Modern thermoelectric modules have emerged as promising platforms for precision thermal analysis in biological and chemical applications. This study presents a high-throughput microcalorimeter employing a patterned bismuth telluride (Bi2Te3) thermopile array as integrated heat flux sensors, overcoming the throughput limitations of conventional calorimetric systems. Through finite element analysis-guided device optimization, we established that increasing thermocouple height from 0.4 mm to 0.8 mm reduces thermal conductance, achieving around 1 power sensitivity. The system demonstrated dual-mode calibration methods using both the electrical (Joule heating) and the chemical (water-ethanol mixing enthalpy) references. Device functionality was validated through real-time monitoring of Escherichia coli metabolism, revealing distinct thermal signatures upon antibiotic challenge. The antimicrobial susceptibility testing (AST) is performed with 4 commonly used antibiotics. The platform achieved 4 h AST with coherent values to Clinical and Laboratory Standards Institute (CLSI) guidelines for minimum inhibitory concentration (MIC) determination. Notably, the modular chip architecture integrates 8 sensing units as a proof-of-concept, coupled with disposable microfluidic chambers that eliminate cross-contamination risks. This chip-calorimeter implementation establishes a new paradigm for chemical reaction heat measurement and rapid clinical diagnostics of infectious diseases.
{"title":"High-throughput chip-calorimeter using a Bi<sub>2</sub>Te<sub>3</sub> thermopile heat flux sensor array.","authors":"Yang Liu, Zhengguang Chen, Yushan Xie, Yinghao Zhang, Guanqin Zhang, Yuchen Wang, Jiale Cheng","doi":"10.1038/s41378-025-01082-3","DOIUrl":"10.1038/s41378-025-01082-3","url":null,"abstract":"<p><p>Modern thermoelectric modules have emerged as promising platforms for precision thermal analysis in biological and chemical applications. This study presents a high-throughput microcalorimeter employing a patterned bismuth telluride (Bi<sub>2</sub>Te<sub>3</sub>) thermopile array as integrated heat flux sensors, overcoming the throughput limitations of conventional calorimetric systems. Through finite element analysis-guided device optimization, we established that increasing thermocouple height from 0.4 mm to 0.8 mm reduces thermal conductance, achieving around 1 <math><mrow><mi>V</mi> <mo>·</mo> <msup><mrow><mi>W</mi></mrow> <mrow><mo>-</mo> <mn>1</mn></mrow> </msup> </mrow> </math> power sensitivity. The system demonstrated dual-mode calibration methods using both the electrical (Joule heating) and the chemical (water-ethanol mixing enthalpy) references. Device functionality was validated through real-time monitoring of Escherichia coli metabolism, revealing distinct thermal signatures upon antibiotic challenge. The antimicrobial susceptibility testing (AST) is performed with 4 commonly used antibiotics. The platform achieved 4 h AST with coherent values to Clinical and Laboratory Standards Institute (CLSI) guidelines for minimum inhibitory concentration (MIC) determination. Notably, the modular chip architecture integrates 8 sensing units as a proof-of-concept, coupled with disposable microfluidic chambers that eliminate cross-contamination risks. This chip-calorimeter implementation establishes a new paradigm for chemical reaction heat measurement and rapid clinical diagnostics of infectious diseases.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"237"},"PeriodicalIF":9.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12672600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661437","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 : 2025-12-02DOI: 10.1038/s41378-025-01098-9
Xiaojun Chen, Xiaodong Lin, Haoran Li, Yanwei Jia
Three-dimensional (3D) cell culture systems better simulate the in vivo microenvironment by promoting intercellular interactions and functional expression, which are crucial for tissue engineering and regenerative medicine. However, conventional two-dimensional (2D) culture platforms fail to mimic the spatial complexity of in vivo tissues, often resulting in altered cellular behavior and limited physiological relevance. In this research, we introduce a 3D cell culture platform based on a digital microfluidic (DMF) system. This platform integrates DMF electrode actuation with 3D-printed microstructure arrays, enabling precise capture and aggregation of cells within a defined 3D scaffold. While cells initially adhere in a 2D structure, they rapidly self-assemble into a 3D cell spheroid on the chip. The platform's capabilities for droplet dispersion, fusion, and movement were validated using the 3D-printed DMF chip. The key parameters, such as applied voltage, microstructure height, and electrode spacing, were systematically investigated for their effects on droplet manipulation. Cell viability and proliferation assays in 24, 48, and 72 hours confirmed that the 3D microstructured scaffolds exhibit excellent biocompatibility and provide a microenvironment favorable for in vivo-like cell growth. Overall, this integrated DMF chip supports robust 3D cell growth and represents a versatile tool for applications in tissue engineering and regenerative medicine.
{"title":"Integrated 3D microstructured digital microfluidic platform for advanced 3D cell culture.","authors":"Xiaojun Chen, Xiaodong Lin, Haoran Li, Yanwei Jia","doi":"10.1038/s41378-025-01098-9","DOIUrl":"10.1038/s41378-025-01098-9","url":null,"abstract":"<p><p>Three-dimensional (3D) cell culture systems better simulate the in vivo microenvironment by promoting intercellular interactions and functional expression, which are crucial for tissue engineering and regenerative medicine. However, conventional two-dimensional (2D) culture platforms fail to mimic the spatial complexity of in vivo tissues, often resulting in altered cellular behavior and limited physiological relevance. In this research, we introduce a 3D cell culture platform based on a digital microfluidic (DMF) system. This platform integrates DMF electrode actuation with 3D-printed microstructure arrays, enabling precise capture and aggregation of cells within a defined 3D scaffold. While cells initially adhere in a 2D structure, they rapidly self-assemble into a 3D cell spheroid on the chip. The platform's capabilities for droplet dispersion, fusion, and movement were validated using the 3D-printed DMF chip. The key parameters, such as applied voltage, microstructure height, and electrode spacing, were systematically investigated for their effects on droplet manipulation. Cell viability and proliferation assays in 24, 48, and 72 hours confirmed that the 3D microstructured scaffolds exhibit excellent biocompatibility and provide a microenvironment favorable for in vivo-like cell growth. Overall, this integrated DMF chip supports robust 3D cell growth and represents a versatile tool for applications in tissue engineering and regenerative medicine.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"239"},"PeriodicalIF":9.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661429","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 : 2025-12-01DOI: 10.1038/s41378-025-01084-1
Zhengkai Tang, Ruchuan Shi, Dapeng Guo, Chengtao Luo, Hualin Li, Tao Han
This study addresses the issue of traditional surface acoustic wave (SAW) tag failure under high-temperature conditions by proposing a SAW tag based on a multilayer structure of SiO2/Pt/128°YX-LiNbO3. The structure has been simulated using the finite element method/wave-number domain analysis (FEM/WDA) approach, which reveal the effects of reflector topological parameters on the scattering characteristics of SAWs. Compared with Pt/128°YX-LiNbO3, the bulk wave scattering in the multilayer structure is reduced by 50%. In the micro-nanofabrication of the tag, a low-roughness, high-density SiO2 film is prepared using physical vapor deposition (PVD). Test results indicate that the tag exhibits a temperature coefficient of frequency (TCF) of -32.38 ppm/°C over a wide temperature range of 30-600°C. After undergoing thermal shock at 600 °C for 336 h, the time-domain reflection amplitude decreases by less than 1%, demonstrating that the SiO2 protective layer effectively suppresses the high-temperature decomposition of LiNbO3 and reduces the agglomeration rate of Pt electrodes. Experimental results confirm that the proposed high-temperature-resistant SAW tag maintains stable performance under prolonged exposure to 600 °C environments. The tag has been installed on the surface of a steel ladle in a steel plant, demonstrating excellent reliability in a vacuum degassing environment.
{"title":"A surface acoustic wave tag utilizing a multilayer structure of SiO<sub>2</sub>/Pt/128°YX-LiNbO<sub>3</sub> for operation at 600 °C.","authors":"Zhengkai Tang, Ruchuan Shi, Dapeng Guo, Chengtao Luo, Hualin Li, Tao Han","doi":"10.1038/s41378-025-01084-1","DOIUrl":"10.1038/s41378-025-01084-1","url":null,"abstract":"<p><p>This study addresses the issue of traditional surface acoustic wave (SAW) tag failure under high-temperature conditions by proposing a SAW tag based on a multilayer structure of SiO<sub>2</sub>/Pt/128°YX-LiNbO<sub>3</sub>. The structure has been simulated using the finite element method/wave-number domain analysis (FEM/WDA) approach, which reveal the effects of reflector topological parameters on the scattering characteristics of SAWs. Compared with Pt/128°YX-LiNbO<sub>3</sub>, the bulk wave scattering in the multilayer structure is reduced by 50%. In the micro-nanofabrication of the tag, a low-roughness, high-density SiO<sub>2</sub> film is prepared using physical vapor deposition (PVD). Test results indicate that the tag exhibits a temperature coefficient of frequency (TCF) of -32.38 ppm/°C over a wide temperature range of 30-600°C. After undergoing thermal shock at 600 °C for 336 h, the time-domain reflection amplitude decreases by less than 1%, demonstrating that the SiO<sub>2</sub> protective layer effectively suppresses the high-temperature decomposition of LiNbO<sub>3</sub> and reduces the agglomeration rate of Pt electrodes. Experimental results confirm that the proposed high-temperature-resistant SAW tag maintains stable performance under prolonged exposure to 600 °C environments. The tag has been installed on the surface of a steel ladle in a steel plant, demonstrating excellent reliability in a vacuum degassing environment.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"236"},"PeriodicalIF":9.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649009","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 : 2025-11-28DOI: 10.1038/s41378-025-01070-7
Jiao Xu, Jingqian Xi, Chen Wang, Michael Kraft, Huafeng Liu, R P Martins, Pui-In Mak, Yuan Wang
<p><p>The development of multifunctional MEMS resonators has long been constrained by the challenge of integrating high-sensitivity sensing and high-stability frequency referencing into a single compact device. This limitation hinders the realization of advanced microsystems for precision sensing, navigation, and signal processing. This paper reports a novel MEMS resonator tailored for the emerging blue-sideband excitation (BSE) scheme, enabling simultaneous multi-mode actuation within a modest frequency band and inducing intricate nonlinear mode coupling. The device serves as an ideal platform to study BSE-induced mode interactions and amplifies the merits of BSE due to its intrinsic clustered vibration modes around 300 kHz. Featuring a dual-cosine structure, the resonator yields abundant in-plane flexural modes while retaining a capacitive transduction mechanism and the standard SOI manufacturing process. Compared to conventional designs such as clamped-clamped (C-C) beams or double-ended tuning forks (DETF), this device achieves multi-mode operation without requiring MHz frequencies or large spans, making its multi-modal response essential for multi-parameter measurements and multifunctional applications. This work ascertains the device's basic characterizations, including temperature effects, electrostatic perturbation sensitivity, and noise floor, when subjected to the BSE scheme. Notably, some modes exhibit counter-intuitive positive frequency shifts with rising temperatures, enabling stabilization via mode summation. Experimentally, a single mode functions as a sensor with a maximum sensitivity of 39.6 mV/V and a noise floor of 1.9 μV/√Hz (Frequency-mode sensing), while the sum frequency of two modes provides a stable reference with 1.5 ppb at 1000 s (Amplitude-mode sensing). Even under combined temperature and electrostatic disturbances, long-term stability remains around 11.9 ppb at 1000 s. These results demonstrate the dual-mode sensing and referencing capabilities of the proposed resonator, addressing fundamental limitations in current MEMS designs and paving the way for advanced, integrated microsystem applications. The development of multifunctional MEMS resonators has long been constrained by the challenge of integrating high-sensitivity sensing and high-stability frequency referencing into a single compact device. This limitation hinders the realization of advanced microsystems for precision sensing, navigation, and signal processing. This paper reports a novel MEMS resonator tailored for the emerging blue-sideband excitation (BSE) scheme, enabling simultaneous multi-mode actuation within a modest frequency band and inducing intricate nonlinear mode coupling. The device serves as an ideal platform to study BSE-induced mode interactions and amplifies the merits of BSE due to its intrinsic clustered vibration modes around 300 kHz. Featuring a dual-cosine structure, the resonator yields abundant in-plane flexural modes while retaining
{"title":"A multi-functional MEMS resonator for simultaneously dual-mode physical sensing and ppb-level timing.","authors":"Jiao Xu, Jingqian Xi, Chen Wang, Michael Kraft, Huafeng Liu, R P Martins, Pui-In Mak, Yuan Wang","doi":"10.1038/s41378-025-01070-7","DOIUrl":"https://doi.org/10.1038/s41378-025-01070-7","url":null,"abstract":"<p><p>The development of multifunctional MEMS resonators has long been constrained by the challenge of integrating high-sensitivity sensing and high-stability frequency referencing into a single compact device. This limitation hinders the realization of advanced microsystems for precision sensing, navigation, and signal processing. This paper reports a novel MEMS resonator tailored for the emerging blue-sideband excitation (BSE) scheme, enabling simultaneous multi-mode actuation within a modest frequency band and inducing intricate nonlinear mode coupling. The device serves as an ideal platform to study BSE-induced mode interactions and amplifies the merits of BSE due to its intrinsic clustered vibration modes around 300 kHz. Featuring a dual-cosine structure, the resonator yields abundant in-plane flexural modes while retaining a capacitive transduction mechanism and the standard SOI manufacturing process. Compared to conventional designs such as clamped-clamped (C-C) beams or double-ended tuning forks (DETF), this device achieves multi-mode operation without requiring MHz frequencies or large spans, making its multi-modal response essential for multi-parameter measurements and multifunctional applications. This work ascertains the device's basic characterizations, including temperature effects, electrostatic perturbation sensitivity, and noise floor, when subjected to the BSE scheme. Notably, some modes exhibit counter-intuitive positive frequency shifts with rising temperatures, enabling stabilization via mode summation. Experimentally, a single mode functions as a sensor with a maximum sensitivity of 39.6 mV/V and a noise floor of 1.9 μV/√Hz (Frequency-mode sensing), while the sum frequency of two modes provides a stable reference with 1.5 ppb at 1000 s (Amplitude-mode sensing). Even under combined temperature and electrostatic disturbances, long-term stability remains around 11.9 ppb at 1000 s. These results demonstrate the dual-mode sensing and referencing capabilities of the proposed resonator, addressing fundamental limitations in current MEMS designs and paving the way for advanced, integrated microsystem applications. The development of multifunctional MEMS resonators has long been constrained by the challenge of integrating high-sensitivity sensing and high-stability frequency referencing into a single compact device. This limitation hinders the realization of advanced microsystems for precision sensing, navigation, and signal processing. This paper reports a novel MEMS resonator tailored for the emerging blue-sideband excitation (BSE) scheme, enabling simultaneous multi-mode actuation within a modest frequency band and inducing intricate nonlinear mode coupling. The device serves as an ideal platform to study BSE-induced mode interactions and amplifies the merits of BSE due to its intrinsic clustered vibration modes around 300 kHz. Featuring a dual-cosine structure, the resonator yields abundant in-plane flexural modes while retaining","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"234"},"PeriodicalIF":9.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12660926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635862","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}
The capacity to generate high-precision droplets within Lab-on-a-Chip (LOC) devices is essential for numerous biochemical applications, such as DNA sequencing and drug delivery. In this study, we introduce an optoelectrowetting (OEW)-based droplet manipulation system that utilizes a novel droplet dispensing strategy, enabling precise nanoliter droplet dispensing with tunable droplet volume. The system comprises an OEW microchip, a liquid crystal display (LCD) projector connected to a laptop for generating customized light patterns, and a microscope equipped with a charge-coupled device (CCD) camera mounted above the OEW microchip for real-time observation. Simulations and experiments were conducted to investigate the optimal conditions for high-precision droplet dispensing. The system demonstrated exceptional stability in generating uniform droplets, with a minimum relative error (RE) of 0.45% and coefficient of variation (CV) of 2.49% for dispensing droplets of a volume of 36.52 nL. An experiment was conducted to dispense droplets of varying sizes, demonstrating the system's exceptional capability to generate droplets across a broad size range. The system was further validated through its application in polymerase chain reaction (PCR) amplification, confirming its performance in small-scale biochemical reactions. The results indicate that the proposed OEW droplet dispensing system is highly proficient in generating high-precision small-scale droplets with tunable volume. It also demonstrates its capability for biochemical processing and superior performance in sub-200 nL droplet dispensing compared to conventional pipetting techniques. This advancement holds significant potential for enhancing the performance and efficiency of LOC devices in biochemical research and clinical applications.
{"title":"A high-precision nanoliter droplet dispensing system based on optoelectrowetting with tunable droplet volume.","authors":"Kaicheng Huang, Zhen Liu, Yu Liu, Liming Deng, Luojia Jiang, Senlin Yan, Sijing Huang, Shuailong Zhang, Xing Cheng","doi":"10.1038/s41378-025-01071-6","DOIUrl":"https://doi.org/10.1038/s41378-025-01071-6","url":null,"abstract":"<p><p>The capacity to generate high-precision droplets within Lab-on-a-Chip (LOC) devices is essential for numerous biochemical applications, such as DNA sequencing and drug delivery. In this study, we introduce an optoelectrowetting (OEW)-based droplet manipulation system that utilizes a novel droplet dispensing strategy, enabling precise nanoliter droplet dispensing with tunable droplet volume. The system comprises an OEW microchip, a liquid crystal display (LCD) projector connected to a laptop for generating customized light patterns, and a microscope equipped with a charge-coupled device (CCD) camera mounted above the OEW microchip for real-time observation. Simulations and experiments were conducted to investigate the optimal conditions for high-precision droplet dispensing. The system demonstrated exceptional stability in generating uniform droplets, with a minimum relative error (RE) of 0.45% and coefficient of variation (CV) of 2.49% for dispensing droplets of a volume of 36.52 nL. An experiment was conducted to dispense droplets of varying sizes, demonstrating the system's exceptional capability to generate droplets across a broad size range. The system was further validated through its application in polymerase chain reaction (PCR) amplification, confirming its performance in small-scale biochemical reactions. The results indicate that the proposed OEW droplet dispensing system is highly proficient in generating high-precision small-scale droplets with tunable volume. It also demonstrates its capability for biochemical processing and superior performance in sub-200 nL droplet dispensing compared to conventional pipetting techniques. This advancement holds significant potential for enhancing the performance and efficiency of LOC devices in biochemical research and clinical applications.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"231"},"PeriodicalIF":9.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12660984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635729","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}
As semiconductor devices approach fundamental physical scaling limits, molecular electronics has emerged as a potential technological paradigm for sustaining Moore's Law through the capabilities of single-molecule-scale functional manipulation and quantum modulation. At the foundational research level, the convergence of atomic-precision fabrication techniques with molecule-electrode interfaces and molecular orbital engineering has enabled the directional construction of electronically functional single-molecule devices, including molecular switches, rectifiers, and field-effect transistors, accompanied by preliminary validations of molecular device array integration. However, molecular electronics confronts multifaceted challenges spanning device-level bottlenecks in precise molecular assembly, accurate quantum charge transport characterizations, and performance reproducibility, coupled with integration-level limitations imposed by conventional two-dimensional planar architectures that fundamentally constrain functional density scaling, rendering the realization of high-density integrated molecular devices with operational logic capabilities exceptionally demanding. To address these critical issues, researchers have developed various device fabrication and characterization techniques in recent years, such as the integration of top-down micro/nano-fabrication technologies with bottom-up atomic manufacturing approaches, which have significantly enhanced the stability of molecular devices and data reproducibility. This review systematically summarizes recent advances in preparation methodologies for molecular electronic devices with high reproducibility and reliability, with prospective emphasis on an integrated architecture strategy combining atomic manufacturing technologies with three-dimensional (3D) integrated manufacturing technologies, offering a potential roadmap to transcend conventional two-dimensional integration paradigms and realize logical computing functionalities in molecular electronic devices.
{"title":"Molecular electronic devices based on atomic manufacturing methods.","authors":"Chengpeng Yao, Yaning Li, Hao Zhang, Dongdong Wang, Jia Wang, Xiaojing Wang, Xiaohui Li, Junyang Liu, Wenjing Hong","doi":"10.1038/s41378-025-01037-8","DOIUrl":"https://doi.org/10.1038/s41378-025-01037-8","url":null,"abstract":"<p><p>As semiconductor devices approach fundamental physical scaling limits, molecular electronics has emerged as a potential technological paradigm for sustaining Moore's Law through the capabilities of single-molecule-scale functional manipulation and quantum modulation. At the foundational research level, the convergence of atomic-precision fabrication techniques with molecule-electrode interfaces and molecular orbital engineering has enabled the directional construction of electronically functional single-molecule devices, including molecular switches, rectifiers, and field-effect transistors, accompanied by preliminary validations of molecular device array integration. However, molecular electronics confronts multifaceted challenges spanning device-level bottlenecks in precise molecular assembly, accurate quantum charge transport characterizations, and performance reproducibility, coupled with integration-level limitations imposed by conventional two-dimensional planar architectures that fundamentally constrain functional density scaling, rendering the realization of high-density integrated molecular devices with operational logic capabilities exceptionally demanding. To address these critical issues, researchers have developed various device fabrication and characterization techniques in recent years, such as the integration of top-down micro/nano-fabrication technologies with bottom-up atomic manufacturing approaches, which have significantly enhanced the stability of molecular devices and data reproducibility. This review systematically summarizes recent advances in preparation methodologies for molecular electronic devices with high reproducibility and reliability, with prospective emphasis on an integrated architecture strategy combining atomic manufacturing technologies with three-dimensional (3D) integrated manufacturing technologies, offering a potential roadmap to transcend conventional two-dimensional integration paradigms and realize logical computing functionalities in molecular electronic devices.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"232"},"PeriodicalIF":9.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12660758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634854","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}
The early and precise diagnosis of suspected pathological tissues or organs has increasingly embraced the utilization of 3D real-time visualization and discrimination of intricate structures facilitated by miniature optical coherence tomography (OCT) endoscopic probes. Those miniature side-viewing endoscopic fiber probes are indispensable for 3D imaging with small, narrow lumens, eliminating the potential for tissue trauma associated with direct-viewing techniques. Nevertheless, current manufacturing techniques pose limitations on the overall imaging prowess of these miniaturized side-viewing probes, hindering their widespread adoption. To surmount this challenge, an ultra-compact side-viewing OCT fiber-optic endoscopic probe with extended depth of focus (DOF) and high lateral resolution is designed based on the all-fiber composite structure. The quantitative relationship between the imaging performance and the fiber structural parameters has been theoretically analyzed. The imaging performance of the fiber probe can be flexibly tailored by adjusting the geometric parameters of the fiber-optic cascade structure. The applicability and feasibility of fiber probe prototype have been convincingly demonstrated through linear scanning and rotational scanning methodologies. This ultra-compact side-viewing OCT fiber probe's capacity to deliver microscopic structural insights paves the way for minimally invasive applications, expected to advance the frontier of early and precise diagnosis and treatment of suspected lesion tissues.
{"title":"Side-viewing axicon-integrated miniature fiber probe for extended depth of focus and ultrahigh lateral resolution endoscopic imaging.","authors":"Yin Liu, Duanhong Zhang, Wenxin Li, Shicheng Zheng, Hong Fan, Tianyuan Lan, Qun Hao, Yong Huang","doi":"10.1038/s41378-025-01034-x","DOIUrl":"10.1038/s41378-025-01034-x","url":null,"abstract":"<p><p>The early and precise diagnosis of suspected pathological tissues or organs has increasingly embraced the utilization of 3D real-time visualization and discrimination of intricate structures facilitated by miniature optical coherence tomography (OCT) endoscopic probes. Those miniature side-viewing endoscopic fiber probes are indispensable for 3D imaging with small, narrow lumens, eliminating the potential for tissue trauma associated with direct-viewing techniques. Nevertheless, current manufacturing techniques pose limitations on the overall imaging prowess of these miniaturized side-viewing probes, hindering their widespread adoption. To surmount this challenge, an ultra-compact side-viewing OCT fiber-optic endoscopic probe with extended depth of focus (DOF) and high lateral resolution is designed based on the all-fiber composite structure. The quantitative relationship between the imaging performance and the fiber structural parameters has been theoretically analyzed. The imaging performance of the fiber probe can be flexibly tailored by adjusting the geometric parameters of the fiber-optic cascade structure. The applicability and feasibility of fiber probe prototype have been convincingly demonstrated through linear scanning and rotational scanning methodologies. This ultra-compact side-viewing OCT fiber probe's capacity to deliver microscopic structural insights paves the way for minimally invasive applications, expected to advance the frontier of early and precise diagnosis and treatment of suspected lesion tissues.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"235"},"PeriodicalIF":9.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12663204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635623","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 : 2025-11-28DOI: 10.1038/s41378-025-01046-7
Sihan Hua, Yaoyao Liu, Jinping Luo, Shangchen Li, Longhui Jiang, Pei Wu, Shutong Sun, Li Shang, Chengji Lu, Kui Zhang, Juntao Liu, Mixia Wang, Huaizhang Shi, Xinxia Cai
Microelectrode arrays (MEAs) cultured with in vitro neural networks are gaining prominence in bio-integrated system research, owing to their inherent plasticity and emergent learning behaviors. Here, recent advances in motion control tasks utilizing MEAs-based bio-integrated systems are presented, with a focus on encoding-decoding techniques. The bio-integrated system comprises MEAs integrated with neural networks, a bidirectional communication system, and an actuator. Classical decoding algorithms, such as firing-rate mapping and central firing-rate methods, along with cutting-edge artificial intelligence (AI) approaches, have been examined. These AI methods enhance the accuracy and adaptability of real-time, closed-loop motion control. A comparative analysis indicates that simpler, lower-complexity algorithms suit basic rapid-decision tasks, whereas deeper models exhibit greater potential in more complex temporal signal processing and dynamically changing environments. The review also systematically analyzes the prospects and challenges of bio-integrated systems for motion control. Future prospects suggest that MEAs cultured with in vitro neural networks may leverage their flexibility and low energy consumption to address diverse motion control scenarios, driving cross-disciplinary research at the intersection of neuroscience and artificial intelligence.
{"title":"Microelectrode arrays cultured with in vitro neural networks for motion control tasks: encoding and decoding progress and advances.","authors":"Sihan Hua, Yaoyao Liu, Jinping Luo, Shangchen Li, Longhui Jiang, Pei Wu, Shutong Sun, Li Shang, Chengji Lu, Kui Zhang, Juntao Liu, Mixia Wang, Huaizhang Shi, Xinxia Cai","doi":"10.1038/s41378-025-01046-7","DOIUrl":"https://doi.org/10.1038/s41378-025-01046-7","url":null,"abstract":"<p><p>Microelectrode arrays (MEAs) cultured with in vitro neural networks are gaining prominence in bio-integrated system research, owing to their inherent plasticity and emergent learning behaviors. Here, recent advances in motion control tasks utilizing MEAs-based bio-integrated systems are presented, with a focus on encoding-decoding techniques. The bio-integrated system comprises MEAs integrated with neural networks, a bidirectional communication system, and an actuator. Classical decoding algorithms, such as firing-rate mapping and central firing-rate methods, along with cutting-edge artificial intelligence (AI) approaches, have been examined. These AI methods enhance the accuracy and adaptability of real-time, closed-loop motion control. A comparative analysis indicates that simpler, lower-complexity algorithms suit basic rapid-decision tasks, whereas deeper models exhibit greater potential in more complex temporal signal processing and dynamically changing environments. The review also systematically analyzes the prospects and challenges of bio-integrated systems for motion control. Future prospects suggest that MEAs cultured with in vitro neural networks may leverage their flexibility and low energy consumption to address diverse motion control scenarios, driving cross-disciplinary research at the intersection of neuroscience and artificial intelligence.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"233"},"PeriodicalIF":9.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12660870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635834","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 : 2025-11-27DOI: 10.1038/s41378-025-01093-0
Seung-Han Chung, Chaesung Kim, Minju Kim, Donggeun Choi, Yunseo Son, Hyeonhee Roh, Byung Chul Lee, Hyung-Min Lee, Yong-Kweon Kim, Seung-Ki Lee, Jae-Hyoung Park, Maesoon Im
The need for spatially-confined electrical stimulation is growing in biomedical applications, for example intracortical stimulation and retinal implant, for enhancement of stimulating resolution. Local grounding techniques have been widely explored to suppress undesired current spread. However, in conventional microneedle arrays like the Utah array, grounding is typically achieved by assigning neighboring electrodes as ground or employing grounding wall around stimulating electrode, which compromises spatial efficiency. In this work, we introduce, for the first time, a bipolar microneedle electrode array (BMEA) that integrates two electrically-independent electrodes within each three-dimensional microneedle structure. The microtip electrode, located at the apex of the microneedle, delivers electrical stimulation, while the local ground electrode, embedded on the sidewall below the microtip, serves to locally confine the spread of current. COMSOL Multiphysics simulations and ex vivo experiments using isolated mouse retina demonstrated that activating the local ground electrode effectively restricts current diffusion, enabling more focused and localized stimulation. This approach offers a compact and efficient solution for focal electrical stimulation with enhanced spatial resolution, providing a promising platform for advanced neural interfacing systems in various biomedical fields.
{"title":"A three-dimensional bipolar microneedle electrode array with local ground integrated at each sidewall for enhanced focal electric stimulation.","authors":"Seung-Han Chung, Chaesung Kim, Minju Kim, Donggeun Choi, Yunseo Son, Hyeonhee Roh, Byung Chul Lee, Hyung-Min Lee, Yong-Kweon Kim, Seung-Ki Lee, Jae-Hyoung Park, Maesoon Im","doi":"10.1038/s41378-025-01093-0","DOIUrl":"https://doi.org/10.1038/s41378-025-01093-0","url":null,"abstract":"<p><p>The need for spatially-confined electrical stimulation is growing in biomedical applications, for example intracortical stimulation and retinal implant, for enhancement of stimulating resolution. Local grounding techniques have been widely explored to suppress undesired current spread. However, in conventional microneedle arrays like the Utah array, grounding is typically achieved by assigning neighboring electrodes as ground or employing grounding wall around stimulating electrode, which compromises spatial efficiency. In this work, we introduce, for the first time, a bipolar microneedle electrode array (BMEA) that integrates two electrically-independent electrodes within each three-dimensional microneedle structure. The microtip electrode, located at the apex of the microneedle, delivers electrical stimulation, while the local ground electrode, embedded on the sidewall below the microtip, serves to locally confine the spread of current. COMSOL Multiphysics simulations and ex vivo experiments using isolated mouse retina demonstrated that activating the local ground electrode effectively restricts current diffusion, enabling more focused and localized stimulation. This approach offers a compact and efficient solution for focal electrical stimulation with enhanced spatial resolution, providing a promising platform for advanced neural interfacing systems in various biomedical fields.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"230"},"PeriodicalIF":9.9,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12661015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635872","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 : 2025-11-26DOI: 10.1038/s41378-025-01052-9
Jongeon Park, Renaud Rovera, Arnaud Bertsch, Nicolas Zaugg, Hiba Hassoun, Evelyne Colomb, Claire Monge, Juergen Brugger
Amphiphilic lipid formulations, such as self-emulsifying drug delivery systems, offer advantages for enhancing drug release control and expanding their applicability across various administration routes. By integrating microfabrication techniques with these lipid-based systems, additional functionalities such as controlled drug release can be introduced. This can broaden lipid's potential for advanced biomedical and pharmaceutical applications. However, lipids face major fabrication challenges due to their thermolability, solvent incompatibility, and poor mechanical properties. Here, we present a novel microfabrication route for self-emulsifying lipid drug delivery systems based on thermal imprinting of a stiffness-tunable mold, which stays inflexible during the thermal imprinting step and softens upon swelling for the demolding step. The stiffness tuning process is reversible to some extent through a simple drying process, allowing reuse of the mold. The presented method resolves the issues of mechanical stress and lipid dissolution during the demolding process, enabling the scalable and cost-efficient fabrication of lipid microstructures down to 20 µm resolution and a 5:1 aspect ratio. As a proof-of-concept, we fabricated honeycomb-shaped self-emulsifying drug delivery lipid microstructures on a mucoadhesive film. Lipid microstructure increases the mechanical robustness and accelerates lipid dissolution for sublingual administration of poorly water-soluble drugs. In vivo testing in mouse models confirmed efficient mucosal penetration and submucosal drug accumulation, showing potential as sublingual drug delivery devices.
{"title":"Fabrication of self-emulsifying lipid microstructure by stiffness-tunable mold for drug delivery applications.","authors":"Jongeon Park, Renaud Rovera, Arnaud Bertsch, Nicolas Zaugg, Hiba Hassoun, Evelyne Colomb, Claire Monge, Juergen Brugger","doi":"10.1038/s41378-025-01052-9","DOIUrl":"10.1038/s41378-025-01052-9","url":null,"abstract":"<p><p>Amphiphilic lipid formulations, such as self-emulsifying drug delivery systems, offer advantages for enhancing drug release control and expanding their applicability across various administration routes. By integrating microfabrication techniques with these lipid-based systems, additional functionalities such as controlled drug release can be introduced. This can broaden lipid's potential for advanced biomedical and pharmaceutical applications. However, lipids face major fabrication challenges due to their thermolability, solvent incompatibility, and poor mechanical properties. Here, we present a novel microfabrication route for self-emulsifying lipid drug delivery systems based on thermal imprinting of a stiffness-tunable mold, which stays inflexible during the thermal imprinting step and softens upon swelling for the demolding step. The stiffness tuning process is reversible to some extent through a simple drying process, allowing reuse of the mold. The presented method resolves the issues of mechanical stress and lipid dissolution during the demolding process, enabling the scalable and cost-efficient fabrication of lipid microstructures down to 20 µm resolution and a 5:1 aspect ratio. As a proof-of-concept, we fabricated honeycomb-shaped self-emulsifying drug delivery lipid microstructures on a mucoadhesive film. Lipid microstructure increases the mechanical robustness and accelerates lipid dissolution for sublingual administration of poorly water-soluble drugs. In vivo testing in mouse models confirmed efficient mucosal penetration and submucosal drug accumulation, showing potential as sublingual drug delivery devices.</p>","PeriodicalId":18560,"journal":{"name":"Microsystems & Nanoengineering","volume":"11 1","pages":"229"},"PeriodicalIF":9.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12647786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604921","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}