dPEG4 biotin acid consists of biotin and a propionic acid-functionalized tetraethylene glycol derivative. Numerous functional or reactive groups can modify the terminal acid moiety, including the acylating agents N-hydroxysuccinimide (NHS) and 2,3,5,6-tetrafluorophenol (TFP). Also, dPEG4 biotin acid reacts directly with primary amines using a suitable carbodiimide such as 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The amphiphilic dPEG linker gives biotin excellent solubility in water and aqueous buffer, where biotin usually is poorly soluble. dPEG4 biotin acid offers significantly superior solubility and performance characteristics compared to the traditional, highly hydrophobic biotinylation reagent known as LC-biotin. Moreover, although dPEG4 biotin acid and LC-biotin have comparable linker lengths, dPEG4 biotin acid will not trigger the aggregation and precipitation of conjugated biomolecules, even at high levels of biotin incorporation on the biomolecule. In contrast, LC-biotin triggers the aggregation and precipitation of biomolecules with the incorporation of a few LC-biotin groups onto the biomolecule.