title: Enzyme-based NAND gate for rapid electrochemical screening of traumatic brain injury in serum.
abstract: We report on the development of a rapid enzyme logic gate-based electrochemical assay for the assessment of traumatic brain injury (TBI). The concept harnesses a biocatalytic cascade that emulates the functionality of a Boolean NAND gate in order to process relevant physiological parameters in the biochemical domain. The enzymatic backbone ensures that a high-fidelity diagnosis of traumatic brain injury can be tendered in a rapid fashion when the concentrations of key serum-based biomarkers reach pathological levels. The excitatory neurotransmitter glutamate and the enzyme lactate dehydrogenase were used here as clinically-relevant input TBI biomarkers, in connection to the low-potential detection of the NADH product in the presence of methylene green at a glassy carbon electrode. A systematic optimization of the gate and the entire protocol has resulted in the effective discrimination between the physiological and pathological logic levels. Owing to its robust design, the enzyme-based logic gate mitigates potential interferences from both physiological and electroactive sources and is able to perform direct measurements in human serum samples. Granted further detailed clinical validation, this proof-of-concept study demonstrates the potential of the electrochemical assay to aid in the rapid and decentralized diagnosis of TBI.
authors.affiliation: Department of NanoEngineering, University of California at San Diego, La Jolla, 92093-0448, USA.
authors.forename: Nandi
authors.initials: N
authors.lastname: Zhou
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Windmiller
authors.forename: Gabriela
authors.initials: G
authors.lastname: Valdés-Ramírez
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Jan
authors.initials: J
authors.lastname: Halámek
authors.forename: Evgeny
authors.initials: E
authors.lastname: Katz
authors.forename: Joseph
authors.initials: J
authors.lastname: Wang
mesh_terms: D055162:Biocatalysis; D015415:Biomarkers / Q000097:blood*; D001930:Brain Injuries / Q000097:blood / Q000175:diagnosis*; D002021:Buffers; D004563:Electrochemistry / Q000379:methods*; D004566:Electrodes; D018698:Glutamic Acid / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008751:Methylene Blue / Q000031:analogs & derivatives / Q000737:chemistry; D009243:NAD / Q000097:blood; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002021:Buffers; D009243:NAD; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; C028673:methylene green; D008751:Methylene Blue