This Mentored Quantitative Research Development Award will facilitate the candidate, an engineer, to become a biologist. It will be achieved by taking courses to gain fundamental knowledge in biology/medicine and developing relevant research skills via mentored research. The selected courses will include core courses encompassing the fundamentals of biomedical sciences and advanced courses. Biomedical research experience will be obtained through lab rotations in the mentor's and co-mentor's laboratories. The mentored research is to develop a platform to concentrate and enrich acute leukemia cells for detection of minimal residual disease (MRD). MRD refers to the presence of residual malignant cells that remain in the patient during treatment or after treatment when the patient is in remission (no symptoms or signs of disease). The current benchmark method is not sufficiently sensitive for detecting all remaining tumor cells in peripheral blood. As a result, a platform with a higher sensitivity will be desirable since MRD can distinguish those who need intensive and potentially more toxic therapy from those who do not.
The specific aims of this project are to (1) design and fabricate a device for enrichment of leukemia cells; (2) demonstrate the enrichment of leukemia cells in the device using aptamers with specific binding to acute lymphoblastic leukemia cells; and (3) validate the platform technology by analyzing leukemia cells in clinical samples and detect MRD. The significance of the research lies in the following aspects. First, the proposed research will lead to a platform for a rapid and efficient enrichment of acute leukemia cells. The platform will offer a measureable approach to determine if any additional chemo-therapy is needed; this will bring significant benefits to leukemia patients since unnecessary toxic therapy can be avoided. Second, the platform can be easily adapted for enrichment of rare circulating cells of other cancers. Isolation of these rare tumor cells could offer an opportunity for early-stage cancer screening and medical diagnostics. Third, the proposed research will advance the fields of cancer biology, biomedical engineering, and micro-nanotechnologies.
Cancer is one of the leading causes of death hence innovative platforms that would accelerate the research and understanding of cancer biology could have significant societal impacts. The goal of the proposed research is to develop a platform for detecting minimal residual disease of acute leukemia, which can effectively guide clinical care and increase the cure rate.
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|Varillas, Jose I; Chen, Kangfu; Zhang, Jinling et al. (2017) A Novel Microfluidic Device for Isolation of Circulating Tumor Cells from Pancreatic Cancer Blood Samples. Methods Mol Biol 1634:33-53|
|Zhang, J; Chen, K; Fan, Z H (2016) Circulating Tumor Cell Isolation and Analysis. Adv Clin Chem 75:1-31|
|Zhang, Jinling; Fan, Z Hugh (2016) A universal tumor cell isolation method enabled by fibrin-coated microchannels. Analyst 141:563-6|
|Cassano, Christopher L; Simon, Andrew J; Liu, Wei et al. (2015) Use of vacuum bagging for fabricating thermoplastic microfluidic devices. Lab Chip 15:62-6|
|Ward, Kevin; Fan, Z Hugh (2015) Mixing in microfluidic devices and enhancement methods. J Micromech Microeng 25:|
|Zhang, Jinling; Sheng, Weian; Fan, Z Hugh (2014) An ensemble of aptamers and antibodies for multivalent capture of cancer cells. Chem Commun (Camb) 50:6722-5|
|George Jr, Thomas J; Ogunwobi, Olorunseun O; Sheng, Weian et al. (2014) ""Tissue is the issue"": circulating tumor cells in pancreatic cancer. J Gastrointest Cancer 45 Suppl 1:222-5|
|Sheng, Weian; Ogunwobi, Olorunseun O; Chen, Tao et al. (2014) Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip. Lab Chip 14:89-98|
|Fan, Z Hugh; Tan, Weihong (2013) DNA nanospheres with microfluidics: a promising platform for cancer diagnosis? Nanomedicine (Lond) 8:1731-3|
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