为解决原子力显微镜(Atomic Force Microscope,AFM)系统更换探针后光路调整复杂耗时、精度不足的问题,本文首次提出通过精密控制探针与探针夹装配位置来实现更换的探针相对AFM系统原光路位置的一致,进而实现免去AFM系统换针后调整光路...为解决原子力显微镜(Atomic Force Microscope,AFM)系统更换探针后光路调整复杂耗时、精度不足的问题,本文首次提出通过精密控制探针与探针夹装配位置来实现更换的探针相对AFM系统原光路位置的一致,进而实现免去AFM系统换针后调整光路步骤。该系统的光路一致性组件采用光束偏转法对探针位置与偏转进行放大与监测,并使用高精度位移与角度调节平台进行探针相对于探针夹的方位调整。通过实物搭建对探针一致性效果进行了验证,并对紫外光(Ultraviolet,UV)胶水固化过程导致探针位置偏移影响;探针不同偏移量时产生的探测器噪音对AFM系统成像质量影响进行了系统分析。实验结果表明:经由该系统装配的探针平均位置精度接近1.1μm;并且在AFM系统中更换一致性探针仅需8 s。该系统实现了高精度且质量稳定的探针一致性装配,极大地简化了AFM系统重新校准光路的操作步骤,其与自动换针装置配合可有效提升工业计量型AFM的操作与测量性能。展开更多
Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgic...Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.展开更多
We demonstrated a chemical process in the fabrication of a SERS fiber probe with an ultrahigh sensitivity.The synthesis was carried out by preparing Au@Ag core-shell nanorods (Au@Ag-NRs) selfassembled on polyelectroly...We demonstrated a chemical process in the fabrication of a SERS fiber probe with an ultrahigh sensitivity.The synthesis was carried out by preparing Au@Ag core-shell nanorods (Au@Ag-NRs) selfassembled on polyelectrolyte (PE) multilayers,for which Au@Ag-NRs were controlled by adjusting the silver layer thickness.The effect of silver layer thickness of Au@Ag-NRs on the SERS performance of the fiber probe was investigated.The SERS fiber probe shows the best performance when the silver layer thickness is controlled at 8.57 nm.Under the condition of optimizing silver layer thickness,the fiber probe exhibits ultra-high sensitivity (i e,10^(-10) M crystalline violet,CV),good reproducibility (i e,RSD of 3.5%) and stability.Besides,electromagnetic field distribution of the SERS fiber probe was also investigated.The strongest enhancement is found within the core of fiber,whereas a weakened electromagnetic field exists in the fiber cladding layer.The SERS fiber probe can be a good candidate in ultra-trace detection for biomedical and environmental areas.展开更多
To detect monoamine oxidase B(MAO-B), the level of which is one of the most important indicators of neurodegenerative diseases such as Parkinson's disease, a new type of cascade reaction based on the formation of ...To detect monoamine oxidase B(MAO-B), the level of which is one of the most important indicators of neurodegenerative diseases such as Parkinson's disease, a new type of cascade reaction based on the formation of coumarin was applied in this research. After the reaction with MAO-B, the protecting group of hydroxyl group in probes(DEAN-MA and DEAB-MA) was removed, and the fluorescence intensity significantly increased(l_(em) 456 nm) as the structure of coumarin was formed subsequently. The probes showed excellent sensitivity and selectivity to MAO-B. The detection limit of DEAN-MA and DEAB-MA were 0.6ng/mL and 0.2 ng/mL, respectively. We succeeded in detecting MAO-B in vitro and imaging it in human astrocyte(U87).展开更多
Fluorescence imaging has facilitated fluorescent probes to analyze the subcellular localization and dynamics of biological targets. In this paper, we reported a fluorogenic probe for bacteria imaging. The probe was an...Fluorescence imaging has facilitated fluorescent probes to analyze the subcellular localization and dynamics of biological targets. In this paper, we reported a fluorogenic probe for bacteria imaging. The probe was an imidazolium-derived pyrene compound, which self-assembled to form nano-particles and the pyrene fluorescence was quenched by the aggregation effects. When the self-assembly nanoparticles interacted with anionic bacteria surfaces, synergistic effects of electrostatic interaction and hydrophobic force caused competing binding between bacteria surfaces and imidazoliums. This binding resulted in the disassembly of the aggregates to give fluorescence turn-on signal. Meanwhile, the probe bound bacteria surfaces and displayed both pyrene-excimer and pyrene-monomer fluorescence, which gave ratiometric signal. Then, fluorescent labeling by the probe enabled the two-photo ratiometric imaging of bacteria.展开更多
Radical detection has attracted significant attention recently. Here we have developed a scaffold through covalent assembly principle（OR570）, which could facile applications in detection of oxidative radicals.The pr...Radical detection has attracted significant attention recently. Here we have developed a scaffold through covalent assembly principle（OR570）, which could facile applications in detection of oxidative radicals.The primary advantage of the assembly type probe lies at the turn-on fluorescence signal from a zero background and hence high fluorescence turn-on ratio for sensitive detection of weak signal.展开更多
Augmenting existing devices and structures at the nanoscale with unique functionalities is an exciting prospect.So is the ability to eventually enable at the nanoscale,a version of rapid prototyping via additive nanom...Augmenting existing devices and structures at the nanoscale with unique functionalities is an exciting prospect.So is the ability to eventually enable at the nanoscale,a version of rapid prototyping via additive nanomanufacturing.Achieving this requires a step-up in manufacturing for industrial use of these devices through fast,inexpensive prototyping with nanoscale precision.In this paper,we combine two very promising techniques—self-assembly and printing—to achieve additively nanomanufactured structures.We start by showing that monolayers can drive the assembly of nanoparticles into pre-defined patterns with single-particle resolution;then crucially we demonstrate for the first time that molecular monolayers can be printed using electrohydrodynamic(EHD)-jet printing.The functionality and resolution of such printed monolayers then drives the self-assembly of nanoparticles,demonstrating the integration of EHD with self-assembly.This shows that such process combinations can lead towards more integrated process flows in nanomanufacturing.Furthermore,in-process metrology is a key requirement for any large-scale nanomanufacturing,and we show that Dual-Harmonic Kelvin Probe Microscopy provides a robust metrology technique to characterising these patterned structures through the convolution of geometrical and environmental constraints.These represent a first step toward combining different additive nanomanufacturing techniques and metrology techniques that could in future provide additively nanomanufactured devices and structures.展开更多
Uniting dual-modality of fluorescence and photoacoustic(PA)imaging into theranostic nanoprobes is imperative for spatiotemporally tracking of drug delivery,distribution,and release.Herein,we present a rational design ...Uniting dual-modality of fluorescence and photoacoustic(PA)imaging into theranostic nanoprobes is imperative for spatiotemporally tracking of drug delivery,distribution,and release.Herein,we present a rational design strategy of molecularly precise amphiphilic prodrugs BP_(n)-Cy-S-CPT(n=0,5,and 20,refers to the degree of polyethylene glycol(PEG)polymerization;CPT=camptothecin)to tune their self-assembly behaviour,innovatively integrating dual-modal PA and near-infrared(NIR)fluorescence imaging in a single-molecular framework.Among these elaborately designed prodrugs,it is found that only BP_(20)-Cy-S-CPT could form uniform and highly stable self-assemblies,especially in showing synergistically enhanced PA and dualchannel NIR signals.In detail,PA signal is employed to trace the in vivo delivery with high spatial resolution,meanwhile the glutathione(GSH)-triggered dual-channel fluorescence response could real-timely monitor drug distribution and release without"blind spot".The results of in vivo dual-modal PA/NIR imaging have verified that BP_(20)-Cy-S-CPT displayed synergistic targeting(including passive,active,and activatable targeting)for tumor-specific delivery,and thereby executed CPT release in the tumor site.Consequently,our molecularly precise BP_(20)-Cy-S-CPT self-assemblies could make a breakthrough to spatiotemporally track the in vivo drug release profile,expanding the intelligent theranostic toolbox for precise cancer treatment.展开更多
文摘为解决原子力显微镜(Atomic Force Microscope,AFM)系统更换探针后光路调整复杂耗时、精度不足的问题,本文首次提出通过精密控制探针与探针夹装配位置来实现更换的探针相对AFM系统原光路位置的一致,进而实现免去AFM系统换针后调整光路步骤。该系统的光路一致性组件采用光束偏转法对探针位置与偏转进行放大与监测,并使用高精度位移与角度调节平台进行探针相对于探针夹的方位调整。通过实物搭建对探针一致性效果进行了验证,并对紫外光(Ultraviolet,UV)胶水固化过程导致探针位置偏移影响;探针不同偏移量时产生的探测器噪音对AFM系统成像质量影响进行了系统分析。实验结果表明:经由该系统装配的探针平均位置精度接近1.1μm;并且在AFM系统中更换一致性探针仅需8 s。该系统实现了高精度且质量稳定的探针一致性装配,极大地简化了AFM系统重新校准光路的操作步骤,其与自动换针装置配合可有效提升工业计量型AFM的操作与测量性能。
基金supported by the National Natural Science Foundation of China(NSFC)projects(22122705,22077139 and 81972400)CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-054 and 2021-I2M-1-015)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China).
文摘Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.
基金Funded by National Natural Science Foundation of China (Nos.51372179, 51772224)the Open Projects Foundation of Yangtze Optical Fiber and Cable Joint Stock Limited Company (YOFC)(No.SKLD1705)。
文摘We demonstrated a chemical process in the fabrication of a SERS fiber probe with an ultrahigh sensitivity.The synthesis was carried out by preparing Au@Ag core-shell nanorods (Au@Ag-NRs) selfassembled on polyelectrolyte (PE) multilayers,for which Au@Ag-NRs were controlled by adjusting the silver layer thickness.The effect of silver layer thickness of Au@Ag-NRs on the SERS performance of the fiber probe was investigated.The SERS fiber probe shows the best performance when the silver layer thickness is controlled at 8.57 nm.Under the condition of optimizing silver layer thickness,the fiber probe exhibits ultra-high sensitivity (i e,10^(-10) M crystalline violet,CV),good reproducibility (i e,RSD of 3.5%) and stability.Besides,electromagnetic field distribution of the SERS fiber probe was also investigated.The strongest enhancement is found within the core of fiber,whereas a weakened electromagnetic field exists in the fiber cladding layer.The SERS fiber probe can be a good candidate in ultra-trace detection for biomedical and environmental areas.
基金financially supported by the National Natural Science Foundation of China (Nos. 21572147 and 21472131)
文摘To detect monoamine oxidase B(MAO-B), the level of which is one of the most important indicators of neurodegenerative diseases such as Parkinson's disease, a new type of cascade reaction based on the formation of coumarin was applied in this research. After the reaction with MAO-B, the protecting group of hydroxyl group in probes(DEAN-MA and DEAB-MA) was removed, and the fluorescence intensity significantly increased(l_(em) 456 nm) as the structure of coumarin was formed subsequently. The probes showed excellent sensitivity and selectivity to MAO-B. The detection limit of DEAN-MA and DEAB-MA were 0.6ng/mL and 0.2 ng/mL, respectively. We succeeded in detecting MAO-B in vitro and imaging it in human astrocyte(U87).
基金financially supported by the National Natural Science Foundation of China(Nos. 21878286, 21502189)DICP (Nos. DMT0201603, TMSR201601)
文摘Fluorescence imaging has facilitated fluorescent probes to analyze the subcellular localization and dynamics of biological targets. In this paper, we reported a fluorogenic probe for bacteria imaging. The probe was an imidazolium-derived pyrene compound, which self-assembled to form nano-particles and the pyrene fluorescence was quenched by the aggregation effects. When the self-assembly nanoparticles interacted with anionic bacteria surfaces, synergistic effects of electrostatic interaction and hydrophobic force caused competing binding between bacteria surfaces and imidazoliums. This binding resulted in the disassembly of the aggregates to give fluorescence turn-on signal. Meanwhile, the probe bound bacteria surfaces and displayed both pyrene-excimer and pyrene-monomer fluorescence, which gave ratiometric signal. Then, fluorescent labeling by the probe enabled the two-photo ratiometric imaging of bacteria.
基金supported by the Fundamental Research Funds for the Central Universities (Nos. 1222201718004, WY1514053 and WY1516017)the National Natural Science Foundation of China (Nos. 21372080, 21572061, and 21236002)
文摘Radical detection has attracted significant attention recently. Here we have developed a scaffold through covalent assembly principle（OR570）, which could facile applications in detection of oxidative radicals.The primary advantage of the assembly type probe lies at the turn-on fluorescence signal from a zero background and hence high fluorescence turn-on ratio for sensitive detection of weak signal.
基金This research was supported via the EPSRC Manufacturing Fellowship EP/J018694/1the WAFT collaboration(EP/M015173/1).
文摘Augmenting existing devices and structures at the nanoscale with unique functionalities is an exciting prospect.So is the ability to eventually enable at the nanoscale,a version of rapid prototyping via additive nanomanufacturing.Achieving this requires a step-up in manufacturing for industrial use of these devices through fast,inexpensive prototyping with nanoscale precision.In this paper,we combine two very promising techniques—self-assembly and printing—to achieve additively nanomanufactured structures.We start by showing that monolayers can drive the assembly of nanoparticles into pre-defined patterns with single-particle resolution;then crucially we demonstrate for the first time that molecular monolayers can be printed using electrohydrodynamic(EHD)-jet printing.The functionality and resolution of such printed monolayers then drives the self-assembly of nanoparticles,demonstrating the integration of EHD with self-assembly.This shows that such process combinations can lead towards more integrated process flows in nanomanufacturing.Furthermore,in-process metrology is a key requirement for any large-scale nanomanufacturing,and we show that Dual-Harmonic Kelvin Probe Microscopy provides a robust metrology technique to characterising these patterned structures through the convolution of geometrical and environmental constraints.These represent a first step toward combining different additive nanomanufacturing techniques and metrology techniques that could in future provide additively nanomanufactured devices and structures.
基金supported by the National Natural Science Foundation of China(21878087,21908060)the Innovation Program of Shanghai Municipal Education Commission,Shuguang Program(18SG27)。
文摘Uniting dual-modality of fluorescence and photoacoustic(PA)imaging into theranostic nanoprobes is imperative for spatiotemporally tracking of drug delivery,distribution,and release.Herein,we present a rational design strategy of molecularly precise amphiphilic prodrugs BP_(n)-Cy-S-CPT(n=0,5,and 20,refers to the degree of polyethylene glycol(PEG)polymerization;CPT=camptothecin)to tune their self-assembly behaviour,innovatively integrating dual-modal PA and near-infrared(NIR)fluorescence imaging in a single-molecular framework.Among these elaborately designed prodrugs,it is found that only BP_(20)-Cy-S-CPT could form uniform and highly stable self-assemblies,especially in showing synergistically enhanced PA and dualchannel NIR signals.In detail,PA signal is employed to trace the in vivo delivery with high spatial resolution,meanwhile the glutathione(GSH)-triggered dual-channel fluorescence response could real-timely monitor drug distribution and release without"blind spot".The results of in vivo dual-modal PA/NIR imaging have verified that BP_(20)-Cy-S-CPT displayed synergistic targeting(including passive,active,and activatable targeting)for tumor-specific delivery,and thereby executed CPT release in the tumor site.Consequently,our molecularly precise BP_(20)-Cy-S-CPT self-assemblies could make a breakthrough to spatiotemporally track the in vivo drug release profile,expanding the intelligent theranostic toolbox for precise cancer treatment.
