Laser tweezers Raman spectroscopy (LTRS) combines optical trapping with micro-Raman spectroscopy to enable label-free
biochemical analysis of individual cells and small biological particles in suspension. The integration of the two
technologies greatly simplifies the sample preparation and handling of suspension cells for spectroscopic analysis in
physiologically meaningful conditions. In our group, LTRS has been used to study the effects of external perturbations,
both chemical and mechanical, on the biochemistry of the cell. Single cell dynamics can be studied by performing
longitudinal studies to continuously monitor the response of the cell as it interacts with its environment. The ability to
carry out these measurements in-vitro makes LTRS an attractive tool for many biomedical applications. Here, we discuss
the use of LTRS to study the response of cancer cells to chemotherapeutics and bacteria cells to antibiotics and show that
the life cycle and apoptosis of the cells can be detected. These results show the promise of LTRS for drug
discovery/screening, antibiotic susceptibility testing, and chemotherapy response monitoring applications. In separate
experiments, we study the response of red blood cells to the mechanical forces imposed on the cell by the optical
tweezers. A laser power dependent deoxygenation of the red blood cell in the single beam trap is reported. Normal,
sickle cell, and fetal red blood cells have a different behavior that enables the discrimination of the cell types based on
this mechanochemical response. These results show the potential utility of LTRS for diagnosing and studying red blood
cell diseases.
Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental
research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D
structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering
could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to
combining these imaging modalities. We present an ex vivo OCT microscope combined with Raman spectroscopy
capable of collecting morphological and molecular information about a sample simultaneously. The combined
instrument will be used to investigate remaining technical challenges to combine these imaging modalities, such
as the laser power levels needed to achieve a Raman signal above the noise level without damaging the sample.
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