한빛사논문
Fu Nan Jua,1, Cheol-Hwi Kima,1, Kwang-Ho Leea, Chang-Dae Kima, Jaesung Limb,c, Taek Leed, Chun Gwon Parkb,c, Tae-Hyung Kima
aSchool of Integrative Engineering Chung-Ang University, Seoul, 306974, Republic of Korea
bDepartment of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, Gyeonggi, 16419, Republic of Korea
cDepartment of Intelligent Precision Healthcare Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, Gyeonggi, 16419, Republic of Korea
dDepartment of Chemical Engineering, Kwangwoon University, Seoul, 01897, Republic of Korea
1These authors contributed equally to this work.
Corresponding authors: Chun Gwon Park, Tae-Hyung Kim
Abstract
Cancer spheroids, which mimic distinct cell-to-cell and cell-extracellular matrix interactions of solid tumors in vitro, have emerged as a promising tumor model for drug screening. However, owing to the unique characteristics of spheroids composed of three-dimensionally densely-packed cells, the precise characterizations of cell viability and function with conventional colorimetric assays are challenging. Herein, we report gold nanostructure-integrated conductive microwell arrays (GONIMA) that enable both highly efficient uniform cancer spheroid formation and precise electrochemical detection of cell viability. A nanostructured gold on indium tin oxide (ITO) substrate facilitated the initial cell aggregation and further 3D cell growth, while the non-cytophilic polymer microwell arrays restricted the size and shape of the spheroids. As a result, approximately 150 human glioblastoma spheroids were formed on a chip area of 1.13 cm2 with an average diameter of 224 μm and a size variation of only 5% (±11.36 μm). The high uniformity of cancer spheroids contributed to the stability of electrical signals measuring cell viability. Using the fabricated GONIMA, the effects of a representative chemotherapeutic agent, hydroxyurea, on the glioblastoma spheroids were precisely monitored under conditions of varying drug concentrations (0–0.3 mg/mL) and incubation times (24–48 hours). Therefore, we conclude that the newly developed platform is highly useful for rapid and precise in vitro drug screening, as well as for the pharmacokinetic analyses of specific drugs using 3D cellular cancer models.
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