text: Fancy and Kodadek's invention of PICUP in 1999 was the first time proteins cross-linking was able to be performed in such a short period of time (1 second) and without modifying the structure of the proteins in question. Additionally, PICUP was able to be performed at physiological pH of 7.4, which opened doors for further application of protein cross-linking such as studying the biochemical mechanisms that proteins participate in the human body. In addition, irradiation by visible light in PICUP is useful because many biomolecules that participate in metabolic pathways to be analyzed do no absorb light with wavelengths below the range for UV light, allowing for cross-links without denaturation.