The long-term objective of this application is to develop an integrated technology platform for highly sensitive detection and molecular analysis of circulating tumor cells (CTCs) from whole blood. The unique working mechanism based on the high affinity nanopillar-grafted substrate confers the advantages of enhanced CTC capture efficiency/purity, low operation cost and ease of use to this new technology. The PI's research group has demonstrated that a silicon nanopillar (SiNP)-covered substrate, coated with anti-EpCAM, exhibits outstanding efficiency when employed to isolate viable CTCs from whole blood samples. With a simple stationary device setting and operation protocol, CTCs can be immobilized onto the SiNP substrates because of enhanced topographic interactions between the SiNPs and cell surface components. The clinical studies of this CTC capture technology have been initiated for side-by-side validation with the FDA-approved CellSearchTM assay. In parallel, a quantitative ICC approach for multiparametric molecular profile of individual cancer cells has been established and can be directly applied for molecular analysis of CTCs. These preliminary results constitute a solid foundation for our proposed research. CTCs are cancer cells that break away from either the primary tumor or metastatic site(s) and circulate in the peripheral blood. Enumeration and characterization of CTCs in patient blood provides valuable information for examining early-stage cancer metastases, predicting patient prognosis and monitoring therapeutic interventions and outcomes. Over the past decade, a variety of technologies capable of isolating and counting CTCs have been developed based on different working mechanisms. Some of these technologies have been demonstrated in the clinical setting and allow reproducible detection of CTCs in the patient blood. However, challenges remain in improving CTC capture efficiency, reducing measurement costs and conducting sequential molecular analysis of these cells. Herein, we propose to first perform a comprehensive optimization of the SiNP-based CTC capture technology by (i) exploring the use of polymer-based nanopillars, (ii) altering the dimension and packing density of nanopillars, (iii) enabling a capability to capture a broader diversity of CTCs, (iv) incorporating anti- biofouling function, and (v) integrating a microfluidic chaotic mixer. In parallel, we will carry out optimization of an operation protocol for ICC quantification of 4-protein molecules, including cytokeratin (CK), CD45, androgen receptor (AR) and CD44, in the isolated CTCs. Next, we will use optimal CTC capture conditions to detect CTCs from whole blood samples obtained from prostate cancer patients at different stages. Sequentially, single-cell multiparametric molecular analysis (i.e., CK, CD45, AR and CD44) of the substrate-immobilized CTCs will be carried out using the quantitative ICC approach to unveil the molecular properties and cellular heterogeneity of the CTCs.
The long term objective of this application is to develop a new technology platform for detection and characterization of circulating tumor cells (CTCs) from cancer patient blood. This new CTC-based diagnostic platform offers the advantages of high CTC capture sensitivity, low operation cost and user-friendliness, thus introducing a valuable point-of-care tool for patients with metastatic cancer.
|Jan, Yu Jen; Chen, Jie-Fu; Zhu, Yazhen et al. (2018) NanoVelcro rare-cell assays for detection and characterization of circulating tumor cells. Adv Drug Deliv Rev 125:78-93|
|Shen, Mo-Yuan; Chen, Jie-Fu; Luo, Chun-Hao et al. (2018) Glycan Stimulation Enables Purification of Prostate Cancer Circulating Tumor Cells on PEDOT NanoVelcro Chips for RNA Biomarker Detection. Adv Healthc Mater 7:|
|Chen, Jie-Fu; Zhu, Yazhen; Lu, Yi-Tsung et al. (2016) Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells. Theranostics 6:1425-39|
|Jiang, Runze; Lu, Yi-Tsung; Ho, Hao et al. (2015) A comparison of isolated circulating tumor cells and tissue biopsies using whole-genome sequencing in prostate cancer. Oncotarget 6:44781-93|
|Ke, Zunfu; Lin, Millicent; Chen, Jie-Fu et al. (2015) Programming thermoresponsiveness of NanoVelcro substrates enables effective purification of circulating tumor cells in lung cancer patients. ACS Nano 9:62-70|
|Court, Colin M; Ankeny, Jacob S; Hou, Shuang et al. (2015) Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis. Expert Rev Mol Diagn 15:1491-504|
|Chen, Jie-Fu; Ho, Hao; Lichterman, Jake et al. (2015) Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases. Cancer 121:3240-51|
|Lin, Millicent; Chen, Jie-Fu; Lu, Yi-Tsung et al. (2014) Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells. Acc Chem Res 47:2941-50|
|Shen, Qinglin; Xu, Li; Zhao, Libo et al. (2013) Specific capture and release of circulating tumor cells using aptamer-modified nanosubstrates. Adv Mater 25:2368-73|
|Zhao, Libo; Lu, Yi-Tsung; Li, Fuqiang et al. (2013) High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing. Adv Mater 25:2897-902|
Showing the most recent 10 out of 16 publications