Detection of cultured breast cancer cells from human tumor-derived matrix by differential ion mobility spectrometry

Abstract

The primary treatment of breast cancer is the surgical removal of the tumor with an adequate healthy tissue margin. An intraoperative method for assessing surgical margins could optimize tumor resection. Differential ion mobility spectrometry (DMS) is applicable for tissue analysis and allows for the differentiation of malignant and benign tissues. However, the number of cancer cells necessary for detection remains unknown. We studied the detection threshold of DMS for cancer cell identification with a widely characterized breast cancer cell line (BT-474) dispersed in a human myoma-based tumor microenvironment mimicking matrix (Myogel). Predetermined, small numbers of cultured BT-474 cells were dispersed into Myogel. Pure Myogel was used as a zero sample. All samples were assessed with a DMS-based custom-built device described as "the automated tissue laser analysis system" (ATLAS). We used machine learning to determine the detection threshold for cancer cell densities by training binary classifiers to distinguish the reference level (zero sample) from single predetermined cancer cell density levels. Each classifier (sLDA, linear SVM, radial SVM, and CNN) was able to detect cell density of 3700 cells μL^-1 and above. These results suggest that DMS combined with laser desorption can detect low densities of breast cancer cells, at levels clinically relevant for margin detection, from Myogel samples in vitro.