Large-scale plasmonic microarrays for label-free high-throughput screening

Abstract

Microarrays allowing simultaneous analysis of thousands of parameters can significantly accelerate screening of large libraries of pharmaceutical compounds and biomolecular interactions. For large-scale studies on diverse biomedical samples, reliable, label-free, and high-content microarrays are needed. In this work, using large-area plasmonic nanohole arrays, we demonstrate for the first time a large-scale label-free microarray technology with over one million sensors on a single microscope slide. A dual-color filter imaging method is introduced to dramatically increase the accuracy, reliability, and signal-to-noise ratio of the sensors in a highly multiplexed manner. We used our technology to quantitatively measure protein-protein interactions. Our platform, which is highly compatible with the current microarray scanning systems can enable a powerful screening technology and facilitate diagnosis and treatment of diseases.

Handheld high-throughput plasmonic biosensor using computational on-chip imaging

“…In order to systematically improve our detection limits (down to ng mL 21 ) we can explore several avenues: (i) spectrally narrow chip-based optoelectronic excitation sources, e.g., laser diodes or resonant-cavity enhanced LEDs can be employed to determine the minute spectral variations in the plasmonic modes; (ii) superior plasmonic designs achieving much sharper plasmonic resonances with stronger near-field enhancements, such as Fano resonant structures, 94,118,119 can be implemented; (iii) the spectral shifts in the transmission resonance of the nanoapertures can be more sensitively tracked by acquiring multiple lens-free images (i.e., each with a different color LED). These lens-free frames can then be digitally merged, producing higher contrast differences between the reference and target images; 84 (iv) better CMOS/CCD imagers, equipped with cooling circuits, can be employed in this plasmonic sensing platform achieving higher sensitivities; (v) advanced computational reconstruction approaches, e.g., based on convex optimization, [120][121][122][123] can be applied to the diffraction images of the plasmonic chips; and (vi) nanoparticle based assays can be also functionalized on the same plasmonic substrates improving the binding sites of biomolecules, and further enhancing the contrast of the low-density biomolecules detected through improved lens-free diffraction patterns. A major advantage of using nanoparticles in this on-chip biosensing platform would be to increase the near-field interactions between the biomolecules and the surface plasmon waves up to the penetration depth of evanescent waves (, 200 nm).…”

“…66 A single sensor with a size of 10 mm310 mm, consisting of more than 200 nanoholes (hole diameter5200 nm and array period 600 nm) should result in sufficient transmitted signal to be captured by the CMOS imager. 84 Based on these numbers, employing a CMOS imager with an active area of 5.7 mm34.3 mm, we could image 170 000 sensor pixels all in parallel, which is highly promising for high-throughput applications.…”

“…Recently, various high-throughput optical detection methods have been investigated to overcome these problems as they offer strong advantages by being compatible with physiological solutions, not affected by the variation in the ionic strengths of biosolutions, and reducing sample contamination via allowing remote transduction of the biomolecular binding signal. [77][78][79][80][81][82][83][84][85] Among optical biosensors, surface plasmon resonance (SPR)-based platforms are one of the most favored. Surface plasmons (SPs) are waves propagating at a metal/dielectric interface associated with the collective electron oscillations.…”

Sensitivity comparison of localized plasmon resonance structures and prism coupler

“…In LSPR sensing using an isolated plasmonic resonator where the mode field can be assumed to isotropically decay into the surrounding medium, the wavelength shift upon binding is given similarly by ı = S ın d (1 − exp(− 2h/1 d )), where s is the sensitivity factor (shift in resonance per RIU change in environment refractive index) and l d is electromagnetic decay length of the LSPR mode [8][9][10][11][12][13][14][15][16][17]. However, for anisotropic resonators, such as prism or disk shaped, the mode field is non-uniformly distributed on the resonator and sensitivity of binding assumes a location dependent form.…”

“…Typically, a simple figureof-merit (FOM), defined as the ratio of sensitivity (shift of the resonance wavelength in nm per change in the bulk refractive index of the sensing medium) to the full-width-at-half-maximum (FWHM) of the resonant line shape, is used to compare the performance [13,14]. We note that, in biomolecular sensing applications, the performance depends not on bulk refractive index change but on molecular binding.…”