Browsing by Subject "Circulating tumor cells"

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Antibody-free isolation of circulating tumor cells by dielectrophoretic field-flow fractionation
(2013-08) Shim, Sangjo; Gascoyne, Peter R. C.
This work focuses on the integration of microfluidics and dielectrophoresis(DEP) with the principles of field flow fractionation (FFF) to create a continuous-flow isolator for rare and viable circulating tumor cells (CTCs) from peripheral blood mononuclear cells (PBMNs) drawn from cancer patients. The method exploits differences in the plasma membrane capacitances of tumor and blood cells, which correspond to differences in the membrane surface areas of these cell types. DEP-FFF was first adapted to measure cell membrane capacitance, cell density and deformability profiles of cell populations. These properties of the NCI-60 panel of cancer cell types, which represents the wide functional diversity of cancers from 9 organs and leukemia, were compared with the normal cell subpopulations of peripheral blood. In every case, the NCI-60 cells exhibited membrane capacitance characteristics that were distinct from blood and, as a result, they could be isolated from blood by DEP. The heightened cancer cell membrane capacitances correlated strongly with membrane-rich morphological characteristics at their growth sites, including cell flattening, dendritic projections, and surface wrinkling. Following harvest from culture and maintenance in suspension, cancer cells were found to shed cytoplasm and membrane area over time and the suspended cell populations developed considerable morphological diversity. The shedding changed the cancer cell DEP properties but they could still be isolated from blood cells. A similar shedding process in the peripheral blood could account for the surprisingly wide morphological diversity seen among circulating cells isolated from clinical specimens. A continuous flow DEP-FFF method was devised to exploit these findings by allowing CTCs to be isolated from the nucleated cells of 10 mL clinical blood specimens in 40 minutes, an extremely high throughput rate for a microfluidic-based method. Cultured cancer cells could be isolated at 70-80% efficiency using this approach and the isolation of CTCs from clinical specimens was demonstrated. The results showed that the continuous DEP-FFF method delivers unmodified, viable CTCs for analysis, is perhaps universally applicable to isolation of CTCs from different cancer types and is independent of surface antigens - making it suitable for cells lacking the epithelial markers used in currently accepted CTC isolation methods.
Fano-resonant plasmonic metasurface for cancer detection using few-cell spectroscopy and other optical applications in mid-infrared
(2016-06-10) Arju, Nihal; Shvets, G.; Alu, Andrea; Florin, Ernst-Ludwig; Li, Xiaoqin; Sokolov, Konstantin
The field of metamaterials holds enormous promise in our ability to engineer artificial (‘meta’) material to suit a wide variety of needs. Metamaterials have been designed to achieve electromagnetic cloaking, negative refractive index, perfect absorption and many other phenomena that were thought to be impossible to achieve. Fano resonant metamaterials form a subclass of metamaterials that possess one or more Fano-type resonances. The Fano resonance arises out of interference between two resonance modes with disparate lifetimes. A variety of Fano resonant asymmetric metamaterials (FRAMMs) have been investigated in this dissertation. A circularly dichroic double continuum FRAMM was constructed and the effect of tuning the interference between modes on a Fano resonance has been examined. These metamaterial surfaces (metasurfaces) have strong field confinement. As a result, a small change in the near vicinity of the metasurface creates a detectable change in the metasurface response, which allows the metasurfaces to be used as sensors. The FRAMM was used to detect monolayer of protein otherwise undetectable using Fluorescence microscopy. It was also used to examine different cell types. One promising strategy for early cancer detection involves detecting cancerous cells in the bloodstream. These circulating tumor cells (CTCs) spread through the body and create tumors. Metasurface sensors may be used to conduct spectroscopy on cells in order to spectroscopically identify different cell types, including whether the cells are cancerous or not. A statistical analysis reveals that it is possible to detect different cell types using metasurfaces.
Immunomagnetic circulating tumor cells (CTCs) detection at small scale : multiphysical modeling, thin-film magnets and cancer screening
(2014-08) Chen, Peng, active 21st century; Zhang, Xiaojing, Ph. D.; Yeh, Tim H. C.; Hoshino, Kazunori; Tunnell, James W; Jiang, Ning
Circulating tumor cells (CTCs) are the cells that are shed from a primary tumor into the vasculature and circulate in the bloodstream. CTCs may trigger cancer metastasis, which leads to most cancer-related deaths. CTCs are widely studied due to their value in cancer diagnosis, prognosis, and oncology studies. The major challenges with CTCs lie in their extremely low concentration in blood, thus requiring an effective enriching system to enable downstream analyses. The immunomagnetic assay has proved to be a promising CTC detection tool with high sensitivity and throughput. Key factors related to the immunomagnetic assay include the capture rate, which indicates the sensitivity, and distributions of target cells after capture, which impact the cell integrity and other biological properties. In this dissertation, we build a sedimentation model, a partial viscosity model, and a cell-tracking model to address the principle of the immunomagnetic cell separation. We examine the channel orientations and determine the favorable inverted condition. In addition, we develop a micromagnet approach to modulate the in-channel magnetic field toward enhanced cell detection and distribution. Through numerical studies, we calculate the magnetic field generated by the thin-film micromagnets, determine its effective ranges, and demonstrate its value in optimizing cell distribution. In the experimental demonstration, we present two types of micromagnets based on e-beam Ni deposition and inkjet printing technology, respectively. In the screening experiments, the Ni micromagnet integrated system achieves over 97% capture rate. It shows a 14% increase in capture rate, and a 14% improvement in distribution uniformity compared with plain slides. We also successfully isolate CTCs from metastatic cancer patients with the micromagnet assay. The inkjet-printed patterns yield a similarly high capture rate of 103%. With the pixel permanent magnet array, the inkjet patterns further increase the distribution uniformity for 20%. The proposed models lay the theoretical foundations for future modification of the immunomagnetic assay, and the micromagnet-integrated system provides a promising tool for translational applications in cancer diagnose and clinical cancer management.