Optical tweezers and Raman spectroscopy for single-cell classification of drug resistance in acute lymphoblastic leukemia.

Laser Tweezers Raman Spectroscopy (LTRS) is a combination of laser tweezers and Raman spectroscopy. It is a physical tool based on the mechanical effects of the laser, which can be used to study single living cells in suspension in a fast and non-destructive way. Our work aims to establish a methodology system based on LTRS to rapidly and non-destructively detect the resistance of acute lymphoblastic leukemia (ALL) cells and to provide a new idea for the evaluation of the resistance of ALL cells. Two specific adriamycin-resistant and parental ALL cells BALL-1 and Nalm6 were included in this study. Adriamycin resistant cells can induce the spectral differences, which can be detected by LTRS initially. To ensure the accuracy of the results, we use the principal components analysis (PCA) as well as the classification and regression trees (CRT) algorithms, which show that the specificity and sensitivity of LTRS are above 90%. In addition, to further clarify the chemoresistance status of ALL cells, we used the CRT models and receiver operating characteristic (ROC) curves which are based on the band data to look for some important bands and band intensity ratios that have strong pointing significance. Our work proves that LTRS analysis combined with multivariate statistical analyses have great potential to be a novel analytical strategy at the single-cell level for rapidly evaluating the chemoresistance status of ALL cells.