This article discusses the design and performance of continuous-flow microfluidic thermal sensors that operate on the principle of heat generation through lateral mixing. The platform under study is a Y-channel microfluidic device in which two laminar streams are brought into side-by-side contact under precise flow control. For this work, the two merging microchannels carry water and ethanol respectively; heat is generated as the liquids diffuse together. While much exists in the literature regarding the magnitude of this heat of mixing, this article examines the spatial distribution of this heat – in particular, the extent of lateral asymmetry in the resultant temperature map. This asymmetry is detected with milli-Kelvin sensitivity using a thin-film thermopile integrated on the exterior surface of the microdevice. Since this experimental configuration is implemented by numerous research groups in the design of biosensors and microfluidic calorimeters, a particular emphasis of this present study is on maximizing the detection sensitivity. The impact of the experimental parameters of volumetric flow rate and flow ratio on detection sensitivity was examined, and the optimum axial location for the thermopile sensor under a range of conditions was determined. Experimental and numerical methods were used in this study.