Shrink-Wrap Technology Helps Enhance Detection of Biomarkers

The new technology may pave the way for low-cost, highly sensitive biomarker detection and diagnostic devices, and for enabling clinics in resource-limited regions provide their communities with more sensitive detection of infectious diseases.

A persistent challenge in fluorescence detection is to increase the signal to noise ratio of weakly fluorescent biomarkers or of biomolecules present at low concentration. Also, current methods for detection of infectious disease agents are predominantly cost-prohibitive in most areas of the world. Now a novel nanotechnology method using common shrink-wrap may help solve both problems.

The new technology, described by H. Sharma et al. in the Optical Society’s (Washington DC, USA) journal Optical Materials Express, on March 20, 2014, 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 1,000-fold, allowing for significantly lower limits of detection,” said Michelle Khine, biomedical engineering professor at the University of California, Irvine (USA); “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 the method, developed by the UC Irvine team led by Prof. Khine, thin layers of gold and nickel are first deposited onto a prestressed thermoplastic polymer (shrink-wrap film). When heated, the shrink-wrap contracts, causing the stiffer metal layers to buckle and wrinkle into flower-like structures that are significantly smaller than previously achieved. Fluorescent-probe tagged biomarkers are added onto the wrinkled metal layer. Specifically, they observed more than three orders of magnitude enhancement in the fluorescence signal emitted from a single molecule of goat anti-mouse immunoglobulin G (IgG) antibody tagged with fluorescein isothiocyanate, FITC, (FITC-IgG), by two-photon excitation.

The enhanced emission is due to the excitation of localized surface plasmons (coherent oscillations of the free electrons in the metal). When light was shined onto the wrinkled surface, the electromagnetic field was amplified within the nanogaps between the shrink-wrap folds. This produced “hotspot” areas characterized by sudden bursts of intense fluorescence signals from the biomarkers. This is the first demonstration of leveraging the plasmons in such hybrid nanostructures by metal enhanced fluorescence (MEF) in the near-infrared wavelengths. The structures can be tuned to have a diverse range of architectures and nanogap sizes with tunable plasmon resonances, to achieve large fluorescence enhancements in other regions of the excitation wavelength spectrum.

Though the current setup requires expensive equipment, the team believes this approach will pave the way to creating an integrated, low-cost device to magnetically trap and sensitively detect labeled molecules and nanoparticles. However, biological sample testing is itself another technical challenge: “The technique should work with measuring fluorescent markers in biological samples, but we have not yet tested bodily fluids,” said Prof. Khine, who cautions that the technique is far from ready for clinical use. For example, she notes, “We are currently working on trying to detect Rotavirus, but one of the main challenges is that our surface is hydrophobic so diffusion of the biomarker onto our composite structures is limited."

University of California, Irvine
The Optical Society

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