title: Characterization of a microfluidic dispensing system for localised stimulation of cellular networks.
abstract: We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. The device features a flow cell comprising a main channel for nutrient delivery as well as multiple channels for drug delivery. This device is one key component of a larger, fully integrated system now under development, based upon a microelectrode array (MEA) with on-chip CMOS circuitry for recording and stimulation of electrogenic cells (e.g. neurons, cardiomyocytes). As a critical system unit, the microfluidics must be carefully designed and characterized to ensure that candidate drugs are delivered to specific regions of the culture at known concentrations. Furthermore, microfluidic design and functionality is dictated by the size, geometry, and material/electrical characteristics of the CMOS MEA. Therefore, this paper reports on the design considerations and fabrication of the flow cell, including theoretical and experimental analysis of the mass transfer properties of the nutrient and drug flows, which are in good agreement with one another. To demonstrate proof of concept, the flow cell was mounted on a dummy CMOS chip, which had been plated with HL-1 cardiomyocytes. A test chemical compound was delivered to the cell culture in a spatially resolved manner. Envisioned applications of this stand-alone system include simultaneous toxicological testing of multiple compounds and chemical stimulation of natural neural networks for neuroscience investigations.
authors.affiliation: University of Neuchâtel, Institute of Microtechnology, Rue Jaquet-Droz 1, 2000 Neuchâtel, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kraus
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Verpoorte
authors.forename: Vincent
authors.initials: V
authors.lastname: Linder
authors.forename: Wendy
authors.initials: W
authors.lastname: Franks
authors.forename: Andreas
authors.initials: A
authors.lastname: Hierlemann
authors.forename: Flavio
authors.initials: F
authors.lastname: Heer
authors.forename: Sadik
authors.initials: S
authors.lastname: Hafizovic
authors.forename: Teruo
authors.initials: T
authors.lastname: Fujii
authors.forename: Nico F
authors.initials: NF
authors.lastname: de Rooij
authors.forename: Sander
authors.initials: S
authors.lastname: Koster
mesh_terms: D000465:Algorithms; D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002460:Cell Line; D016503:Drug Delivery Systems; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*
chemical_list: D007211:Indoles; C007293:DAPI