title: A simple method for producing multiple copies of controlled release small molecule microarrays for cell-based screening.
abstract: Traditional drug discovery involves the screening of lead compounds from a chemical library by using cell-based high throughput screening (HTS) procedures. This has created a demand for the development of cell-based microarray chips for HTS of compounds. Although several cell-based microarray devices and procedures for screening of chemical libraries have been reported, each has limitations in terms of simplicity, speed, and cost. Here, we sought to make a simple method for producing multiple copies of microarray chips for the controlled release of small molecules during cell-based screening. Arrays of polytetrafluoroethylene microchannels were set in poly(dimethylsiloxane) and were formed in a metal mold. Subsequently, a biodegradable polymer, PLGAs, with chemical compounds was injected into each channel, and the array was sliced perpendicular to the channels to create multiple copies of the microarray chip. After seeding the cells on the microarray chip, we were able to successfully control the diffusion of small molecules and locally introduce the compounds into cells. The described method enables the production of multiple copies of the chip by using an easy, rapid, and inexpensive array fabrication without any specialized devices. Moreover, screening using the microarray chip minimizes the consumption of cells and chemicals. Both the biodegradable material and compound injected into each channel can be individually tuned for optimized performance. Therefore, we expect that this method will be useful for developing cell-based HTS assays for small chemical compounds to find drug candidates.
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujita
authors.forename: Reiko
authors.initials: R
authors.lastname: Onuki-Nagasaki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ikuta
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hara
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D003692:Delayed-Action Preparations; D006367:HeLa Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011138:Polytetrafluoroethylene / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000295:instrumentation* / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D054852:Small Molecule Libraries; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011138:Polytetrafluoroethylene