105 research outputs found
Control of Noise in Chemical and Biochemical Information Processing
We review models and approaches for error-control in order to prevent the
buildup of noise when gates for digital chemical and biomolecular computing
based on (bio)chemical reaction processes are utilized to realize stable,
scalable networks for information processing. Solvable rate-equation models
illustrate several recently developed methodologies for gate-function
optimization. We also survey future challenges and possible new research
avenues.Comment: 39 pages, 8 figures, PD
Biosensors for Biomolecular Computing: a Review and Future Perspectives
Biomolecular computing is the field of engineering where computation, storage, communication, and coding are obtained by exploiting interactions between biomolecules, especially DNA, RNA, and enzymes. They are a promising solution in a long-term vision, bringing huge parallelism and negligible power consumption. Despite significant efforts in taking advantage of the massive computational power of biomolecules, many issues are still open along the way for considering biomolecular circuits as an alternative or a complement to competing with complementary metalâoxideâsemiconductor (CMOS) architectures. According to the Von Neumann architecture, computing systems are composed of a central processing unit, a storage unit, and input and output (I/O). I/O operations are crucial to drive and read the computing core and to interface it to other devices. In emerging technologies, the complexity overhead and the bottleneck of I/O systems are usually limiting factors. While computing units and memories based on biomolecular systems have been successfully presented in literature, the published I/O operations are still based on laboratory equipment without a real development of integrated I/O. Biosensors are suitable devices for transducing biomolecular interactions by converting them into electrical signals. In this work, we explore the latest advancements in biomolecular computing, as well as in biosensors, with focus on technology suitable to provide the required and still missing I/O devices. Therefore, our goal is to picture out the present and future perspectives about DNA, RNA, and enzymatic-based computing according to the progression in its I/O technologies, and to understand how the field of biosensors contributes to the research beyond CMOS
Integration of biomolecular logic principles with electronic transducers on a chip
Boolean operations applied in biology and integrated with electronic transducers allow the development of a new class of digital biosensors for the detection of multiple input signals simultaneously and in real-time. With the help of Boolean functions (AND, OR, etc.), an electrical output signal will be directly delivered, representing a â1â or â0â binary notation, corresponding to a âtrueâ or âfalseâ statement, respectively. Such digital biosensors have the future potential to create medical devices and systems for intelligent or smart diagnostics.
The present thesis describes the realization of different enzyme-based biomolecular logic gates combined with electronic transducers for the possible application in medicine or food industry. In a first concept, a so called BioLogicChip is developed combining a âsense-act-treatâ function integrated on one chip. The present system exemplarily mimics an âartificial pancreasâ designed as a closed-loop drug-release system. A glucose sensor is constructed as enzyme-based AND logic gate, a temperature-depending hydrogel imitates the actuator function switching ON and OFF with its shrinking or swelling property, and an additional insulin sensor is developed to monitor and control the release of the drug (here: insulin) from the actuator. In this study, the results of the individual components such as the amperometric glucose sensor, the temperature-dependent hydrogel and the amperometric insulin sensor are presented, which are necessary to create such BioLogicChip.
Moreover, a digital adrenaline biosensor is developed to proof the catheter position during adrenal vein sampling. The sensor consists of an oxygen electrode modified by a bi-enzyme system with the enzymes laccase and pyrroloquinoline quinone-dependent glucose dehydrogenase (PQQ-GDH) to realize substrate-recycling principle to detect low adrenaline concentrations (in the nanomolar concentration range). The sensor`s behavior at different pH values and at different temperatures is studied. Measurements in Ringer`s solution are performed. In addition, the sensitivity of the biosensor to other catecholamines such as noradrenaline, dopamine and dobutamine is investigated. Furthermore, the adrenaline biosensor is successfully examined in human blood plasma. Finally, âproof-of-principleâ experiments have been performed by combining the adrenaline biosensor with Boolean operations to get a rapid qualitative statement of the presence or absence of adrenaline, thus validating the correct position of the catheter in a YES/NO form.
This adrenaline biosensor is further miniaturized as a thin-film platinum adrenaline biosensor. Here, the bioelectrocatalytical measurement principle is applied by immobilization of the enzyme PQQ-GDH to detect adrenaline in the nanomolar concentration range, too. The measurement conditions such as pH value, glucose concentration in the analyte solution and temperature are optimized with regard to a high sensitivity and low detection limit. Also, this sensor has been verified towards other catecholamines (noradrenaline, dopamine and dobutamine). The platinum thin-film adrenaline biosensor is successfully applied in blood plasma for the detection of different spiked adrenaline concentrations. Furthermore, the developed adrenalin biosensor is able to detect the concentration difference between adrenal blood and peripheral blood.
In contrast to the above-mentioned amperometric biosensor examples for biomolecular gates, also a field-effect-based platform is given attention in this thesis. The field-effect electrolyte-insulator-semiconductor (EIS) sensor consists of a layer structure of Al/p-Si/SiO2/Ta2O5 and is used to create an acetoin biosensor for the first time to control different fermentation processes. The sensor chip is modified by the enzyme acetoin reductase from B. clausii DSM 8716T for the catalytical reaction of (R)-acetoin to (R,R)-butanediol and meso-butanediol, respectively, in the presence of NADH. The linear measurement range, the optimal immobilization strategy (cross-linking by using glutaraldehyde and adsorptive binding) as well as the optimal working pH value and long-term stability are investigated by means of constant-capacitance measurements. Finally, the acetoin sensor was successfully applied in wine probes to detect different spiked acetoin concentrations. The sensor shows opportunities to be further developed as digital acetoin biosensor
Can bio-inspired information processing steps be realized as synthetic biochemical processes?
We consider possible designs and experimental realiza-tions in synthesized
rather than naturally occurring bio-chemical systems of a selection of basic
bio-inspired information processing steps. These include feed-forward loops,
which have been identified as the most common information processing motifs in
many natural pathways in cellular functioning, and memory-involving processes,
specifically, associative memory. Such systems should not be designed to
literally mimic nature. Rather, we can be guided by nature's mechanisms for
experimenting with new information/signal processing steps which are based on
coupled biochemical reactions, but are vastly simpler than natural processes,
and which will provide tools for the long-term goal of understanding and
harnessing nature's information processing paradigm. Our biochemical processes
of choice are enzymatic cascades because of their compatibility with
physiological processes in vivo and with electronics (e.g., electrodes) in
vitro allowing for networking and interfacing of enzyme-catalyzed processes
with other chemical and biochemical reactions. In addition to designing and
realizing feed-forward loops and other processes, one has to develop approaches
to probe their response to external control of the time-dependence of the
input(s), by measuring the resulting time-dependence of the output. The goal
will be to demonstrate the expected features, for example, the delayed response
and stabilizing effect of the feed-forward loops
Logic Functions with Stimuli-Responsive Single Nanopores
"This is the peer reviewed version of the following article: Logic Functions with Stimuli-Responsive Single Nanopores, which has been published in final form at https://doi.org/10.1002/celc.201300255. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] We present the concept of logic functions based on a single stimuli-responsive nanopore and analyze its potential for electrochemical transducers and actuators. The responsive molecules at the surface of the polymeric nanopore immersed in an electrolyte solution are sensitive to thermal, chemical, electrical, and optical stimuli, which are the input signals required to externally tune the conductance of the nanopore (the logical output). A single nanostructure can be operated as a resistor or as a diode with a broad range of rectifying properties, allowing for logical information-processing schemes that are useful pH and temperature sensors, electro-optical detectors, and electrochemical actuators and transducers. Some of the limitations to be addressed in practical applications are also cited.P. R., J. C., and S. M. acknowledge financial support from the Generalitat Valenciana (Project Prometeo/GV/0069), the Ministry of Economy and Competitiveness of Spain (Materials Program, project No. MAT2012-32084), and FEDER. M. A. and W. E. gratefully acknowledge financial support by the Beilstein-Institut, Frankfurt/Main, Germany, within the research collaboration NanoBiC.Ramirez Hoyos, P.; Cervera Montesinos, J.; Ali, M.; Ensinger, W.; MafĂ©, S. (2014). Logic Functions with Stimuli-Responsive Single Nanopores. ChemElectroChem. 1(4):698-705. https://doi.org/10.1002/celc.201300255S69870514Siwy, Z., Gu, Y., Spohr, H. 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