In the later stages of cancer, carcinoma cells are shed into the blood stream to become circulating tumor cells (CTCs). These cells spread cancer throughout the body in the deadly process known as tumor metastasis. CTCs are present at extremely low concentrations in the blood, making them difficult to isolate and study. In order to develop new life-saving cancer treatments, clinicians and researchers need to learn more about CTCs and the processes of change that allow them to travel the bloodstream and colonize new tissues. To help meet this need, a new method for CTC isolation was recently developed that utilizes immunoaffinity to antibodies immobilized on microchannel surfaces to bind and sequester CTCs. We have investigated a number of methods for improving the efficiency and purity of this microfluidic immunoaffinity based tumor cell isolation. These include: a biomimetic combination of cell capture proteins, surface protein patterning, microfluidic mixers, and dendrimer facilitated multivalent binding. Furthermore, we have developed a blood analog for use in the initial validation of microfluidic CTC isolation devices.