title: A multifunctional pipette for localized drug administration to brain slices.
abstract: We have developed a superfusion method utilizing an open-volume microfluidic device for administration of pharmacologically active substances to selected areas in brain slices with high spatio-temporal resolution. The method consists of a hydrodynamically confined flow of the active chemical compound, which locally stimulates neurons in brain slices, applied in conjunction with electrophysiological recording techniques to analyze the response. The microfluidic device, which is a novel free-standing multifunctional pipette, allows diverse superfusion experiments, such as testing the effects of different concentrations of drugs or drug candidates on neurons in different cell layers with high positional accuracy, affecting only a small number of cells. We demonstrate herein the use of the method with electrophysiological recordings of pyramidal cells in hippocampal and prefrontal cortex brain slices from rats, determine the dependence of electric responses on the distance of the superfusion device from the recording site, document a multifold gain in solution exchange time as compared to whole slice perfusion, and show that the device is able to store and deliver up to four solutions in a series. Localized solution delivery by means of open-volume microfluidic technology also reduces reagent consumption and tissue culture expenses significantly, while allowing more data to be collected from a single tissue slice, thus reducing the number of laboratory animals to be sacrificed for a study.
authors: Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-41296 Göteborg, Sweden.
authors: Aikeremu
authors: A
authors: Ahemaiti
authors: Alar
authors: A
authors: Ainla
authors: Gavin D M
authors: GD
authors: Jeffries
authors: Holger
authors: H
authors: Wigström
authors: Owe
authors: O
authors: Orwar
authors: Aldo
authors: A
authors: Jesorka
authors: Kent
authors: K
authors: Jardemark
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D004594:Electrophysiology / Q000295:instrumentation* / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Brain slices; Electrophysiological techniques; Glutamate; Hippocampus; Microfluidic technology; Perfusion; Prefrontal cortex
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