1. Department of Biological Engineering,
2. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3. Innovative Micro Technology, Santa Barbara, California 93117, USA
4. Affinity Biosensors, Santa Barbara, California 93117, USA
5. These authors contributed equally to this work.

Correspondence to: Scott R. Manalis^1,2 Correspondence and requests for materials should be addressed to S.R.M. (Email: scottm@media.mit.edu).

Abstract

Nanomechanical resonators enable the measurement of mass with extraordinary sensitivity^{1, 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 vacuum^{11, 12, 13, 14}. An entirely different approach eliminates viscous damping by placing the solution inside a hollow resonator that is surrounded by vacuum^{15, 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.

1. Department of Biological Engineering,
2. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3. Innovative Micro Technology, Santa Barbara, California 93117, USA
4. Affinity Biosensors, Santa Barbara, California 93117, USA
5. These authors contributed equally to this work.

Correspondence to: Scott R. Manalis^1,2 Correspondence and requests for materials should be addressed to S.R.M. (Email: scottm@media.mit.edu).

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