Lerner, Mitchell BryantMatsunaga, FelipeHan, Gang HeeHong, Sung JuXi, JinPerez Aguilar, Jose ManuelCrook, AlexanderSaven, Jeffery G.Park, Yung WooLiu, RenyuJohnson, A. T. Charlie2023-05-222023-05-222014-04-172016-06-13https://repository.upenn.edu/handle/20.500.14332/6093We have developed a novel, all-electronic biosensor for opioids that consists of an engineered μ-opioid receptor protein, with high binding affinity for opioids, chemically bonded to a graphene field-effect transistor to read out ligand binding. A variant of the receptor protein that provided chemical recognition was computationally redesigned to enhance its solubility and stability in an aqueous environment. A shadow mask process was developed to fabricate arrays of hundreds of graphene transistors with average mobility of ∼1500 cm2 V–1 s–1 and yield exceeding 98%. The biosensor exhibits high sensitivity and selectivity for the target naltrexone, an opioid receptor antagonist, with a detection limit of 10 pg/mL.This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html).Graphenebiosensorfield effect transistorμ-opioid receptorcomputational protein designBiochemistryOrganic ChemistryPhysical ChemistryArticle