Abstract LB-72: Rapid detection and profiling of breast cancer cells in blood applied to arrays of carbon nanotube thin film biosensors

Abstract

Abstract Breast cancer is the most frequently diagnosed cancer in women. Developing breast cancers shed transformed cells into the blood. More malignant breast cancer cells appear in the blood at later stages. Early detection of circulating breast cancer cells might improve diagnosis of early breast cancer and ultimately might reduce deaths from breast cancer. We hypothesized that nanotube-antibody arrays could detect circulating human breast cancer cells in a drop of blood. Breast cancer cell surfaces show high levels of insulin-like growth factor 1 receptor (IGF1R), human epidermal growth factor receptor 1 (Her1, EGFR), and Her2 (Erb-B2, neu), among others. We have previously demonstrated antibody-specific nanodevice detection of ER+/Her2- MCF7 and ER+/Her2+ BT474 breast cancer cells suspended in a physiological buffer, and in fresh human blood. We discovered significant changes in conductance of single wall carbon nanotube-monoclonal antibody nanodevices upon exposure to human breast cancer cells in 2-5 microliter drops of physiological buffer or fresh donor blood. The nanodevices detected the cancer cells within 60 seconds and stabilized by five minutes. Control cells did not change nanodevice conductance. Breast cancer cells did not perturb the conductance of nanodevices with adsorbed anti-PSMA or nonspecific antibodies. Hence, the conductance change required a specific antigen-antibody complex between the live, intact breast cancer cell and the nanotube surface in blood. We postulate that sensing of breast cancer cell binding is due to cooperative stress on the surface of the nanotubes due to cellular binding to multiple antibodies. The stress on the nanotube is then thought to change its electron transport properties. Five microliter drops of blood from patients with metastatic breast cancer changed nanodevice conductance similarly to 10-100 MCF7 cells. Comparable circulating tumor cell numbers were obtained from 7.5 mL blood draws from the same patients analyzed by EpCAM bead capture and anti-cytokeratin staining. Single wall carbon nanotube-monoclonal antibody nanodevices provide the simplest and quickest method for direct detection of live cancer cells circulating in blood. Supported by a grant from the Breast Cancer Alliance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-72.