Date of Graduation

12-2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Biological Sciences

Advisor/Mentor

Ryan Tian

Committee Member

Yuchun Du

Second Committee Member

David Paul

Third Committee Member

Ralph Henry

Fourth Committee Member

Radwan Alfaouri

Keywords

Bioscafold, Biosensor, Cancer, Metabolic waste, TiO2, Warburg effect

Abstract

Cancer cell research has been growing for decades. In the field of cancer pathology, there is an increasing and long-unmet need to develop a new technology for low-cost, rapid, sensitive, selective, label-free (i.e. direct), simple and reliable screening, diagnosis, and monitoring of live cancer and normal cells in same shape and size from the same anatomic region. For the first time on using an impedance signal, the breast cancer and normal cells have been thus screened, diagnosed and monitored on a smart bioscaffold of entangled nanowires of bioceramics titanate grown directly on the surface of implantable Ti-metal and characterized by SEM, XRD, etc. following a technology patented by Tian-lab. In experiment in the aqueous solution of phosphate buffer saline (PBS), human breast benign (MCF7) and aggressive (MDA-MB231) cancer cells, normal (MCF10A) cells, and colon cancer cells (HCT116) showed characteristic impedance spectrum highly different than that of the blank sensor (i.e. no cells on the bioscaffold surface). For two sets of mixtures each containing the normal and cancer cells over a wide range of mixing ratios, the shift of impedance signals has been linearly correlated with the mixing ratios which supports the biosensor’s selectivity and reliability. After being treated with pure glucose and chemotherapeutic drug (i.e. doxorubicin of DOX) and with one after the other, the breast cancer cells showed different impedance signals corresponding to their difference in glucose metabolisms (i.e. Warburg Effect) and resistances to the Dox, thus-fingerprinting the cells easily. Based on the nanostructure chemistry, impedance equivalent circuitry and cancer cell biology, it’s the different cells surface binding on the nanowires, and different cancer cells metabolic wastes from the different treatments on the nanowires that changed the charge density on the scaffolding nanowire surface and in turn changed the impedance signals. This new method is believed expandable to quantifying and characterizing live cells and even biological tissues of different types in general.

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