Electrochemical tracing of hypoxia glycolysis by carbon nanotube sensors, a new hallmark for intraoperative detection of suspicious margins to breast neoplasia

Abstract For most people, the first step in treatment is to take out the tumor (surgery), so precise and fast diagnosis of any sign of high‐risk and neoplastic cells, especially in surgical cavity margins, is significant. The frozen pathology method is the conventional standard of intraoperative diagnosis, but the low number of slides prepared from non‐fixed tissues prevents us from achieving a perfect diagnosis. Although many improvements in intraoperative margin detection were achieved, still real‐time detection of neoplastic lesions is crucial to improving diagnostic quality. Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer/atypical cells through reverse Warburg effect and hypoxia assisted glycolysis pathways in a quantitative electrochemical manner. The study was carried out on cell lines, 57 in vivo mice models with breast cancer, and 258 fresh in vitro samples of breast cancer tumors. A real‐time electrotechnical system, named cancer diagnostic probe (CDP) (US Patent Pub. No.: US 2018/02991 A1, US 2021/0007638 A1, and US 2021/0022650 A1 [publications], and US 10,786,188 B1 [granted]), has been developed to find pre‐neoplastic/neoplastic cells in vivo in a quantitative electrochemical manner by tracing hypoxia glycolysis byproducts. Matched pathological evaluations with response peaks of CDP were found based on the presence of neoplasia (from atypia to invasive carcinoma) in live breast tissues. The ability of CDP to find neoplastic lesions in mice models in vivo and fresh breast tumors in vitro was verified with sensitivity and specificity of 95% and 97%, respectively. The system may help a surgeon assistant system for usage in the operating room after passing many trials and standard examinations in the future.