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• Different strategies are analyzed to enhanced microchannels based heat sinks. • Nanofluids to enhance heat performance of microchannel based heat sinks is analyzed. • Experiments are performed for Al 2 O 3 , Au and Ag nanoparticles at various concentrations. • The flow-boiling regimes are identified and discussed for the working conditions considered. • Two-phase flow conditions may not always be beneficial, low concentrations of nanoparticles (ϕ ≪ 1%) can have a notable impact on heat transfer mechanisms. This paper investigates the advantages and challenges associated with two-phase flows, specifically flow boiling of pure liquids and nanofluids, for cooling applications in microchannel heat sinks. The study explores various two-phase flow patterns, their related issues, and examines the potential of nanoparticles to enhance heat transfer. Alumina (Al 2 O 3), gold (Au), and silver (Ag) nanoparticles at different concentrations were tested. Experimental tests were conducted under different working conditions using various working fluids, including water, Al 2 O 3 1 wt%, Ag 1 wt%, Au 1 wt%, Au 0.75 wt%, Au 0.5 wt%. The heat fluxes used were 1.026 kW/m2, 1.696 W/m2 and 2.403 kW/m2, while the volumetric flows ranged between 0.5 mL/min and 1.5 mL/min. The observed results indicate that even for the lowest particle concentration tested, the water-Au nanofluid exhibits superior cooling performance compared to the other examined fluids. The findings suggest that although two-phase flow conditions may not yield significant benefits, even small concentrations of nanoparticles (ϕ ≪ 1%) can significantly impact heat transfer mechanisms. This approach provides a cost-effective and efficient alternative for cooling microchannel heat sinks without necessitating the use of two-phase flow conditions. [ABSTRACT FROM AUTHOR]