Stochastic optical reconstruction microscopy (STORM) achieves super-resolution imaging by blinking individual dye molecules in thiol-containing media. While STORM is well-established for imaging thin biological specimens, its application to thick tissues has been limited by light scattering. Mounting media with an oil refractive index have shown promise in improving imaging depth and resolution in optical microscopy, but such buffers have not been explored for STORM. Here, we present a 3-pyridinemethanol-based STORM buffer with a refractive index matching standard immersion oil. Our buffer demonstrates comparable performance to conventional STORM buffers and exceptional stability for 5 weeks, enabling imaging of numerous cells on a single slide and larger field-of-view imaging. With perfect index matching, our buffer simplifies imaging and holds potential for lightsheet STORM applications in thick tissues.
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