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Manipulating the duration of picoinjection controls the injected volume of individual droplets 控制皮米注射的持续时间可控制单个液滴的注射量
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-07-02 DOI: 10.1063/5.0206830
R. Thakur, D. Weitz
The ability to add reagents into droplets is required in many microfluidic workflows. Picoinjection can address this need; however, it is unable to control the injection volume for each individual droplet. Here, we present an improved picoinjection method that can inject controlled volumes into individual droplets. We achieve this by adjusting the injection duration for each picoinjection event. This improved picoinjection method can be used to create complex microfluidic workflows that are able to control the biochemical composition of individual droplets.
在许多微流体工作流程中,都需要将试剂添加到液滴中。皮膜注射法可以满足这一需求,但它无法控制每个液滴的注射量。在这里,我们提出了一种改进的皮膜注射方法,它可以向单个液滴注射可控的体积。我们通过调整每个微微注塑事件的注塑持续时间来实现这一目标。这种改进的微微注射方法可用于创建复杂的微流体工作流程,从而控制单个液滴的生化成分。
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引用次数: 0
A method to prevent clogging and clustering in microfluidic systems using microbubble streaming 利用微气泡流防止微流体系统堵塞和聚集的方法
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-07-02 DOI: 10.1063/5.0214436
Amirabas Bakhtiari, Christian J. Kähler
This paper presents an innovative strategy to address the issues of clogging and cluster-related challenges in microchannels within microfluidic devices. Leveraging three-dimensional (3D) microbubble streaming as a dynamic solution, our approach involves the controlled activation of microbubbles near channel constrictions, inducing microstreaming with distinctive features. This microstreaming, characterized by a high non-uniform 3D gradient and significant shear stress, effectively inhibits arch formation at constrictions and disintegrates particle clusters, demonstrating real-time prevention of clogging incidents and blockages. This study includes experimental validation of the anti-clogging technique, a detailed examination of microstreaming phenomena, and their effects on clogging and clustering issues. It also incorporates statistical analyses performed in various scenarios to verify the method’s effectiveness and adaptability. Moreover, a versatile control system has been designed that operates in event-triggered, continuous, or periodic modes, which suits different lab-on-a-chip applications and improves the overall functionality of microfluidic systems.
本文提出了一种创新策略,以解决微流控设备中微通道的堵塞问题和与团聚相关的难题。利用三维(3D)微气泡流作为动态解决方案,我们的方法涉及在通道收缩附近受控激活微气泡,从而诱发具有独特特征的微流。这种微流的特点是具有高度非均匀的三维梯度和显著的剪切应力,可有效抑制收缩处拱形的形成并分解颗粒团,从而实时防止堵塞事件和堵塞。本研究包括防堵塞技术的实验验证、微流现象的详细研究及其对堵塞和团聚问题的影响。研究还纳入了在各种情况下进行的统计分析,以验证该方法的有效性和适应性。此外,还设计了一个多功能控制系统,可在事件触发、连续或周期模式下运行,适合不同的片上实验室应用,并提高了微流控系统的整体功能。
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引用次数: 0
A novel viscoelastic microfluidic platform for nanoparticle/small extracellular vesicle separation through viscosity gradient-induced migration. 通过粘度梯度诱导迁移实现纳米粒子/小细胞外囊泡分离的新型粘弹性微流体平台。
IF 2.6 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-26 eCollection Date: 2024-05-01 DOI: 10.1063/5.0208417
Han Guo, Dayin Wang, Shilun Feng, Kaihuan Zhang, Yuan Luo, Jianlong Zhao

Small extracellular vesicles (sEVs) are extracellular vesicles with diameters ranging from 30 to 150 nm, harboring proteins and nucleic acids that reflect their source cells and act as vital mediators of intercellular communication. The comprehensive analysis of sEVs is hindered by the complex composition of biofluids that contain various extracellular vesicles. Conventional separation methods, such as ultracentrifugation and immunoaffinity capture, face routine challenges in operation complexity, cost, and compromised recovery rates. Microfluidic technologies, particularly viscoelastic microfluidics, offer a promising alternative for sEV separation due to its field-free nature, fast and simple operation procedure, and minimal sample consumption. In this context, we here introduce an innovative viscoelastic approach designed to exploit the viscosity gradient-induced force with size-dependent characteristics, thereby enabling the efficient separation of nano-sized particles and sEVs from larger impurities. We first seek to illustrate the underlying mechanism of the viscosity gradient-induced force, followed by experimental validation with fluorescent nanoparticles demonstrating separation results consistent with qualitative analysis. We believe that this work is the first to report such viscosity gradient-induced phenomenon in the microfluidic context. The presented approach achieves ∼80% for both target purity and recovery rate. We further demonstrate effective sEV separation using our device to showcase its efficacy in the real biological context, highlighting its potential as a versatile, label-free platform for sEV analysis in both fundamental biological research and clinical applications.

小细胞外囊泡(sEVs)是直径介于 30 纳米到 150 纳米之间的细胞外囊泡,内含蛋白质和核酸,能反映其来源细胞,是细胞间通信的重要媒介。由于含有各种细胞外囊泡的生物流体成分复杂,阻碍了对 sEVs 的全面分析。超速离心和免疫亲和捕获等传统分离方法在操作复杂性、成本和回收率方面面临常规挑战。微流控技术,尤其是粘弹性微流控技术,因其无需现场操作、操作过程快速简单、样品消耗量极少等优点,为 sEV 分离提供了一种前景广阔的替代方法。在此背景下,我们在此介绍一种创新的粘弹性方法,旨在利用粘度梯度诱导力的尺寸依赖特性,从而实现纳米级颗粒和 sEV 与较大杂质的高效分离。我们首先试图说明粘度梯度诱导力的基本机制,然后用荧光纳米粒子进行实验验证,证明分离结果与定性分析一致。我们相信,这项工作是首次在微流控背景下报告这种粘度梯度诱导现象。该方法的目标纯度和回收率都达到了 80%。我们进一步展示了使用我们的设备进行有效的 sEV 分离,展示了其在实际生物环境中的功效,突出了其作为基础生物研究和临床应用中 sEV 分析的多功能、无标记平台的潜力。
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引用次数: 0
Microfluidic gut-axis-on-a-chip models for pharmacokinetic-based disease models. 基于药物动力学的疾病模型的微流控芯片肠道轴模型。
IF 2.6 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-26 eCollection Date: 2024-05-01 DOI: 10.1063/5.0206271
Raehyun Kim, Jong Hwan Sung

The low success rate of new drugs transitioning from animal testing to human clinical trials necessitates the development of more accurate and representative in vitro models. Recent advances in multi-organ-on-a-chip technology offer promising avenues for studying complex organ-organ interactions. Gut-liver-on-a-chip systems hold particular promise for mimicking the intricate interplay between the gut and liver, which play crucial roles in nutrient absorption, drug metabolism, detoxification, and immune response. Here, we discuss the key components of the gut-liver axis, including the gut epithelium, liver cells, gut microbiota, and their roles in the organ functions. We then explore the potential of gut-liver-on-a-chip models to replicate the intricate interactions between the two organs for pharmacokinetic studies and their expansion to more complicated multi-organ models. Finally, we provide perspectives and future directions for developing more physiologically relevant gut-liver-axis models for more efficient drug development, studying liver diseases, and personalizing treatment strategies.

新药从动物试验过渡到人体临床试验的成功率很低,因此有必要开发更准确、更具代表性的体外模型。多器官芯片技术的最新进展为研究复杂的器官间相互作用提供了前景广阔的途径。肠肝芯片系统尤其有望模拟肠道和肝脏之间错综复杂的相互作用,这两个器官在营养吸收、药物代谢、解毒和免疫反应中发挥着至关重要的作用。在此,我们将讨论肠肝轴的关键组成部分,包括肠道上皮细胞、肝细胞、肠道微生物群及其在器官功能中的作用。然后,我们探讨了片上肠道-肝脏模型复制两个器官之间错综复杂的相互作用以进行药代动力学研究的潜力,以及将其扩展到更复杂的多器官模型的可能性。最后,我们为开发更多生理相关的肠肝轴模型提供了展望和未来方向,以便更有效地开发药物、研究肝脏疾病和个性化治疗策略。
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引用次数: 0
Application and prospect of microfluidic devices for rapid assay of cell activities in the tumor microenvironment. 微流控装置在快速检测肿瘤微环境中细胞活性方面的应用和前景。
IF 2.6 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-17 eCollection Date: 2024-05-01 DOI: 10.1063/5.0206058
Linjing Zhu, Xueling Cui, Lingling Jiang, Fang Fang, Boyang Liu

The global impact of cancer on human health has raised significant concern. In this context, the tumor microenvironment (TME) plays a pivotal role in the tumorigenesis and malignant progression. In order to enhance the accuracy and efficacy of therapeutic outcomes, there is an imminent requirement for in vitro models that can accurately replicate the intricate characteristics and constituents of TME. Microfluidic devices exhibit notable advantages in investigating the progression and treatment of tumors and have the potential to become a novel methodology for evaluating immune cell activities in TME and assist clinicians in assessing the prognosis of patients. In addition, it shows great advantages compared to traditional cell experiments. Therefore, the review first outlines the applications and advantages of microfluidic chips in facilitating tumor cell culture, constructing TME and investigating immune cell activities. Second, the roles of microfluidic devices in the analysis of circulating tumor cells, tumor prognosis, and drug screening have also been mentioned. Moreover, a forward-looking perspective is discussed, anticipating the widespread clinical adoption of microfluidic devices in the future.

癌症对人类健康的全球性影响已引起人们的极大关注。在此背景下,肿瘤微环境(TME)在肿瘤发生和恶性进展中起着举足轻重的作用。为了提高治疗结果的准确性和有效性,迫切需要能够准确复制肿瘤微环境复杂特征和成分的体外模型。微流控装置在研究肿瘤的进展和治疗方面具有显著优势,有可能成为评估 TME 中免疫细胞活动的新方法,并协助临床医生评估患者的预后。此外,与传统的细胞实验相比,它还显示出巨大的优势。因此,本综述首先概述了微流控芯片在促进肿瘤细胞培养、构建 TME 和研究免疫细胞活性方面的应用和优势。其次,还提到了微流控设备在循环肿瘤细胞分析、肿瘤预后和药物筛选方面的作用。此外,还从前瞻性的角度探讨了微流控设备在未来临床广泛应用的前景。
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引用次数: 0
Microfluidic technologies for advanced antimicrobial susceptibility testing. 用于高级抗菌药物药敏试验的微流控技术。
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-07 eCollection Date: 2024-05-01 DOI: 10.1063/5.0190112
Wenshuai Wu, Ying Mu

Antimicrobial resistance is getting serious and becoming a threat to public health worldwide. The improper and excessive use of antibiotics is responsible for this situation. The standard methods used in clinical laboratories, to diagnose bacterial infections, identify pathogens, and determine susceptibility profiles, are time-consuming and labor-intensive, leaving the empirical antimicrobial therapy as the only option for the first treatment. To prevent the situation from getting worse, evidence-based therapy should be given. The choosing of effective drugs requires powerful diagnostic tools to provide comprehensive information on infections. Recent progress in microfluidics is pushing infection diagnosis and antimicrobial susceptibility testing (AST) to be faster and easier. This review summarizes the recent development in microfluidic assays for rapid identification and AST in bacterial infections. Finally, we discuss the perspective of microfluidic-AST to develop the next-generation infection diagnosis technologies.

抗菌药耐药性日益严重,已成为全球公共卫生的威胁。抗生素的不当和过度使用是造成这种情况的原因。临床实验室用于诊断细菌感染、鉴定病原体和确定药敏谱的标准方法耗时耗力,因此经验性抗菌疗法成为首次治疗的唯一选择。为防止情况恶化,应采取循证疗法。选择有效的药物需要强大的诊断工具来提供全面的感染信息。微流控技术的最新进展正在推动感染诊断和抗菌药物药敏试验(AST)变得更快、更简单。本综述总结了用于细菌感染快速鉴定和 AST 的微流控检测的最新进展。最后,我们将从微流控-AST 的角度探讨下一代感染诊断技术的发展。
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引用次数: 0
Recent advances in microfluidic-based spectroscopic approaches for pathogen detection. 基于微流体的病原体检测光谱方法的最新进展。
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-06-07 eCollection Date: 2024-05-01 DOI: 10.1063/5.0204987
Mubashir Hussain, Xu He, Chao Wang, Yichuan Wang, Jingjing Wang, Mingyue Chen, Haiquan Kang, Na Yang, Xinye Ni, Jianqing Li, Xiuping Zhou, Bin Liu

Rapid identification of pathogens with higher sensitivity and specificity plays a significant role in maintaining public health, environmental monitoring, controlling food quality, and clinical diagnostics. Different methods have been widely used in food testing laboratories, quality control departments in food companies, hospitals, and clinical settings to identify pathogens. Some limitations in current pathogens detection methods are time-consuming, expensive, and laborious sample preparation, making it unsuitable for rapid detection. Microfluidics has emerged as a promising technology for biosensing applications due to its ability to precisely manipulate small volumes of fluids. Microfluidics platforms combined with spectroscopic techniques are capable of developing miniaturized devices that can detect and quantify pathogenic samples. The review focuses on the advancements in microfluidic devices integrated with spectroscopic methods for detecting bacterial microbes over the past five years. The review is based on several spectroscopic techniques, including fluorescence detection, surface-enhanced Raman scattering, and dynamic light scattering methods coupled with microfluidic platforms. The key detection principles of different approaches were discussed and summarized. Finally, the future possible directions and challenges in microfluidic-based spectroscopy for isolating and detecting pathogens using the latest innovations were also discussed.

以更高的灵敏度和特异性快速鉴定病原体在维护公共卫生、环境监测、控制食品质量和临床诊断方面发挥着重要作用。食品检测实验室、食品公司质量控制部门、医院和临床机构已广泛采用不同的方法来识别病原体。目前的病原体检测方法存在一些局限性,如耗时长、成本高、样品制备费力,不适合快速检测。微流控技术能够精确操控小体积流体,因此已成为生物传感应用中一项前景广阔的技术。微流控平台与光谱技术相结合,能够开发出能够检测和量化病原体样本的微型设备。本综述重点介绍了过去五年来在微流体设备与光谱方法相结合检测细菌微生物方面取得的进展。综述基于几种光谱技术,包括荧光检测、表面增强拉曼散射和动态光散射方法与微流控平台的结合。讨论并总结了不同方法的主要检测原理。最后,还讨论了利用最新创新技术分离和检测病原体的微流体光谱技术的未来可能发展方向和挑战。
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引用次数: 0
Microfluidic sweat patch based on capillary force and evaporation pump for real-time continuous sweat analysis 基于毛细管力和蒸发泵的微流控汗液贴片,用于实时连续汗液分析
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-05-31 DOI: 10.1063/5.0208075
Xiujun Fu, Ye Qiu, Hengjie Zhang, Ye Tian, Aiping Liu, Huaping Wu
In addition to the common blood and urine, fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body’s state. Wearable sweat sensors are crucial for understanding human physiological health; however, real-time in situ measurement of multiple biomarkers in sweat remains a significant challenge. Here, we propose a wearable microfluidic patch featuring an integrated microfluidic channel and evaporation pump for accelerated and continuous sweat collection, eliminating the need for additional sweat storage cavities that typically impede real-time detection. Capillary forces are harnessed to facilitate the rapid flow of sweat through the detection area, while an evaporation pump based on porous laser-induced graphene enhances sweat evaporation. The synergistic integration of these two components enables an uninterrupted flow of fresh sweat within the patch, ensuring real-time monitoring. The influence of channel size parameters on sweat flow velocity is analyzed, and the optimal width-to-height ratio for achieving the desired flow velocity is determined. By implementing a multi-channel parallel design with chamfering, liquid flow resistance is effectively reduced. Furthermore, the patch integrates sensor modules for sodium ion, chloride ion, glucose, and pH value measurements, ensuring excellent sealing and stability of the assembled system. This work presents a simplified approach to developing wearable sweat sensors that hold the potential for health monitoring and disease diagnosis.
除常见的血液和尿液外,新鲜汗液中还含有多种生理指标,可有效反映人体状态的变化。可穿戴汗液传感器对于了解人体生理健康状况至关重要;然而,对汗液中的多种生物标志物进行实时原位测量仍是一项重大挑战。在这里,我们提出了一种可穿戴式微流体贴片,其特点是集成了微流体通道和蒸发泵,可加速和持续收集汗液,无需额外的汗液存储腔,而这种存储腔通常会阻碍实时检测。利用毛细管力促进汗液快速流经检测区域,而基于多孔激光诱导石墨烯的蒸发泵则能增强汗液蒸发。这两个元件的协同整合使新鲜汗液在贴片内不间断地流动,确保了实时监测。分析了通道尺寸参数对汗液流速的影响,并确定了达到理想流速的最佳宽高比。通过采用带倒角的多通道并行设计,有效降低了液体流动阻力。此外,该贴片还集成了用于测量钠离子、氯离子、葡萄糖和 pH 值的传感器模块,确保了组装系统出色的密封性和稳定性。这项研究提出了一种开发可穿戴汗液传感器的简化方法,有望用于健康监测和疾病诊断。
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引用次数: 0
Hepatic spheroid-on-a-chip: Fabrication and characterization of a spheroid-based in vitro model of the human liver for drug screening applications 肝脏球形芯片:为药物筛选应用制作和表征基于球形的人体肝脏体外模型
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-05-28 DOI: 10.1063/5.0210955
Sultan K. AlShmmari, Roa S. Fardous, Zakia Shinwari, Dana Cialla-May, Jürgen Popp, Qasem Ramadan, Mohammed Zourob
The integration of microfabrication and microfluidics techniques into cell culture technology has significantly transformed cell culture conditions, scaffold architecture, and tissue biofabrication. These tools offer precise control over cell positioning and enable high-resolution analysis and testing. Culturing cells in 3D systems, such as spheroids and organoids, enables recapitulating the interaction between cells and the extracellular matrix, thereby allowing the creation of human-based biomimetic tissue models that are well-suited for pre-clinical drug screening. Here, we demonstrate an innovative microfluidic device for the formation, culture, and testing of hepatocyte spheroids, which comprises a large array of patterned microwells for hosting hepatic spheroid culture in a reproducible and organized format in a dynamic fluidic environment. The device allows maintaining and characterizing different spheroid sizes as well as exposing to various drugs in parallel enabling high-throughput experimentation. These liver spheroids exhibit physiologically relevant hepatic functionality, as evidenced by their ability to produce albumin and urea at levels comparable to in vivo conditions and the capability to distinguish the toxic effects of selected drugs. This highlights the effectiveness of the microenvironment provided by the chip in maintaining the functionality of hepatocyte spheroids. These data support the notion that the liver-spheroid chip provides a favorable microenvironment for the maintenance of hepatocyte spheroid functionality.
微加工和微流体技术与细胞培养技术的整合极大地改变了细胞培养条件、支架结构和组织生物制造。这些工具可精确控制细胞定位,实现高分辨率分析和测试。在球形和有机体等三维系统中培养细胞,可以重现细胞与细胞外基质之间的相互作用,从而创建出非常适合临床前药物筛选的人体生物仿真组织模型。在这里,我们展示了一种用于肝细胞球体的形成、培养和测试的创新型微流体设备,它包括一个大型图案微孔阵列,用于在动态流体环境中以可重现和有组织的形式进行肝球体培养。该装置可维持和表征不同大小的球体,并可同时接触各种药物,从而实现高通量实验。这些肝脏球体表现出了与生理相关的肝脏功能,其产生白蛋白和尿素的能力可与体内条件相媲美,并能区分特定药物的毒性作用。这凸显了芯片提供的微环境在维持肝细胞球体功能方面的有效性。这些数据支持肝球芯片为维持肝细胞球功能提供有利微环境的观点。
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引用次数: 0
Manipulation of magnetic beads for actively capturing Vibrio parahaemolyticus and nucleic acid based on microfluidic system. 基于微流体系统的磁珠主动捕获副溶血性弧菌和核酸的操作。
IF 3.2 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-05-10 eCollection Date: 2024-05-01 DOI: 10.1063/5.0193442
Zhaoxuan Zhang, Xue Deng, Wenqiang Zhang, Kehan Chen, Yuan Su, Chao Gao, De Gong, Longjiao Zhu, Jun Cai

Rapid biological detection of pathogen micro-organisms has attracted much attention for practical biomedical applications. Despite the development in this field, it is still challenging to achieve simple and rapid biological detection using the microfluidic method. Herein, we propose a novel strategy of biological detection that combines precise detection control of the capillary microfluidic chip and versatile manipulation of magnetic beads. The microfluidic chip was fabricated via laser cutting, which utilized capillary pressure to realize rapid passive injection of liquid samples. Under an external magnetic field, the aptamer-modified magnetic beads were actuated to mix with Vibrio parahaemolyticus (V. parahaemolyticus) and its nucleic acid in the capillary microfluidic chip for rapid selective capture and detection, which could be achieved within 40 min. The experimental results demonstrated that V. parahaemolyticus could be captured using on-chip immunomagnetic beads with a high efficiency and significantly enhanced detection value. Due to these superior performances, the capillary microfluidic system, based on the manipulation of magnetic beads, demonstrated great potential for automatic biological detection.

病原微生物的快速生物检测在实际生物医学应用中备受关注。尽管这一领域在不断发展,但利用微流体方法实现简单快速的生物检测仍具有挑战性。在此,我们提出了一种新型生物检测策略,将毛细管微流控芯片的精确检测控制与磁珠的多功能操作相结合。微流控芯片通过激光切割制作而成,利用毛细管压力实现液体样品的快速被动注入。在外加磁场的作用下,合子修饰的磁珠被驱动与毛细管微流控芯片中的副溶血弧菌及其核酸混合,实现快速选择性捕获和检测,整个过程可在 40 分钟内完成。实验结果表明,使用芯片上的免疫磁珠可高效捕获副溶血性弧菌,并显著提高检测值。由于这些优异的性能,基于磁珠操作的毛细管微流控系统在生物自动检测方面展现出巨大的潜力。
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引用次数: 0
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