Weighing nanoparticles in solution at the attogram scale.

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.

Toward attogram mass measurements in solution with suspended nanochannel resonators.

Using suspended nanochannel resonators (SNRs), we demonstrate measurements of mass in solution with a resolution of 27 ag in a 1 kHz bandwidth, which represents a 100-fold improvement over existing suspended microchannel resonators and, to our knowledge, is the most precise mass measurement in liquid today. The SNR consists of a cantilever that is 50 microm long, 10 microm wide, and 1.3 microm thick, with an embedded nanochannel that is 2 microm wide and 700 nm tall. The SNR has a resonance frequency near 630 kHz and exhibits a quality factor of approximately 8000 when dry and when filled with water. In addition, we introduce a new method that uses centrifugal force caused by vibration of the cantilever to trap particles at the free end. This approach eliminates the intrinsic position dependent error of the SNR and also improves the mass resolution by increasing the averaging time for each particle.

Using buoyant mass to measure the growth of single cells.

We used a suspended microchannel resonator (SMR) combined with picoliter-scale microfluidic control to measure buoyant mass and determine the 'instantaneous' growth rates of individual cells. The SMR measures mass with femtogram precision, allowing rapid determination of the growth rate in a fraction of a complete cell cycle. We found that for individual cells of Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae and mouse lymphoblasts, heavier cells grew faster than lighter cells.