S. Kim, Y. Zhu, L. Apontti, R. Yan
University of California, Riverside,
Keywords: nanowire endoscopy, single living cell, plasmonic, surface-enhanced raman spectroscopy
Summary:When SnO2 nanowire waveguide single living cell endoscopy was first introduced to the scientific public, it seemed that it would open new avenues for biologists to gain complete insight into the cellular process and diseases-causing mechanisms in the immediate future. Despite of significant efforts to bring this idea to fruition, quantitative analysis of biological molecules without perturbing the outer cell membranes has not been demonstrated yet since then due to the following reasons: (1) photo-damage to living cells due to the low coupling efficiency of incident light to nanowire waveguide, (2) large insertion volume of dielectric nanowire due to diffraction limit which results in a significant damage to outer cell membrane, (3) low signal to noise ratio due to inefficient usage of photon energy for sensing (4) difficulties of multiplexed sensing of targeted bio-species (5) complicating fabrication method. Here, we have developed a novel nanowire-based endoscope for label-free quantitative biomolecule sensing in single living cell. By coupling excitation laser from a tapered optical fiber to a plasmonic nanowire with high crystallinity and atomically smooth surface, significant reduction of both scattering loss and insertion volume could be accomplished. Using an interfacial photothermal assembly method, silver nanocubes functionalized with Raman marker specific to a target molecule were able to be integrated on the very tip of silver nanowire waveguide with a high reliability. In nanogaps between the silver nanowire and nanocubes, all guided photon energy through the waveguide could have been localized and used to enhance Raman signal intensity. In addition to the enhancement of Raman signal, the silver nanocubes acting as antennas can radiate Raman signal in free space efficiently and result in increased collection efficiency of Raman signal. Furthermore, the nano-cavity antennas can reduce the sensing volume in living cells down to pL~fL since electromagnetic fields are tightly localized in the nanogaps. To demonstrate the feasibility of a noninvasive measurement of biomolecules in single living cell, we measured intracellular pH of a living HeLa cell with membrane integrity and cytotoxicity tests of the probe.