Current methods of detecting HIV/AIDS, tuberculosis, malaria, and other deadly infectious diseases quickly can help prevent their rapid spread and allow for more effective treatments. But, most current disease detection methods are cost-prohibitive in many areas of the world. Researchers at the University of California, Irvine, say that they have developed a new nanotechnology method that employs common, everyday shrink wrap, that may make highly sensitive, extremely low-cost diagnosis of infectious disease agents possible.

Fig. 1 – Close-up images of the new shrink wrap nanostructures taken with a scanning electron microscope. Each image depicts the shrink wrap’s surface with a fixed amount of nickel (5 nm) and different thicknesses of gold in the metal coating. Top: 10 nm thick. Middle: 20 nm thick. Bottom: 30 nm thick. The black arrows in the top image indicate a nanogap. (Credit: Optical Materials Express)

The new technique, described in a paper published in The Optical Society’s journal, Optical Materials Express, offers a way to significantly boost the signal of fluorescent markers used in biosensing, by depositing a combination of metals onto shrink wrap.

“Using commodity shrink wrap and bulk manufacturing processes, we can make low-cost nanostructures to enable fluorescence enhancements greater than a thousand-fold, allowing for significantly lower limits of detection,” said coauthor Michelle Khine, a biomedical engineering professor at the university. “If you have a solution with very few molecules that you are trying to detect—as in the case of infectious diseases—this platform will help amplify the signal so that a single molecule can be detected.”

In this new method, thin layers of gold and nickel are first deposited onto a thermoplastic polymer (shrink wrap film). When heated, the shrink wrap contracts, causing the stiffer metal layers to buckle and wrinkle into small flower-like structures. On top of the wrinkled metal layer, the researchers add samples of biomarkers, antibodies generated by the immune system in response to infection with a certain pathogen, which are tagged with fluorescent probes to allow their detection under near-infrared light. (See Figure 1)

The team found that the shrink wrap’s wrinkles significantly enhanced the signal intensity emitted by the biomarkers, which, they say, is due to the excitation of localized surface plasmons—coherent oscillations of the free electrons in the metal. When researchers shined a light on their wrinkled creation, the electromagnetic field was amplified within the nanoscale gaps between the shrink wrap’s folds, and produced “hotspots,” areas characterized by sudden bursts of intense fluorescence signals from the biomarkers.

In this study, the researchers used an immune system molecule known as immunoglobin G, or IgG, as the biomarker. IgG is one of the most common circulating antibodies in the immune system, and is found in most bodily fluids. It tends to be a particularly good biomarker to detect rotavirus, which is the leading cause of severe diarrheal infection in infants and young children worldwide. IgG is also a biomarker for infection with the Epstein-Barr virus and Herpes simplex virus.

The researchers say that, in the future, additional antibodies, such as immunoglobulin A and immunoglobulin M might be used to detect other agents including cytomegalovirus and the pathogen that causes typhoid fever. They believe their work will pave the way to creating an integrated, low-cost device to trap and identify biomarkers.


Medical Design Briefs Magazine

This article first appeared in the May, 2014 issue of Medical Design Briefs Magazine.

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