title: A multicellular spheroid array to realize spheroid formation, culture, and viability assay on a chip.
abstract: We describe a novel multicellular spheroid culture system that facilitates the easy preparation and culture of a spheroid microarray for the long-term monitoring of cellular activity. A spheroid culture device with an array of pyramid-like microholes was constructed in a silicon chip that was equipped with elastomeric microchannels. A cell suspension was introduced via the microfluidic channel into the microstructure that comprised silicon microholes and elastomeric microwells. A single spheroid can be formed and localized precisely within each microstructure. Since the culture medium could be replaced via the microchannels, a long-term culture (of approximately 2 weeks) is available on the chip. Measurement of albumin production in the hepatoma cell line (HepG2) showed that the liver-specific functions were maintained for 2 weeks. Based on the cellular respiratory activity, the cellular viability of the spheroid array on the chip was evaluated using scanning electrochemical microscopy. Responses to four different chemical stimulations were simultaneously detected on the same chip, thus demonstrating that each channel could be evaluated independently under various stimulation conditions. Our spheroid culture system facilitated the understanding of spheroid formation, culture, and viability assay on a single chip, thus functioning as a useful drug-screening device for cancer and liver cells.
authors.affiliation: Graduate School of Environmental Studies, Tohoku University, Sendai 980-8579, Japan.
authors.forename: Yu-suke
authors.initials: YS
authors.lastname: Torisawa
authors.forename: Airi
authors.initials: A
authors.lastname: Takagi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nashimoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yasukawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsue
mesh_terms: D000418:Albumins / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D001681:Biological Assay; D001943:Breast Neoplasms / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D004563:Electrochemistry / Q000379:methods*; D004867:Equipment Design; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008113:Liver Neoplasms / Q000378:metabolism; D046208:Microchip Analytical Procedures / Q000379:methods*; D012828:Silicones / Q000737:chemistry*; D018874:Spheroids, Cellular
chemical_list: D000418:Albumins; D001672:Biocompatible Materials; D004129:Dimethylpolysiloxanes; D012828:Silicones; C013830:baysilon