Weighing of biomolecules, single cells and single nanoparticles in fluid
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Nanomechanical resonators enable the measurement of mass with extraordinary sensitivity. 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 reach. Resolving small mass changes requires the resonator to be light and to ring at a very pure tone-that is, with a high quality factor. In solution, viscosity severely degrades both of these characteristics, thus preventing many applications in nanotechnology and the life sciences where fluid is required. Although the resonant structure can be designed to minimize viscous loss, resolution is still substantially degraded when compared to measurements made in air or vacuum. An entirely different approach eliminates viscous damping by placing the solution inside a hollow resonator that is surrounded by vacuum. 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 microbalance. 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.
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The suspended microchannel resonator measures buoyant mass of live single cells with resolution near 50 femtograms, which is precise given that a hematopoietic cell has an average buoyant mass of about 75 picograms.
“The SMR is a cantilever-based microfluidic mass sensor that measures the buoyant mass (referred to hereafter simply as mass) of live single cells with a resolution near 50 fg, which is highly precise given that the average buoyant mass of a hematopoietic cell is ~75 pg11.”
From Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate (2016) · cites this paper as [11]
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- Authors
- Burg, T. P., Godin, M., Knudsen, S. M., Shen, W., Carlson, G., Foster, J. S., Babcock, K., & Manalis, S. R.
- Affiliations
- Massachusetts Institute of Technology (US)
- Innovative Micro Technology (United States) (US)
- Corresponding author
- Manalis, Scott R.
- Venue
- Nature
- Published
- 2007-04
- Volume
- 446
- Issue
- 7139
- Pages
- 1066-1069
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2149562261
- Cited by
- 1,213
- References
- 35
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 39 · 2023: 46 · 2022: 39 · 2021: 58 · 2020: 68 · 2019: 70 · 2018: 75 · 2017: 65 · 2016: 78 · 2015: 78 · 2014: 85 · 2013: 81 · 2012: 84
- FWCI
- 42.64
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- TUbilio (Technical University of Darmstadt) (submittedVersion)
- Funders
- National Institutes of Health (5p50gm068762-10)
- National Institute of General Medical Sciences (P50-GM068762)
- Topics
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Mechanical and Optical Resonators
- Physical Sciences › Engineering › Biomedical Engineering › Acoustic Wave Resonator Technologies
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Advanced MEMS and NEMS Technologies
- Keywords
- nanomechanical resonators, suspended microchannel resonators, viscous damping, microfluidic channels, protein adsorption, quality factor, silicon resonators, medical diagnostics, environmental monitoring
- MeSH terms
- Bacteria, Biological Products, Cells, Colloids, Molecular Weight, Proteins, Quartz, Solutions, Vacuum, Microfluidics, Nanoparticles
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