title: Polymer-based, flexible glutamate and lactate microsensors for in vivo applications.
abstract: We present a flexible microsensor, based on a polymer substrate, for multiparametric, electrochemical in vivo monitoring. The sensor strip with a microelectrode array at the tip was designed for insertion into tissue, for fast and localized online monitoring of physiological parameters. The microsystem fabrication on a wafer-level is based on a polyimide substrate and includes the patterning of platinum microelectrodes as well as epoxy and dry-film-resist insulation in a cost-effective thin-film and laminate process. A stable, electrodeposited silver/silver chloride reference electrode on-chip and a perm-selective membrane as an efficient interference rejection scheme are integrated on a wafer-level. Amperometric, electrochemical, enzyme-based biosensors for the neurotransmitter L-glutamate and the energy metabolite L-lactate have been developed. Hydrogel membranes or direct cross-linking as stable concepts for the enzyme immobilization are shown. Sensor performance including high selectivity, tailoring of sensitivity and long-term stability is discussed. For glutamate, a high sensitivity of 2.16 nAmm(-2) µM(-1) was found. For lactate, a variation in sensitivity between 2.6 and 32 nAmm(-2)mM(-1) was achieved by different membrane compositions. The in vivo application in an animal model is demonstrated by glutamate measurements in the brain of rats. Local glutamate alterations in the micromolar range and in nanoliter-range volumes can be detected and quantified with high reproducibility and temporal resolution. A novel, versatile platform for the integration of various electrochemical sensors on a small, flexible sensor strip for a variety of in vivo applications is presented.
authors.affiliation: Laboratory for Sensors, Department of Microsystems Engineering - IMTEK, University of Freiburg, Germany. Electronic address: weltin@imtek.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weltin
authors.affiliation: Laboratory for Sensors, Department of Microsystems Engineering - IMTEK, University of Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kieninger
authors.affiliation: Laboratory for Sensors, Department of Microsystems Engineering - IMTEK, University of Freiburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Enderle
authors.affiliation: Department of Neurology, University of Freiburg, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Gellner
authors.affiliation: Department of Neurology, University of Freiburg, Germany.
authors.forename: Brita
authors.initials: B
authors.lastname: Fritsch
authors.affiliation: Laboratory for Sensors, Department of Microsystems Engineering - IMTEK, University of Freiburg, Germany.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Urban
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation*; D001923:Brain Chemistry; D055664:Electrochemical Techniques / Q000295:instrumentation*; D004800:Enzymes, Immobilized / Q000737:chemistry; D018698:Glutamic Acid / Q000032:analysis*; D019344:Lactic Acid / Q000032:analysis*; D008297:Male; D008839:Microelectrodes; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D004800:Enzymes, Immobilized; D011108:Polymers; D019344:Lactic Acid; D018698:Glutamic Acid
keywords: Biosensor; Brain; Glutamate; Lactate; Microsensor; in vivo