title: Enzyme logic gates for the digital analysis of physiological level upon injury.
abstract: A biocomputing system composed of a combination of AND/IDENTITY logic gates based on the concerted operation of three enzymes: lactate oxidase, horseradish peroxidase and glucose dehydrogenase was designed to process biochemical information related to pathophysiological conditions originating from various injuries. Three biochemical markers: lactate, norepinephrine and glucose were applied as input signals to activate the enzyme logic system. Physiologically normal concentrations of the markers were selected as logic 0 values of the input signals, while their abnormally increased concentrations, indicative of various injury conditions were defined as logic 1 input. Biochemical processing of different patterns of the biomarkers resulted in the formation of norepiquinone and NADH defined as the output signals. Optical and electrochemical means were used to follow the formation of the output signals for eight different combinations of three input signals. The enzymatically processed biochemical information presented in the form of a logic truth table allowed distinguishing the difference between normal physiological conditions, pathophysiological conditions corresponding to traumatic brain injury and hemorrhagic shock, and abnormal situations (not corresponding to injury). The developed system represents a biocomputing logic system applied for the analysis of biomedical conditions related to various injuries. We anticipate that such biochemical logic gates will facilitate decision-making in connection to an integrated therapeutic feedback-loop system and hence will revolutionize the monitoring and treatment of injured civilians and soldiers.
authors.affiliation: Department of NanoEngineering, University of California - San Diego, La Jolla, CA 92093, USA.
authors.forename: Kalayil Manian
authors.initials: KM
authors.lastname: Manesh
authors.forename: Jan
authors.initials: J
authors.lastname: Halámek
authors.forename: Marcos
authors.initials: M
authors.lastname: Pita
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Tsz Kin
authors.initials: TK
authors.lastname: Tam
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Santhosh
authors.forename: Min-Chieh
authors.initials: MC
authors.lastname: Chuang
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Windmiller
authors.forename: Dewi
authors.initials: D
authors.lastname: Abidin
authors.forename: Evgeny
authors.initials: E
authors.lastname: Katz
authors.forename: Joseph
authors.initials: J
authors.lastname: Wang
mesh_terms: D015415:Biomarkers / Q000032:analysis; D015374:Biosensing Techniques / Q000295:instrumentation*; D001930:Brain Injuries / Q000175:diagnosis* / Q000378:metabolism; D039301:Computers, Molecular; D003936:Diagnosis, Computer-Assisted / Q000295:instrumentation; D004563:Electrochemistry / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005947:Glucose / Q000032:analysis*; D006801:Humans; D019344:Lactic Acid / Q000032:analysis*; D009638:Norepinephrine / Q000032:analysis*; D055096:Optical Devices; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation
chemical_list: D015415:Biomarkers; D019344:Lactic Acid; D005947:Glucose; D009638:Norepinephrine