“…Many studies aimed at developing new PKU monitoring strategies, relying on several different approaches, have been published. These include enzyme-based (Gubica et al 2015;Mangombo et al 2013;Naghib, Rabiee, Omidinia, and Khoshkenar 2012;Naghib, Rabiee, Omidinia, Khoshkenara, et al 2012;Omidinia 2014a, 2014b;Omidinia, Khanehzar, et al 2013;Omidinia, Shadjou, and Hasanzadeh 2014b;Villalonga et al 2007Villalonga et al , 2008Weiss et al 2007;Zhuo Wang et al 2005), aptamer-based (Idili et al 2021), (Omidinia, Shadjou, and Hasanzadeh 2014a) and nanomaterials (Hasanzadeh et al 2009(Hasanzadeh et al , 2012Hasanzadeh, Shadjou, and Omidinia 2013;Omidinia, Shadjou, and Hasanzadeh 2013;Wu et al 2017) based electrochemical sensors, as well as immune sensors, (Kubota, Mizukoshi, and Miyano 2013) quartz crystal microbalance (QCM), (Cho et al 2017;Emir Diltemiz et al 2017;Mirmohseni, Shojaei, and Farbodi 2008) extended field gate field effect transistor (Iskierko et al 2017) and photometricbased strategies. Some of the principle challenges facing the development of an effective biosensor for PKU monitoring include (1) having a linear range which covers the 120 mol/L and 360 mol/L key threshold values for L-Phe described previously, (2) being able to detect L-Phe in patient-derived samples with low chemical interference (e.g.…”