Microphysiological systems(MPS)are advanced in vitro platforms engineered to replicate in vivo conditions forstudying human biology,disease mechanisms,and drug responses with greater physiological relevance.Fluorescen...Microphysiological systems(MPS)are advanced in vitro platforms engineered to replicate in vivo conditions forstudying human biology,disease mechanisms,and drug responses with greater physiological relevance.Fluorescencesensing is widely used as a functional readout in MPS due to its high sensitivity,selectivity,and stability.However,conventional fluorescence sensing systems often rely on bulky instrumentation with limited integration,whichrestricts continuous in situ monitoring,scalable high-throughput analysis,and spatially resolved investigation in multiorgan-on-a-chip models.To address these limitations,we present a highly miniaturized,fully integrated optical systemwith a 1 mm2 footprint,enabling continuous in situ fluorescence monitoring of three-dimensional microtissues inclose proximity.The system integrates microscale illumination and sensing units for fluorescence excitation andselective detection,an optical element for guided light propagation,and a microcage for mechanical confinement ofmicrotissues.To demonstrate its capabilities,we integrated the miniaturized optical system with an MPS-relevantplatform to monitor fluorescence signals in transgenic mouse pancreatic islets expressing genetically encoded calciumindicators.The integrated platform enables real-time,continuous monitoring of islet responses to potassium chloridestimulation and tracking of calcium oscillations for over two hours,providing valuable information about thefunctional status of the pancreatic islets.Our work enhances the analytical capabilities of MPS through the integrationof miniaturized on-chip quantitative assessment tools,enabling precise,in situ,and continuous monitoring ofbiological activities in close proximity.展开更多
基金supported by the Swedish Foundation for Strategic Research(SSF Grant project no.RMX18-0066)The Family Erling-Persson Foundation,The Jonas&Christina af Jochnick Foundation,ERC-2018-AdG 834860-EYELETSThe Swedish Research Council.H.K.acknowledges funding from the Wenner-Gren foundation(UPD2021-0185)。
文摘Microphysiological systems(MPS)are advanced in vitro platforms engineered to replicate in vivo conditions forstudying human biology,disease mechanisms,and drug responses with greater physiological relevance.Fluorescencesensing is widely used as a functional readout in MPS due to its high sensitivity,selectivity,and stability.However,conventional fluorescence sensing systems often rely on bulky instrumentation with limited integration,whichrestricts continuous in situ monitoring,scalable high-throughput analysis,and spatially resolved investigation in multiorgan-on-a-chip models.To address these limitations,we present a highly miniaturized,fully integrated optical systemwith a 1 mm2 footprint,enabling continuous in situ fluorescence monitoring of three-dimensional microtissues inclose proximity.The system integrates microscale illumination and sensing units for fluorescence excitation andselective detection,an optical element for guided light propagation,and a microcage for mechanical confinement ofmicrotissues.To demonstrate its capabilities,we integrated the miniaturized optical system with an MPS-relevantplatform to monitor fluorescence signals in transgenic mouse pancreatic islets expressing genetically encoded calciumindicators.The integrated platform enables real-time,continuous monitoring of islet responses to potassium chloridestimulation and tracking of calcium oscillations for over two hours,providing valuable information about thefunctional status of the pancreatic islets.Our work enhances the analytical capabilities of MPS through the integrationof miniaturized on-chip quantitative assessment tools,enabling precise,in situ,and continuous monitoring ofbiological activities in close proximity.
