Laser tweezer Raman spectroscopy combined with deep neural networks for identification of liver cancer cells

Rapid identification of cancer cells is crucial for clinical treatment guidance. Laser tweezer Raman spectroscopy (LTRS) that provides biochemical characteristics of cells can be used to identify cell phenotypes through classification models in a non-invasive and label-free manner. However, traditional classification methods require extensive reference databases and clinical experience, which is challenging when sampling at inaccessible locations. Here, we describe a classification method combing LTRS with deep neural network (DNN) for differential and discriminative analysis of multiple liver cancer (LC) cells. By using LTRS, we obtained high-quality single-cell Raman spectra of normal hepatocytes (HL-7702) and liver cancer cell lines (SMMC-7721, Hep3B, HepG2, SK-Hep1 and Huh7). The tentative assignment of Raman peaks indicated that arginine content was elevated and phenylalanine, glutathione and glutamate content was decreased in liver cancer cells. Subsequently, we randomly selected 300 spectra from each cell line for DNN model analysis, achieving a mean accuracy of 99.2%, a mean sensitivity of 99.2% and a mean specificity of 99.8% for the identification and classification of multiple LC cells and hepatocyte cells. These results demonstrate the combination of LTRS and DNN is a promising method for rapid and accurate cancer cell identification at single cell level.