The strategic integration of micro/nano-engineering with controlled optical responses is pivotal for advancing solid tumor therapy. We have constructed a biomimetic nanosystem via the precise encapsulation of a flexible-chain iridium complex (IrC8) within giant plasma membrane vesicles (GPMVs) derived from tumor cells. This micro/nano-scale design leverages the endogenous structure of GPMVs to achieve superior biocompatibility and enhance homologous targeting, resulting in a 4.7% increase in cellular uptake compared to the free complex. The encapsulated IrC8 complex serves as a highly efficient photosensitizer, exhibiting a strong optical response characterized by an aggregation-induced emission enhancement factor (I/I₀) > 10 and a high singlet-oxygen quantum yield (ΦΔ = 0.18). Upon photoactivation, this system generates reactive oxygen species (ROS) with an 18-fold increase in yield, leading to potent phototoxicity with over 90% tumor cell apoptosis. Furthermore, the systematic integration of the vesicular carrier and the photosensitizer initiates a cascade reaction: the photodynamic effect not only directly eradicates tumor cells but also triggers immunogenic cell death (ICD), leading to potent immune activation. This synergistic combination of targeted delivery, photodynamic therapy, and immune stimulation within a single nanosystem demonstrates a remarkable synergistic therapeutic effect against solid tumors.
{"title":"Iridium complex-loaded biomimetic vesicles enable enhanced photodynamic therapy and immune modulation.","authors":"Zhang Xiaohui, Tang Xuelin, Lin Bai, Rui Zhao, Yaohui Chen, Xiaohe Tian","doi":"10.1038/s41378-025-01146-4","DOIUrl":"10.1038/s41378-025-01146-4","url":null,"abstract":"<p><p>The strategic integration of micro/nano-engineering with controlled optical responses is pivotal for advancing solid tumor therapy. We have constructed a biomimetic nanosystem via the precise encapsulation of a flexible-chain iridium complex (IrC8) within giant plasma membrane vesicles (GPMVs) derived from tumor cells. This micro/nano-scale design leverages the endogenous structure of GPMVs to achieve superior biocompatibility and enhance homologous targeting, resulting in a 4.7% increase in cellular uptake compared to the free complex. The encapsulated IrC8 complex serves as a highly efficient photosensitizer, exhibiting a strong optical response characterized by an aggregation-induced emission enhancement factor (I/I₀) > 10 and a high singlet-oxygen quantum yield (ΦΔ = 0.18). Upon photoactivation, this system generates reactive oxygen species (ROS) with an 18-fold increase in yield, leading to potent phototoxicity with over 90% tumor cell apoptosis. Furthermore, the systematic integration of the vesicular carrier and the photosensitizer initiates a cascade reaction: the photodynamic effect not only directly eradicates tumor cells but also triggers immunogenic cell death (ICD), leading to potent immune activation. This synergistic combination of targeted delivery, photodynamic therapy, and immune stimulation within a single nanosystem demonstrates a remarkable synergistic therapeutic effect against solid tumors.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"33"},"PeriodicalIF":9.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1038/s41378-025-01125-9
Björn Altenburger, Joachim Fritzsche, Christoph Langhammer
Fluidics on the micro- and nanoscale have been revolutionary for the fields of biology and medicine, and they are gaining a strong foothold in chemistry with the rise of micro and nanoscale reactors. These systems are based on fluidic platforms crafted into polymer or silicon-based substrates, and are comprised of channels with different functions and sizes that span from the micro- to the nanoscale. However, to fully capitalize on the possibilities offered by such highly integrated fluidic systems, the periphery that connects the fluidic chip to the macroscopic world, and thereby makes it accessible for the envisioned functions and applications, is equally important but receives much less attention. Such periphery needs to be versatile and enable accurate control of pressures and flow of liquids or gases, of sample temperature, and for certain applications even electric fields. Here, we report the development of a temperature-controlled fluidic chip holder for heating and cooling that is integrated with electrodes for the creation of electric fields across the fluidic system. It interfaces 1 cm2 silicon-based nanofluidic chips with up to 12 fluidic connection points and optically transparent lid, that makes them compatible with optical microscopy techniques. We demonstrate the different functionalities of the sample holder by using nanofluidic scattering spectroscopy (NSS) to monitor the on-chip mixing of two different dyes, the diffusion of fluorescein into water at different temperatures, and the diffusion of fluorescein into water at different strengths of an electric field applied along a nanochannel.
{"title":"A temperature-controlled chip holder with integrated electrodes for nanofluidic scattering spectroscopy on highly integrated nanofluidic systems.","authors":"Björn Altenburger, Joachim Fritzsche, Christoph Langhammer","doi":"10.1038/s41378-025-01125-9","DOIUrl":"10.1038/s41378-025-01125-9","url":null,"abstract":"<p><p>Fluidics on the micro- and nanoscale have been revolutionary for the fields of biology and medicine, and they are gaining a strong foothold in chemistry with the rise of micro and nanoscale reactors. These systems are based on fluidic platforms crafted into polymer or silicon-based substrates, and are comprised of channels with different functions and sizes that span from the micro- to the nanoscale. However, to fully capitalize on the possibilities offered by such highly integrated fluidic systems, the periphery that connects the fluidic chip to the macroscopic world, and thereby makes it accessible for the envisioned functions and applications, is equally important but receives much less attention. Such periphery needs to be versatile and enable accurate control of pressures and flow of liquids or gases, of sample temperature, and for certain applications even electric fields. Here, we report the development of a temperature-controlled fluidic chip holder for heating and cooling that is integrated with electrodes for the creation of electric fields across the fluidic system. It interfaces 1 cm<sup>2</sup> silicon-based nanofluidic chips with up to 12 fluidic connection points and optically transparent lid, that makes them compatible with optical microscopy techniques. We demonstrate the different functionalities of the sample holder by using nanofluidic scattering spectroscopy (NSS) to monitor the on-chip mixing of two different dyes, the diffusion of fluorescein into water at different temperatures, and the diffusion of fluorescein into water at different strengths of an electric field applied along a nanochannel.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"32"},"PeriodicalIF":9.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the past two decades, silica-based nanobiomaterials (SNs) have emerged as a promising frontier in regenerative medicine, garnering substantial interest for their potential applications. Despite this growing interest, a notable lack of comprehensive and dynamic analyses remains, examining the evolution, development trends, research hotspots, and prospects of SNs in this field. To address this gap, we systematically analyzed 853 research articles published between 2006 and 2025 in the Science Citation Index Expanded (Web of Science Core Collection). Using bibliometric tools-CiteSpace, VOSviewer, and Biblioshiny-we generated data-driven visualizations to elucidate publication trends, contributions by countries/regions and institutions, journal distributions, research categories, thematic focuses, reference networks, and keyword dynamics. Our findings reveal a rapid acceleration in research output. While China leads in academic output volume, the United States maintains a significant advantage in average citation frequency, highlighting disparities in research impact. Current research hotspots include drug delivery systems, antimicrobial activity, bone regeneration, and wound healing. Keyword burst analysis identifies emerging frontiers such as mesoporous bioactive glass nanoparticles, wound healing, and zinc ion dopants. This study not only maps the trajectory of SNs in regenerative medicine but also discusses critical challenges and future directions, offering valuable insights for advancing the field.
在过去的二十年里,硅基纳米生物材料(SNs)已经成为再生医学的一个有前途的前沿,其潜在的应用获得了极大的兴趣。尽管人们对社交网络的兴趣日益浓厚,但对社交网络在这一领域的演变、发展趋势、研究热点和前景的全面和动态分析仍然缺乏。为了解决这一差距,我们系统地分析了2006年至2025年间发表在科学引文索引扩展(Web of Science核心馆藏)中的853篇研究论文。利用文献计量工具——citespace、VOSviewer和biblioshini,我们生成了数据驱动的可视化,以阐明出版趋势、国家/地区和机构的贡献、期刊分布、研究类别、主题焦点、参考文献网络和关键字动态。我们的研究结果显示,研究产出正在迅速增加。中国在学术产出上领先,而美国在平均被引频次上保持着显著优势,凸显了研究影响力上的差异。目前的研究热点包括药物输送系统、抗菌活性、骨再生和伤口愈合。关键词爆发分析确定了新兴的前沿领域,如介孔生物活性玻璃纳米颗粒、伤口愈合和锌离子掺杂剂。本研究不仅描绘了再生医学中SNs的发展轨迹,而且讨论了关键挑战和未来方向,为推进该领域提供了有价值的见解。
{"title":"Data-driven visualization of silica-based nanobiomaterial dynamics for tissue regeneration.","authors":"Chengxi Yang, Zhenhuan Xie, Sihua Liang, Zhan Liu, Luís Cardoso, Dan Hou, Janak Lal Pathak, Qing Zhang","doi":"10.1038/s41378-025-01120-0","DOIUrl":"10.1038/s41378-025-01120-0","url":null,"abstract":"<p><p>Over the past two decades, silica-based nanobiomaterials (SNs) have emerged as a promising frontier in regenerative medicine, garnering substantial interest for their potential applications. Despite this growing interest, a notable lack of comprehensive and dynamic analyses remains, examining the evolution, development trends, research hotspots, and prospects of SNs in this field. To address this gap, we systematically analyzed 853 research articles published between 2006 and 2025 in the Science Citation Index Expanded (Web of Science Core Collection). Using bibliometric tools-CiteSpace, VOSviewer, and Biblioshiny-we generated data-driven visualizations to elucidate publication trends, contributions by countries/regions and institutions, journal distributions, research categories, thematic focuses, reference networks, and keyword dynamics. Our findings reveal a rapid acceleration in research output. While China leads in academic output volume, the United States maintains a significant advantage in average citation frequency, highlighting disparities in research impact. Current research hotspots include drug delivery systems, antimicrobial activity, bone regeneration, and wound healing. Keyword burst analysis identifies emerging frontiers such as mesoporous bioactive glass nanoparticles, wound healing, and zinc ion dopants. This study not only maps the trajectory of SNs in regenerative medicine but also discusses critical challenges and future directions, offering valuable insights for advancing the field.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"31"},"PeriodicalIF":9.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12800079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1038/s41378-025-01133-9
Jufeng Deng, Chong Liu, Xueye Chen, Marc Madou
Current carbonaceous fibers with 0.3-7 GPa tensile strength are ideally crystallized towards graphitized carbon nanowires for highly mechanical and conductive properties. An essential approach for this case is being challenged by the formation of graphitized carbon microstructures and the reduction of size to the nanoscale in the fabrication of carbonaceous fibers at a low temperature (1000 °C) that the chip can withstand without melting. Here the method for orienting carbon molecular chains in carbon microstructures is developed by chemical modification of polymer structure, conformational structuration of polymer molecular chains and axial orientation of carbon molecular chains. Using this method, carbon molecular chains are nearly all oriented along the axial directions, but are entangle in very small amounts. Our results demonstrate the presence of graphitized carbon microstructure in the carbon nanowires integrated with microstructure-based chips. We find that the graphitized nanowires exhibit unexpected tensile strength up to 24.74 GPa while having superior modulus and highly electrical conductivity up to 501.06 GPa and 1.16 × 105 S/m, respectively. The ability to synthesize patternable graphitized carbon nanowires on micro-pillars and micro-scaffolds of chips creates opportunities for research into correlated carbon microstructure and chip-based superior performances that are dependent on the nano-scaling and graphitizing of carbonaceous fibers.
{"title":"Mechanically strong and highly conductive graphitized carbon nanowire arrays for nano-fabrication of carbon-based chips.","authors":"Jufeng Deng, Chong Liu, Xueye Chen, Marc Madou","doi":"10.1038/s41378-025-01133-9","DOIUrl":"10.1038/s41378-025-01133-9","url":null,"abstract":"<p><p>Current carbonaceous fibers with 0.3-7 GPa tensile strength are ideally crystallized towards graphitized carbon nanowires for highly mechanical and conductive properties. An essential approach for this case is being challenged by the formation of graphitized carbon microstructures and the reduction of size to the nanoscale in the fabrication of carbonaceous fibers at a low temperature (1000 °C) that the chip can withstand without melting. Here the method for orienting carbon molecular chains in carbon microstructures is developed by chemical modification of polymer structure, conformational structuration of polymer molecular chains and axial orientation of carbon molecular chains. Using this method, carbon molecular chains are nearly all oriented along the axial directions, but are entangle in very small amounts. Our results demonstrate the presence of graphitized carbon microstructure in the carbon nanowires integrated with microstructure-based chips. We find that the graphitized nanowires exhibit unexpected tensile strength up to 24.74 GPa while having superior modulus and highly electrical conductivity up to 501.06 GPa and 1.16 × 10<sup>5 </sup>S/m, respectively. The ability to synthesize patternable graphitized carbon nanowires on micro-pillars and micro-scaffolds of chips creates opportunities for research into correlated carbon microstructure and chip-based superior performances that are dependent on the nano-scaling and graphitizing of carbonaceous fibers.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"30"},"PeriodicalIF":9.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12800162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1038/s41378-025-01124-w
Rui Ran, Xiaojing Dong, Yang Yang, Sana Shakeel, Xiaoyu Liu, Richard Saffery, Jing Yang, Ting-Li Han
Placental vascular anastomoses are a relatively common occurrence in monochorionic twin pregnancies, potentially leading to unbalanced blood supply to the developing twins, higher rates of perinatal mortality and long term morbidity. Unfortunately, our understanding of these conditions and their treatment strategies remains limited due to the lack of suitable in vitro and vivo twin models. Herein, we presented a microfluidic-based Monochorionic-Twin-on-a-Chip (MTOC) model designed to simulate monochorionic diamnionic (MCDA) pregnancies. The aim was to model the impact of an unbalanced nutrition supply on fetal organ growth using hepatic cells grown in vitro. Our findings confirm that an unbalanced nutrition supply from the donor circulation reduces cellular growth relative to the recipient system. This recapitulates the situation of the smaller (donor) and larger twins (recipient) within an MCDA pregnancy in vivo. Furthermore, hepatic cells exposed to the donor circulation exhibited a relative hypoxia state. Metabolite profiling of intracellular, extracellular, and biomass samples from small twins revealed lower levels of amino acids, fatty acids, and TCA cycle intermediates compared to large twins. Additionally, 13C metabolic flux showed upregulation of TCA cycle activity in the large twin, whereas the small twin would utilize more glutamine for energy supply and lipid synthesis. These results suggest that the unbalanced nutrient supply associated with some MC twin pregnancies restricts fetal liver growth in association with altered metabolic profiles. Moreover, our MTOC model represents a novel system for studying a range of other physiological intrauterine environments and pregnancy outcomes associated with MC twin pregnancies.
{"title":"Monochorionic-twin-on-a-chip for investigating fetal organ growth and metabolism.","authors":"Rui Ran, Xiaojing Dong, Yang Yang, Sana Shakeel, Xiaoyu Liu, Richard Saffery, Jing Yang, Ting-Li Han","doi":"10.1038/s41378-025-01124-w","DOIUrl":"10.1038/s41378-025-01124-w","url":null,"abstract":"<p><p>Placental vascular anastomoses are a relatively common occurrence in monochorionic twin pregnancies, potentially leading to unbalanced blood supply to the developing twins, higher rates of perinatal mortality and long term morbidity. Unfortunately, our understanding of these conditions and their treatment strategies remains limited due to the lack of suitable in vitro and vivo twin models. Herein, we presented a microfluidic-based Monochorionic-Twin-on-a-Chip (MTOC) model designed to simulate monochorionic diamnionic (MCDA) pregnancies. The aim was to model the impact of an unbalanced nutrition supply on fetal organ growth using hepatic cells grown in vitro. Our findings confirm that an unbalanced nutrition supply from the donor circulation reduces cellular growth relative to the recipient system. This recapitulates the situation of the smaller (donor) and larger twins (recipient) within an MCDA pregnancy in vivo. Furthermore, hepatic cells exposed to the donor circulation exhibited a relative hypoxia state. Metabolite profiling of intracellular, extracellular, and biomass samples from small twins revealed lower levels of amino acids, fatty acids, and TCA cycle intermediates compared to large twins. Additionally, <sup>13</sup>C metabolic flux showed upregulation of TCA cycle activity in the large twin, whereas the small twin would utilize more glutamine for energy supply and lipid synthesis. These results suggest that the unbalanced nutrient supply associated with some MC twin pregnancies restricts fetal liver growth in association with altered metabolic profiles. Moreover, our MTOC model represents a novel system for studying a range of other physiological intrauterine environments and pregnancy outcomes associated with MC twin pregnancies.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"27"},"PeriodicalIF":9.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Infrared (IR) gas sensors have an urgent demand for high-reliability MEMS IR emitters. In this study, a wafer-level self-packaged MEMS IR emitter (SPIRE) has been designed and manufactured to enhance the durability of devices in high temperatures and ambient air. In the state-of-the-art design, Pt-wire heating and temperature sensing elements were fabricated onto a silicon (Si) membrane and vacuum-sealed within a glass cavity utilizing the Si-glass anodic bonding technique. Additionally, a black-Si nanostructure was prepared on the opposite side of the Si membrane to enhance IR light emissivity. The electrical-thermal-mechanical properties were simulated using COMSOL Multiphysics to optimize the structural design. The devices were fabricated through wafer-level MEMS processing techniques. Testing results demonstrated that the SPIREs were capable of achieving a light-emitting power intensity of 172 mW/Sr/µm at a peak wavelength of 6.1 µm and a 3-dB bandwidth of 52 Hz, corresponding to a surface temperature of 400 °C at a driving power of 850 mW. Long-term reliability was assessed through an accelerated aging test and a life prediction method. The estimated lifespan of the SPIREs can reach 10 years at a working temperature of 500 °C.
{"title":"Wafer-level self-packaged MEMS infrared emitters with high-emissivity black silicon surface.","authors":"Zhiwei Li, Hongliang Zu, Hongyu Chen, Minghao Liu, Haisheng San, Daquan Yu","doi":"10.1038/s41378-025-01114-y","DOIUrl":"10.1038/s41378-025-01114-y","url":null,"abstract":"<p><p>Infrared (IR) gas sensors have an urgent demand for high-reliability MEMS IR emitters. In this study, a wafer-level self-packaged MEMS IR emitter (SPIRE) has been designed and manufactured to enhance the durability of devices in high temperatures and ambient air. In the state-of-the-art design, Pt-wire heating and temperature sensing elements were fabricated onto a silicon (Si) membrane and vacuum-sealed within a glass cavity utilizing the Si-glass anodic bonding technique. Additionally, a black-Si nanostructure was prepared on the opposite side of the Si membrane to enhance IR light emissivity. The electrical-thermal-mechanical properties were simulated using COMSOL Multiphysics to optimize the structural design. The devices were fabricated through wafer-level MEMS processing techniques. Testing results demonstrated that the SPIREs were capable of achieving a light-emitting power intensity of 172 mW/Sr/µm at a peak wavelength of 6.1 µm and a 3-dB bandwidth of 52 Hz, corresponding to a surface temperature of 400 °C at a driving power of 850 mW. Long-term reliability was assessed through an accelerated aging test and a life prediction method. The estimated lifespan of the SPIREs can reach 10 years at a working temperature of 500 °C.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"28"},"PeriodicalIF":9.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1038/s41378-025-01117-9
M J I Airaghi Leccardi, B X E Desbiolles, S Yadav, Y Yu, D Sarkar
Freestanding micro-nanodevices stand out as excellent candidates for the next generation of neural interfaces. Their wireless nature, coupled with their subcellular dimensions, promises to enable minimally invasive neuromodulation with high spatial resolution within three-dimensional tissues. Nevertheless, their practical implementation is hindered by technical challenges. Specifically, fabricating and harvesting freestanding devices with subcellular sizes proves exceedingly difficult, and characterizing their functionality in a representative freestanding configuration presents an even greater challenge. In this work, we present a comprehensive framework for fabricating, collecting, and characterizing freestanding micro-nanodevices to advance progress in neural interfaces. We developed three distinct micro-nanofabrication methods tailored for manufacturing freestanding micro-nanodevices with varying characteristics. These methods include a very large-scale integration process for manufacturing and manipulating freestanding microdevices (2-200 µm) with high throughput, a cell-friendly approach utilizing only biocompatible materials and solvents for rapid microdevice production, and a protocol for fabricating and handling freestanding devices with even smaller size scale (200 nm to 3 µm). We subsequently devised an effective approach to rapidly characterize the electrical modulation capabilities of freestanding micro-nanodevices in a cell-like environment, employing artificial bilayer lipid membranes. We showcased this method by studying the variation of bilayer lipid membrane transmembrane potential in response to a light stimulus when sprinkled with organic semiconductor devices. Ultimately, we established an analytical model of the characterization system to translate experimental findings made with bilayer lipid membrane into single cells. By overcoming the technical limitations hindering the fabrication, manipulation, and characterization of freestanding micro-nanodevices, we hope that our research efforts will contribute to accelerating progress in the development of next-generation neural interfaces and unlock the full potential of neuromodulation technologies in fundamental and clinical research.
{"title":"Advancing neural interfaces: a framework for the fabrication and characterization of freestanding micro-nanodevices.","authors":"M J I Airaghi Leccardi, B X E Desbiolles, S Yadav, Y Yu, D Sarkar","doi":"10.1038/s41378-025-01117-9","DOIUrl":"10.1038/s41378-025-01117-9","url":null,"abstract":"<p><p>Freestanding micro-nanodevices stand out as excellent candidates for the next generation of neural interfaces. Their wireless nature, coupled with their subcellular dimensions, promises to enable minimally invasive neuromodulation with high spatial resolution within three-dimensional tissues. Nevertheless, their practical implementation is hindered by technical challenges. Specifically, fabricating and harvesting freestanding devices with subcellular sizes proves exceedingly difficult, and characterizing their functionality in a representative freestanding configuration presents an even greater challenge. In this work, we present a comprehensive framework for fabricating, collecting, and characterizing freestanding micro-nanodevices to advance progress in neural interfaces. We developed three distinct micro-nanofabrication methods tailored for manufacturing freestanding micro-nanodevices with varying characteristics. These methods include a very large-scale integration process for manufacturing and manipulating freestanding microdevices (2-200 µm) with high throughput, a cell-friendly approach utilizing only biocompatible materials and solvents for rapid microdevice production, and a protocol for fabricating and handling freestanding devices with even smaller size scale (200 nm to 3 µm). We subsequently devised an effective approach to rapidly characterize the electrical modulation capabilities of freestanding micro-nanodevices in a cell-like environment, employing artificial bilayer lipid membranes. We showcased this method by studying the variation of bilayer lipid membrane transmembrane potential in response to a light stimulus when sprinkled with organic semiconductor devices. Ultimately, we established an analytical model of the characterization system to translate experimental findings made with bilayer lipid membrane into single cells. By overcoming the technical limitations hindering the fabrication, manipulation, and characterization of freestanding micro-nanodevices, we hope that our research efforts will contribute to accelerating progress in the development of next-generation neural interfaces and unlock the full potential of neuromodulation technologies in fundamental and clinical research.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"26"},"PeriodicalIF":9.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dual-mode sensing represents a highly promising strategy for resonant sensors to achieve in-situ compensation and high-accuracy parameter detection. Micromechanical resonators typically exhibit multiple vibration modes, each with distinct sensitivities to external parameters. By employing different modes for sensing and simultaneously reading out their respective frequencies, cross-sensitivity in multi-parameter detection can be effectively mitigated while fully exploiting the advantages of frequency output in resonant sensors. To address the challenges of inter-modal interaction and vibration signal coupling in dual-mode vibration, this paper investigates dispersive coupling in a double-clamped microbeam, and analyzes the mutual influence between the amplitudes and frequencies of the modes under dual-mode excitation, as well as the implications for sensing applications. Based on constant-amplitude automatic gain control (AGC) and dual differential detection, a dual-mode vibration signal decoupling and stable closed-loop control approach is proposed, achieving a simple and efficient decoupled detection of the dual-mode vibration signals and enabling real-time, synchronous readout of the dual-mode frequencies. The effectiveness of the proposed method was experimentally validated using a resonant pressure sensor. Test results of the pressure sensor demonstrate excellent in-situ temperature compensation effects, with a fitting accuracy of ±0.009% full scale (FS), a maximum repeatability error of 0.0042% FS, a maximum pressure hysteresis error of 0.0068% FS, and an overall pressure accuracy of ±0.012% FS. Furthermore, this dual-mode sensing scheme shows significant potential for multi-parameter measurements and contributes to the advancement of resonant sensors toward miniaturization and intelligence.
{"title":"Dispersive coupling and dual-mode sensing of a micromechanical resonator.","authors":"Wenliang Xia, Jiaxin Qin, Yulan Lu, Deyong Chen, Junbo Wang, Bo Xie, Jian Chen","doi":"10.1038/s41378-025-01101-3","DOIUrl":"10.1038/s41378-025-01101-3","url":null,"abstract":"<p><p>Dual-mode sensing represents a highly promising strategy for resonant sensors to achieve in-situ compensation and high-accuracy parameter detection. Micromechanical resonators typically exhibit multiple vibration modes, each with distinct sensitivities to external parameters. By employing different modes for sensing and simultaneously reading out their respective frequencies, cross-sensitivity in multi-parameter detection can be effectively mitigated while fully exploiting the advantages of frequency output in resonant sensors. To address the challenges of inter-modal interaction and vibration signal coupling in dual-mode vibration, this paper investigates dispersive coupling in a double-clamped microbeam, and analyzes the mutual influence between the amplitudes and frequencies of the modes under dual-mode excitation, as well as the implications for sensing applications. Based on constant-amplitude automatic gain control (AGC) and dual differential detection, a dual-mode vibration signal decoupling and stable closed-loop control approach is proposed, achieving a simple and efficient decoupled detection of the dual-mode vibration signals and enabling real-time, synchronous readout of the dual-mode frequencies. The effectiveness of the proposed method was experimentally validated using a resonant pressure sensor. Test results of the pressure sensor demonstrate excellent in-situ temperature compensation effects, with a fitting accuracy of ±0.009% full scale (FS), a maximum repeatability error of 0.0042% FS, a maximum pressure hysteresis error of 0.0068% FS, and an overall pressure accuracy of ±0.012% FS. Furthermore, this dual-mode sensing scheme shows significant potential for multi-parameter measurements and contributes to the advancement of resonant sensors toward miniaturization and intelligence.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"29"},"PeriodicalIF":9.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1038/s41378-025-01111-1
MinHee Kwon, Holger Arthaber, Daniel Platz, Ulrich Schmid
Microelectromechanical systems (MEMS) sensors have been widely used in various fields, but their performance is often limited by thermal fluctuations and detection noise. Inspired by advances in cavity optomechanics, which utilize parametric coupling for precision sensing and noise reduction, we explore a new approach to overcoming these limitations. We demonstrate a purely mechanical parametric coupling system that replaces the optical mode with a GHz surface acoustic wave (SAW) cavity. This system couples the GHz SAW cavity with a kHz micro-cantilever oscillator under ambient conditions, bridging vastly different frequency regimes within a unified framework. This mechano-mechanical coupling is experimentally demonstrated by the generation of red and blue sidebands in the frequency spectrum as direct evidence of energy exchange between the SAW cavity and multiple vibrational modes of the cantilever. Using the standard cavity optomechanics framework, we calculate the coupling strength g0, which is on the order of 10-3 Hz, and compare it with previously reported values in optomechanical and electromechanical systems. Our findings establish mechano-mechanical parametric coupling as a practical alternative to conventional optomechanical interactions, offering a new framework for integrating GHz and kHz mechanical resonators into silicon MEMS-compatible platforms.
{"title":"Mechano-mechanical parametric coupling in MEMS between GHz and kHz frequency regimes at room temperature.","authors":"MinHee Kwon, Holger Arthaber, Daniel Platz, Ulrich Schmid","doi":"10.1038/s41378-025-01111-1","DOIUrl":"10.1038/s41378-025-01111-1","url":null,"abstract":"<p><p>Microelectromechanical systems (MEMS) sensors have been widely used in various fields, but their performance is often limited by thermal fluctuations and detection noise. Inspired by advances in cavity optomechanics, which utilize parametric coupling for precision sensing and noise reduction, we explore a new approach to overcoming these limitations. We demonstrate a purely mechanical parametric coupling system that replaces the optical mode with a GHz surface acoustic wave (SAW) cavity. This system couples the GHz SAW cavity with a kHz micro-cantilever oscillator under ambient conditions, bridging vastly different frequency regimes within a unified framework. This mechano-mechanical coupling is experimentally demonstrated by the generation of red and blue sidebands in the frequency spectrum as direct evidence of energy exchange between the SAW cavity and multiple vibrational modes of the cantilever. Using the standard cavity optomechanics framework, we calculate the coupling strength g<sub>0</sub>, which is on the order of 10<sup>-3</sup> Hz, and compare it with previously reported values in optomechanical and electromechanical systems. Our findings establish mechano-mechanical parametric coupling as a practical alternative to conventional optomechanical interactions, offering a new framework for integrating GHz and kHz mechanical resonators into silicon MEMS-compatible platforms.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"24"},"PeriodicalIF":9.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1038/s41378-025-01140-w
Sungwoo Cho, Quoc Huynh Nguyen, Jose Manolo de Hoyos-Vega, Ananya Bharath, Alan M Gonzalez-Suarez, Kianna M Nguyen, Quang Tuan Che, Kihak Gwon, Aleksey Matveyenko, Gulnaz Stybayeva, Alexander Revzin
There is increasing clinical evidence that pancreatic dysfunction in diabetes needs to be viewed in the context of crosstalk with the liver as well as other organs. Our goal for this study was to develop a pancreas-liver co-culture system suited for mechanistic and therapy testing studies in the context of multi-organ cross talk. To achieve this goal, we developed a co-axial flow-focusing microfluidic device to fabricate multi-compartment hydrogel microcapsules. Each microcapsule contained two aqueous compartments or cores surrounded by poly(ethylene glycol) (PEG) hydrogel. Each microcapsule had pancreatic β-cells loaded into one compartment and hepatic cells into another compartment. Individual encapsulated cells assembled into pancreatic and hepatic cell spheroids over time. Characterization of microcapsules revealed enhanced hepatic and pancreatic function in microcapsules containing pancreas-liver co-cultures compared to microcapsules with one cell type only. Multicompartment microcapsules represent a novel microphysiological system type and hold the promise of increasing experiment throughput for mechanism discovery and drug development studies.
{"title":"Multicompartment hydrogel microcapsules for creating spatially patterned cell co-cultures.","authors":"Sungwoo Cho, Quoc Huynh Nguyen, Jose Manolo de Hoyos-Vega, Ananya Bharath, Alan M Gonzalez-Suarez, Kianna M Nguyen, Quang Tuan Che, Kihak Gwon, Aleksey Matveyenko, Gulnaz Stybayeva, Alexander Revzin","doi":"10.1038/s41378-025-01140-w","DOIUrl":"10.1038/s41378-025-01140-w","url":null,"abstract":"<p><p>There is increasing clinical evidence that pancreatic dysfunction in diabetes needs to be viewed in the context of crosstalk with the liver as well as other organs. Our goal for this study was to develop a pancreas-liver co-culture system suited for mechanistic and therapy testing studies in the context of multi-organ cross talk. To achieve this goal, we developed a co-axial flow-focusing microfluidic device to fabricate multi-compartment hydrogel microcapsules. Each microcapsule contained two aqueous compartments or cores surrounded by poly(ethylene glycol) (PEG) hydrogel. Each microcapsule had pancreatic β-cells loaded into one compartment and hepatic cells into another compartment. Individual encapsulated cells assembled into pancreatic and hepatic cell spheroids over time. Characterization of microcapsules revealed enhanced hepatic and pancreatic function in microcapsules containing pancreas-liver co-cultures compared to microcapsules with one cell type only. Multicompartment microcapsules represent a novel microphysiological system type and hold the promise of increasing experiment throughput for mechanism discovery and drug development studies.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"12 1","pages":"25"},"PeriodicalIF":9.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}