Tumor initiating cells (TICs), also known as cancer stem cells, are a finite population of cancer cells that have the ability to transplant a new tumor from an existing one. They are also putatively responsible for the metastatic properties of tumors. Isolation of TICs is the first step towards understanding the role of these cells in the pathogenesis and progression of cancer and is critical towards the development of improved specific therapies for cancer. The TIC is the most relevant therapeutic target. However, current efforts in isolation and characterization of the TIC are hampered by the lack of suitable high throughput and rapid methods to isolate these cells. Contactless-dielectrophoresis (cDEP) is a new, non-invasive technique to detect and enrich rare cells suspended in a medium based on their physical and electrical properties, independent of their genotype. Dielectrophoresis (DEP) relies upon the motion of a particle due to its polarization induced by a non-uniform electric fiel. Conventional DEP microfluidic systems are susceptible to electrode fouling and require complicated fabrication procedures, because the electrodes are in direct contact with the sample, which limits their lifetime and cost effectiveness. cDEP alleviates these limitations by using external electrodes placed in secondary, highly conductive, channels that are separated from the cell sample by a thin insulating layer. Since the devices do not require complicated fabrication techniques, mass production is readily achievable and, therefore, this technique can be used by a large population of biologists and researchers for cell isolation. The application of DEP to separate target cells has been studied extensively in the last two decades, and the results indicate that rare cells can be separated from other cells in a cell mixture. Our central hypothesis is that cDEP is capable of discriminating between tumor imitating cells (TICs) and non-TICs. We will utilize a multifaceted approach involving experimentation and computational modeling to design new cDEP devices to assess and optimize the effectiveness of cDEP technology to physically separate and enrich tumor initiating cells from other cell populations found in a tumor. This multi-faceted approach will include 1) characterize the dielectrophoretic response of tumor initiating cells compared to typical tumor cells, 2) assess the performance of cDEP at isolating and selectively concentrating tumor initiating cells, 3) investigate possible subpopulation of TICs by sorting cells using cDEP microdevices, and 4) use primary human prostate tissue and repeat Aims 1, 2, and 3 with primary human prostate cells. Success in isolating TICs will lead to increased understanding of the most appropriate therapeutic strategies to ablate this cell population.
Contactless Dielectrophoresis (cDEP) is a new technique to isolate and enrich rare cells from a cell mixture or from biological fluids. The goal of this projet is to develop cDEP as a tool for physicians to isolate patient specific tumor initiating cells (TIC) from non-TICs. This will facilitate understanding of TICs role in the pathogenesis, progression of cancer, and will lead to increased understanding of the most appropriate therapeutic strategies to ablate this cell population.
|Douglas, Temple Anne; Cemazar, Jaka; Balani, Nikita et al. (2017) A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow. Electrophoresis 38:1507-1514|
|?emažar, Jaka; Douglas, Temple A; Schmelz, Eva M et al. (2016) Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures. Biomicrofluidics 10:014109|
|Murovec, Tomo; Sweeney, Daniel C; Latouche, Eduardo et al. (2016) Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation. Biophys J 111:2286-2295|
|Ivey, Jill W; Bonakdar, Mohammad; Kanitkar, Akanksha et al. (2016) Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment. Cancer Lett 380:330-9|
|Bonakdar, Mohammad; Wasson, Elisa M; Lee, Yong W et al. (2016) Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier. Biophys J 110:503-513|
|Gallo-Villanueva, Roberto C; Sano, Michael B; Lapizco-Encinas, Blanca H et al. (2014) Joule heating effects on particle immobilization in insulator-based dielectrophoretic devices. Electrophoresis 35:352-61|
|Salmanzadeh, Alireza; Elvington, Elizabeth S; Roberts, Paul C et al. (2013) Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model. Integr Biol (Camb) 5:843-52|