Microphysiological models, despite their potential, face significant barriers to adoption in standard biological laboratories due to factors such as limited adaptability, high cost, increased biological parameter optimization space, and reduced throughput. This study introduces an innovative, user-friendly method for fabricating microfluidic devices. By leveraging computer numerical control (CNC) micromilling, microscale features are created directly into standard well plates. This simplifies the manufacturing process, requiring only a CNC mill, hot plate, and fume hood. We illustrate how the method integrates microfluidic operation with traditional well plate functionality and provide use-cases for biological laboratories to adopt microfluidic technologies into their assays [1,2]. To further test the robustness of this approach, we machined test features with four different mills at varying price points and quantified each mill’s capability. The test features included a traditional Y channel microfluidic device and a complex pattern of microfluidic features including pillars and channels of varying sizes, phase barriers, curves, outer corners, inner corners, and ports. For the traditional “Y” device, no significance was found between the mills for the width of the phase barrier (P = 0.7855). Significant differences were found for the width of the 800 µm channels and the 1000 µm ports (P = 0.0242, and 0.0093 respectively). In the 800 µm channels, a significant difference was found between mill 1 and mill 2 (P = 0.0266). In the 1000 µm port a difference was found between the mill 1 and mill 3 (P = 0.0086). Our data illustrate the versatility of this approach, enabling potential adopters to assess mill options and determine the required accuracy and precision capabilities for their needs. The devices are compatible with high throughput experimentation, promising to facilitate the broader adoption and use of microphysiological models. Funding: Supported by P42-ES004911 and R00-ES028744 to BPJ. Conflict of Interest: BJ holds equity in Onexio Biosystems, L.L.C. References: [1]Johnson, B. P., Vitek, R. A., Morgan, M. M. et al. (2021). A microphysiological approach to evaluate effectors of intercellular hedgehog signaling in development. Front Cell Dev Biol 9, 621442. doi:10.3389/fcell.2021.621442 [2] Reynolds, J. I., Vitek, R. A., Geiger, P. G. et al. (2022). Engineering epithelial-mesenchymal microtissues to study cell-cell interactions in development. In S. Dworkin (ed.), Craniofacial Development: Methods and Protocols (201-213).