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Influence of a freeze–thaw cycle on the stress–stretch curves of tissues of porcine abdominal organs
(2012)
The paper investigates both fresh porcine spleen and liver and the possible decomposition of these organs under a freeze–thaw cycle. The effect of tissue preservation condition is an important factor which should be taken into account for protracted biomechanical tests. In this work, tension tests were conducted for a large number of tissue specimens from twenty pigs divided into two groups of 10. Concretely, the first group was tested in fresh state; the other one was tested after a freeze-thaw cycle which simulates the conservation conditions before biomechanical experiments. A modified Fung model for isotropic behavior was adopted for the curve fitting of each kind of tissues. Experimental results show strong effects of the realistic freeze–thaw cycle on the capsule of elastin-rich spleen but negligible effects on the liver which virtually contains no elastin. This different behavior could be explained by the autolysis of elastin by elastolytic enzymes during the warmer period after thawing. Realistic biomechanical properties of elastin-rich organs can only be expected if really fresh tissue is tested. The observations are supported by tests of intestines.
Influence of refrigerated storage on tensile mechanical properties of porcine liver and spleen
(2015)
Introduction
In regard of surgical training, the reproducible simulation of life-like proximal humerus fractures in human cadaveric specimens is desirable. The aim of the present study was to develop a technique that allows simulation of realistic proximal humerus fractures and to analyse the influence of rotator cuff preload on the generated lesions in regards of fracture configuration.
Materials and methods
Ten cadaveric specimens (6 left, 4 right) were fractured using a custom-made drop-test bench, in two groups. Five specimens were fractured without rotator cuff preload, while the other five were fractured with the tendons of the rotator cuff preloaded with 2 kg each. The humeral shaft and the shortened scapula were potted. The humerus was positioned at 90° of abduction and 10° of internal rotation to simulate a fall on the elevated arm. In two specimens of each group, the emergence of the fractures was documented with high-speed video imaging. Pre-fracture radiographs were taken to evaluate the deltoid-tuberosity index as a measure of bone density. Post-fracture X-rays and CT scans were performed to define the exact fracture configurations. Neer’s classification was used to analyse the fractures.
Results
In all ten cadaveric specimens life-like proximal humerus fractures were achieved. Two III-part and three IV-part fractures resulted in each group. The preloading of the rotator cuff muscles had no further influence on the fracture configuration. High-speed videos of the fracture simulation revealed identical fracture mechanisms for both groups. We observed a two-step fracture mechanism, with initial impaction of the head segment against the glenoid followed by fracturing of the head and the tuberosities and then with further impaction of the shaft against the acromion, which lead to separation of the tuberosities.
Conclusion
A high energetic axial impulse can reliably induce realistic proximal humerus fractures in cadaveric specimens. The preload of the rotator cuff muscles had no influence on initial fracture configuration. Therefore, fracture simulation in the proximal humerus is less elaborate. Using the presented technique, pre-fractured specimens are available for real-life surgical education.
To gain insight on chemical sterilization processes, the influence of temperature (up to 70 °C), intense green light, and hydrogen peroxide (H₂O₂) concentration (up to 30% in aqueous solution) on microbial spore inactivation is evaluated by in-situ Raman spectroscopy with an optical trap. Bacillus atrophaeus is utilized as a model organism. Individual spores are isolated and their chemical makeup is monitored under dynamically changing conditions (temperature, light, and H₂O₂ concentration) to mimic industrially relevant process parameters for sterilization in the field of aseptic food processing. While isolated spores in water are highly stable, even at elevated temperatures of 70 °C, exposure to H₂O₂ leads to a loss of spore integrity characterized by the release of the key spore biomarker dipicolinic acid (DPA) in a concentration-dependent manner, which indicates damage to the inner membrane of the spore. Intensive light or heat, both of which accelerate the decomposition of H₂O₂ into reactive oxygen species (ROS), drastically shorten the spore lifetime, suggesting the formation of ROS as a rate-limiting step during sterilization. It is concluded that Raman spectroscopy can deliver mechanistic insight into the mode of action of H₂O₂-based sterilization and reveal the individual contributions of different sterilization methods acting in tandem.
In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live–dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.
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.
After a liver tumor intervention the medical doctor has to compare both pre and postoperative CT acquisitions to ensure that all carcinogenic cells are destroyed. A correct assessment of the intervention is of vital importance, since it will reduce the probability of tumor recurrence. Some methods have been proposed to support the medical doctors during the assessment process, however, all of them focus on secondary tumors. In this paper a tool is presented that enables the outcome validation for both primary and secondary tumors. Therefore, a multiphase registration (preoperative arterial and portal phases) followed by a registration between the pre and postoperative CT images is carried out. The first registration is in charge of the primary tumors that are only visible in the arterial phase. The secondary tumors will be incorporated in the second registration step. Finally, the part of the tumor that was not covered by the necrosis is quantified and visualized. The method has been tested in 9 patients, with an average registration error of 1.41 mm.
This study has been performed to design the combination of the new ClearPET (ClearPET is a trademark of the Crystal Clear Collaboration), a small animal positron emission tomography (PET) system, with a micro-computed tomography (microCT) scanner. The properties of different microCT systems have been determined by simulations based on GEANT4. We will demonstrate the influence of the detector material and the X-ray spectrum on the obtained contrast. Four different detector materials (selenium, cadmium zinc telluride, cesium iodide and gadolinium oxysulfide) and two X-ray spectra (a molybdenum and a tungsten source) have been considered. The spectra have also been modified by aluminum filters of varying thickness. The contrast between different tissue types (water, air, brain, bone and fat) has been simulated by using a suitable phantom. The results indicate the possibility to improve the image contrast in microCT by an optimized combination of the X-ray source and detector material.
This study has been performed to design the combination of the new ClearPET TM (ClearPET is a trademark of the Crystal Clear Collaboration), a small animal Positron Emission Tomography (PET) system, with a microComputed Tomography (microCT) scanner. The properties of different microCT systems have been determined by simulations based on GEANT4. We demonstrate the influence of the detector material and the X-ray spectrum on the obtained contrast. Four different detector materials (selenium, cadmium zinc telluride, cesium iodide and gadolinium oxysulfide) and two X-ray spectra (a molybdenum and a tungsten source) have been considered. The spectra have also been modified by aluminum filters of varying thickness. The contrast between different tissue types (water, air, brain, bone and fat) has been simulated by using a suitable phantom. The results indicate the possibility to improve the image contrast in microCT by an optimized combination of the X-ray source and detector material.
Single-photon emission tomography (SPET) with the amino acid analogue l-3-[123I]iodo-α-methyl tyrosine (IMT) is helpful in the diagnosis and monitoring of cerebral gliomas. Radiolabelled amino acids seem to reflect tumour infiltration more specifically than conventional methods like magnetic resonance imaging and computed tomography. Automatic tumour delineation based on maximal tumour uptake may cause an overestimation of mean tumour uptake and an underestimation of tumour extension in tumours with circumscribed peaks. The aim of this study was to develop a program for tumour delineation and calculation of mean tumour uptake which takes into account the mean background activity and is thus optimised to the problem of tumour definition in IMT SPET. Using the frequency distribution of pixel intensities of the tomograms a program was developed which automatically detects a reference brain region and draws an isocontour region around the tumour taking into account mean brain radioactivity. Tumour area and tumour/brain ratios were calculated. A three-compartment phantom was simulated to test the program. The program was applied to IMT SPET studies of 20 patients with cerebral gliomas and was compared to the results of manual analysis by three different investigators. Activity ratios and chamber extension of the phantom were correctly calculated by the automatic analysis. A method based on image maxima alone failed to determine chamber extension correctly. Manual region of interest analysis in patient studies resulted in a mean inter-observer standard deviation of 8.7%±6.1% (range 2.7%–25.0%). The mean value of the results of the manual analysis showed a significant correlation to the results of the automatic analysis (r = 0.91, P<0.0001 for the uptake ratio; r = 0.87, P<0.0001 for the tumour area). We conclude that the algorithm proposed simplifies the calculation of uptake ratios and may be used for observer-independent evaluation of IMT SPET studies. Three-dimensional tumour recognition and transfer to co-registered morphological images based on this program may be useful for the planning of surgical and radiation treatment.
Isomeric state in ¹³⁴ La
(1981)
Isomeric state in ¹³⁶ La
(1981)
Isomeric states in ¹³⁴ Ba
(1980)
Isomeric states in ¹³⁴ Ba
(1980)
Effective training requires high muscle forces potentially leading to training-induced injuries. Thus, continuous monitoring and controlling of the loadings applied to the musculoskeletal system along the motion trajectory is required. In this paper, a norm-optimal iterative learning control algorithm for the robot-assisted training is developed. The algorithm aims at minimizing the external knee joint moment, which is commonly used to quantify the loading of the medial compartment. To estimate the external knee joint moment, a musculoskeletal lower extremity model is implemented in OpenSim and coupled with a model of an industrial robot and a force plate mounted at its end-effector. The algorithm is tested in simulation for patients with varus, normal and valgus alignment of the knee. The results show that the algorithm is able to minimize the external knee joint moment in all three cases and converges after less than seven iterations.
K0 production in e+e− annihilations at 30 GeV center of mass energy. TASSO Collaboration
(1980)
Frequency mixing magnetic detection (FMMD) is a sensitive and selective technique to detect magnetic nanoparticles (MNPs) serving as probes for binding biological targets. Its principle relies on the nonlinear magnetic relaxation dynamics of a particle ensemble interacting with a dual frequency external magnetic field. In order to increase its sensitivity, lower its limit of detection and overall improve its applicability in biosensing, matching combinations of external field parameters and internal particle properties are being sought to advance FMMD. In this study, we systematically probe the aforementioned interaction with coupled Néel–Brownian dynamic relaxation simulations to examine how key MNP properties as well as applied field parameters affect the frequency mixing signal generation. It is found that the core size of MNPs dominates their nonlinear magnetic response, with the strongest contributions from the largest particles. The drive field amplitude dominates the shape of the field-dependent response, whereas effective anisotropy and hydrodynamic size of the particles only weakly influence the signal generation in FMMD. For tailoring the MNP properties and parameters of the setup towards optimal FMMD signal generation, our findings suggest choosing large particles of core sizes dc > 25 nm nm with narrow size distributions (σ < 0.1) to minimize the required drive field amplitude. This allows potential improvements of FMMD as a stand-alone application, as well as advances in magnetic particle imaging, hyperthermia and magnetic immunoassays.
Kyphoplasty of Osteoporotic Fractured Vertebrae: A Finite Element Analysis about Two Types of Cement
(2019)
Light-addressable potentiometric sensors (LAPS) consisting of a p-Si-SiO2 and p-Si-SiO2-Au structure, respectively, have been tested for a label-free electrical detection of DNA (deoxyribonucleic acid) hybridization. Three different strategies for immobilizing single-stranded probe DNA (ssDNA) molecules on a LAPS surface have been studied and compared: (a) immobilization of thiol-modified ssDNA on the patterned Au surface via gold-thiol bond, (b) covalent immobilization of amino-modified ssDNA onto the SiO2 surface functionalized with 3-aminopropyltriethoxysilane and (c) layer-by-layer adsorption of negatively charged ssDNA on a positively charged weak polyelectrolyte layer of poly(allylamine hydrochloride).
A multi-spot (16 spots) light-addressable potentiometric sensor (MLAPS) consisting of an Al–p-Si–SiO2 structure modified with a weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)) was applied for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge for the first time. To achieve a preferentially flat orientation of DNA strands and thus, to reduce the distance between the DNA charge and MLAPS surface, the negatively charged probe single-stranded DNAs (ssDNA) were electrostatically adsorbed onto the positively charged PAH layer using a simple layer-by-layer (LbL) technique. In this way, more DNA charge can be positioned within the Debye length, yielding a higher sensor signal. The surface potential changes in each spot induced due to the surface modification steps (PAH adsorption, probe ssDNA immobilization, hybridization with complementary target DNA (cDNA), non-specific adsorption of mismatched ssDNA) were determined from the shifts of photocurrent–voltage curves along the voltage axis. A high sensor signal of 83 mV was registered after immobilization of probe ssDNA onto the PAH layer. The hybridization signal increases from 5 mV to 32 mV with increasing the concentration of cDNA from 0.1 nM to 5 μM. In contrast, a small signal of 5 mV was recorded in the case of non-specific adsorption of fully mismatched ssDNA (5 μM). The obtained results demonstrate the potential of the MLAPS in combination with the simple and rapid LbL immobilization technique as a promising platform for the future development of multi-spot light-addressable label-free DNA chips with direct electrical readout.
In this study, polyelectrolyte-modified field-effect-based electrolyte-insulator-semiconductor (EIS) devices have been used for the label-free electrical detection of double-stranded deoxyribonucleic acid (dsDNA)molecules. The sensor-chip functionalization with a positively charged polyelectrolyte layer provides the possibility of direct adsorptive binding of negatively charged target DNA oligonucleotides onto theSiO2-chip surface.EIS sensors can be utilized as a tool to detect surface-charge changes; the electrostatic adsorption of oligonucleotides onto the polyelectrolyte layer leads to a measureable surface-potential change. Signals of 39mV have been recorded after the incubation with the oligonucleotide solution. Besides the electrochemical experiments, the successful adsorption of dsDNA onto the polyelectrolyte layer has been verified via fluorescence microscopy. The presented results demonstrate that the signal recording of EISchips, which are modified with a polyelectrolyte layer, canbe used as a favorable approach for a fast, cheap and simple detection method for dsDNA.
Field-effect EIS (electrolyte-insulator-semiconductor) sensors modified with a positively charged weak polyelectrolyte layer have been applied for the electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge. The EIS sensors are able to detect the existence of target DNA amplicons in PCR (polymerase chain reaction) samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process. Due to their miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge, those sensors can serve as possible platform for the development of label-free DNA chips. Possible application fields as well as challenges and limitations will be discussed.
Label-free electrical detection of consecutive deoxyribonucleic acid (DNA) hybridization/denaturation by means of an array of individually addressable field-effect-based nanoplate silicon-on-insulator (SOI) capacitors modified with gold nanoparticles (Au-NP) is investigated. The proposed device detects charge changes on Au-NP/DNA hybrids induced by the hybridization or denaturation event. DNA hybridization was performed in a high ionic-strength solution to provide a high hybridization efficiency. On the other hand, to reduce the screening of the DNA charge by counter ions and to achieve a high sensitivity, the sensor signal induced by the hybridization and denaturation events was measured in a low ionic-strength solution. High sensor signals of about 120, 90, and 80 mV were registered after the DNA hybridization, denaturation, and re-hybridization events, respectively. Fluorescence microscopy has been applied as reference method to verify the DNA immobilization, hybridization, and denaturation processes. An electrostatic charge-plane model for potential changes at the gate surface of a nanoplate field-effect sensor induced by the DNA hybridization has been developed taking into account both the Debye length and the distance of the DNA charge from the gate surface.
A multi-spot (4 × 4 spots) light-addressable potentiometric sensor (MLAPS) consisting of an Al–p-Si–SiO2 structure has been applied for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge for the first time. Single-stranded probe ssDNA molecules (20 bases) were covalently immobilized onto the silanized SiO2 gate surface. The unspecific adsorption of mismatch ssDNA on the MLAPS gate surface was blocked by bovine serum albumin molecules. To reduce the screening effect and to achieve a high sensor signal, the measurements were performed in a low ionic-strength solution. The photocurrent–voltage (I–V) curves were simultaneously recorded on all 16 spots after each surface functionalization step. Large shifts of I–V curves of 25 mV were registered after the DNA immobilization and hybridization event. In contrast, a small potential shift (∼5 mV) was observed in case of mismatch ssDNA, revealing good specificity of the sensor. The obtained results demonstrate the potential of the MLAPS as promising transducer platform for the multi-spot label-free electrical detection of DNA molecules by their intrinsic molecular charge.
Label-free Electrostatic Detection of DNA Amplification by PCR Using Capacitive Field-effect Devices
(2016)
A capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensor modified with a positively charged weak polyelectrolyte of poly(allylamine hydrochloride) (PAH)/single-stranded probe DNA (ssDNA) bilayer has been used for a label-free electrostatic detection of pathogen-specific DNA amplification via polymerase chain reaction (PCR). The sensor is able to distinguish between positive and negative PCR solutions, to detect the existence of target DNA amplicons in PCR samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process.
Label-free sensing of biomolecules by their intrinsic molecular charge using field-effect devices
(2015)
Among the variety of transducer concepts proposed for label-free detection of biomolecules, the semiconductor field-effect device (FED) is one of the most attractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on biomarkers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologically relevant molecules with high specificity and sensitivity offers very promising prospects for their application in point-of-care and personalized medicine for an early diagnosis and treatment of diseases. The presented paper reviews recent advances and current trends in research and development of different FEDs for label-free, direct electrical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-antigen affinity reaction as well as clinically relevant biomolecules such as cardiac and cancer biomarkers.
LAPS-based monitoring of metabolic responses of bacterial cultures in a paper fermentation broth
(2020)
As an alternative renewable energy source, methane production in biogas plants is gaining more and more attention. Biomass in a bioreactor contains different types of microorganisms, which should be considered in terms of process-stability control. Metabolically inactive microorganisms within the fermentation process can lead to undesirable, time-consuming and cost-intensive interventions. Hence, monitoring of the cellular metabolism of bacterial populations in a fermentation broth is crucial to improve the biogas production, operation efficiency, and sustainability. In this work, the extracellular acidification of bacteria in a paper-fermentation broth is monitored after glucose uptake, utilizing a differential light-addressable potentiometric sensor (LAPS) system. The LAPS system is loaded with three different model microorganisms (Escherichia coli, Corynebacterium glutamicum, and Lactobacillus brevis) and the effect of the fermentation broth at different process stages on the metabolism of these bacteria is studied. In this way, different signal patterns related to the metabolic response of microorganisms can be identified. By means of calibration curves after glucose uptake, the overall extracellular acidification of bacterial populations within the fermentation process can be evaluated.
To study chemical and biological processes, spatially resolved determination of the concentrations of one or more analyte species is of distinct interest. With a light-addressable potentiometric sensor (LAPS), chemical images can be created, which visualize the concentration distribution above the sensor plate. One important challenge is to achieve a good lateral resolution in order to detect events that take place in a small and limited region. LAPS utilizes a focused light spot to address the measurement region. By moving this light spot along the semiconductor sensor plate, the concentration distribution can be observed. In this study, we show that utilizing a pulse as light excitation instead of a traditionally used continuously modulated light excitation, the lateral resolution can be improved by a factor of 6 or more.
Rationale: Previous studies [Topolnik et al., Cereb Cortex 2003; 13: 883; Schindler et al., Brain 2007; 130: 65] indicate that the termination of focal onset seizures may be causally related to an increase of global neuronal correlation during the second half of the seizures. This increase was observed to occur earlier in complex partial seizures than in secondarily generalized seizures. We here address the question whether such an increase of neuronal correlation prior to seizure end is indeed a global phenomenon, involving both hemispheres or whether there are side-specific differences. Methods: We analyzed 20 focal onset seizures (10 complex partial, 10 secondarily generalized seizures) recorded in 13 patients who underwent presurgical evaluation of focal epilepsies of different origin. EEG was recorded intracranially from bilaterally implanted subdural strip and intrahippocampal depth electrodes. Utilizing a moving window approach, we investigated the evolution of the maximum cross correlation for all channel combinations during seizures. For each moving window the mean value of the maximum cross correlation (MCC) between all electrode contacts was computed separately for each hemisphere. After normalization of seizure durations, MCC values of the ipsi- and contralateral hemisphere for all seizures were determined. Results: We observed that the MCC of the contralateral hemisphere in complex partial seizures increased during the first half of the seizure, whereas, for the same time interval, the MCC of the ipsilateral hemisphere even declined below the level of the pre-seizure period. In contrast, no significant differences between both hemispheres could be observed for secondarily generalized seizures where both hemispheres showed a simultaneous increase of MCC during the second half of the seizures. The level of MCC for the contralateral hemisphere was higher for complex partial seizures than for secondarily generalized seizures during the first half of the seizure. Conclusions: Our findings indicate that there are indeed lateralized differences in the evolution of global neuronal correlation during complex partial and secondarily generalized seizures. The observed contralateral increase of neuronal correlation during complex partial seizures might indicate an emerging self-organizing mechanism for preventing the spread of seizure activity.
Layer-by-Layer Assembly of Carbon Nanotubes Incorporated in Light-Addressable Potentiometric Sensors
(2009)
Lead and nickel, as heavy metals, are still used in industrial processes, and are classified as “environmental health hazards” due to their toxicity and polluting potential. The detection of heavy metals can prevent environmental pollution at toxic levels that are critical to human health. In this sense, the electrolyte–insulator–semiconductor (EIS) field-effect sensor is an attractive sensing platform concerning the fabrication of reusable and robust sensors to detect such substances. This study is aimed to fabricate a sensing unit on an EIS device based on Sn₃O₄ nanobelts embedded in a polyelectrolyte matrix of polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) using the layer-by-layer (LbL) technique. The EIS-Sn₃O₄ sensor exhibited enhanced electrochemical performance for detecting Pb²⁺ and Ni²⁺ ions, revealing a higher affinity for Pb²⁺ ions, with sensitivities of ca. 25.8 mV/decade and 2.4 mV/decade, respectively. Such results indicate that Sn₃O₄ nanobelts can contemplate a feasible proof-of-concept capacitive field-effect sensor for heavy metal detection, envisaging other future studies focusing on environmental monitoring.
The mechanical behavior of the large intestine beyond the ultimate stress has never been investigated. Stretching beyond the ultimate stress may drastically impair the tissue microstructure, which consequently weakens its healthy state functions of absorption, temporary storage, and transportation for defecation. Due to closely similar microstructure and function with humans, biaxial tensile experiments on the porcine large intestine have been performed in this study. In this paper, we report hyperelastic characterization of the large intestine based on experiments in 102 specimens. We also report the theoretical analysis of the experimental results, including an exponential damage evolution function. The fracture energies and the threshold stresses are set as damage material parameters for the longitudinal muscular, the circumferential muscular and the submucosal collagenous layers. A biaxial tensile simulation of a linear brick element has been performed to validate the applicability of the estimated material parameters. The model successfully simulates the biomechanical response of the large intestine under physiological and non-physiological loads.