Antenna Coupled Plasmonic Nanowire Endoscope for Label-Free Remote Sensing in Single Live-Cells

The ability to perform chemical/biochemical analysis with high spatial and temporal resolution is crucial in describing chemical inhomogeneity, mass transport and reaction dynamics in many areas, such as heterogeneous catalysis, electrochemistry, photochemistry and materials sciences. It is also extremely important in cell biology, where many cellular communication pathways occur within extremely small volumes. Achieving in vivo intracellular chemical analysis is one of the fundamental goals of modern biology to provide foundation for complete understanding of complex biological systems and holds the keys to galvanizing the study of stem cell niches, tumor biology, neurosciences and regenerative medicine. To achieve a better understanding of single, live-cell behavior and intracellular communication, physically or optically addressing different areas of the cell with high spatial and temporal resolution is getting more and more important. The volume of a mammalian cell is typically on the order of femtoliter (1um³) to picoliter (10um³). Therefore, to resolve the chemical heterogeneity within a living mammalian cell, the chemical analysis method needs to have an effective sensing volume much smaller than the cell volume, preferably in the sub-femtoliter to attoliter (100nm)³ regime. Meantime, it should also be able to quickly and quantitatively detect specific chemical or biochemical analytes with very high sensitivity and selectivity, and preferably, in a lable-free manner to avoid interference of chemical interference with cellular functions. Nanowire (NW)-based single cell SERS (Surface enhanced Raman scattering) endoscopes may be uniquely poised to satisfy such stringent requirements. At the center of this platform lies the integrated plasmonic NW waveguide on the tip of a tapered optical fiber. The plasmonic NW waveguide is coupled to SERS antennas near its tip, which offers not only significant improvement in SERS enhancement, but also allows for surface functionalization with bio/chemical receptors for chemical sensitivity and specificity. NW-SERS endoscope provides (1) sub-femotoliter sensing volume; (2) high signal-to-noise ratio due to high optical transmission that boosts the signal, and the highly localized illumination that excludes background noises; (3) label-free sensing; (4) active position control in all three dimensions with ultra-fine resolution through a micromanipulator (40nm/step) or potentially a motorized piezostage (1nm/step); (5) small insertion volume that avoids damages to cellular membranes, structures and functions; (6) remote sensing to avoid direct photo damage of living cells. We have demonstrated the applicability of such antenna coupled SERS endoscope for in-situ bioanalysis inside single living mammalian cells and label-free remote detection of cellular pH.