 3D print metal voxels on a solid surface, resulting in a porous electrocatalytically active gold (Au) electrode film. Porous Au electrodes produced using LIFT showed an increase in the electrochemically active surface area (SA) by a factor of four compared with a sputtered dense Au film when characterized using cyclic voltammetry (CV) in Ar-saturated 0.1 M KOH. Therefore, the LIFT process can be considered very promising for the printing of ordered porous electrodes with high surface areas for electrochemical applications.

The synthesis of nanoparticles in microchannels promises the advantages of small size, uniform shape and narrow size distribution. However, only with insights into the mixing processes can the most suitable designs and operating conditions be systematically determined. Coaxial lamination mixers (CLM) built by 2-photon polymerization can operate long-term stable nanoparticle precipitation without fouling issues. Contact of the organic phase with the microchannel walls is prevented while mixing with the aqueous phase is intensified. A coaxial nozzle allows 3D hydrodynamic focusing followed by a sequence of stretch-and-fold units. By means of a digital twin based on computational fluid dynamics (CFD) and numerical evaluation of mixing progression, the influences of operation conditions are now studied in detail. As a measure for homogenization, the mixing index (MI) was extracted as a function of microchannel position for different operating parameters such as the total flow rate and the share of solvent flow. As an exemplary result, behind a third stretch-and-fold unit, practically perfect mixing (MI>0.9) is predicted at total flow rates between 50 µL/min and 400 µL/min and up to 20% solvent flow share. Based on MI values, the mixing time, which is decisive for the size and dispersity of the nanoparticles, can be determined. Under the conditions considered, it ranges from 5 ms to 54 ms. A good correlation between the predicted mixing time and nanoparticle properties, as experimentally observed in earlier work, could be confirmed. The digital twin combining CFD with the MI methodology can in the future be used to adjust the design of a CLM or other micromixers to the desired total flow rates and flow rate ratios and to provide valuable predictions for the mixing time and even the properties of nanoparticles produced by microfluidic antisolvent precipitation.

An integrable sensor inlay for monitoring crack initiation and growth inside bondlines of structural carbon fiber-reinforced plastic (CFRP) components is presented. The sensing structures are sandwiched between crack-stopping poly(vinyliden fluoride) (PVDF) and a thin reinforcing polyetherimide (PEI) layer. Good adhesion at all interfaces of the sensor system and to the CFRP material is crucial, as weak bonds can counteract the desired crack-stopping functionality. At the same time, the chosen reinforcing layer must withstand high strains, safely support the metallic measuring grids, and possess outstanding fatigue strength. We show that this robust sensor system, which measures the strain at two successive fronts inside the bondline, allows to recognize cracks in the proximity of the inlay regardless of the mechanical loads. Feasibility is demonstrated by static load tests as well as cyclic long-term fatigue testing for up to 1,000,000 cycles. In addition to pure crack detection, crack distance estimation based on sensor signals is illustrated. The inlay integration process is developed with respect to industrial applicability. Thus, implementation of the proposed system will allow the potential of lightweight CFRP constructions to be better exploited by expanding the possibilities of structural adhesive bonding.

Structural health monitoring systems for composite laminates using guided ultrasonic waves become more versatile with the structural integration of sensors. However, the data generated within these sensors have to be transmitted from the laminate to the outside, where polyimide-based printed circuit boards play a major role. This study investigates, to what extent integrated polyimide inlays with applied sensor bodies influence the guided ultrasonic wave propagation in glass fiber-reinforced polymer specimens. For reasons of resource efficiency, narrow specimens are used. Numerical simulations of a damping-free specimen indicate reflections of the S0-mode at the integrated inlay. This is validated experimentally with an air-coupled ultrasonic technique and a 3D laser Doppler vibrometry measurement. The experimental data are evaluated with a method including temporal and spatial continuous wavelet transformations to clearly identify periodically occurring wave packages as edge reflections and distinguish them from possible inlay reflections. However, even when separating in-plane and out-of-plane movements using the 3D measurement, no reflections at the inlays are detected. This leads to the conclusion that polyimide inlays are well suited as substrates for printed circuit boards integrated into fiber-reinforced polymer structures for structural health monitoring, since they do not significantly influence the wave propagation.

The ability to measure the degree of cure of epoxy resins is an important prerequisite for making manufacturing processes for fibre-reinforced plastics controllable. Since a number of physical properties change during the curing reaction of epoxy resins, a wide variety of measurement methods exist. In this article, different methods for cure monitoring of epoxy resins are applied to a room-temperature curing epoxy resin and then directly compared. The methods investigated include a structure-borne sound acoustic, a dielectric, an optical and a strain-based observation method, which for the first time are measured simultaneously on one and the same resin sample. In addition, the degree of cure is determined using a kinetic resin model based on temperature measurement data. The comparison shows that the methods have considerable but well-explainable differences in their sensitivity, interference immunity and repeatability. Some measurement methods are only sensitive before and around the gel point, while the strain-based measurement method only reacts to the curing from the gel point onwards. These differences have to be taken into account when implementing a cure monitoring system. For this reason, a multi-sensor node is suitable for component-integrated curing monitoring, measuring several physical properties of the epoxy resin simultaneously.

Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These advantages are particularly pronounced in small-scale MBRs with a volume below 10 µL. However, most described small-scale MBRs are lacking in process information from integrated sensors due to limited space and sensor technology. Therefore, a novel capillary-wave microbioreactor (cwMBR) with a volume of only 7 µL has the potential to close this gap, as it combines a small volume with integrated sensors for biomass, pH, dissolved oxygen (DO) and glucose concentration. In the cwMBR, pH and DO are measured by established luminescent optical sensors on the bottom of the cwMBR. The novel glucose sensor is based on a modified oxygen sensor, which measures the oxygen uptake of glucose oxidase (GOx) in the presence of glucose up to a concentration of 15 mM. Furthermore, absorbance measurement allows biomass determination. The optical sensors enabled the characterization of an Escherichia coli batch cultivation over 8 h in the cwMBR as proof of concept for further bioprocesses. Hence, the cwMBR with integrated optical sensors has the potential for a wide range of microscale bioprocesses, including cell-based assays, screening applications and process development.

One key application of organ-on-chip systems is the examination of drug transport and absorption through native cell barriers such the blood–brain barrier. To overcome previous hurdles related to the transferability of existing static cell cultivation protocols and polydimethylsiloxane (PDMS) as the construction material, a chip platform with key innovations for practical use in drug-permeation testing is presented. First, the design allows for the transfer of barrier-forming tissue into the microfluidic system after cells have been seeded on porous polymer or Si3N4 membranes. From this, we can follow highly reproducible models and cultivation protocols established for static drug testing, from coating the membrane to seeding the cells and cell analysis. Second, the perfusion system is a microscopable glass chip with two fluid compartments with transparent embedded electrodes separated by the membrane. The reversible closure in a clamping adapter requires only a very thin PDMS sealing with negligible liquid contact, thereby eliminating well-known disadvantages of PDMS, such as its limited usability in the quantitative measurements of hydrophobic drug molecule concentrations. Equipped with tissue transfer capabilities, perfusion chamber inertness and air bubble trapping, and supplemented with automated fluid control, the presented system is a promising platform for studying established in vitro models of tissue barriers under reproducible microfluidic perfusion conditions.

Structural health monitoring of lightweight constructions made of composite materials can be performed using guided ultrasonic waves. If modern fiber metal laminates are used, this requires integrated sensors that can record the inner displacement oscillations caused by the propagating guided ultrasonic waves. Therefore, we developed a robust MEMS vibrometer that can be integrated while maintaining the structural and functional compliance of the laminate. This vibrometer is directly sensitive to the high-frequency displacements from structure-borne ultrasound when excited in a frequency range between its first and second eigenfrequency. The vibrometer is mostly realized by processes earlier developed for a pressure sensor but with additional femtosecond laser ablation and encapsulation. The piezoresistive transducer, made from silicon, is encapsulated between top and bottom glass lids. The eigenfrequencies are experimentally determined using an optical micro vibrometer setup. The MEMS vibrometer functionality and usability for structural health monitoring are demonstrated on a customized test rig by recording application-relevant guided ultrasonic wave packages with a central frequency of 100 kHz at a distance of 0.2 m from the exciting ultrasound transducer.

Systems-in-foil with multi-sensor arrays require extensive wiring with large numbers of data lines. This prevents scalability of the arrays and thus limits the applications. To enable multiplexing and thus reducing the external connections down to few digital data links and a power supply, active circuits in the form of ASICs must be integrated into the foils. However, this requires reliable multilayer wiring of the sensors and contacts for chip integration. As an elegant solution to this, a new manufacturing process for multilayer wiring in polyimide-based sensor foils has been developed that also allows ASIC chips to be soldered. The electrical four-level micro-via connections and the contact pads are generated by galvanic copper deposition after all other process steps, including stacking and curing of polyimide layers, are completed. Compared to layer by layer via technology, the processing time is considerably reduced. Because copper plating of vias and solderable copper contact pads happens as the final step, the risk of copper oxidation during polyimide curing is completely eliminated. The entire fabrication process is demonstrated for six strain sensor nodes connected to a surface-mounted ASIC as a detecting unit for sensing spatially resolved bending states. Each sensor node is a full-bridge configuration consisting of four strain gauges distributed across interconnected layers. The sensor foil allows bending of +/−120° without damage. This technology can be used in future for all kinds of complex flexible systems-in-foil, in particular for large arrays of sensors.

An islet-on-chip system in the form of a completely transparent microscope slide optically accessible from both sides was developed. It is made from laser-structured borosilicate glass and enables the parallel perifusion of five microchannels, each containing one islet precisely immobilized in a pyramidal well. The islets can be in inserted via separate loading windows above each pyramidal well. This design enables a gentle, fast and targeted insertion of the islets and a reliable retention in the well while at the same time permitting a sufficiently fast exchange of the media. In addition to the measurement of the hormone content in the fractionated efflux, parallel live cell imaging of the islet is possible. By programmable movement of the microscopic stage imaging of five wells can be performed. The current chip design ensures sufficient time resolution to characterize typical parameters of stimulus-secretion coupling. This was demonstrated by measuring the reaction of the islets to stimulation by glucose and potassium depolarization. After the perifusion experiment islets can be removed for further analysis. The live-dead assay of the removed islets confirmed that the process of insertion and removal was not detrimental to islet structure and viability. In conclusion, the present islet-on-chip design permits the practical implementation of parallel perifusion experiments on a single and easy to load glass slide. For each immobilized islet the correlation between secretion, signal transduction and morphology is possible. The slide concept allows the scale-up to even higher degrees of parallelization.

Continuous health monitoring in a vehicle enables the earlier detection of symptoms of cardiovascular diseases. In this work, we designed flexible and thin electrodes made of polyurethane for long-term electrocardiogram (ECG) monitoring while driving. We determined the time for reliable ECG recording to evaluate the effectiveness of the electrodes. We recorded data from 19 subjects under four scenarios: rest, city, highway, and rural. The recording time was five min for rest and 15 min for the other scenarios. The total recording (950 min) is publicly available under a CC BY-ND 4.0 license. We used the simultaneous truth and performance level estimation (STAPLE) algorithm to detect the position of R-waves. Then, we derived the RR intervals to compare the estimated heart rate with the ground truth, which we obtained from ECG electrodes on the chest. We calculated the signal-to-noise ratio (SNR) and averaged it for the different scenarios. Highway had the lowest SNR (−6.69 dB) and rural had the highest (−6.80 dB). The usable time of the steering wheel was 42.46% (city), 46.67% (highway), and 47.72% (rural). This indicates that steering-wheel-based ECG recording is feasible and delivers reliable recordings from about 45.62% of the driving time. In summary, the developed electrodes allow continuous in-vehicle heart rate monitoring, and our publicly available recordings provide the opportunity to apply more sophisticated data analytics.

Interferometric biosensing offers the potential of label-free detection with very high sensitivities. In our optofluidic grating detector the accumulation of biological target molecules on the surface of functionalized nanochannels can be detected due to the change in refractive index. Based on an analytical model, the sensitivity of the optofluidic grating detector was improved by a factor of 3.5 to 8.45 RIU−1 (refractive index unit) by adapting the grating geometries. The grating consists of nanochannels, through which the sample flows. This allows transport without diffusion-limitations inside the sensing area, as it is of particular importance when molecule concentration in the sample decreases. The nanochannels were functionalized by silanization and covalent bonding of antibodies. Finally, the binding of Mycobacterium ulcerans specific antigen MUL2232 was detected label-free.

Space debris is a growing problem for the long-term usage of the low earth orbit. Currently no debris capture and removal method is successfully deployed in space. Anisotropic dry adhesive microstructures have a great potential to be an effectual approach for space debris capture. So far, no anisotropic dry adhesive structures have been produced with two-photon polymerization, which can then be replicated using a casting process. We 3D printed master molds with the use of two-photon polymerization and molded anisotropic dry adhesive structures with space rated polydimethylsiloxane. This paper describes the fabrication process and adhesion measurements on glass and acrylic glass surfaces. Our 3D dry adhesive microstructures showed an anisotropic adhesion factor of 7.52:1 and a maximum adhesion strength on glass and acrylic glass to be 1105.29 ± 40.93 and 1002.72 ± 8.24 mN/cm2. In conclusion, two-photon polymerization and the established molding process can be used to develop new types of mass producible anisotropic dry adhesives for the use in space and other applications where a high anisotropy of the holding force is needed. This promising approach can lead to faster design studies for dry adhesive structures.

To improve the predictive value of in vitro experimentation, the use of 3D cell culture models, or organoids, is becoming increasingly popular. However, the current equipment of life science laboratories has been developed to deal with cell monolayers or cell suspensions. To handle 3D cell aggregates and organoids in a well-controlled manner, without causing structural damage or disturbing the function of interest, new instrumentation is needed. In particular, the precise and stable positioning in a cell bath with flow rates sufficient to characterize the kinetic responses to physiological or pharmacological stimuli can be a demanding task. Here, we present data that demonstrate that microgrippers are well suited to this task. The current version is able to work in aqueous solutions and was shown to position isolated pancreatic islets and 3D aggregates of insulin-secreting MIN6-cells. A stable hold required a gripping force of less than 30 μN and did not affect the cellular integrity. It was maintained even with high flow rates of the bath perfusion, and it was precise enough to permit the simultaneous microfluorimetric measurements and membrane potential measurements of the single cells within the islet through the use of patch-clamp electrodes.

This paper presents the novel concept of structuring a planar coil antenna structured into the outermost stainless-steel layer of a fiber metal laminate (FML) and investigating its performance. Furthermore, the antenna is modified to sufficiently work on inhomogeneous conductive substrates such as carbon-fiber-reinforced polymers (CFRP) independent from their application-dependent layer configuration, since the influence on antenna performance was expected to be configuration-dependent. The effects of different stack-ups on antenna characteristics and strategies to cope with these influences are investigated. The purpose was to create a wireless self-sustained sensor node for an embedded structural health monitoring (SHM) system inside the monitored material itself. The requirements of such a system are investigated, and measurements on the amount of wireless power that can be harvested are conducted. Mechanical investigations are performed to identify the antenna shape that produces the least wound to the material, and electrical investigations are executed to prove the on-conductor optimization concept. Furthermore, a suitable process to fabricate such antennas is introduced. First measurements fulfilled the expectations: the measured antenna structure prototype could provide up to 11 mW to a sensor node inside the FML component.

Integrating foil sensors into fibre-reinforced plastics offers the advantage of making manufacturing measurable with spatial resolution and thus simplifies quality control. One challenge here is the possible negative influence of the integrated sensors on the mechanical behaviour of the structure. This article shows how the different parts of a film sensor influence important mechanical strength parameters of fibre composites. A comparison of two thermoplastic carrier films shows that by choosing polyetherimide (PEI) instead of polyimide (PI), a considerably more advantageous failure behaviour of the composite is achieved. While integrated PI films reduce the interlaminar shear strength by 68%, no impairment is noticeable due to PEI films. For the critical energy release rate, PEI-based film sensors even lead to a significant increase, while a significant deterioration of 85% can be observed for PI-based sensors. However, not only the film substrate plays a decisive role for the interlaminar shear strength, but also the sensor structures themselves. In this article, sensor structures made of gold were investigated. The decisive parameter for the impairment seems to be the area share of gold structures in the sensor. For a sensor pattern made of gold lines with an area filling of 50%, a reduction of the interlaminar shear strength of up to 25% was observed depending on the angle between the shear stress and the gold lines. No impairment was observed for sensor structures with less gold area. The results show that PEI substrates can be a superior alternative for sensor integration into fibre composites and suggest that there is a trade-off between sensitivity and degradation of mechanical properties when designing interdigital sensors.

Monitoring process parameters in the manufacture of composite structures is key to ensuring product quality and safety. Ideally, this can be done by sensors that are embedded during production and can remain as devices to monitor structural health. Extremely thin foil-based sensors weaken the finished workpiece very little. Under ideal conditions, the foil substrate bonds with the resin in the autoclaving process, as is the case when polyetherimide is used. Here, we present a temperature sensor as part of an 8 µm thick multi-sensor node foil for monitoring processing conditions during the production and structural health during the lifetime of a construction. A metallic thin film conductor was shaped in the form of a space-filling curve to suppress the influences of resistance changes due to strain, which could otherwise interfere with the measurement of the temperature. FEM simulations as well as experiments confirm that this type of sensor is completely insensitive to the direction of strain and sufficiently insensitive to the amount of strain, so that mechanical strains that can occur in the composite curing process practically do not interfere with the temperature measurement. The temperature sensor is combined with a capacitive sensor for curing monitoring based on impedance measurement and a half-bridge strain gauge sensor element. All three types are made of the same materials and are manufactured together in one process flow. This is the key to cost-effective distributed sensor arrays that can be embedded during production and remain in the workpiece, thus ensuring not only the quality of the initial product but also the operational reliability during the service life of light-weight composite constructions.

Current research in the field of aviation considers actively controlled high-lift structures for future civil airplanes. Therefore, pressure data must be acquired from the airfoil surface without influencing the flow due to sensor application. For experiments in the wind and water tunnel, as well as for the actual application, the requirements for the quality of the airfoil surface are demanding. Consequently, a new class of sensors is required, which can be flush-integrated into the airfoil surface, may be used under wet conditions—even under water—and should withstand the harsh environment of a high-lift scenario. A new miniature silicon on insulator (SOI)-based MEMS pressure sensor, which allows integration into airfoils in a flip-chip configuration, is presented. An internal, highly doped silicon wiring with “butterfly” geometry combined with through glass via (TGV) technology enables a watertight and application-suitable chip-scale-package (CSP). The chips were produced by reliable batch microfabrication including femtosecond laser processes at the wafer-level. Sensor characterization demonstrates a high resolution of 38 mVV−1 bar−1. The stepless ultra-smooth and electrically passivated sensor surface can be coated with thin surface protection layers to further enhance robustness against harsh environments. Accordingly, protective coatings of amorphous hydrogenated silicon nitride (a-SiN:H) and amorphous hydrogenated silicon carbide (a-SiC:H) were investigated in experiments simulating environments with high-velocity impacting particles. Topographic damage quantification demonstrates the superior robustness of a-SiC:H coatings and validates their applicability to future sensors.

Disbond arrest features combined with a structural health monitoring system for permanent bondline surveillance have the potential to significantly increase the safety of adhesive bonds in composite structures. A core requirement is that the integration of such features is achieved without causing weakening of the bondline. We present the design of a smart inlay equipped with a micro strain sensor-system fabricated on a polyvinyliden fluorid (PVDF) foil material. This material has proven disbond arrest functionality, but has not before been used as a substrate in lithographic micro sensor fabrication. Only with special pretreatment can it meet the requirements of thin film sensor elements regarding surface roughness and adhesion. Moreover, the sensor integration into composite material using a standard manufacturing procedure reveals that the smart inlays endure this process even though subjected to high temperatures, curing reactions and plasma treatment. Most critical is the substrate melting during curing when sensory function is preserved with a covering caul plate that stabilizes the fragile measuring grids. The smart inlays are tested by static mechanical loading, showing that they can be stretched far beyond critical elongations of composites before failure. The health monitoring function is verified by testing the specimens with integrated sensors in a cantilever bending setup. The results prove the feasibility of micro sensors detecting strain gradients on a disbond arresting substrate to form a so-called multifunctional bondline.

Automated biomimetic systems for the preclinical testing of drugs are of great interest. Here, an in vitro testing platform for in vivo adapted drug absorption studies is presented. It has been designed with a focus on easy handling and the usability of established cell cultivation techniques in standard well plate inserts. The platform consists of a microfluidic device, which accommodates a well plate insert with pre-cultivated cells, and provides a fluid flow with dynamic drug dilution profiles. A low-cost single-board computer with a touchscreen was used as a control unit. This provides a graphical user interface, controls the syringe pump flow rates, and records the transepithelial electrical resistance. It thereby enables automated parallel testing in multiple devices at the same time. To demonstrate functionality, an MDCK cell layer was used as a model for an epithelial barrier for drug permeation testing. This confirms the possibility of performing absorption studies on barrier tissues under conditions close to those in vivo. Therefore, a further reduction in animal experiments can be expected.

A major disadvantage of inhalation therapy with continuous drug delivery is the loss of medication during expiration. Developing a breath-triggered drug release system can highly decrease this loss. However, there is currently no breath-triggered drug release directly inside the patient interface (nasal prong) for preterm neonates available due to their high breathing frequency, short inspiration time and low tidal volume. Therefore, a nasal prong with an integrated valve releasing aerosol directly inside the patient interface increasing inhaled aerosol efficiency is desirable. We integrated a miniaturized aerosol valve into a nasal prong, controlled by a double-stroke cylinder. Breathing was simulated using a test lung for preterm neonates on CPAP respiratory support. The inhalation flow served as a trigger signal for the valve, releasing humidified surfactant. Particle detection was performed gravimetrically (filter) and optically (light extinction). The integrated miniaturized aerosol valve enabled breath-triggered drug release inside the patient interface with an aerosol valve response time of 4 compared to non-triggered release. This novel nasal prong with integrated valve allows breath-triggered drug release directly inside the nasal prong with short response time.

In order to deliver an aerosolized drug in a breath-triggered manner, the initiation of the patient’s inspiration needs to be detected. The best-known systems monitoring breathing patterns are based on flow sensors. However, due to their large dead space volume, flow sensors are not advisable for monitoring the breathing of (preterm) neonates. Newly-developed respiratory sensors, especially when contact-based (invasive), can be tested on (preterm) neonates only with great effort due to clinical and ethical hurdles. Therefore, a physiological model is highly desirable to validate these sensors. For developing such a system, abdominal movement data of (preterm) neonates are required. We recorded time sequences of five preterm neonates’ abdominal movements with a time-of-flight camera and successfully extracted various breathing patterns and respiratory parameters. Several characteristic breathing patterns, such as forced breathing, sighing, apnea and crying, were identified from the movement data. Respiratory parameters, such as duration of inspiration and expiration, as well as respiratory rate and breathing movement over time, were also extracted. This work demonstrated that respiratory parameters of preterm neonates can be determined without contact. Therefore, such a system can be used for breathing detection to provide a trigger signal for breath-triggered drug release systems. Furthermore, based on the recorded data, a physiological abdominal movement model of preterm neonates can now be developed.

In comparison to bolted joints, structural bonds are the desirable joining method for light-weight composite structures. To achieve a broad implementation of this technology in safety critical structures, the issues of structural bonds due to their complex and often unpredictable failure mechanisms have to be overcome. The proposed multifunctional bondline approach aims at solving this by adding two safety mechanisms to structural bondlines. These are a design feature for limiting damages to a certain size and a structural health monitoring system for damage detection. The key question is whether or not the implementation of both safety features without deteriorating the strength in comparison to a healthy conventional bondline is possible. In previous studies on the hybrid bondline, a design feature for damage limitations in bondlines by means of disbond stopping features was already developed. Thus, the approach to evolve the hybrid bondline to a multifunctional one is followed. A thorough analysis of the shear stress and tensile strain distribution within the hybrid bondline demonstrates the feasibility to access the status of the bondline by monitoring either of these quantities. Moreover, the results indicate that it is sufficient to place sensors within the disbond stopping feature only and not throughout the entire bondline. Based on these findings, the three main working principles of the multifunctional are stated. Finally, two initial concepts for a novel multifunctional disbond arrest feature are derived for testing the fundamental hypothesis that the integration of micro sensors into the disbond stopping feature only enables the crack arrest and the health monitoring functions, while reaching the mechanical strength of a conventional healthy epoxy bondline. This work therefore provides the fundamentals for future investigations in the scope of the multifunctional bondline.

The article presents a study on the adhesion of thermoplastic films to a room temperature-hardening epoxy resin, which deals with an important question on sensor integration into fibre composites. By means of a morphological box, a test specimen is developed, which allows to test strength values for the adhesion of thermoplastic films to epoxy resin. Polyimide (PI), which is typically used as a carrier material for flexible sensors, is compared with the thermoplastics polyetherimide (PEI), polyethersulfone (PES) and polyamide 6 (PA6). To evaluate the spatial formation of the interface, images taken with a light microscope, fluorescence microscope and electron microscope and an energy-dispersive X-ray spectroscopy (EDX) analysis are presented. The images show that during the curing process of the epoxy resin the initially expected pronounced interphase does not form. In this respect, it is surprising that PEI achieves such a high adhesion strength even without extended interphase formation, that the failure of the test specimen occurs in the epoxy resin region at a tensile stress of 70 MPa and not at the interface between epoxy and PEI, as might initially be assumed. It is also surprising that PES exhibits the lowest adhesion strength of 5 MPa to room temperature-hardening epoxy resin, although in previous investigations it was often used as a soluble toughness modifier for epoxy resins. The tensile adhesion strength of PI to epoxy resin was found at 27 MPa and the tensile adhesion strength of PA6 to epoxy resin was found at 13 MPa. For sensor integration, the findings mean that flexible sensors on PEI substrates promise a low tendency to delaminate even in the room temperature-hardening epoxy resin used, while the other materials tested indicate an increased tendency to delaminate.

A methodology is presented for the determination of elastic material properties on laminated and non-laminated decorative veneers of a variety of wood types. For the uniaxial tensile tests performed, at various temperatures and wood moisture values, the metrological challenges as well as the test results are described and discussed. Subsequently, the characteristic values are transferred into corresponding material models. Also, as the inverse, model-based determination of characteristic values that cannot be determined experimentally is carried out.

Infections with antimicrobial resistant bacteria are a rising threat for global healthcare as more and more antibiotics lose their effectiveness against bacterial pathogens. To guarantee the long-term effectiveness of broad-spectrum antibiotics, they may only be prescribed when inevitably required. In order to make a reliable assessment of which antibiotics are effective, rapid point-of-care tests are needed. This can be achieved with fast phenotypic microfluidic tests, which can cope with low bacterial concentrations and work label-free. Here, we present a novel optofluidic chip with a cross-flow immobilization principle using a regular array of nanogaps to concentrate bacteria and detect their growth label-free under the influence of antibiotics. The interferometric measuring principle enabled the detection of the growth of Escherichia coli in under 4 h with a sample volume of 187.2 µL and a doubling time of 79 min. In proof-of-concept experiments, we could show that the method can distinguish between bacterial growth and its inhibition by antibiotics. The results indicate that the nanofluidic chip approach provides a very promising concept for future rapid and label-free antimicrobial susceptibility tests.

During fiber composite production, the quality of the manufactured parts can be assured by measuring the progress of the curing reaction. Dielectric film sensors are particularly suitable for this measurement task, as they can quantify the degree of curing very specifically and locally. These sensors are usually manufactured on PI films, which can lead to delaminations after integration. Other authors report that this negative influence can be reduced by miniaturization and a suitable shaping of the sensors. This article pursues as an alternative, a novel approach to achieve a material closure instead of a geometrically generated form closure by choosing suitable thermoplastic materials. Thermoplastic films made of PEI, PES and PA6 are proposed as carrier substrates for thin film sensors. They are investigated with regard to their mechanical effects in FRP. The experiments show that the integration of PES and PEI in FRP has the best shear strength, but PA6 leads to a higher critical energy release rate during crack propagation in mode I. For PI, a locally strongly scattering critical energy release rate was observed. Neither in tensile nor in Compression After Impact (CAI) tests a significant influence of the films on these characteristic values could be proven.

The fabrication and testing of microfluidic spinning compact discs with embedded trapezoidal microchambers for the purpose of inertial microparticle focusing is reported in this article. Microparticle focusing channels require small features that cannot be easily fabricated in acrylic sheets and are complicated to realize in glass by traditional lithography techniques; therefore, the fabrication of microfluidic discs with femtosecond laser ablation is reported for the first time in this paper. It could be demonstrated that high-efficiency inertial focusing of 5 and 10 µm particles is achieved in a channel with trapezoidal microchambers regardless of the direction of disc rotation, which correlates to the dominance of inertial forces over Coriolis forces. To achieve the highest throughput possible, the suspension concentration was increased from 0.001% (w/v) to 0.005% (w/v). The focusing efficiency was 98.7% for the 10 µm particles and 93.75% for the 5 µm particles.

This study presents experiments and computational simulations of single-layer passive micromixer designs. The proposed designs consist of chains of interlocking semicircles and omega-shaped mixing modules. The performance of the new designs is compared with the concentric spiral channel configuration. The micromixers are intended to be integrated into a lab on chip (LOC) micro-system that operates under continuous flow conditions. The purpose behind the multi-curvature in these designs is the introduction of Dean vortices in addition to molecular diffusion in order to enhance the mixing performance. The micromixers were fabricated in PDMS (Polydimethylsiloxane) and bonded to a glass substrate. A three-dimensional computational model of micromixers was carried out using Fluent ANSYS. In experiments, the mixing of a 1 g/L fluorescein isothiocyanate diluted in distilled water was observed and photographed using a charge-coupled device (CCD) microscopic camera. The obtained images were processed to determine the mixing intensity at different Reynolds numbers. The standard deviation (σ) of the fluorescence indicates the mixing completeness, which was calculated along the width of the channel at various locations downstream from the channel inlet. The value of σ = 0.5 indicates unmixed streams and 0 is for complete mixing. It is found that the two new designs have a standard deviation of nearly 0.05. Additionally, complete mixing was observed at the channel outlet as demonstrated by the fluorescence images and the numerical results. However, the location of complete mixing at different positions depends on the Reynolds number, which varies between 0.01 and 50. Good agreement was found between the experiment and the numerical results. A correlation to predict the length scale where complete mixing can be achieved is given in terms of the radius of curvature, the mixing module, and the Reynolds number.

A pressure resistant and optically accessible deterministic lateral displacement (DLD) device was designed and microfabricated from silicon and glass for high-throughput fractionation of particles between 3.0 and 7.0 µm comprising array segments of varying tilt angles with a post size of 5 µm. The design was supported by computational fluid dynamic (CFD) simulations using OpenFOAM software. Simulations indicated a change in the critical particle diameter for fractionation at higher Reynolds numbers. This was experimentally confirmed by microparticle image velocimetry (µPIV) in the DLD device with tracer particles of 0.86 µm. At Reynolds numbers above 8 an asymmetric flow field pattern between posts could be observed. Furthermore, the new DLD device allowed successful fractionation of 2 µm and 5 µm fluorescent polystyrene particles at Re = 0.5−25.

A new design for a single-use disposable pneumatic microgripper is presented in this paper. It enables very cost-effective batch microfabrication in SU-8 with a single lithography mask by shifting manufacturing complexity into reusable components. An optically readable force sensor with potential to be used in a feedback loop has been integrated in order to enable gripping with a controlled force. The sensors are first examined separately from the gripper and exhibit good linearity. The gripper function utilizes the disposable gripper element together with a reusable gripper fixture. During experiments, the pneumatically actuated microgripper can vary the gripping force within a range of a few mN (up to 5.7 mN was observed). This microgripper is planned to be used in a liquid environment for gripping larger aggregates of cells in combination with the patch clamp technique. This approach will allow Langerhans islets suspended in an electrolyte solution to be grasped and held during electrophysiological measurements without cell damage.

Infections with antimicrobial-resistant (AMR) bacteria are globally on the rise. In the future, multi-resistant infections will become one of the major problems in global health care. In order to enable reserve antibiotics to retain their effect as long as possible, broad-spectrum antibiotics must be used sparingly. This can be achieved by a rapid microfluidic phenotypic antibiotic susceptibility test, which provides the information needed for a targeted antibiotic therapy in less time than conventional tests. Such microfluidic tests must cope with a low bacteria concentration. On-chip filtering of the samples to accumulate bacteria can shorten the test time. By means of fluorescence microscopy, we examined a novel nanogap filtration principle to hold back Escherichia coli and to perform cultivation experiments with and without antibiotics present. Microfluidic chips based on the nanogap flow principle showed to be useful for the concentration and cultivation of E. coli. With a concentration of 106 cells/mL, a specific growth rate of 0.013 min−1 and a doubling time of 53 min were achieved. In the presence of an antibiotic, no growth was observed. The results prove that this principle can, in future, be used in fast and marker-free antimicrobial susceptibility testing (AST).

Point-of-care systems enable fast therapy decisions on site without the need of any healthcare infrastructure. In addition to the sensitive detection, stable measurement by inexperienced persons outside of laboratory facilities is indispensable. A particular challenge in field applications is to reduce interference from environmental factors, such as temperature, to acceptable levels without sacrificing simplicity. Here, we present a smartphone-based point-of-care sensor. The method uses an optofluidic grating composed of alternating detection and reference channels arranged as a reflective phase grating. Biomolecules adsorbing to the detection channel alter the optical path length, while the parallel reference channels enable a direct common mode rejection within a single measurement. The optical setup is integrated in a compact design of a mobile readout device and the usability is ensured by a smartphone application. Our results show that different ambient temperatures do not have any influence on the signal. In a proof-of concept experiment we measured the accumulation of specific molecules in functionalized detection channels in real-time and without the need of any labeling. Therefore, the channel walls have been modified with biotin as capture molecules and the specific binding of streptavidin was detected. A mobile, reliable and robust point-of-care device has been realized by combining an inherently differential measurement concept with a smartphone-based, mobile readout device.

Microbioreactors are gaining increased interest in biopharmaceutical research. Due to their decreasing size, the parallelization of multiple reactors allows for simultaneous experiments. This enables the generation of high amounts of valuable data with minimal consumption of precious pharmaceutical substances. However, in bioreactors of all scales, fast mixing represents a crucial condition. Efficient transportation of nutrients to the cells ensures good growing conditions, homogeneous environmental conditions for all cultivated cells, and therefore reproducible and valid data. For these reasons, a new type of batch microbioreactor was developed in which any moving mixer component is rendered obsolete through the utilization of capillary surface waves for homogenization. The bioreactor was fabricated in photosensitive glass and its fluid volume of up to 8 µL was provided within a bowl-shaped volume. External mechanical actuators excited capillary surface waves and stereo microparticle image velocimetry (µPIV) was used to analyze resulting convection at different excitation conditions in varied reactor geometries. Typical vortex patterns were observed at certain resonance frequencies where best mixing conditions occurred. Based on the results, a simplified 1D model which predicts resonance frequencies was evaluated. Cultivation of Escherichia coli BL21 under various mixing conditions showed that mixing in resonance increased the biomass growth rate, led to high biomass concentrations, and provided favorable growth conditions. Since glass slides containing multiple bowl reactors can be excited as a whole, massive parallelization is foreseen.

Laser induced forward transfer (LIFT) is a flexible digital printing process for maskless, selective pattern transfer, which uses single laser pulses focused through a transparent carrier substrate onto a donor layer to eject a tiny volume of the donor material towards a receiver substrate. Here, we present an advanced method for the high-resolution micro printing of bio-active detection chemicals diluted in a viscous buffer solution by transferring droplets with precisely controllable volumes using blister-actuated LIFT (BA-LIFT). This variant of the LIFT process makes use of an intermediate polyimide layer partially ablated by the laser pulses. The expanding gaseous ablation products lead to blisters in the polyimide and ejection of droplets from the subjacent viscous solution layer. A relative movement of donor and receiver substrates for the transfer of partially overlapping pixels is realized with a custom-made positioning system. Using a specially developed donor ink containing bio-active components presented method allows to transfer droplets with well controllable volumes between 20 fL and 6 pL, which is far more precise than other methods like inkjet or contact printing. The usefulness of the process is demonstrated by locally functionalizing laser-structured nitrocellulose paper-like membranes to form a multiparametric lateral flow test. The recognition zones localized within parallel micro channels exhibit a well-defined and homogeneous color change free of coffee-ring patterns, which is of utmost importance for reliable optical readout in miniature multiparametric test systems.

A key aspect of microfluidic processes is their ability to perform chemical reactions in small volumes under continuous flow. However, a continuous process requires stable reagent flow over a prolonged period. This can be challenging in microfluidic systems, as bubbles or particles easily block or alter the flow. Online analysis of the product stream can alleviate this problem by providing a feedback signal. When this signal exceeds a pre-defined range, the process can be re-adjusted or interrupted to prevent contamination. Here we demonstrate the feasibility of this concept by implementing a microfluidic detector downstream of a segmented-flow system for the synthesis of lipid nanoparticles. To match the flow rate through the detector to the measurement bandwidth independent of the synthesis requirements, a small stream is sidelined from the original product stream and routed through a measuring channel with 2 × 2 µm cross-section. The small size of the measuring channel prevents the entry of air plugs, which are inherent to our segmented flow synthesis device. Nanoparticles passing through the small channel were detected and characterized by quantitative fluorescence measurements. With this setup, we were able to count single nanoparticles. This way, we were able to detect changes in the particle synthesis affecting the size, concentration, or velocity of the particles in suspension. We envision that the flow-splitting scheme demonstrated here can be transferred to detection methods other than fluorescence for continuous monitoring and feedback control of microfluidic nanoparticle synthesis.

Nanoparticles as an application platform for active ingredients offer the advantage of efficient absorption and rapid dissolution in the organism, even in cases of poor water solubility. Active substances can either be presented directly as nanoparticles or can be integrated in a colloidal carrier system (e.g., lipid nanoparticles). For bottom-up nanoparticle production minimizing particle contamination, precipitation processes provide an adequate approach. Microfluidic systems ensure a precise control of mixing for the precipitation, which enables a tunable particle size definition. In this work, a gas/liquid Taylor flow micromixer made of chemically inert glass is presented, in which the organic phases are injected through a symmetric inlet structure. The 3D structuring of the glass was performed by femtosecond laser ablation. Rough microchannel walls are typically obtained by laser ablation but were smoothed by a subsequent annealing process resulting in lower hydrophilicity and even rounder channel cross-sections. Only with such smooth channel walls can a substantial reduction of fouling be obtained, allowing for stable operation over longer periods. The ultrafast mixing of the solutions could be adjusted by simply changing the gas volume flow rate. Narrow particle size distributions are obtained for smaller gas bubbles with a low backflow and when the rate of liquid volume flow has a small influence on particle precipitation. Therefore, nanoparticles with adjustable sizes of down to 70 nm could be reliably produced in continuous mode. Particle size distributions could be narrowed to a polydispersity value of 0.12.