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Microfluidic devices and methods of enrichment and detection of rare cells, e.g. circulating tumor cells (CTC), and other biomarkers including protein and DNA/RNA, from biological fluid samples are disclosed. The device is an improvement over prior micro fluidics devices by having in its capture chamber smooth surfaces which are designed to mimic the floor of a naturally occurring water body, such as a seafloor or river bed, at the micrometer level. The smooth surface features create a gentle environment, and enhance sample mixing, continuous cell-antibody contact, and rare cell capture. Shear- force and cell damage are reduced. The cell capture module is coated with cell-capture ligands. A second optional module binds non-cell biomarkers with high sensitivity due to the large volume of sample used for rare cell isolation to enrich the non-cell biomarkers by at least 100-1000 times.