Due to their label-free and noninvasive nature,impedance measurements have attracted increasing interest in biological research.Advances in microfabrication and integrated-circuit technology have opened a route to usi...Due to their label-free and noninvasive nature,impedance measurements have attracted increasing interest in biological research.Advances in microfabrication and integrated-circuit technology have opened a route to using large-scale microelectrode arrays for real-time,high-spatiotemporal-resolution impedance measurements of biological samples.In this review,we discuss different methods and applications of measuring impedance for cell and tissue analysis with a focus on impedance imaging with microelectrode arrays in in vitro applications.We first introduce how electrode configurations and the frequency range of the impedance analysis determine the information that can be extracted.We then delve into relevant circuit topologies that can be used to implement impedance measurements and their characteristic features,such as resolution and data-acquisition time.Afterwards,we detail design considerations for the implementation of new impedance-imaging devices.We conclude by discussing future fields of application of impedance imaging in biomedical research,in particular applications where optical imaging is not possible,such as monitoring of ex vivo tissue slices or microelectrode-based brain implants.展开更多
In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity,especially when recapitulating conditions involving recirculating cells.Current testing strategies are often ba...In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity,especially when recapitulating conditions involving recirculating cells.Current testing strategies are often based on static co-culturing of cells in suspension and 3D tissue models,where cell sedimentation on the target tissue can occur.The observed effects may then mostly be a consequence of sedimentation and of the corresponding forced cell-tissue interactions.The realization of continuous medium flow helps to better recapitulate physiological conditions and cell-tissue interactions.To tackle current limitations of perfused organ-on-chip approaches,we developed a microfluidic chip and operation concept,which prevents undesired sedimentation and accumulation of suspended cells during multiple days by relying on gravity-driven perfusion.Our platform,which we termed“human immune flow(hiFlow)chip”,enables to co-culture cells in suspension with up to 7 preformed microtissue models.Here,we present the design principle and operation of the platform,and we validate its performance by culturing cells and microtissues of a variety of different origins.Cells and tissues could be monitored on chip via high-resolution microscopy,while cell suspensions and microtissues could be easily retrieved for off-chip analysis.Our results demonstrate that primary immune cells and a range of different spheroid models of healthy and diseased tissues can be maintained for over 6 days on chip.As proof-of-concept cell-tissue interaction assay,we used an antibody treatment against diffuse midline glioma,a highly aggressive pediatric tumor.We are confident that our platform will help to increase the prediction power of in vitro preclinical testing of novel therapeutics that rely on the interaction of circulating cells with organ tissues.展开更多
基金supported by the European Research Council Advanced Grant 694829“neuroXscales”by the Swiss National Science Foundation under Contracts 205320_188910 and CR32I2_166329 and a Marie Heim-Vögtlin grant to R.B.by an ETH Postdoctoral Fellowship to F.C.
文摘Due to their label-free and noninvasive nature,impedance measurements have attracted increasing interest in biological research.Advances in microfabrication and integrated-circuit technology have opened a route to using large-scale microelectrode arrays for real-time,high-spatiotemporal-resolution impedance measurements of biological samples.In this review,we discuss different methods and applications of measuring impedance for cell and tissue analysis with a focus on impedance imaging with microelectrode arrays in in vitro applications.We first introduce how electrode configurations and the frequency range of the impedance analysis determine the information that can be extracted.We then delve into relevant circuit topologies that can be used to implement impedance measurements and their characteristic features,such as resolution and data-acquisition time.Afterwards,we detail design considerations for the implementation of new impedance-imaging devices.We conclude by discussing future fields of application of impedance imaging in biomedical research,in particular applications where optical imaging is not possible,such as monitoring of ex vivo tissue slices or microelectrode-based brain implants.
基金the support for flow cytometry and microscopy by the single cell facility(SCF)at the Department of Biosystems Science and Engineering at ETH Zurichfinancially supported by the Innosuisse grant 38880.1 IP-LS.by the“Personalized Health and Related Technologies(PHRT)”of the ETH Domain(Project#2021-351).
文摘In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity,especially when recapitulating conditions involving recirculating cells.Current testing strategies are often based on static co-culturing of cells in suspension and 3D tissue models,where cell sedimentation on the target tissue can occur.The observed effects may then mostly be a consequence of sedimentation and of the corresponding forced cell-tissue interactions.The realization of continuous medium flow helps to better recapitulate physiological conditions and cell-tissue interactions.To tackle current limitations of perfused organ-on-chip approaches,we developed a microfluidic chip and operation concept,which prevents undesired sedimentation and accumulation of suspended cells during multiple days by relying on gravity-driven perfusion.Our platform,which we termed“human immune flow(hiFlow)chip”,enables to co-culture cells in suspension with up to 7 preformed microtissue models.Here,we present the design principle and operation of the platform,and we validate its performance by culturing cells and microtissues of a variety of different origins.Cells and tissues could be monitored on chip via high-resolution microscopy,while cell suspensions and microtissues could be easily retrieved for off-chip analysis.Our results demonstrate that primary immune cells and a range of different spheroid models of healthy and diseased tissues can be maintained for over 6 days on chip.As proof-of-concept cell-tissue interaction assay,we used an antibody treatment against diffuse midline glioma,a highly aggressive pediatric tumor.We are confident that our platform will help to increase the prediction power of in vitro preclinical testing of novel therapeutics that rely on the interaction of circulating cells with organ tissues.
