Flow-through Single-cell Analysis

The complex interaction of metabolic mechanisms within a single can lead to very individual cell responses to an event or stimulus. To analyze this individual behavior in the context of Systems Biology it is necessary to combine analytical chemistry methods with new instrumentation that allows for investigating the metabolome of a single cell. A major challenge is the minute volume of a single cell, which is in the range of one picoliter for a yeast cell. Therefore, a microfluidic to handle single cells coming from, e.g., a cell reactor, has been developed. It includes detectors to monitor cell properties, like the cell size and fluorescence intensity, while entering the microsystem. Subsequently, the cells are lysed, and the metabolites of each single cell are extracted and handed over to a MALDI-TOF mass spectroscopy substrate in a continuous process.

A glass/polydimethylsiloxane (PDMS) microsystem has been used that consists of three layers (glass, PDMS foil, PDMS block). The chip-holder allows for interfacing the microfluidic device with external electronics and fluidics. It is designed to fit on an inverted light microscope. A stack of two Peltier-elements was used for controlled cooling (stopping of the metabolism upon cell entrance in the microsystem).

Outlook

Future activities will include process optimization for the impedance-based cell sizing and characterization subunit and the cell lysis unit.

Publications

• N. Goedecke, F. Faraci, F. Heer, S. Hafizovic, R. Streichan, A. Hierlemann, "Microfluidic device for continuous-flow cell lysis", Book of Abstracts Eurosensors XXII, Dresden, Germany, 2008, p. 735, ISBN 978-3-00-025218-1.
• N. Goedecke, R. Toelke, F. Heer, A. Hierlemann, “Microsystem for single-cell metabolomics“, Proc. of the IEEE Transducers 2007, Lyon, France, p. 727-730, ISBN 1-4244-0841-5.
• N. Goedecke, R. Tölke, O. Frey, K.U. Kirstein, and A. Hierlemann. Microfluidic System for Single-Cell Metabolomics, Nanotech 2006, Montreux, Switzerland 2006.

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Contact

Dr. Nils Goedecke