Image scanning microscopy(ISM)is a promising imaging technique that offers sub-diffraction-limited resolution and optical sectioning.Theoretically,ISM can improve the optical resolution by a factor of two through pixe...Image scanning microscopy(ISM)is a promising imaging technique that offers sub-diffraction-limited resolution and optical sectioning.Theoretically,ISM can improve the optical resolution by a factor of two through pixel reassignment and deconvolution.Multifocal array illumination and scanning have been widely adopted to implement ISM because of their simplicity.Conventionally,digital micromirror devices(DMDs)1 and microlens arrays(MLAs)2,3 have been used to generate dense and uniform multifocal arrays for ISM,which are critical for achieving fast imaging and high-quality ISM reconstruction.However,these approaches have limitations in terms of cost,numerical aperture(NA),pitch,and uniformity,making it challenging to create dense and high-quality multifocal arrays at high NA.To overcome these limitations,we introduced a novel multifocal metalens design strategy called the hybrid multiplexing method,which combines two conventional multiplexing approaches:phase addition and random multiplexing.Through numerical simulations,we demonstrate that the proposed method generates more uniform and denser multifocal arrays than conventional methods,even at small pitches.As a proof of concept,we fabricated a multifocal metalens generating 40×40 array of foci with a 3μm pitch and NA of 0.7 operating at a wavelength of 488 nm and then constructed the multifocal metalens-based ISM(MMISM).We demonstrated that MMISM successfully resolved sub-diffraction-limited features in imaging of microbead samples and forebrain organoid sections.The results showed that MMISM imaging achieved twice the diffraction-limited resolution and revealed clearer structural features of neurons compared to wide-field images.We anticipate that our novel design strategy can be widely applied to produce multifunctional optical elements and replace conventional optical elements in specialized applications.展开更多
Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy.Lipid nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonst...Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy.Lipid nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 pandemic.This study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid tumor.The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication.Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth inhibition.These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.展开更多
Introduction of the stepwise phase dispersion compensation layer allowed broadband achromatic metalens to have a high numerical aperture,which enabled high-resolution metalens imaging.
基金supported by the Samsung Research Funding&Incubation Center of Samsung Electronics under Project Number SRFC-IT2401-01 and by National Research Foundation(NRF)grants(RS-2024-00462912,RS-2023-00266110,and RS-2020-NR049544)funded by the Ministry of Science and ICT(MSIT)of the Korean governmentI.K.acknowledges the NRF Sejong Science Fellowship(RS-2021-NR061797)funded by the MSIT of the Korean government.We would like to express our sincere gratitude to Yangkyu Kim for his invaluable assistance in correcting the mathematical errors in this paper.
文摘Image scanning microscopy(ISM)is a promising imaging technique that offers sub-diffraction-limited resolution and optical sectioning.Theoretically,ISM can improve the optical resolution by a factor of two through pixel reassignment and deconvolution.Multifocal array illumination and scanning have been widely adopted to implement ISM because of their simplicity.Conventionally,digital micromirror devices(DMDs)1 and microlens arrays(MLAs)2,3 have been used to generate dense and uniform multifocal arrays for ISM,which are critical for achieving fast imaging and high-quality ISM reconstruction.However,these approaches have limitations in terms of cost,numerical aperture(NA),pitch,and uniformity,making it challenging to create dense and high-quality multifocal arrays at high NA.To overcome these limitations,we introduced a novel multifocal metalens design strategy called the hybrid multiplexing method,which combines two conventional multiplexing approaches:phase addition and random multiplexing.Through numerical simulations,we demonstrate that the proposed method generates more uniform and denser multifocal arrays than conventional methods,even at small pitches.As a proof of concept,we fabricated a multifocal metalens generating 40×40 array of foci with a 3μm pitch and NA of 0.7 operating at a wavelength of 488 nm and then constructed the multifocal metalens-based ISM(MMISM).We demonstrated that MMISM successfully resolved sub-diffraction-limited features in imaging of microbead samples and forebrain organoid sections.The results showed that MMISM imaging achieved twice the diffraction-limited resolution and revealed clearer structural features of neurons compared to wide-field images.We anticipate that our novel design strategy can be widely applied to produce multifunctional optical elements and replace conventional optical elements in specialized applications.
基金supported by a Basic Science Research Program grant through the National Research Foundation of Korea(NRF)grants(Nos.2021R1A2C4001776,RS-2023-00218648,RS-2023-00242443,and 2023-00208913)of the Republic of Koreafunded by the Ministry of Science and ICT(MSIT)of the Republic of Korea+2 种基金a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(No.RS-2023-00266015)the KIST Institutional Program(No.2E32351-23-130)of the Republic of Korea.
文摘Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy.Lipid nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 pandemic.This study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid tumor.The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication.Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth inhibition.These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.
文摘Introduction of the stepwise phase dispersion compensation layer allowed broadband achromatic metalens to have a high numerical aperture,which enabled high-resolution metalens imaging.
