@article{ReisertGeisslerWeileretal.2015, author = {Reisert, Steffen and Geissler, H. and Weiler, C. and Wagner, P. and Sch{\"o}ning, Michael Josef}, title = {Multiple sensor-type system for monitoring the microbicidal effectiveness of aseptic sterilisation processes}, series = {Food control}, volume = {47}, journal = {Food control}, issn = {1873-7129 (E-Journal); 0956-7135 (Print)}, doi = {10.1016/j.foodcont.2014.07.063}, pages = {615 -- 622}, year = {2015}, abstract = {The present work describes a novel multiple sensor-type system for the real-time analysis of aseptic sterilisation processes employing gaseous hydrogen peroxide (H2O2) as a sterilant. The inactivation kinetics of Bacillus atrophaeus by gaseous H2O2 have been investigated by means of a methodical calibration experiment, taking into account the process variables H2O2 concentration, humidity and gas temperature. It has been found that the microbicidal effectiveness at H2O2 concentrations above 2\% v/v is largely determined by the concentration itself, while at lower H2O2 concentrations, the gas temperature and humidity play a leading role. Furthermore, the responses of different types of gas sensors towards the influencing factors of the sterilisation process have been analysed within the same experiment. Based on a correlation established between the inactivation kinetics and the sensor responses, a calorimetric H2O2 sensor and a metal-oxide semiconductor (MOX) sensor have been identified as possible candidates for monitoring the microbicidal effectiveness of aseptic sterilisation processes employing gaseous H2O2. Therefore, two linear models that describe the relationship between sensor response and microbicidal effectiveness have been proposed.}, language = {en} } @article{YoshinobuMiyamotoWagneretal.2015, author = {Yoshinobu, Tatsuo and Miyamoto, Ko-ichiro and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Recent developments of chemical imaging sensor systems based on the principle of the light-addressable potentiometric sensor}, series = {Sensors and actuators B: Chemical}, volume = {207, Part B}, journal = {Sensors and actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-3077 (E-Journal); 0925-4005 (Print)}, doi = {10.1016/j.snb.2014.09.002}, pages = {926 -- 932}, year = {2015}, abstract = {The light-addressable potentiometric sensor (LAPS) is an electrochemical sensor with a field-effect structure to detect the variation of the Nernst potential at its sensor surface, the measured area on which is defined by illumination. Thanks to this light-addressability, the LAPS can be applied to chemical imaging sensor systems, which can visualize the two-dimensional distribution of a particular target ion on the sensor surface. Chemical imaging sensor systems are expected to be useful for analysis of reaction and diffusion in various electrochemical and biological samples. Recent developments of LAPS-based chemical imaging sensor systems, in terms of the spatial resolution, measurement speed, image quality, miniaturization and integration with microfluidic devices, are summarized and discussed.}, language = {en} } @article{PoghossianBaeckerMayeretal.2015, author = {Poghossian, Arshak and B{\"a}cker, Matthias and Mayer, Dirk and Sch{\"o}ning, Michael Josef}, title = {Gating capacitive field-effect sensors by the charge of nanoparticle/molecule hybrids}, series = {Nanoscale}, journal = {Nanoscale}, publisher = {Royal Society of Chemistry (RSC)}, address = {Cambridge}, issn = {2040-3372 (E-Journal); 2040-3364 (Print)}, doi = {10.1039/C4NR05987E}, pages = {1023 -- 1031}, year = {2015}, language = {en} } @article{SchusserPoghossianBaeckeretal.2015, author = {Schusser, Sebastian and Poghossian, Arshak and B{\"a}cker, Matthias and Krischer, M. and Leinhos, Marcel and Wagner, P. and Sch{\"o}ning, Michael Josef}, title = {An application of field-effect sensors for in-situ monitoring of degradation of biopolymers}, series = {Sensors and actuators B: Chemical}, volume = {207, Part B}, journal = {Sensors and actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-3077 (E-Journal); 0925-4005 (Print)}, doi = {10.1016/j.snb.2014.10.058}, pages = {954 -- 959}, year = {2015}, abstract = {The characterization of the degradation kinetics of biodegradable polymers is mandatory with regard to their proper application. In the present work, polymer-modified electrolyte-insulator-semiconductor (PMEIS) field-effect sensors have been applied for in-situ monitoring of the pH-dependent degradation kinetics of the commercially available biopolymer poly(d,l-lactic acid) (PDLLA) in buffer solutions from pH 3 to pH 13. PDLLA films of 500 nm thickness were deposited on the surface of an Al-p-Si-SiO2-Ta2O5 structure from a polymer solution by means of spin-coating method. The PMEIS sensor is, in principle, capable to detect any changes in bulk, surface and interface properties of the polymer induced by degradation processes. A faster degradation has been observed for PDLLA films exposed to alkaline solutions (pH 9, pH 11 and pH 13).}, language = {en} } @article{MuribYeapMartensetal.2015, author = {Murib, M. S. and Yeap, W. S. and Martens, D. and Liu, X. and Bienstman, P. and Fahlman, M. and Sch{\"o}ning, Michael Josef and Michiels, L. and Haenen, K. and Serpeng{\"u}zel, A. and Wagner, Patrick}, title = {Photonic studies on polymer-coated sapphire-spheres : a model system for biological ligands}, series = {Sensors and actuators A: Physical}, volume = {222}, journal = {Sensors and actuators A: Physical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-3069 (E-Journal); 0924-4247 (Print)}, doi = {10.1016/j.sna.2014.11.024}, pages = {212 -- 219}, year = {2015}, abstract = {In this study we show an optical biosensor concept, based on elastic light scattering from sapphire microspheres. Transmitted and elastic scattering intensity of the microspheres (radius 500 μm, refractive index 1.77) on an optical fiber half coupler is analyzed at 1510 nm. The 0.43 nm angular mode spacing of the resonances is comparable to the angular mode spacing value estimated using the optical size of the microsphere. The spectral linewidths of the resonances are in the order of 0.01 nm, which corresponds to quality factors of approximately 105. A polydopamine layer is used as a functionalizing agent on sapphire microspherical resonators in view of biosensor implementation. The varying layer thickness on the microsphere is determined as a function of the resonance wavelength shift. It is shown that polymer functionalization has a minor effect on the quality factor. This is a promising step toward the development of an optical biosensor.}, language = {en} } @article{WuBronderPoghossianetal.2015, author = {Wu, Chunsheng and Bronder, Thomas and Poghossian, Arshak and Werner, Frederik and Sch{\"o}ning, Michael Josef}, title = {Label-free detection of DNA using light-addressable potentiometric sensor modified with a positively charged polyelectrolyte layer}, series = {Nanoscale}, volume = {14}, journal = {Nanoscale}, number = {7}, publisher = {Royal Society of Chemistry (RSC)}, address = {Cambridge}, doi = {10.1039/C4NR07225A}, pages = {6143 -- 6150}, year = {2015}, abstract = {A multi-spot (16 spots) light-addressable potentiometric sensor (MLAPS) consisting of an Al-p-Si-SiO2 structure modified with a weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)) was applied for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge for the first time. To achieve a preferentially flat orientation of DNA strands and thus, to reduce the distance between the DNA charge and MLAPS surface, the negatively charged probe single-stranded DNAs (ssDNA) were electrostatically adsorbed onto the positively charged PAH layer using a simple layer-by-layer (LbL) technique. In this way, more DNA charge can be positioned within the Debye length, yielding a higher sensor signal. The surface potential changes in each spot induced due to the surface modification steps (PAH adsorption, probe ssDNA immobilization, hybridization with complementary target DNA (cDNA), non-specific adsorption of mismatched ssDNA) were determined from the shifts of photocurrent-voltage curves along the voltage axis. A high sensor signal of 83 mV was registered after immobilization of probe ssDNA onto the PAH layer. The hybridization signal increases from 5 mV to 32 mV with increasing the concentration of cDNA from 0.1 nM to 5 μM. In contrast, a small signal of 5 mV was recorded in the case of non-specific adsorption of fully mismatched ssDNA (5 μM). The obtained results demonstrate the potential of the MLAPS in combination with the simple and rapid LbL immobilization technique as a promising platform for the future development of multi-spot light-addressable label-free DNA chips with direct electrical readout.}, language = {en} } @article{BegingLeinhosJablonskietal.2015, author = {Beging, Stefan and Leinhos, Marcel and Jablonski, Melanie and Poghossian, Arshak and Sch{\"o}ning, Michael Josef}, title = {Studying the spatially resolved immobilisation of enzymes on a capacitive field-effect structure by means of nano-spotting}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431891}, pages = {1353 -- 1358}, year = {2015}, language = {en} } @article{PoghossianKatzSchoening2015, author = {Poghossian, Arshak and Katz, Evgeny and Sch{\"o}ning, Michael Josef}, title = {Enzyme logic AND-Reset and OR-Reset gates based on a field-effect electronic transducer modified with multi-enzyme membrane}, series = {Chemical Communications}, volume = {51}, journal = {Chemical Communications}, publisher = {Royal Society of Chemistry (RSC)}, address = {Cambridge}, doi = {10.1039/C5CC01362C}, pages = {6564 -- 6567}, year = {2015}, abstract = {Capacitive field-effect sensors modified with a multi-enzyme membrane have been applied for an electronic transduction of biochemical signals processed by enzyme-based AND-Reset and OR-Reset logic gates. The local pH change at the sensor surface induced by the enzymatic reaction was used for the activation of the Reset function for the first time.}, language = {en} } @article{OberlaenderBrommWendeleretal.2015, author = {Oberl{\"a}nder, Jan and Bromm, Alexander and Wendeler, Luisa and Iken, Heiko and Palomar Duran, Marlena and Greeff, Anton and Kirchner, Patrick and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Towards a biosensor to monitor the sterilisation efficiency of aseptic filling machines}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431900}, pages = {1299 -- 1305}, year = {2015}, abstract = {Sterilisation processes are compulsory in medicine, pharmacy, and food industries to prevent infections of consumers and microbiological contaminations of products. Monitoring the sterilisation by conventional microbiological methods is time- and lab-consuming. To overcome this problem, in this work a novel biosensor has been proposed. The sensor enables a fast method to evaluate sterilisation processes. By means of thin-film technology the sensor's transducer structures in form of IDEs (interdigitated electrodes) have been fabricated on a silicon substrate. Physical characterisation of the developed sensor was done by AFM, SEM, and profilometry. Impedance analyses were conducted for the electrical characterisation. As microbiological layer spores of B. atrophaeus have been immobilised on the sensing structure; spores of this type are a well-known sterilisation test organism. Impedance measurements at a fixed frequency over time were performed to monitor the immobilisation process. A sterilisation process according to aseptic filling machines was applied to demonstrate the sensor functionality. After both, immobilisation and sterilisation, a change in impedance could successfully be detected.}, language = {en} } @article{HuckPoghossianBaeckeretal.2015, author = {Huck, Christina and Poghossian, Arshak and B{\"a}cker, Matthias and Reisert, Steffen and Kramer, Friederike and Begoyan, Vardges K. and Buniatyan, Vahe V. and Sch{\"o}ning, Michael Josef}, title = {Multi-parameter sensing using high-k oxide of barium strontium titanate}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431911}, pages = {1259}, year = {2015}, abstract = {High-k perovskite oxide of barium strontium titanate (BST) represents a very attractive multi-functional transducer material for the development of (bio-)chemical sensors. In this work, a Si-based sensor chip containing Pt interdigitated electrodes covered with a thin BST layer (485 nm) has been developed for multi-parameter chemical sensing. The chip has been applied for the contactless measurement of the electrolyte conductivity, the detection of adsorbed charged macromolecules (positively charged polyelectrolytes of polyethylenimine) and the concentration of hydrogen peroxide (H2O2) vapor. The experimental results of functional testing of individual sensors are presented. The mechanism of the BST sensitivity to charged polyelectrolytes and H2O2 vapor has been proposed and discussed.}, language = {en} } @article{JildehWagnerSchoeningetal.2015, author = {Jildeh, Zaid B. and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Pieper, Martin}, title = {Simulating the electromagnetic-thermal treatment of thin aluminium layers for adhesion improvement}, series = {Physica status solidi (a)}, volume = {Vol. 212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431893}, pages = {1234 -- 1241}, year = {2015}, abstract = {A composite layer material used in packaging industry is made from joining layers of different materials using an adhesive. An important processing step in the production of aluminium-containing composites is the surface treatment and consequent coating of adhesive material on the aluminium surface. To increase adhesion strength between aluminium layer and the adhesive material, the foil is heat treated. For efficient heating, induction heating was considered as state-of-the-art treatment process. Due to the complexity of the heating process and the unpredictable nature of the heating source, the control of the process is not yet optimised. In this work, a finite element analysis of the process was established and various process parameters were studied. The process was simplified and modelled in 3D. The numerical model contains an air domain, an aluminium layer and a copper coil fitted with a magnetic field concentrating material. The effect of changing the speed of the aluminium foil (or rolling speed) was studied with the change of the coil current. Statistical analysis was used for generating a general control equation of coil current with changing rolling speed.}, language = {en} } @article{PilasIkenSelmeretal.2015, author = {Pilas, Johanna and Iken, Heiko and Selmer, Thorsten and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Development of a multi-parameter sensor chip for the simultaneous detection of organic compounds in biogas processes}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431894}, pages = {1306 -- 1312}, year = {2015}, abstract = {An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage.}, language = {en} } @article{BreuerRaueKirschbaumetal.2015, author = {Breuer, Lars and Raue, Markus and Kirschbaum, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431944}, pages = {1368 -- 1374}, year = {2015}, abstract = {Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed.}, language = {en} } @article{DantismTakenagaWagneretal.2015, author = {Dantism, S. and Takenaga, S. and Wagner, P. and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Light-addressable Potentiometric Sensor (LAPS) Combined with Multi-chamber Structures to Investigate the Metabolic Activity of Cells}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.647}, pages = {384 -- 387}, year = {2015}, abstract = {LAPS are field-effect-based potentiometric sensors which are able to monitor analyte concentrations in a spatially resolved manner. Hence, a LAPS sensor system is a powerful device to record chemical imaging of the concentration of chemical species in an aqueous solution, chemical reactions, or the growth of cell colonies on the sensor surface, to record chemical images. In this work, multi-chamber 3D-printed structures made out of polymer (PP-ABS) were combined with LAPS chips to analyse differentially and simultaneously the metabolic activity of Escherichia coli K12 and Chinese hamster ovary (CHO) cells, and the responds of those cells to the addition of glucose solution.}, language = {en} } @article{MolinnusBaeckerSiegertetal.2015, author = {Molinnus, Denise and B{\"a}cker, Matthias and Siegert, Petra and Willenberg, H. and Poghossian, Arshak and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Detection of Adrenaline Based on Substrate Recycling Amplification}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.708}, pages = {540 -- 543}, year = {2015}, abstract = {An amperometric enzyme biosensor has been applied for the detection of adrenaline. The adrenaline biosensor has been prepared by modification of an oxygen electrode with the enzyme laccase that operates at a broad pH range between pH 3.5 to pH 8. The enzyme molecules were immobilized via cross-linking with glutaraldehyde. The sensitivity of the developed adrenaline biosensor in different pH buffer solutions 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} } @article{PilasMarianoKeusgenetal.2015, author = {Pilas, Johanna and Mariano, K. and Keusgen, M. and Selmer, Thorsten and Sch{\"o}ning, Michael Josef}, title = {Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.702}, pages = {532 -- 535}, year = {2015}, language = {en} } @article{MiyamotoBingWagneretal.2015, author = {Miyamoto, Ko-ichiro and Bing, Yu and Wagner, Torsten and Yoshinobu, Tatsuo and Sch{\"o}ning, Michael Josef}, title = {Visualization of Defects on a Cultured Cell Layer by Utilizing Chemical Imaging Sensor}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.806}, pages = {936 -- 939}, year = {2015}, abstract = {The chemical imaging sensor is a field-effect sensor which is able to visualize both the distribution of ions (in LAPS mode) and the distribution of impedance (in SPIM mode) inthe sample. In this study, a novel wound-healing assay is proposed, in which the chemical imaging sensor operated in SPIM mode is applied to monitor the defect of a cell layer brought into proximity of the sensing surface.A reduced impedance inside the defect, which was artificially formed ina cell layer, was successfully visualized in a photocurrent image.}, 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{TakenagaSchneiderErbayetal.2015, author = {Takenaga, Shoko and Schneider, Benno and Erbay, E. and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and Wagner, Torsten}, title = {Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201532053}, pages = {1347 -- 1352}, year = {2015}, abstract = {A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation.}, language = {en} }