electrical detection of single virus particles

nanowire.jpg This may be a bona fide breakthrough in virus detection: a Harvard group has reported specific detection of individual virus particles using silicon nanowires coupled to virus-specific antibodies. The article in Proc Natl Acad Sci is open-access, so anyone can read the whole thing and I don’t have to feel bad about swiping their cartoon, which explains the principle at a glance. The authors use simultaneous electrical and light microscopy monitoring of individual nanowires to demonstrate that the changes in conductance are due to binding/unbinding of single virus particles. They show that the duration and magnitude of the conductance changes are characteristic of specific binding events, which are easily distinguished from diffusion events; together with antibody specificity this means that detection is highly selective and the false positive rate extremely low. Multiple viruses (well, at least two, but the system should scale readily) can be detected in parallel in a single sample. These features of the system offer a solution to the problem of antigenic variation that plagues other antibody-based detection methods, since multiple antigens can be targeted simultaneously and molecules other than antibodies, such as cellular virus receptors (e.g. CD4 for HIV), could also be used. The size of the detection units means that multiplex systems will not be physically unwieldy: a tiny array much like a computer chip could contain thousands of different detectors. Virus was detected with similar specificity and selectivity in purified and “unpurified” samples, but the latter just means allantoic fluid so it remains to be demonstrated that the method is robust enough to screen, say, body fluids directly. It’s also not clear from the paper what sort of equipment is involved and whether it will adapt readily to fieldwork, though it’s basically just a bunch of transistors so I don’t imagine it’s intrinsically fragile. The authors don’t discuss virus quantitation, either, but that would seem to be a relatively straighforward issue (they show that event frequency is directly proportional to virus concentration in one figure).
The extreme sensitivity of the method offers hope of detection in the very early stages of infection. This alone could mean many years and much improved quality of life for millions of HIV patients, since it is much easier to maintain than to rebuild the CD4-positive cell population. Furthermore, very early detection may open a window onto a period of viral vulnerability in which medical intervention will be more effective than in later stages. In addition to detection, the method will be readily applicable to the study of viral binding kinetics and possibly to high-throughput screening for drug discovery. (via Eurekalert)