60 research outputs found

    Synthetic biology and microdevices : a powerful combination

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    Recent developments demonstrate that the combination of microbiology with micro-and nanoelectronics is a successful approach to develop new miniaturized sensing devices and other technologies. In the last decade, there has been a shift from the optimization of the abiotic components, for example, the chip, to the improvement of the processing capabilities of cells through genetic engineering. The synthetic biology approach will not only give rise to systems with new functionalities, but will also improve the robustness and speed of their response towards applied signals. To this end, the development of new genetic circuits has to be guided by computational design methods that enable to tune and optimize the circuit response. As the successful design of genetic circuits is highly dependent on the quality and reliability of its composing elements, intense characterization of standard biological parts will be crucial for an efficient rational design process in the development of new genetic circuits. Microengineered devices can thereby offer a new analytical approach for the study of complex biological parts and systems. By summarizing the recent techniques in creating new synthetic circuits and in integrating biology with microdevices, this review aims at emphasizing the power of combining synthetic biology with microfluidics and microelectronics

    Organic semiconductors for biological sensing

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    Semiconducting Polymers for Electronic Biosensors and Biological Interfaces

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    Bioeletronics aims at the direct coupling of biomolecular function units with standard electronic devices. The main limitations of this field are the material needed to interface soft living entities with hard inorganic devices. Conducting polymers enabled the bridging between these two separate worlds, owing to their biocompatibility, soft nature and the ability to be tailored according to the required application. In particular, the intrinsically conductive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) is one of the most promising polymers, having an excellent chemical and thermal stability, reversible doping state and high conductivity. This thesis relies on the use of PEDOT:PSS as semiconducting material for biological interfaces and biosensors. In detail, OECTs were demonstrated to be able to real-time monitor growth and detachment of both strong-barrier and no-barrier cells, according to the patterning of the device active area and the selected geometry. Thus, these devices were employed to assess silver nanoparticles (AgNPs) toxicity effects on cell lines, allowing further insights on citrate-coated AgNPs uptake by the cells and their toxic action, while demonstrating no cytotoxic activity of EG6OH-coated AgNPs. Moreover, PEDOT:PSS OECTs were proved to be capable of detecting oxygen dissolved in KCl or even cell culture medium, in the oxygen partial pressure range of 0-5%. Furthermore, PEDOT:PSS OECTs were biofunctionalized to impart specificity on the device sensing capabilities, through a biochemical functionalization strategy, electrically characterized. The resulting devices showed a proof of concept detection of a fundamental cytokine for cells undergoing osteogenic differentiation. Finally, PEDOT:PSS thickness-controlled films were employed as biocompatible, low-impedance and soft interfaces between the animal nerve and a gold electrode. The introduction of the plasticizer polyethylene glycol (PEG) enhanced the elasticity of the polymer, while keeping good conductivity and low-impedance properties. An in-vivo, chronic recording of the renal sympathetic nerve activity in rats demonstrated the efficiency of the device

    Field-Effect Sensors

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    This Special Issue focuses on fundamental and applied research on different types of field-effect chemical sensors and biosensors. The topics include device concepts for field-effect sensors, their modeling, and theory as well as fabrication strategies. Field-effect sensors for biomedical analysis, food control, environmental monitoring, and the recording of neuronal and cell-based signals are discussed, among other factors

    New materials for electronics applications: nafion-gated nanowire field-effect transistors and metal-organic framework (MOF) single crystals

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    Nafion with its high ionic conductivity has been used as a proton conductor in proton exchange membrane fuel cells. In this study, we develop Nafion as an electronic material based on our finding that it works a negative tone resist in an electron beam lithography (EBL) process. X-ray photoelectron spectroscopy (XPS) studies show cleavage of ether groups in the side chain of Nafion, which causes the insolubility that provides contrast after EBL. There is also evidence that crosslinking between separate Nafion backbones contributes. We show that nanoscale Nafion patterned by EBL provides high performance as an ionic gating structure for n-InAs nanowire field-effect transistors. We also demonstrate the ability to make a complementary inverter by combining nanopatterned Nafion with n-InAs and p-GaAs field-effect transistors monolithically integrated on a common substrate. We used electrochemical impedance spectroscopy to characterize and better understand how the ionic conductivity of Nafion thin-films is affected by EBL exposure. We found that EBL causes an order of magnitude decrease in ionic conductivity for 230 nm thick films compared to only a 50% loss for 30 nm films. We characterized the water uptake of Nafion films using a Quartz Crystal Microbalance (QCM) technique. We found an approximately 30% decrease in the water uptake of 230 nm Nafion films and an approximately 50% increase for the thinner Nafion films. Preliminary neutron reflectometry results show that the water uptake of the 30 nm Nafion film is consistent with our QCM data. Since we can pattern nanoscale Nafion film using EBL, we attempted to use nanoscale EBL patterned Nafion film as an active layer in protonic field-effect transistors. Unfortunately, transistor behaviour could not be obtained, with further work needed to mitigate gate leakage issues. Metal-Organic Framework (MOF) materials with high electrical conductivity are of significant interest. Electrical characterization of these materials has been reported mostly for pressed pellets. In this thesis, we focused on measuring the electrical conductivity of single crystals of a newly-synthesised MOF, Cu(BTDAT)(MeOH). We found that the single crystals show high electrical conductivity, up to 40 uS/cm, at room temperature under ambient conditions with no observed anisotropy. We also performed electrical measurements at low temperatures between 83 K and 300 K. We found that current-voltage characteristics show good linearity at higher temperatures but become non-linear at lower temperatures. The conductivity decreases with reduced temperature. The fitting of an Arrhenius plot in the high-temperature range gave an activation energy Ea = 97 meV. We fabricated a field-effect transistor structure and found that the crystal did not exhibit any n-type or p-type semiconducting behaviour

    Integration of biomolecular logic principles with electronic transducers on a chip

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    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 ”1” or “0” binary notation, corresponding to a “true” or “false” 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 “sense-act-treat” function integrated on one chip. The present system exemplarily mimics an “artificial pancreas” 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, “proof-of-principle” 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

    Nanoparticle Necklace Network Arrays Exhibiting Room Temperature Single-Electron Switching

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    A single nanoparticle is one of the most sensitive electronic devices for sensing chemicals in a gas or liquid. The conductivity of a single Au nanoparticle is significantly modulated by the binding of a molecule that alters charge by just one electron. However, the single-electron sensitivity requires cryogenic temperatures and interconnection is not easy. A patterned two-dimensional network of one-dimensional nanoparticle necklaces made up of 10 nm Au particles are fabricated and shown to exhibit similar single-electron effect at room temperature. Furthermore, the long range conductivity of over 10’s of microns makes the structure easy to self-assemble onto conventional microelectronics circuitry. A device exhibiting single-electron effect is characterized by highly non-linear current-bias behavior where at bias, V \u3e VT current rises rapidly and scales as (V/VT – 1)ζ, where ζ ≥ 1 is the critical exponent and VT is the threshold voltage. Below VT, current does not flow. Thus, VT is the switching voltage and larger ζ signifies sharper switching characteristics. While arrays of one and two dimension are well known to exhibit appreciable VT at cryogenic temperatures, at ambient temperatures the blockade effect vanishes. The unique architecture of the necklace network results in a weak dependence of VT on temperature which leads to room temperature single-electron effect. The high sensitivity of the nanoparticle necklace network array at room temperature allows coupled live cells to electronically switch, or gate, the device through cellular metabolic activity. Additionally, the critical exponent, ζ, which is a measure of how current will rise during switching, can be significantly enhanced by cementing the necklaces with the dielectric material CdS, thereby greatly increasing the switching gain and sensitivity of the device. Given robust room temperature single-electron switching, enhanced ζ values, cellular coupling capability, and natural integrability with microelectronics circuitry, nanoparticle necklace network arrays have the potential to be implemented in a wide range of applications, such as, chemical sensors, biofuel cells, biomedical devices, and data storage devices. Adviser: Ravi F. Sara

    Nanochips and medical applications

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    Ο όρος «νανοτσιπ» αναφέρεται σε ένα ολοκληρωμένο κύκλωμα (τσιπ) με νανοϋλικά και δομές στη νανοκλίμακα (1-100nm). Ένα ολοκληρωμένο κύκλωμα είναι μια συλλογή ηλεκτρονικών εξαρτημάτων, όπως τρανζίστορ, δίοδοι, πυκνωτές και αντιστάσεις. Τα σημερινά τρανζίστορ είναι στη νανοκλίμακα, αλλά μπορούν να τροποποιηθούν με νανοδομές για την κατασκευή βιοαισθητήρων που μπορούν να πραγματοποιούν ανίχνευση βιομορίων, όπως ιόντα, μόρια DNA, αντισώματα και αντιγόνα με μεγάλη ευαισθησία. Υλικά και Μέθοδοι: Πραγματοποιήθηκε συστηματική αναζήτηση βιβλιογραφίας με χρήση των ηλεκτρονικών βάσεων δεδομένων PubMed, Google Scholar και Scopus για την ανάπτυξη και χρήση νανοτσίπ σε ιατρικές εφαρμογές. Για τον προσδιορισμό των σχετικών εργασιών, τα κριτήρια συμπερίληψης αναφέρονται σε άρθρα στην αγγλική γλώσσα, άρθρα βιβλιογραφικού περιεχομένου ή/και έρευνών. Τα κριτήρια αποκλεισμού ήταν άρθρα εφημερίδων, περιλήψεις συνεδρίων και επιστολές. Αποτελέσματα: Τεχνικές in-vivo και in-vitro έχουν χρησιμοποιηθεί για την ανίχνευση μορίων DNA, ιόντων, αντισωμάτων, σημαντικών πρωτεϊνών και καρκινικών δεικτών, όχι μόνο από δείγματα αίματος αλλά και από ιδρώτα, σάλιο και άλλα βιολογικά υγρά. Διαγνωστική εφαρμογή των νανοτσίπ αποτελεί και η ανίχνευση πτητικών οργανικών ενώσεων μέσω τεστ εκπνεόμενης αναπνοής. Υπάρχουν και αρκετές θεραπευτικές εφαρμογές αυτών των συσκευών ημιαγωγών όπως τσιπ διασύνδεσης εγκεφάλου-υπολογιστή για παραλυτικές ή επιληπτικές καταστάσεις, κατασκευή «βιονικών» οργάνων όπως τεχνητός αμφιβληστροειδής, τεχνητό δέρμα και ρομποτικά προθετικά άκρα για ακρωτηριασμένους ή ρομποτική χειρουργική. Συμπέρασμα: Η χρήση των νανοτσίπ στην ιατρική είναι ένας αναδυόμενος τομέας με αρκετές θεραπευτικές εφαρμογές όπως η διάγνωση, η παρακολούθηση της υγείας και της φυσικής κατάστασης και η κατασκευή «βιονικών» οργάνων.Background: The term “nanochip” pertains to an integrated circuit (chip) with nanomaterials and components in the nano-dimension (1-100nm). An integrated circuit is essentially a collection of electronic components, like transistors, diodes, capacitors, and resistors. Current transistors are in the nanoscale but can also be modified with nanostructures like nanoribbons and nanowires to manufacture biosensors that can perform label-free, ultrasensitive detection of biomolecules like ions, DNA molecules, antibodies and antigens. Materials and Methods: A systematic literature search was conducted using the electronic databases PubMed, Google Scholar and Scopus for the development and use of nanochips in medical applications. For the identification of relevant papers, the inclusion criteria referred to articles in the English language, review and/or research articles. The exclusion criteria were newspaper articles, conference abstracts and letters. Results: In-vivo and In-vitro techniques have been used for detection of DNA molecules, ions, antibodies, important proteins, and tumor markers, not only from blood samples but also from sweat, saliva and other biological fluids. Another diagnostic application of nanochips is detection of volatile organic compounds via a breath test. There are also several therapeutic applications of these semiconductor devices like brain-computer interface chips for paralytic or epileptic conditions, manufacture of “bionic” organs like artificial retinas, artificial skin and robotic prostheses for amputees or robotic surgery. Conclusion: The use of nanochips in medicine is an emerging field with several therapeutic applications like diagnostics, health and fitness monitoring, and manufacture of “bionic” organs
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