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Vascularized liver-on-a-chip model to investigate nicotine-induced dysfunction 研究尼古丁诱导的功能障碍的血管化肝芯片模型
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-27 DOI: 10.1063/5.0172677
Eric Wang, Melisa J. Andrade, Quinton Smith
The development of physiologically relevant in vitro systems for simulating disease onset and progression and predicting drug metabolism holds tremendous value in reducing drug discovery time and cost. However, many of these platforms lack accuracy in replicating the tissue architecture and multicellular interactions. By leveraging three-dimensional cell culture, biomimetic soft hydrogels, and engineered stimuli, in vitro models have continued to progress. Nonetheless, the incorporation of the microvasculature has been met with many challenges, specifically with the addition of parenchymal cell types. Here, a systematic approach to investigating the initial seeding density of endothelial cells and its effects on interconnected networks was taken and combined with hepatic spheroids to form a liver-on-a-chip model. Leveraging this system, nicotine's effects on microvasculature and hepatic function were investigated. The findings indicated that nicotine led to interrupted adherens junctions, decreased guanosine triphosphate cyclohydrolase 1 expression, impaired angiogenesis, and lowered barrier function, all key factors in endothelial dysfunction. With the combination of the optimized microvascular networks, a vascularized liver-on-a-chip was formed, providing functional xenobiotic metabolism and synthesis of both albumin and urea. This system provides insight into potential hepatotoxicity caused by various drugs and allows for assessing vascular dysfunction in a high throughput manner.
开发与生理相关的体外系统来模拟疾病的发生和发展以及预测药物代谢,在缩短药物研发时间和降低研发成本方面具有巨大价值。然而,许多此类平台在复制组织结构和多细胞相互作用方面缺乏准确性。通过利用三维细胞培养、仿生软水凝胶和工程刺激,体外模型在不断进步。然而,微血管的加入遇到了许多挑战,特别是在加入实质细胞类型时。在这里,我们采用了一种系统的方法来研究内皮细胞的初始播种密度及其对互连网络的影响,并将其与肝脏球体相结合,形成了肝脏芯片模型。利用这一系统,研究了尼古丁对微血管和肝功能的影响。研究结果表明,尼古丁会导致粘连连接中断、三磷酸鸟苷环醇酶1表达减少、血管生成受损和屏障功能降低,这些都是造成内皮功能障碍的关键因素。结合优化的微血管网络,形成了血管化的芯片肝脏,可进行功能性的异生物代谢并合成白蛋白和尿素。该系统有助于深入了解各种药物可能引起的肝脏毒性,并能以高通量方式评估血管功能障碍。
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引用次数: 0
Acoustophoresis of monodisperse oil droplets in water: Effect of symmetry breaking and non-resonance operation on oil trapping behavior 水中单分散油滴的声震:对称性破坏和非共振操作对油捕集行为的影响
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-27 DOI: 10.1063/5.0175400
H. Bazyar, M. H. Kandemir, J. Peper, M. A. B. Andrade, A. L. Bernassau, K. Schroën, R. G. H. Lammertink
Acoustic manipulation of particles in microchannels has recently gained much attention. Ultrasonic standing wave (USW) separation of oil droplets or particles is an established technology for microscale applications. Acoustofluidic devices are normally operated at optimized conditions, namely, resonant frequency, to minimize power consumption. It has been recently shown that symmetry breaking is needed to obtain efficient conditions for acoustic particle trapping. In this work, we study the acoustophoretic behavior of monodisperse oil droplets (silicone oil and hexadecane) in water in the microfluidic chip operating at a non-resonant frequency and an off-center placement of the transducer. Finite element-based computer simulations are further performed to investigate the influence of these conditions on the acoustic pressure distribution and oil trapping behavior. Via investigating the Gor’kov potential, we obtained an overlap between the trapping patterns obtained in experiments and simulations. We demonstrate that an off-center placement of the transducer and driving the transducer at a non-resonant frequency can still lead to predictable behavior of particles in acoustofluidics. This is relevant to applications in which the theoretical resonant frequency cannot be achieved, e.g., manipulation of biological matter within living tissues.
最近,微通道中颗粒的声学处理技术备受关注。油滴或颗粒的超声驻波(USW)分离是一种成熟的微米级应用技术。声流体设备通常在优化的条件下运行,即共振频率,以最大限度地降低功耗。最近的研究表明,要获得声学粒子捕集的有效条件,需要打破对称性。在这项工作中,我们研究了单分散油滴(硅油和十六烷)在微流体芯片中以非共振频率和偏离中心的换能器位置工作时在水中的声泳行为。我们还进一步进行了基于有限元的计算机模拟,以研究这些条件对声压分布和油捕集行为的影响。通过研究 Gor'kov 电位,我们发现实验和模拟获得的捕集模式存在重叠。我们证明,将换能器置于偏离中心的位置并以非共振频率驱动换能器仍可导致声流体中颗粒的可预测行为。这与无法达到理论共振频率的应用有关,例如在活体组织内操纵生物物质。
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引用次数: 0
Micromixing within microfluidic devices: Fundamentals, design, and fabrication 微流体设备中的微混合:基础、设计和制造
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-12 DOI: 10.1063/5.0178396
Shuxiang Cai, Yawen Jin, Yun Lin, Yingzheng He, Peifan Zhang, Zhixing Ge, Wenguang Yang
As one of the hot spots in the field of microfluidic chip research, micromixers have been widely used in chemistry, biology, and medicine due to their small size, fast response time, and low reagent consumption. However, at low Reynolds numbers, the fluid motion relies mainly on the diffusive motion of molecules under laminar flow conditions. The detrimental effect of laminar flow leads to difficulties in achieving rapid and efficient mixing of fluids in microchannels. Therefore, it is necessary to enhance fluid mixing by employing some external means. In this paper, the classification and mixing principles of passive (T-type, Y-type, obstructed, serpentine, three-dimensional) and active (acoustic, electric, pressure, thermal, magnetic field) micromixers are reviewed based on the presence or absence of external forces in the micromixers, and some experiments and applications of each type of micromixer are briefly discussed. Finally, the future development trends of micromixers are summarized.
作为微流控芯片研究领域的热点之一,微搅拌器因其体积小、响应速度快、试剂消耗低等特点,已被广泛应用于化学、生物和医学领域。然而,在低雷诺数条件下,流体运动主要依靠分子在层流条件下的扩散运动。层流的不利影响导致微通道中的流体难以实现快速有效的混合。因此,有必要通过一些外部手段来加强流体混合。本文根据微搅拌器中有无外力作用,综述了被动式(T 型、Y 型、阻塞式、蛇形、三维)和主动式(声、电、压、热、磁场)微搅拌器的分类和混合原理,并简要讨论了各类微搅拌器的一些实验和应用。最后,总结了微搅拌器的未来发展趋势。
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引用次数: 0
Synchronous oscillatory electro-inertial focusing of microparticles 微颗粒的同步振荡电惯性聚焦
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-12 DOI: 10.1063/5.0162368
Giridar Vishwanathan, Gabriel Juarez
Here, results are presented on the focusing of 1μm polystyrene particle suspensions using a synchronous oscillatory pressure-driven flow and oscillatory electric field in a microfluidic device. The effect of the phase difference between the oscillatory fields on the focusing position and focusing efficiency was investigated. The focusing position of negatively charged polystyrene particles could be tuned anywhere between the channel centerline to the channel walls. Similarly, the focusing efficiency could range from 20% up to 90%, depending on the phase difference, for particle Reynolds numbers of order O(10−4). The migration velocity profile was measured and the peak velocity was found to scale linearly with both the oscillatory pressure-driven flow amplitude and the oscillatory electric field amplitude. Furthermore, the average migration velocity was observed to scale with the cosine of the phase difference between the fields, indicating the coupled non-linear nature of the phenomenon. Last, the peak migration velocity was measured for different particle radii and found to have an inverse relation, where the velocity increased with decreasing particle radius for identical conditions.
本文介绍了在微流控装置中使用同步振荡压力驱动流和振荡电场对 1μm 聚苯乙烯颗粒悬浮液进行聚焦的结果。研究了振荡场之间的相位差对聚焦位置和聚焦效率的影响。带负电的聚苯乙烯颗粒的聚焦位置可在通道中心线到通道壁之间的任何位置进行调整。同样,在粒子雷诺数为 O(10-4)数量级时,聚焦效率可从 20% 到 90% 不等,这取决于相位差。测量了迁移速度曲线,发现峰值速度与振荡压力驱动的流动振幅和振荡电场振幅成线性比例。此外,还观察到平均迁移速度与电场相位差的余弦成正比,这表明了这一现象的非线性耦合性质。最后,测量了不同颗粒半径的峰值迁移速度,发现两者之间存在反比关系,即在相同条件下,迁移速度随颗粒半径的减小而增加。
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引用次数: 0
Microfluidics-enabled intelligent manufacturing of metal halide perovskite nanocrystals 利用微流体技术智能制造金属卤化物过氧化物纳米晶体
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-12 DOI: 10.1063/5.0172135
Xiaobing Tang, Fuqian Yang
Large-scale and controllable fabrication is an indispensable step for the industrialization and commercialization of halide perovskite nanocrystals, which are new-generation semiconductor materials for optoelectronic applications. Microfluidics, which provides continuous and precise synthesis, has been considered as a promising technique to fulfill this aspect. The research studies over the past decades have witnessed the advancement of microfluidics as a powerful tool in the fabrication of halide perovskite nanocrystals. In this Perspective, the state-of-the-art research based on microfluidics is introduced initially, including the synthesis of functional structures and materials, devices, as well as the interdisciplinary interactions between microfluidics and artificial intelligence and machine learning, etc. We then detail the issues and challenges in hindering progress in the above areas. Finally, we provide future directions and trends for the technology to achieve its full potential. This Perspective is expected to benefit the collective efforts between the field of nanomaterials and microfluidics in advanced manufacturing.
卤化物包光体纳米晶体是新一代光电应用半导体材料,大规模可控制造是其工业化和商业化不可或缺的一步。微流控技术可提供连续、精确的合成,被认为是实现这一目标的前景广阔的技术。过去几十年的研究见证了微流控技术作为制造卤化物包晶纳米晶体的强大工具所取得的进步。在本视角中,我们首先介绍了基于微流控技术的最新研究成果,包括功能结构和材料的合成、器件以及微流控技术与人工智能和机器学习之间的跨学科互动等。然后,我们详细介绍了阻碍上述领域取得进展的问题和挑战。最后,我们提出了该技术充分发挥潜力的未来方向和趋势。本视角有望为先进制造业中的纳米材料与微流控领域的共同努力带来裨益。
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引用次数: 0
Toward versatile digital bioanalysis 实现多功能数字生物分析
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-07 DOI: 10.1063/5.0174727
Jun Ando, Rikiya Watanabe
Digital bioanalysis places great emphasis on the highly sensitive and rapid detection of biomolecules at the single-molecule level. Rooted in single-molecule biophysics, this innovative approach offers numerous insights into biomolecular mechanisms with an unprecedented level of sensitivity and precision. Moreover, this method has significant potential to contribute to disease diagnostics, enabling the highly sensitive detection of biomarkers or pathogens for early disease diagnosis and continuous disease monitoring. However, the notable cost of detection and specialized equipment required for fabricating microdevices pose a challenge to accessibility and ease of use. This lack of versatility hinders the widespread adoption of digital bioanalysis. Here, we aim to illuminate the essential requirements for versatile digital bioanalysis and present prospects for biomedical applications that can be facilitated by attaining such versatility.
数字生物分析非常重视在单分子水平上对生物分子进行高灵敏度的快速检测。这种创新方法植根于单分子生物物理学,能以前所未有的灵敏度和精确度洞察生物分子机制。此外,这种方法在疾病诊断方面也大有可为,可以高灵敏度地检测生物标志物或病原体,用于早期疾病诊断和持续疾病监测。然而,显著的检测成本和制造微型装置所需的专业设备对其可及性和易用性构成了挑战。这种多功能性的缺乏阻碍了数字生物分析技术的广泛应用。在此,我们旨在阐明多功能数字生物分析的基本要求,并介绍通过实现这种多功能性可促进生物医学应用的前景。
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引用次数: 0
Vascularized microfluidic models of major organ structures and cancerous tissues 主要器官结构和癌症组织的血管化微流体模型
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-06 DOI: 10.1063/5.0159800
Anagha Rama Varma, Parinaz Fathi
Organ-on-a-chip devices are powerful modeling systems that allow researchers to recapitulate the in vivo structures of organs as well as the physiological conditions those tissues are subject to. These devices are useful tools in modeling not only the behavior of a healthy organ but also in modeling disease pathology or the effects of specific drugs. The incorporation of fluidic flow is of great significance in these devices due to the important roles of physiological fluid flows in vivo. Recent developments in the field have led to the production of vascularized organ-on-a-chip devices, which can more accurately reproduce the conditions observed in vivo by recapitulating the vasculature of the organ concerned. This review paper will provide a brief overview of the history of organ-on-a-chip devices, before discussing developments in the production of vascularized organs-on-chips, and the implications these developments hold for the future of the field.
片上器官设备是一种功能强大的建模系统,研究人员可利用它再现体内器官结构以及这些组织所处的生理条件。这些设备不仅是模拟健康器官行为的有用工具,也是模拟疾病病理或特定药物作用的有用工具。由于生理流体在体内的重要作用,在这些设备中加入流体流动具有重要意义。该领域的最新发展促成了血管化器官芯片设备的诞生,这种设备通过重现相关器官的血管,可以更准确地再现体内观察到的情况。本综述论文将简要概述片上器官设备的历史,然后讨论在生产血管化片上器官方面的发展,以及这些发展对该领域未来的影响。
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引用次数: 0
Effect of the shear rate and residence time on the lysis of AC16 human cardiomyocyte cells via surface acoustic waves 剪切率和停留时间对通过表面声波裂解 AC16 人类心肌细胞的影响
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-06 DOI: 10.1063/5.0158977
G. Almanza, R. M. Trujillo, D. Sanchez-Saldaña, Ø. Rosand, M. Høydal, M. Fernandino, C. A. Dorao
The efficient breakage of one cell or a concentration of cells for releasing intracellular material such as DNA, without damaging it, is the first step for several diagnostics or treatment processes. As the cell membrane is easy to bend but resistant to stretching, the exposure of the cell to a shear rate during a short period of time can be sufficient to damage the membrane and facilitate the extraction of DNA. However, how to induce high shear stresses on cells in small microliter volumes samples has remained an elusive problem. Surface acoustic waves operating at high frequencies can induce acoustic streaming leading to shear rates sufficient to cell lysis. Lysis induced by acoustic streaming in sessile droplets has been investigated in the past from the lysis efficiency point of view. However, the effects of the velocity field and shear rate induced by acoustic streaming on the lysis process remain unexplored. Here, we study the lysis of AC16 human cardiomyocytes in microliter droplets under the effect of the shear rate induced by acoustic streaming. It is identified that for a given shear rate, the extracted DNA is also affected by the actuation period which can be attributed to a cycling process that leads to an accumulation of damage on the cell membrane.
在不损伤细胞的情况下,有效地破碎一个或多个细胞以释放细胞内物质(如 DNA),是多种诊断或治疗过程的第一步。由于细胞膜容易弯曲但不易拉伸,因此在短时间内将细胞暴露在剪切率下就足以破坏细胞膜并促进 DNA 的提取。然而,如何在小微升体积样品中诱导细胞产生高剪切应力仍是一个难以解决的问题。高频率的表面声波可诱导声流,从而产生足以导致细胞裂解的剪切率。过去曾从裂解效率的角度对无柄液滴中声波流诱导的裂解进行过研究。然而,声流诱导的速度场和剪切率对裂解过程的影响仍未得到研究。在此,我们研究了在声流诱导的剪切率作用下,微升液滴中 AC16 人类心肌细胞的裂解过程。研究发现,在给定的剪切率下,提取的 DNA 也会受到致动周期的影响,这可归因于导致细胞膜损伤累积的循环过程。
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引用次数: 0
A method to generate perfusable physiologic-like vascular channels within a liver-on-chip model. 一种在肝脏芯片模型中产生可灌注的生理样血管通道的方法。
IF 2.6 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-04 eCollection Date: 2023-12-01 DOI: 10.1063/5.0170606
E Ferrari, E Monti, C Cerutti, R Visone, P Occhetta, L G Griffith, M Rasponi

The human vasculature is essential in organs and tissues for the transport of nutrients, metabolic waste products, and the maintenance of homeostasis. The integration of vessels in in vitro organs-on-chip may, therefore, improve the similarity to the native organ microenvironment, ensuring proper physiological functions and reducing the gap between experimental research and clinical outcomes. This gap is particularly evident in drug testing and the use of vascularized models may provide more realistic insights into human responses to drugs in the pre-clinical phases of the drug development pipeline. In this context, different vascularized liver models have been developed to recapitulate the architecture of the hepatic sinusoid, exploiting either porous membranes or bioprinting techniques. In this work, we developed a method to generate perfusable vascular channels with a circular cross section within organs-on-chip without any interposing material between the parenchyma and the surrounding environment. Through this technique, vascularized liver sinusoid-on-chip systems with and without the inclusion of the space of Disse were designed and developed. The recapitulation of the Disse layer, therefore, a gap between hepatocytes and endothelial cells physiologically present in the native liver milieu, seems to enhance hepatic functionality (e.g., albumin production) compared to when hepatocytes are in close contact with endothelial cells. These findings pave the way to numerous further uses of microfluidic technologies coupled with vascularized tissue models (e.g., immune system perfusion) as well as the integration within multiorgan-on-chip settings.

人体脉管系统在器官和组织中运输营养物质、代谢废物和维持体内平衡是必不可少的。因此,在体外器官芯片中整合血管可以提高与原生器官微环境的相似性,保证其正常的生理功能,减少实验研究与临床结果之间的差距。这种差距在药物测试中尤其明显,使用血管化模型可以在药物开发管道的临床前阶段为人类对药物的反应提供更现实的见解。在这种情况下,已经开发了不同的血管化肝脏模型来概括肝窦的结构,利用多孔膜或生物打印技术。在这项工作中,我们开发了一种在器官芯片内产生具有圆形横截面的可灌注血管通道的方法,而在薄壁组织和周围环境之间没有任何中间材料。通过该技术,设计和开发了带有或不包含Disse空间的血管化肝窦芯片系统。因此,与肝细胞与内皮细胞密切接触时相比,肝细胞与内皮细胞之间的间隙,即天然肝脏环境中存在的肝细胞与内皮细胞之间的间隙,似乎可以增强肝脏功能(例如,白蛋白的产生)。这些发现为微流控技术与血管化组织模型(如免疫系统灌注)以及多器官芯片集成的大量进一步应用铺平了道路。
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引用次数: 0
On the synergy of biomicrofluidic technologies and real-time 3D tracking: A perspective. 论生物微流控技术与实时3D跟踪的协同作用:一个视角。
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-12-04 eCollection Date: 2023-12-01 DOI: 10.1063/5.0174269
Liu Hong, Leonardo P Chamorro

Particle image velocimetry and particle tracking velocimetry have played pivotal roles in flow and particle characterization, owing to their non-invasive and accurate data collection methods. However, their broader application in the biomicrofluidics field is constrained by challenges, such as intensive calibration, high post-processing costs, and optical compatibility issues, especially in settings where space is a bottleneck. This article describes recent advancements in non-iterative ray tracing that promise more streamlined post-capture calibration and highlights examples of applications and areas that merit further technological investigation. The development and adoption of these techniques may pave the way for new innovations.

颗粒图像测速和颗粒跟踪测速以其无创和准确的数据采集方法在流体和颗粒的表征中发挥着举足轻重的作用。然而,它们在生物微流体领域的广泛应用受到挑战的限制,例如密集的校准,高后处理成本和光学兼容性问题,特别是在空间是瓶颈的环境中。本文介绍了非迭代光线追踪的最新进展,这些进展承诺更简化捕获后校准,并重点介绍了值得进一步技术研究的应用示例和领域。这些技术的发展和采用可能为新的创新铺平道路。
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引用次数: 0
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Biomicrofluidics
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