Soft lithography fabrication of index‐matched microfluidic devices for reducing artifacts in fluorescence and quantitative phase imaging Diane N. H. Kim1 · Kevin T. Kim2 · Carolyn Kim1 · Michael A. Teitell1,3 · Thomas A. Zangle4

Microfluidic devices are widely used for biomedical applications based on microscopy or other optical detection methods. However, the materials commonly used for microfabrication typically have a high refractive index relative to water, which can create artifacts at device edges and limit applicability to applications requiring high-precision imaging or morphological feature detection. Here we present a soft lithography method to fabricate microfluidic devices out of MY133-V2000, a UV-curable, fluorinated polymer with low refractive index that is close to that of water (n = 1.33). The primary challenge in the use of this material (and fluorinated materials in general) is the low adhesion of the fluorinated material; we present several alternative fabrication methods we have tested to improve inter-layer adhesion. The close match between the refractive index of this material and aqueous solutions commonly used in biomedical applications enables fluorescence imaging at microchannel or other microfabricated edges without distortion. The close match in refractive index also enables quantitative phase microscopy imaging across the full width of microchannels without error-inducing artifacts for measurement of cell biomass. Overall, our results demonstrate the utility of low-refractive index microfluidics for biological applications requiring high-precision optical imaging.