Journal articles, book contributions, reviews

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Jaster, Jonas; Dreßler, Elias; Geitner, Robert; Groß, Gregor Alexander
Synthesis and spectroscopic characterization of furan-2-carbaldehyde-d. - In: Molbank, ISSN 1422-8599, Bd. 2023 (2023), 2, M1654, S. 1-9

Here, we present a protocol for the one-step synthesis of the title compound in quantitative yield using adapted Vilsmeier conditions. The product was characterized by 1H-,2H-,13C-NMR-, as well as IR and Raman spectroscopy. Spectral data are given in detail.



https://doi.org/10.3390/M1654
Köhler, Michael; Ehrhardt, Linda; Cao-Riehmer, Jialan; Möller, Frances; Schüler, Tim; Günther, Mike
Beta-diversity enhancement by archaeological structures: bacterial communities of an historical tannery area of the city of Jena (Germany) reflect the ancient human impact. - In: Ecologies, ISSN 2673-4133, Bd. 4 (2023), 2, S. 325-343

Soil samples taken during archaeological investigations of a historical tannery area in the eastern suburb of the medieval city of Jena have been investigated by 16S r-RNA gene profiling. The analyses supplied a large spectrum of interesting bacteria, among them Patescibacteria, Methylomirabilota, Asgardarchaeota, Zixibacteria, Sideroxydans and Sulfurifustis. Samples taken from soil inside the residues of large vats show large differences in comparison to the environmental soil. The PCAs for different abundance classes clearly reflect the higher similarity between the bacterial communities of the outside-vat soils in comparison with three of the inside-vat soil communities. Two of the in-side vat soils are distinguishable from the other samples by separate use of each abundance class, but classes of lower abundance are better applicable than the highly abundant bacteria for distinguishing the sampling sites by PCA, in general. This effect could be interpreted by the assumption that less abundant types in the 16S r-RNA data tend to be more related to an earlier state of soil development than the more abundant and might be, therefore, better suited for conclusions on the state of the soils in an earlier local situation. In addition, the analyses allowed identification of specific features of each single sampling site. In one site specifically, DNA hints of animal residue-related bacteria were found. Obviously, the special situation in the in-site vat soils contributes to the diversity of the place, and enhances its Beta-diversity. Very high abundancies of several ammonia-metabolizing and of sulphur compound-oxidizing genera in the metagenomics data can be interpreted as an echo of the former tannery activities using urine and processing keratin-rich animal materials. In summary, it can be concluded that the 16S r-RNA analysis of such archaeological places can supply a lot of data related to ancient human impacts, representing a kind of “ecological memory of soil”.



https://doi.org/10.3390/ecologies4020021
Tsierkezos, Nikos; Freiberger, Emma; Ritter, Uwe; Krischok, Stefan; Ullmann, Fabian; Köhler, Michael
Application of nitrogen-doped multi-walled carbon nanotubes decorated with gold nanoparticles in biosensing. - In: Journal of solid state electrochemistry, ISSN 1433-0768, Bd. 27 (2023), 10, S. 2645-2658

Novel films consisting of nitrogen-doped multi-walled carbon nanotubes (N-MWCNTs) were fabricated by means of chemical vapor deposition technique and decorated with gold nanoparticles (AuNPs) possessing diameter of 14.0 nm. Electron optical microscopy analysis reveals that decoration of N-MWCNTs with AuNPs does not have any influence on their bamboo-shaped configuration. The electrochemical response of fabricated composite films, further denoted as N-MWCNTs/AuNPs, towards oxidation of dopamine (DA) to dopamine-o-quinone (DAQ) in the presence of ascorbic acid (AA) and uric acid (UA) was probed in real pig serum by means of cyclic voltammetry (CV) and square wave voltammetry (SWV). The findings demonstrate that N-MWCNTs/AuNPs exhibit slightly greater electrochemical response and sensitivity towards DA/DAQ compared to unmodified N-MWCNTs. It is, consequently, obvious that AuNPs improve significantly the electrochemical response and detection ability of N-MWCNTs. The electrochemical response of N-MWCNTs/AuNPs towards DA/DAQ seems to be significantly greater compared to that of conventional electrodes, such as platinum and glassy carbon. The findings reveal that N-MWCNTs/AuNPs could serve as powerful analytical sensor enabling analysis of DA in real serum samples.



https://doi.org/10.1007/s10008-023-05562-2
Xie, Ting; Ehrhardt, Linda; Günther, Mike; Köhler, Michael; Cao-Riehmer, Jialan
Current to biomass: media optimization and strain selection from cathode-associated microbial communities in a two-chamber electro-cultivation reactor. - In: Environments, ISSN 2076-3298, Bd. 10 (2023), 6, 97, S. 1-19

Cathode-associated microbial communities (caMCs) are the functional key elements in the conversion of excess electrical energy into biomass. In this study, we investigated the development of electrochemical caMCs based on two-chamber microbial electrolytic cells (MECs) after optimization of media composition. Microbial communities obtained from a historical soil sample were inoculated into the cathode chamber of MECs. The inorganic medium with (A) carbon dioxide in air or (B) 100 mM sodium bicarbonate as carbon source was used in the absence of any organic carbon source. After 12 days of operation, the experimental results showed that (1) the bacterial community in group B exhibited lush growth and (2) a single strain TX168 Epilithonimonas bovis isolated from group A indicated electrochemical activity and synthesized large volumes of biomass using sodium bicarbonate. We also analyzed the caMCs of the MECs and reference samples without electro-cultivation using 16S rRNA gene sequencing. The results showed that the caMCs of MECs in groups A and B were dominated by the genera Acinetobacter and Pseudomonas. The caMCs were further inoculated and cultured on different agars to isolate specific electroactive bacterial strains. Overall, our study highlights the possibility of converting excess energy into biomass by electro-cultivation and the importance of selecting appropriate media to enrich specific microbial communities and single strains in MECs.



https://doi.org/10.3390/environments10060097
Mazétyté-Stasinskiené, Raminta; Kronfeld, Klaus-Peter; Köhler, Michael
Five-level structural hierarchy: microfluidically supported synthesis of core-shell microparticles containing nested set of dispersed metal and polymer micro and nanoparticles. - In: Particle & particle systems characterization, ISSN 1521-4117, Bd. 14 (2023), 10, 2300030, S. 1-13

This study presents the development of a hierarchical design concept for the synthesis of multi-scale polymer particles with up to five levels of organization. The synthesis of core-shell microparticles containing nested sets of dispersed metal and polymer micro- and nanoparticles is achieved through in situ photopolymerization using a double co-axial capillaries microfluidic device. The flow rates of the carrier, shell, and core phases are optimized to control particle size and result in stable core-shell particles with well-dispersed three-level composites in the shell matrix. The robustness and reversibility of these core-shell particles are demonstrated through five cycles of drying and re-swelling, showing that the size and structure of core-shell particles remain unchanged. Additionally, the permeability and mobility of dye molecules within the shell matrix are tested and showed that different molecular weight dyes have different penetration times. This study highlights the potential of microfluidics as a powerful tool for the controlled and precise synthesis of complex structured materials and demonstrates the versatility and potential of these core-shell particles for sensing applications as particle-based surface-enhanced Raman scattering (SERS).



https://doi.org/10.1002/ppsc.202300030
Köhler, Michael; Ehrhardt, Linda; Günther, Mike
Archaeal and extremophilic bacteria from different archaeological excavation sites. - In: International journal of molecular sciences, ISSN 1422-0067, Bd. 24 (2023), 6, 5519, S. 1-18

Beside natural factors, human activities are important for the development of microbiomes. Thus, local soil bacterial communities are affected by recent activities such as agriculture, mining and industry. In addition, ancient human impacts dating back centuries or millennia have changed soils and can emboss the recent bacterial communities up to now, representing a certain long-term "memory of soil". Soil samples from five different archaeological excavation places were investigated for the presence of Archaea with a Next Generation Sequencing (NGS) analysis of the DNA coding for 16S r-RNA sequences. It was found that the abundance of Archaea differs strongly between less than one and more than 40 percent of bacteria. A Principal Component Analysis (PCA) of all samples shows that the archaeological excavation places can be distinguished from each other by the archaeal component of soil bacterial communities, which presents a typical pattern for each place. Most samples are marked by the dominance of Crenarchaeota, which are presented mainly by ammonia-related types. High contents of Nanoarchaeaota have been observed in one ash deposit of a historical saline and all samples of a historical tannery area. These samples are also marked by a significant presence of Dadabacteria. The specific abundancies of special Archaea - among them ammonia-oxidizing and sulphur-related types - are due obviously to former human activities and support the concept of the "ecological memory of soil".



https://doi.org/10.3390/ijms24065519
Xie, Ting; Köhler, Michael; Heyder, Stefan; Günther, Mike; Cao-Riehmer, Jialan
Microfluidically-assisted isolation and characterization of Achromobacter spanius from soils for microbial degradation of synthetic polymers and organic solvents. - In: Environments, ISSN 2076-3298, Bd. 9 (2022), 12, 147, S. 1-17

A micro segmented-flow approach was utilized for the isolation soil bacteria that can degrade synthetic polymers as polyethylene glycols (PEG) and polyacrylamide (PAM). We had been able to obtain many strains; among them, five Achromobacter spanius strains from soil samples of specific sampling sites that were connected with ancient human impacts. In addition to the characterization of community responses and isolating single strains, this microfluidic approach allowed for investigation of the susceptibility of Achromobacter spanius strains against three synthetic polymers, including PEG, PAM, and Polyvinylpyrrolidone (PVP) and two organic solvents known as 1,4-dioxane and diglyme. The small stepwise variation of effector concentrations in 500 nL droplets provides a detailed reflection of the concentration-dependent response of bacterial growth and endogenous autofluorescence activity. As a result, all five strains can use PEG600 as carbon source. Furthermore, all strains showed similar dose-response characteristics in 1,4-dioxane and diglyme. However, significantly different PAM- and PVP-tolerances were found for these strains. Samples from the surface soil of prehistorical rampart areas supplied a strain capable of degradation of PEG, PVP, and PAM. This study demonstrates on the one hand, the potential of microsegment flow for miniaturized dose-response screening studies and its ability to detect novel strains, and on the other hand, two of five isolated Achromobacter spanius strains may be useful in providing optimal growth conditions in bioremediation and biodegradation processes.



https://doi.org/10.3390/environments9120147
Khan, Nida Zaman; Martin, Daniel; Pliquett, Uwe; Zaikou, Yahor; Thomas, Nacke; Heinrich, Doris; Köhler, Michael; Nguyen, Thi-Huong
High-frequency contactless sensor for the detection of heparin-induced thrombocytopenia antibodies via platelet aggregation. - In: International journal of molecular sciences, ISSN 1422-0067, Bd. 23 (2022), 22, 14395, S. 1-13

Heparin-induced thrombocytopenia (HIT), a severe autoimmune disorder, occurs in patients undergoing heparin therapy. The presence of platelet-activating antibodies against platelet factor 4/Heparin in the blood confirms patients suffering from HIT. The most widely used methods for HIT diagnosis are immunoassays but the results only suit to rule out HIT as the assays provide only around 50% specificity. To confirm HIT, samples with positive results in immunoassays are retested in functional assays (>98% specificity) that track platelet-activating antibodies via platelet aggregation. However, the protocols in functional assays are either time-consuming (due to the requirement of the detection of serotonin release) or require highly trained staff for the visualization of platelets. Here, we applied a cheap and easy-to-use contactless sensor, which employs high-frequency microwaves to detect the changes in the resonant frequency caused by platelet aggregation/activation. Analysis of change in conductivity and permittivity allowed us to distinguish between HIT-like (KKO) and non-HIT-like (RTO) antibodies. KKO caused a stronger reduction of conductivity of platelet samples than RTO. Our results imply that the high-frequency contactless sensor can be a promising approach for the development of a better and easier method for the detection of HIT.



https://doi.org/10.3390/ijms232214395
Richter, Felix; Chen, Minqian; Schaub, Patrick; Wüst, Florian; Zhang, Di; Schneider, Steffen; Groß, Gregor Alexander; Mäder, Patrick; Dovzhenko, Oleksandr; Palme, Klaus; Köhler, Michael; Cao-Riehmer, Jialan
Induction of embryogenic development in haploid microspore stem cells in droplet-based microfluidics. - In: Lab on a chip, ISSN 1473-0189, Bd. 22 (2022), 22, S. 4292-4305

This work presents the application of droplet-based microfluidics for the cultivation of microspores from Brassica napus using the doubled haploid technology. Under stress conditions (e.g. heat shock) or by chemical induction a certain fraction of the microspores can be reprogrammed and androgenesis can be induced. This process is an important approach for plant breeding because desired plant properties can be anchored in the germline on a genetic level. However, the reprogramming rate of the microspores is generally very low, increasing it by specific stimulation is, therefore, both a necessary and challenging task. In order to accelerate the optimisation and development process, the application of droplet-based microfluidics can be a promising tool. Here, we used a tube-based microfluidic system for the generation and cultivation of microspores inside nL-droplets. Different factors like cell density, tube material and heat shock conditions were investigated to improve the yield of vital plant organoids. Evaluation and analysis of the stimuli response were done on an image base aided by an artificial intelligence cell detection algorithm. Droplet-based microfluidics allowed us to apply large concentration programs in small test volumes and to screen the best conditions for reprogramming cells by the histone deacetylase inhibitor trichostatin A and for enhancing the yield of vital microspores in droplets. An enhanced reprogramming rate was found under the heat shock conditions at 32 &ring;C for about 3 to 6 days. In addition, the comparative experiment with MTP showed that droplet cultivation with lower cell density (<10 cells per droplet) or adding media after 3 or 6 days significantly positively affects the microspore growth and embryo rate inside 120 nL droplets. Finally, the developed embryos could be removed from the droplets and further grown into mature plants. Overall, we demonstrated that the droplet-based tube system is suitable for implementation in an automated, miniaturized system to achieve the induction of embryogenic development in haploid microspore stem cells of Brassica napus.



https://doi.org/10.1039/D2LC00788F
Cao-Riehmer, Jialan; Russo, David A.; Xie, Ting; Groß, Gregor Alexander; Zedler, Julie
A droplet-based microfluidic platform enables high-throughput combinatorial optimization of cyanobacterial cultivation. - In: Scientific reports, ISSN 2045-2322, Bd. 12 (2022), 15536, S. 1-12

Cyanobacteria are fast-growing, genetically accessible, photoautotrophs. Therefore, they have attracted interest as sustainable production platforms. However, the lack of techniques to systematically optimize cultivation parameters in a high-throughput manner is holding back progress towards industrialization. To overcome this bottleneck, here we introduce a droplet-based microfluidic platform capable of one- (1D) and two-dimension (2D) screening of key parameters in cyanobacterial cultivation. We successfully grew three different unicellular, biotechnologically relevant, cyanobacteria: Synechocystis sp. PCC 6803, Synechococcus elongatus UTEX 2973 and Synechococcus sp. UTEX 3154. This was followed by a highly-resolved 1D screening of nitrate, phosphate, carbonate, and salt concentrations. The 1D screening results suggested that nitrate and/or phosphate may be limiting nutrients in standard cultivation media. Finally, we use 2D screening to determine the optimal N:P ratio of BG-11. Application of the improved medium composition in a high-density cultivation setup led to an increase in biomass yield of up to 15.7%. This study demonstrates that droplet-based microfluidics can decrease the volume required for cyanobacterial cultivation and screening up to a thousand times while significantly increasing the multiplexing capacity. Going forward, microfluidics have the potential to play a significant role in the industrial exploitation of cyanobacteria.



https://doi.org/10.1038/s41598-022-19773-6
Cao-Riehmer, Jialan; Pliquett, Uwe; Yang, Lin; Wiedemeier, Stefan; Cahill, Brian; Köhler, Michael
Contactless optical and impedimetric sensing for droplet-based dose-response investigations of microorganisms. - In: Sensors and actuators, ISSN 0925-4005, Bd. 372 (2022), 132688

The principle of droplet-based microfluidics was used for the characterization of dose/response functions of the soil bacteria Rhodococcus sp. and Chromobacterium vaccinii using a combination of optical and electrical sensors for the detection of bacterial growth and metabolic activity. For electrical characterization, a micro flow-through impedance module was developed which assessed the response of bacterial populations inside 500 nL fluid segments without direct galvanic contact between the electrodes and the electrolyte. It was found that the impedance sensor can detect an increase in cell density and is particularly suited for monitoring the metabolic response due to changes in the cultivation medium inside the separated fluid segments. Due to this sensitivity, the sensor is useful for investigating growing bacteria or cell cultures in small fluid compartments and obtaining highly resolved dose-response functions by microfluid segment sequences. The impedimetric data agree well with the optical data concerning the characteristic response of bacteria populations in the different concentration regions of heavy metal ions. However, the sensor supplies valuable complementary data on metabolic activity in case of low or negligible cell division rates.



https://doi.org/10.1016/j.snb.2022.132688
Ehrhardt, Linda; Günther, Mike; Böhme, Manfred; Köhler, Michael; Cao-Riehmer, Jialan
Three soil bacterial communities from an archaeological excavation site of an ancient coal mine near Bennstedt (Germany) characterized by 16S r-RNA sequencing. - In: Environments, ISSN 2076-3298, Bd. 9 (2022), 9, 115, S. 1-19

This metagenomics investigation of three closely adjacent sampling sites from an archaeological excavation of a pre-industrial coal mining exploration shaft provides detailed information on the composition of the local soil bacterial communities. The observed significant differences between the samples, reflected in the 16S r-RNA analyses, were consistent with the archaeologically observed situation distinguishing the coal seam, the rapidly deposited bright sediment inside an exploration shaft, and the topsoil sediment. In general, the soils were characterized by a dominance of Proteobacteria, Actinobacteria, Acidobacteria, and Archaea, whereas the coal seam was characterized by the highest proportion of Proteobacteria; the topsoil was characterized by very high proportions of Archaea - in particular, Nitrosotaleaceae - and Acidobacteria, mainly of Subgroup 2. Interestingly, the samples of the fast-deposited bright sediment showed a rank function of OTU abundances with disproportional values in the lower abundance range. This could be interpreted as a reflection of the rapid redeposition of soil material during the refilling of the exploration shaft in the composition of the soil bacterial community. This interpretation is supported by the observation of a comparatively high proportion of reads relating to bacteria known to be alkaliphilic in this soil material. In summary, these investigations confirm that metagenomic analyses of soil material from archaeological excavations can provide valuable information about the local soil bacterial communities and the historical human impacts on them.



https://doi.org/10.3390/environments9090115
Mazétyté-Stasinskiené, Raminta; Freiberger, Emma; Täuscher, Eric; Köhler, Michael
Four-level structural hierarchy: microfluidically supported synthesis of polymer particle architectures incorporating fluorescence-labeled components and metal nanoparticles. - In: Langmuir, ISSN 1520-5827, Bd. 38 (2022), 29, S. 8794-8804

Hierarchical assemblies of functional polymer particles are promising due to their surface as well as physicochemical properties. However, hierarchical composites are complex and challenging to form due to the many steps necessary for integrating different components into one system. Highly structured four-level composite particles were formed in a four-step process. First of all, gold (Au) nanoparticles, poly(methyl methacrylate) (PMMA) nanoparticles, and poly(tripropylene glycol diacrylate) (poly-TPGDA) microparticles were individually synthesized. By applying microfluidic techniques, polymer nano- and microparticles were formed with tunable size and surface properties. Afterwards, the negatively charged gold nanoparticles and PMMA particles functionalized with a positively charged surface were mixed to form Au/PMMA assemblies. The Au/PMMA composites were mixed and incubated with poly-TPGDA microparticles to form ternary Au/PMMA/poly-TPGDA assemblies. For the formation of composite-containing microparticles, Au/PMMA/poly-TPGDA composites were dispersed in an aqueous acrylamide-methylenebisacrylamide solution. Monomer droplets were formed in a co-flow microfluidic device and photopolymerized by UV light. In this way, hierarchically structured four-level composites consisting of four different size ranges - 0.025/0.8/30/1000 μm - were obtained. By functionalizing polymer nano- and microparticles with different fluorescent dyes, it was possible to visualize the same composite particle under two different excitation modes (λex = 395-440 and λex = 510-560 nm). The Au/PMMA/poly-TPGDA composite-embedded polyacrylamide microparticles can be potentially used as a model for the creation of composite particles for sensing, catalysis, multilabeling, and biomedical applications.



https://doi.org/10.1021/acs.langmuir.2c00686
Henkel, Thomas; Mayer, Günter; Hampl, Jörg; Cao-Riehmer, Jialan; Ehrhardt, Linda; Schober, Andreas; Groß, Gregor Alexander
From microtiter plates to droplets - there and back again. - In: Micromachines, ISSN 2072-666X, Bd. 13 (2022), 7, 1022, S. 1-13

Droplet-based microfluidic screening techniques can benefit from interfacing established microtiter plate-based screening and sample management workflows. Interfacing tools are required both for loading preconfigured microtiter-plate (MTP)-based sample collections into droplets and for dispensing the used droplets samples back into MTPs for subsequent storage or further processing. Here, we present a collection of Digital Microfluidic Pipetting Tips (DMPTs) with integrated facilities for droplet generation and manipulation together with a robotic system for its operation. This combination serves as a bidirectional sampling interface for sample transfer from wells into droplets (w2d) and vice versa droplets into wells (d2w). The DMPT were designed to fit into 96-deep-well MTPs and prepared from glass by means of microsystems technology. The aspirated samples are converted into the channel-confined droplets’ sequences separated by an immiscible carrier medium. To comply with the demands of dose-response assays, up to three additional assay compound solutions can be added to the sample droplets. To enable different procedural assay protocols, four different DMPT variants were made. In this way, droplet series with gradually changing composition can be generated for, e.g., 2D screening purposes. The developed DMPT and their common fluidic connector are described here. To handle the opposite transfer d2w, a robotic transfer system was set up and is described briefly.



https://doi.org/10.3390/mi13071022
Cao-Riehmer, Jialan; Chande, Charmi; Köhler, Michael
Microtoxicology by microfluidic instrumentation: a review. - In: Lab on a chip, ISSN 1473-0189, Bd. 22 (2022), 14, S. 2600-2623

Microtoxicology is concerned with the toxic effects of small amounts of substances. This review paper discusses the application of small amounts of noxious substances for toxicological investigation in small volumes. The vigorous development of miniaturized methods in microfluidics over the last two decades involves chip-based devices, micro droplet-based procedures, and the use of micro-segmented flow for microtoxicological studies. The studies have shown that the microfluidic approach is particularly valuable for highly parallelized and combinatorial dose-response screenings. Accurate dosing and mixing of effector substances in large numbers of microcompartments supplies detailed data of dose-response functions by highly concentration-resolved assays and allows evaluation of stochastic responses in case of small separated cell ensembles and single cell experiments. The investigations demonstrate that very different biological targets can be studied using miniaturized approaches, among them bacteria, eukaryotic microorganisms, cell cultures from tissues of multicellular organisms, stem cells, and early embryonic states. Cultivation and effector exposure tests can be performed in small volumes over weeks and months, confirming that the microfluicial strategy is also applicable for slow-growing organisms. Here, the state of the art of miniaturized toxicology, particularly for studying antibiotic susceptibility, drug toxicity testing in the miniaturized system like organ-on-chip, environmental toxicology, and the characterization of combinatorial effects by two and multi-dimensional screenings, is discussed. Additionally, this review points out the practical limitations of the microtoxicology platform and discusses perspectives on future opportunities and challenges.



https://doi.org/10.1039/D2LC00268J
Bača, Martin; Brauer, Dana; Klett, Maren; Fernekorn, Uta; Singh, Sukhdeep; Hampl, Jörg; Groß, Gregor Alexander; Mai, Patrick; Friedel, Karin; Schober, Andreas
Automated analysis of acetaminophen toxicity on 3D HepaRG cell culture in microbioreactor. - In: Bioengineering, ISSN 2306-5354, Bd. 9 (2022), 5, 196, S. 1-16

Real-time monitoring of bioanalytes in organotypic cell cultivation devices is a major research challenge in establishing stand-alone diagnostic systems. Presently, no general technical facility is available that offers a plug-in system for bioanalytics in diversely available organotypic culture models. Therefore, each analytical device has to be tuned according to the microfluidic and interface environment of the 3D in vitro system. Herein, we report the design and function of a 3D automated culture and analysis device (3D-ACAD) which actively perfuses a custom-made 3D microbioreactor, samples the culture medium and simultaneously performs capillary-based flow ELISA. A microstructured MatriGrid® has been explored as a 3D scaffold for culturing HepaRG cells, with albumin investigated as a bioanalytical marker using flow ELISA. We investigated the effect of acetaminophen (APAP) on the albumin secretion of HepaRG cells over 96 h and compared this with the albumin secretion of 2D monolayer HepaRG cultures. Automated on-line monitoring of albumin secretion in the 3D in vitro mode revealed that the application of hepatotoxic drug-like APAP results in decreased albumin secretion. Furthermore, a higher sensitivity of the HepaRG cell culture in the automated 3D-ACAD system to APAP was observed compared to HepaRG cells cultivated as a monolayer. The results support the use of the 3D-ACAD model as a stand-alone device, working in real time and capable of analyzing the condition of the cell culture by measuring a functional analyte. Information obtained from our system is compared with conventional cell culture and plate ELISA, the results of which are presented herein.



https://doi.org/10.3390/bioengineering9050196
Visaveliya, Nikunjkumar R.; Mazétyté-Stasinskiené, Raminta; Köhler, Michael
Stationary, continuous, and sequential surface-enhanced raman scattering sensing based on the nanoscale and microscale polymer-metal composite sensor particles through microfluidics: a review. - In: Advanced optical materials, ISSN 2195-1071, Bd. 10 (2022), 7, 2102757, S. 1-25

Surface-enhanced Raman scattering (SERS) is a label-free and accurate analytical technique for the detection of a broad range of various analytes such as, biomolecules, pesticides, petrochemicals, as well as, cellular and other biological systems. A key component for the SERS analysis is the substrate which is required to be equipped with plasmonic features of metal nanostructures that directly interact with light and targeted analytes. Either metal nanoparticles can be deposited on the solid support (glass or silicon) which is suitable for stationary SERS analysis or dispersed in the solution (freely moving nanoparticles). Besides these routinely utilizing SERS substrates, polymer-metal composite particles are promising for sustained SERS analysis where metal nanoparticles act as plasmon-active (hence SERS-active) components and polymer particles act as support to the metal nanoparticles. Composite sensor particles provide 3D interaction possibilities for analytes, suitable for stationary, continuous, and sequential analysis, and they are reusable/regenerated. Therefore, this review is focused on the experimental procedures for the development of multiscale, uniform, and reproducible composite sensor particles together with their application for SERS analysis. The microfluidic reaction technique is highly versatile in the production of uniform and size-tunable composite particles, as well as, for conducting SERS analysis.



https://doi.org/10.1002/adom.202102757
Visaveliya, Nikunjkumar R.; Mazétyté-Stasinskiené, Raminta; Köhler, Michael
General background of SERS sensing and perspectives on polymer-supported plasmon-active multiscale and hierarchical sensor particles. - In: Advanced optical materials, ISSN 2195-1071, Bd. 10 (2022), 4, 2102001, S. 1-27

Surface-enhanced Raman scattering (SERS) is one of the most powerful analytical techniques for the identification of molecules. The substrate, on which SERS is dependent, contains regions of nanoscale gaps (hotspots) that hold the ability to concentrate incident electromagnetic fields and effectively amplify vibrational scattering signals of adsorbed analytes. While surface plasmon resonance from metal nanostructures is a central focus for the SERS effect, the support of polymers can be significantly advantageous to provide larger exposure of structured metal surfaces for efficient interactions with analytes. Characteristics of the polymer particles such as softness, flexibility, swellability, porosity, optical transparency, metal-loading ability, and high surface area can allow diffusion of analytes and penetrating light deeply that can enormously amplify sensing outcomes. As polymer-supported plasmon-active sensor particles can emerge as versatile SERS substrates, the microfluidic platform is promising for the generation of sensor particles as well as for performing sequential SERS analysis of multiple analytes. Therefore, in this perspective article, the development of multifunctional polymer-metal composite particles, and their applications as potential sensors for SERS sensing through microfluidics are presented. A detailed background from the beginning of the SERS field and perspectives for the multifunctional sensor particles for efficient SERS sensing are provided.



https://doi.org/10.1002/adom.202102001
Köhler, Michael;
Vaccination, immunity and breakthrough: quantitative effects in individual immune responses illustrated by a simple kinetic model. - In: Applied Sciences, ISSN 2076-3417, Bd. 12 (2022), 1, 31, S. 1-15

The personal risks of infection, as well as the conditions for achieving herd immunity, are strongly dependent on an individual’s response to the infective agents on the one hand, and the individual’s reactions to vaccination on the other hand. The main goal of this work is to illustrate the importance of quantitative individual effects for disease risk in a simple way. The applied model was able to illustrate the quantitative effects, in the cases of different individual reactions, after exposition to viruses or bacteria and vaccines. The model was based on simple kinetic equations for stimulation of antibody production using different concentrations of the infective agent, vaccine and antibodies. It gave a qualitative explanation for the individual differences in breakthrough risks and different requirements concerning a second, third or further vaccinations, reconsidering different efficiencies of the stimulation of an immune reaction.



https://doi.org/10.3390/app12010031
Stolle, Heike Lisa Kerstin Stephanie; Kluitmann, Jonas; Csáki, Andrea; Köhler, Michael; Fritzsche, Wolfgang
Shape-dependent catalytic activity of gold and bimetallic nanoparticles in the reduction of methylene blue by sodium borohydride. - In: Catalysts, ISSN 2073-4344, Bd. 11 (2021), 12, 1442, S. 1-20

In this study the catalytic activity of different gold and bimetallic nanoparticle solutions towards the reduction of methylene blue by sodium borohydride as a model reaction is investigated. By utilizing differently shaped gold nanoparticles, i.e., spheres, cubes, prisms and rods as well as bimetallic gold–palladium and gold-platinum core-shell nanorods, we evaluate the effect of the catalyst surface area as available gold surface area, the shape of the nanoparticles and the impact of added secondary metals in case of bimetallic nanorods. We track the reaction by UV/Vis measurements in the range of 190-850 nm every 60 s. It is assumed that the gold nanoparticles do not only act as a unit transferring electrons from sodium borohydride towards methylene blue but can promote the electron transfer upon plasmonic excitation. By testing different particle shapes, we could indeed demonstrate an effect of the particle shape by excluding the impact of surface area and/or surface ligands. All nanoparticle solutions showed a higher methylene blue turnover than their reference, whereby gold nanoprisms exhibited 100% turnover as no further methylene blue absorption peak was detected. The reaction rate constant k was also determined and revealed overall quicker reactions when gold or bimetallic nanoparticles were added as a catalyst, and again these were highest for nanoprisms. Furthermore, when comparing gold and bimetallic nanorods, it could be shown that through the addition of the catalytically active second metal platinum or palladium, the dye turnover was accelerated and degradation rate constants were higher compared to those of pure gold nanorods. The results explore the catalytic activity of nanoparticles, and assist in exploring further catalytic applications.



https://doi.org/10.3390/catal11121442
Kronfeld, Klaus-Peter; Mazétyté-Stasinskiené, Raminta; Zheng, Xuejiao; Köhler, Michael
Textured and hierarchically constructed polymer micro- and nanoparticles. - In: Applied Sciences, ISSN 2076-3417, Bd. 11 (2021), 21, 10421, S. 1-17

Microfluidic techniques allow for the tailored construction of specific microparticles, which are becoming increasingly interesting and relevant. Here, using a microfluidic hole-plate-device and thermal-initiated free radical polymerization, submicrometer polymer particles with a highly textured surface were synthesized. Two types of monomers were applied: (1) methylmethacrylate (MMA) combined with crosslinkers and (2) divinylbenzene (DVB). Surface texture and morphology can be influenced by a series of parameters such as the monomer-crosslinker-solvent composition, surfactants, and additives. Generally, the most structured surfaces with the simultaneously most uniform particles were obtained in the DVB-toluene-nonionic-tensides system. In a second approach, poly-MMA (PMMA) particles were used to build aggregates with bigger polymer particles. For this purpose, tripropyleneglycolediacrylate (TPGDA) particles were synthesized in a microfluidic co-flow arrangement and polymerized by light- irradiation. Then, PMMA particles were assembled at their surface. In a third step, these composites were dispersed in an aqueous acrylamide-methylenebisacrylamide solution, which again was run through a co-flow-device and photopolymerized. As such, entities consisting of particles of three different size ranges - typically 0.7/30/600 [my]m - were obtained. The particles synthesized by both approaches are potentially suitable for loading with or incorporation of analytic probes or catalysts such as dyes or metals.



https://doi.org/10.3390/app112110421
Kronfeld, Klaus-Peter; Ellinger, Thomas; Köhler, Michael
Micro flow photochemical synthesis of Ca-sensitive fluorescent sensor particles. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 21 (2021), 8/9, S. 518-526

Fluorescence probes have widely been used for detecting and imaging Ca2+-enriched parts of cells but more rarely for quantitative determination of concentrations. In this study we show how this can be achieved by a novel approach using hydrogel particles. In a microfluidic co-flow arrangement spherical droplets were generated from an aqueous solution of acrylamide, N,N'-methylenebisacrylamide crosslinker and photoinitiator and subsequently photo-cured in situ yielding gel particles in a sub millimeter range. These particles were separated, dried under reduced pressure and re-swollen in water containing Rhod-5N tri potassium salt as calcium ion selective fluorescence probe. After that the particles were dried again and stored for further investigations. Upon exposure of dried particles to calcium chloride solutions they swell and take up Ca2+-ions forming a strong fluorescing complex with Rhod-5N. Thus, fluorescence intensity increases with calcium ion concentration. Up to ca. 0.50 mM the enhancement effect is strong and then becomes considerably weaker. The intensity-concentration-dependence is well described by an equation derived from the equilibrium of the formation of a 1:1 Ca2+:Rhod-5N complex. The particles allow for a fast optical determination of Ca2+-concentrations up to 0.50 mM in analyte volumes down to below 10 [my]L.



https://doi.org/10.1002/elsc.202100023
Köhler, Michael; Kluitmann, Jonas; Günther, Mike
Metal nanoparticles as free-floating electrodes. - In: Encyclopedia, ISSN 2673-8392, Bd. 1 (2021), 3, S. 551-565

Colloidal metal nanoparticles in an electrolyte environment are not only electrically charged but also electrochemically active objects. They have the typical character of metal electrodes with ongoing charge transfer processes on the metal/liquid interface. This picture is valid for the equilibrium state and also during the formation, growth, aggregation or dissolution of nanoparticles. This behavior can be understood in analogy to macroscopic mixed-electrode systems with a free-floating potential, which is determined by the competition between anodic and cathodic partial processes. In contrast to macroscopic electrodes, the small size of nanoparticles is responsible for significant effects of low numbers of elementary charges and for self-polarization effects as they are known from molecular systems, for example. The electrical properties of nanoparticles can be estimated by basic electrochemical equations. Reconsidering these fundamentals, the assembly behavior, the formation of nonspherical assemblies of nanoparticles and the growth and the corrosion behavior of metal nanoparticles, as well as the formation of core/shell particles, branched structures and particle networks, can be understood. The consequences of electrochemical behavior, charging and self-polarization for particle growth, shape formation and particle/particle interaction are discussed.



https://doi.org/10.3390/encyclopedia1030046
Köhler, Michael;
Challenges for nanotechnology. - In: Encyclopedia, ISSN 2673-8392, Bd. 1 (2021), 3, S. 618-631

The term "Nanotechnology" describes a large field of scientific and technical activities dealing with objects and technical components with small dimensions. Typically, bodies that are in-at least-two dimensions smaller than 0.1 [my]m are regarded as "nanobjects". By this definition, a lot of advanced materials, as well as the advanced electronic devices, are objects of nanotechnology. In addition, many aspects of molecular biotechnology as well as macromolecular and supermolecular chemistry and nanoparticle techniques are summarized under "nanotechnology". Despite this size-oriented definition, nanotechnology is dealing with physics and chemistry as well as with the realization of technical functions in the area between very small bodies and single particles and molecules. This includes the shift from classical physics into the quantum world of small molecules and low numbers or single elementary particles. Besides the already established fields of nanotechnology, there is a big expectation about technical progress and solution to essential economic, medical, and ecological problems by means of nanotechnology. Nanotechnology can only meet these expectations if fundamental progress behind the recent state of the art can be achieved. Therefore, very important challenges for nanotechnology are discussed here.



https://doi.org/10.3390/encyclopedia1030051
Cao-Riehmer, Jialan; Chande, Charmi; Kalensee, Franziska; Schüler, Tim; Köhler, Michael
Microfluidically supported characterization of responses of Rhodococcus erythropolis strains isolated from different soils on Cu-, Ni-, and Co-stress. - In: Brazilian journal of microbiology, ISSN 1678-4405, Bd. 52 (2021), 3, S. 1405-1415

We present a new methodological approach for the assessment of the susceptibility of Rhodococcus erythropolis strains from specific sampling sites in response to increasing heavy metal concentration (Cu2+, Ni2+, and Co2+) using the droplet-based microfluid technique. All isolates belong to the species R. erythropolis identified by Sanger sequencing of the 16S rRNA. The tiny step-wise variation of metal concentrations from zero to the lower mM range in 500 nL droplets not only provided accurate data for critical metal ion concentrations but also resulted in a detailed visualization of the concentration-dependent response of bacterial growth and autofluorescence activity. As a result, some of the isolates showed similar characteristics in heavy metal tolerance against Cu2+, Ni2+, and Co2+. However, significantly different heavy metal tolerances were found for other strains. Surprisingly, samples from the surface soil of ancient copper mining areas supplied mostly strains with a moderate sensitivity to Cu2+, Ni2+, and Co2+, but in contrast, a soil sample from an excavation site of a medieval city that had been covered for about eight centuries showed an extremely high tolerance against cobalt ion (up to 36 mM). The differences among the strains not only may be regarded as results of adaptation to the different environmental conditions faced by the strains in nature but also seem to be related to ancient human activities and temporal partial decoupling of soil elements from the surface. This investigation confirmed that microfluidic screening offers empirical characterization of properties from same species which has been isolated from sites known to have different human activities in the past.



https://doi.org/10.1007/s42770-021-00495-2
Kluitmann, Jonas; Zheng, Xuejiao; Köhler, Michael
Tuning the morphology of bimetallic gold-platinum nanorods in a microflow synthesis. - In: Colloids and surfaces, ISSN 1873-4359, Bd. 626 (2021), 127085

An automated microfluidic system with computer-controlled syringe pumps was applied for screening a three-dimensional concentration space for the formation of binary gold-platinum metal nanorods. Leveraging the micro segmented flow technique, precise residence and reactant addition timings as well as concentration spaces were addressed. The density and thickness of quasi-isotropic platinum shells on gold nanorod cores were tuned from isolated spots to a dense arrangement of high-aspect-ratio columns. The changing optical properties of the particles in the platinum deposition were used for monitoring the reaction progress and the products by the means of a fiber based micro flow-through spectrophotometer allowing to optimize process times. From our data, we propose an electrochemical model, postulating a diode-like effect and limitations for the formation of Pt nuclei on the gold surface and the formation of nano local elements. This point of view is supported by the observed decoration effects of gold facets and to the formation of columnar structures of the platinum shell.



https://doi.org/10.1016/j.colsurfa.2021.127085
Visaveliya, Nikunjkumar R.; Köhler, Michael
Softness meets with brightness: dye-doped multifunctional fluorescent polymer particles via microfluidics for labeling. - In: Advanced optical materials, ISSN 2195-1071, Bd. 9 (2021), 13, 2002219, insges. 22 S.

Fluorogenic labeling strategies have emerged as powerful tools for in vivo and in vitro imaging applications for diagnostic and theranostic purposes. Free organic chromophores (fluorescent dyes) are bright but rapidly degrade. Inorganic nanoparticles (e.g., quantum dots) are photostable but toxic to biological systems. Alternatively, dye-doped polymer particles are promising for labeling and imaging due to their properties that overcome limitations of photodegradation and toxicity. This progress report, therefore, presents various synthesis techniques for the generation of dye-doped fluorescent polymer particles. Polymer particles are relatively soft compared to inorganic nanoparticles and can be synthesized with characteristics like biocompatibility and stimuli responsiveness. Also, their ability of loading fluorophores through various interactions reveals brightness. Here, a multiscale-multicolor library of bright and soft fluorescent polymer particles is generated hierarchically. Various microfluidic supported strategies have been applied where fluorophores can be linked to polymeric networks noncovalently and covalently in the interior, and at the surface of nanoparticles (60-550 nm). Besides, microfluidic strategies for hydrophilic and hydrophobic fluorescent polymer microparticles (20-800 [my]m) have been performed for systematic tuning in size and color combination. Furthermore, soft and bright particulate assemblies are enabled through interfacial interactions at the intermediate scale (600 nm-3 [my]m) between the nanometer and micrometer lengthscale.



https://doi.org/https://doi.org/10.1002/adom.202002219
Köhler, Michael; Beetz, Nancy; Günther, Mike; Möller, Frances; Cao-Riehmer, Jialan
Extremophiles in soil communities of former copper mining sites of the East Harz region (Germany) reflected by re-analyzed 16S rRNA data. - In: Microorganisms, ISSN 2076-2607, Bd. 9 (2021), 7, 1422, insges. 16 S.

The east and southeast rim of Harz mountains (Germany) are marked by a high density of former copper mining places dating back from the late 20th century to the middle age. A set of 18 soil samples from pre- and early industrial mining places and one sample from an industrial mine dump have been selected for investigation by 16S rRNA and compared with six samples from non-mining areas. Although most of the soil samples from the old mines show pH values around 7, RNA profiling reflects many operational taxonomical units (OTUs) belonging to acidophilic genera. For some of these OTUs, similarities were found with their abundances in the comparative samples, while others show significant differences. In addition to pH-dependent bacteria, thermophilic, psychrophilic, and halophilic types were observed. Among these OTUs, several DNA sequences are related to bacteria which are reported to show the ability to metabolize special substrates. Some OTUs absent in comparative samples from limestone substrates, among them Thaumarchaeota were present in the soil group from ancient mines with pH > 7. In contrast, acidophilic types have been found in a sample from a copper slag deposit, e.g., the polymer degrading bacterium Granulicella and Acidicaldus, which is thermophilic, too. Soil samples of the group of pre-industrial mines supplied some less abundant, interesting OTUs as the polymer-degrading Povalibacter and the halophilic Lewinella and Halobacteriovorax. A particularly high number of bacteria (OTUs) which had not been detected in other samples were found at an industrial copper mine dump, among them many halophilic and psychrophilic types. In summary, the results show that soil samples from the ancient copper mining places contain soil bacterial communities that could be a promising source in the search for microorganisms with valuable metabolic capabilities.



https://doi.org/10.3390/microorganisms9071422
Knauer, Andrea; Kuhfuss, Danja; Köhler, Michael
Electrostatic control of Au nanorod formation in automated microsegmented flow synthesis. - In: ACS applied nano materials, ISSN 2574-0970, Bd. 4 (2021), 2, S. 1411-1419

An automated flow rate program was applied for the synthesis of gold nanorods of different aspect ratios dependent on a two-dimensional concentration space of reducing agent and additional silver ions. It was found a regular redshift of the spectral position of the electromagnetic in-axis resonance of metal nanorods with decreasing concentration of reducing agent and increasing concentration of silver ions. The increase of resonance wavelength is strongly correlated with the aspect ratio of the formed nanorods. The experimental results agree with an electrostatic model of self-polarization due to positive excess charge of the nanorods in the presence of CTAB and confirm the crucial role of electrostatic control in the formation of nonspherical and composed nanoparticles in general.



https://doi.org/10.1021/acsanm.0c02941
Schumann, Peter; Kalensee, Franziska; Cao-Riehmer, Jialan; Criscuolo, Alexis; Clermont, Dominique; Köhler, Michael; Meier-Kolthoff, Jan Philipp; Neumann-Schaal, Meina; Tindall, Brian J.; Pukall, Rüdiger
Reclassification of Haloactinobacterium glacieicola as Occultella glacieicola gen. nov., comb. nov., of Haloactinobacterium album as Ruania alba comb. nov, with an emended description of the genus Ruania, recognition that the genus names Haloactinobacterium and Ruania are heterotypic synonyms and description of Occultella aeris sp. nov., a halotolerant isolate from surface soil sampled at an ancient copper smelter. - In: International journal of systematic and evolutionary microbiology, ISSN 1466-5034, Bd. 71 (2021), 4, 004769

In the course of screening the surface soils of ancient copper mines and smelters (East Harz, Germany) an aerobic, non-motile and halotolerant actinobacterium forming small rods or cocci was isolated. The strain designated F300T developed creamy to yellow colonies on tryptone soy agar and grew optimally at 28 &ring;C, pH 7-8 and with 0.5-2% (m/v) NaCl. Its peptidoglycan was of type A4α l-Lys-l-Glu (A11.54). The menaquinone profile was dominated by MK-8(II, III-H4) and contained minor amounts of MK-8(H2), MK-8(H6) and MK-9(H4). The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, mono and diacylated phosphatidylinositol dimannosides, and components that were not fully characterized, including two phospholipids, two glycolipids and an uncharacterized lipid. Major whole-cell sugars were rhamnose and ribose. The fatty acid profile contained mainly iso and anteiso branched fatty acids (anteiso-C15:0, iso-C14:0) and aldehydes/dimethylacetals (i.e. not fatty acids). Sequence analysis of its genomic DNA and subsequent analysis of the data placed the isolate in the group currently defined by members of the genera Ruania and Haloactinobacterium (family Ruaniaceae , order Micrococcales ) as a sister taxon to the previously described species Haloactinobacterium glacieicola , sharing an average nucleotide identity and average amino acid identity values of 85.3 and 85.7%, respectively. Genotypic and chemotaxonomic analyses support the view that strain F300T (=DSM 108350T=CIP 111667T) is the type strain of a new genus and new species for which the name Occultella aeris gen. nov., sp. nov. is proposed. Based on revised chemotaxonomic and additional genome based data, it is necessary to discuss and evaluate the results in the light of the classification and nomenclature of members of the family Ruaniaceae , i.e. the genera Haloactinobacterium and Ruania . Consequently, the reclassification of Haloactinobacterium glacieicola as Occultella glacieicola comb. nov. and Haloactinobacterium album as Ruania alba comb. nov., with an emended description of the genus Ruania are proposed.,



https://doi.org/10.1099/ijsem.0.004769
Visaveliya, Nikunjkumar R.; Köhler, Michael
Hierarchical assemblies of polymer particles through tailored interfaces and controllable interfacial interactions. - In: Advanced functional materials, ISSN 1616-3028, Bd. 31 (2021), 9, 2007407, insges. 22 S.

Hierarchical assembly architectures of functional polymer particles are promising because of their physicochemical and surface properties for multi-labeling and sensing to catalysis and biomedical applications. While polymer nanoparticles' interior is mainly made up of the cross-linked network, their surface can be tailored with soft, flexible, and responsive molecules and macromolecules as potential support for the controlled particulate assemblies. Molecular surfactants and polyelectrolytes as interfacial agents improve the stability of the nanoparticles whereas swellable and soft shell-like cross-linked polymeric layer at the interface can significantly enhance the uptake of guest nano-constituents during assemblies. Besides, layer-by-layer surface-functionalization holds the ability to provide a high variability in assembly architectures of different interfacial properties. Considering these aspects, various assembly architectures of polymer nanoparticles of tunable size, shapes, morphology, and tailored interfaces together with controllable interfacial interactions are constructed here. The microfluidic-mediated platform has been used for the synthesis of constituents polymer nanoparticles of various structural and interfacial properties, and their assemblies are conducted in batch or flow conditions. The assemblies presented in this progress report is divided into three main categories: cross-linked polymeric network's fusion-based self-assembly, electrostatic-driven assemblies, and assembly formed by encapsulating smaller nanoparticles into larger microparticles.



https://doi.org/10.1002/adfm.202007407
Köhler, Michael; Kluitmann, Jonas
In situ assembly of gold nanoparticles in the presence of poly-DADMAC resulting in hierarchical and highly fractal nanostructures. - In: Applied Sciences, ISSN 2076-3417, Bd. 11 (2021), 3, 1191, S. 1-13

The presence of the polycationic macromolecule poly(diallyldimethylammonium chloride) (poly-DADMAC) has a strong effect on the shape and size of colloidal gold nanoparticles formed by the reduction of tetrachloroauric acid with ascorbic acid in aqueous solution. It slows down nanoparticle growth and supports the formation of nonspherical, partially highly fractal and hierarchical nanoparticle shapes. Four structural levels have been recognized from the near-spherical gold nanoparticles in the lower nanometer range over compact aggregates in the midnanometer range and flower and star-like particles in the submicron range up to larger filamentous aggregates. High-contrast scanning electron microscope (SEM) images show that single gold nanoparticles and clusters of them are connected by bundles of macromolecules in large aggregates. The investigation showed that a large spectrum of different nanoparticle shapes and sizes can be accessed by tuning the poly-DADMAC concentrations and their ratio to other reactants. The nanoassemblies with a very high specific surface area might be of interest for SERS and heterogeneous catalysis.



https://doi.org/10.3390/app11031191
Mazétyté-Stasinskiené, Raminta; Köhler, Michael
Sensor micro and nanoparticles for microfluidic application. - In: Applied Sciences, ISSN 2076-3417, Bd. 10 (2020), 23, 8353, S. 1-37

Micro and nanoparticles are not only understood as components of materials but as small functional units too. Particles can be designed for the primary transduction of physical and chemical signals and, therefore, become a valuable component in sensing systems. Due to their small size, they are particularly interesting for sensing in microfluidic systems, in microarray arrangements and in miniaturized biotechnological systems and microreactors, in general. Here, an overview of the recent development in the preparation of micro and nanoparticles for sensing purposes in microfluidics and application of particles in various microfluidic devices is presented. The concept of sensor particles is particularly useful for combining a direct contact between cells, biomolecules and media with a contactless optical readout. In addition to the construction and synthesis of micro and nanoparticles with transducer functions, examples of chemical and biological applications are reported.



https://doi.org/10.3390/app10238353
Visaveliya, Nikunjkumar R.; Köhler, Michael
Emerging structural and interfacial features of particulate polymers at the nanoscale. - In: Langmuir, ISSN 1520-5827, Bd. 36 (2020), 44, S. 13125-13143

Particulate polymers at the nanoscale are exceedingly promising for diversified functional applications ranging from biomedical and energy to sensing, labeling, and catalysis. Tailored structural features (i.e., size, shape, morphology, internal softness, interior cross-linking, etc.) determine polymer nanoparticles' impact on the cargo loading capacity and controlled/sustained release, possibility of endocytosis, degradability, and photostability. The designed interfacial features, however (i.e., stimuli-responsive surfaces, wrinkling, surface porosity, shell-layer swellability, layer-by-layer surface functionalization, surface charge, etc.), regulate nanoparticles interfacial interactions, controlled assembly, movement and collision, and compatibility with the surroundings (e.g., solvent and biological environments). These features define nanoparticles' overall properties/functions on the basis of homogeneity, stability, interfacial tension, and minimization of the surface energy barrier. Lowering of the resultant outcomes is directly influenced by inhomogeneity in the structural and interfacial design through the structure-function relationship. Therefore, a key requirement is to produce well-defined polymer nanoparticles with controlled characteristics. Polymers are amorphous, flexible, and soft, and hence controlling their structural/interfacial features through the single-step process is a challenge. The microfluidics reaction strategy is very promising because of its wide range of advantages such as efficient reactant mixing and fast phase transfer. Overall, this feature article highlights the state-of-the-art synthetic features of polymer nanoparticles with perspectives on their advanced applications.



https://doi.org/10.1021/acs.langmuir.0c02566
Köhler, Michael; Beetz, Nancy; Günther, Mike; Möller, Frances; Schüler, Tim; Cao-Riehmer, Jialan
Microbial community types and signature-like soil bacterial patterns from fortified prehistoric hills of Thuringia (Germany). - In: Community ecology, ISSN 1588-2756, Bd. 21 (2020), 2, S. 107-120

16S rRNA profiling has been applied for the investigation of bacterial communities of surface soil samples from forest-covered areas of ten prehistorical ramparts from different parts of Thuringia. Besides the majority bacterial types that are present in all samples, there could be identified bacteria that are highly abundant in some places and absent or low abundant in others. These differences are mainly related to the acidity of substrate and distinguish the communities of lime stone hills from soils of sand/quartzite and basalt hills. Minority components of bacterial communities show partially large differences that cannot be explained by the pH of the soil or incidental effects, only. They reflect certain relations between the communities of different places and could be regarded as a kind of signature-like patterns. Such relations had also been found in a comparison of the data from ramparts with formerly studied 16S rRNA profiling from an iron-age burial field. The observations are supporting the idea that a part of the components of bacterial communities from soil samples reflect their ecological history and can be understood as the "ecological memory" of a place. Probably such memory effects can date back to prehistoric times and might assist in future interpretations of archaeological findings on the prehistoric use of a place, on the one hand. On the other hand, the genetic profiling of soils of prehistoric places contributes to the evaluation of anthropogenic effects on the development of local soil bacterial diversity.



https://doi.org/10.1007/s42974-020-00017-4
Mendl, Alexander; Köhler, Michael; Boškoviâc, Dušan; Löbbecke, Stefan
Novel SERS-based process analysis for label-free segmented flow screenings. - In: Lab on a chip, ISSN 1473-0189, Bd. 20 (2020), 13, S. 2364-2371

https://doi.org/10.1039/D0LC00367K
Cao-Riehmer, Jialan; Richter, Felix; Kastl, Michael; Erdmann, Jonny; Burgold, Christian; Dittrich, David; Schneider, Steffen; Köhler, Michael; Groß, Gregor Alexander
Droplet-based screening for the investigation of microbial nonlinear dose-response characteristics system, background, and examples. - In: Micromachines, ISSN 2072-666X, Bd. 11 (2020), 6, 577, insges. 19 S.

https://doi.org/10.3390/mi11060577
Kielpinski, Mark; Walther, Oliver; Cao-Riehmer, Jialan; Henkel, Thomas; Köhler, Michael; Groß, Gregor Alexander
Microfluidic chamber design for controlled droplet expansion and coalescence. - In: Micromachines, ISSN 2072-666X, Bd. 11 (2020), 4, 394, insges. 16 S.

https://doi.org/10.3390/mi11040394
Hadzich, Antonella; Groß, Gregor Alexander; Leimbach, Martin; Ispas, Adriana; Bund, Andreas; Flores, Santiago
Effect of polyalcohols on the anticorrosive behaviour of alkyd coatings prepared with drying oils. - In: Progress in organic coatings, Bd. 145 (2020), 105671

https://doi.org/10.1016/j.porgcoat.2020.105671
Kronfeld, Klaus-Peter; Ellinger, Thomas; Köhler, Michael
Microfluidically prepared sensor particles for determination of chloride by fluorescence quenching of matrix-embedded lucigenin. - In: SN applied sciences, ISSN 2523-3971, Bd. 2 (2020), 3, 366, insges. 8 S.

https://doi.org/10.1007/s42452-020-2155-z
Cao-Riehmer, Jialan; Kalensee, Franziska; Günther, Mike; Köhler, Michael
Microsegmented flow-assisted miniaturized culturing for isolation and characterization of heavy metal-tolerant bacteria. - In: International journal of environmental science and technology, ISSN 1735-2630, Bd. 17 (2020), 1, S. 1-16

https://doi.org/10.1007/s13762-019-02424-1
Hadzich, Antonella; Groß, Gregor Alexander; Leimbach, Martin; Ispas, Adriana; Bund, Andreas; Flores, Santiago
Characterization of Plukenetia volubilis L. fatty acid-based alkyd resins. - In: Polymer testing, ISSN 1873-2348, Bd. 82 (2020), 106296

https://doi.org/10.1016/j.polymertesting.2019.106296
Yu, Wei; Visaveliya, Nikunjkumar; Serra, Christophe A.; Köhler, Michael; Ding, Shukai; Bouquey, Michel; Muller, René; Schmutz, Marc; Kraus, Isabelle
Preparation and deep characterization of composite/hybrid multi-scale and multi-domain polymeric microparticles. - In: Materials, ISSN 1996-1944, Bd. 12 (2019), 23, 3921, insges. 13 S.

https://doi.org/10.3390/ma12233921
Köhler, Michael; Kalensee, Franziska; Cao-Riehmer, Jialan; Günther, Mike
Hadesarchaea and other extremophile bacteria from ancient mining areas of the East Harz region (Germany) suggest an ecological long-term memory of soil. - In: SN applied sciences, ISSN 2523-3971, Bd. 1 (2019), 8, 839, insges. 9 S.

https://doi.org/10.1007/s42452-019-0874-9
Köhler, Michael; Kluitmann, Jonas; Knauer, Andrea
Metal nano networks by potential-controlled in situ assembling of gold/silver nanoparticles. - In: ChemistryOpen, ISSN 2191-1363, Bd. 8 (2019), 12, S. 1369-1374

https://doi.org/10.1002/open.201900231
Tovar Ballen, Miguel Angel; Hengoju, Sundar; Weber, Thomas; Mahler, Lisa; Choudhary, Mahipal; Becker, Tino; Roth, Martin
One sensor for multiple colors: fluorescence analysis of microdroplets in microbiological screenings by frequency-division multiplexing. - In: Analytical chemistry, ISSN 1520-6882, Bd. 91 (2019), 4, S. 3055-3061

https://doi.org/10.1021/acs.analchem.8b05451
Lenk, Claudia; Einax, Mario; Köhler, Michael; Maaß, Philipp
Complex oscillation modes in the Belousov-Zhabotinsky reaction by weak diffusive coupling. - In: Physical review, ISSN 2470-0053, Bd. 99 (2019), 2, 022202, insges. 6 S.

https://doi.org/10.1103/PhysRevE.99.022202
Tsierkezos, Nikos; Ritter, Uwe; Thaha, Yudi Nugraha; Knauer, Andrea; Fernandes, Diogo; Kelarakis, Antonios; McCarthy, Eoin K.
Boron-doped multi-walled carbon nanotubes as sensing material for analysis of dopamine and epinephrine in presence of uric acid. - In: Chemical physics letters, Bd. 710 (2018), S. 157-167

https://doi.org/10.1016/j.cplett.2018.09.007
Köhler, Michael; Kuhfuß, Danja; Witthöft, Phillip; Hentschel, Martina; Knauer, Andrea
Single-photon-single-electron transition for interpretation of optical spectra of nonspherical metal nanoparticles in aqueous colloidal solutions. - In: Journal of nanomaterials, ISSN 1687-4129, Bd. 2018 (2018), 1781389, S. 1-8

https://doi.org/10.1155/2018/1781389
Köhler, Michael; Knauer, Andrea
The mixed-electrode concept for understanding growth and aggregation behavior of metal nanoparticles in colloidal solution. - In: Applied Sciences, ISSN 2076-3417, Bd. 8 (2018), 8, 1843, S. 1-12

https://doi.org/10.3390/app8081343
Köhler, Johann Michael; Kalensee, Franziska; Günther, Peter Mike; Schüler, Tim; Cao, Jialan
The local ecological memory of soil: majority and minority components of bacterial communities in prehistorical urns from Schöps (Germany). - In: International journal of environmental research, ISSN 2008-2304, Bd. 12 (2018), 5, S. 575-584

https://doi.org/10.1007/s41742-018-0116-9
Tovar, Miguel; Weber, Thomas; Hengoju, Sundar; Lovera, Andrea; Munser, Anne-Sophie; Shvydkiv, Oksana; Roth, Martin
3D-glass molds for facile production of complex droplet microfluidic chips. - In: Biomicrofluidics, ISSN 1932-1058, Bd. 12 (2018), 2, S. 024115, insges. 9 S.

https://doi.org/10.1063/1.5013325
Visaveliya, Nikunjkumar R.; Köhler, J. Michael
Single-step in situ assembling routes for the shape control of polymer nanoparticles. - In: Biomacromolecules, ISSN 1526-4602, Bd. 19 (2018), 3, S. 1047-1064

https://doi.org/10.1021/acs.biomac.8b00034
Beckmann, Dieter; Köhler, J. Michael
Editorial: Local separation and interface management strategies for biotechnology and life sciences. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 18 (2018), 2, S. 82-83

https://doi.org/10.1002/elsc.201870023
Visaveliya, Nikunjkumar R.; Leishman, Christopher W.; Ng, Kara; Yehya, Nicolas; Tobar, Nelson; Eisele, Dörthe Melitta; Köhler, Michael
Surface wrinkling and porosity of polymer particles toward biological and biomedical applications. - In: Advanced materials interfaces, ISSN 2196-7350, Bd. 4 (2017), 24, 1700929, S. 1-15

https://doi.org/10.1002/admi.201700929
Visaveliya, Nikunjkumar R.; Li, Xiang; Knauer, Andrea; Prasad, Bhagavatula L. V.; Köhler, Michael
Interfacial-active polymer nanoparticles, their assemblies, and SERS application. - In: Macromolecular chemistry and physics, ISSN 1521-3935, Bd. 218 (2017), 23, S. 1700261, insges. 10 S.

https://doi.org/10.1002/macp.201700261
Cao, Jialan; Schüler, Tim; Köhler, J. Michael
Mikrofluidik - großes Potenzial in kleinen Tropfen. - In: Biospektrum, ISSN 1868-6249, Bd. 23 (2017), 4, S. 394-397

https://doi.org/10.1007/s12268-017-0816-2
Li, Xiang; Visaveliya, Nikunjkumar; Hafermann, Lars; Groß, Gregor Alexander; Knauer, Andrea; Köhler, Michael
Hierarchically structured particles for micro flow catalysis. - In: The chemical engineering journal, ISSN 1873-3212, Bd. 326 (2017), S. 1058-1065

https://doi.org/10.1016/j.cej.2017.06.057
Cao, Jialan; Hafermann, Lars; Köhler, J. Michael
Stochastically reduced communities - microfluidic compartments as model and investigation tool for soil microorganism growth in structured spaces. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 17 (2017), 7, S. 792-800

https://doi.org/10.1002/elsc.201600264
Lenk, Claudia; Mattea, Carlos; Stapf, Siegfried; Köhler, J. Michael
Optimising sodium silica gel for Ferroin immobilization. - In: Journal of porous materials, ISSN 1573-4854, Bd. 24 (2017), 4, S. 923-932

https://doi.org/10.1007/s10934-016-0331-8
Thiele, Matthias; Knauer, Andrea; Malsch, Daniéll; Csáki, Andrea; Henkel, Thomas; Köhler, Michael; Fritzsche, Wolfgang
Combination of microfluidic high-throughput production and parameter screening for efficient shaping of gold nanocubes using Dean-flow mixing. - In: Lab on a chip, ISSN 1473-0189, Bd. 17 (2017), 8, S. 1487-1495

https://doi.org/10.1039/c7lc00109f
Visaveliya, Nikunjkumar; Knauer, Andrea; Köhler, Michael
Application of polyionic macromolecules in micro flow syntheses of nanoparticles. - In: Macromolecular chemistry and physics, ISSN 1521-3935, Bd. 218 (2017), 2, S. 1600371, insges. 13 S.

http://dx.doi.org/10.1002/macp.201600371
Tsierkezos, Nikos; Puschner, Max; Ritter, Uwe; Knauer, Andrea; Hafermann, Lars; Köhler, Michael
Electrochemical response of nitrogen-doped multi-walled carbon nanotubes decorated with gold and iridium nanoparticles toward ferrocyanide/ferricyanide redox system. - In: Ionics, ISSN 1862-0760, Bd. 22 (2016), 10, S. 1957-1965

http://dx.doi.org/10.1007/s11581-016-1702-5
Visaveliya, Nikunjkumar; Knauer, Andrea; Yu, Wei; Serra, Christophe A.; Köhler, Michael
Microflow-assisted assembling of multi-scale polymer particles by controlling surface properties and interactions. - In: European polymer journal, Bd. 80 (2016), S. 256-267

http://dx.doi.org/10.1016/j.eurpolymj.2016.03.015
Knauer, Andrea; Köhler, Michael
Explanation of the size dependent in-plane optical resonance of triangular silver nanoprisms. - In: Physical chemistry, chemical physics, ISSN 1463-9084, Bd. 18 (2016), 23, S. 15943-15949

http://dx.doi.org/10.1039/C6CP00953K
Leiterer, Christian; Wünsche, Erik; Singh, Prabha; Albert, Jens; Köhler, Michael; Deckert, Volker; Fritzsche, Wolfgang
High precision attachment of silver nanoparticles on AFM tips by dielectrophoresis. - In: Analytical and bioanalytical chemistry, ISSN 1618-2650, Bd. 408 (2016), 13, S. 3625-3631

https://doi.org/10.1007/s00216-016-9447-6
Visaveliya, Nikunjkumar; Hoffmann, Christian; Groß, Alexander; Täuscher, Eric; Ritter, Uwe; Köhler, J. Michael
Micro-flow assisted synthesis of fluorescent polymer nanoparticles with tuned size and surface properties. - In: Nanotechnology reviews, ISSN 2191-9097, Bd. 5 (2016), 2, S. 259-272

http://dx.doi.org/10.1515/ntrev-2015-0061
Tsierkezos, Nikos; Othman, Shereen Haj; Ritter, Uwe; Hafermann, Lars; Knauer, Andrea; Köhler, Michael; Downing, Clive; McCarthy, Eoin K.
Electrochemical analysis of ascorbic acid, dopamine, and uric acid on nobel metal modified nitrogen-doped carbon nanotubes. - In: Sensors and actuators, ISSN 0925-4005, Bd. 231 (2016), S. 218-229

http://dx.doi.org/10.1016/j.snb.2016.03.032
Thiele, Matthias; Zi En Soh, Joanne; Knauer, Andrea; Malsch, Daniéll; Stranik, Ondrej; Müller, Robert; Csáki, Andrea; Henkel, Thomas; Köhler, Michael; Fritzsche, Wolfgang
Gold nanocubes - direct comparison of synthesis approaches reveals the need for a microfluidic synthesis setup for a high reproducibility. - In: The chemical engineering journal, ISSN 1873-3212, Bd. 288 (2016), S. 432-440

http://dx.doi.org/10.1016/j.cej.2015.12.020
Köhler, J. Michael;
Process control in microreactors. - In: Chemical engineering & technology, ISSN 1521-4125, Bd. 38 (2015), 7, S. 1107-1108
Editorial

https://doi.org/10.1002/ceat.201590037
Visaveliya, Nikunjkumar; Köhler, J. Michael
Microfluidic assisted synthesis of multipurpose polymer nanoassembly particles for fluorescence, LSPR, and SERS activities. - In: Small, ISSN 1613-6829, Bd. 11 (2015), 48, S. 6435-6443

http://dx.doi.org/10.1002/smll.201502364
Wetzel, Katharina; Cao, Jialan; Kothe, Erika; Köhler, J. Michael
Changing growth behavior of heavy-metal tolerant bacteria: media optimization using droplet-based microfluidics. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 15 (2015), 3, S. 327-332

http://dx.doi.org/10.1002/elsc.201400230
Brauer, Dana; Möller, Frances; Groß, Gregor Alexander; Lenk, Claudia; Visaveliya, Nikunjkumar; Schüler, Tim; Köhler, Michael
Identification of response classes from heavy metal-tolerant soil microbial communities by highly resolved concentration-dependent screenings in a microfluidic system. - In: Methods in ecology and evolution, ISSN 2041-210X, Bd. 6 (2015), 5, S. 600-609

https://doi.org/10.1111/2041-210X.12344
Visaveliya, Nikunjkumar; Lenke, Steffen; Köhler, J. Michael
Composite sensor particles for tuned SERS sensing: microfluidic synthesis, properties and applications. - In: ACS applied materials & interfaces, ISSN 1944-8252, Bd. 7 (2015), 20, S. 10742-10754

http://dx.doi.org/10.1021/acsami.5b00604
Visaveliya, Nikunjkumar; Köhler, J. Michael
Role of self-polarization in a single-step controlled synthesis of linear and branched polymer nanoparticles. - In: Macromolecular chemistry and physics, ISSN 1521-3935, Bd. 216 (2015), 11, S. 1212-1219

http://dx.doi.org/10.1002/macp.201500091
Köhler, Michael;
What are proteins teaching us on fundamental strategies for molecular nanotechnology?. - In: Nanotechnology reviews, ISSN 2191-9097, Bd. 4 (2015), 2, S. 145-160

http://dx.doi.org/10.1515/ntrev-2014-0031
Hafermann, Lars; Köhler, Michael;
Small gold nanoparticles formed by rapid photochemical flow-through synthesis using microfluid segment technique. - In: Journal of nanoparticle research, ISSN 1572-896X, Bd. 17 (2015), 2, 99, insges. 8 S.

https://doi.org/10.1007/s11051-015-2914-8
Cao-Riehmer, Jialan; Nagl, Stefan; Kothe, Erika; Köhler, Michael
Oxygen sensor nanoparticles for monitoring bacterial growth and characterization of dose-response functions in microfluidic screenings. - In: Microchimica acta, ISSN 1436-5073, Bd. 182 (2015), 1/2, S. 385-394

https://doi.org/10.1007/s00604-014-1341-3
Visaveliya, Nikunjkumar; Köhler, J. Michael
Simultaneous size and color tuning of polymer microparticles in a single-step microfluidic synthesis: particles for fluorescence labeling. - In: Journal of materials chemistry. Materials for optical and electronic devices / Royal Society of Chemistry. - London [u.a.] : RSC, 2013- , ISSN: 2050-7534 , ZDB-ID: 2702245-6, ISSN 2050-7534, Bd. 3 (2015), 4, S. 844-853

http://dx.doi.org/10.1039/C4TC01809E
Lenk, Claudia; Weber, Frank Michael; Bauer, Martin; Einax, Mario; Maaß, Philipp; Seemann, Gunnar
Initiation of atrial fibrillation by interaction of pacemakers with geometrical constraints. - In: Journal of theoretical biology, ISSN 1095-8541, Bd. 366 (2015), S. 13-23

https://doi.org/10.1016/j.jtbi.2014.10.030
Cao, Jialan; Köhler, J. Michael
Droplet-based microfluidics for microtoxicological studies. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 15 (2015), 3, S. 306-317

http://dx.doi.org/10.1002/elsc.201400074
Köhler, Michael; Visaveliya, Nikunjkumar;
Controlling formation and assembling of nanoparticles by control of electrical charging, polarization, and electrochemical potential. - In: Nanotechnology reviews, ISSN 2191-9097, Bd. 3 (2014), 6, S. 553-568

http://dx.doi.org/10.1515/ntrev-2014-0006
Tsierkezos, Nikos; Othman, Shereen Haj; Ritter, Uwe; Hafermann, Lars; Knauer, Andrea; Köhler, Michael
Nitrogen-doped multi-walled carbon nanotubes modified with platinum, palladium, rhodium and silver nanoparticles in electrochemical sensing. - In: Journal of nanoparticle research, ISSN 1572-896X, Bd. 16 (2014), 10, 2660, insges. 13 S.

https://doi.org/10.1007/s11051-014-2660-3
Brauer, Dana; Kothe, Erika; Wetzel, Katharina; Klein, Katja; Köhler, Michael
Micro-segmented flow and multisensor-technology for microbial activity profiling. - In: Environmental science, ISSN 2050-7895, Bd. 16 (2014), 10, S. 2362-2370

http://dx.doi.org/10.1039/C4EM00255E
Kraus, Isabelle; Li, Shuning; Knauer, Andrea; Schmutz, Marc; Färber, Jacques; Serra, Christophe A.; Köhler, Michael
Continuous-microflow synthesis and morphological characterization of multiscale composite materials based on polymer microparticles and inorganic nanoparticles. - In: Journal of flow chemistry, ISSN 2063-0212, Bd. 4 (2014), 2, S. 72-78

http://dx.doi.org/10.1556/JFC-D-13-00029
Visaveliya, Nikunjkumar; Köhler, J. Michael
Single-step microfluidic synthesis of various nonspherical polymer nanoparticles via in situ assembling: dominating role of polyelectrolytes molecules. - In: ACS applied materials & interfaces, ISSN 1944-8252, Bd. 6 (2014), 14, S. 11254-11264

http://dx.doi.org/10.1021/am501555y
Knauer, Andrea; Köhler, Michael;
Screening of nanoparticle properties in microfluidic syntheses. - In: Nanotechnology reviews, ISSN 2191-9097, Bd. 3 (2014), 1, S. 5-26

http://dx.doi.org/10.1515/ntrev-2013-0018
Knauer, Andrea; Eisenhardt, Anja; Krischok, Stefan; Köhler, Michael
Nanometer precise adjustment of the silver shell thickness during automated Au-Ag core-shell nanoparticle synthesis in micro fluid segment sequences. - In: Nanoscale, ISSN 2040-3372, Bd. 6 (2014), 10, S. 5230-5238

https://doi.org/10.1039/C3NR06438G
Tsierkezos, Nikos; Ritter, Uwe; Knauer, Andrea; Szroeder, Paweł
Electrocatalytic activity of nitrogen-doped carbon nanotubes decorated with gold nanoparticles. - In: Electrocatalysis, ISSN 1868-5994, Bd. 5 (2014), 1, S. 87-95

http://dx.doi.org/10.1007/s12678-013-0175-9
Cao, Jialan; Kürsten, Dana; Funfak, Anette; Schneider, Steffen; Köhler, J. Michael
Characterization of combinatorial effects of toxic substances by cell cultivation in micro segmented flow. - In: Micro-segmented flow, (2014), S. 203-230

Knauer, Andrea; Köhler, Michael;
Micro continuous-flow synthesis of metal nanoparticles using micro fluid segment technology. - In: Micro-segmented flow, (2014), S. 149-200

Budden, Matthias; Schneider, Steffen; Köhler, Michael; Cahill, Brian
Electrical switching of droplets and fluid segments. - In: Micro-segmented flow, (2014), S. 31-54

Serra, Christophe A.; Khan, Ikram U.; Chang, ZhenQi; Bouquey, Michel; Muller, René; Kraus, Isabelle; Schmutz, Marc; Vandamme, Thierry; Anton, Nicolas; Ohm, Christian; Zentel, Rudolf; Knauer, Andrea; Köhler, Michael
Engineering polymer microparticles by droplet microfluidics. - In: Journal of flow chemistry, ISSN 2063-0212, Bd. 3 (2013), 3, S. 66-75

http://dx.doi.org/10.1556/JFC-D-13-00014
Cao-Riehmer, Jialan; Goldhan, Juliane; Martin, Karin; Köhler, Michael
Investigation of mixture toxicity of widely used drugs caffeine and ampicillin in the presence of an ACE inhibitor on bacterial growth using droplet-based microfluidic technique. - In: Green processing & synthesis, ISSN 2191-9550, Bd. 2 (2013), 6, S. 591-601

https://doi.org/10.1515/gps-2013-0078
Visaveliya, Nikunjkumar; Köhler, Michael;
A self-seeding synthesis of Ag microrods of tuned aspect ratio: ascorbic acid plays a key role. - In: Nanotechnology, ISSN 1361-6528, Bd. 24 (2013), 34, 345604, S. 1-11

http://dx.doi.org/10.1088/0957-4484/24/34/345604
Cao, Jialan; Kürsten, Dana; Krause, Katrin; Kothe, Erika; Martin, Karin; Roth, Martin; Köhler, J. Michael
Application of micro-segmented flow for two-dimensional characterization of the combinatorial effect of zinc and copper ions on metal-tolerant Streptomyces strains. - In: Applied microbiology and biotechnology, ISSN 1432-0614, Bd. 97 (2013), 20, S. 8923-8930

http://dx.doi.org/10.1007/s00253-013-5147-8
Li, Yuehao; Yamane, Dawit G.; Li, Shuning; Biswas, Sanchita; Reddy, Rupesh K.; Göttert, Jost S.; Nandakumar, Krishnaswamy; Kumar, Challa S. S. R.
Geometric optimization of liquid-liquid slug flow in a flow-focusing millifluidic device for synthesis of nanomaterials. - In: The chemical engineering journal, ISSN 1873-3212, Bd. 217 (2013), S. 447-459

http://dx.doi.org/10.1016/j.cej.2012.11.111
Köhler, Michael J.;
Biotechnology and microsystems: give and take between enzymatic synthesis, cell cultivation and microstructuring. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 13 (2013), 4, S. 323-324

http://dx.doi.org/10.1002/elsc.201370042
Groß, Gregor Alexander; Singh, Sukhdeep; Schlingloff, Gregor; Schwienhorst, Andreas; Riester, Daniel; Wegener, Dennis; Wurziger, Hanns; Schober, Andreas
Robotic alliance of miniaturized synthesis and screening: a case study for the identification of histone deacetylase inhibitors. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 13 (2013), 4, S. 344-351

http://dx.doi.org/10.1002/elsc.201200090
Visaveliya, Nikunjkumar; Li, Shuning; Köhler, Michael
Heterogeneous nanoassembling: microfluidically prepared poly(methyl methacrylate) nanoparticles on Ag microrods and ZnO microflowers. - In: Particle & particle systems characterization, ISSN 1521-4117, Bd. 30 (2013), 7, S. 614-623

The heterogeneous assembly of colloidal polymer particles on the nano- and microstructures of a metal is a versatile platform for adjusting the mechanical and electrical properties simultaneously. The assemblies of silver (Ag) microrods and flower-like zinc oxide (ZnO) microparticles with poly(methyl methacrylate) (PMMA) nanospheres are presented to prepare advanced composite materials. PMMA nanoparticles are prepared via the emulsion polymerization technique using a microfluidic preparation step in the presence of cationic surfactant. The surface charge of PMMA particles determines the binding interaction strength with inorganic constituents. Ag microrods and ZnO microparticles are prepared in a batch and in a continuous flow process, respectively. The assembling process can be explained by a particle-particle binding process due to the electrostatic interaction for both types of nanoassemblies. The observed binding pattern reveals certain lateral mobility of the small polymer particles at the surface of larger metal particle. The particle ratios in the nanoassemblies can be tuned over a wide range by changing the reaction parameters.



https://doi.org/10.1002/ppsc.201200128
Lenk, Claudia; Einax, Mario; Maaß, Philipp
Irregular excitation patterns in reaction-diffusion systems due to perturbation by secondary pacemakers. - In: Physical review. Statistical, nonlinear, and soft matter physics / American Physical Society. - College Park, Md. : APS, January 1993-December 2015 , ISSN: 1550-2376 , ZDB-ID: 1472725-0, ISSN 1550-2376, Bd. 87 (2013), 4, S. 042904, insges. 8 S.

http://dx.doi.org/10.1103/PhysRevE.87.042904
Köhler, Michael; Li, Shuning; Knauer, Andrea
Why is micro segmented flow particularly promising for the synthesis of nanomaterials?. - In: Chemical engineering & technology, ISSN 1521-4125, Bd. 36 (2013), 6, S. 887-899

https://doi.org/10.1002/ceat.201200695
Knauer, Andrea; Köhler, Michael;
Screening of multiparameter spaces for silver nanoprism synthesis by microsegmented flow technique. - In: Chemie - Ingenieur - Technik, ISSN 1522-2640, Bd. 85 (2013), 4, S. 467-475

https://doi.org/10.1002/cite.201200206
Budden, Matthias; Schneider, Steffen; Groß, Gregor Alexander; Kielpinski, Mark; Henkel, Thomas; Cahill, Brian; Köhler, Michael
Microfluidic encoding: generation of arbitrary droplet sequences by electrical switching in microchannels. - In: Sensors and actuators, ISSN 1873-3069, Bd. 189 (2013), S. 288-297

http://dx.doi.org/10.1016/j.sna.2012.10.013
Köhler, J. Michael; Kraus, Isabelle; Färber, Jacques; Serra, Christophe
Continuous-flow preparation of nanoporous metal/polymer composite particles by in situ synthesis of silver nanoparticles in photopolymerized acrylate/diethylene glycol droplets. - In: Journal of materials science, ISSN 1573-4803, Bd. 48 (2013), 5, S. 2158-2166

http://dx.doi.org/10.1007/s10853-012-6991-0
Knauer, Andrea; Visaveliya, Nikunjkumar; Köhler, Michael;
Spontaneous transformation of polyelectrolyte-stabilized silver nanoprisms by interaction with thiocyanate. - In: Journal of colloid and interface science, ISSN 1095-7103, Bd. 394 (2013), S. 78-84

http://dx.doi.org/10.1016/j.jcis.2012.11.026
Köhler, Michael; März, Anne; Popp, Jürgen; Knauer, Andrea; Kraus, Isabelle; Faerber, Jaques; Serra, Christophe
Polyacrylamid/silver composite particles produced via microfluidic photopolymerization for single particle-based SERS microsensorics. - In: Analytical chemistry, ISSN 1520-6882, Bd. 85 (2013), 1, S. 313-318

http://dx.doi.org/10.1021/ac302751t
Li, Shuning; Knauer, Andrea; Risch, Katrin; Ritter, Uwe; Köhler, Michael
Synthesis and characterization of ZnO/4-mercaptobenzoic acid/Au composite particles. - In: Materials letters, ISSN 1873-4979, Bd. 91 (2013), S. 103-106

http://dx.doi.org/10.1016/j.matlet.2012.09.090
Köhler, Michael; Funfak, Anette; Cao-Riehmer, Jialan; Brauer, Dana; Schneider, Steffen; Günther, Mike
Addressing of concentration spaces for bioscreenings by micro segmented flow with microphotometric and microfluorimetric detection. - In: Optical Nano- and Microsystems for Bioanalytics, (2012), S. 47-81

http://dx.doi.org/10.1007/978-3-642-25498-7_2
Cao, Jialan; Kürsten, Dana; Schneider, Steffen; Köhler, J. Michael
Stimulation and inhibition of bacterial growth by caffeine dependent on chloramphenicol and a phenolic uncoupler - a ternary toxicity study using microfluid segment technique. - In: Journal of biomedical nanotechnology, ISSN 1550-7041, Bd. 8 (2012), 5, S. 770-778

http://dx.doi.org/10.1166/jbn.2012.1447
Knauer, Andrea; Csáki, Andrea; M̈öller, Frances; Hühn, Carolin; Fritzsche, Wolfgang; Köhler, Michael
Microsegmented flow-through synthesis of silver nanoprisms with exact tunable optical properties. - In: The journal of physical chemistry, ISSN 1932-7455, Bd. 116 (2012), 16, S. 9251-9258

http://dx.doi.org/10.1021/jp210842g
Li, Shuning; Roy, Amitava; Lichtenberg, Henning; Merchan, Gregory; Kumar, Challa S. S. R.; Köhler, Michael
Local structure of ZnO micro flowers and nanoparticles obtained by micro-segmented flow synthesis. - In: ChemPhysChem, ISSN 1439-7641, Bd. 13 (2012), 6, S. 1557-1561

http://dx.doi.org/10.1002/cphc.201100960
Cao-Riehmer, Jialan; Brauer, Dana; Schneider, Steffen; Knauer, Andrea; Günther, Mike; Köhler, Michael
Uncovering toxicological complexity by multi-dimensional screenings in microsegmented flow: modulation of antibiotic interference by nanoparticles. - In: Lab on a chip, ISSN 1473-0189, Bd. 12 (2012), 3, S. 474-484

https://doi.org/10.1039/C1LC20584F
Singh, Sukhdeep; Schober, Andreas; Gebinoga, Michael; Groß, Gregor Alexander
ChemInform abstract: Convenient method for synthesis of thiazolo[3,2-a]pyrimidine derivatives in a one-pot procedure. - In: ChemInform, ISSN 1522-2667, Bd. 42 (2011), 44, insges. 1 S.

http://dx.doi.org/10.1002/chin.201144162
Köhler, Michael; Günther, Mike; Funfak, Anette; Cao-Riehmer, Jialan; Knauer, Andrea; Li, Shuning; Schneider, Steffen; Groß, Gregor Alexander
From droplets and particles to hierarchical spatial organization: nanotechnology challenges for microfluidics. - In: Journal of physical science and application, ISSN 2159-5348, Bd. 1 (2011), 3, S. 125-134

The compartimentation of fluids in the microliter, nanoliter and picoliter range leads recently to many applications of microfluidics in material development, diagnostics and biological screenings. Droplet-based microfluidics allows the improvement of nanoparticle homogeneity and the tuning of particle properties. It supports combinatorial synthesis of inorganic as well as organic substances and can be applied for the cultivation and screening of bacteria, eucaryotic cells and fish embryos. The well-ordered handling and the addressing of microfluid segments improves the information transfer between chemical, biological and electronic systems. Despite this remarkable technical progress, there is a particular importance of microfluidics for future nanotechnological solutions. The hierarchical spatial organization of liquids, particles and gels in microfluidics represents a fundamental biomimetic principle which overcomes the limits of planar technology and opens the gate for realizing complex structured threedimensional nanoarchitectures. Recent applications of microstructured fluids in chemistry and biology and concepts for future developments will be discussed.



Singh, Sukhdeep; Köhler, Michael; Schober, Andreas; Groß, Gregor Alexander
The Eschenmoser coupling reaction under continuous-flow conditions. - In: Beilstein journal of organic chemistry, ISSN 1860-5397, Bd. 7 (2011), S. 1164-1172

http://dx.doi.org/10.3762/bjoc.7.135
Abahmane, Lahbib; Köhler, Michael; Groß, Gregor Alexander
Gold nanoparticle-catalyzed synthesis of propargylamines: the traditional A3-multicomponent reaction performed as a two-step flow process. - In: Chemistry - a European journal, ISSN 1521-3765, Bd. 17 (2011), 10, S. 3005-3010

https://doi.org/10.1002/chem.201002043
Boškovic, Dušan; Löbbecke, Stefan; Groß, Alexander; Köhler, Michael
Residence time distribution studies in microfluidic mixing structures. - In: Chemical engineering & technology, ISSN 1521-4125, Bd. 34 (2011), 3, S. 361-370

The residence time distribution (RTD) characteristics of three microreactors containing different passive mixing structures, namely, a three dimensional serpentine structure, a split-and-recombine structure and a staggered herringbone structure, were investigated and compared. An experimental input-response technique was applied which required deconvolution of the measured data by modeling of the RTD. The proposed technique provides useful information on optimized application and operation of microfluidic devices. The serpentine reactor and the split-and-recombine reactor show improvement in RTD behaviour, i.e., narrowing of RTD curves, at Re-numbers > 30 due to effective transversal mixing and therefore reduced axial dispersion. In the case of the staggered herringbone structure, dead volumes could be observed which considerably affect the RTD.



http://dx.doi.org/10.1002/ceat.201000352
Köhler, Michael;
Microtechnology in chemical engineering. - In: Chemical engineering & technology, ISSN 1521-4125, Bd. 34 (2011), 3, S. 330

http://dx.doi.org/10.1002/ceat.201190011
Kürsten, Dana; Cao, Jialan; Funfak, Anette; Müller, Philipp; Köhler, J. Michael
Cultivation of Chlorella vulgaris in microfluid segments and microtoxicological determination of their sensitivity against CuCl2 in the nanoliter range. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 11 (2011), 6, S. 580-587

The cultivation of the monocellular green alga Chlorella vulgaris was implemented into microfluid segments to demonstrate the possibility of an automated screening of toxic effects of the common algaecide CuCl2. Therefore, the nutritional as well as light and carbon dioxide requirements of the algae had to be adapted to the microfluidic device. Generally, sequences of about 350 fluid segments with single volumes of about 500 nL were applied for the dose-response experiments. The growth of algae cultures inside microfluidic segments was noninvasively measured by microflow through techniques using two different optical channels. A multi-endpoint detection was realized by the photometric characterization of cell density by transmission measurements and the measurement of density of autofluorescent cells. The different methods revealed comparable half maximal effective concentrations (EC50) in the range between 34.6 and 39.9 mg/mL for the toxicity of CuCl2 to the green algae C. vulgaris. By reference experiments in microtiter plates lower EC50 were achieved presumably caused by increased alkalinity of the growth medium due to higher photosynthesis. The results show that the microsegmented flow technique is well suited for the automated determination of dose/response functions for microorganisms like C. vulgaris and for the application of multi-endpoint procedures at the nanoliter scale.



http://dx.doi.org/10.1002/elsc.201100023
Köhler, J. Michael;
Editorial: microtechnology for life science applications. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 11 (2011), 2, S. 116-117

http://dx.doi.org/10.1002/elsc.201190011
Funfak, Anette; Cao-Riehmer, Jialan; Knauer, Andrea; Martin, Karin; Köhler, Michael
Synergistic effects of metal nanoparticles and a phenolic uncoupler using microdroplet-based two-dimensional approach. - In: Journal of environmental monitoring, ISSN 1464-0333, Bd. 2 (2011), 13, S. 410-415

A droplet-based microfluidic technique for testing multiple reagent concentrations is presented. We used this experimental approach to study combined effects of gold (AuNP) and silver nanoparticles (AgNP) with the phenolic uncoupler 2,4-dinitrophenol (DNP) with respect to the growth of Escherichia coli. In order to evaluate the toxicity of binary mixtures, we first encapsulated the E. coli cells and particle mixtures inside the microdroplets using PEEK (polyetherketone) modules. Two-dimensional concentration spaces with about 500 well separated droplets were addressed. We subsequently analyzed the cell growth, the viability and the autofluorescence intensity (metabolic activity) of the bacteria with a micro-flow-through fluorometer and photometer. Dose-dependent synergistic effects were found for the binary mixture of AgNPs and DNP, which indicated a stronger interaction in the mixture than it was expected from effect summation. For the binary mixture of DNP and AuNPs in non-toxic concentrations, we found only weak synergistic effects at low DNP concentrations. Furthermore, the non-toxic tested AuNPs causes effect summation in the binary mixture with the phenolic uncoupler. In general, we demonstrated the efficiency of a droplet-based microfluidic system for fast high-throughput screenings of binary and multiple mixtures. This work also confirmed the relevance of highly resolved droplet-based assays for the miniaturization of ecotoxicological aquatic test systems.



http://dx.doi.org/10.1039/C0EM00162G
Singh, Sukhdeep; Schober, Andreas; Gebinoga, Michael; Groß, Gregor Alexander
Convenient method for synthesis of thiazolo[3,2-a]pyrimidine derivatives in a one-pot procedure. - In: Tetrahedron letters, ISSN 1873-3581, Bd. 52 (2011), 29, S. 3814-3817

http://dx.doi.org/10.1016/j.tetlet.2011.05.067
Knauer, Andrea; Thete, Aniket; Li, Shuning; Romanus, Henry; Csáki, Andrea; Fritzsche, Wolfgang; Köhler, Michael
Au/Ag/Au double shell nanoparticles with narrow size distribution obtained by continuous micro segmented flow synthesis. - In: The chemical engineering journal, ISSN 1873-3212, Bd. 166 (2011), 3, S. 1164-1169

http://dx.doi.org/10.1016/j.cej.2010.12.028
Günther, Mike; Knauer, Andrea; Köhler, Michael;
Metal nanoparticle synthesis in microreactors. - In: Applications, (2010), S. 361-393

Groß, Gregor Alexander; Köhler, Johann Michael
Residence time distribution and nanoparticle formation in microreactors. - In: Fundamental concepts, (2010), S. 317-340

Singh, Sukhdeep; Schober, Andreas; Groß, Gregor Alexander
Ethyl 2-[(Z)-2-(4-cyanophenyl)-2-hydroxyvinyl]-4-(4-methoxyphenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate. - In: Molbank, ISSN 1422-8599, Bd. 2010 (2010), 1, M655, S. 1-4

A one-pot, two-step method has been developed for the synthesis of ethyl 2-[(Z)-2-(4-cyanophenyl)-2-hydroxyvinyl]-4-(4-methoxyphenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate, including a sulfide contraction step utilizing solution and solid phase synthesis.



https://doi.org/10.3390/M655
Groß, Alexander; Schneider, Steffen; Abahmane, Lahbib; Köhler, Michael
Pressure loss - educational experiments for microreaction technology using an universal experiment platform. - In: Chemie - Ingenieur - Technik, ISSN 1522-2640, Bd. 82 (2010), 10, S. 1789-1798

https://doi.org/10.1002/cite.201000002
Li, Shuning; Meierott, Stefan; Köhler, J. Michael
Effect of water content on growth and optical properties of ZnO nanoparticles generated in binary solvent mixtures by micro-continuous flow synthesis. - In: The chemical engineering journal, ISSN 1873-3212, Bd. 165 (2010), 3, S. 958-965

http://dx.doi.org/10.1016/j.cej.2010.08.033
Chang, Zhenqi; Serra, Christophe A.; Bouquey, Michel; Kraus, Isabelle; Li, Shuning; Köhler, Michael
Multiscale materials from microcontinuous-flow synthesis: ZnO and Au nanoparticle-filled uniform and homogeneous polymer microbeads. - In: Nanotechnology, ISSN 1361-6528, Bd. 21 (2010), 1, 015605, S. 1-5

http://dx.doi.org/10.1088/0957-4484/21/1/015605
Singh, Sukhdeep; Schober, Andreas; Gebinoga, Michael; Groß, Gregor Alexander
ChemInform abstract: Facile conversion of Biginelli 3,4-dihydropyrimidin-2(1H)-thiones to 2-(2-hydroxy-2-arylvinyl) dihydropyrimidines via Eschenmoser coupling. - In: ChemInform, ISSN 1522-2667, Bd. 40 (2009), 31, insges. 1 S.

http://dx.doi.org/10.1002/chin.200931161
Abahmane, Lahbib; Knauer, Andrea; Ritter, Uwe; Köhler, Michael; Groß, Gregor Alexander
Heterogeneous catalyzed pyridine synthesis using montmorillionite and nanoparticle-impregnated alumina in a continuous micro flow system. - In: Chemical engineering & technology, ISSN 1521-4125, Bd. 32 (2009), 11, S. 1799-1805

http://dx.doi.org/10.1002/ceat.200900368
Li, Shuning; Günther, Peter Mike; Köhler, Johann Michael
Micro segmented-flow technique for continuous synthesis of different kinds of ZnO nanoparticles in aqueous and in DMSO solution. - In: Journal of chemical engineering of Japan, ISSN 1881-1299, Bd. 42 (2009), 5, S. 338-345

http://dx.doi.org/10.1252/jcej.08we242
Funfak, Anette; Hartung, Regina; Cao, Jialan; Martin, Karin; Wiesmüller, Karl-Heinz; Wolfbeis, Otto S.; Köhler, J. Michael
Highly resolved doseresponse functions for drug-modulated bacteria cultivation obtained by fluorometric and photometric flow-through sensing in microsegmented flow. - In: Sensors and actuators. Chemical. - Amsterdam [u.a.] : Elsevier Science, 1990- , ISSN: 0925-4005 , ZDB-ID: 1500731-5, ISSN 0925-4005, Bd. 142 (2009), 1, S. 66-72

http://dx.doi.org/10.1016/j.snb.2009.07.017
Thete, Aniket; Henkel, Thomas; Göckeritz, R.; Endlich, M.; Köhler, Michael; Groß, G. Alexander
A hydrogel based fluorescent micro array used for the characterization of liquid analytes. - In: Analytica chimica acta, ISSN 1873-4324, Bd. 633 (2009), 1, S. 81-89

http://dx.doi.org/10.1016/j.aca.2008.11.030
Steinbrück, Andrea; Csáki, Andrea; Ritter, Kathrin; Leich, Martin; Köhler, Michael; Fritzsche, Wolfgang
Gold and gold-silver core-shell nanoparticle constructs with defined size based on DNA hybridization. - In: Journal of nanoparticle research, ISSN 1572-896X, Bd. 11 (2009), 3, S. 623-633

https://doi.org/10.1007/s11051-008-9401-4
Thete, Aniket R.; Groß, G. Alexander; Hausotte, Tino; Jäger, Gerd; Dorozhovets, Nataliya; Köhler, J. Michael
Nanotopographic characterization of spotted micro arrays on polyvinyl alcohol films by high-resolution long-range nanoprofiling. - In: Scanning, ISSN 1932-8745, Bd. 31 (2009), 1, S. 35-48

http://dx.doi.org/10.1002/sca.20136
Funfak, Anette; Cao-Riehmer, Jialan; Wolfbeis, Otto S.; Martin, Karin; Köhler, Michael
Monitoring cell cultivation in microfluidic segments by optical pH sensing with a micro flow-through fluorometer using dye-doped polymer particles. - In: Microchimica acta, ISSN 1436-5073, Bd. 164 (2009), 3/4, S. 279-286

https://doi.org/10.1007/s00604-008-0096-0
Hartung, Regina; Brösing, Andreas; Sczcepankiewicz, G.; Liebert, Uwe; Häfner, Norman; Dürst, Matthias; Felbel, Jana; Lassner, D.; Köhler, Michael
Application of an asymmetric helical tube reactor for fast identification of gene transcripts of pathogenic viruses by micro flow-through PCR. - In: Biomedical microdevices, ISSN 1572-8781, Bd. 11 (2009), 3, S. 685-692

http://dx.doi.org/10.1007/s10544-008-9280-6
Kysil, Olena; Simonova, K.; Frolov, V.; Buzaneva, Eugenia; Köhler, Michael; Gobsch, Gerhard; Ritter, Uwe; Scharff, Peter
Photoluminescence effects on gold nano-particles modified by short single stranded DNA molecules. - In: Materials science and engineering technology, ISSN 1521-4052, Bd. 40 (2009), 4, S. 290-293

http://dx.doi.org/10.1002/mawe.200800443
Singh, Sukhdeep; Schober, Andreas; Gebinoga, Michael; Groß, Gregor Alexander
Facile conversion of Biginelli 3,4-dihydropyrimidin-2(1H)-thiones to 2-(2-hydroxy-2-arylvinyl) dihydropyrimidines via Eschenmoser coupling. - In: Tetrahedron letters, ISSN 1873-3581, Bd. 50 (2009), 16, S. 1838-1843

http://dx.doi.org/10.1016/j.tetlet.2009.02.027
Köhler, Michael;
Inorganic particles. - In: Devices, reactions and applications, (2009), S. 273-288

Thete, Aniket R.; Groß, Gregor Alexander; Köhler, Michael;
Differentiation of liquid analytes in gel films by permeability-modulated double-layer chemo-chips/ Aniket R. Thete; G. Alexander Gross and J. Michael Koehler. - In: The analyst, ISSN 1364-5528, Bd. 134 (2009), 2, S. 394-400

http://dx.doi.org/10.1039/b808257j
Thete, Aniket R.; Henkel, Thomas; Göckeritz, R.; Endlich, M.; Köhler, J. Michael; Groß, G. Alexander
A hydrogel based fluorescent micro array used for the characterization of liquid analytes. - In: Analytica chimica acta, ISSN 1873-4324, Bd. 633 (2009), 1, S. 81-89

http://dx.doi.org/10.1016/j.aca.2008.11.030
Köhler, Michael;
Isotropic etching. - In: Encyclopedia of Microfluidics and Nanofluidics, (2008), S. 877-884

http://dx.doi.org/10.1007/978-0-387-48998-8_751
Köhler, Michael;
PCR Lab-on-Chip devices. - In: Encyclopedia of Microfluidics and Nanofluidics, (2008), S. 1618-1626

http://dx.doi.org/10.1007/978-0-387-48998-8_1193
Köhler, Michael;
Microsegmented flow. - In: Encyclopedia of Microfluidics and Nanofluidics, (2008), S. 1335-1342

http://dx.doi.org/10.1007/978-0-387-48998-8_1012
Garwe, Frank; Bauerschäfer, U.; Csáki, Andrea; Steinbrück, Andrea; Ritter, Kathrin; Bochmann, A.; Bergmann, J.; Weise, A.; Akimov, D.; Maubach, G.; König, K.; Hüttmann, G.; Paa, W.; Popp, Jürgen; Fritzsche, Wolfgang
Optically controlled thermal management on the nanometer length scale. - In: Nanotechnology, ISSN 1361-6528, Bd. 19 (2008), 5, 055207, S. 1-12

http://dx.doi.org/10.1088/0957-4484/19/05/055207
Groß, G. Alexander; Thelemann, Torsten; Schneider, S.; Boškoviâc, Dušan; Köhler, Michael J.
Fabrication and fluidic characterization of static micromixers made of low temperature cofired ceramic (LTCC). - In: Chemical engineering science, Bd. 63 (2008), 10, S. 2773-2784

http://dx.doi.org/10.1016/j.ces.2008.02.030
Köhler, J. Michael; Abahmane, Lahbib; Wagner, Jörg; Albert, Jens; Mayer, Günter
Preparation of metal nanoparticles with varied composition for catalytical applications in microreactors. - In: Chemical engineering science, Bd. 63 (2008), 20, S. 5048-5055

http://dx.doi.org/10.1016/j.ces.2007.11.038
Lerchner, Johannes; Wolf, A.; Schneider, H.-J.; Mertens, F.; Kessler, E.; Baier, Volker; Funfak, Anette; Nietzsch, M.; Krügel, M.
Nano-calorimetry of small-sized biological samples. - In: Thermochimica acta, Bd. 477 (2008), 1/2, S. 48-53

http://dx.doi.org/10.1016/j.tca.2008.08.007
Groß, Gregor Alexander; Thyagarajan, Venkatesh; Kielpinski, Mark; Henkel, Thomas; Köhler, Michael
Viscosity-dependent enhancement of fluid resistance in water/glycerol micro fluid segments. - In: Microfluidics and nanofluidics, ISSN 1613-4990, Bd. 5 (2008), 2, S. 281-287

https://doi.org/10.1007/s10404-007-0244-6
Felbel, Jana; Reichert, Anett; Kielpinski, Mark; Urban, Matthias; Häfner, Norman; Dürst, Matthias; Köhler, Michael; Weber, Jörg; Henkel, Thomas
Technical concept of a flow-through microreactor for in-situ RT-PCR. - In: Engineering in life sciences, ISSN 1618-2863, Bd. 8 (2008), 1, S. 68-72

http://dx.doi.org/10.1002/elsc.200720222
Strehle, Katrin R.; Cialla, Dana; Rösch, Petra; Henkel, Thomas; Köhler, Michael; Popp, Jürgen
A reproducible surface-enhanced raman spectroscopy approach : online SERS measurements in a segmented microfluidic system. - In: Analytical chemistry, ISSN 1520-6882, Bd. 79 (2007), 4, S. 1542-1547

http://dx.doi.org/10.1021/ac0615246
Brösing, Andreas; Richter, Stefan; Scholtz, Gerhard
Phylogenetic analysis of the Brachyura (Crustacea, Decapoda) based on characters of the foregut with establishment of a new taxon. - In: Journal of zoological systematics and evolutionary research, ISSN 1439-0469, Bd. 45 (2007), 1, S. 20-32

http://dx.doi.org/10.1111/j.1439-0469.2006.00367.x
Funfak, Anette; Brösing, Andreas; Brand, Michael; Köhler, Michael
Micro fluid segment technique for screening and development studies on Danio rerio embryos. - In: Lab on a chip, ISSN 1473-0189, Bd. 7 (2007), 9, S. 1132-1138

https://doi.org/10.1039/b701116d
Köhler, Michael; Groß, Gregor Alexander
Microphotometric characterization of fluid segment populations generated in different simple microfluidic networks. - In: Microfluidics and nanofluidics, ISSN 1613-4990, Bd. 3 (2007), 6, S. 653-663
Richtiger Name des Verf.: G. Alexander Groß

https://doi.org/10.1007/s10404-007-0157-4
Schuch, Michael; Groß, G. Alexander; Köhler, J. Michael
Formation and fluorimetric characterization of micelles in a micro-flow through system with static micro mixer. - In: Sensors, ISSN 1424-8220, Bd. 7 (2007), 11, S. 2499-2509

http://dx.doi.org/10.3390/s7112499
Köhler, Michael; Romanus, Henry; Hübner, Uwe; Wagner, Jörg
Formation of star-like and core-shell AuAg nanoparticles during two- and three-step preparation in batch and in microfluidic systems. - In: Journal of nanomaterials, ISSN 1687-4129, Bd. 2007 (2007), 98134, S. 1-7

https://doi.org/10.1155/2007/98134
Groß, Gregor Alexander; Mayer, Günther; Albert, Jens; Riester, Daniel; Osterodt, Jens; Wurziger, Hanns; Schober, Andreas
Spatially encoded single-bead Biginelli synthesis in a microstructured silicon array. - In: Angewandte Chemie, ISSN 1521-3757, Bd. 118 (2006), 19, S. 3174-3178

http://dx.doi.org/10.1002/ange.200503041
Groß, Gregor Alexander; Wurziger, Hanns; Schlingloff, Gregor; Schober, Andreas
Microreactor array assembly, designed for diversity oriented synthesis using a multiple core structure library on solid support. - In: QSAR & combinatorial science, ISSN 1611-0218, Bd. 25 (2006), 11, S. 1055-1062

http://dx.doi.org/10.1002/qsar.200640120
Gebinoga, Michael; Groß, Gregor Alexander; Albrecht, Arne; Lübeck, Thomas; Henkel, Thomas; Hoffmann, Patrick; Klemz, Uwe; Schlingloff, Gregor; Frank, Thomas; Schober, Andreas
"Syn&Sort": a chip-based tool for combinatorial synthesis. - In: QSAR & combinatorial science, ISSN 1611-0218, Bd. 25 (2006), 11, S. 1063-1068
Erratum. - Bd. 26.2007, 4, S. 581

http://dx.doi.org/10.1002/qsar.200640113
Klemm, Walther; Ondruschka, Bernd; Köhler, Michael; Günther, Mike
Laboratory applications of microstructured devices in student education. - In: Micro process engineering, (2006), S. 463-495

Köhler, Michael; Wagner, Jörg; Albert, Jens; Mayer, Günter; Hübner, Uwe
Bildung von Goldnanopartikeln und Nanopartikelaggregaten in statischen Mikromischern in Gegenwart von Rinderserumalbumin (BSA). - In: Chemie - Ingenieur - Technik, ISSN 1522-2640, Bd. 77 (2005), 7, S. 867-873

https://doi.org/10.1002/cite.200500065
Wagner, Jörg; Görls, Helmar; Keutel, Heike
Novel trigonal prismatic iron complexes of expanded hexadentate Jäger type ligands: synthesis and X-ray analysis. - In: Inorganica chimica acta, ISSN 0020-1693, Bd. 358 (2005), 3, S. 808-813

http://dx.doi.org/10.1016/j.ica.2004.08.006
Köhler, J. Michael; Henkel, Thomas
Chip devices for miniaturized biotechnology. - In: Applied microbiology and biotechnology, ISSN 1432-0614, Bd. 69 (2005), 2, S. 113-125

http://dx.doi.org/10.1007/s00253-005-0176-6
Köhler, J. Michael; Wagner, Jörg; Albert, Jens
Formation of isolated and clustered Au nanoparticles in the presence of polyelectrolyte molecules using a flow-through Si chip reactor. - In: Journal of materials chemistry, ISSN 1364-5501, Bd. 15 (2005), 19, S. 1924-1930

http://dx.doi.org/10.1039/b417868h
Wagner, Jörg; Köhler, J. Michael
Continuous synthesis of gold nanoparticles in a microreactor. - In: Nano letters, ISSN 1530-6992, Bd. 5 (2005), 4, S. 685-691

http://dx.doi.org/10.1021/nl050097t
Günther, P. Mike; Möller, Frances; Henkel, Thomas; Köhler, J. Michael; Groß, G. Alexander
Formation of monomeric and novolak azo dyes in nanofluid segments by use of a double injector chip reactor. - In: Chemical engineering & technology, ISSN 1521-4125, Bd. 28 (2005), 4, S. 520-527

http://dx.doi.org/10.1002/ceat.200407122
Köhler, J. Michael; Kirner, Thomas
Nanoliter segment formation in micro fluid devices for chemical and biological micro serial flow processes in dependence on flow rate and viscosity. - In: Sensors and actuators. Physical. - Amsterdam [u.a.] : Elsevier Science, 1990- , ISSN: 1873-3069 , ZDB-ID: 1500729-7, ISSN 1873-3069, Bd. 119 (2005), 1, S. 19-27

http://dx.doi.org/10.1016/j.sna.2004.07.010
Köhler, Michael;
Chipreaktoren im Labor - ein Beitrag zur nachhaltigen Umweltvorsorge. - In: Chemie - Ingenieur - Technik, ISSN 1522-2640, Bd. 76 (2004), 5, S. 605-606

https://doi.org/10.1002/cite.200403400
Günther, Mike; Köhler, Michael;
Elektrochemische Mikrodurchflussanordnung für Standardexperimente im Studium. - In: Chemie - Ingenieur - Technik, ISSN 1522-2640, Bd. 19 (2004), 5, S. 522-526

https://doi.org/10.1002/cite.200403415
Reichert, J.; Köhler, J. Michael
Characterisation of lithographically patterned organosilane monolayers by preferential adsorption of dye molecules. - In: Biosensors and bioelectronics, ISSN 1873-4235, Bd. 19 (2004), 11, S. 1387-1393

http://dx.doi.org/10.1016/j.bios.2003.12.018
Grodrian, Andreas; Metze, Josef; Henkel, Thomas; Martin, Karin; Roth, Martin; Köhler, J. Michael
Segmented flow generation by chip reactors for highly parallelized cell cultivation. - In: Biosensors and bioelectronics, ISSN 1873-4235, Bd. 19 (2004), 11, S. 1421-1428

http://dx.doi.org/10.1016/j.bios.2003.12.021
Martin, Karin; Henkel, Thomas; Baier, Volker; Grodrian, Andrea; Schön, Thore; Roth, Martin; Köhler, Michael; Metze, Josef
Generation of larger numbers of separated microbial populations by cultivation in segmented-flow microdevices. - In: Lab on a chip, ISSN 1473-0189, Bd. 3 (2003), 3, S. 202-207

https://doi.org/10.1039/b301258c
Köhler, Michael;
Ätztechniken. - In: Handbuch Mikrotechnik, (2002), S. 279-322

Mayer, Günter; Schober, Andreas; Schober, Andreas *1961-*; Köhler, Michael;
Nanotiterplates for combinatorial chemistry. - In: Reviews in molecular biotechnology, ISSN 1878-4305, Bd. 82 (2001), 2, S. 137-159

http://dx.doi.org/10.1016/S1389-0352(01)00035-6
Schneegaß, Ivonne; Köhler, Johann Michael
Flow-through polymerase chain reactions in chip thermocyclers. - In: Reviews in molecular biotechnology, ISSN 1878-4305, Bd. 82 (2001), 2, S. 101-121

http://dx.doi.org/10.1016/S1389-0352(01)00033-2
Schneegaß, Ivonne; Bräutigam, Reiner; Köhler, Michael;
Miniaturized flow-through PCR with different template types in a silicon chip thermocyler. - In: Lab on a chip, ISSN 1473-0189, Bd. 1 (2001), 1, S. 42-49

https://doi.org/10.1039/b103846j
Csáki, Andrea; Möller, R.; Straube, W.; Köhler, J. Michael; Fritzsche, Wolfgang
DNA monolayer on gold substrates characterized by nanoparticle labeling and scanning force microscopy. - In: Nucleic acids research, ISSN 03015610, Bd. 29.2001, 16, e81, insges. 5 S.