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Molecules can be portrayed as “ball-and-spring” models, where the balls are atoms and the springs are the chemical bonds that tether them. Just as a spring, the chemical bonds can be moved around in a variety of ways to cause masses to vibrate as well as move differently and in different directions. For example, they can be bending, stretching, twisting, or rocking back and forth. These sets of movements are called molecular vibrations. All these vibrations and interactions either within the molecule itself or with another molecule can have different levels of energy such that when incident light source is directed towards the molecule, the molecule can react to the incoming light in a few ways. One way is that it can absorb the light particles, called photons, thereby increasing its energy levels. Another possibility is that light can scatter, that is, the photons can pass through the molecule but are then deflected.
This scattering mostly occurs at the same frequency as the incident light. But because of molecular vibrations, sometimes scattering occurs at frequencies different from the incident light. These differences in frequency between the incident and scattered light are then said to be the frequencies of vibration. These vibrational frequencies can then be measured and represented as peaks in a spectrum, a graph that plots the intensity of scattered light as a function of frequency. This is the idea behind the technique known as Raman spectroscopy.
Depending on the types of atoms and bonds present, there can be different modes of vibration associated with the molecule, which in turn correspond to different vibrational frequencies. In other words, each vibrational mode can be associated with a specific molecular characteristic, which is represented by a particular vibrational frequency. Because of this, it can be said that by analyzing the sample with Raman spectroscopy, you can find out the chemical composition, structure, and bonding interactions of a sample, providing a sort of “spectroscopic fingerprint”.
You are probably wondering what do balls and springs have to do with cancer research? Well, just as Raman spectroscopy can provide the molecular identity of a sample, this tool can also be used to distinguish between various tissue types. Because tissue samples are made up of different amounts of nucleic acids, proteins, carbohydrates, and lipids, each with their own signature functional groups, Raman can help identify these functional groups and in turn help characterize these samples. More specifically, Raman can help distinguish normal tissue from diseased tissue, as they have varying macromolecular contents.
Raman spectroscopy has been used in the diagnosis of several types of cancers. For example, by analyzing protein and lipid content in excised, frozen brain tissue samples using standard Raman, normal brain tissues were able to be distinguished from tissues affected by glioblastoma, a type of brain cancer, and from tissues in necrosis. Additionally, with a handheld Raman probe that can be directly inserted into the brain, it is also possible to diagnose cancer progression in patients during surgery. In fact, this probe has been shown to be able to detect cancer cells that even an MRI scan might miss. Furthermore, modified versions of Raman spectroscopy, each with their own pros and cons, allow for even more accurate assessment.
Some other types of cancer that Raman has helped diagnose are ovarian, pancreatic, prostate, breast, and oral cancer. Moreover, analyses can be done with cancer cell lines and blood samples as well. Generally for these diagnoses, scientists evaluate the amounts of certain proteins or lipids that they know exist in higher or lower amounts in cells of those cancers.
Raman spectroscopy is a rapid and noninvasive technique, which makes it useful for clinical applications. There are still issues of cost and technical expertise required to operate the equipment, but this technology is continuously being developed to work on these problems and to allow for more efficient use. More recently, Zúñiga et al. have evaluated the efficacy of two commercially available Raman systems that are portable, more affordable, and easier to use than the traditional Raman instrumental setup. With these systems, they have evaluated tissue samples of breast cancer patients undergoing mastectomy and have found that these relatively cheaper systems have a few shortcomings but are still effective in differentiating tissue types during the patients’ surgeries.
Other factors may need to be considered before clinical use of this technique can be widespread, such as possible tissue damage from the lasers. But with continued improvements on this technology, Raman spectroscopy has the potential to be a powerful tool for rapid, accurate cancer diagnosis in a clinical setting.
Edited by Payal Yokota
Auner, G.W. et al. (2018). Applications of Raman spectroscopy in cancer diagnosis. Cancer and Metastasis Reviews 37, 691-717. https://doi.org/10.1007/s10555-018-9770-9
Zúñiga, W.C. et al. (2019). Raman spectroscopy for rapid evaluation of surgical margins during breast cancer lumpectomy. Scientific Reports 9, 14639. https://doi.org/10.1038/s41598-019-51112-0