Detection of small cancer biomarkers with low molecular weight and a low concentration range has always been challenging yet urgent in many clinical applications such as diagnosing early-stage cancer,monitoring treatm...Detection of small cancer biomarkers with low molecular weight and a low concentration range has always been challenging yet urgent in many clinical applications such as diagnosing early-stage cancer,monitoring treatment and detecting relapse.Here,a highly enhanced plasmonic biosensor that can overcome this challenge is developed using atomically thin two-dimensional phase change nanomaterial.By precisely engineering the configuration with atomically thin materials,the phase singularity has been successfully achieved with a significantly enhanced lateral position shift effect.Based on our knowledge,it is the first experimental demonstration of a lateral position signal change>340μm at a sensing interface from all optical techniques.With this enhanced plasmonic effect,the detection limit has been experimentally demonstrated to be 10^(-15) mol L^(−1) for TNF-α cancer marker,which has been found in various human diseases including inflammatory diseases and different kinds of cancer.The as-reported novel integration of atomically thin Ge_(2)Sb_(2)Te_(5) with plasmonic substrate, which results in a phase singularity and thus a giant lateral position shift, enables the detection of cancer markers with low molecular weight at femtomolar level. These results will definitely hold promising potential in biomedical application and clinical diagnostics.展开更多
Rapid plasmonic biosensing has attracted wide attention in early disease diagnosis and molecular biology research.However,it was still challenging for conventional angle-interrogating plasmonic sensors to obtain highe...Rapid plasmonic biosensing has attracted wide attention in early disease diagnosis and molecular biology research.However,it was still challenging for conventional angle-interrogating plasmonic sensors to obtain higher sensitivity without secondary amplifying labels such as plasmonic nanoparticles.To address this issue,we developed a plasmonic biosensor based on the enhanced lateral position shift by phase singularity.Such singularity presents as a sudden phase retardation at the dark point of reflection from resonating plasmonic substrate,leading to a giant position shift on reflected beam.Herein,for the first time,the atomically thin layer of Ge2Sb2Te5(GST)on silver nanofilm was demonstrated as a novel phase-response-enhancing plasmonic material.The GST layer was not only precisely engineered to singularize phase change but also served as a protective layer for active silver nanofilm.This new configuration has achieved a record-breaking largest position shift of 439.3μm measured in calibration experiments with an ultra-high sensitivity of 1.72×10^(8)nm RIU−1(refractive index unit).The detection limit was determined to be 6.97×10^(−7)RIU with a 0.12μm position resolution.Besides,a large figure of merit(FOM)of 4.54×10^(11)μm(RIU∙°)^(−1)was evaluated for such position shift interrogation,enabling the labelfree detection of trace amounts of biomolecules.In targeted biosensing experiments,the optimized sensor has successfully detected small cytokine biomarkers(TNF-αand IL-6)with the lowest concentration of 1×10^(−16)M.These two molecules are the key proinflammatory cancer markers in clinical diagnosis,which cannot be directly screened by current clinical techniques.To further validate the selectivity of our sensing systems,we also measured the affinity of integrin binding to arginylglycylaspartic acid(RGD)peptide(a key protein interaction in cell adhesion)with different Mn2+ion concentrations,ranging from 1 nM to 1 mM.展开更多
基金We thank Shiyue Liu from School of Life Sciences in The Chinese University of Hong Kong for helpful discussions.This work is supported under the PROCORE-France/Hong Kong Joint Research Scheme(F-CUHK402/19)the Research Grants Council,Hong Kong Special Administration Region(AoE/P-02/12,14210517,14207419,N_CUHK407/16)the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No.798916.Y.Wang is supported under the Hong Kong PhD Fellowship Scheme.
文摘Detection of small cancer biomarkers with low molecular weight and a low concentration range has always been challenging yet urgent in many clinical applications such as diagnosing early-stage cancer,monitoring treatment and detecting relapse.Here,a highly enhanced plasmonic biosensor that can overcome this challenge is developed using atomically thin two-dimensional phase change nanomaterial.By precisely engineering the configuration with atomically thin materials,the phase singularity has been successfully achieved with a significantly enhanced lateral position shift effect.Based on our knowledge,it is the first experimental demonstration of a lateral position signal change>340μm at a sensing interface from all optical techniques.With this enhanced plasmonic effect,the detection limit has been experimentally demonstrated to be 10^(-15) mol L^(−1) for TNF-α cancer marker,which has been found in various human diseases including inflammatory diseases and different kinds of cancer.The as-reported novel integration of atomically thin Ge_(2)Sb_(2)Te_(5) with plasmonic substrate, which results in a phase singularity and thus a giant lateral position shift, enables the detection of cancer markers with low molecular weight at femtomolar level. These results will definitely hold promising potential in biomedical application and clinical diagnostics.
基金the UTT Project Stratégique NanoSPR(OPE-2022-0293)the Graduate School(Ecole Universitaire de Recherche)“NANOPHOT”(ANR-18-EURE-0013)+1 种基金PHC PROCORE-Campus France/Hong Kong Joint Research Scheme(No.44683Q)AAP1-LABEX SigmaPIX 2021.
文摘Rapid plasmonic biosensing has attracted wide attention in early disease diagnosis and molecular biology research.However,it was still challenging for conventional angle-interrogating plasmonic sensors to obtain higher sensitivity without secondary amplifying labels such as plasmonic nanoparticles.To address this issue,we developed a plasmonic biosensor based on the enhanced lateral position shift by phase singularity.Such singularity presents as a sudden phase retardation at the dark point of reflection from resonating plasmonic substrate,leading to a giant position shift on reflected beam.Herein,for the first time,the atomically thin layer of Ge2Sb2Te5(GST)on silver nanofilm was demonstrated as a novel phase-response-enhancing plasmonic material.The GST layer was not only precisely engineered to singularize phase change but also served as a protective layer for active silver nanofilm.This new configuration has achieved a record-breaking largest position shift of 439.3μm measured in calibration experiments with an ultra-high sensitivity of 1.72×10^(8)nm RIU−1(refractive index unit).The detection limit was determined to be 6.97×10^(−7)RIU with a 0.12μm position resolution.Besides,a large figure of merit(FOM)of 4.54×10^(11)μm(RIU∙°)^(−1)was evaluated for such position shift interrogation,enabling the labelfree detection of trace amounts of biomolecules.In targeted biosensing experiments,the optimized sensor has successfully detected small cytokine biomarkers(TNF-αand IL-6)with the lowest concentration of 1×10^(−16)M.These two molecules are the key proinflammatory cancer markers in clinical diagnosis,which cannot be directly screened by current clinical techniques.To further validate the selectivity of our sensing systems,we also measured the affinity of integrin binding to arginylglycylaspartic acid(RGD)peptide(a key protein interaction in cell adhesion)with different Mn2+ion concentrations,ranging from 1 nM to 1 mM.
