Identification and Drug Screening of Single Cells from Human Tumors on Semiconductor Chip for Cancer Precision Medicine.

Drug screening of primary tumor cells directly assesses the drug efficacy on specific tumors, promoting personalized cancer treatment. The application of a microfluidic platform has realized drug screening using a limited amount of biopsy samples for cancer precision medicine. However, all the techniques face an inevitable issue of not all the primary tumor cells being cancer cells. Here, a system is introduced that integrates single-cell identification and drug screening on one semiconductor chip so that both drug efficacy on cancer cells and drug toxicity on noncancerous cells can be obtained simultaneously. An integrated circuit is built on the semiconductor chip for single-cell electric impedance sensing (IC-ECIS) of ultra-weak signals for distinguishing cancer cells from noncancerous cells without affecting cell vitality. Single-cell identification is validated using breast, lung, and liver cell lines as well as liver cancer specimens from clinical patients. The accuracy on commercial cell lines is ≈80%, and the diagnostic results of tumor tissues are consistent with clinical pathology results. Drug screening is run on the same chip after single cell identification for dual evaluation of drug efficacy and toxicity in both breast cancer models and clinical liver cancer patients. The on-chip drug screening is confirmed with off-chip counterpart experiments in breast cell lines. The effectiveness or ineffectiveness of a drug screened on the IC-ECIS chip demonstrated consistency in the presence or absence of specific mutations in the drug-related genes determined via exome sequencing of individual liver tumors, validating the method for precision medicine.