(4ed) Nano-Plasmonics for Transformative Biosensors

Accurate, fast and low-cost detection of biomarkers is essiential for effective prescreening of many chronic diseases and cancers.  However, current biosensors, DNA microarray (Affymetrix) and surface plasmon resonance SPR (Bia Core) for example, are too costly and too labor/time intensive to allow frequent and individualized screening. There is hence a need for a new integrated home-use diagnostic platform if personalized healthcare is to become a reality.

Nanoplasmonics involves surface electromagnetic (EM) waves confined to a nano-scale region (hot spot) sustained by a plasmon resonator, thus allowing sensitive biomolecule sensing. Many different designs of plasmonic nano-resonators for biosensing have been proposed like fano-resonator, nano-crescent, bow-tie antena, etc. However, the fabrication of these nano-structures is complicated and expensive. This is because their design has been highly empirical, with heavy reliance on FDTD (Finite Differential Time Domain) simulation. Despite well-known facts that SERS are unique to nanospheres/flowers and nanoparticle catalysts have favorable electron-transfer and bulk mass transport properties,  a holistic approach that extrapolates the unique optical, solutal and electrical physics at small scales to design low-cost macroscopic sensors has yet to appear for the desired biomarker diagnostic platform.

We embark in this direction by using a multi-scale approach that exploits the separation of length/time scales of such nanostructures. For example, our analysis of SPR near geometric singularities (tips and wedges) reveal unique and useful features that have been supported by simulation (Wang et al, Optics Exp, 21, 6609(2013); AIChE J review May 2013). In addition to high-field intensification due to plasmonic focusing, broad-band resonance and red-shifted resonant are also found because of the lack of a natural length scale—or a diminishingly small one. I have used these unique plasmonic dispersion features of a single cone to build a sensor array at larger scales (mm) with optimum bulk/waveguide-plasmonic coupling, interference pattern and nonlinear optics. I also design into this biosensor array enhanced biomarker transport (by 100 fold) to the nanosensors with sub-micron diffusion lengths.

A first prototype with plasmonically for small-panel miRNA profiling is near maturity. A conical array is fabricated by wet etching commercial imaging fiber bundles, with thousands of small fiber cores at optimum spacing from my theory. The cone tip has a radius of curvature below 10 nm and a thin gold layer (at a theoretically determined thickness of 5 nm) is thermally evaporated onto the array to sustain plasmonics. Hairpin probes with fluorophore tags quenched by the gold film are functionalized to the gold surface. Plasmonically enhanced fluorescent reporting of hybridization occurs when the target molecule breaks the hairpin. Detection of multiple targets in a panel can be achieved by addressing each fiber core optically and using photochemistry to selectively attach different probes. Detailed spectral measurements show broadbanded plasmonic excitation of 3 fluorophores per cone to minimize interference. Intensity tracking in time show a signature constant rapid absorption flux to a conic tip, followed by a slow t^-1/2 diffusive flux to the substrate. The enhanced tip fluorescence allows detection of the approximately 100 miRNA at the tip in the first region within 15 minutes. Profiling data for miRNA of oral cancer cells from a heterogeneous sample are being collected.

In my future work,  I intend to design smart nonlinear nanoplasmonic sensor arrays, with compound plasmonic Kerr materials, that are fully integrated with the micro/nanofluidic, surface acoustic wave (SAW) and micro-electronic circuitries on the same biochip. The individual nonlinear plasmonic oscillator can interact with each other to further maximize sensitivity and to interact with the other circuitries for a fully automated platform. I will explore the mutual resonance of SAW with low-frequency Bloch plasmon waves intensified by a nonlinear cone grid, thus allowing SAW amplification of plasmon intensity or vice-versa. I shall employ the high dielectrophoretic and plasmonic fields at the tips for molecular separation, ionization, transport and concentration at the nanoscale. An ambitious goal is to develop patterned plasmonic travelling waves in the array that will serve as molecular-specific nano-conveyor belt that will sequentially carry different species to different chemically active sites where single-electron tunneling events can be registered in a well-controlled nanoscale chemical environment. I have been exposed to all these technologies in my PhD career and will use my multi-scale analysis to facilitate their optimum integration. The goal is to design a broad-bandwidth and multi-functional screening chip that can detect a massively large number of protein and nucleic biomarkers, whose concentrations span 6 decades, by local separation/concentration and automated introduction of specific buffer and nanofluorescent reporters for enzymatic and optical amplification, preferably delivered with single-molecule/nanoparticle resolution.

Reference:

[1]Wang Y, Cheng X, Chang H-C, Celebrating Singularities: Mathematics and Chemical Engineering. AIChE J, Accepted, (Feature Cover) (2013) DOI: 10.1002/aic.14123

[2]Wang Y, Plouraboue F and Chang H-C, Broadband converging plasmon resonance at a conical nanotip. Opt Express, 21 6609-6617 (2013)

[3]Wang Y, Tan M.K, Go D.B and Chang H-C, Electrospray Cone-Jet Breakup and Droplet Production for Electrolyte Solutions. Europhys. Lett. 99 64003 (2012) (Editor’s highlight).

[4] Xie F, Wang Y, Wang W, Li Z, Yossifon G, and Chang H-C, An Experimental Study on the Side-Opening Filling Process at the Interface between Microchannels with Different Widths. J. Nanosci. Nanotechnol. 10 7277 (2011).

[5] Chen Z, Wang Y, Wang W, and Li Z, Nanofluidic Electrokinetics in Nanoparticle Crystal. Appl. Phys. Lett. 95 102105 (2009).