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Institute
- Fachbereich Medizintechnik und Technomathematik (2052) (remove)
Enzyme-catalyzed reactions have been designed to mimic various Boolean logic gates in the general framework of unconventional biomolecular computing. While some of the logic gates, particularly OR, AND, are easy to realize with biocatalytic reactions and have been reported in numerous publications, some other, like NXOR, are very challenging and have not been realized yet with enzyme reactions. The paper reports on a novel approach to mimicking the NXOR logic gate using the bell-shaped enzyme activity dependent on pH values. Shifting pH from the optimum value to the acidic or basic values by using acid or base inputs (meaning 1,0 and 0,1 inputs) inhibits the enzyme reaction, while keeping the optimum pH (assuming 0,0 and 1,1 input combinations) preserves a high enzyme activity. The challenging part of the present approach is the selection of an enzyme with a well-demonstrated bell-shape activity dependence on the pH value. While many enzymes can satisfy this condition, we selected pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase as this enzyme has the optimum pH center-located on the pH scale allowing the enzyme activity change by the acidic and basic pH shift from the optimum value corresponding to the highest activity. The present NXOR gate is added to the biomolecular “toolbox” as a new example of Boolean logic gates based on enzyme reactions.
Electrolyte-insulator-semiconductor capacitors (EISCAP) belong to field-effect sensors having an attractive transducer architecture for constructing various biochemical sensors. In this study, a capacitive model of enzyme-modified EISCAPs has been developed and the impact of the surface coverage of immobilized enzymes on its capacitance-voltage and constant-capacitance characteristics was studied theoretically and experimentally. The used multicell arrangement enables a multiplexed electrochemical characterization of up to sixteen EISCAPs. Different enzyme coverages have been achieved by means of parallel electrical connection of bare and enzyme-covered single EISCAPs in diverse combinations. As predicted by the model, with increasing the enzyme coverage, both the shift of capacitance-voltage curves and the amplitude of the constant-capacitance signal increase, resulting in an enhancement of analyte sensitivity of the EISCAP biosensor. In addition, the capability of the multicell arrangement with multi-enzyme covered EISCAPs for sequentially detecting multianalytes (penicillin and urea) utilizing the enzymes penicillinase and urease has been experimentally demonstrated and discussed.
In comparison to single-analyte devices, multiplexed systems for a multianalyte detection offer a reduced assay time and sample volume, low cost, and high throughput. Herein, a multiplexing platform for an automated quasi-simultaneous characterization of multiple (up to 16) capacitive field-effect sensors by the capacitive–voltage (C–V) and the constant-capacitance (ConCap) mode is presented. The sensors are mounted in a newly designed multicell arrangement with one common reference electrode and are electrically connected to the impedance analyzer via the base station. A Python script for the automated characterization of the sensors executes the user-defined measurement protocol. The developed multiplexing system is tested for pH measurements and the label-free detection of ligand-stabilized, charged gold nanoparticles.
Hydrophobic magnetic nanoparticles (NPs) consisting of undecanoate-capped magnetite (Fe3O4, average diameter ca. 5 nm) are used to control quantized electron transfer to surface-confined redox units and metal NPs. A two-phase system consisting of an aqueous electrolyte solution and a toluene phase that includes the suspended undecanoatecapped magnetic NPs is used to control the interfacial properties of the electrode surface. The attracted magnetic NPs form a hydrophobic layer on the electrode surface resulting in the change of the mechanisms of the surface-confined electrochemical processes. A quinone-monolayer modified Au electrode demonstrates an aqueous-type of the electrochemical process (2e-+2H+ redox mechanism) for the quinone units in the absence of the hydrophobic magnetic NPs, while the attraction of the magnetic NPs to the surface results in the stepwise single-electron transfer mechanism characteristic of a dry nonaqueous medium. Also, the attraction of the hydrophobic magnetic NPs to the Au electrode surface modified with Au NPs (ca. 1.4 nm) yields a microenvironment with a low dielectric constant that results in the single-electron quantum charging of the Au NPs.
Enzyme-based logic gates and circuits - analytical applications and interfacing with electronics
(2017)
The paper is an overview of enzyme-based logic gates and their short circuits, with specific examples of Boolean AND and OR gates, and concatenated logic gates composed of multi-step enzyme-biocatalyzed reactions. Noise formation in the biocatalytic reactions and its decrease by adding a “filter” system, converting convex to sigmoid response function, are discussed. Despite the fact that the enzyme-based logic gates are primarily considered as components of future biomolecular computing systems, their biosensing applications are promising for immediate practical use. Analytical use of the enzyme logic systems in biomedical and forensic applications is discussed and exemplified with the logic analysis of biomarkers of various injuries, e.g., liver injury, and with analysis of biomarkers characteristic of different ethnicity found in blood samples on a crime scene. Interfacing of enzyme logic systems with modified electrodes and semiconductor devices is discussed, giving particular attention to the interfaces functionalized with signal-responsive materials. Future perspectives in the design of the biomolecular logic systems and their applications are discussed in the conclusion.
Sleep spindles are neurophysiological phenomena that appear to be linked to memory formation and other functions of the central nervous system, and that can be observed in electroencephalographic recordings (EEG) during sleep. Manually identified spindle annotations in EEG recordings suffer from substantial intra- and inter-rater variability, even if raters have been highly trained, which reduces the reliability of spindle measures as a research and diagnostic tool. The Massive Online Data Annotation (MODA) project has recently addressed this problem by forming a consensus from multiple such rating experts, thus providing a corpus of spindle annotations of enhanced quality. Based on this dataset, we present a U-Net-type deep neural network model to automatically detect sleep spindles. Our model’s performance exceeds that of the state-of-the-art detector and of most experts in the MODA dataset. We observed improved detection accuracy in subjects of all ages, including older individuals whose spindles are particularly challenging to detect reliably. Our results underline the potential of automated methods to do repetitive cumbersome tasks with super-human performance.
In the presented paper data collected from the field related to damage statistics of electrical and electronic apparatus in household are reported and investigated. These damages (total number approx. 74000 cases), registered by five German insurance companies in 2005 and 2006, were adviced by customers as caused by lightning overvoltages. With the use of stochastical methods it is possible, to reasses the collected data and to distinguish between cases, which are with high probability caused by lightning overvoltages, and those, which are not. If there was an indication for a direct strike, this case was excluded, so the focus was only on indirect lightning flashes, i.e. only flashes to ground near the structure and flashes to or nearby an incoming service line were investigated. The data from the field contain the location of damaged apparatus (residence of the policy holder) and the distances of the nearest cloud-to-ground stroke to the location of the damage registered by the German lightning location network BLIDS at the date of damage. The statistical data along with some complementary numerical simulations allow to verify the correspondence of the Standards rules used for IEC 62305-2 with the field data and to define some correction needs. The results could lead to a better understanding whether a damage reported to an insurance company is really caused by indirect lightning, or not.