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Analytical Chemistry

Easy Mass Measurement Of Viruses And Nanoparticles

Mass Spectrometry: Technique enables analysis of previously hard-to-measure particles

by Katharine Sanderson
May 22, 2012

Viruses Sorted
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Credit: Centers for Disease Control and Prevention
Mass spectrometry can now measure individual viruses, such as these HIV particles (small spheres), shown growing on human lymphocytes, in a scanning electron micrograph.
Micrograph of HIV growing on human lymphocytes
Credit: Centers for Disease Control and Prevention
Mass spectrometry can now measure individual viruses, such as these HIV particles (small spheres), shown growing on human lymphocytes, in a scanning electron micrograph.

A fast, simple way to find the mass of nanoparticles and viruses has been developed by researchers in Taiwan (Anal. Chem., DOI: 10.1021/ac300615v).

For quality control, manufacturers need to know the mass of nanoparticles they produce. But measuring the particles’ masses quickly is difficult. Calculating mass based on particle volumes obtained from electron micrographs and density is fairly fast but inaccurate for oddly shaped particles, says Chung-Hsuan Chen of Academia Sinica, in Taipei. In addition, he says, mass spectrometry techniques that researchers have tried are slow and expensive.

Similarly, the mass distribution of virus particles, which are about the same size as nanoparticles (between 1 megadalton and 1 gigadalton) is hard to measure. If viruses in a sample vary in mass, researchers might want to know why, Chen says.

Mass spectrometry measures a molecule’s or particle’s mass-to-charge ratio. Most viruses and nanoparticles have around 50 charges or fewer when ionized. This range lies in a detection black hole: Mass spectrometry can easily cope with small molecules with one or a few charges, and techniques exist for much larger biomolecules or cells with thousands of charges. But in between, noise from the instrument’s electronics wipes out the signal.

Chen and his team used a technique they recently developed based on laser-induced acoustic desorption spectroscopy. Unlike other techniques for large particles, Chen’s method doesn’t need a matrix to hold the sample before it is ionized; matrices can form aggregates with the sample and thereby distort its mass spectral signal. It also doesn’t blast the particles apart when they are ionized, which would decrease accuracy, Chen says.

In the technique, after the sample ionizes, the ions collect in an ion trap. Chen’s team introduced a steel shield around their charge detector to reduce the electronic noise. When the researchers analyzed either spherical polystyrene nanoparticles or HIV particles, the whole process took less than a minute, Chen says – one-tenth the time of the team’s previous best efforts, which analyzed cells (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200700309).

The work is a “great example of how scientists are bridging the gap” in large particle analysis, says Mark Bier, an expert in mass spectrometry of biological samples at Carnegie Mellon University.

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