This paper presents a thermal-bubble-actuated microfluidic chip with cross-shaped microchannels for evaluating the effect of different microchannel designs on microparticle manipulation. Four cross-shaped microchannel designs, with orthogonal, misaligned, skewed, and antiskewed types, were proposed in this study. The thermal bubble micropump, which is based on a resistive bulk microheater, was used to drive fluid transportation, and it can be realized using a simple microfabrication process with a silicon-on-isolator wafer. Using commercial COMSOL software, the flow profiles of microfluidics in various cross-shaped microchannels were simulated qualitatively under different pumping pressures. Microbeads, with a diameter of 20 μm, manipulated in four cross-shaped microchannels, were also implemented in this experiment. The results showed that a skewed microchannel design has a higher sorting rate compared with orthogonal, misaligned, and antiskewed microchannels because its flow velocity in the main microchannel is significantly reduced by pumping pressure. Typically, the successful sorting rate for this type of skewed microchannel can reach 30% at a pumping frequency of 100 Hz.