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9.1 Introduction
Imaging with optics, and specifically optical microscopy, has many advantages since
it allows to perform non-distractive imaging of samples via low cost and portable
means being much simpler than scanning electron microscopes (SEM), focused ion
beam microscopes and so on. However, the use of optical means also has limitations.
Mainly, the law of diffraction limits the imaging resolution to be half the optical
wavelength, which for visible light is about 250 nm. Since the size of a typical biological cell is about 10 μm, this resolution is not sufficient to allow observing internal
cellular structures or understanding key biological processes and procedures. In the
last two decades, various approaches have been used to break the law of diffraction
and allow optically perform imaging with much better resolution. Those approaches
include: confocal microscopy [1], multi-photon microscopy [2], structured illumination microscopy [3] and total internal reflection fluorescence microscopy [4]. These
methods provide lateral resolutions in the 100 nm scale.
Another category includes methods that are based on labeling the sample with
specific fluorophores. Sub-wavelength information can be obtained using a priori
knowledge of the imaging parameters and the excitation pattern. Such techniques
include near-field scanning optical microscopy [5], which uses an ultra-sharp tip
that scans the inspected sample and collects sub-wavelength data point-by-point [6].
Instead of a physical tip, other approaches as stimulated emission depletion (STED)
microscopy [7] and nonlinear (saturated) structured illumination microscopy (SSIM)
[8], use excitation pattern to realize scanning sub-wavelength light structure. The
super-resolution image is obtained because the scan is performed by PSF with higher
spatial frequencies instead of ordinary Gaussian PSF, and also due to the nonlinear
response of the fluorophore. The above-mentioned approaches indeed improve the
resolution to be much below the optical wavelength and help to reach lateral resolution of 20–50 nm, but it also depends on the physical/chemical properties of the
fluorophore which has the disadvantages such as autofluorescence of live cells, the
phototoxicity against living organisms and photobleaching [9–13]. Another research
direction includes use of gold nanoparticles (GNPs) as biomarkers in a variety of
applications such as medical diagnostic [14], drug delivery [15], therapeutic [16, 17]
and cellular imaging [18]. The main interest in these nanoparticles is because of the
localized surface plasmonic resonance (LSPR), which results in high optical crosssections at the plasmonic resonance wavelength. The resonance wavelength depends
on the properties of the nanoparticles, such as its shape and refractive index, as well
as the characteristics of its environment. The commonly used GNPs include spheres
and rods. The spheres have one LSPR peak, while the gold nanorods (GNRs) have
two peaks because of LSPR in its transverse and longitudinal dimensions. The LSPR
wavelength will become longer at larger aspect ratio [19, 20].
In this chapter, we discuss the research we have performed in the field of optical
super-resolution method based on the PDE of silicon that is either coated with gold
and encapsulated into nanoparticles or used as a silicon wafer as part of the micro-
H. Pinhas et al.
9.1 Introduction
Imaging with optics, and specifically optical microscopy, has many advantages since
it allows to perform non-distractive imaging of samples via low cost and portable
means being much simpler than scanning electron microscopes (SEM), focused ion
beam microscopes and so on. However, the use of optical means also has limitations.
Mainly, the law of diffraction limits the imaging resolution to be half the optical
wavelength, which for visible light is about 250 nm. Since the size of a typical biological cell is about 10 μm, this resolution is not sufficient to allow observing internal
cellular structures or understanding key biological processes and procedures. In the
last two decades, various approaches have been used to break the law of diffraction
and allow optically perform imaging with much better resolution. Those approaches
include: confocal microscopy [1], multi-photon microscopy [2], structured illumination microscopy [3] and total internal reflection fluorescence microscopy [4]. These
methods provide lateral resolutions in the 100 nm scale.
Another category includes methods that are based on labeling the sample with
specific fluorophores. Sub-wavelength information can be obtained using a priori
knowledge of the imaging parameters and the excitation pattern. Such techniques
include near-field scanning optical microscopy [5], which uses an ultra-sharp tip
that scans the inspected sample and collects sub-wavelength data point-by-point [6].
Instead of a physical tip, other approaches as stimulated emission depletion (STED)
microscopy [7] and nonlinear (saturated) structured illumination microscopy (SSIM)
[8], use excitation pattern to realize scanning sub-wavelength light structure. The
super-resolution image is obtained because the scan is performed by PSF with higher
spatial frequencies instead of ordinary Gaussian PSF, and also due to the nonlinear
response of the fluorophore. The above-mentioned approaches indeed improve the
resolution to be much below the optical wavelength and help to reach lateral resolution of 20–50 nm, but it also depends on the physical/chemical properties of the
fluorophore which has the disadvantages such as autofluorescence of live cells, the
phototoxicity against living organisms and photobleaching [9–13]. Another research
direction includes use of gold nanoparticles (GNPs) as biomarkers in a variety of
applications such as medical diagnostic [14], drug delivery [15], therapeutic [16, 17]
and cellular imaging [18]. The main interest in these nanoparticles is because of the
localized surface plasmonic resonance (LSPR), which results in high optical crosssections at the plasmonic resonance wavelength. The resonance wavelength depends
on the properties of the nanoparticles, such as its shape and refractive index, as well
as the characteristics of its environment. The commonly used GNPs include spheres
and rods. The spheres have one LSPR peak, while the gold nanorods (GNRs) have
two peaks because of LSPR in its transverse and longitudinal dimensions. The LSPR
wavelength will become longer at larger aspect ratio [19, 20].
In this chapter, we discuss the research we have performed in the field of optical
super-resolution method based on the PDE of silicon that is either coated with gold
and encapsulated into nanoparticles or used as a silicon wafer as part of the micro-