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Journal Article

Weighing of biomolecules, single cells and single nanoparticles in fluid.


Burg,  T. P.
Research Group of Biological Micro- and Nanotechnology, MPI for biophysical chemistry, Max Planck Society;

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Burg, T. P., Godin, M., Shen, W., Carlson, G., Foster, J. S., Babcock, K., et al. (2007). Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature, 446, 1066-1069. doi:10.1038/nature05741.

Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-9C58-F
Nanomechanical resonators enable the measurement of mass with extraordinary sensitivity1, 2, 3, 4, 5, 6, 7. Previously, samples as light as 7 zeptograms (1 zg = 10-21 g) have been weighed in vacuum, and proton-level resolution seems to be within reach8. Resolving small mass changes requires the resonator to be light and to ring at a very pure tone—that is, with a high quality factor9. In solution, viscosity severely degrades both of these characteristics, thus preventing many applications in nanotechnology and the life sciences where fluid is required10. Although the resonant structure can be designed to minimize viscous loss, resolution is still substantially degraded when compared to measurements made in air or vacuum11, 12, 13, 14. An entirely different approach eliminates viscous damping by placing the solution inside a hollow resonator that is surrounded by vacuum15, 16. Here we demonstrate that suspended microchannel resonators can weigh single nanoparticles, single bacterial cells and sub-monolayers of adsorbed proteins in water with sub-femtogram resolution (1 Hz bandwidth). Central to these results is our observation that viscous loss due to the fluid is negligible compared to the intrinsic damping of our silicon crystal resonator. The combination of the low resonator mass (100 ng) and high quality factor (15,000) enables an improvement in mass resolution of six orders of magnitude over a high-end commercial quartz crystal microbalance17. This gives access to intriguing applications, such as mass-based flow cytometry, the direct detection of pathogens, or the non-optical sizing and mass density measurement of colloidal particles.