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R. W. Taylor and V. Sandoghdar
for cell biology applications, such as imaging microtubules [75, 76, 91, 184], actin
[120], the actomyosin network [185], as well as organelles and micron or smaller
sized vesicle containers which assist in the transport of material throughout the
cell [186]. Echoing previous efforts from the holographic community [187, 188],
interferometric efforts are now also focusing on identifying the small changes in the
cell membrane, whereas previously the whole cell was profiled. Examples include
the progression of ideas from holography to gradient light interference microscopy
[105], recent efforts to profile membrane adhesion sites and topology in both widefield [189] and confocal-scanning reflection interference microscopy [94] or widefield iSCAT [190].
Similarly, there have been increasing efforts to harness interferometric imaging
to investigate the mechanical properties of the cell membrane. Building upon initial
efforts from quantitative phase imaging [191, 192], recent works have sought to
turn attention to fast and nanometer-level dynamics that require high sensitivity to
elucidate inherent fluctuations [193–196]. Results provide insight into the mechanical
properties or changes in the membrane following the execution of action potentials
and sub-nanometer-level twitching across the neuronal cell in response to stimulation.
Finally, it is interesting to note that some of the early efforts of the 1990s actually
used iSCAT in transmission mode to track membrane proteins in living cells [197]
although the underlying physics was not formulated, and thus, the virtues of iSCAT
were not harnessed to reach the quality of trajectories that are accessible today.
2.4.2.4 Other Emerging Applications
More recently, iSCAT imaging was also used to visualize excitation and relaxation of
charge carriers within various semiconductor and organic crystals, following ultrafast pumping [107]. The changes in local carrier density (refractive index) induced
by the pump excitation mark the flow of energy in the material, which is visualized
as local changes in contrast, with contrast sensitivity down to 10
−4 . The relaxation
dynamics could thus be imaged through microscopy, and the role of grain boundaries
and material anisotropy explored. In the wake of such efforts, we also anticipate great
utility of this technique in the field of atomic physics.
2.5 Summary and Outlook
We began this chapter with a historical overview of different microscopy modalities
where interference plays a central role. In particular, we emphasized that the physical
mechanism behind conventional bright-field microscopy is extinction, which follows
from formulating an interference problem between the illumination and the field that
has interacted with the object. Methods such as phase contrast microscopy, differential interference microscopy, various versions of interference reflection microscopy
and digital holography all share the same fundamental physics and only differ in the
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