The biomechanics and dielectric properties of mammalian oocytes are key determinants of developmental competence. However, conventional approaches such as optical deformation cytometry are limited by their reliance on high-resolution imaging, requiring complex image analysis techniques and making them unsuitable for large, optically dense cells like oocytes. Here, we present a differential microfluidic impedance cytometry platform that integrates frequency-resolved dielectric profiling with constriction-based deformation analysis. The hybrid glass-SU-8 chip with integrated coplanar electrodes enables high-fidelity measurements up to 30 MHz. Using hydrogel microspheres for calibration, we confirmed that their impedance response was largely frequency-independent. In contrast, porcine oocytes displayed classical β-dispersion, reflecting membrane capacitance and cytoplasmic conductivity, as well as pressure-dependent impedance dynamics indicating viscoelastic resistance. Two-dimensional impedance mapping enabled robust discrimination between hydrogels and oocytes. In addition, fresh oocytes and oocytes recovered from a severe freeze–thaw injury model showed separable electrical and transit-dynamic signatures. Impedance-derived peak-to-valley transit (PVT) analysis notably provided a fully electrical surrogate for deformation dynamics, eliminating the need for video-based tracking. To our knowledge, this is the first application of impedance cytometry to mammalian oocytes and the first demonstration of frequency-resolved differential impedance analysis of mammalian oocytes during pressure-driven constriction transit. Compared with subjective morphological assessment and imaging-dependent deformation analysis, this approach provides objective electrical readouts of dielectric and transit-dynamic phenotypes without labelling. Uniting dielectric profiling with mechanically coupled transit metrics in a single, label-free assay enables discrimination of individual treatment-associated electromechanical phenotypes within oocyte populations. These findings establish the technical feasibility of label-free single-oocyte electromechanical phenotyping.
This study presents a bistable micro-structure. The bistable behavior is achieved using a pair of antagonistic pre-shaped double beams, which offer the advantages of a simple pre-loading process and symmetric output displacement. The micro-structure was fabricated in silicon using inductively coupled plasma micro-machining technology. The beams have a width of 25 µm and a thickness of 450 µm. The design of the actuator delivers a theoretical stroke of 100 µm. Moreover, the force generated by the shape memory alloy wire has been experimentally measured and found to be 92 mN from the perspective to achieve an in-plane integration in the bistable structure for the bistable switching.
Flexible hand exoskeletons commonly employ underactuated mechanisms to reduce system complexity, making accurate estimation of multijoint motions difficult. To address this, this work presents a compact, flexible multijoint sensing module for direct finger joint angle measurement. Unlike conventional discrete sensors causing redundant wiring clutter, the proposed sensor features a monolithically integrated multichannel layout on a polyimide (PI) substrate, covering eight joint locations of the thumb, index, and middle fingers for high spatial efficiency tracking. To overcome the intrinsic nonstretchability of PI without complex material synthesis, an optimized horseshoe geometry under an island‐bridge configuration is introduced to compliantly accommodate large joint skin deformations. Furthermore, a highly integrated readout circuit based on a programmable system‐on‐chip microcontroller unit (PSoC MCU) is proposed, which implements a double‐layer routing topology to compress the 11‐channel analog signals into a compact matrix, significantly reducing wiring complexity and electronic hardware footprints. The sensing principle, mechanical behavior, and structural reliability are evaluated via finite element simulations. A compact readout circuit with offset‐compensated amplification processes the strain‐induced voltage variations. Validation through experimental calibration and practical deployment trials demonstrates that the system achieves reliable dynamic joint tracking, showing high consistency with optical motion capture references.
Adhesive bonding is ideal for joining lightweight components made of composite materials. However, the reliability of these structural bonds, particularly in terms of fatigue crack growth, is a major concern. To mitigate this risk, structural health monitoring of the bonding is desired. This can be achieved by measuring strains at different locations in the adhesive bondline. Here, we present screen-printing on polyetherimide to realize a smart inlay that can be placed into the adhesive bondline during CFRP integration and can replace cleanroom-fabricated crack propagation sensors demonstrated earlier. The sensor layout is designed to enable crack monitoring by evaluating strain differences between two sensor rows. For the first time, smart inlays were fabricated and encapsulated entirely on polyetherimide, which has excellent adhesion strength to the epoxy matrix of CFRP. For strain detection, we used screen-printed carbon sensors. We selected screen-printing inks that could withstand the harsh conditions during CFRP fabrication. For the characterization of our smart inlay, we analyzed the screen-printed carbon sensors before and after integration into composites. After integration, the sensors were fully functional. As a striking result, after the entire fabrication and integration, the sensitivity of the screen-printed carbon sensors reached a gauge factor of up to 49.
Conventional transepithelial electrical resistance (TEER) technique provides only a low-content analysis of cell-layer conditions, necessitating repeated microscopic assessments of morphology and cell-cell contacts outside the incubator for barrier-on-chip systems. This work presents a novel high-content TEER device in the form of a novel nanoporous membrane that facilitates continuous electrical measurement of cell-substrate impedance sensing (ECIS). The ultrathin (700 nm) membrane, composed of ultra-low-stress SixNy, is monolithically integrated into wafer-level fabricated chips sealed with glass lids. Coplanar ECIS electrodes were connected to custom electronics to record impedance under sinusoidal excitation. Human umbilical vein endothelial cells (HUVECs) were seeded and continuously recorded impedance spectra were compared with bright-field and fluorescence microscopy, revealing distinct phases of monolayer formation. With one-dimensional convolutional neural network (Conv1d) and Kolmogorov-Arnold Network (KAN) trained with a small amount of Nyquist-diagrams, phases of (I) adherence, (II) outspreading, (III) confluence and (IV) barrier maturity with tight junction formation could be recognized with 95
INTRODUCTION:The blood-brain barrier (BBB) maintains brain homeostasis, and its dysfunction is a critical pathological mechanism for many neurological disorders. However, current BBB models lack functional brain parenchyma, hindering mechanistic studies of BBB-parenchyma interactions and limiting drug evaluation for barrier penetration and neural targeting. OBJECTIVES:To develop an integrated human blood-brain barrier-brain organoid-on-a-chip (BBOC) model that replicates physiological interaction and pathological disruption between the BBB and brain parenchyma. METHODS:A bioengineered BBB model was constructed on a millifluidic plate using human brain microvascular endothelial cells and pericytes under dynamic flow. Human brain organoids (hBOs) derived from pluripotent stem cells were co-cultured to form the BBOC model. Parenchymal pathology was induced by Aβ42 oligomers (Aβ42O) to examine their effects on BBB function and integrity. RESULTS:Conditioned medium and dynamic flow improved endothelial cell viability. Co-culture with hBOs significantly enhanced the engineered BBB function, increasing TEER values and reducing molecular permeability. Aβ42O-treated hBOs exhibited the pathological phenotypes of brain parenchyma, including notable neurite loss, impaired stem cell proliferation, increased cell apoptosis, and transcriptional upregulation of cytokine genes. The pathological hBOs disrupted the BBB, including decreased tight junction protein expression, increased barrier permeability, and impaired barrier integrity. CONCLUSION:The BBOC model reproduced physiological and pathological interactions between parenchyma and the BBB, collectively confirming that brain parenchymal states can modulate BBB integrity. Functionally, hBOs strengthened endothelial barrier integrity, indicating that parenchymal-derived signals actively promote the BBB maturation and stability. In contrast, pathological hBOs induced pericyte degeneration and tight junction disruption of BBB, demonstrating that pathological brain environments can impair BBB function. By bridging neurobiology and bioengineering, the BBOC model will facilitate investigations into neurological mechanisms and drug discovery for barrier penetration and neural targeting.
Structural adhesive bonds are a desirable joining method for lightweight composite structures, but they are currently not certifiable as the sole joining method for primary joints in aircraft structures. The multifunctional bondline approach, which includes a disbond arrest technology and strain monitoring, aims to solve this problem. The multifunctional bondline consists of, in addition to the adhesive bondline, a thin film Polyetherimide (PEI) based sensor and a Poly(vinylidene fluoride) (PVDF) layer toughening the fiber reinforced plastic surface. Previous studies have shown that adhesive failures in the PEI-PVDF interface impair the functionality of the toughening layer. This study, therefore, analyzes methods to increase the interfacial adhesion between PEI and PVDF to eliminate this weak point of the multifunctional bondline. Using physical vacuum ultraviolet (VUV), Corona, and mechanical Peel Ply methods, the adhesion enhancement is analyzed using Double Cantilever Beam and End Notched Flexure tests to determine critical energy release rate (cERR) under Mode I and II. Under Mode II, for Corona and VUV pretreatments, only the standard deviation of cERR could be reduced. However, under Mode I, the cERR value could be increased by 80 % with VUV pretreatment. Results of Energy Dispersive X-ray Spectroscopy (EDX) analysis suggest that the crack path is transferred from the PEI-PVDF interface to the PVDF film because fluoride elements were detected on the specimen half covered with PEI. This shows that the adhesive failure observed in previous studies was caused by a weak PEI-PVDF interface resulting from insufficient surface pretreatment. Peel Ply structured PEI surface decreases interfacial adhesion under Modes I and II. The significantly improved interfacial strength resulting from VUV pretreatment can pave the way for a robust multifunctional bondline. Avoiding the PEI-PVDF interface from being the weakest link in the structural bond enables the PVDF disbond-arrest function and the PEI sensor function to be retained, allowing the full potential of the base materials to be utilized.
A versatile microbioreactor platform is essential for early-stage bioprocess development and scale-up. In this study, a micro bubble column reactor (MBCR) with a microscale working volume was redesigned, and characterization methods demonstrated its flexibility in investigating gas-liquid systems. 3D-printing (rapid prototyping) was used to manufacture the MBCR, while novel gas distribution units were developed: a sintered stainless steel filter disc and a custom-made porous glass filter (uncoated or zinc oxide coated). The MBCR was characterized using integrated online sensors and a camera-based image analysis setup. Established methods were used to characterize mass transfer using the volumetric mass transfer coefficient kLa, bubble size distribution, and mixing time. The sintered sparger yielded the highest kLa of 249.1 h- 1 in the homogeneous flow regime. The coated glass filter was excluded from further analysis due to poor bubble formation. The glass filter showed the smallest median values for the area equivalent diameter at 805.5 & micro;m. Nevertheless, bimodal distributions were observed in the histograms, suggesting pronounced coalescence effects at small-scale. Relocating the liquid inlet position helped to overcome dead zones and resulted in a 3.5-fold reduction of the mixing time for the sintered sparger. Therefore, the presented workflow enables rapid integration of novel gas distribution units in the 3Dprinted MBCR and provides an adaptable platform for future investigations of gas-liquid bioprocess applications.
Continuous and long-term pressure monitoring by devices implanted in the human body promises substantial improvements for diagnosis, health monitoring, surveillance of disease progression, or surveillance of the response to a treatment but also for precision during surgeries. Here, we report on a piezoresistive sensor made entirely of parylene-C eliminating the need for heterogeneous encapsulation. Material characterization demonstrated that parylene-C is excellently suited as a construction material. The pressure sensor comprises a parylene-C membrane, which is functionalized with gold strain sensors for pressure sensitivity. It was bonded to the reference pressure cavity, thereby establishing a long-time stable hermetic sealing. The presented design and fabrication enable for the first time a monolithic, highly soft and flexible pressure sensor entirely made of biocompatible material. It exhibited high pressure sensitivity of up to 6.2 & micro;V & centerdot;mmHg-1 with very good repeatability and negligible hysteresis, made possible by thin-film strain sensors on a parylene-C membrane with a gauge factor of 7.5. Simulations show how the design can be easily even further miniaturized. Initial in vitro assay confirmed that parylene-C is biocompatible on cell culture level. Such biocompatible and chronically implantable pressure sensors are opening new possibilities in medical treatments and long-term supervision.
This paper describes and evaluates the embedding of sensors and electronic sensor nodes into fiber metal laminate (FML) plates to achieve material-integrated, guided ultrasonic wave based structural health monitoring for hybrid materials. It evaluates how embedded electronics can enhance the process of sensor data acquisition and at the same time critically investigates the drawbacks that accompany the embedding approach regarding the influence on the received signal. A FML specimen with single sensors in one half of the plate and sensors with attached electronic sensor nodes for wireless readout in the other half is manufactured, introducing the detailed embedding process for such systems. Ultrasonic through-thickness scans of the manufactured plate are presented and analyzed to assess the achieved embedding quality. Together with electric sensor signals from both, wireless and wirebound micro-electromechanical system vibrometers and data from a scanning laser Doppler vibrometer (SLDV) the influence of material-integrated components on the wave propagation around the locations of integration is discussed. Further, the signals of wirebound sensors are successfully correlated with measurements performed using the SLDV and directly compared to data provided by wirelessly readout sensor nodes having the same type of sensor attached. This work shows how reflections occurring due to a material integration of components influence the recorded sensor data. At the same time, it is discussed how, for baseline-based damage detection methods, the influence of this is assumed to be a minor problem, and proof for advantages provided by the integration of complete sensor systems directly into the host material is provided.
Abstract The applications of three-dimensional Si nanowire anodes in lithium-ion microbatteries have attracted great interest in the realization of high-capacity and integrated energy storage devices for microelectronics. Combining Si nanowires with carbon can improve the anode performance by aiding its mechanical stability during cycling. Here, we incorporate photolithography, cryogenic dry etching, and thermal evaporation as the commonly used methods in semiconductor technologies to fabricate carbon-coated Si nanowire anodes. The addition of amorphous carbon to Si nanowire anodes has an impact on increasing the initial areal capacity. However, a gradual decrease to 0.3 mAh cm−2 at the 100th cycle can be observed. The post-mortem analyses reveal different morphologies of Si nanowire anodes after cycling. It is indicated that carbon coating can help Si nanowires to suppress their volume expansion and reduce the excessively produced amorphous Si granules found in pristine Si nanowire anodes.
This study presents the development of a cost-effective, non-invasive system for synchronized artificial respiration to support preterm infants with underdeveloped lungs. Synchronizing airflow with the infant’s natural breathing cycle is crucial for efficient respiratory support. To achieve this, we developed a stretchable, skin-like, sensor array using screen printing on Silpuran substrate. The sensor’s ultrasensitive, multielement design enabled detection of subtle, multidirectional strain, produced by breathing. These signals were filtered and processed using advanced electronics to generate precise trigger points for real-time synchronization of artificial ventilation with the infant’s natural breathing pattern. The system was tested on a dummy, where airflow from a diaphragm (ventilator) was controlled and synchronized with simulated breathing (dummy). This non-invasive mechanism can provide continuous monitoring, ensure safer respiratory support for infants and a potential alternative to traditional invasive incubation methods.
Bead formation is a typical ramification of electrospun fibers during electrospinning. Presence or absence of beads controls the fiber properties, which dictates its usefulness in diverse applications. However, bead formation is a complex non-linear process influenced by solution properties as well as electrospinning process parameters, mostly explored through trial-and-error experiments. Thus, being able to predict bead formation and identify its causal properties could have tremendous techno-economic value by reducing cost of experimentation. This is challenging as these structure-property relationships between experimental features and bead formation are inherently complex and modelling them requires large datasets from diverse experiments with multiple solvents, which are not commonly available. Here, we developed our own Electrospun Fiber Experimental Attributes Dataset (FEAD) dataset, a curated meta-database of experimental data available in literature, supplemented with our own experiments. Combining it with multiple machine learning models, we showed that while an increase in polymer concentration and applied voltage leads to fewer beads, a higher Flory-Huggins parameter supports increased bead formation. Further, we adopted a game theory-based model agnostic interpretation technique called SHAP (SHapley Additive exPlanations) to identify features contributing towards the occurrence of beads and their relative significance. This novel framework successfully predicted bead formation across various PVDF-polymer solvent systems and demonstrates how community meta datasets, cutting-edge machine learning techniques, and model interpretability methods could be seamlessly integrated to reduce the number of experiments required for developing high quality PVDF fibers.
Guided ultrasonic wave-based structural health monitoring utilizes propagating elastic waves to identify, locate, and characterize damage within aviation structures. Fiber metal laminates, which are composite materials made by layering metal sheets with fiber-reinforced polymers, combine the high strength of composites with the ductility and impact resistance of metals. However, structural health monitoring methods suitable for these materials have to be developed, allowing to monitor also the inner laminate layers. Therefore, laminate-embedded MEMS vibrometers have been introduced recently. Due to the quasi-free operation of these inertial sensors, they are directly sensitive to the displacement induced by propagating guided ultrasonic waves. However, the multimodal excitation of the sensor’s core resonator, when exposed to ultrasound bursts, leads to a pseudo-nonlinear sensor response, which is attributed to the spectrum of guided ultrasonic waves and their interference with higher harmonics of the continuum resonator. The transfer behavior of the sensor can be improved by implementing electrical mode suppression. This research involves analytically modeling the continuous resonator with multiple aggregated resonators, numerically simulating sensor responses to 100 kHz ultrasound bursts, and using a laser scanning micro vibrometer setup for experimental validation, providing a deeper understanding of MEMS vibrometer dynamics for ultrasonic monitoring and demonstrating their applicability.
The integration of a Low Aspect Ratio Laminar Mixer (LARLM) with inline dynamic light scattering (inline DLS) for the first time offers controlled and continuous lipid nanoparticle preparation with in situ size monitoring. The LARLM, a 3D micromixer fabricated by two-photon polymerisation (2PP), ensures that the aqueous phase flow completely envelops the organic phase flow, creating a thin and uniform layer with a thickness of down to 5 mu m. The thickness of the layer determining particle size is controlled. Inline DLS could prove the continuous production of lipid nanoparticles (LNPs) while their size was tunable between 60nm and 160 nm. Such stable and tunable process will ultimately contribute to better results in the formulation of mRNA drugs.
Carrier nanoparticles facilitate the encapsulation of drug or mRNA molecules thereby enhancing their bioavailability. Microfluidic mixers provide a unique environment for the precise and continuous generation of nanoparticles by antisolvent precipitation. A major challenge is to understand the influence of microfluidic channel designs and geometries on the continuous production of small, uniform lipid nanoparticles (LNPs) and to identify conditions that ensure effective and controllable mixing of aqueous and organic phases in laminar flows. Another important challenge is that sufficient quantities for preclinical and clinical studies must be produced within a reasonable period of time. With this dual objective, different versions of a low aspect ratio laminar mixer (LARLM) were produced using two-photon polymerization (2PP). In the LARLM the organic phase forms a thin layer a few micrometers with a uniform velocity distribution in the center of the channel, surrounded by the aqueous phase. This concept has three major advantages: Firstly, it keeps all particles centralized in the channel, thus preventing contamination during prolonged particle generation. Secondly, diffusive mixing in the thin central stream occurs very quickly, and thirdly, the growing nanoparticles move at a homogeneous speed, which enables inline measurement of the particles. In systematic experiments with design versions of varied channel dimensions the operational parameters such as lipid concentrations and flow rates and the capability to produce LNPs with desired properties and loading capacities were explored. An interfacial dispersion model (IDM) could explain the surprising reduction of particle sizes with increased productivity. The latter allowed us to produce nanoparticles in the range of 50 nm to 180 nm (with 0.02 < PDI < 0.1) under stable conditions with a productivity of around one liter of LNP suspensions every three hours. Such performance has never been reached before with microfluidics. Moreover, LNPs loaded with coumarine-6 and various drugs were produced in the LARLM. Moreover, in-vitro experiments could confirm an improved bioavailability of coumarin-6 in cell culture experiments when loaded in LNPs by the LARLM. These results highlight the unique capabilities of LARLM devices and their potential to support nanoparticle formulation studies including preclinical and in further developments also clinical studies as required for approval as a marketable medicine. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, 426328385
Adhesive bonding is a promising approach for joining lightweight composite components. However, the reliability remains a major challenge, because failures due to fatigue are difficult. In this study, we report on the integration of a screen-printed sensor on polyetherimide substrate into the adhesive layer during CFRP fabrication, enabling in-situ monitoring of potential crack propagation due to internal strain measurement under service loading. The sensor concept is based on the comparison of strain measurements in two different sensor rows to detect deviations in the sensor signal that indicate damage. This work marks the first successful fabrication by screenprinting of a fully polyetherimide-based sensor inlay that exhibits excellent adhesion to the epoxy matrix in CFRP. We used carbon-based inks that withstand the harsh conditions during the co-curing during the CFRP-prepreg-autoclave process. After the integration process, the sensors remained fully functional and achieved a gauge factor of up to 49.
Respiratory distress is a major contributor to neonatal morbidity and mortality. Preterm infants often require continuous monitoring and artificial respiratory support due to underdeveloped lungs. Effective respiratory support requires precise synchronization of oxygen delivery with an infant's natural breathing to minimize lung injury, air leaks, or impaired cerebral blood flow. This requires noninvasive systems with intelligent sensors capable of capturing high‐fidelity respiratory signals in real‐time to accurately detect breathing cycles. However, such systems typically involve complex and costly sensor fabrication processes, energy‐intensive designs, and extensive computational demands. This study presents a low‐cost, portable, and real‐time neonatal respiration monitoring system with synchronized oxygen delivery. The skin‐like sensor patch, fabricated through screen‐printing, demonstrated high sensitivity (≈75/με) within 0–20 000 με, rapid response time (≈140 ms), minimal drift (2%) over 7,000 cyclic tests, and negligible thermal variation (<0.5 °C over 8 h). A multistage signal processing algorithm, combined with machine learning‐based classification facilitates accurate real‐time differentiation among normal breathing, tachypnea, and apnea episodes. The developed system offers a practical, noninvasive, and comfortable solution for continuous neonatal respiratory monitoring, significantly benefiting neonates in remote areas where continuous monitoring and sophisticated equipment are unavailable.
This paper numerically investigates and detects the liquid-liquid two-phase flow patterns in a T-junction microchannel for shear-thinning non-Newtonian fluids to observe the effects of rheology, microchannel diameter, flow rate, and the surface tension on the two-phase flow patterns. The study employs water and three different shear-thinning aqueous solutions at different concentrations. The simulations were conducted using the conservative Level-set Method, and four main flow patterns of droplet flow, slug flow, jet flow, and parallel flow are observed, and the flow map is then identified. Weber and Reynolds numbers were then used in this study to predict the flow patterns. The results represent that fluid viscosity can shift the transition line in the flow map in a way that an increase in the viscosity improves the probability of forming the droplet flow pattern since growing viscous forces help the jet flow to separate and create the droplets. To investigate whether the different flow regimes can also be identified continuously in the experiment, the impedance pulse sensor principle was analyzed numerically. Unlike microscopic analysis, this technique allows online detection and provides feed-back regulation with which the flow regimes can be stabilized by regulating the inflows. The results show that by comparing two separate sensor zones, the change in the impedance signal characterizes different flow regimes, and the sizes of droplets or slugs can be recognized. This technique can therefore be used in the future to experimentally verify flow maps and to stabilize the two-phase flow patterns by feed-back regulation.
Resistive Pulse Sensing has recently emerged as a promising technique for measuring and counting particles in electrolyte solutions, with applications in nanoparticle characterization, biomolecule analysis in micro-fluidic sensing. Resistive Pulse Sensing offers high single-particle sensitivity, real-time, and label-free detection. It can provide detailed information on particles including size and shape. Small pore diameters are required to detect small particles, but they limit the measurable range and carry the risk of clogging. This paper presents recent advancements in wafer-level Micro-Electro-Mechanical Systems technology specifically tailored for fabrication of microflow cells for Resistive Pulse Sensing. Key processes include femtosecond laser structuring, photolithography, etching, deposition, and bonding technologies which allow to enhance the scalability and reproducibility of the sensing platforms because they enable precise control of dimensional parameters that determine the sensitivity. To avoid clogging of very sensitive systems with very narrow pores, a bypass flow architecture was implemented that allows particles that are too large to pass through the pores to leave the sensor system. The bypass system also offers the advantage of operating without the need for sample filtration. The fabricated sensors are reusable, durable, and practical for diverse applications. Two types of micropores were fabricated, each 100 μm in length and square cross-sections with nominal edge lengths of 8 μm and 1 μm. The RPS measurement using both pores demonstrated the ability of the system to determine particle sizes with an uncertainty of +/- 10