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学者姓名：王秀红
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Abstract ：
Intracellular probing at single cell resolution is key to revealing the heterogeneity of cells, learning new cell subtypes and functions, understanding the pathophysiology of disease, and ensuring precise diagnosis and treatment. Despite the best efforts, an enormous challenge remains due to the very small size, extremely low content, and dynamic microenvironment of a single cell. Whispering gallery mode (WGM) micro/nanolasers (active WGM) offer unique advantages of small mode volume, high quality factors, bright and low threshold laser emission, and narrow line width, particularly suitable for integration within a single cell. In this review, we provide a focused overview of WGM micro/nanolasers for intracellular probing. We deliver information on WGM micro/nanolaser concepts, sensing mechanism, and biocompatibility, as well as recent progress in intracellular probing applications mainly covering cellular-level sensing, molecular-level detection, and feasibility for cellular imaging. At the end, challenges and prospects of WGM micro/nanolasers for intracellular applications are discussed.
Keyword ：
Sensitivity enhancement Sensitivity enhancement Intracellular molecular quantification Intracellular molecular quantification Cell tracking Cell tracking Single cell resolution Single cell resolution Deep tissue imaging Deep tissue imaging Cellular heterogeneity Cellular heterogeneity Cell tagging Cell tagging Dynamic monitoring Dynamic monitoring WGM micro/nanolaser WGM micro/nanolaser Intracellular sensing Intracellular sensing
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| GB/T 7714 | Fu, Yiqian , Lin, Siqi , Wang, Xiu-Hong . Whispering Gallery Mode Micro/Nanolasers for Intracellular Probing at Single Cell Resolution [J]. | ACS SENSORS , 2024 , 9 (11) : 5683-5698 . |
| MLA | Fu, Yiqian 等. "Whispering Gallery Mode Micro/Nanolasers for Intracellular Probing at Single Cell Resolution" . | ACS SENSORS 9 . 11 (2024) : 5683-5698 . |
| APA | Fu, Yiqian , Lin, Siqi , Wang, Xiu-Hong . Whispering Gallery Mode Micro/Nanolasers for Intracellular Probing at Single Cell Resolution . | ACS SENSORS , 2024 , 9 (11) , 5683-5698 . |
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Abstract ：
Exosome-based liquid biopsies highlight potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. However, the existing techniques are severely limited for practical applications due to the complications of high cost, low sensitivity, tedious procedures, and large sample consumption. Herein, we report a microstructured optical fiber sensor for fast, sensitive, and accurate quantification of exosomes in blood samples of breast cancer patients. Numerical simulations are applied to demonstrate that hollow-core microstructured anti-resonant fibers (HARFs) can stringently confine light in the fiber core, ensuring strong light-matter interaction and thus maximumly amplifying the signal. Taking this advantage, a AuNPs-dsDNA assembly containing gold nanoparticles, a recognizing DNA aptamer, and a fluorescent reporter DNA sequence is fabricated followed by immobilization on the fiber wall to form a AuNPs- dsDNA-HARF sensor. Cancer-derived exosomes can be recognized and captured in the fiber channel and generate dose-dependent fluorescent signals for quantification. The microfiber sensor demonstrates enhanced sensitivity and specificity, enabling the detection of single digits of exosome particles at the nanoliter sample level. In addition, by tracking exosome phenotypic changes, the proposed fiber sensor can facilitate precise drug treatment monitoring. This work provides a robust platform for exosome-based biopsy for cancer diagnosis and prediction of therapeutic outcomes.
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| GB/T 7714 | Liu, Zihao , Zhang, Wen , Zhang, Xin et al. Microstructured Optical Fiber-Enhanced Light-Matter Interaction Enables Highly Sensitive Exosome-Based Liquid Biopsy of Breast Cancer [J]. | ANALYTICAL CHEMISTRY , 2023 , 95 (2) : 1095-1105 . |
| MLA | Liu, Zihao et al. "Microstructured Optical Fiber-Enhanced Light-Matter Interaction Enables Highly Sensitive Exosome-Based Liquid Biopsy of Breast Cancer" . | ANALYTICAL CHEMISTRY 95 . 2 (2023) : 1095-1105 . |
| APA | Liu, Zihao , Zhang, Wen , Zhang, Xin , Wang, Shijia , Xia, Zhiwen , Guo, Xiaoyan et al. Microstructured Optical Fiber-Enhanced Light-Matter Interaction Enables Highly Sensitive Exosome-Based Liquid Biopsy of Breast Cancer . | ANALYTICAL CHEMISTRY , 2023 , 95 (2) , 1095-1105 . |
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Abstract ：
Microstructured optical fibers (MOFs) provide solutions for breaking through the bottlenecks in areas of high-power transmission and high-efficiency optical waveguides. Other than transporting light waves, MOFs can synergistically combine microfluidics and optics in a single fiber with an unprecedented light path length not readily achievable by planar optofluidic configurations. Here, we demonstrate that hollow-core anti-resonant optical fibers (HcARFs) can significantly enhance Raman scattering by over three orders of magnitude (EF approximate to 5000) compared with a planar setup, due to the joint mechanisms of strong light-matter interaction in the fiber core and the cumulative effect of the fiber. The giant enhancement enables us to develop the first optical fiber sensor to achieve single cancer exosome detection via a sandwich-structured strategy. This enables a multiplexed analysis of surface proteins of exosome samples, potentially allowing an accurate identification of the cellular origin of exosomes for cancer diagnosis. Our findings could expand the applications of HcARF in many exciting areas beyond the waveguide.
Keyword ：
hollow-core anti-resonant optical fiber hollow-core anti-resonant optical fiber cancer diagnosis cancer diagnosis single exosome detection single exosome detection strong light-matter interaction strong light-matter interaction enhancement of Raman scattering enhancement of Raman scattering
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| GB/T 7714 | Xia, Zhiwen , Zhang, Xin , Yao, Jingyuan et al. Giant Enhancement of Raman Scattering by a Hollow-Core Microstructured Optical Fiber Allows Single Exosome Probing [J]. | ACS SENSORS , 2023 , 8 (4) : 1799-1809 . |
| MLA | Xia, Zhiwen et al. "Giant Enhancement of Raman Scattering by a Hollow-Core Microstructured Optical Fiber Allows Single Exosome Probing" . | ACS SENSORS 8 . 4 (2023) : 1799-1809 . |
| APA | Xia, Zhiwen , Zhang, Xin , Yao, Jingyuan , Liu, Zihao , Jin, Yulong , Yin, Huabing et al. Giant Enhancement of Raman Scattering by a Hollow-Core Microstructured Optical Fiber Allows Single Exosome Probing . | ACS SENSORS , 2023 , 8 (4) , 1799-1809 . |
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Abstract ：
The authors introduce an active-mode optical microcavity sensor with enhanced sensitivity via Forster resonant energy transfer. Changes in lasing wavelengths of both donor and acceptor enable quantitative molecular analysis and real-time monitoring of intracellular molecules. Single cell analysis is crucial for elucidating cellular diversity and heterogeneity as well as for medical diagnostics operating at the ultimate detection limit. Although superbly sensitive biosensors have been developed using the strongly enhanced evanescent fields provided by optical microcavities, real-time quantification of intracellular molecules remains challenging due to the extreme low quantity and limitations of the current techniques. Here, we introduce an active-mode optical microcavity sensing stage with enhanced sensitivity that operates via Forster resonant energy transferring (FRET) mechanism. The mutual effects of optical microcavity and FRET greatly enhances the sensing performance by four orders of magnitude compared to pure Whispering gallery mode (WGM) microcavity sensing system. We demonstrate distinct sensing mechanism of FRET-WGM from pure WGM. Predicted lasing wavelengths of both donor and acceptor by theoretical calculations are in perfect agreement with the experimental data. The proposed sensor enables quantitative molecular analysis at single cell resolution, and real-time monitoring of intracellular molecules over extended periods while maintaining the cell viability. By achieving high sensitivity at single cell level, our approach provides a path toward FRET-enhanced real-time quantitative analysis of intracellular molecules.
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| GB/T 7714 | Wang, Yaping , Lang, Marion C. , Lu, Jinsong et al. Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity [J]. | NATURE COMMUNICATIONS , 2022 , 13 (1) . |
| MLA | Wang, Yaping et al. "Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity" . | NATURE COMMUNICATIONS 13 . 1 (2022) . |
| APA | Wang, Yaping , Lang, Marion C. , Lu, Jinsong , Suo, Mingqian , Du, Mengcong , Hou, Yubin et al. Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity . | NATURE COMMUNICATIONS , 2022 , 13 (1) . |
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Abstract ：
Whispering gallery mode is a type of optical mode where photons move in a quasi-two-dimensional plane, and the total reflection occurs at the boundary of the microcavity without reflecting out of the cavity. This mode has a high Q value and small mode volume, and it is extremely sensitive to changes in the surrounding environment. A broadband fluorescence can be transformed into narrow-spectrum laser output by using the whispering gallery mode. In this paper, polystyrene microspheres doped with the dragon green fluorescent dye arc used as whispering gallery mode optical microcavity. Through the phagocytosis of cells, the fluorescent microspheres reach inside cells and then arc pumped by nanosecond pulsed laser to achieve the output of whispering gallery mode laser in cells. In comparison with the laser output in the pure-water environment, a redshift of the intracellular fluorescent microsphere whispering gallery mode resonance emission can be observed, and the redshift is related to cell type; therefore, it can be used for unlabeled identification of cell type.
Keyword ：
biotechnology biotechnology wavelength shift wavelength shift endocytosis endocytosis microsphere cavity microsphere cavity biosensing biosensing whispering gallery mode whispering gallery mode
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| GB/T 7714 | Wang Yaping , Wang Xiuhong , Wang Pu . Identifying Single Cell Types via Whispering Gallery Mode Optical Microcavities [J]. | CHINESE JOURNAL OF LASERS-ZHONGGUO JIGUANG , 2020 , 47 (2) . |
| MLA | Wang Yaping et al. "Identifying Single Cell Types via Whispering Gallery Mode Optical Microcavities" . | CHINESE JOURNAL OF LASERS-ZHONGGUO JIGUANG 47 . 2 (2020) . |
| APA | Wang Yaping , Wang Xiuhong , Wang Pu . Identifying Single Cell Types via Whispering Gallery Mode Optical Microcavities . | CHINESE JOURNAL OF LASERS-ZHONGGUO JIGUANG , 2020 , 47 (2) . |
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Abstract ：
Photoacoustic imaging, a novel biomedical imaging technique that combines the advantages of optical imaging and acoustic imaging, offers high-resolution biological tissue imaging to facilitate the observation of deeper imaging sites. In other words, it breaks the "soft limit" of conventional optical bioimaging techniques. However, many diseases, especially in the early stage, present no obvious photoacoustic contrast; therefore, it is crucial to identify effective exogenous photoacoustic contrast agents. Here we introduce a novel two-dimensional material, antimonene nanoflakes (AMNFs), which demonstrates great optical absorption from 300 nm to 900 nm as well as excellent photothermal conversion efficiency and photoacoustic performance. This material is expected to be useful as a contrast agent, helping to achieve excellent photoacoustic imaging of ultra-small tumors in vivo.
Keyword ：
biological optics biological optics two-dimensional materials two-dimensional materials tumor imaging tumor imaging contrast agent contrast agent photoacoustic imaging photoacoustic imaging
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| GB/T 7714 | Yu Jingwen , Wang Xiuhong , Feng Jinchao et al. Antimonene Nanoflakes as a Photoacoustic Imaging Contrast Agent for Tumor in vivo Imaging [J]. | CHINESE JOURNAL OF LASERS-ZHONGGUO JIGUANG , 2020 , 47 (2) . |
| MLA | Yu Jingwen et al. "Antimonene Nanoflakes as a Photoacoustic Imaging Contrast Agent for Tumor in vivo Imaging" . | CHINESE JOURNAL OF LASERS-ZHONGGUO JIGUANG 47 . 2 (2020) . |
| APA | Yu Jingwen , Wang Xiuhong , Feng Jinchao , Zhang Na , Wang Pu . Antimonene Nanoflakes as a Photoacoustic Imaging Contrast Agent for Tumor in vivo Imaging . | CHINESE JOURNAL OF LASERS-ZHONGGUO JIGUANG , 2020 , 47 (2) . |
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Abstract ：
Hollow core anti-resonant fiber (HARE) has found a handful applications in optical communications, nonlinear optics and high power delivery. The intrinsic property of the fiber also renders it an ideal candidate for biosensing, which has not been explored intensively. Herein, we demonstrate an optical fiber sensing platform, taking advantages of the state-of-the-art HARP technology and superior physicochemical properties of 2D material black phosphorus, for ultra-sensitive detection of bisphenol A (BPA) in blood and environmental samples. The specially designed HARP can not only achieve broadband transmission of light, but also confine light in the low refractive-index liquid core, ensuring maximum overlap of light and liquid core. Modification of the inner surface of HARP with 2D black phosphorus nanoflakes functionalized with fluorescently labeled BPA-specific aptamer provides a smart sensing interface enabling highly selective detection of BPA via measuring the fluorescence. The limit of detection is 1.69pM, which is more than two orders of magnitude enhancement compared to the conventional plate assay. The proposed assay is not interfered with the BPA analogues BPB and BPS. The long optical path with tight optical confinement greatly enhances the analyte-light interaction and improves the sensitivity of the sensing platform. The proposed sensing platform can be further developed for versatile applications.
Keyword ：
Hollow core anti-resonant fiber Hollow core anti-resonant fiber Black phosphorus Black phosphorus Bisphenol A Bisphenol A Aptamer Aptamer Sensor Sensor
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| GB/T 7714 | Qiao, Pengfei , Wang, Xiu-Hong , Gao, Shoufei et al. Integration of black phosphorus and hollow-core anti-resonant fiber enables two-order magnitude enhancement of sensitivity for bisphenol A detection [J]. | BIOSENSORS & BIOELECTRONICS , 2020 , 149 . |
| MLA | Qiao, Pengfei et al. "Integration of black phosphorus and hollow-core anti-resonant fiber enables two-order magnitude enhancement of sensitivity for bisphenol A detection" . | BIOSENSORS & BIOELECTRONICS 149 (2020) . |
| APA | Qiao, Pengfei , Wang, Xiu-Hong , Gao, Shoufei , Yin, Xiaoyan , Wang, Yingying , Wang, Pu . Integration of black phosphorus and hollow-core anti-resonant fiber enables two-order magnitude enhancement of sensitivity for bisphenol A detection . | BIOSENSORS & BIOELECTRONICS , 2020 , 149 . |
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Abstract ：
In this paper, we present a novel optical microfluidic cytometry scheme for label-free detection of cells that is based on the self-mixing interferometry (SMI) technique. This device enables simple, fast and accurate detection of the individual cell characteristics and efficient cell type classification. We also propose a novel parameter to classify the cell or particle size. Artificial polystyrene beads and human living cells were measured using this system, and the SMI signal properties were statistically evaluated. The capability of the proposed cytometer for cell type discrimination and size classification has been validated by the measurement results. Our study can provide a very simple technique for cell enumeration and classification without any extra devices such as high-speed camera, photomultiplier and spectrometer. Moreover, the fluorescence staining operation which is necessary in traditional flow cytometry methods is not required either in our system.
Keyword ：
flow cytometry flow cytometry self-mixing interferometry self-mixing interferometry label-free label-free microfluidic chip microfluidic chip hydrodynamic focusing hydrodynamic focusing
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| GB/T 7714 | Zhao, Yu , Shen, Xuefei , Zhang, Menglei et al. Self-Mixing Interferometry-Based Micro Flow Cytometry System for Label-Free Cells Classification [J]. | APPLIED SCIENCES-BASEL , 2020 , 10 (2) . |
| MLA | Zhao, Yu et al. "Self-Mixing Interferometry-Based Micro Flow Cytometry System for Label-Free Cells Classification" . | APPLIED SCIENCES-BASEL 10 . 2 (2020) . |
| APA | Zhao, Yu , Shen, Xuefei , Zhang, Menglei , Yu, Jingwen , Li, Jintao , Wang, Xiuhong et al. Self-Mixing Interferometry-Based Micro Flow Cytometry System for Label-Free Cells Classification . | APPLIED SCIENCES-BASEL , 2020 , 10 (2) . |
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Abstract ：
Whispering gallery mode is a type of optical mode where photons move in a quasi-two-dimensional plane, and the total reflection occurs at the boundary of the microcavity without reflecting out of the cavity. This mode has a high Q value and small mode volume, and it is extremely sensitive to changes in the surrounding environment. A broadband fluorescence can be transformed into narrow-spectrum laser output by using the whispering gallery mode. In this paper, polystyrene microspheres doped with the dragon green fluorescent dye are used as whispering gallery mode optical microcavity. Through the phagocytosis of cells, the fluorescent microspheres reach inside cells and then are pumped by nanosecond pulsed laser to achieve the output of whispering gallery mode laser in cells. In comparison with the laser output in the pure-water environment, a redshift of the intracellular fluorescent microsphere whispering gallery mode resonance emission can be observed, and the redshift is related to cell type; therefore, it can be used for unlabeled identification of cell type. © 2020, Chinese Lasers Press. All right reserved.
Keyword ：
Optical pumping Optical pumping Microcavities Microcavities Red Shift Red Shift Antigen-antibody reactions Antigen-antibody reactions Fluorescence Fluorescence Microspheres Microspheres Cytology Cytology Molecular biology Molecular biology Polystyrenes Polystyrenes Optical resonators Optical resonators Pulsed lasers Pulsed lasers Biotechnology Biotechnology Ultrafast lasers Ultrafast lasers Whispering gallery modes Whispering gallery modes Cells Cells
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| GB/T 7714 | Wang, Yaping , Wang, Xiuhong , Wang, Pu . Identifying Single Cell Types via Whispering Gallery Mode Optical Microcavities [J]. | Chinese Journal of Lasers , 2020 , 47 (2) . |
| MLA | Wang, Yaping et al. "Identifying Single Cell Types via Whispering Gallery Mode Optical Microcavities" . | Chinese Journal of Lasers 47 . 2 (2020) . |
| APA | Wang, Yaping , Wang, Xiuhong , Wang, Pu . Identifying Single Cell Types via Whispering Gallery Mode Optical Microcavities . | Chinese Journal of Lasers , 2020 , 47 (2) . |
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Abstract ：
Photoacoustic imaging, a novel biomedical imaging technique that combines the advantages of optical imaging and acoustic imaging, offers high-resolution biological tissue imaging to facilitate the observation of deeper imaging sites. In other words, it breaks the 'soft limit' of conventional optical bioimaging techniques. However, many diseases, especially in the early stage, present no obvious photoacoustic contrast; therefore, it is crucial to identify effective exogenous photoacoustic contrast agents. Here we introduce a novel two-dimensional material, antimonene nanoflakes (AMNFs), which demonstrates great optical absorption from 300 nm to 900 nm as well as excellent photothermal conversion efficiency and photoacoustic performance. This material is expected to be useful as a contrast agent, helping to achieve excellent photoacoustic imaging of ultra-small tumors in vivo. © 2020, Chinese Lasers Press. All right reserved.
Keyword ：
Tumors Tumors Light absorption Light absorption Photoacoustic effect Photoacoustic effect Medical imaging Medical imaging
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| GB/T 7714 | Yu, Jingwen , Wang, Xiuhong , Feng, Jinchao et al. Antimonene Nanoflakes as a Photoacoustic Imaging Contrast Agent for Tumor in vivo Imaging [J]. | Chinese Journal of Lasers , 2020 , 47 (2) . |
| MLA | Yu, Jingwen et al. "Antimonene Nanoflakes as a Photoacoustic Imaging Contrast Agent for Tumor in vivo Imaging" . | Chinese Journal of Lasers 47 . 2 (2020) . |
| APA | Yu, Jingwen , Wang, Xiuhong , Feng, Jinchao , Zhang, Na , Wang, Pu . Antimonene Nanoflakes as a Photoacoustic Imaging Contrast Agent for Tumor in vivo Imaging . | Chinese Journal of Lasers , 2020 , 47 (2) . |
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