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FluidFM: Combining Atomic Force Microscopy and Nanofluidics in a Universal Liquid Delivery System for Single Cell Applications and Beyond

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André Meister^†^§, Michael Gabi^‡^§, Pascal Behr^‡, Philipp Studer^‡, János Vörös^‡, Philippe Niedermann^†, Joanna Bitterli^†, Jérôme Polesel-Maris^†, Martha Liley^†, Harry Heinzelmann^† and Tomaso Zambelli*^‡

Swiss Center for Electronics and Microtechnology, CSEM SA, rue Jaquet Droz 1, 2002 Neuchâtel, Switzerland, and Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland

Nano Lett., 2009, 9 (6), pp 2501–2507

DOI: 10.1021/nl901384x

Publication Date (Web): May 19, 2009

* To whom correspondence should be addressed. E-mail: zambelli@biomed.ee.ethz.ch., †

Swiss Center for Electronics and Microtechnology, CSEM SA.

, ‡

Institute for Biomedical Engineering, ETH Zurich.

, §

These authors contributed equally to the work.

Present address: London Centre for Nanotechnology, 17-19 Gordon Street, London WC1H 0AH, United Kingdom.

Present address: CEA Saclay, DSM/IRAMIS/SPCSI, 91191 Gif-sur-Yvette, France.

Section:

Biochemical Methods

Abstract

We describe the fluidFM, an atomic force microscope (AFM) based on hollow cantilevers for local liquid dispensing and stimulation of single living cells under physiological conditions. A nanofluidic channel in the cantilever allows soluble molecules to be dispensed through a submicrometer aperture in the AFM tip. The sensitive AFM force feedback allows controlled approach of the tip to a sample for extremely local modification of surfaces in liquid environments. It also allows reliable discrimination between gentle contact with a cell membrane or its perforation. Using these two procedures, dyes have been introduced into individual living cells and even selected subcellular structures of these cells. The universality and versatility of the fluidFM will stimulate original experiments at the submicrometer scale not only in biology but also in physics, chemistry, and material science.

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