Correction: Metasurface-enhanced infrared spectroscopy in multiwell format for real-time assaying of live cells.

Correction for 'Metasurface-enhanced infrared spectroscopy in multiwell format for real-time assaying of live cells' by Steven H. Huang et al., Lab Chip, 2023, 23, 2228-2240, https://doi.org/10.1039/d3lc00017f.

Metasurface-enhanced infrared spectroscopy in multiwell format for real-time assaying of live cells.

Fourier transform infrared (FTIR) spectroscopy is a popular technique for the analysis of biological samples, yet its application in characterizing live cells is limited due to the strong attenuation of mid-IR light in water. Special thin flow cells and attenuated total reflection (ATR) FTIR spectroscopy have been used to mitigate this problem, but these techniques are difficult to integrate into a standard cell culture workflow. In this work, we demonstrate that the use of a plasmonic metasurface fabricated on planar substrates and the probing of cellular IR spectra through metasurface-enhanced infrared spectroscopy (MEIRS) can be an effective technique to characterize the IR spectra of live cells in a high-throughput manner. Cells are cultured on metasurfaces integrated with multiwell cell culture chambers and are probed from the bottom using an inverted FTIR micro-spectrometer. To demonstrate the use of MEIRS as a cellular assay, cellular adhesion on metasurfaces with different surface coatings and cellular response to the activation of the protease-activated receptor (PAR) signaling pathway were characterized through the changes in cellular IR spectra.

Probing the Drug Dynamics of Chemotherapeutics Using Metasurface-Enhanced Infrared Reflection Spectroscopy of Live Cells.

Infrared spectroscopy has drawn considerable interest in biological applications, but the measurement of live cells is impeded by the attenuation of infrared light in water. Metasurface-enhanced infrared reflection spectroscopy (MEIRS) had been shown to mitigate the problem, enhance the cellular infrared signal through surface-enhanced infrared absorption, and encode the cellular vibrational signatures in the reflectance spectrum at the same time. In this study, we used MEIRS to study the dynamic response of live cancer cells to a newly developed chemotherapeutic metal complex with distinct modes of action (MoAs): tricarbonyl rhenium isonitrile polypyridyl (TRIP). MEIRS measurements demonstrated that administering TRIP resulted in long-term (several hours) reduction in protein, lipid, and overall refractive index signals, and in short-term (tens of minutes) increase in these signals, consistent with the induction of endoplasmic reticulum stress. The unique tricarbonyl IR signature of TRIP in the bioorthogonal spectral window was monitored in real time, and was used as an infrared tag to detect the precise drug delivery time that was shown to be closely correlated with the onset of the phenotypic response. These results demonstrate that MEIRS is an effective label-free real-time cellular assay capable of detecting and interpreting the early phenotypic responses of cells to IR-tagged chemotherapeutics.

Temperature- and roughness- dependent permittivity of annealed/unannealed gold films.

Intrinsic absorption and subsequent heat generation have long been issues for metal-based plasmonics. Recently, thermo-plasmonics, which takes the advantage of such a thermal effect, is emerging as an important branch of plasmonics. However, although significant temperature increase is involved, characterization of metal permittivity at different temperatures and corresponding thermo-derivative are lacking. Here we measure gold permittivity from 300K to 570K, which the latter is enough for gold annealing. More than one order difference in thermo-derivative is revealed between annealed and unannealed films, resulting in a large variation of plasmonic properties. In addition, an unusual increase of imaginary permittivity after annealing is found. Both these effects can be attributed to the increased surface roughness incurred by annealing. Our results are valuable for characterizing extensively used unannealed nanoparticles, or annealed nanostructures, as building blocks in future thermo-nano-plasmonic systems.

3D resolution enhancement of deep-tissue imaging based on virtual spatial overlap modulation microscopy.

During the last decades, several resolution enhancement methods for optical microscopy beyond diffraction limit have been developed. Nevertheless, those hardware-based techniques typically require strong illumination, and fail to improve resolution in deep tissue. Here we develop a high-speed computational approach, three-dimensional virtual spatial overlap modulation microscopy (3D-vSPOM), which immediately solves the strong-illumination issue. By amplifying only the spatial frequency component corresponding to the un-scattered point-spread-function at focus, plus 3D nonlinear value selection, 3D-vSPOM shows significant resolution enhancement in deep tissue. Since no iteration is required, 3D-vSPOM is much faster than iterative deconvolution. Compared to non-iterative deconvolution, 3D-vSPOM does not need a priori information of point-spread-function at deep tissue, and provides much better resolution enhancement plus greatly improved noise-immune response. This method is ready to be amalgamated with two-photon microscopy or other laser scanning microscopy to enhance deep-tissue resolution.

Ultrasmall all-optical plasmonic switch and its application to superresolution imaging.

Because of their exceptional local-field enhancement and ultrasmall mode volume, plasmonic components can integrate photonics and electronics at nanoscale, and active control of plasmons is the key. However, all-optical modulation of plasmonic response with nanometer mode volume and unity modulation depth is still lacking. Here we show that scattering from a plasmonic nanoparticle, whose volume is smaller than 0.001 µm(3), can be optically switched off with less than 100 µW power. Over 80% modulation depth is observed, and shows no degradation after repetitive switching. The spectral bandwidth approaches 100 nm. The underlying mechanism is suggested to be photothermal effects, and the effective single-particle nonlinearity reaches nearly 10(-9) m(2)/W, which is to our knowledge the largest record of metallic materials to date. As a novel application, the non-bleaching and unlimitedly switchable scattering is used to enhance optical resolution to λ/5 (λ/9 after deconvolution), with 100-fold less intensity requirement compared to similar superresolution techniques. Our work not only opens up a new field of ultrasmall all-optical control based on scattering from a single nanoparticle, but also facilitates superresolution imaging for long-term observation.

Measurement of Scattering Nonlinearities from a Single Plasmonic Nanoparticle.

Plasmonics, which are based on the collective oscillation of electrons due to light excitation, involve strongly enhanced local electric fields and thus have potential applications in nonlinear optics, which requires extraordinary optical intensity. One of the most studied nonlinearities in plasmonics is nonlinear absorption, including saturation and reverse saturation behaviors. Although scattering and absorption in nanoparticles are closely correlated by the Mie theory, there has been no report of nonlinearities in plasmonic scattering until very recently. Last year, not only saturation, but also reverse saturation of scattering in an isolated plasmonic particle was demonstrated for the first time. The results showed that saturable scattering exhibits clear wavelength dependence, which seems to be directly linked to the localized surface plasmon resonance (LSPR). Combined with the intensity-dependent measurements, the results suggest the possibility of a common mechanism underlying the nonlinear behaviors of scattering and absorption. These nonlinearities of scattering from a single gold nanosphere (GNS) are widely applicable, including in super-resolution microscopy and optical switches. In this paper, it is described in detail how to measure nonlinearity of scattering in a single GNP and how to employ the super-resolution technique to enhance the optical imaging resolution based on saturable scattering. This discovery features the first super-resolution microscopy based on nonlinear scattering, which is a novel non-bleaching contrast method that can achieve a resolution as low as l/8 and will potentially be useful in biomedicine and material studies.