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Research Article

Weighing nanoparticles in solution at the attogram scale

Selim Olcum, Nathan Cermak, Steven C. Wasserman, Kathleen S. Christine, Hiroshi Atsumi, Kris R. Payer, Wenjiang Shen, Jungchul Lee, Angela M. Belcher, Sangeeta N. Bhatia, and Scott R. Manalis
PNAS first published January 13, 2014; https://doi.org/10.1073/pnas.1318602111
Selim Olcum
Departments of aBiological Engineering,
bKoch Institute for Integrative Cancer Research,
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Nathan Cermak
cComputational and Systems Biology Initiative,
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Steven C. Wasserman
Departments of aBiological Engineering,
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Kathleen S. Christine
dHarvard–MIT Health Sciences and Technology,
eInstitute for Medical Engineering and Science, and
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Hiroshi Atsumi
fMaterials Science and Engineering,
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Kris R. Payer
gMicrosystems Technology Laboratories, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Wenjiang Shen
hInnovative Micro Technology, Santa Barbara, CA 93117;
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Jungchul Lee
iDepartment of Mechanical Engineering, Sogang University, Seoul 121-742, Korea; and
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Angela M. Belcher
Departments of aBiological Engineering,
bKoch Institute for Integrative Cancer Research,
fMaterials Science and Engineering,
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Sangeeta N. Bhatia
bKoch Institute for Integrative Cancer Research,
dHarvard–MIT Health Sciences and Technology,
eInstitute for Medical Engineering and Science, and
jElectrical Engineering and Computer Science, and
kHoward Hughes Medical Institute, Cambridge, MA 02139
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Scott R. Manalis
Departments of aBiological Engineering,
bKoch Institute for Integrative Cancer Research,
cComputational and Systems Biology Initiative,
lMechanical Engineering,
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  • For correspondence: scottm@media.mit.edu
  1. Edited by Alexis T. Bell, University of California, Berkeley, CA, and approved December 13, 2013 (received for review October 4, 2013)

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Significance

Naturally occurring and engineered nanoparticles (e.g., exosomes, viruses, protein aggregates, and self-assembled nanostructures) have size- and concentration-dependent functionality, yet existing characterization methods in solution are limited for diameters below ∼50 nm. In this study, we developed a nanomechanical resonator that can directly measure the mass of individual nanoparticles down to 10 nm with single-attogram (10−18 g) precision, enabling access to previously difficult-to-characterize natural and synthetic nanoparticles.

Abstract

Physical characterization of nanoparticles is required for a wide range of applications. Nanomechanical resonators can quantify the mass of individual particles with detection limits down to a single atom in vacuum. However, applications are limited because performance is severely degraded in solution. Suspended micro- and nanochannel resonators have opened up the possibility of achieving vacuum-level precision for samples in the aqueous environment and a noise equivalent mass resolution of 27 attograms in 1-kHz bandwidth was previously achieved by Lee et al. [(2010) Nano Lett 10(7):2537–2542]. Here, we report on a series of advancements that have improved the resolution by more than 30-fold, to 0.85 attograms in the same bandwidth, approaching the thermomechanical noise limit and enabling precise quantification of particles down to 10 nm with a throughput of more than 18,000 particles per hour. We demonstrate the potential of this capability by comparing the mass distributions of exosomes produced by different cell types and by characterizing the yield of self-assembled DNA nanoparticle structures.

  • nanoparticle characterization
  • NEMS
  • microfluidics
  • mechanical oscillators

Footnotes

  • ↵1S.O. and N.C. contributed equally to this work.

  • ↵2To whom correspondence should be addressed. E-mail: scottm{at}media.mit.edu.
  • Author contributions: S.O., J.L., A.M.B., S.N.B., and S.R.M. designed research; S.O., N.C., S.C.W., K.S.C., and H.A. performed research; K.R.P. and W.S. contributed new reagents/analytic tools; S.O. and N.C. analyzed data; and S.O., N.C., S.C.W., and S.R.M. wrote the paper.

  • Conflict of interest statement: S.R.M. declares competing financial interests as a cofounder of Affinity Biosensors, which develops techniques relevant to the research presented.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1318602111/-/DCSupplemental.

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Weighing nanoparticles at the attogram scale
Selim Olcum, Nathan Cermak, Steven C. Wasserman, Kathleen S. Christine, Hiroshi Atsumi, Kris R. Payer, Wenjiang Shen, Jungchul Lee, Angela M. Belcher, Sangeeta N. Bhatia, Scott R. Manalis
Proceedings of the National Academy of Sciences Jan 2014, 201318602; DOI: 10.1073/pnas.1318602111

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Weighing nanoparticles at the attogram scale
Selim Olcum, Nathan Cermak, Steven C. Wasserman, Kathleen S. Christine, Hiroshi Atsumi, Kris R. Payer, Wenjiang Shen, Jungchul Lee, Angela M. Belcher, Sangeeta N. Bhatia, Scott R. Manalis
Proceedings of the National Academy of Sciences Jan 2014, 201318602; DOI: 10.1073/pnas.1318602111
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