title: Microfluidic assessment of mechanical cell damage by extensional stress.
abstract: Mammalian cells have been widely used in bioreactors to produce biological products such as pharmaceutical materials. The productivity of such bioreactors is vastly affected by flow-induced cell damage in complicated flow environments, such as agitation-driven turbulence and oxygen bubble bursting at the interface between the culturing medium and air. However, there is no systematic approach to diagnose the cell damage caused by the hydrodynamic stress. In this work, we propose a novel microfluidic method to accurately assess the mechanical cell damage under a controlled extensional stress field, generated in a microfluidic cross-slot geometry. The cell damage in the extensional field is related to the oxygen bubble bursting process. We employed viscoelasticity-induced particle focusing to align the cells along the shear-free channel centerline, so that all the cells experience a similar extensional stress field, which also precludes the cell damage due to wall shear stress. We applied our novel microfluidic sensor to find the critical extensional stress to damage Chinese hamster ovary (CHO) cells; the critical stress is found to be ∼250 Pa. Our current results are relevant in the design of practical bioreactors, as our results clearly demonstrate that the control of the bubble bursting process is critical in minimizing cell damage in bioreactor applications. Further, our results will provide useful information on the biophysical cell properties under fluid flow environments.
authors.affiliation: Department of Energy Systems Research, Ajou University, Suwon 443-749, Republic of Korea. jumin@ajou.ac.kr.
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Bae
authors.affiliation: School of Mechanical Engineering, Research Center for Aircraft Parts Technology, Gyeongsang National University, Jinju 660-701, Republic of Korea. wrhwang@gnu.ac.kr.
authors.forename: Hye Kyeong
authors.initials: HK
authors.lastname: Jang
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-721, Republic of Korea and Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Shin
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Geetika
authors.initials: G
authors.lastname: Phukan
authors.affiliation: School of Mechanical Engineering, Research Center for Aircraft Parts Technology, Gyeongsang National University, Jinju 660-701, Republic of Korea. wrhwang@gnu.ac.kr.
authors.forename: Thanh Tinh
authors.initials: TT
authors.lastname: Tran
authors.affiliation: Department of Physiology and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Gwang
authors.initials: G
authors.lastname: Lee
authors.affiliation: School of Mechanical Engineering, Research Center for Aircraft Parts Technology, Gyeongsang National University, Jinju 660-701, Republic of Korea. wrhwang@gnu.ac.kr.
authors.forename: Wook Ryol
authors.initials: WR
authors.lastname: Hwang
authors.affiliation: Department of Energy Systems Research, Ajou University, Suwon 443-749, Republic of Korea. jumin@ajou.ac.kr and Department of Chemical Engineering, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Ju Min
authors.initials: JM
authors.lastname: Kim
mesh_terms: D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D002477:Cells / Q000473:pathology*; D003412:Cricetulus; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D010316:Particle Size; D013314:Stress, Mechanical; D013499:Surface Properties; D014783:Viscosity