Three-Dimensional Microposts Covered with Nanostructures for Circulating Tumor Cell and Small Molecule Detection

Description

Many new cases of cancer are reported each year around the world. In Hong Kong, more than 14,000 deaths in 2018 were related to cancer, and the number of new patients with cancer is increasing each year. When patients are diagnosed at the early stages, they have good chances of being cured. However, when cancer is detected at the advanced stages, the patient survival rates become much lower. Cancer metastasis occurs when cancer cells migrate out of the primary tumor due to hematogenous spreading and invade other organs. Metastatic cancer is difficult to treat, especially when the invasive cells have spread to multiple organs. Patients not only suffer physically and mentally but also must pay expensive medical bills. Therefore, developing a biosensing system that could detect cancer early, way before spreading occurs, is beneficial. In this study, a development of novel three-dimensional (3D) microstructures surrounded with nanostructures that serve as biosensors is proposed. With the appropriate design and nanofabrication technology for the proposed sensing system, cells and biomolecules could be captured with high efficiency and detected with high sensitivity. Detecting the circulating tumor cells (CTCs) and the related small biomolecules, such as microvesicles (MVs), is important for early cancer diagnosis. CTCs and MVs are good indicators of cancer prognosis, but they are often in low concentrations. Therefore, a biosensing system that could detect them even when their concentrations are low could be useful for early cancer diagnostics that could lead to increased survival rates. A new approach to create 3D microstructures completely covered with nanostructures will be developed in this study. Such designs will promote increases in cell and biomolecule attachments to the 3D system densely packed with micro- and nanostructures. Typically, surface topography or sensors could only be built on a top surface. With the proposed technology that utilizes the special characteristics of shape memory polymer, nanotopographies and biosensors could be formed not only on the top surface but also along the sidewalls and the bottom surface, making the system much more effective for CTC and MV capturing. Moreover, the nanostructures patterned around the 3D microstructures will be integrated as nanoplasmonic sensors, which provide a dense array of detectors for sensing. The combined micro- and nanostructures with the built-in biosensors will form a highly efficient capturing and highly sensitive detection system needed for the detection of low-concentration CTCs and MVs. The proposed sensing system could provide the high sensitivity and efficiency needed for early cancer diagnostics.