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Nanoparticles are recognized as highly attractive tunable materials for designing field-effect biosensors with enhanced performance. In this work, we present a theoretical model for electrolyte-insulator-semiconductor capacitors (EISCAP) decorated with ligand-stabilized charged gold nanoparticles. The charged AuNPs are taken into account as additional, nanometer-sized local gates. The capacitance-voltage (C–V) curves and constant-capacitance (ConCap) signals of the AuNP-decorated EISCAPs have been simulated. The impact of the AuNP coverage on the shift of the C–V curves and the ConCap signals was also studied experimentally on Al–p-Si–SiO₂ EISCAPs decorated with positively charged aminooctanethiol-capped AuNPs. In addition, the surface of the EISCAPs, modified with AuNPs, was characterized by scanning electron microscopy for different immobilization times of the nanoparticles.
Capacitive field-effect sensors modified with a multi-enzyme membrane have been applied for an electronic transduction of biochemical signals processed by enzyme-based AND-Reset and OR-Reset logic gates. The local pH change at the sensor surface induced by the enzymatic reaction was used for the activation of the Reset function for the first time.
Application of a (bio-)chemical sensor (ISFET) for the detection of physical parameters in liquids
(2003)
Functional testing and characterisation of ISFETs on wafer level by means of a micro-droplet cell
(2006)
A wafer-level functionality testing and characterisation system for ISFETs (ionsensitive field-effect transistor) is realised by means of integration of a specifically designed capillary electrochemical micro-droplet cell into a commercial wafer prober-station. The developed system allows the identification and selection of “good” ISFETs at the earliest stage and to avoid expensive bonding, encapsulation and packaging processes for nonfunctioning ISFETs and thus, to decrease costs, which are wasted for bad dies. The developed system is also feasible for wafer-level characterisation of ISFETs in terms of sensitivity, hysteresis and response time. Additionally, the system might be also utilised for wafer-level testing of further electrochemical sensors.
Biologically sensitive field-effect devices (BioFEDs) advantageously combine the electronic field-effect functionality with the (bio)chemical receptor’s recognition ability for (bio)chemical sensing. In this review, basic and widely applied device concepts of silicon-based BioFEDs (ion-sensitive field-effect transistor, silicon nanowire transistor, electrolyte-insulator-semiconductor capacitor, light-addressable potentiometric sensor) are presented and recent progress (from 2019 to early 2021) is discussed. One of the main advantages of BioFEDs is the label-free sensing principle enabling to detect a large variety of biomolecules and bioparticles by their intrinsic charge. The review encompasses applications of BioFEDs for the label-free electrical detection of clinically relevant protein biomarkers, deoxyribonucleic acid molecules and viruses, enzyme-substrate reactions as well as recording of the cell acidification rate (as an indicator of cellular metabolism) and the extracellular potential.
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.
The coupling of charged molecules, nanoparticles, and more generally, inorganic/organic nanohybrids with semiconductor field-effect devices based on an electrolyte–insulator–semiconductor (EIS) system represents a very promising strategy for the active tuning of electrochemical properties of these devices and, thus, opening new opportunities for label-free biosensing by the intrinsic charge of molecules. The simplest field-effect sensor is a capacitive EIS sensor, which represents a (bio-)chemically sensitive capacitor. In this chapter, selected examples of recent developments in the field of label-free biosensing using nanomaterial-modified capacitive EIS sensors are summarized. In the first part, we present applications of EIS sensors modified with negatively charged gold nanoparticles for the label-free electrostatic detection of positively charged small proteins and macromolecules, for monitoring the layer-by-layer formation of oppositely charged polyelectrolyte (PE) multilayers as well as for the development of an enzyme-based biomolecular logic gate. In the second part, examples of a label-free detection by means of EIS sensors modified with a positively charged weak PE layer are demonstrated. These include electrical detection of on-chip and in-solution hybridized DNA (deoxyribonucleic acid) as well as an EIS sensor with pH-responsive weak PE/enzyme multilayers for enhanced field-effect biosensing.
Electrolyte-insulator-semiconductor (EIS) field-effect sensors belong to a new generation of electronic chips for biochemical sensing, enabling a direct electronic readout. The review gives an overview on recent advances and current trends in the research and development of chemical sensors and biosensors based on the capacitive field-effect EIS structure—the simplest field-effect device, which represents a biochemically sensitive capacitor. Fundamental concepts, physicochemical phenomena underlying the transduction mechanism and application of capacitive EIS sensors for the detection of pH, ion concentrations, and enzymatic reactions, as well as the label-free detection of charged molecules (nucleic acids, proteins, and polyelectrolytes) and nanoparticles, are presented and discussed.
An ISFET-based penicillin sensor with high sensitivity, low detection limit and long lifetime
(2001)
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.
Field-effect capacitive electrolyte-insulator-semiconductor (EIS) sensors functionalised with citrate-capped gold nanoparticles (AuNP) have been used for the electrostatic detection of macromolecules by their intrinsic molecular charge. The EIS sensor detects the charge changes in the AuNP/macromolecule hybrids induced by the adsorption or binding events. A feasibility of the proposed detection scheme has been exemplary demonstrated by realising EIS sensors for the detection of poly-D-lysine molecules.
An array of electrically isolated nanoplate field-effect silicon-on-insulator (SOI) capacitors as a new transducer structure for multiparameter (bio-)chemical sensing is presented. The proposed approach allows addressable biasing and electrical readout of multiple nanoplate field-effect capacitive (bio-)chemical sensors on the same SOI chip, as well as differential-mode measurements. The realized sensor chip has been applied for pH and penicillin concentration measurements, electrical monitoring of polyelectrolyte multilayer formation, and the label-free electrical detection of consecutive deoxyribonucleic acid (DNA) hybridization and denaturation events.
The on-chip integration of multiple biochemical sensors based on field-effect electrolyte-insulator-semiconductor capacitors (EISCAP) is challenging due to technological difficulties in realization of electrically isolated EISCAPs on the same Si chip. In this work, we present a new simple design for an array of on-chip integrated, individually electrically addressable EISCAPs with an additional control gate (CG-EISCAP). The existence of the CG enables an addressable activation or deactivation of on-chip integrated individual CG-EISCAPs by simple electrical switching the CG of each sensor in various setups, and makes the new design capable for multianalyte detection without cross-talk effects between the sensors in the array. The new designed CG-EISCAP chip was modelled in so-called floating/short-circuited and floating/capacitively-coupled setups, and the corresponding electrical equivalent circuits were developed. In addition, the capacitance-voltage curves of the CG-EISCAP chip in different setups were simulated and compared with that of a single EISCAP sensor. Moreover, the sensitivity of the CG-EISCAP chip to surface potential changes induced by biochemical reactions was simulated and an impact of different parameters, such as gate voltage, insulator thickness and doping concentration in Si, on the sensitivity has been discussed.
The LAPS (light-addressable potentiometric sensor) platform is one of the most attractive approaches for chemical and biological sensing with many applications ranging from pH and ion/analyte concentration measurements up to cell metabolism detection and chemical imaging. However, although it is generally accepted that LAPS measurements are spatially resolved, the light-addressability feature of LAPS devices has not been discussed in detail so far. In this work, an extended electrical equivalent-circuit model of the LAPS has been presented, which takes into account possible cross-talk effects due to the capacitive coupling of the non-illuminated region. A shunting effect of the non-illuminated area on the measured photocurrent and addressability of LAPS devices has been studied. It has been shown, that the measured photocurrent will be determined not only by the local interfacial potential in the illuminated region but also by possible interfacial potential changes in the non-illuminated region, yielding cross-talk effects. These findings were supported by the experimental investigations of a penicillin-sensitive multi-spot LAPS and a metal-insulator-semiconductor LAPS as model systems.
Penicillin detection by means of field-effect based sensors: EnFET, capacitive EIS sensor or LAPS?
(2000)
Penicillin detection by means of field-effect based sensors: EnFET, capacitive EIS sensor or LAPS?
(2001)
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.
Bacterial cellulose (BC) is a promising material for biomedical applications due to its unique properties such as high mechanical strength and biocompatibility. This article describes the microbiological synthesis, modification, and characterization of the obtained BC-nanocomposites originating from symbiotic consortium Medusomyces gisevii. Two BC-modifications have been obtained: BC-Ag and BC-calcium phosphate (BC-Ca3(PO4)2). Structure and physicochemical properties of the BC and its modifications were investigated by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), and infrared Fourier spectroscopy as well as by measurements of mechanical and water holding/absorbing capacities. Topographic analysis of the surface revealed multicomponent thick fibrils (150–160 nm in diameter and about 15 µm in length) constituted by 50–60 nm nanofibrils weaved into a left-hand helix. Distinctive features of Ca-phosphate-modified BC samples were (a) the presence of 500–700 nm entanglements and (b) inclusions of Ca3(PO4)2 crystals. The samples impregnated with Ag nanoparticles exhibited numerous roundish inclusions, about 110 nm in diameter. The boundaries between the organic and inorganic phases were very distinct in both cases. The Ag-modified samples also showed a prominent waving pattern in the packing of nanofibrils. The obtained BC gel films possessed water-holding capacity of about 62.35 g/g. However, the dried (to a constant mass) BC-films later exhibited a low water absorption capacity (3.82 g/g). It was found that decellularized BC samples had 2.4 times larger Young’s modulus and 2.2 times greater tensile strength as compared to dehydrated native BC films. We presume that this was caused by molecular compaction of the BC structure.
We compare four different algorithms for automatically estimating the muscle fascicle angle from ultrasonic images: the vesselness filter, the Radon transform, the projection profile method and the gray level cooccurence matrix (GLCM). The algorithm results are compared to ground truth data generated by three different experts on 425 image frames from two videos recorded during different types of motion. The best agreement with the ground truth data was achieved by a combination of pre-processing with a vesselness filter and measuring the angle with the projection profile method. The robustness of the estimation is increased by applying the algorithms to subregions with high gradients and performing a LOESS fit through these estimates.
Purpose
Two semi-empirical models were recently published, both making use of existing literature data, but each taking into account different physical phenomena that trigger hemolysis. In the first model, hemoglobin (Hb) release is described as a permeation procedure across the membrane, assuming a shear stress-dependent process (sublethal model). The second model only accounts for hemoglobin release that is caused by cell membrane breakdown, which occurs when red blood cells (RBC) undergo mechanically induced shearing for a period longer than the threshold time (nonuniform threshold model). In this paper, we introduce a model that considers the hemolysis generated by both these possible phenomena.
Methods
Since hemolysis can possibly be caused by permeation of hemoglobin through the RBC functional membrane as well as by release of hemoglobin from RBC membrane breakdown, our proposed model combines both these models. An experimental setup consisting of a Couette device was utilized for validation of our proposed model.
Results
A comparison is presented between the damage index (DI) predicted by the proposed model vs. the sublethal model vs. the nonthreshold model and experimental datasets. This comparison covers a wide range of shear stress for both human and porcine blood. An appropriate agreement between the measured DI and the DI predicted by the present model was obtained.
Conclusions
The semiempirical hemolysis model introduced in this paper aims for significantly enhanced conformity with experimental data. Two phenomenological outcomes become possible with the proposed approach: an estimation of the average time after which cell membrane breakdown occurs under the applied conditions, and a prediction of the ratio between the phenomena involved in hemolysis.
Tumour cell death can be evaluated in the living mouse by externally measuring the rate of loss of tumour-bound DNA tracer. By sequentially labelling the tumour-bearing animals with ¹²⁵IUdR and ¹³¹IUdR 50 h apart, the average tumour cells at the time of the second injection are labelled by ¹²⁵IUdR and the euoxic tumour cells are specifically labelled with ¹³¹IUdR. Tumour treatment at this stage of labelling permits the observation of the reaction of euoxic cells and average tumour cells and finally yields data on hypoxic cells and thus on the oxygen enhancement ratio. This information adds to results from tumour control and growth delay.
With this technique effects were analysed of 60-Co γ-rays, cyclotron neutrons (E = 6 MeV), misonidazole (500 mg/kg body wt) and hyperthermia (42°C water-bath), or combinations of these.
Misonidazole (15 min before irradiation) altered the oxygen enhancement ratio by a factor of 1·5 for γ-rays and of 1·1 for neutrons; when evaluated from tumour-growth delay and TCD-50 misonidazole gave a dose modifying factor of 1·47 for γ-rays and of 1·2-1·3 for neutrons.
Based on percentage tumour regression 100 days after treatment, the enhancement ratio from hyperthermia (after irradiation) was 2·75 for γ-rays (at 10 Gray) and 2·2 for neutrons (at 3·2 Gray). For neutrons combined with misonidazole and hyperthermia the ratio was 2·4.
These results demonstrate that effects of neutron irradiation may be modified by electron-affinic substances and/or hyperthermia.
Lignocellulosic biorefinery: Process integration of hydrolysis and fermentation (SSF process)
(2011)
The aim of the present work is the process integration and the optimization of the enzymatic hydrolysis of wood and the following fermentation of the products to ethanol. The substrate is a fiber fraction obtained by organosolv pre-treatment of beech wood. For the ethanol production, a co-fermentation by two different yeasts (Saccharomyces cerevisiae and Pachysolen tannophilus) was carried out to convert glucose as well as xylose. Two approaches has been followed: 1. A two step process, in which the hydrolysis of the fiber fraction and the fermentation to product are separated from each other. 2. A process, in which the hydrolysis and the fermentation are carried out in one single process step as simultaneous saccharification and fermentation (SSF). Following the first approach, a yield of about 0.15 g ethanol per gram substrate can be reached. Based on the SSF, one process step can be saved, and additionally, the gained yield can be raised up to 0.3 g ethanol per gram substrate.
Magnetic immunoassays employing Frequency Mixing Magnetic Detection (FMMD) have recently become increasingly popular for quantitative detection of various analytes. Simultaneous analysis of a sample for two or more targets is desirable in order to reduce the sample amount, save consumables, and save time. We show that different types of magnetic beads can be distinguished according to their frequency mixing response to a two-frequency magnetic excitation at different static magnetic offset fields. We recorded the offset field dependent FMMD response of two different particle types at frequencies ƒ₁ + n⋅ƒ₂, n = 1, 2, 3, 4 with ƒ₁ = 30.8 kHz and ƒ₂ = 63 Hz. Their signals were clearly distinguishable by the locations of the extremes and zeros of their responses. Binary mixtures of the two particle types were prepared with different mixing ratios. The mixture samples were analyzed by determining the best linear combination of the two pure constituents that best resembled the measured signals of the mixtures. Using a quadratic programming algorithm, the mixing ratios could be determined with an accuracy of greater than 14%. If each particle type is functionalized with a different antibody, multiplex detection of two different analytes becomes feasible.
Frequency mixing magnetic detection (FMMD) has been explored for its applications in fields of magnetic biosensing, multiplex detection of magnetic nanoparticles (MNP) and the determination of core size distribution of MNP samples. Such applications rely on the application of a static offset magnetic field, which is generated traditionally with an electromagnet. Such a setup requires a current source, as well as passive or active cooling strategies, which directly sets a limitation based on the portability aspect that is desired for point of care (POC) monitoring applications. In this work, a measurement head is introduced that involves the utilization of two ring-shaped permanent magnets to generate a static offset magnetic field. A steel cylinder in the ring bores homogenizes the field. By variation of the distance between the ring magnets and of the thickness of the steel cylinder, the magnitude of the magnetic field at the sample position can be adjusted. Furthermore, the measurement setup is compared to the electromagnet offset module based on measured signals and temperature behavior.
Frequency mixing magnetic detection (FMMD) has been widely utilized as a measurement technique in magnetic immunoassays. It can also be used for the characterization and distinction (also known as “colourization”) of different types of magnetic nanoparticles (MNPs) based on their core sizes. In a previous work, it was shown that the large particles contribute most of the FMMD signal. This leads to ambiguities in core size determination from fitting since the contribution of the small-sized particles is almost undetectable among the strong responses from the large ones. In this work, we report on how this ambiguity can be overcome by modelling the signal intensity using the Langevin model in thermodynamic equilibrium including a lognormal core size distribution fL(dc,d0,σ) fitted to experimentally measured FMMD data of immobilized MNPs. For each given median diameter d0, an ambiguous amount of best-fitting pairs of parameters distribution width σ and number of particles Np with R2 > 0.99 are extracted. By determining the samples’ total iron mass, mFe, with inductively coupled plasma optical emission spectrometry (ICP-OES), we are then able to identify the one specific best-fitting pair (σ, Np) one uniquely. With this additional externally measured parameter, we resolved the ambiguity in core size distribution and determined the parameters (d0, σ, Np) directly from FMMD measurements, allowing precise MNPs sample characterization.
Plant physiology and plant stress: Plant physiology will be much more important for human mankind because of yield and cultivation limits of crops determined by their resistance to stress. To assess and counteract various stress factors it is necessary to conduct plant research to gain information and results on plant physiology.
Patients after coarctation repair still have an increased risk of cardiovascular or cerebrovascular events. This has been explained by the persisting hypertension and alterations in the peripheral vessels. However, involvement of the central vessels such as the retinal arteries is virtually unknown. A total of 34 patients after coarctation repair (22 men and 12 women; 23 to 58 years old, age range 0 to 32 years at surgical repair) and 34 nonhypertensive controls underwent structural and functional retinal vessel analysis. Using structural analysis, the vessel diameters were measured. Using functional analysis, the endothelium-dependent vessel dilation in response to flicker light stimulation was assessed. In the patients after coarctation repair, the retinal arteriolar diameter was significantly reduced compared to that of the controls (median 182 μm, first to third quartile 171 to 197; vs 197 μm, first to third quartile 193 to 206; p <0.001). These findings were independent of the peripheral blood pressure and age at intervention. No differences were found for venules. The functional analysis findings were not different between the patients and controls (maximum dilation 3.5%, first to third quartile 2.1% to 4.5% vs 3.6%, first to third quartile 2.2% to 4.3%; p = 0.81), indicating preserved autoregulative mechanisms. In conclusion, the retinal artery diameter is reduced in patients after coarctation repair, independent of their current blood pressure level and age at intervention. As a structural marker of chronic vessel damage associated with past, current, or future hypertension, retinal arteriolar narrowing has been linked to stroke incidence. These results indicate an involvement of cerebral microcirculation in aortic coarctation, despite timely repair, and might contribute to explain the increased rate of cerebrovascular events in such patients.
Hollow core fiber delivery of sub-ps pulses from a TruMicro 5000 Femto edition thin disk amplifier
(2015)
Many biped robots deploy a form of gait that follows the zero moment point (ZMP) approach, that is, the robot is in a stable position at any point in time. This requires the robot to be fully actuated. While very stable, the draw-backs of this approach are a fairly slow gait and high energy consumption. An alternative approach is the so-called passive-dynamic walking, where the gait makes use of the inertia and dynamic stability of the robot. In this paper we describe our ongoing work of combining the principles of passive-dynamic walking on the fully-actuated biped robot Nao, which is also deployed for robotic soccer applications. We present a simple controller that allows the robot to stably rock sidewards, showing a closed limit-cycle. We discuss first results of superimposing a forward motion on the sidewards motion. Based on this we expect to endow the Nao with a fast, robust, and stable passive-dynamic walk on the fully-actuated Nao in the future.