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Geometric anisotropy driven control of viscous fingering for deterministic square-mesh formation in a lifting multi-port Hele Shaw cell 基于几何各向异性驱动的多端口Hele Shaw单元中确定方形网格形成的粘性指进控制
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2026-01-07 DOI: 10.1007/s10404-025-02868-7
Sharad Rajaram Valvi, Kiran Suresh Bhole

The present study explores anisotropy driven regulation of viscous fingering in a lifting Hele Shaw cell, enabling deterministic square mesh formation. A multiport plate with 0.5 mm source holes coupled with circumferential grooves of 1.5 mm width was investigated under controlled lifting and airflow and interpreted using a Darcy Herschel–Bulkley framework. Under moderate lifting rates of 4 to 5 mm per minute and a high-viscosity resin of approximately 1.57 × 10⁶ cP, the initially stochastic interface transitions into reproducible 5 × 5 mm lattices, consistent with analytical predictions for a stable composite regime ((varLambda = {C}_{a}^{*}/{B}_{n}) ≈ 10⁻² to 10⁻¹). The measured finger-to-pitch ratio (w/ ≈ 0.22 to 0.25) closely matches model estimates, confirming the predictive linkage between gap dynamics and pressure-field anisotropy created by groove–hole coupling. Experiments further reveal fractal-like kinetics with a confined fractal dimension of about 1.75 ± 0.05, while higher lifting velocities or reduced viscosities induce morphological disorder due to elevated (:{C}_{a}^{*}) and weakened tip shielding. Perfect mesh formation requires the combined effects of geometric anisotropy, which defines orthogonal pressure minima, and boundary-controlled air entry that homogenizes the pressure gradient. These findings establish a predictive, lithography-free framework for template-assisted microfluidic patterning and tuneable porous architectures guided by controlled interfacial anisotropy.

本研究探讨了各向异性驱动的调节粘性指法在一个提升Hele Shaw细胞,使确定的方形网格形成。在可控升力和气流作用下,研究了具有0.5 mm源孔和1.5 mm宽周向凹槽的多孔板,并使用Darcy Herschel-Bulkley框架进行了解释。在每分钟4到5毫米的中等升力和大约1.57 × 10⁶cP的高粘度树脂下,最初的随机界面转变为可重复的5 × 5毫米晶格,与稳定复合体系的分析预测一致((varLambda = {C}_{a}^{*}/{B}_{n})≈10⁻²至10⁻¹)。测量到的指节比(w/p≈0.22 ~ 0.25)与模型估计非常吻合,证实了间隙动力学与槽孔耦合产生的压力场各向异性之间的预测联系。实验进一步揭示了分形动力学,分形维数约为1.75±0.05,而更高的提升速度或降低的粘度会导致(:{C}_{a}^{*})升高和尖端屏蔽减弱导致形态紊乱。完美的网格形成需要几何各向异性(定义正交压力最小值)和边界控制的空气进入(均匀化压力梯度)的综合作用。这些发现为模板辅助微流控图形和可调的多孔结构建立了一个预测性的、无光刻的框架,该框架由受控的界面各向异性引导。
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引用次数: 0
Area-selective patterning of a liquid-infused surface for droplet manipulation 用于液滴操作的液体注入表面的区域选择图形
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2026-01-07 DOI: 10.1007/s10404-025-02862-z
Zhen Liu, Rifei Chen, Chunhui Wu, Hongjun Liu, Liqiu Wang, Xing Cheng

The fabrication process of the liquid-infused surface (LIS) usually involves complicated surface modifications or is substrate-limited. In this study, a new LIS coating on various material surfaces is reported, in which a highly porous polytetrafluoroethylene (p-PTFE) film is initially deposited and followed by the lubricant infusing into the nanostructures. The LIS-coated glass slides present improved transparency compared to bare ones and low contact angle hysteresis with different droplets. The capability of p-PTFE film in lubricant retention is demonstrated, and the durability test of the LIS is conducted. Small droplets (5 µL) can slide easily in a stereoscopic LIS-coated resin channel, exhibiting the adaptation of LIS in coating on complex topography surfaces. By applying a metallic shadow mask during the p-PTFE film deposition, the substrate’s surface is thus selectively modified, presenting various hydrophobic-hydrophilic patterns. Lastly, this LIS is applied in a digital microfluidics (DMF) chip on the Parylene-C and Indium Tin Oxide (ITO) surface. By patterning the chip’s surface, the precision of the droplets’ separation is significantly improved, and single polystyrene bead isolation is realized.

Graphical Abstract

液体注入表面(LIS)的制造过程通常涉及复杂的表面修饰或受衬底限制。在这项研究中,报告了一种新的LIS涂层在各种材料表面,其中一种高孔聚四氟乙烯(p-PTFE)薄膜最初沉积,然后将润滑剂注入纳米结构。与裸玻片相比,涂覆lis的玻片具有更好的透明度和低接触角迟滞。论证了聚四氟乙烯膜的保油性能,并对其进行了耐久性试验。小液滴(5µL)可以很容易地在立体的LIS涂层树脂通道中滑动,显示了LIS在复杂地形表面涂层中的适应性。通过在p-PTFE薄膜沉积过程中施加金属阴影掩膜,基材的表面因此被选择性地修饰,呈现出各种疏水-亲水性图案。最后,将该LIS应用于二甲苯- c和氧化铟锡(ITO)表面的数字微流控(DMF)芯片。通过对芯片表面进行图形化处理,大大提高了液滴分离的精度,实现了单个聚苯乙烯珠的分离。图形抽象
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引用次数: 0
Manipulation of microparticles using acoustic actuators: a review 利用声学致动器操纵微粒:综述
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2026-01-07 DOI: 10.1007/s10404-025-02866-9
Samira Sourani, Morteza Bayareh

One of the key technologies for developing materials science, microfabrication, and biomedical engineering is the manipulation of microparticles in microfluidic systems. Among the five main manipulation techniques, mechanical, electrical, magnetic, optical, and acoustic, acoustic manipulation has shown great promise because of its special benefits, which include label-free operation, biocompatibility, and efficiency in optically opaque surroundings. With an emphasis on surface acoustic waves (SAWs), bulk acoustic waves (BAWs), acoustic holography, and hybrid acoustic-optical platforms, this paper thoroughly investigates current advancements in acoustic manipulation techniques. In addition to outlining the governing equations and recent advancements in the field, this review paper addresses the key challenges, identifies research gaps, and explores future directions.

在微流体系统中对微粒的操纵是发展材料科学、微制造和生物医学工程的关键技术之一。在机械、电、磁、光学和声学五种主要操作技术中,声学操作由于其特殊的优点,包括无标签操作、生物相容性和在光学不透明环境中的效率,显示出巨大的前景。本文以表面声波(saw)、体声波(baw)、声全息和混合声光平台为重点,深入研究了声学操纵技术的最新进展。除了概述控制方程和该领域的最新进展外,本文还讨论了关键挑战,确定了研究差距,并探索了未来的方向。
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引用次数: 0
A review on advanced nanocomposite-based electrochemical biosensors for healthcare monitoring using human sweat 基于纳米复合材料的人体汗液监测电化学生物传感器研究进展
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2026-01-05 DOI: 10.1007/s10404-025-02865-w
Perumal Kirubha, Sreeja Balakrishnapillai Suseela, Fouziya Sulthana Shoukath, A. Rajesh, Rengarajan Amirtharajan

Among other things, sweat is the ultrafiltrate of blood plasma, an essential physiological fluid in the human body. It harbours a wide range of metabolites, electrolytes, and other biologically relevant markers that are directly correlated with human health. Relative to other body fluids e.g. blood, tears, interstitial fluid and saliva, sweat has specific benefits of ease of collection and detection that is non-invasive. During recent years, much focus was put on wearable sweat sensors because of their possibility to provide permanent monitoring of biomarkers. The use of wearable bioelectronics has attracted great attention even in the world of medicine due to its vast potential of predictive medical modelling and the ability to conduct personalised Point of Care Testing (POCT). These devices have many attractive features which include lightweight, flexible, great stretchability, and low price. In situ analysis of sweat biomarkers through electrochemical methods has been extensively used as widely reviewed by different researchers. The aim of this paper is to present a literature review of the latest advancements in non-invasive, continuous glucose monitoring with sweat sensors. It will point out various strategies and devices, which can be used in wearable platforms. This review provides insight knowledge that is essential in carrying out effective critical analysis of current problems. In it, wearable glucose biosensors have been classified based on the methodology, and the challenges of each specific approach have been discussed.

除其他外,汗液是血浆的超滤液,血浆是人体必不可少的生理液体。它含有广泛的代谢物、电解质和其他与人类健康直接相关的生物学相关标记物。与血液、眼泪、组织液和唾液等其他体液相比,汗液具有易于收集和检测的特殊优点,而且是非侵入性的。近年来,可穿戴式汗液传感器备受关注,因为它们有可能提供对生物标志物的永久监测。可穿戴生物电子设备的使用即使在医学界也引起了极大的关注,因为它具有预测医学建模的巨大潜力和进行个性化护理点测试(POCT)的能力。这些设备有许多吸引人的特点,包括重量轻、灵活、可拉伸性好、价格低。电化学方法在汗液生物标志物的原位分析中得到了广泛的应用,并得到了不同研究者的广泛评价。本文的目的是介绍无创、连续血糖监测与汗液传感器的最新进展的文献综述。它将指出各种策略和设备,可用于可穿戴平台。这篇综述提供了对当前问题进行有效批判性分析所必需的洞察力知识。其中,可穿戴式葡萄糖生物传感器根据方法进行了分类,并讨论了每种特定方法的挑战。
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引用次数: 0
Topology optimization of multichannel step emulsification droplet generators 多通道阶梯乳化液滴发生器的拓扑优化
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-22 DOI: 10.1007/s10404-025-02858-9
Zelong Zhang, Shi Feng, Hao Li, Tianshun Ding, Shengyang Tao

Microfluidics is pivotal in producing monodisperse microemulsions and microspheres. However, lower output efficiency hinders its practical application. Although multichannel droplet generators offer a promising solution for increased productivity, their design is inherently complex, and achieving uniform fluid distribution across channels is a significant challenge. Hence, in this paper, a novel rapid-design approach is introduced for multichannel droplet generators and employs topology optimization to enhance the structure, leading to significant improvements in droplet generation efficiency and uniformity. It can automatically generate a multichannel droplet generator structure that meets experimental conditions within five hours and is compatible with 3D printing technology. By employing topology optimization, the design achieves an average inter-channel flow rate variation of less than 1%, even with 81 channels, while reducing the inlet-outlet pressure drop by 19.75% compared to unoptimized configurations. The optimized device can produce both water-in-oil (W/O) and oil-in-water (O/W) droplets at a maximum throughput of 65 mL·min⁻¹, with a coefficient of variation (CV) below 5%, ensuring excellent monodispersity. Moreover, the topology optimization approach provides a comprehensive analytical framework for droplet generators with a matrix of microchannels, thereby facilitating rational design and scalability.

Graphical abstract

微流体是生产单分散微乳液和微球的关键。然而,较低的输出效率阻碍了其实际应用。尽管多通道液滴发生器为提高生产效率提供了一种很有前途的解决方案,但其设计本身就很复杂,实现跨通道均匀的流体分布是一个重大挑战。为此,本文提出了一种新的多通道液滴发生器的快速设计方法,并采用拓扑优化方法对其结构进行优化,显著提高了液滴生成效率和均匀性。它可以在5小时内自动生成满足实验条件的多通道液滴发生器结构,并与3D打印技术兼容。通过拓扑优化,即使有81个通道,该设计也实现了平均通道间流量变化小于1%,同时与未优化配置相比,进出口压降降低了19.75%。优化设备可以产生油包水(W / O)和水包油(O / W)液滴的最大吞吐量65毫升·敏⁻¹,用变异系数(CV)低于5%,确保良好的单分散性。此外,拓扑优化方法为微通道矩阵液滴发生器提供了一个全面的分析框架,从而促进了合理的设计和可扩展性。图形抽象
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引用次数: 0
A comprehensive literature review on microfluidic biochip technologies: techniques, challenges and future trends 微流控生物芯片技术综述:技术、挑战和未来趋势
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-12 DOI: 10.1007/s10404-025-02864-x
Chandan Das, Arindam Mondal, Anirban Bose, Bappaditya Das

The biochip is a solid, miniature substrate that may accommodate several test locations, allowing for concurrent biochemical investigations and reactions. In essence, it is a “miniaturized laboratory” or “microarray” where certain bio-molecules are immobilized on a surface. Over the past few decades, Continuous-Flow Microfluidic Biochips (CFMB) has been widely used to automate lab processes in molecular biology and biochemistry. In the recent years the lab automation in the field of molecular biology and biochemistry has been progressed through the development of Digital Microfluidic Biochips (DMFBs). DMFB was rapidly used during 2019 coronavirus disease pandemic (COVID-19). In critical diseases identification, the volume of the reagent or the samples play important role. The major challenges in the DMFB technology such as fixed electrode structure, variable sample or reagent size, non availability of in-process error recovery, limited sensor integration and high cost of production makes the conventional DMFB biochips less popular now a days. To circumvent the associated problems with DMFBs, the researchers came up with new solution is the field of microfluidic biochips is called Micro-Electrode-Dot-Array (MEDA)-based biochips. In this work a comprehensive review of the studies has been made regarding architecture, sample preparation, routing algorithm and synthesis of three different kinds of microfluidic biochip technologies. To begin the review, 327 research papers were chosen from the different academic databases within a span of 55 years starting from 1971. After deploying comprehensive screening process, this review considered 188 studies based on the relevance and importance. The different methodologies, benefits, and shortcomings of microfluidic biochip technologies have been lucidly elaborated in this paper which will be beneficial for biochip researchers.

该生物芯片是一种固体的微型衬底,可以容纳多个测试位置,允许同时进行生化调查和反应。从本质上讲,它是一个“微型实验室”或“微阵列”,某些生物分子被固定在一个表面上。在过去的几十年里,连续流微流控生物芯片(CFMB)已被广泛应用于分子生物学和生物化学的自动化实验室过程。近年来,随着数字微流控生物芯片(dmfb)的发展,分子生物学和生物化学领域的实验室自动化得到了很大的发展。DMFB在2019冠状病毒病大流行(COVID-19)期间迅速使用。在重大疾病鉴定中,试剂或样品的体积起着重要的作用。DMFB技术面临的主要挑战是电极结构固定、样品或试剂大小可变、过程中错误恢复不可用、传感器集成有限以及生产成本高,这使得传统的DMFB生物芯片现在不太受欢迎。为了规避dmfb的相关问题,研究人员提出了一种新的解决方案,即微流控生物芯片领域的微电极-点阵列(MEDA)生物芯片。本文对三种不同的微流控生物芯片技术的结构、样品制备、路由算法和合成等方面的研究进行了综述。为了开始审查,从1971年开始的55年间,从不同的学术数据库中选择了327篇研究论文。在采用综合筛选过程后,本综述根据相关性和重要性考虑了188项研究。本文对微流控生物芯片技术的不同方法、优点和缺点进行了清晰的阐述,以供生物芯片研究人员参考。
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引用次数: 0
Ultrasensitive liquid density measurement using virtual coupling microchannel stainless steel cantilever 采用虚拟耦合微通道不锈钢悬臂梁的超灵敏液体密度测量
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-09 DOI: 10.1007/s10404-025-02859-8
Takumi Nakamura, Hiroshi Yabuno, Yasuyuki Yamamoto, Sohei Matsumoto

A microbalance that uses a microchannel resonator requires several samples to perform high-sensitivity measurements. However, multiple procedures are required to embed the resonator’s microchannels, which results in high fabrication costs. In this study, we establish a high-sensitivity mass measurement method based on the eigenmode shift in virtually-coupled stainless steel microchannel resonators. We use a pin-shaped electrode to excite the microchannel resonators via electrostatic force. The microresonator does not require semiconductor-specific fabrication equipment because we use a combination of metal etching and diffusion bonding to bury the channels. We combine this approach with the use of a virtually-coupled resonator with dynamics calculated in a computer and verify its effectiveness as a small mass measurement method. Self-excitation of the weakly coupled resonators induced by nonlinear feedback control compensates for increments in viscosity through corresponding increments in the internal viscosity. We measure the densities of distilled water, ethanol, and saline water to compare the sensitivities of methods using eigenfrequency and eigenmode shifts. Use of virtual coupling realizes eigenmode shifts that are two orders of magnitude higher than the corresponding eigenfrequency shifts.

使用微通道谐振器的微天平需要几个样品来进行高灵敏度测量。然而,嵌入谐振器的微通道需要多个程序,这导致了高昂的制造成本。在本研究中,我们建立了一种基于虚拟耦合不锈钢微通道谐振器本征模位移的高灵敏度质量测量方法。我们使用针形电极通过静电力激发微通道谐振器。微谐振器不需要半导体专用的制造设备,因为我们使用金属蚀刻和扩散键的组合来埋藏通道。我们将这种方法与在计算机中计算动力学的虚拟耦合谐振器的使用相结合,并验证了其作为小质量测量方法的有效性。非线性反馈控制引起的弱耦合谐振腔的自激励通过相应的内部粘度增量来补偿粘度增量。我们测量了蒸馏水、乙醇和盐水的密度,以比较使用特征频率和特征模移的方法的灵敏度。利用虚拟耦合实现的本征模位移比相应的本征频移高两个数量级。
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引用次数: 0
Parallel microwave heating at different temperatures in multiple microchannels using a post-wall waveguide for combinatorial synthesis 利用后壁波导在多个微通道中进行不同温度下的平行微波加热,用于组合合成
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-05 DOI: 10.1007/s10404-025-02860-1
Kaito Fujitani, Hiroshi Nakamura, Taki Watanabe, Mitsuyoshi Kishihara, Yoshiaki Ukita, Kazuhiro Kanda, Yuichi Utsumi

In this study, we developed novel microwave microfluidics that enable the parallel heating of two microchannels at different temperatures within a single post-wall waveguide to accelerate the search for optimal temperature conditions in combinatorial synthesis. The proposed structure consists of two transversely arranged microchannels embedded in a post-wall waveguide whose sidewalls are formed by metal posts. This enables both single-mode microwave propagation and suppression of microwave leakage. A temperature gradient is established between the two channels by exploiting the difference in the microwave absorption between the upstream (CH-A) and downstream (CH-B) channel solvents. Water temperature measurements in each channel under a 3.0 W microwave input demonstrate a steady-state temperature of 82.8 ± 1.6 °C in CH-A and 72.1 ± 0.7 °C in CH-B, confirming the formation of a 10 °C temperature difference. Furthermore, the on-chip synthesis of 4-phenyltoluene, a pharmaceutical intermediate, was conducted via Suzuki–Miyaura coupling using this heating structure, and the product yield was quantified by gas chromatography. The reaction yield depends on the microwave input power and reaction time, with CH-A consistently yielding a higher product conversion than CH-B. These results demonstrate that the proposed device enables the formation of a temperature gradient and parallel synthesis under different thermal conditions within a single waveguide. This suggests that the device is an effective heating platform for combinatorial synthesis, offering a high-density selective temperature control. Accordingly, this structure is expected to contribute to the rapid optimization of reaction conditions for pharmaceutical and material development.

在这项研究中,我们开发了一种新型的微波微流体,可以在单个后壁波导中平行加热两个不同温度的微通道,以加速组合合成中对最佳温度条件的搜索。所提出的结构由嵌入后壁波导的两个横向排列的微通道组成,后壁波导的侧壁由金属桩形成。这使得单模微波传播和抑制微波泄漏。利用上游(CH-A)和下游(CH-B)通道溶剂对微波吸收的差异,在两个通道之间建立了温度梯度。在3.0 W微波输入下,每个通道的水温测量结果表明,CH-A的稳态温度为82.8±1.6°C, CH-B的稳态温度为72.1±0.7°C,证实了10°C温差的形成。利用该加热结构通过Suzuki-Miyaura偶联在芯片上合成了医药中间体4-苯基甲苯,并用气相色谱法定量了产物收率。反应产率取决于微波输入功率和反应时间,CH-A的产物转化率始终高于CH-B。这些结果表明,所提出的器件能够在单个波导内形成不同热条件下的温度梯度和平行合成。这表明该装置是一种有效的组合合成加热平台,提供了高密度的选择性温度控制。因此,该结构有望为药物和材料开发的反应条件的快速优化做出贡献。
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引用次数: 0
In silico approach for validating organ-on-chips: exemplifying through a skin-on-chip device 芯片上器官验证的计算机方法:通过皮肤芯片设备举例说明
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-05 DOI: 10.1007/s10404-025-02863-y
Deepa Chaturvedi, Joydeb Mukherjee, Ratnesh Jain, Prajakta Dandekar

The limitations of traditional, animal-model-based preclinical drug testing methodologies have contributed to an extremely high failure rate of new drug candidates in various phases of clinical trials. Organ-on-chip (OoC) technology has emerged as a promising alternative, providing a physiologically relevant microenvironment for drug testing. However, challenges such as high costs, inadequate physiological replication, and particularly the lack of standardized validation approaches have undermined the widespread adoption of OoCs. Additionally, the need for in silico-assisted functional verification to accelerate drug development, reduce investigational expenses, and enhance ethical feasibility has been increasingly experienced by researchers. In this study, we developed and validated a microfluidic skin-on-chip (SoC) platform that supports dynamic skin co-culture for 11 days. The model was characterized by using live-dead cell staining, fluorescent cell tracking, hematoxylin and eosin (H&E) staining, and immune-histochemistry analysis. In vitro drug diffusion studies with caffeine and salicylic acid were performed and quantified using high-performance liquid chromatography. To enhance predictive accuracy, a mathematical model based on the convection–diffusion equation was developed to simulate passive drug permeation across skin layers. Analytical modeling, solved using a closed-form solution, captured diffusion kinetics and flow patterns, while numerical modeling validated the results through finite element analysis. The model exhibited strong agreement with experimental data (relative error: ±12%) for both drugs, at an initial concentration of 1 mg mL−1. Our microfluidic SoC device, functionally verified using experimental and in silico-assisted approaches, offers a reliable pre-clinical tool for testing chemicals, cosmetics, pharmaceuticals, and allergens. The investigations support a step forward in the use of new approach methodologies (NAMs) for improving predictive accuracy and standardizing drug permeability assays during the drug development process.

Graphical abstract

传统的、基于动物模型的临床前药物测试方法的局限性导致新药候选物在临床试验的各个阶段失败率极高。器官芯片(OoC)技术已成为一种有前途的替代方案,为药物测试提供了生理相关的微环境。然而,诸如高成本、不充分的生理复制、特别是缺乏标准化验证方法等挑战阻碍了ooc的广泛采用。此外,为了加速药物开发,减少研究费用,提高伦理可行性,对硅辅助功能验证的需求已经越来越多地为研究人员所体验。在这项研究中,我们开发并验证了一种微流体皮肤芯片(SoC)平台,该平台支持11天的动态皮肤共培养。采用活死细胞染色、荧光细胞跟踪、苏木精和伊红(H&;E)染色、免疫组织化学分析对模型进行表征。采用高效液相色谱法对咖啡因和水杨酸进行体外药物扩散研究。为了提高预测的准确性,建立了一个基于对流扩散方程的数学模型来模拟药物在皮肤层间的被动渗透。分析模型采用封闭形式求解,捕获了扩散动力学和流动模式,而数值模型通过有限元分析验证了结果。两种药物在初始浓度为1mg mL−1时,模型与实验数据非常吻合(相对误差:±12%)。我们的微流控SoC设备,使用实验和硅辅助方法进行功能验证,为测试化学品,化妆品,药品和过敏原提供了可靠的临床前工具。这些研究支持了在药物开发过程中使用新方法方法(NAMs)提高预测准确性和标准化药物渗透性分析的一步。图形抽象
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引用次数: 0
High throughput synthesis of liposomes using vibrating sharp-tip mixing 利用振动尖端混合技术合成高通量脂质体
IF 2.5 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION Pub Date : 2025-12-05 DOI: 10.1007/s10404-025-02861-0
Toktam Godary, Kathrine Curtin, Peng Li

Lipid nanoparticles (LNPs) have emerged as a promising drug delivery system due to their biocompatibility, biodegradability, and ability to deliver a wide range of therapeutic agents. While conventional bulk synthesis of LNPs results in batch-to-batch variability in particle physiochemical properties, microfluidic-based synthesis enables highly controllable outcomes. In recent years, acoustics have emerged as a powerful tool for LNP synthesis due to its flexibility and contactless operation. However, implementing acoustic-based methods in microfluidic devices usually requires precise microstructure fabrication within the channels, limiting scalability for large-scale synthesis. To overcome these challenges, we present a 3D-printed microfluidic device equipped with an acoustically driven, vibrating sharp-tip glass capillary, engineered to accommodate a wide range of flow rates and enable the scalable production of phosphatidylcholine (POPC) liposomes. Additionally, the impact of crucial parameters including total flow rates and flow rate ratios on the final product was assessed. To validate the results obtained from the sharp-tip mixing method, we compared the device with two widely used microfluidic devices for synthesizing liposomes: the NanoAssembler™ Ignite™ NxGen mixing device and the commercial herringbone mixing device. The mixing characterization results demonstrated that the sharp-tip mixer microfluidic device achieved optimal mixing across a broad range of total flow rates, from 30 µL/min to 3500 µL/min. Size distribution characterization of the final products showed that the sharp-tip mixer device produces homogeneous POPC liposomes with tunable sizes ranging from 60 to 150 nm.

脂质纳米颗粒(LNPs)由于其生物相容性、生物可降解性和输送多种治疗药物的能力而成为一种很有前途的药物输送系统。传统的大量合成LNPs会导致颗粒理化性质批次之间的变化,而基于微流体的合成可以实现高度可控的结果。近年来,声学由于其灵活性和非接触式操作而成为LNP合成的有力工具。然而,在微流控器件中实现基于声学的方法通常需要在通道内精确地制造微观结构,这限制了大规模合成的可扩展性。为了克服这些挑战,我们提出了一种3d打印的微流体装置,该装置配备了声学驱动的振动尖端玻璃毛细管,设计用于适应大范围的流速,并能够大规模生产磷脂酰胆碱(POPC)脂质体。此外,还评估了总流量和流量比等关键参数对最终产品的影响。为了验证尖端混合方法获得的结果,我们将该设备与两种广泛用于合成脂质体的微流体设备进行了比较:NanoAssembler™Ignite™NxGen混合设备和商用人形混合设备。混合表征结果表明,尖端混合器微流控装置在30µL/min至3500µL/min的大流量范围内实现了最佳混合。最终产物的粒径分布表征表明,尖尖混合器装置产生均匀的POPC脂质体,尺寸可调范围为60 ~ 150 nm。
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Microfluidics and Nanofluidics
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