Membrane Voltage Profiling: A Bioelectricity-Based Intraoperative Imaging Methodology for Rapid Surgical Margin Analysis

Abstract

Surgeons face serious challenges removing cancer fully during surgery, with incomplete cancer removal posing significant risks to patients. To address this problem, Lucell Diagnostics Inc. is developing an innovative cancer detection platform called membrane voltage profiling (MVPro; patent pending). This groundbreaking method exploits the discovery that cancer cells exhibit a physiological biomarker, depolarization, as revealed by fluorescent voltage-sensitive dyes. Cancer cells fluoresce in specific patterns and intensities that differ from normal cells, allowing precise identification. We present here our preliminary results on the feasibility of using voltage to locate cancer cells. The aims were: to perform controls showing whether MVPro affects the normal pathology process; to optimize tissue transfer for margin cell collection; to confirm that the VSD DiBAC₄(3) is appropriate for MVPro of skin cells; to determine whether MVPro finds cancer in the same specimens as pathological analysis. These studies on nonmelanoma skin cancer specimens reveal that MVPro is low risk to the patient, integrates with existing surgical protocols, finds cancer in the same specimens as does pathology, and presents no complications for pathological analysis. Once development of this methodology is complete, MVPro will yield an annotated, 2D heat map covering the entire surgical margin, indicating the location of cells with a high likelihood of being cancer. This will empower surgeons to confirm a negative surgical margin before closing. This simple type of intraoperative imaging, performed in or near the operating theater, has the potential to improve surgical outcome, cut health care costs, and enhance post-surgical quality of life by preserving healthy tissue. Because the setup costs are relatively small and the reagents are inexpensive, we believe MVPro could be of great benefit to underserved areas. Indeed, MVPro could benefit health care systems globally, from cutting-edge hospitals to small clinics in underserved regions.