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High-throughput chip-calorimeter using a Bi2Te3 thermopile heat flux sensor array. 采用Bi2Te3热电堆热流传感器阵列的高通量芯片量热计。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-02 DOI: 10.1038/s41378-025-01082-3
Yang Liu, Zhengguang Chen, Yushan Xie, Yinghao Zhang, Guanqin Zhang, Yuchen Wang, Jiale Cheng

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 V · W - 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.

现代热电模块已成为生物和化学应用中精密热分析的有前途的平台。本研究提出了一种采用图案化碲化铋(Bi2Te3)热电堆阵列作为集成热通量传感器的高通量微量热计,克服了传统量热系统的通量限制。通过有限元分析导向的器件优化,我们确定将热电偶高度从0.4 mm增加到0.8 mm可以降低热导率,实现约1 V·W - 1的功率灵敏度。该系统演示了使用电学(焦耳加热)和化学(水-乙醇混合焓)参考的双模式校准方法。通过实时监测大肠杆菌代谢来验证设备功能,揭示抗生素挑战时不同的热特征。采用4种常用抗生素进行药敏试验(AST)。该平台达到4小时AST,与临床和实验室标准协会(CLSI)最低抑制浓度(MIC)测定指南的值一致。值得注意的是,模块化芯片架构集成了8个传感单元作为概念验证,再加上一次性微流体室,消除交叉污染风险。这种芯片量热计的实现为化学反应热测量和传染病的快速临床诊断建立了新的范例。
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引用次数: 0
Integrated 3D microstructured digital microfluidic platform for advanced 3D cell culture. 集成三维微结构数字微流控平台先进的三维细胞培养。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-02 DOI: 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.

三维(3D)细胞培养系统通过促进细胞间相互作用和功能表达来更好地模拟体内微环境,这对组织工程和再生医学至关重要。然而,传统的二维(2D)培养平台无法模拟体内组织的空间复杂性,经常导致细胞行为改变和有限的生理相关性。在这项研究中,我们介绍了一个基于数字微流体(DMF)系统的三维细胞培养平台。该平台将DMF电极驱动与3D打印微观结构阵列集成在一起,能够在定义的3D支架内精确捕获和聚集细胞。当细胞最初以二维结构附着时,它们会迅速自组装成芯片上的三维细胞球体。使用3d打印DMF芯片验证了平台的液滴分散、融合和移动能力。系统地研究了施加电压、微结构高度和电极间距等关键参数对液滴操纵的影响。24,48和72小时的细胞活力和增殖试验证实,3D微结构支架具有良好的生物相容性,并提供了有利于体内样细胞生长的微环境。总的来说,这种集成的DMF芯片支持强大的3D细胞生长,代表了组织工程和再生医学应用的多功能工具。
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引用次数: 0
A surface acoustic wave tag utilizing a multilayer structure of SiO2/Pt/128°YX-LiNbO3 for operation at 600 °C. 采用SiO2/Pt/128°YX-LiNbO3多层结构的表面声波标签,可在600°C下工作。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-01 DOI: 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.

本研究提出了一种基于SiO2/Pt/128°YX-LiNbO3多层结构的表面声波(SAW)标签,解决了传统表面声波标签在高温条件下失效的问题。采用有限元法/波数域分析(FEM/WDA)方法对结构进行了仿真,揭示了反射面拓扑参数对saw散射特性的影响。与Pt/128°YX-LiNbO3相比,多层结构中的体波散射降低了50%。在标签的微纳加工中,采用物理气相沉积(PVD)制备了低粗糙度、高密度的SiO2薄膜。测试结果表明,在30-600°C的宽温度范围内,该标签的温度频率系数(TCF)为-32.38 ppm/°C。经过600℃高温冲击336 h后,时域反射幅值下降幅度小于1%,说明SiO2保护层有效抑制了LiNbO3的高温分解,降低了Pt电极的团聚率。实验结果证实,所提出的耐高温SAW标签在长时间暴露于600°C环境下仍保持稳定的性能。该标签已安装在某钢厂的钢包表面,在真空脱气环境中表现出优异的可靠性。
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引用次数: 0
A multi-functional MEMS resonator for simultaneously dual-mode physical sensing and ppb-level timing. 一种同时实现双模物理传感和ppb级定时的多功能MEMS谐振器。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-11-28 DOI: 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
长期以来,多功能MEMS谐振器的发展一直受到将高灵敏度传感和高稳定频率参考集成到单个紧凑器件中的挑战的限制。这种限制阻碍了精密传感、导航和信号处理的先进微系统的实现。本文报道了一种为新兴的蓝带激励(BSE)方案量身定制的新型MEMS谐振器,能够在适度的频带内同时进行多模式驱动,并诱导复杂的非线性模式耦合。该装置是研究疯牛病诱导模式相互作用的理想平台,并且由于其固有的300 kHz左右的群集振动模式而放大了疯牛病的优点。具有双余弦结构,谐振器产生丰富的面内弯曲模式,同时保留电容转导机制和标准的SOI制造工艺。与传统设计(如夹紧-夹紧(C-C)梁或双端音叉(DETF))相比,该设备无需MHz频率或大跨度即可实现多模式操作,使其多模态响应对于多参数测量和多功能应用至关重要。这项工作确定了器件的基本特性,包括温度效应、静电扰动灵敏度和噪声底,当受到BSE方案时。值得注意的是,随着温度的升高,一些模式表现出反直觉的正频移,通过模式求和实现稳定。实验中,单模作为传感器的最大灵敏度为39.6 mV/V,本底噪声为1.9 μV/√Hz(频模传感),而两种模式的频率总和在1000 s时提供了1.5 ppb的稳定参考(幅模传感)。即使在温度和静电干扰下,在1000秒内,长期稳定性仍保持在11.9 ppb左右。这些结果证明了所提出的谐振器的双模传感和参考能力,解决了当前MEMS设计的基本限制,并为先进的集成微系统应用铺平了道路。长期以来,多功能MEMS谐振器的发展一直受到将高灵敏度传感和高稳定频率参考集成到单个紧凑器件中的挑战的限制。这种限制阻碍了精密传感、导航和信号处理的先进微系统的实现。本文报道了一种为新兴的蓝带激励(BSE)方案量身定制的新型MEMS谐振器,能够在适度的频带内同时进行多模式驱动,并诱导复杂的非线性模式耦合。该装置是研究疯牛病诱导模式相互作用的理想平台,并且由于其固有的300 kHz左右的群集振动模式而放大了疯牛病的优点。具有双余弦结构,谐振器产生丰富的面内弯曲模式,同时保留电容转导机制和标准的SOI制造工艺。与传统设计(如夹紧-夹紧(C-C)梁或双端音叉(DETF))相比,该设备无需MHz频率或大跨度即可实现多模式操作,使其多模态响应对于多参数测量和多功能应用至关重要。这项工作确定了器件的基本特性,包括温度效应、静电扰动灵敏度和噪声底,当受到BSE方案时。值得注意的是,随着温度的升高,一些模态表现出反直觉的正频移,从而通过模态求和实现稳定。实验中,单模作为传感器的最大灵敏度为39.6 mV/V,本底噪声为1.9 μV/√Hz(频模传感),而两种模式的频率总和在1000 s时提供了1.5 ppb的稳定参考(幅模传感)。即使在温度和静电干扰下,在1000秒内,长期稳定性仍保持在11.9 ppb左右。这些结果证明了所提出的谐振器的双模传感和参考能力,解决了当前MEMS设计的基本限制,并为先进的集成微系统应用铺平了道路。
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引用次数: 0
A high-precision nanoliter droplet dispensing system based on optoelectrowetting with tunable droplet volume. 一种基于光电润湿、液滴体积可调的高精度纳升点胶系统。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-11-28 DOI: 10.1038/s41378-025-01071-6
Kaicheng Huang, Zhen Liu, Yu Liu, Liming Deng, Luojia Jiang, Senlin Yan, Sijing Huang, Shuailong Zhang, Xing Cheng

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.

在芯片实验室(LOC)设备中产生高精度液滴的能力对于许多生化应用至关重要,例如DNA测序和药物输送。在这项研究中,我们介绍了一种基于光电润湿(OEW)的液滴操作系统,该系统利用一种新颖的液滴点胶策略,实现了精确的纳米升液滴点胶,液滴体积可调。该系统包括一个OEW微芯片,一个连接到笔记本电脑的液晶显示器(LCD)投影仪,用于生成定制的光模式,以及一个安装在OEW微芯片上方的配备电荷耦合器件(CCD)相机的显微镜,用于实时观察。通过仿真和实验研究了高精度液滴点胶的最佳条件。该系统在生成均匀液滴方面表现出优异的稳定性,对于36.52 nL的液滴,最小相对误差(RE)为0.45%,变异系数(CV)为2.49%。进行了不同尺寸的液滴分配实验,证明了该系统在广泛尺寸范围内产生液滴的卓越能力。通过聚合酶链反应(PCR)扩增,进一步验证了该系统在小规模生化反应中的性能。结果表明,所提出的OEW液滴点胶系统能够高效地生成体积可调的高精度小液滴。与传统移液技术相比,它还展示了其生化处理能力和在低于200 nL的液滴分配中的优越性能。这一进展对于提高LOC装置在生化研究和临床应用中的性能和效率具有重要的潜力。
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引用次数: 0
Molecular electronic devices based on atomic manufacturing methods. 基于原子制造方法的分子电子器件。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-11-28 DOI: 10.1038/s41378-025-01037-8
Chengpeng Yao, Yaning Li, Hao Zhang, Dongdong Wang, Jia Wang, Xiaojing Wang, Xiaohui Li, Junyang Liu, Wenjing Hong

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.

随着半导体器件接近基本的物理尺度极限,分子电子学已经成为一种潜在的技术范例,通过单分子尺度的功能操纵和量子调制的能力来维持摩尔定律。在基础研究层面,原子精密制造技术与分子电极界面和分子轨道工程的融合,使定向构建电子功能单分子器件成为可能,包括分子开关、整流器和场效应晶体管,并伴随着分子器件阵列集成的初步验证。然而,分子电子学面临着多方面的挑战,包括精确分子组装、精确量子电荷输运表征和性能再现方面的器件级瓶颈,以及传统二维平面架构带来的集成级限制,这些限制从根本上限制了功能密度缩放。实现具有操作逻辑能力的高密度集成分子器件的要求非常高。为了解决这些关键问题,近年来研究人员开发了各种器件制造和表征技术,例如自顶向下的微纳米制造技术与自底向上的原子制造方法的集成,这大大提高了分子器件的稳定性和数据的可重复性。本文系统总结了具有高可重复性和高可靠性的分子电子器件的制备方法的最新进展,并展望了原子制造技术与三维集成制造技术相结合的集成架构策略。提供一个潜在的路线图,超越传统的二维集成范式和实现逻辑计算功能的分子电子器件。
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引用次数: 0
Side-viewing axicon-integrated miniature fiber probe for extended depth of focus and ultrahigh lateral resolution endoscopic imaging. 侧视轴突集成微型光纤探头,用于扩展聚焦深度和超高横向分辨率内窥镜成像。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-11-28 DOI: 10.1038/s41378-025-01034-x
Yin Liu, Duanhong Zhang, Wenxin Li, Shicheng Zheng, Hong Fan, Tianyuan Lan, Qun Hao, Yong Huang

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.

对疑似病理组织或器官的早期和精确诊断越来越多地采用三维实时可视化和微型光学相干断层扫描(OCT)内窥镜探针对复杂结构的识别。这些微型侧面观察内窥镜纤维探头对于小而窄的腔体的3D成像是必不可少的,消除了与直接观察技术相关的组织损伤的可能性。然而,目前的制造技术限制了这些小型化侧视探头的整体成像能力,阻碍了它们的广泛采用。为了克服这一挑战,基于全光纤复合材料结构设计了一种具有扩展焦深(DOF)和高横向分辨率的超紧凑侧视OCT光纤内窥镜探头。从理论上分析了成像性能与光纤结构参数之间的定量关系。通过调整光纤级联结构的几何参数,可以灵活地定制光纤探头的成像性能。通过线性扫描和旋转扫描两种方法,令人信服地证明了光纤探针原型的适用性和可行性。这种超紧凑的侧面观察OCT纤维探针能够提供微观结构的洞察力,为微创应用铺平了道路,有望推进早期和精确诊断和治疗可疑病变组织的前沿。
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引用次数: 0
Microelectrode arrays cultured with in vitro neural networks for motion control tasks: encoding and decoding progress and advances. 用于运动控制任务的体外神经网络培养微电极阵列:编码和解码的进展和进展。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-11-28 DOI: 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.

体外神经网络培养的微电极阵列(MEAs)由于其固有的可塑性和突发性学习行为,在生物集成系统研究中越来越受到重视。本文介绍了基于mea的生物集成系统在运动控制任务方面的最新进展,重点介绍了编码-解码技术。该生物集成系统包括与神经网络集成的mea、双向通信系统和执行器。经典的解码算法,如发射速率映射和中央发射速率方法,以及尖端的人工智能(AI)方法,已经进行了研究。这些人工智能方法提高了实时闭环运动控制的准确性和适应性。对比分析表明,更简单、更低复杂度的算法适用于基本的快速决策任务,而更深层次的模型在更复杂的时间信号处理和动态变化的环境中表现出更大的潜力。本文还系统地分析了生物集成运动控制系统的发展前景和面临的挑战。未来的前景表明,体外神经网络培养的mea可以利用其灵活性和低能耗来解决各种运动控制场景,推动神经科学和人工智能交叉的跨学科研究。
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引用次数: 0
A three-dimensional bipolar microneedle electrode array with local ground integrated at each sidewall for enhanced focal electric stimulation. 一种三维双极微针电极阵列,在每个侧壁集成局部接地,用于增强局部电刺激。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-11-27 DOI: 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.

在生物医学应用中,对空间限制电刺激的需求越来越大,例如皮质内刺激和视网膜植入,以提高刺激分辨率。局部接地技术已被广泛探索以抑制不希望的电流扩散。然而,在传统的微针阵列中,如犹他阵列,接地通常是通过分配相邻电极作为接地或在刺激电极周围使用接地墙来实现的,这损害了空间效率。在这项工作中,我们首次介绍了一种双极微针电极阵列(BMEA),该阵列在每个三维微针结构中集成了两个电独立的电极。微针尖电极位于微针的顶端,提供电刺激,而局部接地电极嵌入微针尖下方的侧壁,用于局部限制电流的传播。COMSOL Multiphysics模拟和离体小鼠视网膜实验表明,激活局部接地电极有效地限制了电流扩散,实现了更集中和局部的刺激。该方法为增强空间分辨率的局部电刺激提供了一种紧凑高效的解决方案,为各种生物医学领域的先进神经接口系统提供了一个有前途的平台。
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引用次数: 0
Fabrication of self-emulsifying lipid microstructure by stiffness-tunable mold for drug delivery applications. 用刚度可调模具制备用于药物输送的自乳化脂质微观结构。
IF 9.9 1区 工程技术 Q1 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-11-26 DOI: 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.

两亲性脂类制剂,如自乳化给药系统,在加强药物释放控制和扩大其在各种给药途径中的适用性方面具有优势。通过将微加工技术与这些基于脂质的系统集成,可以引入额外的功能,例如控制药物释放。这可以扩大脂质在先进生物医学和制药应用方面的潜力。然而,由于其耐热性、溶剂不相容性和机械性能差,脂质面临着主要的制造挑战。在这里,我们提出了一种基于刚度可调模具热印迹的自乳化脂质药物递送系统的新型微加工路线,该模具在热印迹步骤中保持不灵活,在脱模步骤中肿胀时软化。通过简单的干燥过程,刚度调整过程在某种程度上是可逆的,允许模具的重复使用。该方法解决了脱模过程中的机械应力和脂质溶解问题,使脂质微结构的制造具有可扩展性和成本效益,分辨率低至20微米,宽高比为5:1。作为概念验证,我们在粘接膜上制造了蜂窝状自乳化给药脂质微观结构。脂质微观结构增加机械稳健性,加速脂质溶解,用于舌下给药的低水溶性药物。在小鼠模型中的体内测试证实了有效的粘膜渗透和粘膜下药物蓄积,显示出作为舌下给药装置的潜力。
{"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}
引用次数: 0
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Microsystems & Nanoengineering
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