Search

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 (<35 MPa) SixNy for culturing and testing reconstructed tissue. The membrane is designed to support various in vitro tissues including co-cultures and to allow passage of molecules but not of cells. A digital laser write method was used to produce nanopores with deterministic but highly flexible positioning within the membrane. A thin layer of photoresist was exposed by accumulation of femtosecond pulses for local two-photon polymerization, which allowed nanopores as small as 350 nm in diameter to be generated through the membranes in a subsequent plasma etch process. The fabricated membranes were used to separate a microfluidic chip into two compartments, which are connected to the outside by microchannel structures. With unique side inlets for fluids, all cells are exposed to identical flow velocities and shear stresses. With the hydrophilic nature of chip materials the self-loading seeding is controlled bottom-up by capillary forces, which makes the seeding procedure homogeneous and less dependent on the operator. The chip is designed to allow fabrication by wafer-level MEMS manufacturing technologies without critical assembly steps, thereby promoting reproducibility and scale-up of fabrication. In order to establish a fully functional test system to be used in a lab incubator, a holder for the bare chip was designed and 3D-printed with additional elements for gravity driven pumping. In order to mimic physiological conditions, the holder was designed to provide not only media delivery but also appropriate shear stress to the tissue. To prove usability, murine microvascular endothelial cells (muMEC) were seeded on the membrane within the chip. Cell compatibility was confirmed after 3 days of dynamic cultivation using fluorescence live/dead assays. Cultivation proved to be reproducible and led to confluent layers with cells preferentially grown on nanoporous areas. The system can in future be cost effectively manufactured in larger quantities in MEMS foundries and can be used for a wide variety of in vitro tissues and test scenarios including pumpless operation within cell incubator cabinets.

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.

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.

Electronic devices are progressively fabricated on flexible substrates allowing new fields of applications. A maskless and very flexible structuring process is offered by ablation using ultra-short pulse laser irradiation. Usually, certain areas of a functional thin film coating are locally removed to yield the needed device structures. Micro laser patterning quality is not only influenced by the beam properties (beam profile, fluence) but also by pulse overlap, scan repetitions and many other factors such as substrate and coating material. This makes process parameter optimization a challenging task. In this paper, we present a systematic approach to efficiently find suitable parameters for laser-induced ablation of thin films on susceptible polymer substrates. As an example, we use a sputtered NiCr coating with a thickness of 100 $nm$ on a polyimide film made by spin coating of PI-2611 precursor (@ 2000 $rpm$ > ca. 8 ${\mu}m$, HD microsystems). Irradiation is conducted using a fs-laser with infrared wavelength of 1030 $nm$ and a pulse length of 212 $fs$. The energy per pulse is varied in the range of 0,29 ${\mu}J$ to 4,83 ${\mu}J$, yielding fluence values between 70 $mJ/cm^2$ and 1,11 $J/cm^2$. Ablation threshold fluence for a 100 $nm$ layer of NiCr was found to be ${\phi}_{th}$ ($N_P$:1)=0,50 $J/cm^2$ and the incubation factor was evaluated to be ${\xi}$=0,53. A clear distinction must be made between the material ablation at the surface of a bulk material and the selective removal of a thin film. In the second case effects such as flaking occur in practice and influence the ablation characteristic. We then investigate different varieties of thin film removal including dot-, line- and areal-ablation. The methodology is presented using a practical example, but can be applied to selective ablation of a wide range of thin film systems., Comment: 11 pages, 23 figures

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.

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.

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 &micro, L was provided within a bowl-shaped volume. External mechanical actuators excited capillary surface waves and stereo microparticle image velocimetry (&micro, PIV) 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.

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.

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.

Microfluidic quartz crystal microbalances (QCM) can be used as powerful biosensors that not only allow quantifying a target analyte, but also provide kinetic information about the surface processes of binding and release. Nevertheless, their practical use as point-of-care devices is restricted by a limit of detection (LoD) of some ng/cm². It prohibits the measurement of small molecules in low concentrations within the initial sample. Here, two concepts based on superparamagnetic particles are presented that allow enhancing the LoD of a QCM. First, a particle-enhanced C-reactive protein (CRP) measurement on a QCM is shown. The signal response could be increased by a factor of up to five by utilizing the particles for mass amplification. Further, a scheme for sample pre-preparation utilizing convective up-concentration involving magnetic bead manipulation is investigated. These experiments are carried out with a glass device that is fabricated by utilizing a femtosecond laser. Operation regimes for the magnetic manipulation of particles within the microfluidic channel with integrated pole pieces that are activated by external permanent magnets are described. Finally, the potential combination of the concepts of mass amplification and up-concentration within an integrated lab-on-a chip device is discussed.

The fabrication and testing of spiral microchannels with a trapezoidal cross section for the passive separation of microparticles is reported in this article. In contrast to previously reported fabrication methods, the fabrication of trapezoidal spiral channels in glass substrates using a femtosecond laser is reported for the first time in this paper. Femtosecond laser ablation has been proposed as an accurate and fast prototyping method with the ability to create 3D features such as slanted-base channels. Moreover, the fabrication in borosilicate glass substrates can provide high optical transparency, thermal resistance, dimensional stability, and chemical inertness. Post-processing steps of the laser engraved glass substrate are also detailed in this paper including hydrogen fluoride (HF) dipping, chemical cleaning, surface activation, and thermal bonding. Optical 3D images of the fabricated chips confirmed a good fabrication accuracy and acceptable surface roughness. To evaluate the particle separation function of the microfluidic chip, 5 μm, 10 μm, and 15 μm particles were focused and recovered from the two outlets of the spiral channel. In conclusion, the new chemically inert separation chip can be utilized in biological or chemical processes where different sizes of cells or particles must be separated, i.e., red blood cells, circulating tumor cells, and technical particle suspensions.

Zur Entwicklung einer Dünnschicht für piezoresistive Sensoren wurden in unterschiedlichem Ausmaß drei Materialsysteme untersucht: a-C, a-C:H:Nb und NiCr als Referenzmaterial, wobei der Hauptfokus auf a-C:H:Nb lag. Die Schichten wurden in einem Magnetronsputterprozess hergestellt, wobei DCMS- und HIPIMS-Prozesse miteinander verglichen wurden. Für die Herstellung der a-C:H:Nb-Schichten wurde zusätzlich Acetylen als Precursorgas eingelassen, das im Plasma aufgespalten wird und so die a-C:H-Phase der Schicht bildet. Für die amorphen, undotierten Kohlenstoffschichten konnten k-Faktoren bis 16 und bei einem TCR von -6360 ppm/K entwickelt werden, die eine ausreichende Leitfähigkeit und Schichthaftung auf den Polymersubstraten aufwiesen. Aufgrund ihrer hohen Schichtspannung und verhältnismäßig hohem TCRs kamen sie jedoch nicht für die Entwicklung von 3D-strukturierten Sensorfolien in Frage. Für das Metall-Kohlenstoff-Komposit a-C:H:Nb erfolgte eine umfassende Analyse der Materialstruktur und der elektrischen und mechanischen Eigenschaften der Dünnschichten. Die Analyseergebnisse wurden in einem Strukturzonenmodell zusammengefasst, das Aufschluss über Art und Zusammensetzung des Kompositmaterials in Abhängigkeit vom Nb-Gehalt gibt. Es liefert die grundlegenden Erkenntnisse zur folgenden Interpretation der elektrischen und mechanischen Eigenschaften des Materials. Mit a-C:H:Nb konnten k-Faktoren bis 59 in Kombination mit TCRs zwischen -10 und -400 ppm/K erzielt werden, die allerdings aufgrund einer Rissbildung in der Dünnschicht entstehen. Rissfreie Schichten erzeugten niedrige k-Faktoren von 2 bis 3 in Kombination mit TCRs zwischen -200 und -400 ppm/K, die dennoch durch ihre biokompatiblen Eigenschaften als Ersatzmaterial für NiCr von Interesse sind. Die Untersuchung der 3D-Konformität der a-C:H:Nb-Schichten ergab, dass es möglich ist, mittels HIPIMS-Prozess mit hohem Spitzenstrom, auch auf geneigt zum Target ausgerichteten Flanken ein Schichtwachstum senkrecht zur Substratoberfläche zu erzielen. Es konnte gezeigt werden, dass die k-Faktoren und TCRs winkelunabhängig sind und die Beschichtung somit – bezogen auf die elektrischen Eigenschaften - als ausreichend 3D-konform angesehen werden kann. Die 3D-Konformitätstests der NiCr-Beschichtungen zeigten ähnliche Ergebnisse. Die NiCr-Beschichtungen bildeten allerdings auch unter bestimmten Bedingungen Risse, was einerseits zu sehr hohen k-Faktoren (>300) aber zugleich zu instabilen Messkurven führte. Generell ist bei der Beschichtung von Polymerfolien mit Dünnschichten, die deutlich unterschiedliche mechanische Eigenschaften aufweisen, auf die Vermeidung von Rissbildungen zu achten., For the development of thin films for piezoresistive sensors, three material systems were investigated to different extent: a-C, a-C:H:Nb and NiCr as reference material, with the main focus on a-C:H:Nb. The layers were produced in a magnetron sputtering process comparing DCMS and HIPIMS processes. For the production of the a-C:H:Nb coatings, acetylene was added as precursor gas, which is split up in the plasma and thus forms the a-C:H phase of the layer. For the amorphous, undoped carbon layers, gauge factors up to 16 combined with a TCR of -6360 ppm/K could be developed, which showed sufficient conductivity and layer adhesion on the polymer substrates. Due to their high film tension and relatively high TCRs, however, they were not suitable for the development of 3D-structured sensor films. For the metal-carbon composite a-C:H:Nb, a comprehensive analysis of the material structure and the electrical and mechanical properties of the thin films was performed. The results of the analysis were summarized in a structure zone model, which provides information on the type and composition of the composite material as a function of the Nb content. It provides the basic knowledge for the following interpretation of the electrical and mechanical properties of the material. With a-C:H:Nb, gauge factors up to 59 combined with TCRs between -10 and -400 ppm/K could be achieved, which, however, are caused by crack formation in the thin film. Crack-free layers produced low gauge factors of 2 to 3 in combination with TCRs between -200 and -400 ppm/K, which are nevertheless of interest as NiCr substitutes due to their biocompatible properties. The investigation of the 3D conformity of the a-C:H:Nb layers showed that it is possible to achieve layer growth perpendicular to the substrate surface by means of a HIPIMS process with high peak current, even on surfaces inclined to the target. It could be shown that the gauge factors and TCRs are angle-independent and the coating can therefore be regarded as sufficiently 3D-conform with respect to the electrical properties. The 3D conformity tests of the NiCr coatings showed similar results. However, the NiCr coatings also formed cracks under certain conditions, which led to very high gauge factors (>300) but also to unstable measurement curves. In general, when coating polymer films with thin layers that have clearly different mechanical properties, care must be taken to avoid cracking.