4 Tomographic Diffractive Microscopy …
103
a reference arm and an object arm. To facilitate alignment, common-path tomography has been proposed [162–164]. Use of partially coherent interferometry can
also be helpful, leveraging the illumination source requirements, and contributing to
increase image quality (no speckle noise), but may require more stringent alignment
and stability of the interferometer [165–167].
Wavefront analyzers, which allows for direct measurement of amplitude and
phase, have also been used with success for tomographic investigations at the microscopic scale [168–171]. They present the advantage that they can be directly fitted
to standard microscopes, adding a new imaging modality to existing setups, while
specific TDM instruments often lack the possibility of doing multimodal imaging.
At the present time, fluorescence imaging is for example proposed to be added
to commercial TDM systems, but not yet laser confocal fluorescence microscopy,
and associated imaging modes like fluorescence life-time imaging (FLIM), or fluorescence recovery after photobleaching (FRAP), or modern superresolution methods like structured illumination microscopy (SIM), or stimulated emission depletion
(STED) microscopy.
It is likely, that, offering complementary information, more imaging modalities
will be added to TDM systems in the future, to enlarge the investigations it allows
for. Among new approaches are multispectral or hyperspectral imaging [109, 172,
173], which could be especially interesting when considering absorbing samples,
as absorption in natural sample is often very variable with wavelength. Polarization
delivers specific information about birefringent samples, and can even be used to
further improve resolution [174]. Extension of the technique in the infrared has also
been considered, giving access to new characterizations [175]. TDM has also been
considered to investigate turbid media [176], and it has also been shown that 3D
differential interference contrast microscopy mode can be computed from synthetic
aperture microscopy data [177].
A possible limitation for a wide adoption of TDM is its associated costs, because
of the use of high numerical aperture objectives when high resolution is needed, the
complex interferometric systems to be used to record the diffracted field, or the cost
of wavefront analyzers. Several groups are therefore active in developing simplified,
low-cost approaches, based on lensless imaging techniques [178–182]. Conversely,
illumination angular scanning, usually performed using tip-tilt or galvanometric mirrors, or digital micromirror devices, can be replaced by an all-electronic, led-based
illumination array [183, 184].
In this overview of TDM, we have introduced the most straightforward image
reconstruction method, based on the first Born approximation, therefore allowing
for very simple and fast image reconstructions based on Fourier inversions. This
obviously limits the class of objects, which can be imaged, but a large literature has
been devoted to develop inversion approaches going beyond this limitation, involving
deconvolution, techniques to decrease the number of images to be taken, approaches
taking into account large phase changes in thick samples, and/or absorption, as well
as possible multiscattering [185–201].
103
a reference arm and an object arm. To facilitate alignment, common-path tomography has been proposed [162–164]. Use of partially coherent interferometry can
also be helpful, leveraging the illumination source requirements, and contributing to
increase image quality (no speckle noise), but may require more stringent alignment
and stability of the interferometer [165–167].
Wavefront analyzers, which allows for direct measurement of amplitude and
phase, have also been used with success for tomographic investigations at the microscopic scale [168–171]. They present the advantage that they can be directly fitted
to standard microscopes, adding a new imaging modality to existing setups, while
specific TDM instruments often lack the possibility of doing multimodal imaging.
At the present time, fluorescence imaging is for example proposed to be added
to commercial TDM systems, but not yet laser confocal fluorescence microscopy,
and associated imaging modes like fluorescence life-time imaging (FLIM), or fluorescence recovery after photobleaching (FRAP), or modern superresolution methods like structured illumination microscopy (SIM), or stimulated emission depletion
(STED) microscopy.
It is likely, that, offering complementary information, more imaging modalities
will be added to TDM systems in the future, to enlarge the investigations it allows
for. Among new approaches are multispectral or hyperspectral imaging [109, 172,
173], which could be especially interesting when considering absorbing samples,
as absorption in natural sample is often very variable with wavelength. Polarization
delivers specific information about birefringent samples, and can even be used to
further improve resolution [174]. Extension of the technique in the infrared has also
been considered, giving access to new characterizations [175]. TDM has also been
considered to investigate turbid media [176], and it has also been shown that 3D
differential interference contrast microscopy mode can be computed from synthetic
aperture microscopy data [177].
A possible limitation for a wide adoption of TDM is its associated costs, because
of the use of high numerical aperture objectives when high resolution is needed, the
complex interferometric systems to be used to record the diffracted field, or the cost
of wavefront analyzers. Several groups are therefore active in developing simplified,
low-cost approaches, based on lensless imaging techniques [178–182]. Conversely,
illumination angular scanning, usually performed using tip-tilt or galvanometric mirrors, or digital micromirror devices, can be replaced by an all-electronic, led-based
illumination array [183, 184].
In this overview of TDM, we have introduced the most straightforward image
reconstruction method, based on the first Born approximation, therefore allowing
for very simple and fast image reconstructions based on Fourier inversions. This
obviously limits the class of objects, which can be imaged, but a large literature has
been devoted to develop inversion approaches going beyond this limitation, involving
deconvolution, techniques to decrease the number of images to be taken, approaches
taking into account large phase changes in thick samples, and/or absorption, as well
as possible multiscattering [185–201].