Flu Testing and Biosensors

Signs are everywhere. Everytime I turn on my TV I hear the statistics about the number of new cases of swine flu in Wisconsin. Every cough and sneeze get me thinking -is it a regular cold, allergy may be, what if it is early sign of swine flu. Hand sanitizers have popped up everywhere-in the bathrooms, next to the water cooler, or coffee machine.  Though we are not in a panic mode, recent swine flu outbreak is certainly on top of make-me-nervous list . So this got me thinking what if we can have access to a simple pregnancy kind of dipstick kit that we can use to see if we have flu or something else. What if we can have a tricorder (now that StarTrek is back in fashion-tricorder should be selfexplanatory!) that can be used to screen everybody walking into emergency room complaining about swine flu. And so I went hunting for commercial or early prototype reserach POC devices for quick diagnosis of flu virus. 

But before I talk about diagnosis-little 101 on Influenza (flu) virus.

Influenza Virus (Credit Florida State University (http://micro.magnet.fsu.edu/cells/viruses/influenzavirus.html)

Influenza Virus (Credit Florida State University (http://micro.magnet.fsu.edu/cells/viruses/influenzavirus.html)

Three type of Influenza types are A, B and C and the classification is based on antigenicity of nucleoprotein (NP) and matrix protein (MP). Influenza type A (The current swine flu) is further divided depending on combinattion of  hemagglutinin (HA) and neuraminidase (NA). There are 15 types of HA (H1-H15) and 9 types of NA (NI-N9). Current version of swine flu is H1N1. What makes the flu infectious hence the need to get a flu shot every year is the mutations leading to small changes in HA and NA proteins that defeat the immunity from previous infection/shots. What makes flu scary is the cross between human and avian flu viruses resulting in new types for which we have no immunity. Combined this with the fact that incubation period for virus is 24hrs and virus reaches a peak within 48hrs of infection and there is no easy way to preempt the virus except for giving anti-virals to whole population. OR quickly diagnose the individuals with flu within first 48hrs of infection and isolate/treat them aggressively. Biosenors promises to do just that-quick onsite diagnosis.
Are biosensors available for flu diagnosis?  Most of the commercial kits available are ELISA type of dipstick type kits-not really biosensors but pretty close.
CDC (http://www.cdc.gov/flu/professionals/diagnosis/labprocedures.htm#table) has a nice summary of the commercial kits available for flu diagnosis. According to CDC “Most of the rapid tests that can be done in a physician’s office are approximately 50-70% sensitive for detecting influenza and approximately greater than 90% specific. Therefore, false negative results are more common than false positive results, especially during peak influenza activity.” 
They go on to say that
“During outbreaks of respiratory illness when influenza is suspected, some respiratory samples should be tested by both rapid tests and by viral culture. The collection of some respiratory samples for viral culture is essential for determining the influenza A subtypes and influenza A and B strains causing illness”
ELISA type of ready-to-use kits have limited sensitivity of 10^3  to 10^5 virus particles that is 1000 fold lower than the conventional laboratory based method of virus isolation. These methods may not be suitable to detect early stages of flu but can be used in endemic areas with high virus loads. RT-PCR (reverse transcriptase-PCR) are several log order sensitive and are capable of detecting 5-100 particles but need trained technicians and several hours and hence not suitable for on-site testing .
However recent advances in Biosensors to improve sensitivity, specificity as well as easy handling gives reason for hope. Most promising are the LAB-ON-CHIP for PCR (http://nar.oxfordjournals.org/cgi/reprint/35/13/4223) that will bring the sensitivity of the PCR methods and ready-to-use format of chip format. Some other advances are to use label free sensing  based on surface plasmon resonance (www.biacore.com) or quartz crystal microbalance.
Hopefully, before the next big flu pandemic strikes humans we will have a TRICORDER ready to deal with it.

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