Single-Cell Systems
Transparent microfluidic single-cell culture systems that enable manipulation, cultivation, and on-site release of selected individual cells are fabricated in a simple hybrid glass-photoresist (external pageSU-8)-polymer (external pagePDMS) approach. Single cells are trapped in a microfluidic channel by using mild suction at cell immobilization orifices, where the cells can be cultivated under controlled environmental conditions or be subjected to on-site analysis.
Cells of interest can be individually and independently released for further downstream treatment by applying negative dielectrophoretic forces via the microelectrodes at each immobilization site. The combination of hydrodynamic cell-trapping and dielectrophoretic methods for cell release enables highly versatile single-cell manipulation in an array-based format.
Elucidation of cell-to-cell variability and associated hereditary transmission are an important aspect in current research on single-cell analysis. In order to investigate the reasons for cell-to-cell variability – for example, stochastic noise in gene expression, cell aging, or differences in microenvironments – experimental setups are required that enable to monitor cells and their progeny at single-cell resolution over their whole life span.
We are developing microfluidic chips that feature simple but robust operation and cell loading for live-cell imaging of bacteria, yeast and mammalian cells. Cell growth is constrained to a horizontal plane, which enables high-resolution time-lapse imaging using automated microscope control and image acquisition.
Collaborations
Groups at ETH Zurich, Switzerland.
Recent publications
Z. Zhu, Y. Wang, R. Peng, P. Chen, Y. Geng, B. He, S. Ouyang, K.Zheng, Y. Fan, D. Pan, N. Jin, F. Rudolf, A. Hierlemann, "A microfluidic single-cell array for in situ laminar-flow-based comparative culturing of budding yeast cells", Talanta 2021, in press (DOI: 10.1016/j.talanta.2021.122401). external pageOnline
K. Chawla, S Bürgel, G. Schmidt, H-M. Kaltenbach, F. Rudolf, O. Frey, Andreas Hierlemann, "Integrating impedance-based growth-rate monitoring into a microfluidic cell culture platform for live-cell microscopy", Microsystems & Nanoengineering 2018, 4:8 (DOI 10.1038/s41378-018-0006-5). external pageOnline
M. Modena, K. Chawla, P. Misun, A. Hierlemann, "Smart cell-culture systems: Integration of sensors and actuators into microphysiological systems", ACS Chem. Biol. 2018, 13 (7), pp 1767–1784 (DOI: 10.1021/acschembio.7b01029). external pageOnline
N. Haandbaek, S. C. Bürgel, F. Rudolf, F. Heer, and A. Hierlemann, "Characterization of single yeast cell phenotypes using microfluidic impedance cytometry and optical imaging", ACS Sensors 2016, 1 (8), pp 1020–1027 (DOI: 10.1021/acssensors.6b00286). external pageOnline
B. Sorce, C. Escobedo, Y. Toyoda, M. Stewart, C. Cattin, R. Newton, I. Banerjee, A. Stettler, B. Roska, S. Eaton, A. Hyman, A. Hierlemann, D. J. Müller, "Mitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement", Nature Commununications, 2015, 6:8872 (DOI: 10.1038/ncomms9872). external pageOnline