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Retinal Vessel Analysis (RVA) in the context of subarachnoid hemorrhage: A proof of concept study
(2016)
Background
Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH.
Methods
In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling.
Results
Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion.
Conclusion
RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.
The conjunction of (bio-)chemical recognition elements with nanoscale biological building blocks such as virus particles is considered as a very promising strategy for the creation of biohybrids opening novel opportunities for label-free biosensing. This work presents a new approach for the development of biosensors using tobacco mosaic virus (TMV) nanotubes or coat proteins (CPs) as enzyme nanocarriers. Sensor chips combining an array of Pt electrodes loaded with glucose oxidase (GOD)-modified TMV nanotubes or CP aggregates were used for amperometric detection of glucose as a model system for the first time. The presence of TMV nanotubes or CPs on the sensor surface allows binding of a high amount of precisely positioned enzymes without substantial loss of their activity, and may also ensure accessibility of their active centers for analyte molecules. Specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CPs was achieved via bioaffinity binding. These layouts were tested in parallel with glucose sensors with adsorptively immobilized [SA]-GOD, as well as [SA]-GOD crosslinked with glutardialdehyde, and came out to exhibit superior sensor performance. The achieved results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for future applications in biosensorics and biochips.
Four members of a homologous series of chlorinated poly(vinyl ester) oligomers CCl₃–(CH₂CH (OCO(CH₂)ₘCH₃))ₙ–Cl with degrees of polymerization of 10 and 20 were prepared by telomerisation using carbon tetrachloride. The number of side chain carbon atoms ranges from 2 (poly(vinyl acetate) to 18 (poly(vinyl stearate)). The effect of the n-alkyl side chain length and of the degree of polymerization on the thermal stability and crystallization behaviour of the synthesized compounds was investigated.
All oligomers degrade in two major steps by first losing HCl and side chains with subsequent breakdown of the backbone. The members with short side chains, up to poly(vinyl octanoate), are amorphous and show internal plasticization, whereas those with high number of side chain carbon atoms are semi-crystalline due to side-chain crystallization. A better packing for poly(vinyl stearate) is also noticeable. The glass transition and melting temperatures as well as the onset temperature of decomposition are influenced to a larger extent by the side chain length than by the degree of polymerization. Thermal stability is improved if both the size and number of side chains increase, but only a long side chain causes a significant increase of the resistance to degradation. This results in a stabilization of PVAc so that oligomers from poly(vinyl octanoate) on are stable under atmospheric conditions. Thus, the way to design stable, chlorinated PVEs oligomers is to use a long n-alkyl side chain.
Today, the assembly of laser systems requires a large share of manual operations due to its complexity regarding the optimal alignment of optics. Although the feasibility of automated alignment of laser optics has been shown in research labs, the development effort for the automation of assembly does not meet economic requirements – especially for low-volume laser production. This paper presents a model-based and sensor-integrated assembly execution approach for flexible assembly cells consisting of a macro-positioner covering a large workspace and a compact micromanipulator with camera attached to the positioner. In order to make full use of available models from computer-aided design (CAD) and optical simulation, sensor systems at different levels of accuracy are used for matching perceived information with model data. This approach is named "chain of refined perception", and it allows for automated planning of complex assembly tasks along all major phases of assembly such as collision-free path planning, part feeding, and active and passive alignment. The focus of the paper is put on the in-process image-based metrology and information extraction used for identifying and calibrating local coordinate systems as well as the exploitation of that information for a part feeding process for micro-optics. Results will be presented regarding the processes of automated calibration of the robot camera as well as the local coordinate systems of part feeding area and robot base.
Sensitivity of turbulent Schmidt number and turbulence model to simulations of jets in crossflow
(2016)
Environmental discharges have been traditionally designed by means of cost-intensive and time-consuming experimental studies. Some extensively validated models based on an integral approach have been often employed for water quality problems, as recommended by USEPA (i.e.: CORMIX). In this study, FLOW-3D is employed for a full 3D RANS modelling of two turbulent jet-to-crossflow cases, including free surface jet impingement. Results are compared to both physical modelling and CORMIX to better assess model performance. Turbulence measurements have been collected for a better understanding of turbulent diffusion's parameter sensitivity. Although both studied models are generally able to reproduce jet trajectory, jet separation downstream of the impingement has been reproduced only by RANS modelling. Additionally, concentrations are better reproduced by FLOW-3D when the proper turbulent Schmidt number is used. This study provides a recommendation on the selection of the turbulence model and the turbulent Schmidt number for future outfall structures design studies.
The performance and biomass yield of the perennial energy plant Sida hermaphrodita (hereafter referred to as Sida) as a feedstock for biogas and solid fuel was evaluated throughout one entire growing period at agricultural field conditions. A Sida plant development code was established to allow comparison of the plant growth stages and biomass composition. Four scenarios were evaluated to determine the use of Sida biomass with regard to plant development and harvest time: (i) one harvest for solid fuel only; (ii) one harvest for biogas production only; (iii) one harvest for biogas production, followed by a harvest of the regrown biomass for solid fuel; and (iv) two consecutive harvests for biogas production. To determine Sida's value as a feedstock for combustion, we assessed the caloric value, the ash quality, and melting point with regard to DIN EN ISO norms. The results showed highest total dry biomass yields of max. 25 t ha⁻¹, whereas the highest dry matter of 70% to 80% was obtained at the end of the growing period. Scenario (i) clearly indicated the highest energy recovery, accounting for 439 288 MJ ha⁻¹; the energy recovery of the four scenarios from highest to lowest followed this order: (i) ≫ (iii) ≫ (iv) > (ii). Analysis of the Sida ashes showed a high melting point of >1500 °C, associated with a net calorific value of 16.5–17.2 MJ kg⁻¹. All prerequisites for DIN EN ISO norms were achieved, indicating Sida's advantage as a solid energy carrier without any post-treatment after harvesting. Cell wall analysis of the stems showed a constant lignin content after sampling week 16 (July), whereas cellulose had already reached a plateau in sampling week 4 (April). The results highlight Sida as a promising woody, perennial plant, providing biomass for flexible and multipurpose energy applications.
Autoradiography is a well-established method of nuclear imaging. When different radionuclides are present simultaneously, additional processing is needed to distinguish distributions of radionuclides. In this work, a method is presented where aluminium absorbers of different thickness are used to produce images with different cut-off energies. By subtracting images pixel-by-pixel one can generate images representing certain ranges of β-particle energies. The method is applied to the measurement of irradiated reactor graphite samples containing several radionuclides to determine the spatial distribution of these radionuclides within pre-defined energy windows. The process was repeated under fixed parameters after thermal treatment of the samples. The greyscale images of the distribution after treatment were subtracted from the corresponding pre-treatment images. Significant changes in the intensity and distribution of radionuclides could be observed in some samples. Due to the thermal treatment parameters the most significant differences were observed in the ³H and ¹⁴C inventory and distribution.
Self-aeration is traditionally explained by the water turbulent boundary layer outer edge intersection with the free surface. This paper presents a discussion on the commonly accepted hypothesis behind the computation of the critical point of self-aeration in spillway flows and a new formulation is proposed based on the existence of a developing air flow over the free surface. Upstream of the inception point of self-aeration, some surface roughening has been often reported in previous studies which consequently implies some entrapped air transport and air–water flows coupling. Such air flow is proven in this study by presenting measured air velocities and computing the air boundary layer thickness for a 1V:2H smooth chute flow. Additionally, the growth rate of free surface waves has been analysed by means of Ultrasonic Sensors measurements, obtaining also the entrapped air concentration. High-speed camera imaging has been used for qualitative study of the flow perturbations.
An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer’s solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure.
Purpose
The most commonly used mobility assessments for screening risk of falls among older adults are rating scales such as the Tinetti performance oriented mobility assessment (POMA). However, its correlation with falls is not always predictable and disadvantages of the scale include difficulty to assess many of the items on a 3-point scale and poor specificity. The purpose of this study was to describe the ability of the new Aachen Mobility and Balance Index (AMBI) to discriminate between subjects with a fall history and subjects without such events in comparison to the Tinetti POMA Scale.
Methods
For this prospective cohort study, 24 participants in the study group and 10 in the control group were selected from a population of patients in our hospital who had met the stringent inclusion criteria. Both groups completed the Tinetti POMA Scale (gait and balance component) and the AMBI (tandem stance, tandem walk, ten-meter-walk-test, sit-to-stand with five repetitions, 360° turns, timed-up-and-go-test and measurement of the dominant hand grip strength). A history of falls and hospitalization in the past year were evaluated retrospectively. The relationships among the mobility tests were examined with Bland–Altmananalysis. Receiver-operated characteristics curves, sensitivity and specificity were calculated.
Results
The study showed a strong negative correlation between the AMBI (17 points max., highest fall risk) and Tinetti POMA Scale (28 points max., lowest fall risk; r = −0.78, p < 0.001) with an excellent discrimination between community-dwelling older people and a younger control group. However, there were no differences in any of the mobility and balance measurements between participants with and without a fall history with equal characteristics in test comparison (AMBI vs. Tinetti POMA Scale: AUC 0.570 vs. 0.598; p = 0.762). The Tinetti POMA Scale (cut-off <20 points) showed a sensitivity of 0.45 and a specificity of 0.69, the AMBI a sensitivity of 0.64 and a specificity of 0.46 (cut-off >5 points).
Conclusion
The AMBI comprises mobility and balance tasks with increasing difficulty as well as a measurement of the dominant hand-grip strength. Its ability to identify fallers was comparable to the Tinetti POMA Scale. However, both measurement sets showed shortcomings in discrimination between fallers and non-fallers based on a self-reported retrospective falls-status.
The light-addressable potentiometric sensor (LAPS) has the unique feature to address different regions of a sensor surface without the need of complex structures. Measurements at different locations on the sensor surface can be performed in a common analyte solution, which distinctly simplifies the fluidic set-up. However, the measurement in a single analyte chamber prevents the application of different drugs or different concentrations of a drug to each measurement spot at the same time as in the case of multi-reservoir-based set-ups. In this work, the authors designed a LAPS-based set-up for cell culture screening that utilises magnetic beads loaded with the endotoxin (lipopolysaccharides, LPS), to generate a spatially distributed gradient of analyte concentration. Different external magnetic fields can be adjusted to move the magnetic beads loaded with a specific drug within the measurement cell. By recording the metabolic activities of a cell layer cultured on top of the LAPS surface, this work shows the possibility to apply different concentrations of a sample along the LAPS measurement spots within a common analyte solution.
Light-addressable potentiometric sensor as a sensing element in plug-based microfluidic devices
(2016)
A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, ion sensing can be performed anywhere inside the microfluidic channel. In this study, the sample solution to be measured was introduced into the channel in a form of a plug with a volume in the range of microliters. Taking advantage of the light-addressability, the position of the plug could be monitored and pneumatically controlled. With the developed system, the pH value of a plug with a volume down to 400 nL could be measured. As an example of plug-based operation, two plugs were merged in the channel, and the pH change was detected by differential measurement.
We analyze the influence of dipole-dipole interactions in an electromagnetically induced transparency set up for a density at the onset of cooperative effects. To this end, we include mean-field models for the influence of local-field corrections and radiation trapping into our calculation. We show both analytically and numerically that the polarization contribution to the local field strongly modulates the phase of a weak pulse. We give an intuitive explanation for this local-field-induced phase modulation and demonstrate that it distinctively differs from the nonlinear self-phase-modulation that a strong pulse experiences in a Kerr medium.
The msprop program presented in this work is capable of solving the Maxwell–Schrödinger equations for one or several laser fields propagating through a medium of quantum optical few-level systems in one spatial dimension and in time. In particular, it allows to numerically treat systems in which a laser field interacts with the medium with both its electric and magnetic component at the same time. The internal dynamics of the few-level system is modeled by a quantum optical master equation which includes coherent processes due to optical transitions driven by the laser fields as well as incoherent processes due to decay and dephasing. The propagation dynamics of the laser fields is treated in slowly varying envelope approximation resulting in a first order wave equation for each laser field envelope function. The program employs an Adams predictor formula second order in time to integrate the quantum optical master equation and a Lax–Wendroff scheme second order in space and time to evolve the wave equations for the fields. The source function in the Lax–Wendroff scheme is specifically adapted to allow taking into account the simultaneous coupling of a laser field to the polarization and the magnetization of the medium. To reduce execution time, a customized data structure is implemented and explained. In three examples the features of the program are demonstrated and the treatment of a system with a phase-dependent cross coupling of the electric and magnetic field component of a laser field is shown.
While plate fixation of proximal ulna fractures might lead to superior clinical results compared to tension band wiring, regular plates represent an established risk factor for wound complications. The olecranon double plates (Medartis, Basel, CH) might decrease complications related to the osteosynthesis because of their low profile and better anatomical fit. This study aimed to evaluate the biomechanical performance and clinical results of the olecranon double plates.
Surgical reconstruction of the interosseous membrane (IOM) could restore longitudinal forearm stability to avoid persisting disability due to capituloradial and ulnocarpal impingement in Essex Lopresti lesions. This biomechanical study aimed to assess longitudinal forearm stability of intact specimens, after sectioning of the IOM and after reconstruction with a TightRope construct using either a single or double bundle technique.
Treatment of posttraumatic osteoarthritis of the radial column of the elbow joint remains a challenging yet common issue.
While partial joint replacement leads to high revision rates, radial head excision has shown to severely increase joint instability. Shortening osteotomy of the radius could be an option to decrease the contact pressure of the radiohumeral joint and thereby pain levels without causing valgus instability. Hence, the aim of this biomechanical study was to evaluate the effects of radial shortening on axial load distribution and valgus stability of the elbow joint.
Plate osteosynthesis of displaced proximal phalangeal neck fractures of the hand allows early mobilization due to a stable internal fixation. Nevertheless, joint stiffness—because of soft tissue irritation—represents a common complication leading to high complication rates. Del Pinal et al. recently reported promising clinical results for a new, minimally invasive fixation technique with a cannulated headless intramedullary compression screw. Hence, the aim of this study was to compare plate fixation of proximal phalangeal neck fractures to less two less invasive techniques: Crossed k-wire fixation and intramedullary screw fixation. We hypothesized that these fixation techniques provide inferior stability when compared to plate osteosynthesis.
Purpose
Two semi-empirical models were recently published, both making use of existing literature data, but each taking into account different physical phenomena that trigger hemolysis. In the first model, hemoglobin (Hb) release is described as a permeation procedure across the membrane, assuming a shear stress-dependent process (sublethal model). The second model only accounts for hemoglobin release that is caused by cell membrane breakdown, which occurs when red blood cells (RBC) undergo mechanically induced shearing for a period longer than the threshold time (nonuniform threshold model). In this paper, we introduce a model that considers the hemolysis generated by both these possible phenomena.
Methods
Since hemolysis can possibly be caused by permeation of hemoglobin through the RBC functional membrane as well as by release of hemoglobin from RBC membrane breakdown, our proposed model combines both these models. An experimental setup consisting of a Couette device was utilized for validation of our proposed model.
Results
A comparison is presented between the damage index (DI) predicted by the proposed model vs. the sublethal model vs. the nonthreshold model and experimental datasets. This comparison covers a wide range of shear stress for both human and porcine blood. An appropriate agreement between the measured DI and the DI predicted by the present model was obtained.
Conclusions
The semiempirical hemolysis model introduced in this paper aims for significantly enhanced conformity with experimental data. Two phenomenological outcomes become possible with the proposed approach: an estimation of the average time after which cell membrane breakdown occurs under the applied conditions, and a prediction of the ratio between the phenomena involved in hemolysis.
Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium.
On-line monitoring of the metabolic activity of microorganisms involved in intermediate stages of biogas production plays an important role to avoid undesirable “down times” during the biogas production. In order to control this process, an on-chip differential measuring system based on the light-addressable potentiometric sensor (LAPS) principle combined with a 3D-printed multi-chamber structure has been realized. As a test microorganism, Escherichia coli K12 (E. coli K12) were used for cell-based measurements. Multi-chamber structures were developed to determine the metabolic activity of E. coli K12 in suspension for a different number of cells, responding to the addition of a constant or variable amount of glucose concentrations, enabling differential and simultaneous measurements.
A comparative performance analysis of the CFD platforms OpenFOAM and FLOW-3D is presented, focusing on a 3D swirling turbulent flow: a steady hydraulic jump at low Reynolds number. Turbulence is treated using RANS approach RNG k-ε. A Volume Of Fluid (VOF) method is used to track the air–water interface, consequently aeration is modeled using an Eulerian–Eulerian approach. Structured meshes of cubic elements are used to discretize the channel geometry. The numerical model accuracy is assessed comparing representative hydraulic jump variables (sequent depth ratio, roller length, mean velocity profiles, velocity decay or free surface profile) to experimental data. The model results are also compared to previous studies to broaden the result validation. Both codes reproduced the phenomenon under study concurring with experimental data, although special care must be taken when swirling flows occur. Both models can be used to reproduce the hydraulic performance of energy dissipation structures at low Reynolds numbers.
A multi-spot light-addressable potentiometric sensor (LAPS), which belongs to the family of semiconductor field-effect devices, was applied for label-free detection of double-stranded deoxyribonucleic acid (dsDNA) molecules by their intrinsic molecular charge. To reduce the distance between the DNA charge and sensor surface and thus, to enhance the electrostatic coupling between the dsDNA molecules and the LAPS, the negatively charged dsDNA molecules were electrostatically adsorbed onto the gate surface of the LAPS covered with a positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)). The surface potential changes in each spot of the LAPS, induced by the layer-by-layer adsorption of a PAH/dsDNA bilayer, were recorded by means of photocurrent-voltage and constant-photocurrent measurements. In addition, the surface morphology of the gate surface before and after consecutive electrostatic adsorption of PAH and dsDNA layers was studied by atomic force microscopy measurements. Moreover, fluorescence microscopy was used to verify the successful adsorption of dsDNA molecules onto the PAH-modified LAPS surface. A high sensor signal of 25 mV was registered after adsorption of 10 nM dsDNA molecules. The lower detection limit is down to 0.1 nM dsDNA. The obtained results demonstrate that the PAH-modified LAPS device provides a convenient and rapid platform for the direct label-free electrical detection of in-solution hybridized dsDNA molecules.
Optimization of the immobilization of bacterial spores on glass substrates with organosilanes
(2016)
Spores can be immobilized on biosensors to function as sensitive recognition elements. However, the immobilization can affect the sensitivity and reproducibility of the sensor signal. In this work, three different immobilization strategies with organosilanes were optimized and characterized to immobilize Bacillus atrophaeus spores on glass substrates. Five different silanization parameters were investigated: nature of the solvent, concentration of the silane, silanization time, curing process, and silanization temperature. The resulting silane layers were resistant to a buffer solution (e.g., Ringer solution) with a polysorbate (e.g., Tween®80) and sonication.
A refined substructure technique in the frequency domain is developed, which permits consideration of the interaction effects among adjacent containers through the supporting deformable soil medium. The tank-liquid systems are represented by means of mechanical models, whereas discrete springs and dashpots stand for the soil beneath the foundations. The proposed model is employed to assess the responses of adjacent circular, cylindrical tanks for harmonic and seismic excitations over wide range of tank proportions and soil conditions. The influence of the number, spatial arrangement of the containers and their distance on the overall system's behavior is addressed. The results indicate that the cross-interaction effects can substantially alter the impulsive components of response of each individual element in a tank farm. The degree of this impact is primarily controlled by the tank proportions and the proximity of the predominant natural frequencies of the shell-liquid-soil systems and the input seismic motion. The group effects should be not a priori disregarded, unless the tanks are founded on shallow soil deposit overlying very stiff material or bedrock.
Based on an identifying Volterra type integral equation for randomly right censored observations from a lifetime distribution function F, we solve the corresponding estimating equation by an explicit and implicit Euler scheme. While the first approach results in some known estimators, the second one produces new semi-parametric and pre-smoothed Kaplan–Meier estimators which are real distribution functions rather than sub-distribution functions as the former ones are. This property of the new estimators is particular useful if one wants to estimate the expected lifetime restricted to the support of the observation time.
Specifically, we focus on estimation under the semi-parametric random censorship model (SRCM), that is, a random censorship model where the conditional expectation of the censoring indicator given the observation belongs to a parametric family. We show that some estimated linear functionals which are based on the new semi-parametric estimator are strong consistent, asymptotically normal, and efficient under SRCM. In a small simulation study, the performance of the new estimator is illustrated under moderate sample sizes. Finally, we apply the new estimator to a well-known real dataset.
We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures.
Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
Operational Modal Analysis (OMA) is a promising candidate for flutter testing and Structural Health Monitoring (SHM) of aircraft wings that are passively excited by wind loads. However, no studies have been published where OMA is tested in transonic flows, which is the dominant condition for large civil aircraft and is characterized by complex and unique aerodynamic phenomena. We use data from the HIRENASD large-scale wind tunnel experiment to automatically extract modal parameters from an ambiently excited wing operated in the transonic regime using two OMA methods: Stochastic Subspace Identification (SSI) and Frequency Domain Decomposition (FDD). The system response is evaluated based on accelerometer measurements. The excitation is investigated from surface pressure measurements. The forcing function is shown to be non-white, non-stationary and contaminated by narrow-banded transonic disturbances. All these properties violate fundamental OMA assumptions about the forcing function. Despite this, all physical modes in the investigated frequency range were successfully identified, and in addition transonic pressure waves were identified as physical modes as well. The SSI method showed superior identification capabilities for the investigated case. The investigation shows that complex transonic flows can interfere with OMA. This can make existing approaches for modal tracking unsuitable for their application to aircraft wings operated in the transonic flight regime. Approaches to separate the true physical modes from the transonic disturbances are discussed.
Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing.
In this study, we show that synthetic sapphire (Al₂O₃), an established implant material, can also serve as a platform material for biosensors comparable to nanocrystalline diamond. Sapphire chips, beads, and powder were first modified with (3-aminopropyl) triethoxysilane (APTES), followed by succinic anhydride (SA), and finally single-stranded probe DNA was EDC coupled to the functionalized layer. The presence of the APTES-SA layer on sapphire powders was confirmed by thermogravimetric analyis and Fourier-transform infrared spectroscopy. Using planar sapphire chips as substrates and X-ray photoelectron spectroscopy (XPS) as surface-sensitive tool, the sequence of individual layers was analyzed with respect to their chemical state, enabling the quantification of areal densities of the involved molecular units. Fluorescence microscopy was used to demonstrate the hybridization of fluorescently tagged target DNA to the probe DNA, including denaturation- and re-hybridization experiments. Due to its high thermal conductivity, synthetic sapphire is especially suitable as a chip material for the heat-transfer method, which was employed to distinguish complementary- and non-complementary DNA duplexes containing single-nucleotide polymorphisms. These results indicate that it is possible to detect mutations electronically with a chemically resilient and electrically insulating chip material.
The sterilization of packages in aseptic food processes is highly significant to maintain a consumer-safe product with extended shelf-life. Today, the sterilization of food packages is predominantly accomplished by gaseous hydrogen peroxide (H2O2) in combination with heat. In order to monitor this sterilization process, calorimetric gas sensors as differential set-up of two platinum temperature sensors representing a catalytically active (additionally deposition of MnO2) and a passive segment have been recently developed. The temperature rise of the exothermic decomposition serves as an indicator of the present H2O2 concentration. In the present work, a theoretical approach considering the sensor’s thermochemistry and physical transport phenomena was formulated to evaluate the temperature rise based on the energy content of gaseous H2O2. In a further part of this work, three polymers have been analyzed with respect to their application as passivation materials. The examined polymers are photoresist SU-8, perfluoroalkoxy (PFA) and fluorinated ethylene propylene (FEP). Thermal analyses by means of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) have been conducted to determine the operation limits of the polymers. The overall chemical resistance and stability of the polymers against the harsh environmental conditions during the sterilization process have been examined by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR).
The chemical imaging sensor was applied to in-situ pH imaging of the solution in the vicinity of a corroding surface of stainless steel under potentiostatic polarization. A test piece of polished stainless steel was placed on the sensing surface leaving a narrow gap filled with artificial seawater and the stainless steel was corroded under polarization. The pH images obtained during polarization showed correspondence between the region of lower pH and the site of corrosion. It was also found that the pH value in the gap became as low as 2 by polarization, which triggered corrosion.
Designing novel or optimizing existing biodegradable polymers for biomedical applications requires numerous tests on the effect of substances on the degradation process. In the present work, polymer-modified electrolyte–insulator–semiconductor (PMEIS) sensors have been applied for monitoring an enzymatically catalyzed degradation of polymers for the first time. The thin films of biodegradable polymer poly(d,l-lactic acid) and enzyme lipase were used as a model system. During degradation, the sensors were read-out by means of impedance spectroscopy. In order to interpret the data obtained from impedance measurements, an electrical equivalent circuit model was developed. In addition, morphological investigations of the polymer surface have been performed by means of in situ atomic force microscopy. The sensor signal change, which reflects the progress of degradation, indicates an accelerated degradation in the presence of the enzyme compared to hydrolysis in neutral pH buffer media. The degradation rate increases with increasing enzyme concentration. The obtained results demonstrate the potential of PMEIS sensors as a very promising tool for in situ and real-time monitoring of degradation of polymers.
The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept.
Ground or aerial robots equipped with advanced sensing technologies, such as three-dimensional laser scanners and advanced mapping algorithms, are deemed useful as a supporting technology for first responders. A great deal of excellent research in the field exists, but practical applications at real disaster sites are scarce. Many projects concentrate on equipping robots with advanced capabilities, such as autonomous exploration or object manipulation. In spite of this, realistic application areas for such robots are limited to teleoperated reconnaissance or search. In this paper, we investigate how well state-of-the-art and off-the-shelf components and algorithms are suited for reconnaissance in current disaster-relief scenarios. The basic idea is to make use of some of the most common sensors and deploy some widely used algorithms in a disaster situation, and to evaluate how well the components work for these scenarios. We acquired the sensor data from two field experiments, one from a disaster-relief operation in a motorway tunnel, and one from a mapping experiment in a partly closed down motorway tunnel. Based on these data, which we make publicly available, we evaluate state-of-the-art and off-the-shelf mapping approaches. In our analysis, we integrate opinions and replies from first responders as well as from some algorithm developers on the usefulness of the data and the limitations of the deployed approaches, respectively. We discuss the lessons we learned during the two missions. These lessons are interesting for the community working in similar areas of urban search and rescue, particularly reconnaissance and search.
Block ramps are ecologically oriented drop structures with adequate energy dissipation and partially moderate flow velocities. A special case is given with crossbar block ramps, where the upstream and downstream level difference is reduced by a series of basins. To prevent the total structure from failing, the stability of single boulders within the crossbars and the bed material in between must be guaranteed. The present paper addresses the stability of bed material and scour development for various flow regimes. Any bed material erosion may affect the stability of the crossbar boulders, which in turn can result in major damages of the ramp. Therefore new design approaches are developed to choose an appropriate bed material size and to avoid failures of crossbar block ramp structures.
In this work, a sensor to evaluate sterilization processes with hydrogen peroxide vapor has been characterized. Experimental, analytical and numerical methods were applied to evaluate and study the sensor behavior. The sensor set-up is based on planar interdigitated electrodes. The interdigitated electrode structure consists of 614 electrode fingers spanning over a total sensing area of 20 mm2. Sensor measurements were conducted with and without microbiological spores as well as after an industrial sterilization protocol. The measurements were verified using an analytical expression based on a first-order elliptical integral. A model based on the finite element method with periodic boundary conditions in two dimensions was developed and utilized to validate the experimental findings.
Miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge favor the semiconductor field-effect platform as one of the most attractive approaches for the development of label-free DNA chips. In this work, a capacitive field-effect EIS (electrolyte–insulator–semiconductor) sensor covered with a layer-by-layer prepared, positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)) was used for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization. The negatively charged probe single-stranded DNA (ssDNA) molecules were electrostatically adsorbed onto the positively charged PAH layer, resulting in a preferentially flat orientation of the ssDNA molecules within the Debye length, thus yielding a reduced charge-screening effect and a higher sensor signal. Each sensor-surface modification step (PAH adsorption, probe ssDNA immobilization, hybridization with complementary target DNA (cDNA), reducing an unspecific adsorption by a blocking agent, incubation with noncomplementary DNA (ncDNA) solution) was monitored by means of capacitance–voltage and constant-capacitance measurements. In addition, the surface morphology of the PAH layer was studied by atomic force microscopy and contact-angle measurements. High hybridization signals of 34 and 43 mV were recorded in low-ionic strength solutions of 10 and 1 mM, respectively. In contrast, a small signal of 4 mV was recorded in the case of unspecific adsorption of fully mismatched ncDNA. The density of probe ssDNA and dsDNA molecules as well as the hybridization efficiency was estimated using the experimentally measured DNA immobilization and hybridization signals and a simplified double-layer capacitor model. The results of field-effect experiments were supported by fluorescence measurements, verifying the DNA-immobilization and hybridization event.
Following earlier studies, we present forward and inverse simulations of heat and fluid transport of the upper crust using a local 3-D model of the Kola area. We provide best estimates for palaeotemperatures and permeabilities, their errors and their dependencies. Our results allow discriminating between the two mentioned processes to a certain extent, partly resolving the non-uniqueness of the problem. We find clear indications for a significant contribution of advective heat transport, which, in turn, imply only slightly lower ground surface temperatures during the last glacial maximum relative to the present value. These findings are consistent with the general background knowledge of (i) the fracture zones and the corresponding fluid movements in the bedrock and (ii) the glacial history of the Kola area.
Modeling contribution to risk assessment of thermal production power for geothermal reservoirs
(2013)
We present an effective finite difference formulation for implementing and modeling multiple borehole heat exchangers (BHE) in the general 3-D coupled heat and flow transport code SHEMAT. The BHE with arbitrary length can be either coaxial or double U-shaped. It is particularly suitable for modeling deep BHEs which contain varying pipe diameters and materials.
Usually, in numerical simulations, a fine discretization of the BHE assemblage is required, due to the large geometric aspect ratios involved. This yields large models and long simulation times. The approach avoids this problem by considering heat transport between fluid and the soil through pipes and grout via thermal resistances. Therefore, the simulation time can be significantly reduced.
The coupling with SHEMAT is realized by introducing an effective heat generation. Due to this connection, it is possible to consider heterogeneous geological models, as well as the influence of groundwater flow. This is particularly interesting when studying the long term behavior of a single BHE or a BHE field. Heating and cooling loads can enter the model with an arbitrary interval, e.g. from hourly to monthly values. When dealing with large BHE fields, computing times can be further significantly reduced by focusing on the temperature field around the BHEs, without explicitly modeling inlet and outlet temperatures. This allows to determine the possible migration of cold and warm plumes due to groundwater flow, which is of particular importance in urban areas with a high BHE installation density.
The model is validated against the existing BHE modeling codes EWS and EED. A comparison with monitoring data from a deep BHE in Switzerland shows a good agreement. Synthetic examples demonstrate the field of application of this model.
The proposed Den Haag Zuidwest district heating system of the city of The Hague consists of a deep doublet in a Jurassic sandstone layer that is designed for a production temperature of 75 °C and a reinjection temperature of 40 °C at a flow rate of 150 m3 h−1. The prediction of reservoir temperature and production behavior is crucial for success of the proposed geothermal doublet. This work presents the results of a study of the important geothermal and geohydrological issues for the doublet design. In the first phase of the study, the influences of the three-dimensional (3D) structures of anticlines and synclines on the temperature field were examined. A comprehensive petrophysical investigation was performed to build a large scale 3D-model of the reservoir. Several bottomhole temperatures (BHTs), as well as petrophysical logs were used to calibrate the model using thermal conductivity measurements on 50 samples from boreholes in different lithological units in the study area. Profiles and cross sections extracted from the calculated temperature field were used to study the temperature in the surrounding areas of the planned doublet. In the second phase of the project, a detailed 3D numerical reservoir model was set up, with the aim of predicting the evolution of the producer and injector temperatures, and the extent of the cooled area around the injector. The temperature model from the first phase provided the boundary conditions for the reservoir model. Hydraulic parameters for the target horizons, such as porosity and permeability, were taken from data available from the nearby exploration wells. The simulation results are encouraging as no significant thermal breakthrough is predicted. For the originally planned location of the producer, the extracted water temperature is predicted to be around 79 °C, with an almost negligible cooling in the first 50 years of production. When the producer is located shallower parts of the reservoir, the yield water temperatures is lower, starting at ≈76 °C and decreasing to ≈74 °C after 50 years of operation. This comparatively larger decrease in temperature with time is caused by the structural feature of the reservoir, namely a higher dip causes the cooler water to easily move downward. In view of the poor reservoir data, the reservoir simulation model is constructed to allow iterative updates using data assimilation during planned drilling, testing, and production phases. Measurements during an 8 h pumping test carried out in late 2010 suggest that a flow rate of 150 m3 h−1 is achievable. Fluid temperatures of 76.5 °C were measured, which is very close to the predicted value.
Quantifying and minimizing uncertainty is vital for simulating technically and economically successful geothermal reservoirs. To this end, we apply a stochastic modelling sequence, a Monte Carlo study, based on (i) creating an ensemble of possible realizations of a reservoir model, (ii) forward simulation of fluid flow and heat transport, and (iii) constraining post-processing using observed state variables. To generate the ensemble, we use the stochastic algorithm of Sequential Gaussian Simulation and test its potential fitting rock properties, such as thermal conductivity and permeability, of a synthetic reference model and—performing a corresponding forward simulation—state variables such as temperature. The ensemble yields probability distributions of rock properties and state variables at any location inside the reservoir. In addition, we perform a constraining post-processing in order to minimize the uncertainty of the obtained distributions by conditioning the ensemble to observed state variables, in this case temperature. This constraining post-processing works particularly well on systems dominated by fluid flow. The stochastic modelling sequence is applied to a large, steady-state 3-D heat flow model of a reservoir in The Hague, Netherlands. The spatial thermal conductivity distribution is simulated stochastically based on available logging data. Errors of bottom-hole temperatures provide thresholds for the constraining technique performed afterwards. This reduce the temperature uncertainty for the proposed target location significantly from 25 to 12 K (full distribution width) in a depth of 2300 m. Assuming a Gaussian shape of the temperature distribution, the standard deviation is 1.8 K. To allow a more comprehensive approach to quantify uncertainty, we also implement the stochastic simulation of boundary conditions and demonstrate this for the basal specific heat flow in the reservoir of The Hague. As expected, this results in a larger distribution width and hence, a larger, but more realistic uncertainty estimate. However, applying the constraining post-processing the uncertainty is again reduced to the level of the post-processing without stochastic boundary simulation. Thus, constraining post-processing is a suitable tool for reducing uncertainty estimates by observed state variables.
Capacitive field-effect electrolyte-insulator-semiconductor sensors consisting of an Al-p-Si-SiO2 structure have been used for the electrical detection of unlabelled single- and double-stranded DNA (dsDNA) molecules by their intrinsic charge. A simple functionalization protocol based on the layer-by-layer (LbL) technique was used to prepare a weak polyelectrolyte/probe-DNA bilayer, followed by the hybridization with complementary target DNA molecules. Due to the flat orientation of the LbL-adsorbed DNA molecules, a high sensor signal has been achieved. In addition, direct label-free detection of in-solution hybridized dsDNA molecules has been studied.
The chemical imaging sensor is a field-effect sensor which is able to visualize both the distribution of ions (in LAPS mode) and the distribution of impedance (in SPIM mode) inthe sample. In this study, a novel wound-healing assay is proposed, in which the chemical imaging sensor operated in SPIM mode is applied to monitor the defect of a cell layer brought into proximity of the sensing surface.A reduced impedance inside the defect, which was artificially formed ina cell layer, was successfully visualized in a photocurrent image.
A sensor system for investigating (bio)degradationprocesses of polymers is presented. The system utilizes semiconductor field-effect sensors and is capable of monitoring the degradation process in-situ and in real-time. The degradation of the polymer poly(d,l-lactic acid) is exemplarily monitored in solutions with different pH value, pH-buffer solution containing the model enzyme lipase from Rhizomucormiehei and cell-culture medium containing supernatants from stimulated and non-stimulated THP-1-derived macrophages mimicking activation of the immune system.
An amperometric enzyme biosensor has been applied for the detection of adrenaline. The adrenaline biosensor has been prepared by modification of an oxygen electrode with the enzyme laccase that operates at a broad pH range between pH 3.5 to pH 8. The enzyme molecules were immobilized via cross-linking with glutaraldehyde. The sensitivity of the developed adrenaline biosensor in different pH buffer solutions has been studied.
LAPS are field-effect-based potentiometric sensors which are able to monitor analyte concentrations in a spatially resolved manner. Hence, a LAPS sensor system is a powerful device to record chemical imaging of the concentration of chemical species in an aqueous solution, chemical reactions, or the growth of cell colonies on the sensor surface, to record chemical images. In this work, multi-chamber 3D-printed structures made out of polymer (PP-ABS) were combined with LAPS chips to analyse differentially and simultaneously the metabolic activity of Escherichia coli K12 and Chinese hamster ovary (CHO) cells, and the responds of those cells to the addition of glucose solution.
Various models have been proposed for the prediction of the necessary support pressure at the face of a shallow tunnel. To assess their quality, the collapse of a tunnel face was modelled with small-scale model tests at single gravity. The development of the failure mechanism and the support force at the face in dry sand were investigated. The observed displacement patterns show a negligible influence of overburden on the extent and evolution of the failure zone. The latter is significantly influenced, though, by the initial density of the sand: in dense sand a chimney-wedge-type collapse mechanism developed, which propagated towards the soil surface. Initially, loose sand did not show any discrete collapse mechanism. The necessary support force was neither influenced by the overburden nor the initial density. A comparison with quantitative predictions by several theoretical models showed that the measured necessary support pressure is overestimated by most of the models. Those by Vermeer/Ruse and Léca/Dormieux showed the best agreement to the measurements.
This paper proposes an approach to the choice and evaluation of engineering models with the aid of a typical application in geotechnics. An important issue in the construction of shallow tunnels, especially in weak ground conditions, is the tunnel face stability. Various theoretical and numerical models for predicting the necessary support pressure have been put forth in the literature. In this paper, we combine laboratory experiments performed at the University of Innsbruck with current methods of uncertainty and sensitivity analysis for assessing adequacy, predictive power and robustness of the models. The major issues are the handling of the twofold uncertainty of test results and of model predictions as well as the decision about what are the influential input parameters.
Influence of refrigerated storage on tensile mechanical properties of porcine liver and spleen
(2015)
Detection of triacetone triperoxide using temperature cycled metal-oxide semiconductor gas sensors
(2015)
A concept for a new generation of an integrated multi-functional biosensor/actuator system is developed, which is based on biomolecular logic principles. Such a system is expected to be able to detect multiple biochemical input signals simultaneously and in real-time and convert them into electrical output signals with logical operations such as OR, AND, etc. The system can be designed as a closed-loop drug release device triggered by an enzyme logic gate, while the release of the drug induced by the actuator at the required dosage and timing will be controlled by an additional drug sensor. Thus, the system could help to make an accurate and specific diagnosis. The presented concept is exemplarily demonstrated by using an enzyme logic gate based on a glucose/glucose oxidase system, a temperature-responsive hydrogel mimicking the actuator function and an insulin (drug) sensor. In this work, the results of functional testing of individual amperometric glucose and insulin sensors as well as an impedimetric sensor for the detection of the hydrogel swelling/shrinking are presented.
A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation.
Chelate stabilization of a titanium(IV)–salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.
Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.