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Institute
- Fachbereich Medizintechnik und Technomathematik (1545) (remove)
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.
A graphene-functionalized carbon fiber electrode was modified with adsorbed polyethylenimine to introduce amino functionalities and then with trigonelline and 4-carboxyphenylboronic acid covalently bound to the amino groups. The trigonelline species containing quarterized pyridine groups produced positive charge on the electrode surface regardless of the pH value, while the phenylboronic acid species were neutral below pH 8 and negatively charged above pH 9 (note that their pKa=8.4). The total charge on the monolayer-modified electrode was positive at the neutral pH and negative at pH > 9. Note that 4-carboxyphenylboronic acid was attached to the electrode surface in molar excess to trigonelline, thus allowing the negative charge to dominate on the electrode surface at basic pH. Negatively charged fluorescent dye-labeled insulin (insulin-FITC) was loaded on the modified electrode surface at pH 7.0 due to its electrostatic attraction to the positively charged interface. The local pH in close vicinity to the electrode surface was increased to ca. 9–10 due to consumption of H+ ions upon electrochemical reduction of oxygen proceeding at the potential of −1.0 V (vs. Ag/AgCl) applied on the modified electrode. The process resulted in recharging of the electrode surface to the negative value due to the formation of the negative charge on the phenylboronic acid groups, thus resulting in the electrostatic repulsion of insulin-FITC and stimulating its release from the electrode surface. The insulin release was characterized by fluorescence spectroscopy (using the FITC-labeled insulin), by electrochemical measurements on an iridium oxide, IrOx, electrode and by mass spectrometry. The graphene-functionalized carbon fiber electrode demonstrated significant advantages in the signal-stimulated insulin release comparing with the carbon fiber electrode without the graphene species.
In lab-on-chip systems, electrodes are important for the manipulation (e.g., cell stimulation, electrolysis) within such systems. An alternative to commonly used electrode structures can be a light-addressable electrode. Here, due to the photoelectric effect, the conducting area can be adjusted by modification of the illumination area which enables a flexible control of the electrode. In this work, titanium dioxide based light-addressable electrodes are fabricated by a sol–gel technique and a spin-coating process, to deposit a thin film on a fluorine-doped tin oxide glass. To characterize the fabricated electrodes, the thickness, and morphological structure are measured by a profilometer and a scanning electron microscope. For the electrochemical behavior, the dark current and the photocurrent are determined for various film thicknesses. For the spatial resolution behavior, the dependency of the photocurrent while changing the area of the illuminated area is studied. Furthermore, the addressing of single fluid compartments in a three-chamber system, which is added to the electrode, is demonstrated.
The semiconductor field-effect platform represents a powerful tool for detecting the adsorption and binding of charged macromolecules with direct electrical readout. In this work, a capacitive electrolyte–insulator–semiconductor (EIS) field-effect sensor consisting of an Al-p-Si-SiO2 structure has been applied for real-time in situ electrical monitoring of the layer-by-layer formation of polyelectrolyte (PE) multilayers (PEM). The PEMs were deposited directly onto the SiO2 surface without any precursor layer or drying procedures. Anionic poly(sodium 4-styrene sulfonate) and cationic weak polyelectrolyte poly(allylamine hydrochloride) have been chosen as a model system. The effect of the ionic strength of the solution, polyelectrolyte concentration, number and polarity of the PE layers on the characteristics of the PEM-modified EIS sensors have been studied by means of capacitance–voltage and constant-capacitance methods. In addition, the thickness, surface morphology, roughness and wettabilityof the PE mono- and multilayers have been characterised by ellipsometry, atomic force microscopy and water contact-angle methods, respectively. To explain potential oscillations on the gate surface and signal behaviour of the capacitive field-effect EIS sensor modified with a PEM, a simplified electrostatic model that takes into account the reduced electrostatic screening of PE charges by mobile ions within the PEM has been proposed and discussed.
Cell spraying has become a feasible application method for cell therapy and tissue engineering approaches. Different devices have been used with varying success. Often, twin-fluid atomizers are used, which require a high gas velocity for optimal aerosolization characteristics. To decrease the amount and velocity of required air, a custom-made atomizer was designed based on the effervescent principle. Different designs were evaluated regarding spray characteristics and their influence on human adipose-derived mesenchymal stromal cells. The arithmetic mean diameters of the droplets were 15.4–33.5 µm with decreasing diameters for increasing gas-to-liquid ratios. The survival rate was >90% of the control for the lowest gas-to-liquid ratio. For higher ratios, cell survival decreased to approximately 50%. Further experiments were performed with the design, which had shown the highest survival rates. After seven days, no significant differences in metabolic activity were observed. The apoptosis rates were not influenced by aerosolization, while high gas-to-liquid ratios caused increased necrosis levels. Tri-lineage differentiation potential into adipocytes, chondrocytes, and osteoblasts was not negatively influenced by aerosolization. Thus, the effervescent aerosolization principle was proven suitable for cell applications requiring reduced amounts of supplied air. This is the first time an effervescent atomizer was used for cell processing.
Background
Minor changes in protein structure induced by small organic and inorganic molecules can result in significant metabolic effects. The effects can be even more profound if the molecular players are chemically active and present in the cell in considerable amounts. The aim of our study was to investigate effects of a nitric oxide donor (spermine NONOate), ATP and sodium/potassium environment on the dynamics of thermal unfolding of human hemoglobin (Hb). The effect of these molecules was examined by means of circular dichroism spectrometry (CD) in the temperature range between 25°C and 70°C. The alpha-helical content of buffered hemoglobin samples (0.1 mg/ml) was estimated via ellipticity change measurements at a heating rate of 1°C/min.
Results
Major results were:
1) spermine NONOate persistently decreased the hemoglobin unfolding temperature T u irrespectively of the Na + /K + environment,
2) ATP instead increased the unfolding temperature by 3°C in both sodium-based and potassium-based buffers and
3) mutual effects of ATP and NO were strongly influenced by particular buffer ionic compositions. Moreover, the presence of potassium facilitated a partial unfolding of alpha-helical structures even at room temperature.
Conclusion
The obtained data might shed more light on molecular mechanisms and biophysics involved in the regulation of protein activity by small solutes in the cell.
The ClearPET® scanners developed by the Crystal Clear Collaboration use multichannel PMTs as photodetectors with scintillator pixels coupled individually to each channel. In order to localize an event each channel anode is connected to a comparator that triggers when the anode signal exceeds a common predefined threshold. Two major difficulties here are crosstalk of light and the gain nonuniformity of the PMT channels. Crosstalk can generate false triggering in channels adjacent to the actual event. On the one hand this can be suppressed by sufficiently increasing the threshold, but on the other hand a threshold too high can already prevent valid events on the lower gain channels from being detected. Finally, both effects restrict the dynamic range of pulse heights that can be processed. The requirements to the dynamic range are not low as the ClearPET® scanners detect the depth of interaction by phoswich pixels consisting of LSO and Lu0.7Y0.3AP, two scintillators with different light yields. We will present a model to estimate the achievable dynamic range and show solutions to increase it.
Effectiveness of the edge-based smoothed finite element method applied to soft biological tissues
(2012)
During rapid deceleration of the body, tendons buffer part of the elongation of the muscle-tendon unit (MTU), enabling safe energy dissipation via eccentric muscle contraction. Yet, the influence of changes in tendon stiffness within the physiological range upon these lengthening contractions is unknown. This study aimed to examine the effect of training-induced stiffening of the Achilles tendon on triceps surae muscle-tendon behavior during a landing task. Twenty-one male subjects were assigned to either a 10-week resistance-training program consisting of single-leg isometric plantarflexion (n = 11) or to a non-training control group (n = 10). Before and after the training period, plantarflexion force, peak Achilles tendon strain and stiffness were measured during isometric contractions, using a combination of dynamometry, ultrasound and kinematics data. Additionally, testing included a step-landing task, during which joint mechanics and lengths of gastrocnemius and soleus fascicles, Achilles tendon, and MTU were determined using synchronized ultrasound, kinematics and kinetics data collection. After training, plantarflexion strength and Achilles tendon stiffness increased (15 and 18%, respectively), and tendon strain during landing remained similar. Likewise, lengthening and negative work produced by the gastrocnemius MTU did not change detectably. However, in the training group, gastrocnemius fascicle length was offset (8%) to a longer length at touch down and, surprisingly, fascicle lengthening and velocity were reduced by 27 and 21%, respectively. These changes were not observed for soleus fascicles when accounting for variation in task execution between tests. These results indicate that a training-induced increase in tendon stiffness does not noticeably affect the buffering action of the tendon when the MTU is rapidly stretched. Reductions in gastrocnemius fascicle lengthening and lengthening velocity during landing occurred independently from tendon strain. Future studies are required to provide insight into the mechanisms underpinning these observations and their influence on energy dissipation.
Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.
Prior to immobilization of biomolecules or cells onto biosensor surfaces, the surface must be physically or chemically activated for further functionalization. Organosilanes are a versatile option as they facilitate the immobilization through their terminal groups and also display self-assembly. Incorporating hydroxyl groups is one of the important methods for primary immobilization. This can be done, for example, with oxygen plasma treatment. However, this treatment can affect the performance of the biosensors and this effect is not quite well understood for surface functionalization. In this work, the effect of O2 plasma treatment on EIS sensors was investigated by means of electrochemical characterizations: capacitance–voltage (C–V) and constant capacitance (ConCap) measurements. After O2 plasma treatment, the potential of the EIS sensor dramatically shifts to a more negative value. This was successfully reset by using an annealing process.
Pulmonary arterial cannulation is a common and effective method for percutaneous mechanical circulatory support for concurrent right heart and respiratory failure [1]. However, limited data exists to what effect the positioning of the cannula has on the oxygen perfusion throughout the pulmonary artery (PA). This study aims to evaluate, using computational fluid dynamics (CFD), the effect of different cannula positions in the PA with respect to the oxygenation of the different branching vessels in order for an optimal cannula position to be determined. The four chosen different positions (see Fig. 1) of the cannulas are, in the lower part of the main pulmonary artery (MPA), in the MPA at the junction between the right pulmonary artery (RPA) and the left pulmonary artery (LPA), in the RPA at the first branch of the RPA and in the LPA at the first branch of the LPA.
Many important properties of bacterial cellulose (BC), such as moisture absorption capacity, elasticity and tensile strength, largely depend on its structure. This paper presents a study on the effect of the drying method on BC films produced by Medusomyces gisevii using two different procedures: room temperature drying (RT, (24 ± 2 °C, humidity 65 ± 1%, dried until a constant weight was reached) and freeze-drying (FD, treated at − 75 °C for 48 h). BC was synthesized using one of two different carbon sources—either glucose or sucrose. Structural differences in the obtained BC films were evaluated using atomic force microscopy (AFM), scanning electron microscopy (SEM), and X-ray diffraction. Macroscopically, the RT samples appeared semi-transparent and smooth, whereas the FD group exhibited an opaque white color and sponge-like structure. SEM examination showed denser packing of fibrils in FD samples while RT-samples displayed smaller average fiber diameter, lower surface roughness and less porosity. AFM confirmed the SEM observations and showed that the FD material exhibited a more branched structure and a higher surface roughness. The samples cultivated in a glucose-containing nutrient medium, generally displayed a straight and ordered shape of fibrils compared to the sucrose-derived BC, characterized by a rougher and wavier structure. The BC films dried under different conditions showed distinctly different crystallinity degrees, whereas the carbon source in the culture medium was found to have a relatively small effect on the BC crystallinity.
Conventional EEG devices cannot be used in everyday life and
hence, past decade research has been focused on Ear-EEG for mobile,
at-home monitoring for various applications ranging from
emotion detection to sleep monitoring. As the area available for
electrode contact in the ear is limited, the electrode size and location
play a vital role for an Ear-EEG system. In this investigation, we
present a quantitative study of ear-electrodes with two electrode
sizes at different locations in a wet and dry configuration. Electrode
impedance scales inversely with size and ranges from 450 kΩ to
1.29 MΩ for dry and from 22 kΩ to 42 kΩ for wet contact at 10 Hz.
For any size, the location in the ear canal with the lowest impedance
is ELE (Left Ear Superior), presumably due to increased contact
pressure caused by the outer-ear anatomy. The results can be used
to optimize signal pickup and SNR for specific applications. We
demonstrate this by recording sleep spindles during sleep onset
with high quality (5.27 μVrms).
Die Detektion von Schadstoffen repräsentiert in der Umweltanalytik eine wichtige Aufgabenstellung. Gerade die Abwasser- bzw. Brauchwasseranalytik sowie die Prozesskontrolle haben einen hohen Stellenwert. Siliziumbasierte Dünnschichtsensoren bieten eine kostengünstige Möglichkeit, „online“-Messungen bzw. Vor-Ort-Messungen zeitnah durchzuführen. In dieser Arbeit wird ein potentiometrisches Sensorarray auf der Basis von Chalkogenidgläsern zur Detektion von Schwermetallen in wässrigen Medien vorgestellt.
L.setulosus is offered for creation of biopreparation «Setulin», possesing he- mostatic action, the basic reactant of biopreparation is diterpen – lagochirzin. Results under the maintenance and dynamics of diterpen lagochirzin accumula- tion in various parts of L.setulosus are presented: in roots, stalks, leaves, flowers and calyx lobes during the growing season, and also results on conditions of cultivation L.setulosus in the conditions of a typical sierozem are resulted. From the obtained data is visible, that the given species of a plant is endemic. It is established, that dynamics of accumulation of lagochirzin in phytomass accrues from the beginning to the middle of the growing season. The chemical analysis of L.setulosus on a localization of lagochirzin in various organs of a plant, has shown, that the greatest quantity of lagochirzin collects in calyx lobes of the plants. Also it is established, that L.setulosus can be cultivated in the conditions of the typical sierozem, a mineral food is necessary for the given species of plants of Lagochilus genus, except nitric fertilizers. Comparative studying of wild-growing and cultural forms of L.setulosus has shown, that in the cultivated phytomass of plants the maintenance of lagochirzin on 17-20 % higher than in the wild-growing species.
After a short introduction of a new nonconforming linear finite element on quadrilaterals recently developed by Park, we derive a dual weighted residual-based a posteriori error estimator (in the sense of Becker and Rannacher) for this finite element. By computing a corresponding dual solution we estimate the error with respect to a given target error functional. The reliability and efficiency of this estimator is analyzed in several numerical experiments.
In our case the double-side-method is used to minimize the complexity of a matrix-readout. Here the number of channels is reduced to 2√N̅. It is also possible to benefit from the method in a single pixel readout system. One signal can be used to measure position and energy of the event, the other one can be applied to a fast trigger-circuit at the same time. In a next step we will investigate timing behavior and electrical crosstalk of the circuit.
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.
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.
Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.
DNA-hybridization detection using light-addressable potentiometric sensor modified with gold layer
(2014)
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.
An array of four independently wired indium tin oxide (ITO) electrodes was used for electrochemically stimulated DNA release and activation of DNA-based Identity, AND and XOR logic gates. Single-stranded DNA molecules were loaded on the mixed poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA)/poly(methacrylic acid) (PMAA) brush covalently attached to the ITO electrodes. The DNA deposition was performed at pH 5.0 when the polymer brush is positively charged due to protonation of tertiary amino groups in PDMAEMA, thus resulting in electrostatic attraction of the negatively charged DNA. By applying electrolysis at −1.0 V(vs. Ag/AgCl reference) electrochemical oxygen reduction resulted in the consumption of hydrogen ions and local pH increase near the electrode surface. The process resulted in recharging the polymer brush to the negative state due to dissociation of carboxylic groups of PMAA, thus repulsing the negatively charged DNA and releasing it from the electrode surface. The DNA release was performed in various combinations from different electrodes in the array assembly. The released DNA operated as input signals for activation of the Boolean logic gates. The developed system represents a step forward in DNA computing, combining for the first time DNA chemical processes with electronic input signals.
The deformation and damage laws of non-homogeneous irregular structural planes in rocks are the basis for studying the stability of rock engineering. To investigate the damage characteristics of rock containing non-parallel fissures, uniaxial compression tests and numerical simulations were conducted on sandstone specimens containing three non-parallel fissures inclined at 0°, 45° and 90° in this study. The characteristics of crack initiation and crack evolution of fissures with different inclinations were analyzed. A constitutive model for the discontinuous fractures of fissured sandstone was proposed. The results show that the fracture behaviors of fissured sandstone specimens are discontinuous. The stress–strain curves are non-smooth and can be divided into nonlinear crack closure stage, linear elastic stage, plastic stage and brittle failure stage, of which the plastic stage contains discontinuous stress drops. During the uniaxial compression test, the middle or ends of 0° fissures were the first to crack compared to 45° and 90° fissures. The end with small distance between 0° and 45° fissures cracked first, and the end with large distance cracked later. After the final failure, 0° fissures in all specimens were fractured, while 45° and 90° fissures were not necessarily fractured. Numerical simulation results show that the concentration of compressive stress at the tips of 0°, 45° and 90° fissures, as well as the concentration of tensile stress on both sides, decreased with the increase of the inclination angle. A constitutive model for the discontinuous fractures of fissured sandstone specimens was derived by combining the logistic model and damage mechanic theory. This model can well describe the discontinuous drops of stress and agrees well with the whole processes of the stress–strain curves of the fissured sandstone specimens.
We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements.
We propose a stochastic programming method to analyse limit and shakedown of structures under random strength with lognormal distribution. In this investigation a dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit or the shakedown limit. The edge-based smoothed finite element method (ES-FEM) using three-node linear triangular elements is used.
Differential modulation of valence and arousal in high-alexithymic and low-alexithymic individuals
(2010)
High-alexithymic individuals are characterized by an impaired ability to identify and communicate emotions whereas low-alexithymic individuals have a wide-ranging ability to deal with emotions. This study examined the hypothesis that valence and arousal modifications of emotional stimuli differentially modulate cortical regions in high-alexithymic and low-alexithymic individuals. To this end, 28 high-alexithymic and 25 low-alexithymic individuals were investigated with event-related fMRI using visual emotional stimuli. We found differential neural activations in the dorsal anterior cingulate, the insula and the amygdala. We suggest that these differences may account for the impaired ability of high-alexithymic individuals to appropriately handle emotional stimuli.
A light-addressable potentiometric sensor (LAPS) is a field-effect-based potentiometric sensor with an electrolyte/insulator/semiconductor (EIS) structure, which is able to monitor analyte concentrations of (bio-)chemical species in aqueous solutions in a spatially resolved way. Therefore, it is also an appropriate tool to record 2D-chemical images of concentration variations on the sensor surface. In the present work, two differential, LAPS-based measurement principles are introduced to determine the metabolic activity of Escherichia coli (E. coli) K12 and Chinese hamster ovary (CHO) cells as test microorganisms. Hereby, we focus on i) the determination of the extracellular acidification rate (ΔpH/min) after adding glucose solutions to the cell suspensions; and ii) recording the amplitude increase of the photocurrent (Iph) related to the produced acids from E. coli K12 bacteria and CHO cells on the sensor surface by 2D-chemical imaging. For this purpose, 3D-printed multi-chamber structures were developed and mounted on the planar sensor-chip surface to define four independent compartments, enabling differential measurements with varying cell concentrations. The differential concept allows eliminating unwanted drift effects and, with the four-chamber structures, measurements on the different cell concentrations were performed simultaneously, thus reducing also the overall measuring time.
Extracellular acidification is a basic indicator for alterations in two vital metabolic pathways: glycolysis and cellular respiration. Measuring these alterations by monitoring extracellular acidification using cell-based biosensors such as LAPS plays an important role in studying these pathways whose disorders are associated with numerous diseases including cancer. However, the surface of the biosensors must be specially tailored to ensure high cell compatibility so that cells can represent more in vivo-like behavior, which is critical to gain more realistic in vitro results from the analyses, e.g., drug discovery experiments. In this work, O2 plasma patterning on the LAPS surface is studied to enhance surface features of the sensor chip, e.g., wettability and biofunctionality. The surface treated with O2 plasma for 30 s exhibits enhanced cytocompatibility for adherent CHO–K1 cells, which promotes cell spreading and proliferation. The plasma-modified LAPS chip is then integrated into a microfluidic system, which provides two identical channels to facilitate differential measurements of the extracellular acidification of CHO–K1 cells. To the best of our knowledge, it is the first time that extracellular acidification within microfluidic channels is quantitatively visualized as differential (bio-)chemical images.
A novel photoexcitation method for the light-addressable potentiometric sensor (LAPS) realized a higher spatial resolution of chemical imaging. In this method, a modulated light probe, which generates the alternating photocurrent signal, is surrounded by a ring of constant light, which suppresses the lateral diffusion of photocarriers by enhancing recombination. A device simulation verified that a higher spatial resolution could be obtained by adjusting the gap between the modulated and constant light. It was also found that a higher intensity and a longer wavelength of constant light was more effective. However, there exists a tradeoff between the spatial resolution and the amplitude of the photocurrent, and thus, the signal-to-noise ratio. A tilted incidence of constant light was applied, which could achieve even higher resolution with a smaller loss of photocurrent.
As a semiconductor-based electrochemical sensor, the light-addressable potentiometric sensor (LAPS) can realize two dimensional visualization of (bio-)chemical reactions at the sensor surface addressed by localized illumination. Thanks to this imaging capability, various applications in biochemical and biomedical fields are expected, for which the spatial resolution is critically significant. In this study, therefore, the spatial resolution of the LAPS was investigated in detail based on the device simulation. By calculating the spatiotemporal change of the distributions of electrons and holes inside the semiconductor layer in response to a modulated illumination, the photocurrent response as well as the spatial resolution was obtained as a function of various parameters such as the thickness of the Si substrate, the doping concentration, the wavelength and the intensity of illumination.
The simulation results verified that both thinning the semiconductor substrate and increasing the doping concentration could improve the spatial resolution, which were in good agreement with known experimental results and theoretical analysis. More importantly, new findings of interests were also obtained. As for the dependence on the wavelength of illumination, it was found that the known dependence was not always the case. When the Si substrate was thick, a longer wavelength resulted in a higher spatial resolution which was known by experiments. When the Si substrate was thin, however, a longer wavelength of light resulted in a lower spatial resolution. This finding was explained as an effect of raised concentration of carriers, which reduced the thickness of the space charge region.
The device simulation was found to be helpful to understand the relationship between the spatial resolution and device parameters, to understand the physics behind it, and to optimize the device structure and measurement conditions for realizing higher performance of chemical imaging systems.
Development of an optimized LSO/LuYAP phoswich detector head for the Lausanne ClearPET demonstrator
(2006)
This paper describes the LSO/LuYAP phoswich detector head developed for the ClearPET small animal PET scanner demonstrator that is under construction in Lausanne within the Crystal Clear Collaboration. The detector head consists of a dual layer of 8×8 LSO and LuYAP crystal arrays coupled to a multi-anode photomultiplier tube (Hamamatsu R7600-M64). Equalistion of the LSO/LuYAP light collection is obtained through partial attenuation of the LSO scintillation light using a thin aluminum deposit of 20-35 nm on LSO and appropriate temperature regulation of the phoswich head between 30°C to 60°C. At 511keV, typical FWHM energy resolutions of the pixels of a phoswich head amounts to (28±2)% for LSO and (25±2)% for LuYAP. The LSO versus LuYAP crystal identification efficiency is better than 98%. Six detector modules have been mounted on a rotating gantry. Axial and tangential spatial resolutions were measured up to 4 cm from the scanner axis and compared to Monte Carlo simulations using GATE. FWHM spatial resolution ranges from 1.3 mm on axis to 2.6 mm at 4 cm from the axis.
Hydrogen peroxide (H2O2) is a typical surface sterilization agent for packaging materials used in the pharmaceutical, food and beverage industries. We use the finite-elements method to analyze the conceptual design of an in-line thermal evaporation unit to produce a heated gas mixture of air and evaporated H2O2 solution. For the numerical model, the required phase-transition variables of pure H2O2 solution and of the aerosol mixture are acquired from vapor-liquid equilibrium (VLE) diagrams derived from vapor-pressure formulations. This work combines homogeneous single-phase turbulent flow with heat-transfer physics to describe the operation of the evaporation unit. We introduce the apparent heat-capacity concept to approximate the non-isothermal phase-transition process of the H2O2-containing aerosol. Empirical and analytical functions are defined to represent the temperature- and pressure-dependent material properties of the aqueous H2O2 solution, the aerosol and the gas mixture. To validate the numerical model, the simulation results are compared to experimental data on the heating power required to produce the gas mixture. This shows good agreement with the deviations below 10%. Experimental observations on the formation of deposits due to the evaporation of stabilized H2O2 solution fits the prediction made from simulation results.
Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM−1 (L-malate biosensor) and 0.4 μA mM−1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM−1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.
The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.
In industrial processes there is a variety of heavy metals (e.g., copper, zinc, cadmium, and lead) in use for wires, coatings, paints, alloys, batteries, etc. Since the application of these transition metals for industry is inevitable, it is a vital task to develop proper analytical techniques for their monitoring at low activity levels, especially because most of these elements are acutely toxic for biological organisms. The determination of ions in solution by means of a simple and inexpensive sensor array is, therefore, a promising task. In this work, a sensor array with heavy metal-sensitive chalcogenide glass membranes for the simultaneous detection of the four ions Ag⁺, Cu2⁺, Cd2⁺, and Pb2⁺ in solution is realized. The results of the physical characterization by means of microscopy, profilometry, Rutherford backscattering spectroscopy (RBS), and scanning electron microscopy (SEM) as well as the electrochemical characterization by means of potentiometric measurements are presented. Additionally, the possibility to expand the sensor array by polymeric sensor membranes is discussed.
Glucose oxidase (GOx) is an enzyme frequently used in glucose biosensors. As increased temperatures can enhance the performance of electrochemical sensors, we investigated the impact of temperature pulses on GOx that was drop-coated on flattened Pt microwires. The wires were heated by an alternating current. The sensitivity towards glucose and the temperature stability of GOx was investigated by amperometry. An up to 22-fold increase of sensitivity was observed. Spatially resolved enzyme activity changes were investigated via scanning electrochemical microscopy. The application of short (<100 ms) heat pulses was associated with less thermal inactivation of the immobilized GOx than long-term heating.
Within the present work a sterilization process by a heated gas mixture that contains hydrogen peroxide (H₂O₂) is validated by experiments and numerical modeling techniques. The operational parameters that affect the sterilization efficacy are described alongside the two modes of sterilization: gaseous and condensed H₂O₂. Measurements with a previously developed H₂O₂ gas sensor are carried out to validate the applied H₂O₂ gas concentration during sterilization. We performed microbiological tests at different H₂O₂ gas concentrations by applying an end-point method to carrier strips, which contain different inoculation loads of Geobacillus stearothermophilus spores. The analysis of the sterilization process of a pharmaceutical glass vial is performed by numerical modeling. The numerical model combines heat- and advection-diffusion mass transfer with vapor–pressure equations to predict the location of condensate formation and the concentration of H₂O₂ at the packaging surfaces by changing the gas temperature. For a sterilization process of 0.7 s, a H₂O₂ gas concentration above 4% v/v is required to reach a log-count reduction above six. The numerical results showed the location of H₂O₂ condensate formation, which decreases with increasing sterilant-gas temperature. The model can be transferred to different gas nozzle- and packaging geometries to assure the absence of H₂O₂ residues.
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.
A capacitive electrolyte-insulator-semiconductor (EIS) field-effect biosensor for acetoin detection has been presented for the first time. The EIS sensor consists of a layer structure of Al/p-Si/SiO₂/Ta₂O₅/enzyme acetoin reductase. The enzyme, also referred to as butane-2,3-diol dehydrogenase from B. clausii DSM 8716T, has been recently characterized. The enzyme catalyzes the (R)-specific reduction of racemic acetoin to (R,R)- and meso-butane-2,3-diol, respectively. Two different enzyme immobilization strategies (cross-linking by using glutaraldehyde and adsorption) have been studied. Typical biosensor parameters such as optimal pH working range, sensitivity, hysteresis, linear concentration range and long-term stability have been examined by means of constant-capacitance (ConCap) mode measurements. Furthermore, preliminary experiments have been successfully carried out for the detection of acetoin in diluted white wine samples.
Chemical imaging systems allow the visualisation of the distribution of chemical species on the sensor surface. This work represents a new flexible approach to read out light-addressable potentiometric sensors (LAPS) with the help of a digital light processing (DLP) set-up. The DLP, known well for video projectors, consists of a mirror-array MEMS device, which allows fast and flexible generation of light patterns. With the help of these light patterns, the sensor surface of the LAPS device can be addressed. The DLP approach has several advantages compared to conventional LAPS set-ups, e.g., the spot size and the shape of the light pointer can be changed easily and no mechanical movement is necessary, which reduces the size of the set-up and increases the stability and speed of the measurement. In addition, the modulation frequency and intensity of the light beam are important parameters of the LAPS set-up. Within this work, the authors will discuss two different ways of light modulation by the DLP set-up, investigate the influence of different modulation frequencies and different light intensities as well as demonstrate the scanning capabilities of the new set-up by pH mapping on the sensor surface.
Booster stations can fulfill a varying pressure demand with high energy-efficiency, because individual pumps can be deactivated at smaller loads. Although this is a seemingly simple approach, it is not easy to decide precisely when to activate or deactivate pumps. Contemporary activation controls derive the switching points from the current volume flow through the system. However, it is not measured directly for various reasons. Instead, the controller estimates the flow based on other system properties. This causes further uncertainty for the switching decision. In this paper, we present a method to find a robust, yet energy-efficient activation strategy.