Three-Dimensional Nanostructured Substrates toward Efficient Capture of Circulating Tumor Cells

During the progression of metastasis, cancer cells detach from the solid primary tumor, enter the blood stream, and travel to different tissues of the body. These breakaway cancer cells in the peripheral blood are known as circulating tumor cells (CTCs).[1] In addition to conventional diagnostic imaging and serum marker detection, quantification of CTCs in patient blood provides new and valuable information about managing cancer.[2–5] Over the past decade, CTC counting has been used for examining cancer metastasis, predicting patient prognosis, and monitoring the therapeutic outcomes of cancer.[6] However, isolation of CTCs has been technically challenging due to the extremely low abundance (a few to hundreds per milliliter) of CTCs among a large number of hematologic cells in the blood (109 mL−1).[4, 7, 8] Several technology platforms for isolating/counting CTCs have been developed with strategies that involve immunomagnetic beads or microfluidic devices.[3, 4,9, 10] The former utilizes capture-agent-coated magnetic beads to immunologically recognize CTCs in the blood, followed by magnetic isolation. However, these bead-based approaches are limited by their low CTC-capture yield and purity. Recently, a number of microfluidic technologies[9, 10] has been established for capturing viable CTCs from whole-blood samples with improved efficiency and selectivity compared to the bead-based approach.[3, 7] While different device architectures were applied in these CTC-sorting microchips, the improved CTC-capture efficiencies were achieved by increasing CTC/substrate contact frequency and duration.