Circulating tumor cells (CTCs) are isolated tumor cells disseminated from the site of disease in metastatic or primary cancers, including breast, prostate, and lung cancer. CTCs can be identified and counted in the peripheral blood of patients. The biological analysis of CTCs using lab-on-chip technologies effectively diagnose the disease, determine personalized therapies, and adjust treatments in real time. This significantly increases the survival chance of the patients. Because of their rare occurrence, a few CTCs per 1 mL of blood, the CTCs must be isolated from the blood sample. Recent developments of microfluidic devices made a significant breakthrough in the detection and filtration of CTCs from blood.The aim of the project is to incorporate rigorous optimization techniques in the development of such devices. In the design process of currently manufactured devices, the focus has not been put on the performance optimization. The use of mathematically justified optimization techniques offers huge potential for increasing the efficiency.A computer tool for simulation of complex processes inside microfluidic devices will be developed. A novel capture mechanism based on local affinity interactions will be elaborated. An optimization framework will be established and implemented in the software. With this framework, new devices with higher efficiency will be designed.During the designing process, different concepts will be optimized, e.g. geometry, blood flow velocities, external magnetic fields manipulating ferromagnetic parts of the device, and other. The optimization will be carried out in a rigorous way by applying iterative optimization techniques, which is a novel element in the development of microfluidic devices.The underlying physical models will be properly calibrated and validated, and the simulation and the optimization methods will be mathematically justified.