title: Electrical Property Characterization of Neural Stem Cells in Differentiation.
abstract: Electrical property characterization of stem cells could be utilized as a potential label-free biophysical approach to evaluate the differentiation process. However, there has been a lack of technology or tools that can quantify the intrinsic cellular electrical markers (e.g., specific membrane capacitance (Cspecific membrane) and cytoplasm conductivity (σcytoplasm)) for a large amount of stem cells or differentiated cells. In this paper, a microfluidic platform enabling the high-throughput quantification of Cspecific membrane and σcytoplasm from hundreds of single neural stem cells undergoing differentiation was developed to explore the feasibility to characterize the neural stem cell differentiation process without biochemical staining. Experimental quantification using biochemical markers (e.g., Nestin, Tubulin and GFAP) of neural stem cells confirmed the initiation of the differentiation process featured with gradual loss in cellular stemness and increased cell markers for neurons and glial cells. The recorded electrical properties of neural stem cells undergoing differentiation showed distinctive and unique patterns: 1) in the suspension culture before inducing differentiation, a large distribution and difference in σcytoplasm among individual neural stem cells was noticed, which indicated heterogeneity that may result from the nature of suspension culture of neurospheres; and 2) during the differentiation in adhering monolayer culture, significant changes and a large difference in Cspecific membrane were located indicating different expressions of membrane proteins during the differentiation process, and a small distribution difference in σcytoplasm was less significant that indicated the relatively consistent properties of cytoplasm during the culture. In summary, significant differences in Cspecific membrane and σcytoplasm were observed during the neural stem cell differentiation process, which may potentially be used as label-free biophysical markers to monitor this process.
authors.affiliation: State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Tianjin Weikai Bioeng Ltd., Tianjin, P.R. China.|Tianjin University of Science & Technology, Tianjin, P.R. China.
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Weikai Bioeng Ltd., Tianjin, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Deyong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, Oxford University, Oxford, United Kingdom.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Beiyuan
authors.initials: B
authors.lastname: Fan
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, Oxford University, Oxford, United Kingdom.
authors.forename: Julian
authors.initials: J
authors.lastname: George
authors.affiliation: State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Xue
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, Oxford University, Oxford, United Kingdom.
authors.forename: Zhanfeng
authors.initials: Z
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Jian
authors.identifier: http://orcid.org/0000-0003-4612-3279
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002462:Cell Membrane / Q000502:physiology; D003593:Cytoplasm; D025802:Electric Capacitance; D017097:Electric Impedance; D055724:Electrophysiological Phenomena; D020869:Gene Expression Profiling; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology*; D051381:Rats