Flu Testing: Bio-Nano Sensing

According to FDA website (http://www.fda.gov/cdrh/oivd/tips/rapidflu.html) the rapid flu tests cleared for diagnosis of flu virus have moderate sensitivity (>60%) but the sensitivity is relatively higher (>90-95%). Typical ELISA type format can detect 10^3-10^5 particles compared to less than 100 particles for RT-PCR based methods. That got me thinking about the possibility of combining advances in nanotechnology to improve the current diagnostics methods.

Three recent Nano-bio hybrid technologies come to the mind right away

BIO-BARCODES

This technology claims to attain attomolar sensitivity and will certainly ELISA type detection format close to RT-PCR methods.

Bio-Barcode (Credit: www.rsc.org)

Bio-Barcode (Credit: http://www.rsc.org)

This technology combines microfluidics, magnetic particles and gold nanoparticles encoded with antibodies and DNA to achieve extremely high sensitivity. Magnetic particle labeled with specific antibodies capture analytes of interest and then isolated using magnetic field. Bound analytes are detected using second set of antibodies that are labeled with gold nanoparticles. These nanoparticles are also encoded with specific DNA. In subsequent steps DNA is isolated and detected using combination of gold nanoparticles and silver deposition. The technology for detection of DNA using gold nanoparticles came out of Chad Mirkin’s lab (http://chemgroups.northwestern.edu/mirkingroup/).  Nanosphere ( http://www.nanosphere.us/) a company started by Prof. Mirkin is in the process of commercializing  this technology

Quantum Dot Barcode (QdotB)

(http://faculty.washington.edu/xgao/Images/MDcancer.pdf)

(http://inbs.med.utoronto.ca/)

This technology again combines best of nanotechnology, microfluidics and antibody based detection to significantly improve the sensitivity of the conventional ELISA based assay. Unique feature of this technology is that large number of uniquely encoded particles (QdotB) can be prepared by combining different colored quantum dots (QDs). Each QdotB can be loaded with separate antibody and mixed in single sample to bind specific analyte. Secondary antibody labeled with fluorophore is added and each QdotB-analyte-secondary Ab-fluorophore is detected in the microfluidics channel. The concept is not new, Luminex (www.luminexcorp.com) sells very successful commercial  platform that uses 500 different color coded particles for 500-plex assays. QdotB can achieve much higher multiplexing capability-upto 10^6. Is it needed-moot point.

VIRUS NANOPARTICLES

This technology uses artificial nanoparticles combined with oriented Protein A to achieve 5 log order improvement over commercial kit for detection of Troponin 1. See details in my previous post

 https://biosensing.wordpress.com/2009/05/01/magic-is-in-the-orientation-orienting-antibodies-on-virus-nanoparticles/

Distance from prototype to real kit on the pharmacy shelf is long, very long. But I hope these technologies will change the way we deal with flu outbreaks in near future.

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