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Experimental robobiological physics can bring insights into biological evolution. We present a development of hybrid analog/digital autonomous robots with mutable diploid dominant/recessive 6-byte genomes. The robots are capable of death, rebirth, and breeding. We map the quasi-steady-state surviving local density of the robots onto a multidimensional abstract "survival landscape." We show that robot death in complex, self-adaptive stress landscapes proceeds by a general lowering of the robotic genetic diversity, and that stochastically changing landscapes are the most difficult to survive.
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Robótica , Animales , Mamíferos , Modelos Genéticos , Mutación , Dinámica Poblacional , Probabilidad , Selección GenéticaRESUMEN
Fiber-integrated micro/nanostructures play a crucial role in modern industry, mainly owing to their compact size, high sensitivity, and resistance to electromagnetic interference. However, the three-dimensional manufacturing of fiber-tip functional structures beyond organic polymers remains challenging. It is essential to construct fiber-integrated inorganic silica with designed functional nanostructures for microsystem applications. Here, we develop a strategy for the 3D nanolithography of fiber-integrated silica from hybrid organic-inorganic materials by ultrafast laser-induced multiphoton absorption. Without silica nanoparticles and polymer additives, the acrylate-functionalized precursors can be locally cross-linked through a nonlinear effect. Followed by annealing at low temperature, the as-printed micro/nanostructures are transformed to high-quality silica with sub-100 nm resolution. Silica microcantilever probes and microtoroid resonators are directly integrated onto the optical fiber, showing strong thermal stability and quality factors. This work provides a promising strategy for fabricating desired fiber-tip silica micro/nanostructures, which is helpful for the development of integrated functional device applications.
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Solvatochromes have gained great attention because of their unique roles in monitoring biomolecular location, interaction, and dynamics. Particularly, solvatochromes presenting both red-shifting excitation and dual-band switchable emission are in great demand yet significantly difficult to come true. In this article, we disclose an aromatic alcohol-based pH-sensitive chromophore NIR-HBT that not only presents red-shifting excitation and solvent-dependent dual-band emission but also shows high photostability and excellent brightness. To the best of our knowledge, this is the first solvatochrome to simultaneously display these optical properties. Especially, in contrast to the reported dual-band solvatochromes whose solvatochromism is achieved by affecting their excited state behaviors, the solvatochromism of NIR-HBT is realized by modulating its ground state proton dissociation, which is a new solvatochromic mechanism that has not been reported. Furthermore, based on the dual-band solvatochromism of NIR-HBT and its intrinsic binding ability to GQs, near-infrared ratiometric detection of GQs is achieved. These results indicate that NIR-HBT is an attractive solvatochrome that can be used to develop near-infrared ratiometric biosensors for biological research. More broadly, the discovered solvatochromic mechanism can also open new horizons for exploring the solvatochrome.
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Two-photon fluorescence lifetime microscopy (TP-FLIM) is a powerful quantitative imaging technique that characterizes and analyzes the structure and function of biological samples through a combination of intensity and lifetime imaging. Because TP-FLIM is independent of the fluorescence signal intensity and the fluorophore concentration, it is widely used in high-throughput, high-content drug screening and clinical diagnostics. Second harmonic generation (SHG) imaging technology has the advantages of high spatial resolution and imaging depth inherent to nonlinear optical imaging. Second harmonics often appear in noncentrosymmetric structures. Collagen tissue in biological organisms is a good example of these structures, showing strong harmonic effects. Therefore, SHG has been widely used for imaging of specific tissue structure imaging. TP-FLIM technology is highly sensitive for quantitatively detecting changes in microenvironments. The objective of this study is to examine pathological pulmonary fibrosis slices using a combined approach of TP-FLIM and SHG technology. The fluorescence lifetime data of pulmonary collagen fibers are analyzed by using phasor plot analysis methods, and normal collagen fibers and fibrotic collagen fibers are distinguished by calculating the aspect ratio from the SHG images formed by the collagen fibers. Our study provides a new method for a deeper understanding of the pathological mechanisms and clinical diagnosis of pulmonary fibrosis and other collagen fiber-related disorders.
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To enhance our comprehension of the fundamental mechanisms driving tumor metabolism and metastasis, it is essential to dynamically monitor intratumoral lipid droplet (LD) and collagen processes in vivo. Traditional LD analysis in tumors predominantly relies on observations of in vitro cells or tissue slices, which unfortunately hinder real-time insights into the dynamic behavior of LDs during in vivo tumor progression. In this study, we developed a dual-modality imaging technique that combines coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy for in vivo monitoring of tumor LDs and collagen alterations, assisted by a murine breast cancer 4T1 cell-based dorsal skinfold window. Specifically, we accomplished real-time observations and quantitative analysis of the LD size, density, and collagen alignment within living tumors through CARS/SHG imaging. Additionally, our findings demonstrate that real-time LD monitoring provides a valuable means of assessing the efficacy of anticancer drugs in vivo. We evaluated the impact of adipose activators on lipid metabolism, oxidative stress, and tumor suppression by monitoring changes in LD size and density. Overall, this study highlights the potential of dual-modality CARS/SHG microscopy as a sensitive and flexible tool for antitumor therapeutic strategies.
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Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta-derived MSCs (P-MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co-inoculation of LLC and P-MSCs (LLC + P-MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day. This is explained by the fact of a decrease in the secretion of proangiogenic factors during in vitro co-cultivation of an equal amount of LLC and P-MSCs. When P-MSCs are intravenously (i.v.) injected in the mice with developing LLC (LLC + P-MSCs(i.v.)), the tumor growth and angiogenesis are stimulated on the 15th day. A highly activated secretion of proangiogenic factors by P-MSCs in a similar in vitro model can explain this. In both the models compared to the control on the 23rd day, there is no significant difference in the tumor growth, while angiogenesis remains correspondingly decelerated or stimulated. However, in both the models, the total volume and number of lung metastases constantly increase compared to the control: it is mainly due to small-size metastases for LLC + P-MSCs(i.v.) and larger ones for LLC + P-MSCs. The increase in the rate of LLC cell dissemination after the injection of P-MSCs is explained by the disordered polyploidy and chromosomal instability, leading to an increase in migration and invasion of cancer cells. After LLC + P-MSCs co-inoculation, the tumor cell karyotype has the most complex and heterogeneous chromosomal structure. These findings indicate a bidirectional effect of P-MSCs on the growth of LLC in the early periods after injection, depending on the injection method, and, correspondingly, the number of contacting cells. However, regardless of the injection method, P-MSCs are shown to increase LLC aggressiveness related to cancer-associated angiogenesis and metastasis activation in the long term.
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Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Células Madre Mesenquimatosas , Humanos , Ratones , Animales , Carcinoma Pulmonar de Lewis/patología , Ratones Endogámicos C57BL , Neoplasias Pulmonares/patologíaRESUMEN
Polarization-resolved second-harmonic generation (PSHG) microscopy is widely used in investigating the structural and morphological alterations of collagen. However, the resolution of second-harmonic generation (SHG) imaging remains constrained by optical diffraction, resulting in the polarization extraction of collagen characteristics from the average properties of collagen fibers. In this study, multifocal structured illumination microscopy (MSIM) was combined with PSHG to achieve polarization-resolved super-resolution imaging of second-harmonic generation signals. For the first time to our knowledge, periodic structures with an average pitch of 277â nm were observed in mouse tail tendons using optical microscopy, and the orientation angle of fibrils within each period was found to exhibit an alternating arrangement along the axis in a regular pattern.
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Single-shot spatial light interference microscopy (SS-SLIM) with a pair of non-polarizing beam splitters is proposed for substantially enhancing the speed and efficiency of conventional SLIM systems. Traditional methods are limited by the need for multiple-frame serial modulation and acquisition by spatial light modulators and detectors. Our approach integrates non-polarizing beam splitters to simultaneously capture four phase-shifted intensity images, increasing the imaging speed by at least fourfold while maintaining high quality. This capability is crucial for effectively monitoring the dynamic fluctuations of red blood cell membranes. Furthermore, the potential applications of the SS-SLIM system in biomedical research are demonstrated, particularly in scenarios requiring high temporal resolution and label-free imaging.
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Sapphire fiber Bragg grating (SFBG) is a promising high-temperature strain sensor due to its melting point of 2045°C. However, the study on the long-term stability of SFBG under high temperature with an applied strain is still missing. In this paper, we reported for the first time to our knowledge on the critical temperature point of plastic deformation of the SFBG and demonstrated that the SFBG strain sensor can operate stably below 1200°C. At first, we experimentally investigated the topography and the spectral characteristics of the SFBG at different temperatures (i.e., 25°C, 1180°C, and 1600°C) with applied 650⠵ε. The reflection peak of the SFBG exhibits a redshift of about 15â nm and broadens gradually within 8â h at 1600°C, and the tensile force value decreases by 0.60â N in this process. After the test, the diameter of the SFBG region decreases from 100 to 88.6â µm, and the grating period is extended from 1.76 to 1.79â µm. This indicates that the plastic deformation of the SFBG happened indeed, and it was elongated irreversibly. Moreover, the stability of the Bragg wavelength of the SFBG under high temperature with the applied strain was evaluated. The result demonstrates the SFBG can be used to measure strain reliably below 1200°C. Furthermore, the strain experiments of SFBG at 25°C, 800°C, and 1100°C have been carried out. A linear fitting curve with high fitness (R2 > 0.99) and a lower strain measurement error (<15⠵ε) can be obtained. The aforementioned results make SFBG promising for high-temperature strain sensing in many fields, such as, power plants, gas turbines, and aerospace vehicles.
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This publisher's note contains a correction to Opt. Lett.48, 3219 (2023)10.1364/OL.486644.
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We demonstrate a novel, to the best of our knowledge, high-temperature pressure sensor based on a highly birefringent fiber Bragg grating (Hi-Bi FBG) fabricated in a dual side-hole fiber (DSHF). The Hi-Bi FBG is generated by a femtosecond laser directly written sawtooth structure in the DSHF cladding along the fiber core through the slow axis (i.e., the direction perpendicular to the dual-hole axis). The sawtooth structure serves as an in-fiber stressor and also generates Bragg resonance due to its periodicity. The DSHF was etched by hydrofluoric acid to increase its pressure sensitivity, and the diameter of two air holes was enlarged from 38.2 to 49.6â µm. A Hi-Bi FBG with a birefringence of up to 1.8 × 10-3 was successfully created in the etched DSHF. Two distinct reflection peaks could be observed by using a commercial FBG interrogator. Moreover, pressure measurement from 0 to 3â MPa at a high temperature of 700°C was conducted by monitoring the birefringence-induced peak splits and achieved a high-pressure sensitivity of -21.2â pm/MPa. The discrimination of the temperature and pressure could be realized by simultaneously measuring the Bragg wavelength shifts and peak splits. Furthermore, a wavelength-division-multiplexed (WDM) Hi-Bi FBG array was also constructed in the DSHF and was used for quasi-distributed high-pressure sensing up to 3â MPa. As such, the proposed femtosecond laser-inscribed Hi-Bi FBG is a promising tool for high-temperature pressure sensing in harsh environments, such as aerospace vehicles, nuclear reactors, and petrochemical industries.
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In the realm of biological research, the invention of super-resolution microscopy (SRM) has enabled the visualization of ultrafine sub-cellular structures and their functions in live cells at the nano-scale level, beyond the diffraction limit, which has opened up a new window for advanced biomedical studies to unravel the complex unknown details of physiological disorders at the sub-cellular level with unprecedented resolution and clarity. However, most of the SRM techniques are highly reliant on the personalized special photophysical features of the fluorophores. In recent times, there has been an unprecedented surge in the development of robust new fluorophore systems with personalized features for various super-resolution imaging techniques. To date, xanthene, cyanine, oxazine and BODIPY cores have been authoritatively utilized as the basic fluorophore units in most of the small-molecule-based organic fluorescent probe designing strategies for SRM owing to their excellent photophysical characteristics and easy synthetic acquiescence. Since the future of next-generation SRM studies will be decided by the availability of advanced fluorescent probes and these four fluorescent building blocks will play an important role in progressive new fluorophore design, there is an urgent need to review the recent advancements in designing fluorophores for different SRM methods based on these fluorescent dye cores. This review article not only includes a comprehensive discussion about the recent developments in designing fluorescent probes for various SRM techniques based on these four important fluorophore building blocks with special emphasis on their effective integration into live cell super-resolution bio-imaging applications but also critically evaluates the background of each of the fluorescent dye cores to highlight their merits and demerits towards developing newer fluorescent probes for SRM.
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Second-harmonic generation (SHG) is a noninvasive imaging technique that enables the exploration of physiological structures without the use of an exogenous label. However, traditional SHG imaging is limited by optical diffraction, which restricts the spatial resolution. To break this limitation, we developed a novel approach called multifocal structured illumination microscopy-SHG (MSIM-SHG). By combination of SHG with MSIM, SHG-based super-resolution imaging of material molecules can be achieved, and this SHG super-resolution imaging has a wide range of applications for biological tissues and cells. MSIM-SHG achieved a lateral full width at half-maximum (fwhm) of 147 ± 13 nm and an axial fwhm of 493 ± 47 nm by imaging zinc oxide (ZnO) particles. Furthermore, MSIM-SHG was utilized to quantify collagen fiber alignment in various tissues such as the ovary, muscle, heart, kidney, and cartilage, demonstrating its feasibility for identifying collagen characteristics. MSIM-SHG has potential as a powerful tool for clinical diagnosis and biological research.
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Microscopía , Microscopía de Generación del Segundo Armónico , Femenino , Humanos , Iluminación , Matriz Extracelular , CorazónRESUMEN
Intravital luminescence imaging in the second near-infrared window (NIR-II) enables noninvasive deep-tissue imaging with high spatiotemporal resolution of live mammals because of the properties of suppressed light scattering and diminished autofluorescence in the long-wavelength region. Herein, we present the synthesis of a downconversion luminescence rare-earth nanocrystal with a core-shell-shell structure (NaYF4@NaYbF4:Er,Ce@NaYF4:Ca). The structure efficiently maximized the doping concentration of the sensitizers and increased Er3+ luminescence while preventing cross relaxation. Furthermore, Ce3+ doping in the middle layer efficiently limited the upconversion pathway and increased downconversion by 24-fold to produce bright 1550 nm luminescence under 975 nm excitation. Finally, optimizing the inert shell coating of NaYF4:Ca and liposome encapsulation reduced the luminescence quenching impact by water and improved biological metabolism. Thus, our synthesized biocompatible, ultrabright NIR-II probes provide high contrast and resolution for through-scalp and through-skull luminescence imaging of mice cerebral vasculature without craniotomy as well as imaging of mouse hindlimb microvessels.
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Metales de Tierras Raras , Nanopartículas , Ratones , Animales , Metales de Tierras Raras/química , Diagnóstico por Imagen/métodos , Nanopartículas/química , Luminiscencia , MamíferosRESUMEN
Three-dimensional (3D) cultured tumor spheroid models, as one type of in vitro model, have been proven to have more physiological similarities to in vivo animal models than cells in 2D cultures. Tumor spheroids have been widely used in preclinical experiments of anticancer drug treatments, providing reliable data in pathogenetic research. Currently, different 3D cell culture conditions, even in the same cell line, generate heterogeneous spheroids in morphology and size, resulting in different growth rates or drug-killing responses. Therefore, the measurement and evaluation of the properties of tumor spheroids have become highly demanding tasks with huge challenges. For functional characterization of tumor spheroids, the microenvironment sensitivity and quantitative properties of the fluorescence lifetime microscopy imaging (FLIM) technique have great advantages for improving the reliability of cell physiological testing. In this paper, we have proposed a FLIM-based approach to observe the lipid components labeled with Nile red of cells in both 3D and 2D cultures. The imaging data and analysis provided basic information on the sizes, morphologies, and cell membrane fluorescence lifetime values of the tumor spheroids. FLIM data showed that the microenvironment of the cell membrane in the 3D model was largely altered compared to that in the 2D culture. Next, a series of parameters that may influence the lipid components of tumor cells and tumor spheroids were tested by FLIM, including pH, viscosity, and polarity. The results showed that pH and viscosity contributed little to the change in fluorescence lifetime values, while the change in cell membrane polarity was the main cause of the alterations in fluorescence lifetime data, suggesting that cell membrane polarity should be considered a marker in distinguishing tumor spheroids from cellular physiological status. In conclusion, this FLIM-based testing process has been proven to be a quantitative method for measuring the differences between the cells of the 3D model from the 2D cultured cells with satisfactory sensitivity and accuracy, providing a high potential standard assay in the quality evaluation and control of tumor spheroids for future anticancer drug development.
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Antineoplásicos , Esferoides Celulares , Animales , Reproducibilidad de los Resultados , Células Cultivadas , Microscopía Fluorescente , LípidosRESUMEN
The conventional approach in cancer nanomedicine involves advanced drug nanocarriers delivering preloaded therapeutics to targeted tumor sites to maximize drug efficiency. However, both cancer drugs and nanocarriers inevitably produce side effects and systemic toxicity. Herein, hemoglobin nanocrystals (HbC) as drug-free theranostic nanoformulations with the tumor microenvironment (TME) activated diagnostic and therapeutic abilities towards colon tumors are introduced. HbC can release Fe2+ oxidized to Fe3+ in the Fenton reaction with tumor endogenous H2 O2 , concurrently with the generation of cytotoxic hydroxyl radicals (â¢OH) that allow for chemodynamic therapy (CDT). Furthermore, in situ-produced Fe3+ reacts with colon tumor-abundant H2 S, resulting in the production of Fe1- x S, which provides magnetic resonance imaging (MRI) contrast and allows for NIR light-inducible photothermal therapy (PTT). In vitro and in vivo studies revealed that HbC produced CDT towards 4T1 tumors, and MRI-guided, synergistically enhanced combination of CDT and PTT against H2 S abundant colon tumors (CT26), with negligible toxicity towards normal tissues, enlightening HbC as highly efficient and biocompatible TME activated theranostic nanoplatform specific against colon cancer without any traditional drugs and drug carriers.
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Antineoplásicos , Neoplasias del Colon , Nanopartículas , Neoplasias , Humanos , Línea Celular Tumoral , Medicina de Precisión , Nanopartículas/química , Antineoplásicos/farmacología , Neoplasias/terapia , Neoplasias del Colon/tratamiento farmacológico , Microambiente Tumoral , Nanomedicina Teranóstica , Peróxido de Hidrógeno/farmacologíaRESUMEN
We propose polarization-sensitive second-harmonic generation microscopy based on off-axis interferometry (OI-PSHG) by recording the complex field of a wide-field second-harmonic generation (SHG) image and performing polarization measurements. With the ability to record the SHG signals associated with different positions simultaneously, the proposed method exhibits a higher imaging frame rate than raster scanning-based SHG microscopy. The molecular orientation (in terms of their symmetric axis) of tendon collagen fibrils and myosin in muscle is resolved in three dimensions from a subset of polarization-resolved SHG holograms. With the present configuration, it takes approximately 0.01 s to acquire an image with 128 × 128 pixels, which is mainly limited by the excitation power density for wide-field illumination. For the same data throughput using pixel-by-pixel scanning, 0.16-s-long acquisition is required, with the pixel dwell time of 10 µs. Offering the ability to perform wide-field imaging and polarization measurements, the present work lays the foundation for fast SHG microscopy using complex deconvolution and harmonic tomography.
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In vivo imaging and accurate identification of amyloid-ß (Aß) plaque are crucial in Alzheimer's disease (AD) research. In this work, we propose to combine the coherent anti-Stokes Raman scattering (CARS) microscopy, a powerful detection technology for providing Raman spectra and label-free imaging, with deep learning to distinguish Aß from non-Aß regions in AD mice brains in vivo. The 1D CARS spectra is firstly converted to 2D CARS figures by using two different methods: spectral recurrence plot (SRP) and spectral Gramian angular field (SGAF). This can provide more learnable information to the network, improving the classification precision. We then devise a cross-stage attention network (CSAN) that automatically learns the features of Aß plaques and non-Aß regions by taking advantage of the computational advances in deep learning. Our algorithm yields higher accuracy, precision, sensitivity and specificity than the results of conventional multivariate statistical analysis method and 1D CARS spectra combined with deep learning, demonstrating its competence in identifying Aß plaques. Last but not least, the CSAN framework requires no prior information on the imaging modality and may be applicable to other spectroscopy analytical fields.
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Enfermedad de Alzheimer , Aprendizaje Profundo , Ratones , Animales , Espectrometría Raman , Péptidos beta-Amiloides/análisis , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Microscopía Óptica no Lineal , Placa Amiloide/diagnóstico por imagen , EncéfaloRESUMEN
We propose and experimentally demonstrate a femtosecond laser plane-by-plane (Pl-b-Pl) technology for inscription of high-quality fiber Bragg gratings (FBGs). The spherical aberration (SA) was introduced to elongate the focal volume, and then combined with the scanning process, an expanded rectangular refractive index modification (RIM) region can be achieved. Such RIM regions exhibit a length of 15â µm and a width of 14â µm. Note that it consists of a negative region and a positive region. We have systematically studied the influence of the overlap between the RIM region and fiber core on the spectrum of FBG. After optimizing, the core of a conventional single-mode fiber (SMF) is covered completely by using the positive RIM region, resulting in a significant enhancement of the coupling strength coefficient (i.e., 3177.6â m-1). A 500â µm long FBG assembled by using these RIM regions can achieve a high reflectivity of 95.83%. Moreover, the cladding mode resonances in transmission spectrum are suppressed thoroughly, since the localized effect in RIM region was avoided. In addition, this FBG exhibits a high birefringence of 2.13 × 10-4. Therefore, the proposed fabrication method can be used to inscribe high-quality FBGs that could be used in many fields such as communication, fiber laser, polarization-selective filtering and multi-parameter sensing.
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There are urgent demands of ultraviolet (UV) photodetectors with high sensitivity and fast response due to the wide application of ultraviolet light in the fields of medical treatment, space exploration, optical communication and semiconductor industry. The response speed of traditional ZnO-based UV photodetectors is always limited by the carrier mobility and electrical resistance caused by the external circuits. Utilizing the all-optical detection method may replace the complex circuit structure and effectively improve the response speed of photodetectors. Here, a fast-response fiber-optic UV photodetector is proposed, where a ZnO micro-pillar is fixed on the end face of a fiber-tip and acts as a Fabry-Pérot interferometer (FPI). Under the irradiation of UV light, the photo-generated carriers change the refractive index of the ZnO micro-pillar, leading to a redshift of the interference wavelengths of the ZnO FPI. To enhance this effect, a discontinuous Ag film with an island-like structure is coated on the surface of ZnO micro-pillars through magnetron sputtering, and therefore the sensitivity of the proposed device achieves to 1.13â nm/(W·cm-2), which is 3.9 times higher than that of without Ag-decoration, due to the intensification of photo-carrier change with the help of the Schottky junction formed between Ag film and ZnO micro-pillar. Meanwhile, since the response speed of the proposed device is mainly determined by the temporal RI change of ZnO micro-pillar, the fiber-optic UV photodetector also shows very fast response with a rise time of 35â ns and a decay time of 40 µs. The demonstrated structure takes full advantage of optical fiber devices, exhibiting compactness, flexibility, fast response and immune to electromagnetic interference, which paves a new way for the next generation of photodetection devices.