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As class sizes expand in many U.S. schools, science teachers are exploring ways to adapt instruction. Intensifying this challenge for science teachers is that as class sizes grow, so does the demand to integrate novel content and technology into curriculum. This is especially true for nanoscale education which stands on the vanguard of STEM education. This descriptive case study examined a group of 23 secondary level science and engineering teachers’ perceptions over a two-year period as they worked with the support of Project Nanoscience and Nanotechnology Outreach to develop nanoscale units of instruction. The focus of this paper is on pedagogical and technical strategies teachers in the program developed for working with classes of 38 or more students per course.