Nondestructive Identification of Individual Leukemia Cells by Laser Trapping Raman Spectroscopy

Abstract

Currently, a combination of technologies is typically required to assess the malignancy of cancer cells. These methods often lack the specificity and sensitivity necessary for early, accurate diagnosis. Here we demonstrate using clinical samples the application of laser trapping Raman spectroscopy as a novel approach that provides intrinsic biochemical markers for the noninvasive detection of individual cancer cells. The Raman spectra of live, hematopoietic cells provide reliable molecular fingerprints that reflect their biochemical composition and biology. Populations of normal T and B lymphocytes from four healthy individuals and cells from three leukemia patients were analyzed, and multiple intrinsic Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discriminating power for cancer cell identification. A combination of two multivariate statistical methods, principal component analysis (PCA) and linear discriminant analysis (LDA), was used to confirm the significance of these markers for identifying cancer cells and classifying the data. The results indicate that, on average, 95% of the normal cells and 90% of the patient cells were accurately classified into their respective cell types. We also provide evidence that these markers are unique to cancer cells and not purely a function of differences in their cellular activation.

Label‐free biochemical characterization of stem cells using vibrational spectroscopy

“…In addition, the eventual use of this technology in future clinical cell-based transplantations for purifying and enriching cell populations would obviously require similar cell sorting instrumentation. It is anticipated that optical tweezers [42][43][44] for cell manipulation and advanced nonlinear Raman techniques such as CARS [45,46] and stimulated Raman scattering (SRS) to enhance the weak Raman scattering signals will be important components in future Raman-based cell sorting systems. A study using CARS for stem cell characterization has been reported [46], the results of which were in agreement with the Raman studies discussed above.…”

Raman spectroscopy: techniques and applications in the life sciences

“…LDA has been used with Raman spectroscopy to create binary classification models to identify leukemia [484] and gastric dysplasia [438]. LDA can also be performed multiple times to create a multi-level classification model (i.e.…”

Raman Spectroscopy as a New Biochemical Diagnostic Tool

“…Raman spectroscopy continues to push its frontier, enabling individual neoplastic cell identification, such as shown in the works of Chan et al (34,35). Owing to improved and advanced Raman techniques, Cell surface is a very important target in investigations focused on carcinogenesis processes.…”