Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents.However,current organ-on-a-chip platforms are limited by a“single pot”design...Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents.However,current organ-on-a-chip platforms are limited by a“single pot”design,which inevitably requires holistic analysis and limits parallel processing.Here,we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres,which significantly increased the parallelism over traditional organ-on-a-chip for drug development.Up to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units,allowing for analysis with high consistency and quick response.Our platform displayed evident anti-cancer efficacy at a concentration of 10μM for sorafenib,and had greater alignment than the“single pot”organ-on-a-chip with a previous in vivo study.In addition,this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50μg/mL.The successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities,thereby accelerating the joint endeavor to combat cancer.展开更多
Hydrogel microwell arrays (HMAs) have been wildly used for engineering cell microenvironment by providing well-controlled biophysical and biochemical cues (e.g., three dimensional (3D) physical boundary, biomolecule c...Hydrogel microwell arrays (HMAs) have been wildly used for engineering cell microenvironment by providing well-controlled biophysical and biochemical cues (e.g., three dimensional (3D) physical boundary, biomolecule coating) for cells. Among these cues, the oxygen microenvironment has shown great effect on the cellular physiological processes. However, it is currently technically challenging to characterize the local oxygen microenvironment within HMAs. Here, we prepared HMAs with different crosslinking concentrations to adjust the structural and physical properties of HMAs. Then we introduced a scanning electrochemical microscopy (SECM)-based electrochemical method to map the surface topography and oxygen microenvironment around HMAs. The SECM results show both the 3D topography and the oxygen permeability of HMAs in aqueous solution. The obtained oxygen permeability of HMAs increases with increasing the crosslinking concentration, and the microwell boundaries show the highest oxygen permeability throughout HMAs. This work demonstrates that SECM offers a high spatial resolution and in-situ method for characterization of the topography and the local oxygen permeability of HMAs, which can provide useful information for better engineering cell microenvironment through optimizing HMAs design.展开更多
基金supports from the General Program (No. 31871016)the National Key Scientific Instrument and Equipment Development Projects (No. 61827806) from the National Natural Science Foundation of China+3 种基金the National Major Science and Technology Projects (No. 2018ZX10732401-003-007)the National Key Research and Development Program (No. 2016YFC1101302) from the Ministry of Science and Technology of Chinathe National Natural Science Foundation of China (No. 81770719)Science and Technology Department of Zhejiang Province (No. 2019C03029)
文摘Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents.However,current organ-on-a-chip platforms are limited by a“single pot”design,which inevitably requires holistic analysis and limits parallel processing.Here,we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres,which significantly increased the parallelism over traditional organ-on-a-chip for drug development.Up to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units,allowing for analysis with high consistency and quick response.Our platform displayed evident anti-cancer efficacy at a concentration of 10μM for sorafenib,and had greater alignment than the“single pot”organ-on-a-chip with a previous in vivo study.In addition,this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50μg/mL.The successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities,thereby accelerating the joint endeavor to combat cancer.
基金the National Natural Science Foundation of China (Grant 21775117)the Technology Foundation for Selected Overseas Chinese Scholar of Shannxi Province (Grant 2017010)the General Financial Grant from the China Postdoctoral Science Foundation (Grant 2016M592773).
文摘Hydrogel microwell arrays (HMAs) have been wildly used for engineering cell microenvironment by providing well-controlled biophysical and biochemical cues (e.g., three dimensional (3D) physical boundary, biomolecule coating) for cells. Among these cues, the oxygen microenvironment has shown great effect on the cellular physiological processes. However, it is currently technically challenging to characterize the local oxygen microenvironment within HMAs. Here, we prepared HMAs with different crosslinking concentrations to adjust the structural and physical properties of HMAs. Then we introduced a scanning electrochemical microscopy (SECM)-based electrochemical method to map the surface topography and oxygen microenvironment around HMAs. The SECM results show both the 3D topography and the oxygen permeability of HMAs in aqueous solution. The obtained oxygen permeability of HMAs increases with increasing the crosslinking concentration, and the microwell boundaries show the highest oxygen permeability throughout HMAs. This work demonstrates that SECM offers a high spatial resolution and in-situ method for characterization of the topography and the local oxygen permeability of HMAs, which can provide useful information for better engineering cell microenvironment through optimizing HMAs design.
