Browsing by Subject "Micromagnet"

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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.
Immunomagnetic microfluidic screening system for circulating tumor cells detection and analysis
(2013-12) Huang, Yu-Yen, active 21st century; Zhang, John X. J.
Circulating tumor cells (CTCs) are known to escape from the primary tumor site and may settle down at the distant organ to grow a second tumor. CTCs are one of causes initiating carcinoma metastasis. Detection of CTCs has been considered to be valuable for cancer management, including diagnosis, prognosis, and clinical treatment management. However, efficient isolation, enumeration, characterization, and genetic analysis of CTCs in whole-blood samples from cancer patients are very challenging due to their extremely low concentration and rare nature (per CTC in blood cells is 1:106–109). With the increasing worldwide death rate associated with cancer, there is a desperate demand for a high-sensitivity, high-throughput, and low-cost detection and separation system. My doctoral research focused on the design and fabrications of the screening system for the detection of CTCs with further analysis of captured CTCs, such as immunofluoresce staining and fluorescence in-situ hybridization (FISH). The distinct significance of this research is that the development of the computer-controlled rotational holder with a series of six inverted microfluidic chips reduced the cost by significantly reducing the consumption of magnetic carriers (25% of the consumed amount used in the commercial CellSearch® system), increasing the capture efficiency by manipulating the blood sedimentation in the microchannel, enhancing the system stability by integrating the micromagnets on the plain glass slide substrate, and achieving high throughput because of the high flow rate (2.5 mL/hr) and large screening volume (screening up to six chips in parallel with each containing 2.5 mL of blood). Immunofluorescence staining and the FISH method have been performed to prove the capability of the system. In addition, the system has been successfully applied for patient samples screening. The incorporation of micromagnets has demonstrated that micromagnets provide localized magnetic forces to scatter the target cancer cells and free nanoparticles throughout the whole channel substrate to increase the channel space usage by 13%. Four cancer cell lines, including COLO 205 (colorectal cancer), SK-BR-3 (breast cancer), MCF-7 (breast cancer), and PC3 (prostate cancer), were spiked in blood samples from healthy donors to verify high capture efficiency of the developed system. On average, over a 97% capture rate was demonstrated for all cell lines. Moreover, the developed screening system has been successfully screened over 40 patient samples, including metastatic lung cancer, breast cancer, prostate cancer, and colorectal cancer. After capture of CTCs, immunofluorescence staining was used to identified the captured cancer cells and the FISH method was performed to characterize the isolated cancer cells by studying the gene expression of CTCs from breast cancer. The proposed automated immunomagnetic microchip-based screening system shows high capture efficiency (average 97% for three spiked cell lines), high throughput (15 mL of blood sample per screening), high sensitivity, high specificity, and low nanoparticle consumption (75% less than CellSearch® system). The screening system provides great promise as a clinical tool for early cancer diagnosis, diagnosis, personalized therapy, and treatment monitoring.