Wide-ranging biomedical applications spanning both research and clinical settings rely on microinjection protocols that involve using a long,hollow microneedle to deliver foreign substances directly into biological ta...Wide-ranging biomedical applications spanning both research and clinical settings rely on microinjection protocols that involve using a long,hollow microneedle to deliver foreign substances directly into biological targets,such as embryos.Unfortunately,conventional microneedles are prone to clogging—e.g.,cytoplasmic material from an embryo becoming lodged inside the needle tip during penetration,thereby obstructing delivery—motivating researchers to use top-down microfabrication techniques to modify needle tips and reduce such failure modes.Recent advancements for the submicron-scale additive manufacturing approach,“Two-Photon Direct Laser Writing(DLW)”,offer a new,bottom-up pathway for re-architecting microneedle tips to address clogging susceptibility via geometric means.Here,we investigate this potential by 3D printing monolithic 650-μm-tall,15-μm-diameter hollow microneedles comprising architectural features designed to remediate clogging phenomena:(i)a solid,fine-point tip,(ii)multiple side ports(i.e.,perpendicular to the insertion direction),and(iii)an internal microfilter.Serial microinjection experiments with live zebrafish embryos reveal that the 3D microneedles yield enhanced delivery performance without any instances of complete blockages that are pervasive among both standard glass and 3Dprinted control microneedles.These findings suggest that DLW-based 3D printing holds distinctive promise for highprecision microinjection applications,particularly in scenarios involving extensive serial injections or critical payloads and targets.展开更多
Glass materials are essential for microsystems applications in fields ranging from optics and photonics to microfluidics and biomedicine,which has driven growing interest in additive manufacturing—or“three-dimension...Glass materials are essential for microsystems applications in fields ranging from optics and photonics to microfluidics and biomedicine,which has driven growing interest in additive manufacturing—or“three-dimensional(3D)printing”—to enable glass micro/nanotechnologies.Notably,the recent discovery that 3D-nanostructured fused silica glass components can be produced via“two-photon direct laser writing(DLW)”of hybrid organic-inorganic polyhedral oligomeric silsesquioxanes(POSS)-based resins holds unique promise,particularly due to the advantages of sinterless,low-temperature(i.e.,650℃)post-processing.At present,however,it remains unknown how implementing such methodologies to 3D print larger glass microstructures(e.g.,with≥25-μm-thick features)affects critical material properties,such as the ultimate optical and mechanical characteristics.To address this knowledge gap,here we investigate DLW-printed feature size as a key determinant of the optical and mechanical properties of POSS-based fused silica glass microstructures.Experiments for DLW-printed microlenses reveal comparable optical transparency for initial thicknesses up to 40μm,but increasing to 60μm significantly reduces light transmission from 87.87±1.18%to 63.57±5.10%.Similarly,compressive loading studies for hollow glass cylindrical microstructures show consistent behavior for initial DLW-printed wall thicknesses up to 30μm,but significant performance degradation beyond—e.g.,Young’s modulus decreasing from 251.6±71.9 to 99.7±63.9 MPa for the 30 to 40μm cases,respectively.As an exemplar with relevance to biomedical microinjection applications,we harness this new knowledge to DLW-print POSS-based glass microneedle arrays(MNAs)and demonstrate their ability to penetrate into a medium not possible using standard polymer MNAs.In combination,this study establishes critical optical and mechanical benchmarks that underlie the utility of DLW 3D-printed POSS-based fused silica glass microstructures in emerging applications.展开更多
基金supported in part by U.S.National Institutes of Health(NIH)Award Numbers 1R41GM153053 and 1R41MH135827U.S.National Science Foundation(NSF)Award Numbers 1943356 and 1938527Maryland Industrial Partnerships(MIPS)Award Numbers 6523 and 7422.
文摘Wide-ranging biomedical applications spanning both research and clinical settings rely on microinjection protocols that involve using a long,hollow microneedle to deliver foreign substances directly into biological targets,such as embryos.Unfortunately,conventional microneedles are prone to clogging—e.g.,cytoplasmic material from an embryo becoming lodged inside the needle tip during penetration,thereby obstructing delivery—motivating researchers to use top-down microfabrication techniques to modify needle tips and reduce such failure modes.Recent advancements for the submicron-scale additive manufacturing approach,“Two-Photon Direct Laser Writing(DLW)”,offer a new,bottom-up pathway for re-architecting microneedle tips to address clogging susceptibility via geometric means.Here,we investigate this potential by 3D printing monolithic 650-μm-tall,15-μm-diameter hollow microneedles comprising architectural features designed to remediate clogging phenomena:(i)a solid,fine-point tip,(ii)multiple side ports(i.e.,perpendicular to the insertion direction),and(iii)an internal microfilter.Serial microinjection experiments with live zebrafish embryos reveal that the 3D microneedles yield enhanced delivery performance without any instances of complete blockages that are pervasive among both standard glass and 3Dprinted control microneedles.These findings suggest that DLW-based 3D printing holds distinctive promise for highprecision microinjection applications,particularly in scenarios involving extensive serial injections or critical payloads and targets.
基金support of the Clark School of Engineering’s Materials Characterization Labsupported in part by US National Institutes of Health(NIH)Award Numbers 1R41GM153053 and 1R41MH135827+2 种基金US National Science Foundation(NSF)Award Numbers 1943356 and 1938527Maryland Industrial Partnerships(MIPS)Award Numbers 6523 and 7422US National Science Foundation grants CMMI1943356,DGE2236417,and DGE2139757。
文摘Glass materials are essential for microsystems applications in fields ranging from optics and photonics to microfluidics and biomedicine,which has driven growing interest in additive manufacturing—or“three-dimensional(3D)printing”—to enable glass micro/nanotechnologies.Notably,the recent discovery that 3D-nanostructured fused silica glass components can be produced via“two-photon direct laser writing(DLW)”of hybrid organic-inorganic polyhedral oligomeric silsesquioxanes(POSS)-based resins holds unique promise,particularly due to the advantages of sinterless,low-temperature(i.e.,650℃)post-processing.At present,however,it remains unknown how implementing such methodologies to 3D print larger glass microstructures(e.g.,with≥25-μm-thick features)affects critical material properties,such as the ultimate optical and mechanical characteristics.To address this knowledge gap,here we investigate DLW-printed feature size as a key determinant of the optical and mechanical properties of POSS-based fused silica glass microstructures.Experiments for DLW-printed microlenses reveal comparable optical transparency for initial thicknesses up to 40μm,but increasing to 60μm significantly reduces light transmission from 87.87±1.18%to 63.57±5.10%.Similarly,compressive loading studies for hollow glass cylindrical microstructures show consistent behavior for initial DLW-printed wall thicknesses up to 30μm,but significant performance degradation beyond—e.g.,Young’s modulus decreasing from 251.6±71.9 to 99.7±63.9 MPa for the 30 to 40μm cases,respectively.As an exemplar with relevance to biomedical microinjection applications,we harness this new knowledge to DLW-print POSS-based glass microneedle arrays(MNAs)and demonstrate their ability to penetrate into a medium not possible using standard polymer MNAs.In combination,this study establishes critical optical and mechanical benchmarks that underlie the utility of DLW 3D-printed POSS-based fused silica glass microstructures in emerging applications.
