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Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in-vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom-made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential.
Impedance spectroscopy: A tool for real-time in situ monitoring of the degradation of biopolymers
(2013)
Investigation of the degradation kinetics of biodegradable polymers is essential for the development of implantable biomedical devices with predicted biodegradability. In this work, an impedimetric sensor has been applied for real-time and in situ monitoring of degradation processes of biopolymers. The sensor consists of two platinum thin-film electrodes covered by a polymer film to be studied. The benchmark biomedical polymer poly(D,L-lactic acid) (PDLLA) was used as a model system. PDLLA films were deposited on the sensor structure from a polymer solution by using the spin-coating method. The degradation kinetics of PDLLA films have been studied in alkaline solutions of pH 9 and 12 by means of an impedance spectroscopy (IS) method. Any changes in a polymer capacitance/resistance induced by water uptake and/or polymer degradation will modulate the global impedance of the polymer-covered sensor that can be used as an indicator of the polymer degradation. The degradation rate can be evaluated from the time-dependent impedance spectra. As expected, a faster degradation has been observed for PDLLA films exposed to pH 12 solution.
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.
Microbial diversity studies regarding the aquatic communities that experienced or are experiencing environmental problems are essential for the comprehension of the remediation dynamics. In this pilot study, we present data on the phylogenetic and ecological structure of microorganisms from epipelagic water samples collected in the Small Aral Sea (SAS). The raw data were generated by massive parallel sequencing using the shotgun approach. As expected, most of the identified DNA sequences belonged to Terrabacteria and Actinobacteria (40% and 37% of the total reads, respectively). The occurrence of Deinococcus-Thermus, Armatimonadetes, Chloroflexi in the epipelagic SAS waters was less anticipated. Surprising was also the detection of sequences, which are characteristic for strict anaerobes—Ignavibacteria, hydrogen-oxidizing bacteria, and archaeal methanogenic species. We suppose that the observed very broad range of phylogenetic and ecological features displayed by the SAS reads demonstrates a more intensive mixing of water masses originating from diverse ecological niches of the Aral-Syr Darya River basin than presumed before.
A light-addressable potentiometric sensor (LAPS) is a field-effect-based (bio-) chemical sensor, in which a desired sensing area on the sensor surface can be defined by illumination. Light addressability can be used to visualize the concentration and spatial distribution of the target molecules, e.g., H+ ions. This unique feature has great potential for the label-free imaging of the metabolic activity of living organisms. The cultivation of those organisms needs specially tailored surface properties of the sensor. O2 plasma treatment is an attractive and promising tool for rapid surface engineering. However, the potential impacts of the technique are carefully investigated for the sensors that suffer from plasma-induced damage. Herein, a LAPS with a Ta2O5 pH-sensitive surface is successfully patterned by plasma treatment, and its effects are investigated by contact angle and scanning LAPS measurements. The plasma duration of 30 s (30 W) is found to be the threshold value, where excessive wettability begins. Furthermore, this treatment approach causes moderate plasma-induced damage, which can be reduced by thermal annealing (10 min at 300 °C). These findings provide a useful guideline to support future studies, where the LAPS surface is desired to be more hydrophilic by O2 plasma treatment.
An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage.
It has been shown that muscle fascicle curvature increases with increasing contraction level and decreasing muscle–tendon complex length. The analyses were done with limited examination windows concerning contraction level, muscle–tendon complex length, and/or intramuscular position of ultrasound imaging. With this study we aimed to investigate the correlation between fascicle arching and contraction, muscle–tendon complex length and their associated architectural parameters in gastrocnemius muscles to develop hypotheses concerning the fundamental mechanism of fascicle curving. Twelve participants were tested in five different positions (90°/105°*, 90°/90°*, 135°/90°*, 170°/90°*, and 170°/75°*; *knee/ankle angle). They performed isometric contractions at four different contraction levels (5%, 25%, 50%, and 75% of maximum voluntary contraction) in each position. Panoramic ultrasound images of gastrocnemius muscles were collected at rest and during constant contraction. Aponeuroses and fascicles were tracked in all ultrasound images and the parameters fascicle curvature, muscle–tendon complex strain, contraction level, pennation angle, fascicle length, fascicle strain, intramuscular position, sex and age group were analyzed by linear mixed effect models. Mean fascicle curvature of the medial gastrocnemius increased with contraction level (+5 m−1 from 0% to 100%; p = 0.006). Muscle–tendon complex length had no significant impact on mean fascicle curvature. Mean pennation angle (2.2 m−1 per 10°; p < 0.001), inverse mean fascicle length (20 m−1 per cm−1; p = 0.003), and mean fascicle strain (−0.07 m−1 per +10%; p = 0.004) correlated with mean fascicle curvature. Evidence has also been found for intermuscular, intramuscular, and sex-specific intramuscular differences of fascicle curving. Pennation angle and the inverse fascicle length show the highest predictive capacities for fascicle curving. Due to the strong correlations between pennation angle and fascicle curvature and the intramuscular pattern of curving we suggest for future studies to examine correlations between fascicle curvature and intramuscular fluid pressure.
The integration of biomolecular logic principles with electronic transducers allows designing novel digital biosensors with direct electrical output, logically triggered drug-release, and closed-loop sense/act/treat systems. This opens new opportunities for advanced personalized medicine in the context of theranostics. In the present work, we will discuss selected examples of recent developments in the field of interfacing enzyme logic gates with electrodes and semiconductor field-effect devices. Special attention is given to an enzyme OR/Reset logic gate based on a capacitive field-effect electrolyte-insulator-semiconductor sensor modified with a multi-enzyme membrane. Further examples are a digital adrenaline biosensor based on an AND logic gate with binary YES/NO output and an integrated closed-loop sense/act/treat system comprising an amperometric glucose sensor, a hydrogel actuator, and an insulin (drug) sensor.
We present a sensor concept based on copper(II)oxide (CuO) nanofibres for the detection of hydrogen peroxide (H2O2) vapour in the percent per volume (% v/v) range. The fibres were produced by using the electrospinning technique. To avoid water condensation in the pores, the fibres were initially modified by an exposure to H2S to get an enclosed surface. By a thermal treatment at 350 °C the fibres were oxidised back to CuO. Thereby, the visible pores disappear which was verified by SEM analysis. The fibres show a decrease of resistance with increasing H2O2 concentration which is due to the fact that hydrogen peroxide is an oxidising gas and CuO a p-type semiconductor. The sensor shows a change of resistance within the minute range to the exposure until the maximum concentration of 6.9% v/v H2O2. At operating temperatures below 450 °C the corresponding sensor response to a concentration of 4.1% v/v increases. The sensor shows a good reproducibility of the signal at different measurements. CuO seems to be a suitable candidate for the detection of H2O2 vapour at high concentrations.
Resistance behaviour of the sensor under exposure to H2O2 vapours between 2.3 and 6.9% v/v at an operating temperature of 450 °C.
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.
This paper presents a novel numerical procedure for computing limit and shakedown loads of structures using a node-based smoothed FEM in combination with a primal–dual algorithm. An associated primal–dual form based on the von Mises yield criterion is adopted. The primal-dual algorithm together with a Newton-like iteration are then used to solve this associated primal–dual form to determine simultaneously both approximate upper and quasi-lower bounds of the plastic collapse limit and the shakedown limit. The present formulation uses only linear approximations and its implementation into finite element programs is quite simple. Several numerical examples are given to show the reliability, accuracy, and generality of the present formulation compared with other available methods.