@article{KarschuckPoghossianSeretal.2024, author = {Karschuck, Tobias and Poghossian, Arshak and Ser, Joey and Tsokolakyan, Astghik and Achtsnicht, Stefan and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Capacitive model of enzyme-modified field-effect biosensors: Impact of enzyme coverage}, series = {Sensors and Actuators B: Chemical}, volume = {408}, journal = {Sensors and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005 (Print)}, doi = {10.1016/j.snb.2024.135530}, pages = {12 Seiten}, year = {2024}, abstract = {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.}, language = {en} } @article{KarschuckSchmidtAchtsnichtetal.2023, author = {Karschuck, Tobias and Schmidt, Stefan and Achtsnicht, Stefan and Poghossian, Arshak and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Multiplexing system for automated characterization of a capacitive field-effect sensor array}, series = {Physica Status Solidi A}, volume = {220}, journal = {Physica Status Solidi A}, number = {22}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6300 (Print)}, doi = {10.1002/pssa.202300265}, pages = {7 Seiten}, year = {2023}, abstract = {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.}, language = {en} } @article{WendlandtKochBritzetal.2023, author = {Wendlandt, Tim and Koch, Claudia and Britz, Beate and Liedek, Anke and Schmidt, Nora and Werner, Stefan and Gleba, Yuri and Vahidpour, Farnoosh and Welden, Melanie and Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Facile Purification and Use of Tobamoviral Nanocarriers for Antibody-Mediated Display of a Two-Enzyme System}, series = {Viruses}, volume = {9}, journal = {Viruses}, number = {15}, publisher = {MDPI}, address = {Basel}, issn = {1999-4915}, doi = {doi.org/10.3390/v15091951}, pages = {Artikel 1951}, year = {2023}, abstract = {Immunosorbent turnip vein clearing virus (TVCV) particles displaying the IgG-binding domains D and E of Staphylococcus aureus protein A (PA) on every coat protein (CP) subunit (TVCVPA) were purified from plants via optimized and new protocols. The latter used polyethylene glycol (PEG) raw precipitates, from which virions were selectively re-solubilized in reverse PEG concentration gradients. This procedure improved the integrity of both TVCVPA and the wild-type subgroup 3 tobamovirus. TVCVPA could be loaded with more than 500 IgGs per virion, which mediated the immunocapture of fluorescent dyes, GFP, and active enzymes. Bi-enzyme ensembles of cooperating glucose oxidase and horseradish peroxidase were tethered together on the TVCVPA carriers via a single antibody type, with one enzyme conjugated chemically to its Fc region, and the other one bound as a target, yielding synthetic multi-enzyme complexes. In microtiter plates, the TVCVPA-displayed sugar-sensing system possessed a considerably increased reusability upon repeated testing, compared to the IgG-bound enzyme pair in the absence of the virus. A high coverage of the viral adapters was also achieved on Ta2O5 sensor chip surfaces coated with a polyelectrolyte interlayer, as a prerequisite for durable TVCVPA-assisted electrochemical biosensing via modularly IgG-assembled sensor enzymes.}, language = {en} } @article{SchoeningBronderWuetal.2017, author = {Sch{\"o}ning, Michael Josef and Bronder, Thomas and Wu, Chunsheng and Scheja, Sabrina and Jessing, Max and Metzger-Boddien, Christoph and Keusgen, Michael and Poghossian, Arshak}, title = {Label-Free DNA Detection with Capacitive Field-Effect Devices—Challenges and Opportunities}, series = {Proceedings}, volume = {1}, journal = {Proceedings}, number = {8}, publisher = {MDPI}, address = {Basel}, issn = {2504-3900}, doi = {10.3390/proceedings1080719}, pages = {Artikel 719}, year = {2017}, abstract = {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.}, language = {en} } @article{WeldenPoghossianVahidpouretal.2022, author = {Welden, Melanie and Poghossian, Arshak and Vahidpour, Farnoosh and Wendlandt, Tim and Keusgen, Michael and Wege, Christina and Sch{\"o}ning, Michael Josef}, title = {Towards multi-analyte detection with field-effect capacitors modified with tobacco mosaic virus bioparticles as enzyme nanocarriers}, series = {Biosensors}, volume = {12}, journal = {Biosensors}, number = {1}, publisher = {MDPI}, address = {Basel}, issn = {2079-6374}, doi = {10.3390/bios12010043}, pages = {Artikel 43}, year = {2022}, abstract = {Utilizing an appropriate enzyme immobilization strategy is crucial for designing enzyme-based biosensors. Plant virus-like particles represent ideal nanoscaffolds for an extremely dense and precise immobilization of enzymes, due to their regular shape, high surface-to-volume ratio and high density of surface binding sites. In the present work, tobacco mosaic virus (TMV) particles were applied for the co-immobilization of penicillinase and urease onto the gate surface of a field-effect electrolyte-insulator-semiconductor capacitor (EISCAP) with a p-Si-SiO₂-Ta₂O₅ layer structure for the sequential detection of penicillin and urea. The TMV-assisted bi-enzyme EISCAP biosensor exhibited a high urea and penicillin sensitivity of 54 and 85 mV/dec, respectively, in the concentration range of 0.1-3 mM. For comparison, the characteristics of single-enzyme EISCAP biosensors modified with TMV particles immobilized with either penicillinase or urease were also investigated. The surface morphology of the TMV-modified Ta₂O₅-gate was analyzed by scanning electron microscopy. Additionally, the bi-enzyme EISCAP was applied to mimic an XOR (Exclusive OR) enzyme logic gate.}, language = {en} } @inproceedings{WeldenSeverinsPoghossianetal.2022, author = {Welden, Melanie and Severins, Robin and Poghossian, Arshak and Wege, Christina and Siegert, Petra and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Studying the immobilization of acetoin reductase with Tobacco mosaic virus particles on capacitive field-effect sensors}, series = {2022 IEEE International Symposium on Olfaction and Electronic Nose (ISOEN)}, booktitle = {2022 IEEE International Symposium on Olfaction and Electronic Nose (ISOEN)}, publisher = {IEEE}, isbn = {978-1-6654-5860-3 (Online)}, doi = {10.1109/ISOEN54820.2022.9789657}, pages = {4 Seiten}, year = {2022}, abstract = {A capacitive electrolyte-insulator-semiconductor (EISCAP) biosensor modified with Tobacco mosaic virus (TMV) particles for the detection of acetoin is presented. The enzyme acetoin reductase (AR) was immobilized on the surface of the EISCAP using TMV particles as nanoscaffolds. The study focused on the optimization of the TMV-assisted AR immobilization on the Ta 2 O 5 -gate EISCAP surface. The TMV-assisted acetoin EISCAPs were electrochemically characterized by means of leakage-current, capacitance-voltage, and constant-capacitance measurements. The TMV-modified transducer surface was studied via scanning electron microscopy.}, language = {en} } @article{WeldenSeverinsPoghossianetal.2022, author = {Welden, Melanie and Severins, Robin and Poghossian, Arshak and Wege, Christina and Bongaerts, Johannes and Siegert, Petra and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Detection of acetoin and diacetyl by a tobacco mosaic virus-assisted field-effect biosensor}, series = {Chemosensors}, volume = {10}, journal = {Chemosensors}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2227-9040}, doi = {10.3390/chemosensors10060218}, pages = {Artikel 218}, year = {2022}, abstract = {Acetoin and diacetyl have a major impact on the flavor of alcoholic beverages such as wine or beer. Therefore, their measurement is important during the fermentation process. Until now, gas chromatographic techniques have typically been applied; however, these require expensive laboratory equipment and trained staff, and do not allow for online monitoring. In this work, a capacitive electrolyte-insulator-semiconductor sensor modified with tobacco mosaic virus (TMV) particles as enzyme nanocarriers for the detection of acetoin and diacetyl is presented. The enzyme acetoin reductase from Alkalihalobacillus clausii DSM 8716ᵀ is immobilized via biotin-streptavidin affinity, binding to the surface of the TMV particles. The TMV-assisted biosensor is electrochemically characterized by means of leakage-current, capacitance-voltage, and constant capacitance measurements. In this paper, the novel biosensor is studied regarding its sensitivity and long-term stability in buffer solution. Moreover, the TMV-assisted capacitive field-effect sensor is applied for the detection of diacetyl for the first time. The measurement of acetoin and diacetyl with the same sensor setup is demonstrated. Finally, the successive detection of acetoin and diacetyl in buffer and in diluted beer is studied by tuning the sensitivity of the biosensor using the pH value of the measurement solution.}, language = {en} } @article{PoghossianWeldenBuniatyanetal.2021, author = {Poghossian, Arshak and Welden, Rene and Buniatyan, Vahe V. and Sch{\"o}ning, Michael Josef}, title = {An Array of On-Chip Integrated, Individually Addressable Capacitive Field-Effect Sensors with Control Gate: Design and Modelling}, series = {Sensors}, volume = {21}, journal = {Sensors}, number = {18}, publisher = {MDPI}, address = {Basel}, issn = {1424-8220}, doi = {10.3390/s21186161}, pages = {17}, year = {2021}, abstract = {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.}, language = {en} } @article{KarschuckKaulenPoghossianetal.2021, author = {Karschuck, Tobias and Kaulen, Corinna and Poghossian, Arshak and Wagner, Patrick H. and Sch{\"o}ning, Michael Josef}, title = {Gold nanoparticle-modified capacitive field-effect sensors: Studying the surface density of nanoparticles and coupling of charged polyelectrolyte macromolecules}, series = {Electrochemical Science Advances}, volume = {2}, journal = {Electrochemical Science Advances}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0938-5193}, doi = {10.1002/elsa.202100179}, pages = {10 Seiten}, year = {2021}, abstract = {The coupling of ligand-stabilized gold nanoparticles with field-effect devices offers new possibilities for label-free biosensing. In this work, we study the immobilization of aminooctanethiol-stabilized gold nanoparticles (AuAOTs) on the silicon dioxide surface of a capacitive field-effect sensor. The terminal amino group of the AuAOT is well suited for the functionalization with biomolecules. The attachment of the positively-charged AuAOTs on a capacitive field-effect sensor was detected by direct electrical readout using capacitance-voltage and constant capacitance measurements. With a higher particle density on the sensor surface, the measured signal change was correspondingly more pronounced. The results demonstrate the ability of capacitive field-effect sensors for the non-destructive quantitative validation of nanoparticle immobilization. In addition, the electrostatic binding of the polyanion polystyrene sulfonate to the AuAOT-modified sensor surface was studied as a model system for the label-free detection of charged macromolecules. Most likely, this approach can be transferred to the label-free detection of other charged molecules such as enzymes or antibodies.}, language = {en} } @article{PoghossianKarschuckWagneretal.2022, author = {Poghossian, Arshak and Karschuck, Tobias and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Field-Effect Capacitors Decorated with Ligand-Stabilized Gold Nanoparticles: Modeling and Experiments}, series = {Biosensors}, volume = {12}, journal = {Biosensors}, number = {5}, publisher = {MDPI}, address = {Basel}, issn = {2079-6374}, doi = {10.3390/bios12050334}, pages = {Artikel 334}, year = {2022}, abstract = {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.}, language = {en} } @article{JablonskiPoghossianKeusgenetal.2021, author = {Jablonski, Melanie and Poghossian, Arshak and Keusgen, Michael and Wege, Christina and Sch{\"o}ning, Michael Josef}, title = {Detection of plant virus particles with a capacitive field-effect sensor}, series = {Analytical and Bioanalytical Chemistry}, volume = {413}, journal = {Analytical and Bioanalytical Chemistry}, publisher = {Springer Nature}, address = {Cham}, issn = {1618-2650}, doi = {10.1007/s00216-021-03448-8}, pages = {5669 -- 5678}, year = {2021}, abstract = {Plant viruses are major contributors to crop losses and induce high economic costs worldwide. For reliable, on-site and early detection of plant viral diseases, portable biosensors are of great interest. In this study, a field-effect SiO2-gate electrolyte-insulator-semiconductor (EIS) sensor was utilized for the label-free electrostatic detection of tobacco mosaic virus (TMV) particles as a model plant pathogen. The capacitive EIS sensor has been characterized regarding its TMV sensitivity by means of constant-capacitance method. The EIS sensor was able to detect biotinylated TMV particles from a solution with a TMV concentration as low as 0.025 nM. A good correlation between the registered EIS sensor signal and the density of adsorbed TMV particles assessed from scanning electron microscopy images of the SiO2-gate chip surface was observed. Additionally, the isoelectric point of the biotinylated TMV particles was determined via zeta potential measurements and the influence of ionic strength of the measurement solution on the TMV-modified EIS sensor signal has been studied.}, language = {en} } @article{MolinnusIkenJohnenetal.2022, author = {Molinnus, Denise and Iken, Heiko and Johnen, Anna Lynn and Richstein, Benjamin and Hellmich, Lena and Poghossian, Arshak and Knoch, Joachim and Sch{\"o}ning, Michael Josef}, title = {Miniaturized pH-Sensitive Field-Effect Capacitors with Ultrathin Ta₂O₅ Films Prepared by Atomic Layer Deposition}, series = {physica status solidi (a) applications and materials science}, volume = {219}, journal = {physica status solidi (a) applications and materials science}, number = {8}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.202100660}, pages = {7 Seiten}, year = {2022}, abstract = {Miniaturized electrolyte-insulator-semiconductor capacitors (EISCAPs) with ultrathin gate insulators have been studied in terms of their pH-sensitive sensor characteristics: three different EISCAP systems consisting of Al-p-Si-Ta2O5(5 nm), Al-p-Si-Si3N4(1 or 2 nm)-Ta2O5 (5 nm), and Al-p-Si-SiO2(3.6 nm)-Ta2O5(5 nm) layer structures are characterized in buffer solution with different pH values by means of capacitance-voltage and constant capacitance method. The SiO2 and Si3N4 gate insulators are deposited by rapid thermal oxidation and rapid thermal nitridation, respectively, whereas the Ta2O5 film is prepared by atomic layer deposition. All EISCAP systems have a clear pH response, favoring the stacked gate insulators SiO2-Ta2O5 when considering the overall sensor characteristics, while the Si3N4(1 nm)-Ta2O5 stack delivers the largest accumulation capacitance (due to the lower equivalent oxide thickness) and a higher steepness in the slope of the capacitance-voltage curve among the studied stacked gate insulator systems.}, language = {en} } @article{PoghossianSchoening2021, author = {Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Recent progress in silicon-based biologically sensitive field-effect devices}, series = {Current Opinion in Electrochemistry}, journal = {Current Opinion in Electrochemistry}, number = {Article number: 100811}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2451-9103}, doi = {10.1016/j.coelec.2021.100811}, year = {2021}, abstract = {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.}, language = {en} } @article{JablonskiPoghossianSeverinetal.2021, author = {Jablonski, Melanie and Poghossian, Arshak and Severin, Robin and Keusgen, Michael and Wege, Christian and Sch{\"o}ning, Michael Josef}, title = {Capacitive Field-Effect Biosensor Studying Adsorption of Tobacco Mosaic Virus Particles}, series = {Micromachines}, volume = {12}, journal = {Micromachines}, number = {1}, publisher = {MDPI}, address = {Basel}, doi = {10.3390/mi12010057}, pages = {Artikel 57}, year = {2021}, abstract = {Plant virus-like particles, and in particular, tobacco mosaic virus (TMV) particles, are increasingly being used in nano- and biotechnology as well as for biochemical sensing purposes as nanoscaffolds for the high-density immobilization of receptor molecules. The sensitive parameters of TMV-assisted biosensors depend, among others, on the density of adsorbed TMV particles on the sensor surface, which is affected by both the adsorption conditions and surface properties of the sensor. In this work, Ta₂O₅-gate field-effect capacitive sensors have been applied for the label-free electrical detection of TMV adsorption. The impact of the TMV concentration on both the sensor signal and the density of TMV particles adsorbed onto the Ta₂O₅-gate surface has been studied systematically by means of field-effect and scanning electron microscopy methods. In addition, the surface density of TMV particles loaded under different incubation times has been investigated. Finally, the field-effect sensor also demonstrates the label-free detection of penicillinase immobilization as model bioreceptor on TMV particles.}, language = {en} } @article{PoghossianJablonskiMolinnusetal.2020, author = {Poghossian, Arshak and Jablonski, Melanie and Molinnus, Denise and Wege, Christina and Sch{\"o}ning, Michael Josef}, title = {Field-Effect Sensors for Virus Detection: From Ebola to SARS-CoV-2 and Plant Viral Enhancers}, series = {Frontiers in Plant Science}, volume = {11}, journal = {Frontiers in Plant Science}, number = {Article 598103}, publisher = {Frontiers}, address = {Lausanne}, doi = {10.3389/fpls.2020.598103}, pages = {1 -- 14}, year = {2020}, abstract = {Coronavirus disease 2019 (COVID-19) is a novel human infectious disease provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, no specific vaccines or drugs against COVID-19 are available. Therefore, early diagnosis and treatment are essential in order to slow the virus spread and to contain the disease outbreak. Hence, new diagnostic tests and devices for virus detection in clinical samples that are faster, more accurate and reliable, easier and cost-efficient than existing ones are needed. Due to the small sizes, fast response time, label-free operation without the need for expensive and time-consuming labeling steps, the possibility of real-time and multiplexed measurements, robustness and portability (point-of-care and on-site testing), biosensors based on semiconductor field-effect devices (FEDs) are one of the most attractive platforms for an electrical detection of charged biomolecules and bioparticles by their intrinsic charge. In this review, recent advances and key developments in the field of label-free detection of viruses (including plant viruses) with various types of FEDs are presented. In recent years, however, certain plant viruses have also attracted additional interest for biosensor layouts: Their repetitive protein subunits arranged at nanometric spacing can be employed for coupling functional molecules. If used as adapters on sensor chip surfaces, they allow an efficient immobilization of analyte-specific recognition and detector elements such as antibodies and enzymes at highest surface densities. The display on plant viral bionanoparticles may also lead to long-time stabilization of sensor molecules upon repeated uses and has the potential to increase sensor performance substantially, compared to conventional layouts. This has been demonstrated in different proof-of-concept biosensor devices. Therefore, richly available plant viral particles, non-pathogenic for animals or humans, might gain novel importance if applied in receptor layers of FEDs. These perspectives are explained and discussed with regard to future detection strategies for COVID-19 and related viral diseases.}, language = {en} } @article{PoghossianSchoening2020, author = {Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Capacitive field-effect eis chemical sensors and biosensors: A status report}, series = {Sensors}, volume = {20}, journal = {Sensors}, number = {19}, publisher = {MDPI}, address = {Basel}, issn = {1424-8220}, doi = {10.3390/s20195639}, pages = {Artikel 5639}, year = {2020}, abstract = {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.}, language = {en} } @incollection{SchoeningWagnerPoghossianetal.2018, author = {Sch{\"o}ning, Michael Josef and Wagner, Torsten and Poghossian, Arshak and Miyamoto, K.I. and Werner, C.F. and Krause, S. and Yoshinobu, T.}, title = {Light-addressable potentiometric sensors for (bio-)chemical sensing and imaging}, series = {Encyclopedia of Interfacial Chemistry: Surface Science and Electrochemistry. Vol. 7}, booktitle = {Encyclopedia of Interfacial Chemistry: Surface Science and Electrochemistry. Vol. 7}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {9780128097397}, pages = {295 -- 308}, year = {2018}, language = {en} } @article{PoghossianGeisslerSchoening2019, author = {Poghossian, Arshak and Geissler, Hanno and Sch{\"o}ning, Michael Josef}, title = {Rapid methods and sensors for milk quality monitoring and spoilage detection}, series = {Biosensors and Bioelectronics}, volume = {140}, journal = {Biosensors and Bioelectronics}, number = {Article 111272}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0956-5663}, doi = {10.1016/j.bios.2019.04.040}, year = {2019}, language = {en} } @article{BronderPoghossianJessingetal.2019, author = {Bronder, Thomas and Poghossian, Arshak and Jessing, Max P. and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Surface regeneration and reusability of label-free DNA biosensors based on weak polyelectrolyte-modified capacitive field-effect structures}, series = {Biosensors and Bioelectronics}, volume = {126}, journal = {Biosensors and Bioelectronics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0956-5663}, doi = {10.1016/j.bios.2018.11.019}, pages = {510 -- 517}, year = {2019}, language = {en} } @incollection{SchoeningPoghossian2018, author = {Sch{\"o}ning, Michael Josef and Poghossian, Arshak}, title = {Enzyme und Biosensorik}, series = {Einf{\"u}hrung in die Enzymtechnologie}, booktitle = {Einf{\"u}hrung in die Enzymtechnologie}, publisher = {Springer Spektrum}, address = {Berlin}, isbn = {978-3-662-57619-9}, doi = {10.1007/978-3-662-57619-9_18}, pages = {323 -- 347}, year = {2018}, abstract = {Enzymbasierte Biosensoren finden seit mehr als f{\"u}nf Jahrzehnten einen prosperierenden Wachstumsmarkt und werden zunehmend auch in biotechnologischen Prozessen eingesetzt. In diesem Kapitel werden, ausgehend vom Sensorbegriff und typischen Kenngr{\"o}ßen f{\"u}r Biosensoren (Abschn. 18.1), elektrochemische Enzym-Biosensoren vorgestellt und deren typischen Einsatzgebiete diskutiert (Abschn. 18.2). Ein Blick {\"u}ber den „Tellerrand" hinaus zeigt alternative Transduktorprinzipien (Abschn. 18.3) und f{\"u}hrt abschließend in aktuelle Forschungstrends ein (Abschn. 18.4).}, language = {de} } @incollection{YoshinobuKrauseMiyamotoetal.2018, author = {Yoshinobu, Tatsuo and Krause, Steffi and Miyamoto, Ko-ichiro and Werner, Frederik and Poghossian, Arshak and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {(Bio-)chemical Sensing and Imaging by LAPS and SPIM}, series = {Label-free biosensing: advanced materials, devices and applications}, booktitle = {Label-free biosensing: advanced materials, devices and applications}, publisher = {Springer}, address = {Cham}, isbn = {978-3-319-75219-8}, pages = {103 -- 132}, year = {2018}, abstract = {The light-addressable potentiometric sensor (LAPS) and scanning photo-induced impedance microscopy (SPIM) are two closely related methods to visualise the distributions of chemical species and impedance, respectively, at the interface between the sensing surface and the sample solution. They both have the same field-effect structure based on a semiconductor, which allows spatially resolved and label-free measurement of chemical species and impedance in the form of a photocurrent signal generated by a scanning light beam. In this article, the principles and various operation modes of LAPS and SPIM, functionalisation of the sensing surface for measuring various species, LAPS-based chemical imaging and high-resolution sensors based on silicon-on-sapphire substrates are described and discussed, focusing on their technical details and prospective applications.}, language = {en} } @book{SchoeningPoghossian2018, author = {Sch{\"o}ning, Michael Josef and Poghossian, Arshak}, title = {Label-free biosensing: advanced materials, devices and applications}, publisher = {Springer}, address = {Cham}, isbn = {978-3-319-75219-8}, pages = {xii, 480 Seiten ; Illustrationen, Diagramme}, year = {2018}, language = {en} } @article{BronderJessingPoghossianetal.2018, author = {Bronder, Thomas and Jessing, Max P. and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Detection of PCR-Amplified Tuberculosis DNA Fragments with Polyelectrolyte-Modified Field-Effect Sensors}, series = {Analytical Chemistry}, volume = {90}, journal = {Analytical Chemistry}, number = {12}, publisher = {ACS Publications}, address = {Washington, DC}, issn = {0003-2700}, doi = {10.1021/acs.analchem.8b01807}, pages = {7747 -- 7753}, year = {2018}, abstract = {Field-effect-based electrolyte-insulator-semiconductor (EIS) sensors were modified with a bilayer of positively charged weak polyelectrolyte (poly(allylamine hydrochloride) (PAH)) and probe single-stranded DNA (ssDNA) and are used for the detection of complementary single-stranded target DNA (cDNA) in different test solutions. The sensing mechanism is based on the detection of the intrinsic molecular charge of target cDNA molecules after the hybridization event between cDNA and immobilized probe ssDNA. The test solutions contain synthetic cDNA oligonucleotides (with a sequence of tuberculosis mycobacteria genome) or PCR-amplified DNA (which origins from a template DNA strand that has been extracted from Mycobacterium avium paratuberculosis-spiked human sputum samples), respectively. Sensor responses up to 41 mV have been measured for the test solutions with DNA, while only small signals of ∼5 mV were detected for solutions without DNA. The lower detection limit of the EIS sensors was ∼0.3 nM, and the sensitivity was ∼7.2 mV/decade. Fluorescence experiments using SybrGreen I fluorescence dye support the electrochemical results.}, language = {en} } @incollection{KochPoghossianWegeetal.2018, author = {Koch, Claudia and Poghossian, Arshak and Wege, Christina and Sch{\"o}ning, Michael Josef}, title = {TMV-Based Adapter Templates for Enhanced Enzyme Loading in Biosensor Applications}, series = {Virus-Derived Nanoparticles for Advanced Technologies}, booktitle = {Virus-Derived Nanoparticles for Advanced Technologies}, editor = {Wege, Christina}, publisher = {Humana Press}, address = {New York, NY}, isbn = {978-1-4939-7808-3}, doi = {10.1007/978-1-4939-7808-3}, pages = {553 -- 568}, year = {2018}, abstract = {Nanotubular tobacco mosaic virus (TMV) particles and RNA-free lower-order coat protein (CP) aggregates have been employed as enzyme carriers in different diagnostic layouts and compared for their influence on biosensor performance. In the following, we describe a label-free electrochemical biosensor for improved glucose detection by use of TMV adapters and the enzyme glucose oxidase (GOD). A specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CP aggregates was achieved via bioaffinity binding. Glucose sensors with adsorptively immobilized [SA]-GOD, and with [SA]-GOD cross-linked with glutardialdehyde, respectively, were tested in parallel on the same sensor chip. Comparison of these sensors revealed that TMV adapters enhanced the amperometric glucose detection remarkably, conveying highest sensitivity, an extended linear detection range and fastest response times. These results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for applications in biosensorics and biochips. Here, we describe the fabrication and use of amperometric sensor chips combining an array of circular Pt electrodes, their loading with GOD-modified TMV nanotubes (and other GOD immobilization methods), and the subsequent investigations of the sensor performance.}, language = {en} } @article{MolinnusHardtKaeveretal.2018, author = {Molinnus, Denise and Hardt, G. and K{\"a}ver, L. and Willenberg, H.S. and Kr{\"o}ger, J.-C. and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Chip-based biosensor for the detection of low adrenaline concentrations to support adrenal venous sampling}, series = {Sensor and Actuators B: Chemical}, volume = {272}, journal = {Sensor and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2018.05.136}, pages = {21 -- 27}, year = {2018}, abstract = {A chip-based amperometric biosensor referring on using the bioelectrocatalytical amplification principle for the detection of low adrenaline concentrations is presented. The adrenaline biosensor has been prepared by modification of a platinum thin-film electrode with an enzyme membrane containing the pyrroloquinoline quinone-dependent glucose dehydrogenase and glutaraldehyde. Measuring conditions such as temperature, pH value, and glucose concentration have been optimized to achieve a high sensitivity and a low detection limit of about 1 nM adrenaline measured in phosphate buffer at neutral pH value. The response of the biosensor to different catecholamines has also been proven. Long-term stability of the adrenaline biosensor has been studied over 10 days. In addition, the biosensor has been successfully applied for adrenaline detection in human blood plasma for future biomedical applications. Furthermore, preliminary experiments have been carried to detect the adrenaline-concentration difference measured in peripheral blood and adrenal venous blood, representing the adrenal vein sampling procedure of a physician.}, language = {en} } @article{KochPoghossianSchoeningetal.2018, author = {Koch, Claudia and Poghossian, Arshak and Sch{\"o}ning, Michael Josef and Wege, Christian}, title = {Penicillin Detection by Tobacco Mosaic Virus-Assisted Colorimetric Biosensors}, series = {Nanotheranostics}, volume = {2}, journal = {Nanotheranostics}, number = {2}, publisher = {Ivyspring}, address = {Sydney}, issn = {2206-7418}, doi = {10.7150/ntno.22114}, pages = {184 -- 196}, year = {2018}, abstract = {The presentation of enzymes on viral scaffolds has beneficial effects such as an increased enzyme loading and a prolonged reusability in comparison to conventional immobilization platforms. Here, we used modified tobacco mosaic virus (TMV) nanorods as enzyme carriers in penicillin G detection for the first time. Penicillinase enzymes were conjugated with streptavidin and coupled to TMV rods by use of a bifunctional biotin-linker. Penicillinase-decorated TMV particles were characterized extensively in halochromic dye-based biosensing. Acidometric analyte detection was performed with bromcresol purple as pH indicator and spectrophotometry. The TMV-assisted sensors exhibited increased enzyme loading and strongly improved reusability, and higher analysis rates compared to layouts without viral adapters. They extended the half-life of the sensors from 4 - 6 days to 5 weeks and thus allowed an at least 8-fold longer use of the sensors. Using a commercial budget-priced penicillinase preparation, a detection limit of 100 µM penicillin was obtained. Initial experiments also indicate that the system may be transferred to label-free detection layouts.}, language = {en} } @article{PoghossianJablonskiKochetal.2018, author = {Poghossian, Arshak and Jablonski, Melanie and Koch, Claudia and Bronder, Thomas and Rolka, David and Wege, Christina and Sch{\"o}ning, Michael Josef}, title = {Field-effect biosensor using virus particles as scaffolds for enzyme immobilization}, series = {Biosensors and Bioelectronics}, volume = {110}, journal = {Biosensors and Bioelectronics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0956-5663}, doi = {10.1016/j.bios.2018.03.036}, pages = {168 -- 174}, year = {2018}, abstract = {A field-effect biosensor employing tobacco mosaic virus (TMV) particles as scaffolds for enzyme immobilization is presented. Nanotubular TMV scaffolds allow a dense immobilization of precisely positioned enzymes with retained activity. To demonstrate feasibility of this new strategy, a penicillin sensor has been developed by coupling a penicillinase with virus particles as a model system. The developed field-effect penicillin biosensor consists of an Al-p-Si-SiO₂-Ta₂O₅-TMV structure and has been electrochemically characterized in buffer solutions containing different concentrations of penicillin G. In addition, the morphology of the biosensor surface with virus particles was characterized by scanning electron microscopy and atomic force microscopy methods. The sensors possessed a high penicillin sensitivity of ~ 92 mV/dec in a nearly-linear range from 0.1 mM to 10 mM, and a low detection limit of about 50 µM. The long-term stability of the penicillin biosensor was periodically tested over a time period of about one year without any significant loss of sensitivity. The biosensor has also been successfully applied for penicillin detection in bovine milk samples.}, language = {en} } @article{MolinnusHardtSiegertetal.2018, author = {Molinnus, Denise and Hardt, Gabriel and Siegert, Petra and Willenberg, Holger S. and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Detection of Adrenaline in Blood Plasma as Biomarker for Adrenal Venous Sampling}, series = {Electroanalysis}, volume = {30}, journal = {Electroanalysis}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-4109}, doi = {10.1002/elan.201800026}, pages = {937 -- 942}, year = {2018}, abstract = {An amperometric bi-enzyme biosensor based on substrate recycling principle for the amplification of the sensor signal has been developed for the detection of adrenaline in blood. Adrenaline can be used as biomarker verifying successful adrenal venous sampling procedure. The adrenaline biosensor has been realized via modification of a galvanic oxygen sensor with a bi-enzyme membrane combining a genetically modified laccase and a pyrroloquinoline quinone-dependent glucose dehydrogenase. The measurement conditions such as pH value and temperature were optimized to enhance the sensor performance. A high sensitivity and a low detection limit of about 0.5-1 nM adrenaline have been achieved in phosphate buffer at pH 7.4, relevant for measurements in blood samples. The sensitivity of the biosensor to other catecholamines such as noradrenaline, dopamine and dobutamine has been studied. Finally, the sensor has been successfully applied for the detection of adrenaline in human blood plasma.}, language = {en} } @article{HonarvarfardGamellaPoghossianetal.2017, author = {Honarvarfard, Elham and Gamella, Maria and Poghossian, Arshak and Sch{\"o}ning, Michael Josef and Katz, Evgeny}, title = {An enzyme-based reversible Controlled NOT (CNOT) logic gate operating on a semiconductor transducer}, series = {Applied Materials Today}, volume = {9}, journal = {Applied Materials Today}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2352-9407}, doi = {10.1016/j.apmt.2017.08.003}, pages = {266 -- 270}, year = {2017}, abstract = {An enzyme-based biocatalytic system mimicking operation of a logically reversible Controlled NOT (CNOT) gate has been interfaced with semiconductor electronic transducers. Electrolyte-insulator-semiconductor (EIS) structures have been used to transduce chemical changes produced by the enzyme system to an electronically readable capacitive output signal using field-effect features of the EIS device. Two enzymes, urease and esterase, were immobilized on the insulating interface of EIS structure producing local pH changes performing XOR logic operation controlled by various combinations of the input signals represented by urea and ethyl butyrate. Another EIS transducer was functionalized with esterase only, thus performing Identity (ID) logic operation for the ethyl butyrate input. Both semiconductor devices assembled in parallel operated as a logically reversible CNOT gate. The present system, despite its simplicity, demonstrated for the first time logically reversible function of the enzyme system transduced electronically with the semiconductor devices. The biomolecular realization of a CNOT gate interfaced with semiconductors is promising for integration into complex biomolecular networks and future biosensor/biomedical applications.}, language = {en} } @incollection{PoghossianSchoening2017, author = {Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Nanomaterial-Modified Capacitive Field-Effect Biosensors}, series = {Springer Series on Chemical Sensors and Biosensors (Methods and Applications)}, booktitle = {Springer Series on Chemical Sensors and Biosensors (Methods and Applications)}, publisher = {Springer}, address = {Berlin, Heidelberg}, doi = {10.1007/5346_2017_2}, pages = {1 -- 25}, year = {2017}, abstract = {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.}, language = {en} } @article{MolinnusPoghossianKeusgenetal.2017, author = {Molinnus, Denise and Poghossian, Arshak and Keusgen, Michael and Katz, Evgeny and Sch{\"o}ning, Michael Josef}, title = {Coupling of Biomolecular Logic Gates with Electronic Transducers: From Single Enzyme Logic Gates to Sense/Act/Treat Chips}, series = {Electroanalysis}, volume = {29}, journal = {Electroanalysis}, number = {8}, publisher = {Wiley}, address = {Weinheim}, issn = {1521-4109}, doi = {10.1002/elan.201700208}, pages = {1840 -- 1849}, year = {2017}, abstract = {The integration of biomolecular logic principles with electronic transducers allows designing novel digital biosensors with direct electrical output, logically triggered drug-release, and closed-loop sense/act/treat systems. This opens new opportunities for advanced personalized medicine in the context of theranostics. In the present work, we will discuss selected examples of recent developments in the field of interfacing enzyme logic gates with electrodes and semiconductor field-effect devices. Special attention is given to an enzyme OR/Reset logic gate based on a capacitive field-effect electrolyte-insulator-semiconductor sensor modified with a multi-enzyme membrane. Further examples are a digital adrenaline biosensor based on an AND logic gate with binary YES/NO output and an integrated closed-loop sense/act/treat system comprising an amperometric glucose sensor, a hydrogel actuator, and an insulin (drug) sensor.}, language = {en} } @inproceedings{MolinnusHardtKaeveretal.2017, author = {Molinnus, Denise and Hardt, Gabriel and K{\"a}ver, Larissa and Willenberg, Holger S. and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Detection of Adrenaline Based on Bioelectrocatalytical System to Support Tumor Diagnostic Technology}, series = {MDPI Proceedings}, booktitle = {MDPI Proceedings}, doi = {10.3390/proceedings1040506}, pages = {4 Seiten}, year = {2017}, language = {en} } @inproceedings{JablonskiKochBronderetal.2017, author = {Jablonski, Melanie and Koch, Claudia and Bronder, Thomas and Poghossian, Arshak and Wege, Christina and Sch{\"o}ning, Michael Josef}, title = {Field-Effect Biosensors Modified with Tobacco Mosaic Virus Nanotubes as Enzyme Nanocarrier}, series = {MDPI Proceeding}, volume = {1}, booktitle = {MDPI Proceeding}, number = {4}, doi = {10.3390/proceedings1040505}, pages = {4}, year = {2017}, language = {en} } @article{YoshinobuMiyamotoWerneretal.2017, author = {Yoshinobu, Tatsuo and Miyamoto, Ko-ichiro and Werner, Frederik and Poghossian, Arshak and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Light-addressable potentiometric sensors for quantitative spatial imaging of chemical species}, series = {Annual Review of Analytical Chemistry}, volume = {10}, journal = {Annual Review of Analytical Chemistry}, publisher = {Annual Reviews}, address = {Palo Alto, Calif.}, issn = {1936-1327}, doi = {10.1146/annurev-anchem-061516-045158}, pages = {225 -- 246}, year = {2017}, abstract = {A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed.}, language = {en} } @article{GamellaZakharchenkoGuzetal.2017, author = {Gamella, Maria and Zakharchenko, Andrey and Guz, Nataliia and Masi, Madeline and Minko, Sergiy and Kolpashchikov, Dmitry M. and Iken, Heiko and Poghossian, Arshak and Sch{\"o}ning, Michael Josef and Katz, Evgeny}, title = {DNA computing system activated by electrochemically triggered DNA realease from a polymer-brush-modified electrode array}, series = {Electroanalysis}, volume = {29}, journal = {Electroanalysis}, number = {2}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-4109}, doi = {10.1002/elan.201600389}, pages = {398 -- 408}, year = {2017}, abstract = {An array of four independently wired indium tin oxide (ITO) electrodes was used for electrochemically stimulated DNA release and activation of DNA-based Identity, AND and XOR logic gates. Single-stranded DNA molecules were loaded on the mixed poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA)/poly(methacrylic acid) (PMAA) brush covalently attached to the ITO electrodes. The DNA deposition was performed at pH 5.0 when the polymer brush is positively charged due to protonation of tertiary amino groups in PDMAEMA, thus resulting in electrostatic attraction of the negatively charged DNA. By applying electrolysis at -1.0 V(vs. Ag/AgCl reference) electrochemical oxygen reduction resulted in the consumption of hydrogen ions and local pH increase near the electrode surface. The process resulted in recharging the polymer brush to the negative state due to dissociation of carboxylic groups of PMAA, thus repulsing the negatively charged DNA and releasing it from the electrode surface. The DNA release was performed in various combinations from different electrodes in the array assembly. The released DNA operated as input signals for activation of the Boolean logic gates. The developed system represents a step forward in DNA computing, combining for the first time DNA chemical processes with electronic input signals.}, language = {en} } @article{BronderPoghossianKeusgenetal.2017, author = {Bronder, Thomas and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Label-free detection of double-stranded DNA molecules with polyelectrolyte-modified capacitive field-effect sensors}, series = {tm - Technisches Messen}, volume = {84}, journal = {tm - Technisches Messen}, number = {10}, publisher = {De Gruyter}, address = {Oldenbourg}, doi = {10.1515/teme-2017-0015}, pages = {628 -- 634}, year = {2017}, abstract = {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.}, language = {en} } @article{HonarvarfardGamellaChannaveerappaetal.2017, author = {Honarvarfard, Elham and Gamella, Maria and Channaveerappa, Devika and Darie, Costel C. and Poghossian, Arshak and Sch{\"o}ning, Michael Josef and Katz, Evgeny}, title = {Electrochemically Stimulated Insulin Release from a Modified Graphene-functionalized Carbon Fiber Electrode}, series = {Electroanalysis}, volume = {29}, journal = {Electroanalysis}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-4109}, doi = {10.1002/elan.201700095}, pages = {1543 -- 1553}, year = {2017}, abstract = {A graphene-functionalized carbon fiber electrode was modified with adsorbed polyethylenimine to introduce amino functionalities and then with trigonelline and 4-carboxyphenylboronic acid covalently bound to the amino groups. The trigonelline species containing quarterized pyridine groups produced positive charge on the electrode surface regardless of the pH value, while the phenylboronic acid species were neutral below pH 8 and negatively charged above pH 9 (note that their pKa=8.4). The total charge on the monolayer-modified electrode was positive at the neutral pH and negative at pH > 9. Note that 4-carboxyphenylboronic acid was attached to the electrode surface in molar excess to trigonelline, thus allowing the negative charge to dominate on the electrode surface at basic pH. Negatively charged fluorescent dye-labeled insulin (insulin-FITC) was loaded on the modified electrode surface at pH 7.0 due to its electrostatic attraction to the positively charged interface. The local pH in close vicinity to the electrode surface was increased to ca. 9-10 due to consumption of H+ ions upon electrochemical reduction of oxygen proceeding at the potential of -1.0 V (vs. Ag/AgCl) applied on the modified electrode. The process resulted in recharging of the electrode surface to the negative value due to the formation of the negative charge on the phenylboronic acid groups, thus resulting in the electrostatic repulsion of insulin-FITC and stimulating its release from the electrode surface. The insulin release was characterized by fluorescence spectroscopy (using the FITC-labeled insulin), by electrochemical measurements on an iridium oxide, IrOx, electrode and by mass spectrometry. The graphene-functionalized carbon fiber electrode demonstrated significant advantages in the signal-stimulated insulin release comparing with the carbon fiber electrode without the graphene species.}, language = {en} } @article{PoghossianWernerBuniatyanetal.2017, author = {Poghossian, Arshak and Werner, Frederik and Buniatyan, V. V. and Wagner, Torsten and Miamoto, K. and Yoshinobu, T. and Sch{\"o}ning, Michael Josef}, title = {Towards addressability of light-addressable potentiometric sensors: Shunting effect of non-illuminated region and cross-talk}, series = {Sensor and Actuators B: Chemical}, journal = {Sensor and Actuators B: Chemical}, number = {244}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2017.01.047}, pages = {1071 -- 1079}, year = {2017}, abstract = {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.}, language = {en} } @inproceedings{PoghossianBronderSchejaetal.2016, author = {Poghossian, Arshak and Bronder, Thomas and Scheja, S. and Wu, Chunsheng and Metzger-Boddien, C. and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Label-free Electrostatic Detection of DNA Amplification by PCR Using Capacitive Field-effect Devices}, series = {Procedia Engineering}, volume = {Vol. 168}, booktitle = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2016.11.512}, pages = {514 -- 517}, year = {2016}, abstract = {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.}, language = {en} } @article{KatzPoghossianSchoening2017, author = {Katz, Evgeny and Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Enzyme-based logic gates and circuits - analytical applications and interfacing with electronics}, series = {Analytical and Bioanalytical Chemistry}, volume = {409}, journal = {Analytical and Bioanalytical Chemistry}, publisher = {Springer}, address = {Berlin}, issn = {1618-2650}, doi = {10.1007/s00216-016-0079-7}, pages = {81 -- 94}, year = {2017}, abstract = {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.}, language = {en} } @inproceedings{BaeckerKochGeigeretal.2016, author = {B{\"a}cker, Matthias and Koch, C. and Geiger, F. and Eber, F. and Gliemann, H. and Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {A New Class of Biosensors Based on Tobacco Mosaic Virus and Coat Proteins as Enzyme Nanocarrier}, series = {Procedia Engineering}, volume = {Vol. 168}, booktitle = {Procedia Engineering}, issn = {1877-7058}, doi = {10.1016/j.proeng.2016.11.228}, pages = {618 -- 621}, year = {2016}, language = {en} } @article{BaeckerKochEibenetal.2017, author = {B{\"a}cker, Matthias and Koch, Claudia and Eiben, Sabine and Geiger, Fania and Eber, Fabian and Gliemann, Hartmut and Poghossian, Arshak and Wege, Christina and Sch{\"o}ning, Michael Josef}, title = {Tobacco mosaic virus as enzyme nanocarrier for electrochemical biosensors}, series = {Sensors and Actuators B: Chemical}, volume = {238}, journal = {Sensors and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2016.07.096}, pages = {716 -- 722}, year = {2017}, abstract = {The conjunction of (bio-)chemical recognition elements with nanoscale biological building blocks such as virus particles is considered as a very promising strategy for the creation of biohybrids opening novel opportunities for label-free biosensing. This work presents a new approach for the development of biosensors using tobacco mosaic virus (TMV) nanotubes or coat proteins (CPs) as enzyme nanocarriers. Sensor chips combining an array of Pt electrodes loaded with glucose oxidase (GOD)-modified TMV nanotubes or CP aggregates were used for amperometric detection of glucose as a model system for the first time. The presence of TMV nanotubes or CPs on the sensor surface allows binding of a high amount of precisely positioned enzymes without substantial loss of their activity, and may also ensure accessibility of their active centers for analyte molecules. Specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CPs was achieved via bioaffinity binding. These layouts were tested in parallel with glucose sensors with adsorptively immobilized [SA]-GOD, as well as [SA]-GOD crosslinked with glutardialdehyde, and came out to exhibit superior sensor performance. The achieved results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for future applications in biosensorics and biochips.}, language = {en} } @article{MolinnusSorichBartzetal.2016, author = {Molinnus, Denise and Sorich, Maren and Bartz, Alexander and Siegert, Petra and Willenberg, Holger S. and Lisdat, Fred and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Towards an adrenaline biosensor based on substrate recycling amplification in combination with an enzyme logic gate}, series = {Sensors and Actuators B: Chemical}, volume = {237}, journal = {Sensors and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2016.06.064}, pages = {190 -- 195}, year = {2016}, abstract = {An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer's solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure.}, language = {en} } @article{WuPoghossianBronderetal.2016, author = {Wu, Chunsheng and Poghossian, Arshak and Bronder, Thomas and Sch{\"o}ning, Michael Josef}, title = {Sensing of double-stranded DNA molecules by their intrinsic molecular charge using the light-addressable potentiometric sensor}, series = {Sensors and Actuators B: Chemical}, journal = {Sensors and Actuators B: Chemical}, number = {229}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2016.02.004}, pages = {506 -- 512}, year = {2016}, abstract = {A multi-spot light-addressable potentiometric sensor (LAPS), which belongs to the family of semiconductor field-effect devices, was applied for label-free detection of double-stranded deoxyribonucleic acid (dsDNA) molecules by their intrinsic molecular charge. To reduce the distance between the DNA charge and sensor surface and thus, to enhance the electrostatic coupling between the dsDNA molecules and the LAPS, the negatively charged dsDNA molecules were electrostatically adsorbed onto the gate surface of the LAPS covered with a positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)). The surface potential changes in each spot of the LAPS, induced by the layer-by-layer adsorption of a PAH/dsDNA bilayer, were recorded by means of photocurrent-voltage and constant-photocurrent measurements. In addition, the surface morphology of the gate surface before and after consecutive electrostatic adsorption of PAH and dsDNA layers was studied by atomic force microscopy measurements. Moreover, fluorescence microscopy was used to verify the successful adsorption of dsDNA molecules onto the PAH-modified LAPS surface. A high sensor signal of 25 mV was registered after adsorption of 10 nM dsDNA molecules. The lower detection limit is down to 0.1 nM dsDNA. The obtained results demonstrate that the PAH-modified LAPS device provides a convenient and rapid platform for the direct label-free electrical detection of in-solution hybridized dsDNA molecules.}, language = {en} } @inproceedings{PoghossianBronderWuetal.2015, author = {Poghossian, Arshak and Bronder, Thomas and Wu, Chunsheng and Sch{\"o}ning, Michael Josef}, title = {Label-free sensing of biomolecules by their intrinsic molecular charge using field-effect devices}, series = {Semiconductor Micro- and Nanoelectonics : Proceedings of the tenth international conference, Yerevan, Armenia, September 11-13}, booktitle = {Semiconductor Micro- and Nanoelectonics : Proceedings of the tenth international conference, Yerevan, Armenia, September 11-13}, isbn = {978-5-8084-1991-9}, pages = {61 -- 63}, year = {2015}, language = {en} } @incollection{PoghossianSchusserBaeckeretal.2015, author = {Poghossian, Arshak and Schusser, Sebastian and B{\"a}cker, M. and Leinhos, Marcel and Sch{\"o}ning, Michael Josef}, title = {Real-time in-situ electrical monitoring of the degradation of biopolymers using semiconductor field-effect devices}, series = {Biodegradable biopolymers. Vol. 1}, booktitle = {Biodegradable biopolymers. Vol. 1}, publisher = {Nova Science Publ.}, address = {Hauppauge}, isbn = {978-1-63483-632-6}, pages = {135 -- 153}, year = {2015}, language = {en} } @article{SchusserKrischerBaeckeretal.2015, author = {Schusser, Sebastian and Krischer, Maximillian and B{\"a}cker, Matthias and Poghossian, Arshak and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Monitoring of the Enzymatically Catalyzed Degradation of Biodegradable Polymers by Means of Capacitive Field-Effect Sensors}, series = {Analytical Chemistry}, volume = {87}, journal = {Analytical Chemistry}, number = {13}, publisher = {ACS Publications}, address = {Washington, DC}, issn = {1520-6882}, doi = {10.1021/acs.analchem.5b00617}, pages = {6607 -- 6613}, year = {2015}, abstract = {Designing novel or optimizing existing biodegradable polymers for biomedical applications requires numerous tests on the effect of substances on the degradation process. In the present work, polymer-modified electrolyte-insulator-semiconductor (PMEIS) sensors have been applied for monitoring an enzymatically catalyzed degradation of polymers for the first time. The thin films of biodegradable polymer poly(d,l-lactic acid) and enzyme lipase were used as a model system. During degradation, the sensors were read-out by means of impedance spectroscopy. In order to interpret the data obtained from impedance measurements, an electrical equivalent circuit model was developed. In addition, morphological investigations of the polymer surface have been performed by means of in situ atomic force microscopy. The sensor signal change, which reflects the progress of degradation, indicates an accelerated degradation in the presence of the enzyme compared to hydrolysis in neutral pH buffer media. The degradation rate increases with increasing enzyme concentration. The obtained results demonstrate the potential of PMEIS sensors as a very promising tool for in situ and real-time monitoring of degradation of polymers.}, language = {en} } @article{BronderPoghossianSchejaetal.2015, author = {Bronder, Thomas and Poghossian, Arshak and Scheja, Sabrina and Wu, Chunsheng and Keusgen, Michael and Mewes, Dieter and Sch{\"o}ning, Michael Josef}, title = {DNA Immobilization and Hybridization Detection by the Intrinsic Molecular Charge Using Capacitive Field-Effect Sensors Modified with a Charged Weak Polyelectrolyte Layer}, series = {Applied Materials \& Interfaces}, volume = {36}, journal = {Applied Materials \& Interfaces}, number = {7}, publisher = {American Chemical Society}, address = {Washington, DC}, doi = {10.1021/acsami.5b05146}, pages = {20068 -- 20075}, year = {2015}, abstract = {Miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge favor the semiconductor field-effect platform as one of the most attractive approaches for the development of label-free DNA chips. In this work, a capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensor covered with a layer-by-layer prepared, positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)) was used for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization. The negatively charged probe single-stranded DNA (ssDNA) molecules were electrostatically adsorbed onto the positively charged PAH layer, resulting in a preferentially flat orientation of the ssDNA molecules within the Debye length, thus yielding a reduced charge-screening effect and a higher sensor signal. Each sensor-surface modification step (PAH adsorption, probe ssDNA immobilization, hybridization with complementary target DNA (cDNA), reducing an unspecific adsorption by a blocking agent, incubation with noncomplementary DNA (ncDNA) solution) was monitored by means of capacitance-voltage and constant-capacitance measurements. In addition, the surface morphology of the PAH layer was studied by atomic force microscopy and contact-angle measurements. High hybridization signals of 34 and 43 mV were recorded in low-ionic strength solutions of 10 and 1 mM, respectively. In contrast, a small signal of 4 mV was recorded in the case of unspecific adsorption of fully mismatched ncDNA. The density of probe ssDNA and dsDNA molecules as well as the hybridization efficiency was estimated using the experimentally measured DNA immobilization and hybridization signals and a simplified double-layer capacitor model. The results of field-effect experiments were supported by fluorescence measurements, verifying the DNA-immobilization and hybridization event.}, language = {en} } @article{BronderPoghossianSchejaetal.2015, author = {Bronder, Thomas and Poghossian, Arshak and Scheja, S. and Wu, Chunsheng and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Electrostatic Detection of Unlabelled Single- and Double-stranded DNA Using Capacitive Field-effect Devices Functionalized with a Positively Charged Polyelectrolyte Layer}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.710}, pages = {544 -- 547}, year = {2015}, abstract = {Capacitive field-effect electrolyte-insulator-semiconductor sensors consisting of an Al-p-Si-SiO2 structure have been used for the electrical detection of unlabelled single- and double-stranded DNA (dsDNA) molecules by their intrinsic charge. A simple functionalization protocol based on the layer-by-layer (LbL) technique was used to prepare a weak polyelectrolyte/probe-DNA bilayer, followed by the hybridization with complementary target DNA molecules. Due to the flat orientation of the LbL-adsorbed DNA molecules, a high sensor signal has been achieved. In addition, direct label-free detection of in-solution hybridized dsDNA molecules has been studied.}, language = {en} } @article{SchusserKrischerMolinetal.2015, author = {Schusser, Sebastian and Krischer, M. and Molin, D. G. M. and Akker, N. M. S. van den and B{\"a}cker, Matthias and Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Sensor System for in-situ and Real-time Monitoring of Polymer (bio) degradation}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.815}, pages = {948 -- 951}, year = {2015}, abstract = {A sensor system for investigating (bio)degradationprocesses of polymers is presented. The system utilizes semiconductor field-effect sensors and is capable of monitoring the degradation process in-situ and in real-time. The degradation of the polymer poly(d,l-lactic acid) is exemplarily monitored in solutions with different pH value, pH-buffer solution containing the model enzyme lipase from Rhizomucormiehei and cell-culture medium containing supernatants from stimulated and non-stimulated THP-1-derived macrophages mimicking activation of the immune system.}, language = {en} }