2 Interferometric Scattering (iSCAT) Microscopy and Related Techniques
31
demonstrated along with an improved detection sensitivity. This scheme would be
refined further by Batchelder and Taubenblatt in 1989 [57].
The 1980s also saw the field of nanoscience emerge out of the collective invention
of advanced scanning probe techniques, such as the Scanning Tunneling Microscope
(STM) in 1981, Scanning Near-Field Optical Microscopy (SNOM) in 1984 [58],
and the Atomic Force Microscope (AFM) in 1986 [59] as well as the discovery of
new materials such as carbon nanotubes and fullerenes. Optical microscopy would
similarly undergo great advances in performance following demonstration of the
optical detection of single dye molecules in 1989 [60]. Complemented by the general
political optimism at the end of the cold war, these developments launched a euphoria
in accessing the nano-world at the turn of the 1990s, as had been imagined by Richard
Feynman almost 30 years prior [61].
With the emergence of SNOM, optical microscopy experienced a revolutionary
era as it was now freed of the century-long bounds of the diffraction limit, and brought
promise of the detection and spectroscopy of individual molecules in contexts ranging from materials science to chemistry, physics and biology. As in conventional
light microscopy, the main contrast mechanism in SNOM is based on the extinction of light, now exiting a scanning subwavelength aperture. However, the physical
interaction at work in SNOM should be understood in the context of scattering rather
than reflection or transmission as considered in far-field imaging. In practice, SNOM
suffered from very weak signals stemming from faint illumination out of a nanometric aperture and weak scattering from nanoscopic features on the sample surface.
One of the efforts in tackling the limited throughput were put forth in 1994 by the
group of Wickramasinghe, who demonstrated interferometric (homodyne) detection
of the field scattered from a sharp solid tip (apertureless SNOM) [62]. Interpretation
of the SNOM signal in this mode and similar configurations presented a great challenge caused by spurious interference effects [63], which hampered adoption of this
technique until they were overcome a few years later [64–66].
In this nascent era of nanoscience, reappraisal of the optical functionality of gold
and silver nanoparticles and thin films, under the modern label of Plasmonics, led a
new generation of scientists to explore the detection and spectroscopy of individual
metallic nanoparticles. The first spectroscopy reported from single gold nanoparticles
appeared in 1998 using SNOM [67]. Detection of individual gold nanoparticles
was soon pursued by a number of methods, including conventional dark-field [68]
and total internal reflection dark-field microscopy [69]. A particularly promising
impetus was the biocompatibility of gold and its indefinite photostability, which
prompted the use of colloidal nanoparticles as optical immunolabels for biology [68].
Interestingly, while just a few years earlier, the common wisdom would have been
that Rayleigh scattering was too weak for the detection of individual nanoparticles,
this techniques also found application in the detection of single nanoparticles such
as carbon nanotubes [70].
By the end of the twentieth century, the achievements in detecting single nanoparticles with diameter on the order of 50 nm marked a milestone in detection sensitivity
[67–69]. However, most applications, especially those concerning biology, wished
to work with much smaller particles, e.g., 5 nm in diameter, corresponding to a
31
demonstrated along with an improved detection sensitivity. This scheme would be
refined further by Batchelder and Taubenblatt in 1989 [57].
The 1980s also saw the field of nanoscience emerge out of the collective invention
of advanced scanning probe techniques, such as the Scanning Tunneling Microscope
(STM) in 1981, Scanning Near-Field Optical Microscopy (SNOM) in 1984 [58],
and the Atomic Force Microscope (AFM) in 1986 [59] as well as the discovery of
new materials such as carbon nanotubes and fullerenes. Optical microscopy would
similarly undergo great advances in performance following demonstration of the
optical detection of single dye molecules in 1989 [60]. Complemented by the general
political optimism at the end of the cold war, these developments launched a euphoria
in accessing the nano-world at the turn of the 1990s, as had been imagined by Richard
Feynman almost 30 years prior [61].
With the emergence of SNOM, optical microscopy experienced a revolutionary
era as it was now freed of the century-long bounds of the diffraction limit, and brought
promise of the detection and spectroscopy of individual molecules in contexts ranging from materials science to chemistry, physics and biology. As in conventional
light microscopy, the main contrast mechanism in SNOM is based on the extinction of light, now exiting a scanning subwavelength aperture. However, the physical
interaction at work in SNOM should be understood in the context of scattering rather
than reflection or transmission as considered in far-field imaging. In practice, SNOM
suffered from very weak signals stemming from faint illumination out of a nanometric aperture and weak scattering from nanoscopic features on the sample surface.
One of the efforts in tackling the limited throughput were put forth in 1994 by the
group of Wickramasinghe, who demonstrated interferometric (homodyne) detection
of the field scattered from a sharp solid tip (apertureless SNOM) [62]. Interpretation
of the SNOM signal in this mode and similar configurations presented a great challenge caused by spurious interference effects [63], which hampered adoption of this
technique until they were overcome a few years later [64–66].
In this nascent era of nanoscience, reappraisal of the optical functionality of gold
and silver nanoparticles and thin films, under the modern label of Plasmonics, led a
new generation of scientists to explore the detection and spectroscopy of individual
metallic nanoparticles. The first spectroscopy reported from single gold nanoparticles
appeared in 1998 using SNOM [67]. Detection of individual gold nanoparticles
was soon pursued by a number of methods, including conventional dark-field [68]
and total internal reflection dark-field microscopy [69]. A particularly promising
impetus was the biocompatibility of gold and its indefinite photostability, which
prompted the use of colloidal nanoparticles as optical immunolabels for biology [68].
Interestingly, while just a few years earlier, the common wisdom would have been
that Rayleigh scattering was too weak for the detection of individual nanoparticles,
this techniques also found application in the detection of single nanoparticles such
as carbon nanotubes [70].
By the end of the twentieth century, the achievements in detecting single nanoparticles with diameter on the order of 50 nm marked a milestone in detection sensitivity
[67–69]. However, most applications, especially those concerning biology, wished
to work with much smaller particles, e.g., 5 nm in diameter, corresponding to a