Raman intraoperative investigation was focused on breast cancer [23].

Raman spectroscopy (Fig.2.1) is a powerful technique
to solve the issues mentioned in chapter I compared to other currently
available methods. It can detect essential characteristics of the human body
such as indicated ones in Fig.1.2, which are crucial for pre-diagnosis of
diseases like cancer and intraoperative imaging for resection of cancer cells.
Several scientific publications have previously attempted to show the
effectiveness of this solution23-25. The first striving of Raman spectroscopy
based intraoperative investigation was focused on breast cancer 23. Other
studies with sensitivities more than 80% have been done for detection and the diagnosis
of different tumors 24, 25. However, detection of brain cancer based on the
Raman spectroscopy has been mostly studied in the rodent models or ex vivo
human brain. Raman spectroscopy has been also used previously to model human
glioma in a mouse has been done towards medical use 12-17. For testing
patients during surgical resection, other groups designed a new powerful
intraoperative probe to detect cancer cells 3. Thanks to a Raman spectroscopy
probe, surgeons can accurately identify almost all invasive cancer cells in
real time during the operation. The accuracy of the Raman spectroscopy probe in
detecting cancer cells having invaded normal tissues is higher than 92%. They
demonstrated that Raman spectroscopy can accurately identify grade 2 to grade 4
gliomas in vivo during human brain cancer surgery. Fig.1.2 shows the
output Raman shifts for distinguishing healthy brain cells from cancer cells 3.
Fig.2.1 shows the utilized system to detect the essential molecules using Raman
spectrometry 3. Raman spectroscopy is a continuously improving technique to
identify such vital molecules that are necessary for monitoring human health
issues. Biological tissues, including brain, contain a large number of
Raman-active molecules, resulting in spectroscopic measurements. Acetylcholine
is an important neurotransmitter that conveys the neural signal to other cell
types. Label-free imaging of acetylcholine is achieved by frequency-modulated
spectral-focusing stimulated Raman scattering (FMSF-SRS) microscopy (a
technical improvement over traditional SRS microscopy that effectively removes
imaging backgrounds). Compared to multiphoton fluorescence imaging, SRS uses
longer wavelength and longer pulses and therefore it is less damaging to live
cells and tissues. Moreover, the same approach has been used for quantifying the
local concentration of acetylcholine at the neuromuscular junction of frog
muscle. The same methodology could potentially be used for imaging other
important neurotransmitters such as dopamine, serotonin, glutamate, GABA etc. 26.
The work done by Sharma et al. 27, the researchers apply Surface-Enhanced
Raman Spectroscopy (SERS), which provides greatly enhanced Raman signals from
very low concentration analytes that have been adsorbed to metal nanoparticles,
for the detection of neurotransmitters. The metal nanoparticles create an
oscillating electric field called the Localized Surface Plasmon Resonance
(LSPR) when excited with a laser, which results in the enhancement of the weak
Raman signal. SERS is surface selective, highly sensitive, rapid, label-free
and requires little to no sample processing 27. As the primary excitatory and
inhibitory neurotransmitters in the human brain, ?-amino-butyric acid (GABA) is
involved in nearly all brain circuits at millimolar levels and its fluctuation
is important for a variety of neurological and psychiatric disorders including
epilepsy, schizophrenia, and Parkinson’s disease 28. An LSPR enhancement at
near-infrared region has been achieved by constructing raspberry-like
nanospheres with an outer nanoparticle coating like Ag or Au. The device
captures GABA targets through size selectivity and enhances the sensitivity by
the LSPR effect (three orders of magnitude higher than that without LSPR
enhancement) 28. The inherent advantages of the proposed sensors, including
their low cost, ultra-sensitivity, small size, lightweight provide the
potential to incorporate them into various biomedical applications 28-30.
Table 1-1 presents some of the biological molecules that are detected by Raman
spectroscopy, which can help us to recognize cancer cells from healthy cells.

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