The isolation of circulating tumor cells(CTCs)from complex biological samples is of paramount signifi-cance for advancing cancer diagnosis,prognosis,and treatment.However,the low concentration of CTCs and nonspecific ...The isolation of circulating tumor cells(CTCs)from complex biological samples is of paramount signifi-cance for advancing cancer diagnosis,prognosis,and treatment.However,the low concentration of CTCs and nonspecific adhesion of white blood cells(WBCs)present challenges that hinder the efficiency and purity of captured CTCs.Microfluidic-based strategies utilize precise fluid control at the micron level to incorporate specific micro/nanostructures or recognition molecules,enabling effective CTCs separation.Moreover,by employing surface modification designs that exhibit exceptional anti-adhesion properties against WBCs,the purity of isolated CTCs can be further enhanced.This review offers an in-depth explo-ration of recent advancements,challenges,and opportunities associated with microfluidic-based CTCs iso-lation from biological samples.Firstly,we will comprehensively introduce the microfluidic-based strate-gies for achieving high-efficiency CTCs isolation,which includes the morphological design of microchan-nels for physical force-based CTCs isolation and the specific modification of microchannel surfaces for affinity-based CTCs isolation.Subsequently,a review of recent research advances in microfluidic-based high-purity CTCs isolation is presented,focusing on strategies that decrease the nonspecific adhesion of WBCs through surface micro-/nanostructure construction or chemical and biological modification.Finally,we will summarize the article by providing the prospective opportunities and challenges for the future development of microfluidic-based CTCs isolation.展开更多
In the SILER （Seismic-Initiated events risk mitigation in LEad-cooled Reactors） Project, it is interesting to apply seismic isolation technology for the reactor assembly of the fixed base reactor building for ADS （...In the SILER （Seismic-Initiated events risk mitigation in LEad-cooled Reactors） Project, it is interesting to apply seismic isolation technology for the reactor assembly of the fixed base reactor building for ADS （Acceleration Driven System） heavy liquid reactor MYRRHA （Multipurpose Hybrid Research Reactor for High-Tech Application） which contains the most critical safety related components, such as reactor vessel, safe shutdown and control rod mechanisms, primary heat exchangers, primary pumps, spoliation target assembly and fuel assemblies, etc. The purpose of this paper is to investigate the possibility of an application of a partial seismic isolation to the safety critical components only, here, the reactor assembly. This paper presents the preliminary analysis results of the isolated reactor assembly and compares these with those of seismic isolated ADS reactor building. The analysis results show the reduction of the seismic acceleration response but the increase of the relative displacement for the reactor assembly. Some safety issues, especially, coolant＇s incapable covering the reactor core make difficult to apply for the partial seismic isolation of the ADS reactor assembly due to large relative displacement occurring the partial isolation system. Further study on the partial seismic isolation application of the critical safety components are also discussed.展开更多
Circulating tumor cells(CTCs) are the cancer cells that circulate in the peripheral blood after escaping from the original or metastatic tumors. CTCs could be used as non-invasive source of clinical information in ear...Circulating tumor cells(CTCs) are the cancer cells that circulate in the peripheral blood after escaping from the original or metastatic tumors. CTCs could be used as non-invasive source of clinical information in early diagnosis of cancer and evaluation of cancer development. In recent years, CTC research has become a hotspot field wherein many novel CTC detection technologies based on microfluidics have been developed. Great advances have been made that exhibit obvious technical advantages, but cannot yet satisfy the current clinical requirements. In this study, we review the main advances in isolation and detection methods of CTC based on microfluidics research over several years, propose five technical indicators for evaluating these methods, and explore the application prospects. We also discuss the concepts, issues, approaches, advantages, limitations, and challenges with an aim of stimulating a broader interest in developing microfluidics-based CTC detection technology.展开更多
Isolating rare circulating tumor cells(CTCs)from blood is critical for the downstream analysis that is important in cancer-related research,diagnosis,and medicine,and efforts are ongoing to increase the efficiency and...Isolating rare circulating tumor cells(CTCs)from blood is critical for the downstream analysis that is important in cancer-related research,diagnosis,and medicine,and efforts are ongoing to increase the efficiency and purity of CTC isolation in microfluidics.Reported in this paper is a two-stage integrated microfluidic chip for coarse-to-fine CTC isolation from whole blood.First,blood cells are removed by filtration using a micropore-array membrane,then CTCs and other cells that are trapped in the micropores are peeled off the membrane by a novel release method based on air–liquid interfacial tension,which significantly increases the recovery rate of CTCs.The second stage is CTC capture based on an on-chip dense immuno-magnetic-bead clump,which offers high capture efficiency and purity.Both the micropore filtration and immuno-magnetic-bead capture are validated and optimized experimentally.Overall,the integrated microfluidic chip can realize a recovery rate of 85.5%and a purity of 37.8%for rare cancer cells spiked in whole blood.展开更多
Although various strategies have been proposed for enrichment of circulating tumor cells(CTCs),the clinical outcomes of CTC detection are far from satisfactory.The prevailingmethodologies for CTC detection are general...Although various strategies have been proposed for enrichment of circulating tumor cells(CTCs),the clinical outcomes of CTC detection are far from satisfactory.The prevailingmethodologies for CTC detection are generally oriented towardnaturallyoccurring targets;however,misdetection and interference are prevalent due to the diverse phenotypes and subpopulations of CTCs,which are highly heterogeneous.Here,a CTC isolation system based on the“labelcapture-release”process is demonstrated for the precise and highly efficient enrichment of CTCs fromclinical blood samples.On the basis of the abnormal glycometabolism of tumor cells,the surface of CTCs can be decorated with artificial azido groups.By utilizing bio-orthogonal plates designed with dibenzocyclooctane(DBCO)and disulfide groups,withthe aid of anti-fouling effects,CTCs labeled with azido groups can be captured through a copper-free click reaction and subsequently released via disulfide reduction.The technique has been shown to label tumor cells with the epithelial cell adhesion molecule(EpCAM)+and EpCAM~phenotypes in both adherent and suspended states.Moreover,it effectively isolates all epithelial,interstitial,and hybrid phenotypes of CTCs from clinical blood samples collected from dozens of patients across more than 10 cancer types.Compared to the clinically approved CTC detection system,our strategy demonstrates superior performance from the perspective of broad-spectrum and accurate recognition of heterogeneous CTCs.More importantly,most of the captured CTCs can be released with the retention of living activity,making this technique well suited for downstream applications such as drug susceptibility tests involving viable CTCs.展开更多
基金supported by the National Natural Science Foundation of China(Nos.52025132,22005255,21975209,21621091,22021001,T2241022)the National Science Foundation of Fujian Province of China(No.2022J02059)+2 种基金the Fundamental Research Funds for the Central Universities of China(No.20720220085)the 111 Project(Nos.B17027,B16029)the Science and Technology Projects of Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(No.RD2022070601),the New Cornerstone Science Foundation through the XPLORER PRIZE.
文摘The isolation of circulating tumor cells(CTCs)from complex biological samples is of paramount signifi-cance for advancing cancer diagnosis,prognosis,and treatment.However,the low concentration of CTCs and nonspecific adhesion of white blood cells(WBCs)present challenges that hinder the efficiency and purity of captured CTCs.Microfluidic-based strategies utilize precise fluid control at the micron level to incorporate specific micro/nanostructures or recognition molecules,enabling effective CTCs separation.Moreover,by employing surface modification designs that exhibit exceptional anti-adhesion properties against WBCs,the purity of isolated CTCs can be further enhanced.This review offers an in-depth explo-ration of recent advancements,challenges,and opportunities associated with microfluidic-based CTCs iso-lation from biological samples.Firstly,we will comprehensively introduce the microfluidic-based strate-gies for achieving high-efficiency CTCs isolation,which includes the morphological design of microchan-nels for physical force-based CTCs isolation and the specific modification of microchannel surfaces for affinity-based CTCs isolation.Subsequently,a review of recent research advances in microfluidic-based high-purity CTCs isolation is presented,focusing on strategies that decrease the nonspecific adhesion of WBCs through surface micro-/nanostructure construction or chemical and biological modification.Finally,we will summarize the article by providing the prospective opportunities and challenges for the future development of microfluidic-based CTCs isolation.
文摘In the SILER （Seismic-Initiated events risk mitigation in LEad-cooled Reactors） Project, it is interesting to apply seismic isolation technology for the reactor assembly of the fixed base reactor building for ADS （Acceleration Driven System） heavy liquid reactor MYRRHA （Multipurpose Hybrid Research Reactor for High-Tech Application） which contains the most critical safety related components, such as reactor vessel, safe shutdown and control rod mechanisms, primary heat exchangers, primary pumps, spoliation target assembly and fuel assemblies, etc. The purpose of this paper is to investigate the possibility of an application of a partial seismic isolation to the safety critical components only, here, the reactor assembly. This paper presents the preliminary analysis results of the isolated reactor assembly and compares these with those of seismic isolated ADS reactor building. The analysis results show the reduction of the seismic acceleration response but the increase of the relative displacement for the reactor assembly. Some safety issues, especially, coolant＇s incapable covering the reactor core make difficult to apply for the partial seismic isolation of the ADS reactor assembly due to large relative displacement occurring the partial isolation system. Further study on the partial seismic isolation application of the critical safety components are also discussed.
基金supported by National Key Basic Research Program of China (Grant No.2017FYA0205300 and No.2015 CB931802)National Natural Scientific Foundation of China (No. 81571835)
文摘Circulating tumor cells(CTCs) are the cancer cells that circulate in the peripheral blood after escaping from the original or metastatic tumors. CTCs could be used as non-invasive source of clinical information in early diagnosis of cancer and evaluation of cancer development. In recent years, CTC research has become a hotspot field wherein many novel CTC detection technologies based on microfluidics have been developed. Great advances have been made that exhibit obvious technical advantages, but cannot yet satisfy the current clinical requirements. In this study, we review the main advances in isolation and detection methods of CTC based on microfluidics research over several years, propose five technical indicators for evaluating these methods, and explore the application prospects. We also discuss the concepts, issues, approaches, advantages, limitations, and challenges with an aim of stimulating a broader interest in developing microfluidics-based CTC detection technology.
基金This work was funded by the National Natural Science Foundation of China(Grant Nos.61774095 and 21727813)the Beijing Research Institute of Mechanical Equipment.
文摘Isolating rare circulating tumor cells(CTCs)from blood is critical for the downstream analysis that is important in cancer-related research,diagnosis,and medicine,and efforts are ongoing to increase the efficiency and purity of CTC isolation in microfluidics.Reported in this paper is a two-stage integrated microfluidic chip for coarse-to-fine CTC isolation from whole blood.First,blood cells are removed by filtration using a micropore-array membrane,then CTCs and other cells that are trapped in the micropores are peeled off the membrane by a novel release method based on air–liquid interfacial tension,which significantly increases the recovery rate of CTCs.The second stage is CTC capture based on an on-chip dense immuno-magnetic-bead clump,which offers high capture efficiency and purity.Both the micropore filtration and immuno-magnetic-bead capture are validated and optimized experimentally.Overall,the integrated microfluidic chip can realize a recovery rate of 85.5%and a purity of 37.8%for rare cancer cells spiked in whole blood.
基金supported by the National Key R&D Program of China(2021YFB3800800)the National Natural Science Foundation of China(81903057,82073284,32000962,82402491,and 82272157)+2 种基金Shenzhen Science and Technology Research Funding(JCYJ20200109115601720)the Hong Kong PDFS-RGC Postdoctoral Fellowship Scheme(PDFS2122-1S08 and CityU 9061014)Hong Kong HMRF(Health and Medical Research Fund)(2120972 and CityU 9211320)。
文摘Although various strategies have been proposed for enrichment of circulating tumor cells(CTCs),the clinical outcomes of CTC detection are far from satisfactory.The prevailingmethodologies for CTC detection are generally oriented towardnaturallyoccurring targets;however,misdetection and interference are prevalent due to the diverse phenotypes and subpopulations of CTCs,which are highly heterogeneous.Here,a CTC isolation system based on the“labelcapture-release”process is demonstrated for the precise and highly efficient enrichment of CTCs fromclinical blood samples.On the basis of the abnormal glycometabolism of tumor cells,the surface of CTCs can be decorated with artificial azido groups.By utilizing bio-orthogonal plates designed with dibenzocyclooctane(DBCO)and disulfide groups,withthe aid of anti-fouling effects,CTCs labeled with azido groups can be captured through a copper-free click reaction and subsequently released via disulfide reduction.The technique has been shown to label tumor cells with the epithelial cell adhesion molecule(EpCAM)+and EpCAM~phenotypes in both adherent and suspended states.Moreover,it effectively isolates all epithelial,interstitial,and hybrid phenotypes of CTCs from clinical blood samples collected from dozens of patients across more than 10 cancer types.Compared to the clinically approved CTC detection system,our strategy demonstrates superior performance from the perspective of broad-spectrum and accurate recognition of heterogeneous CTCs.More importantly,most of the captured CTCs can be released with the retention of living activity,making this technique well suited for downstream applications such as drug susceptibility tests involving viable CTCs.
