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PicoBalance: The unparalleled precision balance

Unparalleled precision

All over natural sciences and engineering mass is being measured to characterize and design a large variety of high performance systems. Yet there existed an instrumentational void for weighing microscopically sized systems such as single cells or colloidal microparticles. Motivated by this problem and driven by innovation, Nanosurf now offers a unique solution that allows nanotechnological measurements of a new dimension: the PicoBalance. Whether as a stand-alone instrument or as an add-on to the DriveAFM, the PicoBalance enables users to noninvasively measure microscopic biological or material science systems reaching sub-picogram and millisecond resolution.

Key Features & Benefits

  • Direct measurement of the total mass in liquids
  • Mass resolution: 5 pg; range: tens of pg to tens of ng*
  • Time resolution: 100 ms; range: from seconds to days*
  • Long-term stability enabling day-long experiments
  • Compatible with LiveCell chamber, inverted light microscopy, FluidFM and DriveAFM

* as measured with an NSC35

 

schematic-picobalance
Schematic of the PicoBalance.
mass-induced-frequency-shift-1

Mass induced frequency shift as seen in the amplitude response of the cantilever.

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Characterizing material science systems

Mass determination with the PicoBalance is based on the measurement of the frequency shift that is induced by attaching the sample to the mass sensor, the cantilever. One area of application is the static size and mass characterization of colloidal systems, and their dynamic swelling properties in solvents. The combination with the FluidFM technology is of particular advantage – it allows fast and reversible attachment of the systems or the research of droplet-liquid interactions. Nanosurf has refined the mass measurement workflow and supplemented it with automatic procedures for preparing and executing the measurement.

colloids-attached-to-a-Fluid-FM-cantilever

Differently sized colloids attached to a Fluid-FM cantilever for mass measurement.
Image width: 220 µm.

Mass-increase-of-paraffin-bubble-over-time-at-an-applied-pressure-of-700-mbar

Mass increase of paraffin bubble over time at an applied pressure of 700 mbar.

mass-measurements-charted

Measured vs expected bead masses. A straight line of slope 1 indicates the expected behaviour for an accurate, linear measurement.

Getting a new perspective on cellular systems

The PicoBalance also reveals new perspective on cellular systems found in fundamental, biotechnological and pharmacological research. Cells of varying sizes can be hosted on the cantilever, made to adhere by physiologically relevant substrates such as collagen, fibronectin, laminin etc. Researching the cell growth behaviour or the influence of chemicals on the cellular proliferation or function. The PicoBalance unlocks new applications in cell nutrition, mass regulation, disease related processes, and drug screening. The compatibility with transmitted light and fluorescence microscopy allows the correlation of mass measurements with cell morphology or cell state. All measurements can be performed under physiological conditions.

Actin-(red)-and-H2B-(green)-labelled-HeLa-kyoto-cell-on-a-NSC25-cantilever-during-a-long-term-measurement (2)

Actin (red) and H2B (green) labelled HeLa kyoto cell on a NSC25 cantilever during a long-term measurement.
Image width: 110 µm

Budding-yeast-proliferating-on-a-cantilever.-Fluorescent-markers-indicate-the-stage-of-the-cell-cycle

Budding yeast proliferating on a cantilever. Fluorescent markers indicate the stage of the cell cycle.
Cantilever width: 16 µm
Image courtesy: Computational systems biology group, ETH, Zurich.

Budding-yeast-cell-shows-segments-of-different-growth-rates

Budding yeast cell shows segments of different growth rates.
Scale bar: 10 µm
A.P. Cuny et al. (2022), DOI: 10.1038/s41467-022-30781-y

Contact-with-a-virus-infected-BSC40-cell-to-infect-a-HeLa-CLL-2-cell-on-the-cantilever-prior-to-mass-measurement

Contact with a virus infected BSC40 cell to infect a HeLa CLL-2 cell on the cantilever prior to mass measurement.
Image width: 120 µm
Image courtesy: Biophysics group, ETH, Zurich.

Healthy-cell-accumulates-mass,-meanwhile-the-other-cell-has-stopped-growing-as-a-result-of-its-infection-with-a-smallpox-virus

Healthy cell accumulates mass, meanwhile the other cell has stopped growing as a result of its infection with a smallpox virus.
Martínez-Martín et
al., Nature (2017). DOI: 10.1038/nature24288

Fibroblast-nucleus-mass-measurement-on-a-FluidFM-cantilever

Fibroblast nucleus mass measurement on a FluidFM cantilever.
Image width: 190 µm

Publications

PicoBalance technology in the scientific literature

The PicoBalance and its underlying technology has been subject to several publications in leading journals:

  • Martínez-Martín, D., Fläschner, G., Gaub, B. et al. Inertial picobalance reveals fast mass fluctuations in mammalian cells. Nature 550, 500–505 (2017). https://doi.org/10.1038/nature24288
  • Fläschner, G., Roman, C.I., Strohmeyer, N. et al. Rheology of rounded mammalian cells over continuous high-frequencies. Nat Commun 12, 2922 (2021). https://doi.org/10.1038/s41467-021-23158-0
  • Andreas P. Cuny, David Martínez-Martín, Gotthold Fläschner. pyIMD: Automated analysis of inertial mass measurements of single cells. SoftwareX, Volume 10, 2019, 100303, ISSN 2352-7110.
    https://doi.org/10.1016/j.softx.2019.100303
  • Andreas P. Cuny, K. Tanuj Sapra, David Martinez-Martin, Gotthold Fläschner, Jonathan D. Adams, Sascha Martin, Christoph Gerber, Fabian Rudolf and Daniel J. Müller. High-resolution mass measurements of single budding yeast reveal linear growth segments. Nat Commun (2022)
    https://doi.org/10.1038/s41467-022-30781-y