Quantum Cascade Laser Spectroscopy
379
7 Application of QCL in Spectroscopic Microscopy
and Imaging Platforms
Mid-infrared spectroscopic imaging using quantum cascade lasers has become a
rapidly emerging technique for clinical diagnostic in digital histopathology and
biofluid monitoring. Traditionally, histopathology has been used as a gold standard
method to identify the changes in morphology and architecture of the tissue due to
manifestation of the disease [90, 91]. Conventionally, every biopsy tissue is required
to do thin-sectioned and proper staining and subsequently, they are examined by a
trained and expert pathologist with the laborious process. However, the variation of
the experiences along with expertise between the pathologists for disease diagnosis
has been inherently subjected to intra-and inter-observer error [92, 93]. Moreover,
the time-consuming process between biopsy collection and clinical diagnosis has
significantly delayed patient care and the treatment. Although the recent advancement of the computer-aided diagnosis (CAD) [94], the manual inspection of strained
tissue for disease diagnosis is still widely used worldwide. The increasing demand
for tissue biopsy examination for specifically cancer affected patient annually desires
the high throughput measurement with better accuracy.
Recently, quantum cascade laser (QCL) has been exploited as a widely tunable
source with high optical fluxes in a new generation optical microscopic imaging
within the mid-infrared fingerprint region. Moreover, QCL coupled imaging microscope offers the discrete frequency imaging, which is advantageous for retrieving
the wavenumber specific analytical information from the target. Eventually, this
wavenumber specific investigation helps to drop the measuring time and reduce the
data analysis procedure. Moreover, QCL coupled imaging microscopes employs
uncooled bolometer detectors instead of using cryogenic cooled mercury cadmium
telluride (MCT) detectors and focal plane array. So far, EC-QCLs have been exclusively exploited as an optical source for IR-microscopy and imaging for application
in discrete frequency imaging, which is quite beneficial for optimising optical focus
for each wavenumber of interest [95]. Recent studies have shown that QCL based
imaging offered 150 times faster acquisition than FTIR with the equivalent signal to
noise ration despite acquiring full spectra. Few early studies demonstrated the feasibility of IR-QCL for chemical imaging. However, pioneer works based on tissue
imaging were carried away by bhargov et al. and Petrich et al. using homemade QCL
based set up microscope set up. Bhergov et al., exploited a multi QCL units, which
was covering entire mid-infrared (776–1904 cm
−1 ) spectral region with scanning
speed upto 25 cm
−1 /ms and emission powers between 0.5 and 15 mW [96]. The
wide spectral coverage with high intensity became advent for wide-field detection
and diffraction-limited spectral imaging. Moreover, they successfully achieved to
record the high throughput IR imaging of breast tissue (BRC1501 TMA) using the
potential of the QCL set-up and subsequently compared the results with the fastest
available HD FT-IR imaging system.
However, Petrich et al. demonstrated the visualisation of colonic mucosa by
exploiting QCL-coupled hyperspectral imaging instrument for investigation goblet
379
7 Application of QCL in Spectroscopic Microscopy
and Imaging Platforms
Mid-infrared spectroscopic imaging using quantum cascade lasers has become a
rapidly emerging technique for clinical diagnostic in digital histopathology and
biofluid monitoring. Traditionally, histopathology has been used as a gold standard
method to identify the changes in morphology and architecture of the tissue due to
manifestation of the disease [90, 91]. Conventionally, every biopsy tissue is required
to do thin-sectioned and proper staining and subsequently, they are examined by a
trained and expert pathologist with the laborious process. However, the variation of
the experiences along with expertise between the pathologists for disease diagnosis
has been inherently subjected to intra-and inter-observer error [92, 93]. Moreover,
the time-consuming process between biopsy collection and clinical diagnosis has
significantly delayed patient care and the treatment. Although the recent advancement of the computer-aided diagnosis (CAD) [94], the manual inspection of strained
tissue for disease diagnosis is still widely used worldwide. The increasing demand
for tissue biopsy examination for specifically cancer affected patient annually desires
the high throughput measurement with better accuracy.
Recently, quantum cascade laser (QCL) has been exploited as a widely tunable
source with high optical fluxes in a new generation optical microscopic imaging
within the mid-infrared fingerprint region. Moreover, QCL coupled imaging microscope offers the discrete frequency imaging, which is advantageous for retrieving
the wavenumber specific analytical information from the target. Eventually, this
wavenumber specific investigation helps to drop the measuring time and reduce the
data analysis procedure. Moreover, QCL coupled imaging microscopes employs
uncooled bolometer detectors instead of using cryogenic cooled mercury cadmium
telluride (MCT) detectors and focal plane array. So far, EC-QCLs have been exclusively exploited as an optical source for IR-microscopy and imaging for application
in discrete frequency imaging, which is quite beneficial for optimising optical focus
for each wavenumber of interest [95]. Recent studies have shown that QCL based
imaging offered 150 times faster acquisition than FTIR with the equivalent signal to
noise ration despite acquiring full spectra. Few early studies demonstrated the feasibility of IR-QCL for chemical imaging. However, pioneer works based on tissue
imaging were carried away by bhargov et al. and Petrich et al. using homemade QCL
based set up microscope set up. Bhergov et al., exploited a multi QCL units, which
was covering entire mid-infrared (776–1904 cm
−1 ) spectral region with scanning
speed upto 25 cm
−1 /ms and emission powers between 0.5 and 15 mW [96]. The
wide spectral coverage with high intensity became advent for wide-field detection
and diffraction-limited spectral imaging. Moreover, they successfully achieved to
record the high throughput IR imaging of breast tissue (BRC1501 TMA) using the
potential of the QCL set-up and subsequently compared the results with the fastest
available HD FT-IR imaging system.
However, Petrich et al. demonstrated the visualisation of colonic mucosa by
exploiting QCL-coupled hyperspectral imaging instrument for investigation goblet