Single-molecule detection is one of the fundamental challenges of modern biology.Such experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events b...Single-molecule detection is one of the fundamental challenges of modern biology.Such experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events being studied.Analyte size plays an important role in determining detectability.Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius,and 15.5 kDa molecules are detected in aqueous solution,thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell.Our results,covering several orders of magnitude of particle radius(100 nm to 2 nm),agree with the‘reactive’model prediction for the frequency shift of the resonator upon particle binding.This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle.We anticipate that our results will enable many applications,including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.展开更多
Whispering gallery mode(WGM) microtoroid optical resonators have been effectively used to sense low concentrations of biomolecules down to the single molecule limit. Optical WGM biochemical sensors such as the microto...Whispering gallery mode(WGM) microtoroid optical resonators have been effectively used to sense low concentrations of biomolecules down to the single molecule limit. Optical WGM biochemical sensors such as the microtoroid operate by tracking changes in resonant frequency as particles enter the evanescent near field of the resonator.Previously, gold nanoparticles have been coupled to WGM resonators to increase the magnitude of resonance shifts via plasmonic enhancement of the electric field. However, this approach results in increased scattering from the WGM, which degrades its quality(Q) factor, making it less sensitive to extremely small frequency shifts caused by small molecules or protein conformational changes. Here, we show using simulation that precisely positioned trimer gold nanostructures generate dark modes that suppress radiation loss and can achieve high (> 10~6) Q with an electric-field intensity enhancement of 4300, which far exceeds that of a single rod(~2500 times). Through an overall evaluation of a combined enhancement factor, which includes the Q factor of the system, the sensitivity of the trimer system was improved 105× versus 84× for a single rod. Further simulations demonstrate that unlike a single rod system, the trimer is robust to orientation changes and has increased capture area. We also conduct stability tests to show that small positioning errors do not greatly impact the result.展开更多
Ultra-high quality(Q) whispering gallery mode(WGM) microtoroid optical resonators have demonstrated highly sensitive biomolecular detection down to the single molecule limit;however, the lack of a robust coupling meth...Ultra-high quality(Q) whispering gallery mode(WGM) microtoroid optical resonators have demonstrated highly sensitive biomolecular detection down to the single molecule limit;however, the lack of a robust coupling method has prevented their widespread adoption outside the laboratory. We demonstrate through simulation that a phased array of nanorods can enable free-space coupling of light both into and out of a microtoroid while maintaining a high Q. To simulate large nanostructured WGM resonators, we developed a new approach known as FloWBEM,which is an efficient and compact 3D wedge model with custom boundary conditions that accurately simulate the resonant Fano interference between the traveling WGM waves and a nanorod array. Depending on the excitation conditions, we find loaded Q factors of the driven system as high as 2.1 × 10~7 and signal-to-background ratios as high as 3.86%, greater than the noise levels of many commercial detectors. These results can drive future experimental implementation.展开更多
Whispering gallery mode(WGM)microtoroid resonators are one of the most sensitive biochemical sensors in existence,capable of detecting single molecules.The main barrier for translating these devices out of the laborat...Whispering gallery mode(WGM)microtoroid resonators are one of the most sensitive biochemical sensors in existence,capable of detecting single molecules.The main barrier for translating these devices out of the laboratory is that light is evanescently coupled into these devices though a tapered optical fiber.This hinders translation of these devices as the taper is fragile,suffers from mechanical vibration,and requires precise positioning.Here,we eliminate the need for an optical fiber by coupling light into and out from a toroid via free-space coupling and monitoring the scattered resonant light.A single long working distance objective lens combined with a digital micromirror device(DMD)was used for light injection,scattered light collection,and imaging.We obtain Q-factors as high as 1:6´108 with this approach.Electromagnetically induced transparency(EIT)-like and Fano resonances were observed in a single cavity due to indirect coupling in free space.This enables improved sensing sensitivity.The large effective coupling area(~10μm in diameter for numerical aperture=0.14)removes the need for precise positioning.Sensing performance was verified by combining the system with the frequency locked whispering evanescent resonator(FLOWER)approach to perform temperature sensing experiments.A thermal nonlinear optical effect was examined by tracking the resonance through FLOWER while adjusting the input power.We believe that this work will be a foundation for expanding the implementation of WGM microtoroid resonators to real-world applications.展开更多
Label-free detection techniques for single particles and molecules play an important role in basic science,disease diagnostics,and nanomaterial investigations.While fluorescence-based methods are tools for single mole...Label-free detection techniques for single particles and molecules play an important role in basic science,disease diagnostics,and nanomaterial investigations.While fluorescence-based methods are tools for single molecule detection and imaging,they are limited by available molecular probes and photoblinking and photobleaching.Photothermal microscopy has emerged as a label-free imaging technique capable of detecting individual nanoabsorbers with high sensitivity.Whispering gallery mode(WGM)microresonators can confine light in a small volume for enhanced light-matter interaction and thus are a promising ultra-sensitive photothermal microscopy platform.Previously,microtoroid optical resonators were combined with photothermal microscopy to detect 250 nm iong gold nanorods and 100 nm long polymers.Here,we combine microtoroids with photothermal microscopy to spatially detect single 5 nm diameter quantum dots(QDs)with a signal-to-noise ratio exceeding 10*.Photothermal images were generated by point-by-point scanning of the pump laser.Single particle detection was confrmed for 18 nm QDs by high sensitivity fluorescence imaging and for 5 nm QDs via comparison with theory.Our system demonstrates the capability to detect a minimum heat dissipation of o.75 pW.To achieve this,we integrated our microtoroid based photothermal microscopy setup with a low amplitude modulated pump laser and utilized the proportional-integral-derivative controller output as the photothermal signal source to reduce noise and enhance signal stability.The heat dissipation of these QDs is below that from single dye molecules.We anticipate that our work will have application in a wide variety of fields,including the biological sciences,nanotechnology,materials science,chemistry and medicine.展开更多
A compact optical nanofiber sensor enables detection of 100 nm particles in the field.This device improves our ability to track air quality with high spatiotemporal resolution.Air pollution has enormous health and eco...A compact optical nanofiber sensor enables detection of 100 nm particles in the field.This device improves our ability to track air quality with high spatiotemporal resolution.Air pollution has enormous health and economic costs,causing an estimated 7 million deaths per year1 and costing US$225 billion globally in 2013 according to the most recent data from the World Health Organization(WHO)and World Bank,respectively2.Despite this impact,air pollution levels continue to increase,with 92%of the world’s population living in environments in which WHO air quality guidelines are not met3.展开更多
文摘Single-molecule detection is one of the fundamental challenges of modern biology.Such experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events being studied.Analyte size plays an important role in determining detectability.Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius,and 15.5 kDa molecules are detected in aqueous solution,thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell.Our results,covering several orders of magnitude of particle radius(100 nm to 2 nm),agree with the‘reactive’model prediction for the frequency shift of the resonator upon particle binding.This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle.We anticipate that our results will enable many applications,including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.
基金supported by the Defense Threat Reduction Agency(DTRA)-Joint Science and Technology Office for Chemical and Biological Defense(grant HDTRA11810044)The University of ArizonaDeMund Foundation Graduate Student Endowed Scholarship in Optical and Medical Sciences
文摘Whispering gallery mode(WGM) microtoroid optical resonators have been effectively used to sense low concentrations of biomolecules down to the single molecule limit. Optical WGM biochemical sensors such as the microtoroid operate by tracking changes in resonant frequency as particles enter the evanescent near field of the resonator.Previously, gold nanoparticles have been coupled to WGM resonators to increase the magnitude of resonance shifts via plasmonic enhancement of the electric field. However, this approach results in increased scattering from the WGM, which degrades its quality(Q) factor, making it less sensitive to extremely small frequency shifts caused by small molecules or protein conformational changes. Here, we show using simulation that precisely positioned trimer gold nanostructures generate dark modes that suppress radiation loss and can achieve high (> 10~6) Q with an electric-field intensity enhancement of 4300, which far exceeds that of a single rod(~2500 times). Through an overall evaluation of a combined enhancement factor, which includes the Q factor of the system, the sensitivity of the trimer system was improved 105× versus 84× for a single rod. Further simulations demonstrate that unlike a single rod system, the trimer is robust to orientation changes and has increased capture area. We also conduct stability tests to show that small positioning errors do not greatly impact the result.
基金National Key R&D Program of China(2016YFA0301300)National Natural Science Foundation of China(NSFC)(61671090,61875021)+4 种基金Natural Science Foundation of Beijing Municipality(2192036)China Scholarship Council(CSC)(201706470049)Beijing University of Posts and Telecommunications Excellent Ph.D.Students Foundation(CX2017302)DeMund Foundation Graduate Student Endowed Scholarship in Optical and Medical Sciences Friends of Tucson Optics(FOTO)ScholarshipDefense Threat Reduction Agency(DTRA)(HDTRA1-18-1-0044)
文摘Ultra-high quality(Q) whispering gallery mode(WGM) microtoroid optical resonators have demonstrated highly sensitive biomolecular detection down to the single molecule limit;however, the lack of a robust coupling method has prevented their widespread adoption outside the laboratory. We demonstrate through simulation that a phased array of nanorods can enable free-space coupling of light both into and out of a microtoroid while maintaining a high Q. To simulate large nanostructured WGM resonators, we developed a new approach known as FloWBEM,which is an efficient and compact 3D wedge model with custom boundary conditions that accurately simulate the resonant Fano interference between the traveling WGM waves and a nanorod array. Depending on the excitation conditions, we find loaded Q factors of the driven system as high as 2.1 × 10~7 and signal-to-background ratios as high as 3.86%, greater than the noise levels of many commercial detectors. These results can drive future experimental implementation.
文摘Whispering gallery mode(WGM)microtoroid resonators are one of the most sensitive biochemical sensors in existence,capable of detecting single molecules.The main barrier for translating these devices out of the laboratory is that light is evanescently coupled into these devices though a tapered optical fiber.This hinders translation of these devices as the taper is fragile,suffers from mechanical vibration,and requires precise positioning.Here,we eliminate the need for an optical fiber by coupling light into and out from a toroid via free-space coupling and monitoring the scattered resonant light.A single long working distance objective lens combined with a digital micromirror device(DMD)was used for light injection,scattered light collection,and imaging.We obtain Q-factors as high as 1:6´108 with this approach.Electromagnetically induced transparency(EIT)-like and Fano resonances were observed in a single cavity due to indirect coupling in free space.This enables improved sensing sensitivity.The large effective coupling area(~10μm in diameter for numerical aperture=0.14)removes the need for precise positioning.Sensing performance was verified by combining the system with the frequency locked whispering evanescent resonator(FLOWER)approach to perform temperature sensing experiments.A thermal nonlinear optical effect was examined by tracking the resonance through FLOWER while adjusting the input power.We believe that this work will be a foundation for expanding the implementation of WGM microtoroid resonators to real-world applications.
基金support in part from NIH R35GM137988 and the Gordon and Betty Moore Foundation through Grant GBMF7555.14 to Judith Su.We thank G.Mouneimne for assistance with the STORM microscopy system.
文摘Label-free detection techniques for single particles and molecules play an important role in basic science,disease diagnostics,and nanomaterial investigations.While fluorescence-based methods are tools for single molecule detection and imaging,they are limited by available molecular probes and photoblinking and photobleaching.Photothermal microscopy has emerged as a label-free imaging technique capable of detecting individual nanoabsorbers with high sensitivity.Whispering gallery mode(WGM)microresonators can confine light in a small volume for enhanced light-matter interaction and thus are a promising ultra-sensitive photothermal microscopy platform.Previously,microtoroid optical resonators were combined with photothermal microscopy to detect 250 nm iong gold nanorods and 100 nm long polymers.Here,we combine microtoroids with photothermal microscopy to spatially detect single 5 nm diameter quantum dots(QDs)with a signal-to-noise ratio exceeding 10*.Photothermal images were generated by point-by-point scanning of the pump laser.Single particle detection was confrmed for 18 nm QDs by high sensitivity fluorescence imaging and for 5 nm QDs via comparison with theory.Our system demonstrates the capability to detect a minimum heat dissipation of o.75 pW.To achieve this,we integrated our microtoroid based photothermal microscopy setup with a low amplitude modulated pump laser and utilized the proportional-integral-derivative controller output as the photothermal signal source to reduce noise and enhance signal stability.The heat dissipation of these QDs is below that from single dye molecules.We anticipate that our work will have application in a wide variety of fields,including the biological sciences,nanotechnology,materials science,chemistry and medicine.
文摘A compact optical nanofiber sensor enables detection of 100 nm particles in the field.This device improves our ability to track air quality with high spatiotemporal resolution.Air pollution has enormous health and economic costs,causing an estimated 7 million deaths per year1 and costing US$225 billion globally in 2013 according to the most recent data from the World Health Organization(WHO)and World Bank,respectively2.Despite this impact,air pollution levels continue to increase,with 92%of the world’s population living in environments in which WHO air quality guidelines are not met3.
