Characterization of vaccinia virus particles using microscale silicon cantilever resonators and atomic force microscopy

Rapid means of characterizing and detecting virus particles are very important for a wide variety of applications. We have used vaccinia virus, a member of the Poxviridae virus family and the basis of the smallpox vaccine, as the test case and characterized these particles using atomic force microscopy and micron-scale cantilever beams, with the long-term goal of developing devices for the direct rapid detection of air-borne virus particles. The cantilever beams, driven by thermal noise and a PZT piezoelectric ceramic, served as resonating sensors to measure the mass of these virus particles. Two different size cantilevers were used, with dimensions of 21 μm × 9 μm and 6 μm × 4 μm. All cantilevers measured approximately 200 nm in thickness. The resonant frequency spectra of the cantilevers were measured using a microscope scanning laser Doppler vibrometer before and after the addition of virus particles, and scanning electron micrographs were taken in order to quantify the number of virus particles attached to the cantilevers. The change in resonant frequency as a function of the number of adsorbed virus particles was the basis of the mass detection scheme. We have measured the average mass of a single vaccinia virus particle to be 12.4 ± 1.3 fg and 7.9 ± 4.6 fg, obtained from the larger and smaller cantilever beams, respectively, which is in the expected range of 5-10 fg. The measurable mass sensitivity of cantilevers driven by the piezoelectric ceramic is found to be an order of magnitude greater than the sensitivity of cantilevers driven by thermal noise. These cantilever structures can be integral parts of biosensors for the detection of airborne virus particles.