This paper presents an X-ray compatible microfluidic platform for in situ characterization of chemical reactions at synchrotron light sources. We demonstrate easy to implement techniques to probe reacting solutions as they first come into contact, and study the very first milliseconds of their reaction in real-time through X-ray absorption spectroscopy (XAS). The devices use polydimethylsiloxane (PDMS) microfluidic channels sandwiched between ultrathin, X-ray transparent silicon nitride observation windows and rigid substrates. The new approach has three key advantages: i) owing to the assembly techniques employed, the devices are suitable for both high energy and tender (1–5 keV) X-rays; ii) they can operate in a vacuum environment (a must for low energy X-rays) and iii) they are robust enough to survive a full 8 hour shift of continuous scanning with a micro-focused beam, providing higher spatial and thus greater time resolution than previous studies. The combination of these opens new opportunities for in situ studies. This has so far not been possible with Kapton or glass-based flow cells due to increased attenuation of the low energy beam passing through these materials. The devices provide a well-defined mixing region to collect spatial maps of spatially stable concentration profiles, and XAS point spectra to elucidate the chemical structure and characterize the chemical reactions. The versatility of the approach is demonstrated through in situ XAS measurements on the mixing of two reactants in a microfluidic laminar flow device, as well as a segmented droplet based system for time resolved analysis.