Project overview

Project 1

Single particle catalysis in microfluidic systems
The integration of chemical syntheses and analysis in the microscale enables to study organic reactions at lowest dimensions. The scientific focus in project 1 is on the development of methods to investigate catalytic transformations at the single particle level. The preferred approach to study single catalyst particles in solution is the application of chip-based droplet microfluidics in combination with appropriate inline detection techniques. A central aspect is the efficient coupling of microfluidic processes with highly sensitive analytical systems. One of the main challenges is the realization of controlled reaction processes at the single particle level in combination with high performance analytical techniques with appropriate sensitivity for the detection of minimal sample amounts. This should lead to the development of novel tools based on lab-on-a-chip technology for a rapid development and optimization of chemical processes at unrivaled dimensions with regard to space, time and material usage.

Figure 1: Schematic depiction and operating principle of a polymer based microfluidic chip for reaction monitoring of organic syntheses in individual droplets.

Project 2

Empirical understanding of glycosylation reactions
Oligosaccharides are ubiquitous in biological systems. The key step to synthesize these complex structures by glycosylation reactions is the coupling of two individual sugar units. The reaction conditions are almost always substrate dependent, significantly delaying any synthetic route. They are highly sensitive two-stage reactions, proposed to first form a reactive acyloxonium ion intermediate which is trapped by the second sugar unit. To date, optimization of these processes occurs exclusively in a manual fashion via analysis of the products obtained. In this project the first automated reaction optimizer for glycosylation reactions will be developed, where the formation of the key reactive intermediate formed upon activation of monosaccharides on a microfluidic platform will be monitored in situ for the first time using Raman spectroscopy. The system will utilize multivariate analysis of the Raman data for characterization of the reaction mixture in position and time. In this way, intermediate basis spectra will be obtained. By controlling the reaction conditions, the concentration of the key reactive intermediate can be maximized at the site where the trapping agent (second sugar) is added. The Raman data will feed into the computer program LabVIEW, which, based on the results received, will automatically control pumps and temperature in order to optimize the chemical processes. Apart from the development of a new characterization approach, this system will give us tremendous insight into how glycosylation reactions work, how reaction conditions and substituents affect the formation of the key reactive intermediate, as well as to the rates of both acyloxonium ion formation as well as intermolecular trapping. This system will transform the way glycosylation reactions are both performed and understood.

Project 3

Inline characterization in microfluidic reaction systems by SERS
The application of SERS in microfluidic structures enables the sensitive detection of reacting species. Therefore it is, in principle, possible to monitor chemical reactions in situ. Apart from the identification and quantification of reactants, SERS sensors enable the precise characterization of micro-envoíronments (e.g., regarding pH or temperature). In the proposed project, we will develop SERS in order to attain in-line monitoring and control of chemical reactions. To achieve this goal, we will generate and exploit multifunctional nanostructures that, apart from serving as SERS substrate, can also influence the course of chemical reactions due to their plasmonic properties, resulting in photocatalytic activities and photothermal effects that can be used to control temperature very locally. The new methodological concepts will be applied to two types of reaction, (i) the characterization of a known plasmon-supported reaction and (ii), monitoring the decomposition of artesunate, an anti-malarial / anti-tumoral compound. To vary the chemical composition of reaction mixtures at the microscale and to monitor and image them over time by SERS is only possible in a microfluidic system. Apart from sensitive detection, SERS enables inline structural characterization of the reacting molecules. In addition to this methodlogical innovation, the project will generate new basic insights into plasmon- and nanostructure supported reactions.

Project 4

Integrated microfluidic systems for the elucidation of reaction mechanism, optimization and further development of selective, sequential heterocycles syntheses using a novel 1,2-dinucleophile
In this project we intend to study integrated microfluidic systems in the context of a new recently discovered and currently quite limited heterocycle synthesis and take advantage of the full potential of microfluidic processes for mechanistic analysis, optimization, and further development of novel organic transformations. Through direct coupling of the domino multicomponent reaction with inline nanoelectrospray mass spectrometry on a microchip we intend to detect the relevant reaction intermediates and unambiguously elucidate the reaction mechanism. With the help of a highly efficient micromixer and a flow reactor controlled by inline IR-spectroscopy the selectivity of the overall process shall be better controlled and the scope of the reaction significantly widened. In addition, we intend to access enantiomerically enriched products using chiral catalysts and more complex heterocyclic structures via subsequent transformations.

Project 5

Transient intermediates and product distributions of organic reactions in free flow microfluidic reaction systems
Within the present project fast microfluidic mixers and free liquid beam (droplet) mixer reactors will be developed, validated and employed for the measurement of kinetic parameters and intermediates, as well as products of fast organic reactions. The organic reactions under study are i) those in which an organic catalyst in involved. In this particular case photo-switchable molecules that are able to efficiently bind a catalyst enable to selectively control the catalyst and thus in turn the organic reaction. The other type of reaction is ii) a complex (one pot) organic reaction which can be used to rapidly build up complexity in one reaction. Although, the type of reaction is efficient the mechanism is hardly known. Both reactions will be investigated with in situ fluorescence and FT-IR spectroscopies as well as liquid beam desorption mass spectrometry. The approach will enable new possibilities for an optimization of the reactions.

Project 6

Impedimetric monitoring in microfluidic reaction systems for small molecule detection in flow
Project 6 deals with the development and integration of cell based analytical modules and their integration into chip-based micro reaction systems. The objective is a flow-through label-free and online analysis of small molecules and compounds. To this end, multi-zone microelectrode arrays will be developed and incorporated into one microfluidic chip in order to combine all modules – integrated micro reactors, microfluidic free-flow electrophoresis (μFFE) and cell-based analysis. The microelectrode array based analytical module will allow (a) a label-free impedimetric monitoring of chemical micro syntheses in a continuous flow and (b) a real-time and serial monitoring of cell functions. In addition to bioelectrical monitoring, the continuously separated reaction products (small molecules) will also be detected and characterized in viable cells by optical monitoring. For the first time, chemical synthesis, separation and detection of biological function will be combined on a minimum of space. Such a novel integrated system will certainly increase the effectiveness, safety and efficacy of the selection process of bioactive lead substances.

Project 7

Multistep chip reactors with an integrated continuous separation
In Project 7 chip-based multistep flow reactors are being developed, which allow a continuous synthesis in two stages with an intermediate micro free flow electrophoresis. The fabrication, adaptation and application of combined microreactor-microFFE platforms for organic synthesis will be pursued. For method development the synthesis of quinoline-substituted cyclopentenes is investigated. The main product of the synthesis is to be separated from a by-product in the microFFE. Subsequently, the integration of a second reactor stage downstream to the preparative separation, which is suitable for increased temperatures and which allows to control and monitor the temperature on the micro scale, will be performed. In this flow reactor stage a Diels-Alder reaction to build up a multicyclic system in the quinoline side chain is to be carried out. Optical fluorescence detection in the UV region for inline monitoring of chemical reactions and separations will be developed and the coupling of multistage reactors to (bio-)impedance spectroscopy will demonstrated to enable an integrated biosensor. Via the integration of these functions, a continuous multistep organic synthesis, which requires a separation step, on a single microfluidic chip and its inline monitoring and biological testing will be enabled for the first time.

Project 8

Synergistic Photocatalysis with short-lived intermediates in microfluidic systems
The proposed project is focussed on photochemical and/or photocatalytical flow-based syntheses in classical flow or microchip reaction systems. In this context, the combination of photoredox catalytic reactions with instable intermediates, which will be generated in parallel, will be investigated to provide a facile access to highly functionalized heterocycles. In addition to the known benefits like improved irradiation and acceleration of the reaction as well as better mixing of the reactants, we want to build on the intrinsic analytical advantages of lab-on-a-chip technology to apply these in challenging optimizations of dual and synergistic catalyses.

Project 9

Central project
Scientific and technical aspects relevant for the whole research unit are processed, coordinated and provided by the central project. Besides technical support of all project teams in the fields of microsystem technology and instrumental analysis various approaches for coupling microfluidic chips to nano electrospray mass spectrometry and liquid beam desorption mass spectrometry will be developed. A major focus of basic research is the development of analytical techniques for ultrafast enantiomer differentiation in microfluidic devices. In this context, the coupling of microfluidic chips to ion mobility spectrometry and mass spectrometry will be evaluated and further developed. This should open up new avenues for on-the-fly monitoring of enantioselective processes, such as catalyses in chemical micro systems.

last modified: 29.03.2016