The aim of this study is to analyze the techno-economic performance of process configurations for ethanol production involving solid-liquid separators and reactors in the saccharification and fermentation stage, a family of process configurations where few alternatives have been proposed. Since including these process alternatives creates a large number of possible process configurations, a framework for process synthesis and optimization is proposed. This approach is supported on kinetic models fed with experimental data and a plant-wide techno-economic model. Among 150 process configurations, 40 show an improved MESP compared to a well-documented base case (BC), almost all include solid separators and some show energy retrieved in products 32% higher compared to the BC. Moreover, 16 of them also show a lower capital investment per unit of ethanol produced per year. Several of the process configurations found in this work have not been reported in the literature.