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Research Projects

PhD project Christoph Westerwalbesloh M.Sc., December 2015 - May 2019

„Model-based Analysis and Design of Microfluidic Single-cell Cultivation Devices“

Microfluidic devices offer new opportunities for research and optimization of microorganisms on single-cell level, e.g. regarding the causes of cell-to-cell heterogeneity, which has been found to influence biotechnological processes. Microfluidic platforms allow cultivation of several hundred microcolonies, each consisting of up to several hundred cells, in separate cultivation chambers on one device. Data, e.g. growth rates, can be generated by automated time-lapse microscopy with spatiotemporal resolution on single-cell level. The small length scale in the micrometer range provides good environmental control with regard to the cultivation medium, i.e. constant substrate and low product and byproduct concentrations. Due to the corresponding small volumes of several picoliters per reaction chamber it is currently impossible to directly measure those concentrations and their gradients within the devices. Moreover, many different designs, varying in cultivation chamber size and nutrient supply channel configuration, have been implemented. Therefore, in this project the microfluidic devices are modeled and simulated computationally. The liquid velocity field and the mass transfer within the supply channels and cultivation chambers are calculated to gain insight in the spatial distribution of supplied nutrients and metabolic products secreted by the cultivated bacteria. The goal is to identify potential substrate limitations or product accumulations within the cultivation devices and the resulting inhomogeneity experienced by single cells. This lays the foundation for further studies and the optimization of existing microfluidic bioreactor systems.

Contact: c.westerwalbesloh@fz-juelich.de

Model-based Analysis and Design of Microfluidic Single-cell Cultivation DevicesExample for the influence of growth chamber design on the nutrient supply for a bacterial colony. The nutrient profile for three different designs was simulated with a colony of 300 bacterial cells in each chamber. Blue areas have good supply, red areas lack nutrients due to the bacterial uptake and limited diffusive transport.

PhD project M.Sc. Eugen Kaganovitch, September 2015–February 2019

„Environmental control for microfluidic single-cell analysis“

Population heterogeneity has a major impact on biotechnological production processes. In order to understand the mechanisms which underlie the formation of different bacterial phenotypes, the cultivation of single cells under well controlled environmental conditions is essential.
This project focusses on the development of microfluidic devices for single-cell analysis offering the manipulation and measurement of vital parameters such as oxygen, pH or media composition.

Graphic Environmental control for microfluidic single-cell analysisCultivation of E. coli in microfluidic batch reactors. a) Microfluidic chip (left) and channel structure (right). b) Series of phase contrast images showing limited E. coli growth in isolated batch reactors.

PhD project Dipl.-Ing. Christina E. M. Krämer B.Sc., October 2012 – September 2015

“Bacterial Growth and Stress Studies in Controlled Microfluidic Environments”

Microfluidic devices incorporate microstructures in which the bacterial environment is well controlled by the systems operator. Thus, rapidly changing microenvironments and stressful growth conditions, bacteria have to cope in bioprocesses and in nature, can be simulated to study the physiology of prokaryotes by single cell resolution microscopy techniques. Therefore, microfluidic platform technology optimization is a major scope of this research project. This includes also the modification of cell cultivation structures and the modification of their polymer material surfaces.
The work is part of the DFG research project SPP1617 – Phenotypic heterogeneity and sociobiology of bacterial populations (link: http://spp1617.de/frunzke). This PhD project is strongly related to in-house and extern cooperations. Contact: c.kraemer@fz-juelich.de

Graphic Bacterial Growth and Stress Studies in Controlled Microfluidic Environments

1 Phenotypical Heterogeneity of Stressed C. glutamicum Cells Expressing YFP
2 Microfluidic Device as Controllable Microenvironment to Study Stressor Cell Response Interactions: M. luteus Cultivated in Microstructure
3 Lysing Bacteria with Released DNA (Stained Red)
4 Intracellular Metabolic Activity (Violet Fluorochrome) Combined with a Vital Stain Showing Dead Cells (Red)


Principal of optical trappingPrincipal of optical trapping; A transparent sphere is held near the focus point of a Gaussian laser beam. The forces created by the laser beam are referred to as gradient force, which keeps an object at a certain equilibrium position inside the beam, and the scattering force, due reflection of light, which tries to push out any object.



PhD project Dipl. -Ing. (FH) Christopher Probst, May 2011-May 2014

Optical manipulation in Microfluidic Single-Cell-Analysis of Prokaryotic Production Strains

Optical manipulation offers the possibility to manipulate particles in a range from just a few nanometer (e.g. Atoms) up to micrometer. By using an optical manipulation instrument, known as optical tweezers, single or multiple living objects can be addressed. In our research, single prokaryote cells will be optically manipulated as a tool for single cell analysis in microfluidic environments.  Primary task is to investigate the influence by the 1064nm IR laser beam to cell viability and productivity.  Contact: c.probst@fz-juelich.de










PhD project Dipl. -Ing.  Alexander Grünberger, October 2010-March 2014

Single Cell Investigation of Microbial Production Strains in Microfluidic Bioreactors

The impact of single cell behaviour and population heterogeneity on the productivity of industrial bioprocesses is still not well understood. Microfluidic devices offer a unique facility to investigate the dynamic behaviour of single cells under well controlled environmental conditions. Miniaturized chip-based systems have been successfully demonstrated in various fields, like chemical synthesis, biological analysis, medical diagnostics, optics and information technology. In the field of cell biology and biotechnology microfluidic chips enable the investigation of single organisms in “single cell bioreactors”. In this project single cell trapping arrays are developed and fabricated applying soft lithography. Industrial relevant production organism, mainly based on E.Coli and C. Glutamicum, are investigated with respect to cell growth and productivity. There is a strong cooperation with many groups of our institute, especially the Amino Acid and Cell Wall Group and Population Heterogeneity and Signal Transduction Group.  Contact: a.gruenberger@fz-juelich.de

PDMS chip with fluidic networkImage series showing a fabricated PDMS chip with fluidic network for nutrient supply and cell trapping area. Single, e.g., E.Coli cells are trapped in an array like manner in hydrodynamic cell traps.


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