This paper reports on the comparison analysis of four main types of silicon-based microfilter for isolation of white blood cells (WBCs) from red blood cells (RBCs) in a given whole blood. The microfilter designs, namely, weir, pillar, crossflow, and membrane, all impose the same cut-off size of 3.5 mum to selectively trap WBCs. Using human whole blood, the microfilters have been characterized and compared for their blood handling capacity, WBCs trapping efficiency and RBCs passing efficiency. Based on the experimental results, the crossflow microfilter is superior and can be integrated with downstream components for on-chip genomic analysis.