According to a news release from the Massachusetts Institute of Technology, MIT engineers have come up with a novel way to determine the mass of particles with a resolution better than an attogram (one millionth of a trillionth of a gram). Weighing these small particles could help engineers gain a deeper understanding of their composition and function.

MIT engineer reduced the size of a system originally created by Scott Manalis, an MIT professor of biological and mechanical engineering, to determine the mass of bigger particles, like cells. The system is called a suspended microchannel resonator (SMR) and it determines the particles’ mass as they travel through a narrow channel. Shrinking the size of the system, enhanced its resolution to 0.85 attograms.

“Now we can weigh small viruses, extracellular vesicles, and most of the engineered nanoparticles that are being used for nanomedicine,” notes Selim Olcum, a postdoc in Manalis’ lab.

Olcum and graduate student Nathan Cermak are lead authors of the paper appearing in the journal Proceedings of the National Academy of Sciences. Manalis is the paper’s senior author. Researchers from the labs of MIT professors and Koch Institute members Angela Belcher and Sangeeta Bhatia also helped with this research.

Manalis first constructed the SMR system in 2007 to determine the mass of living cells, as well as particles as tiny as a femtogram. His lab has utilized the device to track cell development over time, determine cell density, and determine other physical properties, life stiffness.

The first mass sensor has a fluid-filled microchannel etched in a small silicon cantilever that vibrates inside a vacuum cavity. As cells or particles move through the channel, one at a time, their mass slightly changes the cantilever’s vibration frequency. The mass of the particle can be determined from that alteration in frequency.

The engineers reduced the size of the cantilever to make the device sensitive to smaller masses. “If you’re measuring nanoparticles with a large cantilever, it’s like having a huge diving board with a tiny fly on it. When the fly jumps off, you don’t notice any difference. That’s why we had to make very tiny diving boards,” Olcum explains.

Researchers in Manalis’ lab previously constructed a 50-micron cantilever. The system, called a suspended nanochannel resonator (SNR), was able to measure the mass of particles as light as 77 attograms.

The cantilever in the new version of the SNR device is 22.5 microns long. Making the cantilever smaller makes the system more sensitive because it augments the cantilever’s vibration frequency. At greater frequencies, the cantilever is more sensitive to tinier alterations in mass.

The researchers also enhanced the resolution by switching the source for the cantilever’s vibration from an electrostatic to a piezoelectric excitation. The new system allows the researchers to measure almost 30,000 particles in a little more than 90 minutes.

The researchers proved the device’s utility by weighing nanoparticles made of DNA bound to small gold spheres, which allowed them to measure how many gold spheres were bound to each DNA-origami scaffold. This information can be utilized to determine yield, which is crucial for creating accurate nanostructures.

The researchers also tested the SNR system on biological nanoparticles known as exosomes which are believed to play a role in signaling between distant locations in the body.

They discovered that exosomes secreted by liver cells and fibroblasts had dissimilar profiles of mass distribution, implying that it may be possible to differentiate vesicles that originate from different cells and may have different biological functions.

“We’re particularly excited about using the high precision of the SNR to quantify microvesicles in the blood of GBM patients. Although affinity-based approaches do exist for isolating subsets of microvesicles, the SNR could potentially provide a label-free means of enumerating microvesicles that is independent of their surface expression,” Manalis adds.