title: Drug-eluting microarrays for cell-based screening of chemical-induced apoptosis.
abstract: Traditional high-throughput screening (HTS) is carried out in centralized facilities that require extensive robotic liquid and plate handling equipment. This model of HTS is restrictive as such facilities are not accessible to many researchers. We have designed a simple microarray platform for cell-based screening that can be carried out at the benchtop. The device creates a microarray of 2100 individual cell-based assays in a standard microscope slide format. A microarray of chemical-laden hydrogels addresses a matching array of cell-laden microwells thus creating a microarray of sealed microscale cell cultures each with unique conditions. We demonstrate the utility of the device by screening the extent of apoptosis and necrosis in MCF-7 breast cancer cells in response to exposure to a small library of chemical compounds. From a set of screens we produced a rank order of chemicals that preferentially induce apoptosis over necrosis in MCF-7 cells. Treatment with doxorubicin induced high levels of apoptosis in comparison with staurosporine, ethanol, and hydrogen peroxide, whereas treatment with 100 μM ethanol induced minimal apoptosis with high levels of necrosis. We anticipate broad application of the device for various research and discovery applications as it is easy to use, scalable, and can be fabricated and operated with minimal peripheral equipment.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Cheong Hoon
authors.initials: CH
authors.lastname: Kwon
authors.forename: Ian
authors.initials: I
authors.lastname: Wheeldon
authors.forename: Nezamoddin N
authors.initials: NN
authors.lastname: Kachouie
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Hojae
authors.initials: H
authors.lastname: Bae
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sant
authors.forename: Junji
authors.initials: J
authors.lastname: Fukuda
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Kang
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000633:toxicity; D046228:Microarray Analysis / Q000379:methods*; D054852:Small Molecule Libraries / Q000633:toxicity*; D019311:Staurosporine / Q000633:toxicity
chemical_list: D020100:Hydrogels; D054852:Small Molecule Libraries; D000431:Ethanol; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D019311:Staurosporine