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Detection and characterization of nano-particles
WHAT IS ES-DMA?
Electro-spray Differential Mobility Analysis (ES-DMA) is an analytical procedure for detecting, separating and counting nano-particles in the range of 1-200 nanometers.
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ES-DMA (also known as GEMMA, SMPS, or more broadly as ion mobility spectrometry/IMS) combines two powerful methods:
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Electro-spray aerosolizes and ionizes a liquid sample (gas samples can bypass this step). Electro-spray relies on the creation of a "Taylor cone" at the tip of a thin capillary to capture nano-particles within tiny droplets. When the droplets evaporate, the particles are left in an ionized gaseous state. To maximize the number of particles with a single positive charge, especially for larger particles, ES-DMAs may also use various charge reduction techniques to partially "neutralize" the sample (our systems use a second electro-spray; other options are radioisotopes or soft x-ray).
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Differential mobility analysis separates the ionized particles by exposure to two orthogonal forces: (i) fast-flowing air at normal air pressure, and (ii) a high voltage electrical field. These forces establish a one-to-one correspondence between the electro-magnetic voltage and the "flight path" of the particles. A small opening in the DMA chamber allows only particles of a particular size to flow out of the main air flow and into a detector.
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ES-DMA produces a spectral output that is normally shown as a 2D graph with size or voltage on the X axis and particle counts/second on the Y axis. Spectra generally show "peaks" for singly charged particles of common size, as well as smaller peaks for multiply charged particles. Also like MS, analysis of the spectra, including the application of de-convolution algorithms, is applied to optimize the identification of such particles.
MULTI-STEP PROCESS
Liquid samples are aerosolized, ionized and neutralized (to maximize +1,2 and 3 charges) after sample preparation. Gas samples require only ionization.
EVOLUTION OF ES-DMA
The scientific roots of ES-DMA are in electro-spray mass spectrometry (“ES-MS”), a technique developed at Yale University by John Fenn in the late 1980s. Prof. Fenn's discovery enabled ES-MS to expand into larger molecules and proteins, essentially spawning the science of proteomics. Prof. Fenn and others were awarded the Nobel Prize in Chemistry in 2002 in recognition of their achievements.
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ES-DMA shares key basic components with ES-MS, such as (i) sample collection and preparation, (ii) electro-spray (iii) separation, and (iv) detectors. Both use an electrospray to aerosolize and ionize substances dissolved in a liquid sample, then separate macromolecule particles to identify specific proteins and organic molecules. Both exploit the fact that each copy of such proteins and molecules is nearly identical, creating a recognizable spectrum.
There are, however several important differences:
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ES-MS struggles with the hundreds of elementary charges carried by larger particles when electro-sprayed, precluding the formation of recognizable viral peaks in mass spectra. ES-DMA, this problem is overcome by "neutralizing", reducing charges to unity, a technique which is not viable in mass spectrometry because the mass/charge ratio of singly charged viruses greatly exceeds the range of existing mass spectrometers.
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DMA operates at atmospheric pressure, eliminating the need for the costly and bulky high vacuum system required in mass spectrometry.
The potential of ES-DMA for virus detection has been discussed in the literature for nearly twenty years, and ES-DMA instruments have been sold commercially for nearly as long. However, DMAs have lacked the resolving power to differentiate among species of viruses….
…Until now. NanoEngineering, and Prof. Juan Fernandez de la Mora and his team at Yale University, have worked for 18 years to optimize ES-DMA methods, focusing in recent years on resolving power (size discrimination) for virus detection. The team has developed successive generations of high resolution viral DMA devices, publishing peer reviewed papers that show first quadrupled resolving power (vs. commercially alternatives) to 30, then to 50, and by early 2022 reaching 75 (corresponding to discrimination between particles varying by ± 1/75 or ±1.3% in diameter). Yale and the NanoEngineering team have also achieved steady increases in the upper limit of the size range at which these resolutions may be achieved.
The next target for performance optimization will be in sensitivity. The target is 10^5 VLPs/mL for purified and concentrated samples, suggesting >90% sensitivity in clinical testing.
MOBILITY DIAMETER
he characterization of nano-particles depends on the nature of the instrument used to measure them.
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Mass spectrometry measures the mass of particles (actually mass/charge ratio), which is especially useful for atoms and small molecules. Electron MIcroscopy measures the cross-sectional diameter of a particle, which is great provided the cross-sectional angle is understood. Spoiler alert - this can be a problem.
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ES-DMA, and other forms of IMS measure the ratio of mobility diameter (MD) to the number of discrete charges on a particle. MD is also known as "collisional cross section", concepts that are related to drag coefficient on a nano-scale.
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All these measurements are complementary and effective in characterizing nano-particles because they are demonstrate reasonable linear correlation over a wide range of particle size.
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