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  • Primer
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Fluidic force microscopy

Nature Reviews Methods Primers volume 6, Article number: 15 (2026) Cite this article

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Abstract

Fluidic force microscopy is a versatile bionanotechnology platform that integrates atomic force microscopy with microfluidic probes. This hybrid approach enables precise measurement and application of forces across sub-nanonewton to micronewton ranges while simultaneously dispensing or sampling sub-femtolitre to picolitre volumes, all with real-time optical visualization at sub-micrometre resolution. In recent years, fluidic force microscopy has emerged as an enabling tool for minimally invasive single-cell manipulation, subcellular analysis and high-resolution nanoprinting applications. This Primer describes the fundamental principles underlying the combination of atomic force microscopy with microchannelled cantilevers, providing a comprehensive framework for understanding the unique capabilities of fluidic force microscopy and its rapidly expanding range of applications in biological research and nanotechnology.

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Fig. 1: Basic principles of FluidFM.
Fig. 2: Scanning electron micrographs of FluidFM probe tips.
Fig. 3: Calibration of the FluidFM system.
Fig. 4: FluidFM operating modes.
Fig. 5: Example of experimental results.
Fig. 6: Local dispensing experiments.
Fig. 7: Indentation and adhesion experiments.
Fig. 8: Injection, extraction and transplantation experiments.
Fig. 9: Ionic current experiments.

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Acknowledgements

The authors thank all the doctoral students and post-doctoral fellows who invaluably contributed to the progress of the FluidFM. The authors thank D. Ossola, P. Dörig, P. Behr and M. Gabi (Cytosurge AG, CH), D. Bijl (Smarttip BV, NL) as well as P. Frederix, C. Bippes and M. Portalupi (Nanosurf AG, CH) for their constant support. T.Z. is indebted to J. Vörös (ETH Zurich) for his generous continuous trust. The development of the FluidFM and its applications has been enabled by several grants of the Swiss KTI-CTI agency (now Innosuisse) to T.Z. and J.A.V., grants from the Swiss National Science Foundation to T.Z., and a European Research Council Advanced Grant (number 883077) as well as funding from the Swiss State Secretariat for Education, Research and Innovation (SERI) to J.A.V. The contribution of R.H. was supported by the Momentum (Lendület) Program of the Hungarian Academy of Sciences and the National Research, Development, and Innovation Fund (NKFIH) of Hungary under grant TKP2021-EGA-04, ADVANCED 153121 and 2024-1.2.10-TÉT-IPARI-IL-2024-00030. The contribution of M.L. was supported by the National Natural Science Foundation of China (no. 62573403) and the Natural Science Foundation of Liaoning Province (no. 2024JH3/50100021). The contribution of G.-y.L. was supported the National Science Foundation of USA (CHE-2304986).

Author information

Authors and Affiliations

  1. Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland

    Tomaso Zambelli

  2. Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland

    Orane Guillaume-Gentil

  3. Bruker Nederland BV, Leiderdorp, The Netherlands

    Edin Sarajlic

  4. Department of Physical Chemistry II, University of Bayreuth, Bayreuth, Germany

    Georg Papastavrou

  5. Nanobiosensorics Laboratory, Institute of Technical Physics and Materials Science, HUN-REN Centre for Energy Research, Budapest, Hungary

    Robert Horvath

  6. Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary

    Robert Horvath

  7. Department of Chemistry, University of California, Davis, CA, USA

    Gang-yu Liu

  8. State Key Laboratory of Robotics and Intelligent Systems, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, China

    Mi Li

  9. Department of Biology, Institute of Microbiology, ETH Zurich, Zurich, Switzerland

    Julia A. Vorholt

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  1. Tomaso Zambelli
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  4. Georg Papastavrou
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Contributions

Introduction (T.Z., O.G.-G., G.P., R.H., G.-y.L., M.L. and J.A.V.); Experimentation (T.Z., O.G.-G., E.S., G.P., R.H., G.-y.L., M.L. and J.A.V.); Results (T.Z., O.G.-G., G.P., R.H., G.-y.L., M.L. and J.A.V.); Applications (T.Z., O.G.-G., G.P., R.H., G.-y.L., M.L. and J.A.V.); Reproducibility and data deposition (T.Z., O.G.-G., G.P., R.H., G.-y.L., M.L. and J.A.V.); Limitations and optimizations (T.Z., O.G.-G., E.S., G.P., R.H., G.-y.L., M.L. and J.A.V.); Outlook (T.Z., O.G.-G., E.S., G.P., R.H., G.-y.L., M.L. and J.A.V.); overview of the Primer (T.Z. and J.A.V.).

Corresponding author

Correspondence to Tomaso Zambelli.

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Competing interests

E.S. oversees the production of FluidFM probes and is employed by Bruker Nederland BV (NL). The other authors declare no competing interests.

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Nature Reviews Methods Primers thanks Ricardo Garcia, Ana Sancho and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Zambelli, T., Guillaume-Gentil, O., Sarajlic, E. et al. Fluidic force microscopy. Nat Rev Methods Primers 6, 15 (2026). https://doi.org/10.1038/s43586-025-00463-2

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