Existing laboratory protocols for investigating the effects of factors affecting enzyme activity often require extensive hands-on manipulations and time. This can result in students either not getting the desired results or being distracted from thinking about the scientific ideas underlying the experimental designs and procedures of these protocols. In this paper, we present a lesson plan that includes a simple microscale laboratory protocol that allows students to study the action of amylase on starch and to investigate the effects of various factors (i.e., temperature, pH, substrate concentration, enzyme concentration, and competitive reversible inhibitors) on enzyme activity using immobilized amylase beads. We also show how to engage students in thinking about procedural knowledge, such as repeating measurements, measurement range, and interval. These concepts are critical to designing valid and reliable scientific investigations.