Single-molecule detection at high concentrations with optical aperture nanoantennas

Abstract

Single-molecule detection has become an indispensable technology in life science, and medical research. In order to get meaningful information on many biological processes, single-molecule analysis is required in micro-molar concentrations. At such high concentrations, it is very challenging to isolate a single molecule with conventional diffraction-limited optics. Recently, optical aperture nanoantennas (OANs) have emerged as a powerful tool to enhance the single-molecule detection under a physiological environment. The OANs, which consist of nano-scale apertures on a metallic film, have the following unique properties: (1) nanoscale light confinement; (2) enhanced fluorescence emission; (3) tunable radiation pattern; (4) reduced background noise; and (5) massive parallel detection. This review presents the fundamentals, recent developments and future perspectives in this emerging field.

Mapping the electromagnetic field confinement in the gap of germanium nanoantennas with plasma wavelength of 4.5 micrometers

“…5 Subwavelength confinement is critical for near-field microscopy 6 and few-molecule spectroscopy. 7 Both features depend on the nanoantenna geometry and on the dielectric function of the metal used to make the antenna e m ðxÞ ¼ e 0 m ðxÞ þ ie 00 m ðxÞ, where x ¼ c=k is the electromagnetic frequency. In many truly plasmonic designs, the field enhancement and confinement arise naturally at a metal/ dielectric interface and are not limited to the "lightning rod" effect or to the exploitation of specific boundary conditions in sub-nm gaps; the device performances rely on having e 0 m % À1, i.e., on the break-up of the perfect electric-conductor (PEC) approximation.…”

Plasmonic zero mode waveguide for highly confined and enhanced fluorescence emission

“…Single-molecule fluorescence [1][2][3][4][5][6][7] has been successfully applied to many areas of biomedicine, including DNA sequencing, 8,9 diagnostics, 10 and molecular biology. 11 In particular, in the field of next generation sequencing (NGS), single molecule fluorescence detection is the technique at the core of commercially available devices.…”

Review of optical detection of single molecules beyond the diffraction and diffusion limit using plasmonic nanostructures

“…Optical aperture nanoantennas (OANs), which consist of nanoapertures formed on a metallic film, have been developed to overcome this limitation. 8,9,75,76 The OANs can effectively block the incident light and confine the excitation light in the nanoaperture. Therefore, it can excite only one molecule at a time and gives near-zero background noise.…”

“…For example, plasmonic nanostructures, which consist of carefully designed metallic nanostructures, have been used to enhance the single-molecule detection at both ultralow and high concentrations. [7][8][9][10][11][12] Another easy-to-ignore but critically important factor for singlemolecule detection is the time required for a successful detection. Due to the small size of the active detection area, it can take an impractically long time for the molecules to diffuse into the detection area, especially at ultralow concentrations.…”