Fluorescence microscopy has been the workhorse for investigating optical phenomena at the nanometer scale but this approach confronts several fundamental limits. As a result, there have been a ...growing number of activities toward the development of fluorescent-free imaging methods. In this Mini Review, we demonstrate that elastic scattering, the most ubiquitous and oldest optical contrast mechanism, offers excellent opportunities for sensitive detection and imaging of nanoparticles and molecules at very high spatiotemporal resolution. We present interferometric scattering (iSCAT) microscopy as the method of choice, explain its theoretical foundation, discuss its experimental nuances, elaborate on its deep connection to bright-field imaging and other established microscopies, and discuss its promise as well as challenges. A showcase of numerous applications and avenues made possible by iSCAT demonstrates its rapidly growing impact on various disciplines concerned with nanoscopic phenomena.
Ambitions to reach atomic resolution with light have been a major force in shaping nano-optics, whereby a central challenge is achieving highly localized optical fields. A promising approach employs ...plasmonic nanoantennas, but fluorescence quenching in the vicinity of metallic structures often imposes a strict limit on the attainable spatial resolution, and previous studies have reached only 8 nm resolution in fluorescence mapping. Here, we demonstrate spatially and spectrally resolved photoluminescence imaging of a single phthalocyanine molecule coupled to nanocavity plasmons in a tunnelling junction with a spatial resolution down to ∼8 Å and locally map the molecular exciton energy and linewidth at sub-molecular resolution. This remarkable resolution is achieved through an exquisite nanocavity control, including tip-apex engineering with an atomistic protrusion, quenching management through emitter–metal decoupling and sub-nanometre positioning precision. Our findings provide new routes to optical imaging, spectroscopy and engineering of light–matter interactions at sub-nanometre scales.Through the use of a plasmon-active atomically sharp tip and an ultrathin insulating film, and precise junction control in a highly confined nanocavity plasmon field at the scanning tunnelling microscope junction, sub-nanometre-resolved single-molecule near-field photoluminescence imaging with a spatial resolution down to ∼8 Å is achieved.
Many of the biological functions of a cell are dictated by the intricate motion of proteins within its membrane over a spatial range of nanometres to tens of micrometres and time intervals of ...microseconds to minutes. This rich parameter space is not accessible by fluorescence microscopy, but it is within reach of interferometric scattering (iSCAT) particle tracking. However, as iSCAT is sensitive even to single unlabelled proteins, it is often accompanied by a large speckle-like background, which poses a substantial challenge for its application to cellular imaging. Here, we employ a new image processing approach to overcome this difficulty and demonstrate tracking of transmembrane epidermal growth factor receptors with nanometre precision in all three dimensions at up to microsecond speeds and for durations of tens of minutes. We provide examples of nanoscale motion and confinement in ubiquitous processes such as diffusion in the plasma membrane, transport on filopodia and rotational motion during endocytosis.Interferometric scattering microscopy is employed to track proteins in live cell membranes, demonstrating tracking of transmembrane epidermal growth factor receptors with nanometre precision in all three dimensions at up to microsecond speeds and for durations of tens of minutes.
The use of molecules in quantum optical applications has been hampered by incoherent internal vibrations and other phononic interactions with their environment. Here we show that an organic molecule ...placed into an optical microcavity behaves as a coherent two-level quantum system. This allows the observation of 99% extinction of a laser beam by a single molecule, saturation with less than 0.5 photons and non-classical generation of few-photons super-bunched light. Furthermore, we demonstrate efficient interaction of the molecule–microcavity system with single photons generated by a second molecule in a distant laboratory. Our achievements represent an important step towards linear and nonlinear quantum photonic circuits based on organic platforms.A molecule placed in an optical microcavity behaves as a model two-level quantum system, as demonstrated via laser extinction and interaction with single photons.
Characterization of the size and material properties of particles in liquid suspensions is in very high demand, for example, in the analysis of colloidal samples or of bodily fluids such as urine or ...blood plasma. However, existing methods are limited in their ability to decipher the constituents of realistic samples. Here we introduce iNTA as a new method that combines interferometric detection of scattering with nanoparticle tracking analysis to reach unprecedented sensitivity and precision in determining the size and refractive index distributions of nanoparticles in suspensions. After benchmarking iNTA with samples of colloidal gold, we present its remarkable ability to resolve the constituents of various multicomponent and polydisperse samples of known origin. Furthermore, we showcase the method by elucidating the refractive index and size distributions of extracellular vesicles from Leishmania parasites and human urine. The current performance of iNTA already enables advances in several important applications, but we also discuss possible improvements.
The ability to trap an object-whether a single atom or a macroscopic entity-affects fields as diverse as quantum optics, soft condensed-matter physics, biophysics and clinical medicine. Many ...sophisticated methodologies have been developed to counter the randomizing effect of Brownian motion in solution, but stable trapping of nanometre-sized objects remains challenging. Optical tweezers are widely used traps, but require sufficiently polarizable objects and thus are unable to manipulate small macromolecules. Confinement of single molecules has been achieved using electrokinetic feedback guided by tracking of a fluorescent label, but photophysical constraints limit the trap stiffness and lifetime. Here we show that a fluidic slit with appropriately tailored topography has a spatially modulated electrostatic potential that can trap and levitate charged objects in solution for up to several hours. We illustrate this principle with gold particles, polymer beads and lipid vesicles with diameters of tens of nanometres, which are all trapped without external intervention and independently of their mass and dielectric function. The stiffness and stability of our electrostatic trap is easily tuned by adjusting the system geometry and the ionic strength of the solution, and it lends itself to integration with other manipulation mechanisms. We anticipate that these features will allow its use for contact-free confinement of single proteins and macromolecules, and the sorting and fractionation of nanometre-sized objects or their assembly into high-density arrays.
A two-level atom cannot emit more than one photon at a time. As early as the 1980s, this quantum feature was identified as a gateway to 'single-photon sources', where a regular excitation sequence ...would create a stream of light particles with photon number fluctuations below the shot noise. Such an intensity-squeezed beam of light would be desirable for a range of applications, such as quantum imaging, sensing, enhanced precision measurements and information processing. However, experimental realizations of these sources have been hindered by large losses caused by low photon-collection efficiencies and photophysical shortcomings. By using a planar metallodielectric antenna applied to an organic molecule, we demonstrate the most regular stream of single photons reported to date. The measured intensity fluctuations were limited by our detection efficiency and amounted to 2.2dB squeezing.
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