title: Microfabrication and in Vivo Performance of a Microdialysis Probe with Embedded Membrane.
abstract: Microdialysis sampling is an essential tool for in vivo neurochemical monitoring. Conventional dialysis probes are over 220 μm in diameter and have limited flexibility in design because they are made by assembly using preformed membranes. The probe size constrains spatial resolution and governs the amount of tissue damaged caused by probe insertion. To overcome these limitations, we have developed a method to microfabricate probes in Si that are 45 μm thick × 180 μm wide. The probes contain a buried, U-shaped channel that is 30 μm deep × 60 μm wide and terminates in ports for external connection. A 4 mm length of the probe is covered with a 5 μm thick nanoporous membrane. The membrane was microfabricated by deep reactive ion etching through a porous aluminum oxide layer. The microfabricated probe has cross-sectional area that is 79% less than that of the smallest conventional microdialysis probes. The probes yield 2-20% relative recovery at 100 nL/min perfusion rate for a variety of small molecules. The probe was successfully tested in vivo by sampling from the striatum of live rats. Fractions were collected at 20 min intervals (2 μL) before and after an intraperitoneal injection of 5 mg/kg amphetamine. Analysis of fractions by liquid chromatography-mass spectrometry revealed reliable detection of 14 neurochemicals, including dopamine and acetylcholine, at basal conditions. Amphetamine evoked a 43-fold rise in dopamine, a result nearly identical to a conventional dialysis probe in the same animal. The microfabricated probes have potential for sampling with higher spatial resolution and less tissue disruption than conventional probes. It may also be possible to add functionality to the probes by integrating other components, such as electrodes, optics, and additional channels.
authors.affiliation: Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Woong Hee
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Thitaphat
authors.initials: T
authors.lastname: Ngernsutivorakul
authors.affiliation: Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Mabrouk
authors.affiliation: Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Jenny-Marie T
authors.initials: JM
authors.lastname: Wong
authors.affiliation: Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Colleen E
authors.initials: CE
authors.lastname: Dugan
authors.affiliation: Department of Neurology, University of Michigan , 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-5316, United States.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Pappas
authors.affiliation: Department of Chemical Engineering, University of Michigan , 2300 Hayward Street, Ann Arbor, Michigan 48109-2136, United States.
authors.forename: Hyeun Joong
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Kennedy
mesh_terms: D000109:Acetylcholine / Q000032:analysis*; D000661:Amphetamine / Q000737:chemistry; D000818:Animals; D002853:Chromatography, Liquid; D004298:Dopamine / Q000032:analysis*; D004867:Equipment Design; D008297:Male; D013058:Mass Spectrometry; D017551:Microdialysis / Q000295:instrumentation*; D046210:Microfluidic Analytical Techniques; D055616:Microtechnology; D017072:Neostriatum / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000661:Amphetamine; D000109:Acetylcholine; D004298:Dopamine