[Biomicrofluidics] On chip two-photon metabolic imaging for drug toxicity testing
We have developed a microfluidic system suitable to be incorporated with a metabolic imaging method to monitor the drug response of cells cultured on a chip. The cells were perfusion-cultured to mimic the blood flow in vivo. Label-free optical measurements and imaging of nicotinamide adenine dinucleotide and flavin adenine dinucleotide fluorescence intensity and morphological changes were evaluated non-invasively. Drug responses calculated using redox ratio imaging were compared with the drug toxicity testing results obtained with a traditional well-plate system. We found that our method can accurately monitor the cell viability and drug response and that the IC50 value obtained from imaging analysis was sensitive and comparable with a commonly used cell viability assay: MTS (3–(4,5-dimethylthiazol-2-yl)–5–(3-carboxymethoxyphenyl)-2–(4-sulfo-phenyl)-2H-tetrazolium) assay. Our method could serve as a fast, non-invasive, and reliable way for drug screening and toxicity testing as well as enabling real-time monitoring of in vitro cultured cells.
Fang Yu1,2,3, Shuangmu Zhuo1,4,a), Yinghua Qu1,5, Deepak Choudhury3, Zhiping Wang3, Ciprian Iliescu1,6,7,8,a), and Hanry Yu1,2,9,10,11lessHide Affiliations 1Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #09-01, 31 Biopolis Way, Singapore, Singapore, 138669 2NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), #28 Medical Drive, Singapore, Singapore, 117456 3Singapore Institute of Manufacturing Technology, A*STAR, 71 Nanyang Dr, Singapore, Singapore, 638075 4Fujian Normal University, Fuzhou 350007, China 5Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Engineering Block 4, #04-08, Singapore 117583 6National Institute for Research and Development in Microtechnologies, (IMT-Bucharest), 126A Erou Iancu Nicolae Str, Bucharest 077190, Romania 7Academy of Romanian Scientists, Splaiul Independentei nr. 54, sector 5, Bucharest 050094, Romania 8BIGHEART, National University of Singapore, ND6, 14 Medical Drive, #14-01, Singapore 117599 9MechanoBiology Institute, National University of Singapore, T-Lab, 5A Engineering Drive 1, Singapore, Singapore, 117411 10Department of Physiology, National University of Singapore, MD9 #03-03, 2 Medical Drive, Singapore, Singapore, 117597 11Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, #10-01 CREATE Tower, Singapore, Singapore, 138602 a)Authors to whom correspondence should be addressed: firstname.lastname@example.org; email@example.com; and firstname.lastname@example.org