An innovative cellular medicine approach via the utilization of novel nanotechnology-based biomechatronic platforms as a label-free biomarker for early melanoma diagnosis.

Innovative cellular medicine (ICM) is an exponentially emerging field with a promising approach to combating complex and ubiquitous life-threatening diseases such as multiple sclerosis (MS), arthritis, Parkinson's disease, Alzheimer's, heart disease, and cancer. Together with the advancement of nanotechnology and bio-mechatronics, ICM revolutionizes cellular therapy in understanding the essence and nature of the disease initiated at a single-cell level. This paper focuses on the intricate nature of cancer that requires multi-disciplinary efforts to characterize it well in order to achieve the objectives of modern world contemporary medicine in the early detection of the disease at a cellular level and potentially arrest its proliferation mechanism. This justifies the multidisciplinary research backgrounds of the authors of this paper in advancing cellular medicine by bridging the gap between experimental biology and the engineering field. Thus, in pursuing this approach, two novel miniaturized and highly versatile biomechatronic platforms with dedicated operating software and microelectronics are designed, modeled, nanofabricated, and tested in numerous in vitro experiments to investigate a hypothesis and arrive at a proven theorem in carcinogenesis by interrelating cellular contractile force, membrane potential, and cellular morphology for early detection and characterization of melanoma cancer cells. The novelties that flourished within this work are manifested in sixfold: (1) developing a mathematical model that utilizes a Heaviside step function, as well as a pin-force model to compute the contractile force of a living cell, (2) deriving an expression of cell-membrane potential based on Laplace and Fourier Transform and their Inverse Transform functions by encountering Warburg diffusion impedance factor, (3) nano-fabricating novel biomechatronic platforms with associated microelectronics and customized software that extract cellular physics and mechanics, (4) developing a label-free biomarker, (5) arrive at a proved theorem in developing a mathematical expression in relating cancer cell mechanobiology to its biophysics in connection to the stage of the disease, and (6) to the first time in literature, and to the best of the authors' knowledge, discriminating different stages and morphology of cancer cell melanoma based on their cell-membrane potentials, and associated contractile forces that could introduce a new venue of cellular therapeutic modalities, preclinical early cancer diagnosis, and a novel approach in immunotherapy drug development. The proposed innovative technology-based versatile bio-mechatronic platforms shall be extended for future studies, investigating the role of electrochemical signaling of the nervous system in cancer formation that will significantly impact modern oncology by pursuing a targeted immunotherapy approach. This work also provides a robust platform for immunotherapy practitioners in extending the study of cellular biophysics in stalling neural-cancer interactions, of which the FDA-approved chimeric antigen receptor (CAR)-T cell therapies can be enhanced (genetically engineered) in a lab by improving its receptors to capture cancer antigens. This work amplifies the importance of studying neurotransmitters and electrochemical signaling molecules in shaping the immune T-cell function and its effectiveness in arresting cancer proliferation rate (mechanobiology mechanism).