Microfluidic devices

  • 文章类型: Journal Article
    许多生物系统的工作温度范围很窄,这意味着需要高精度和空间分布水平来研究这些系统。大多数温度传感器不能同时满足微流体系统所需的精度和空间分布,微流体系统通常用于单独研究这些系统。本文介绍了一种称为多方向荧光温度长短期记忆网络(MFTLSTM)的神经网络,该网络可以准确计算荧光图像中每个像素的温度,以改进标准拟合实践和其他机器学习方法用于将荧光数据与温度相关联。该网络利用图像中热扩散的性质,以模拟数据在298K至308K的温度范围内实现±0.0199KRMSE的精度。当应用于温度范围为290K至380K的3D打印微流体设备的实验数据时,精度为±0.0684KRMSE。这些结果具有在生物系统中允许比在许多微流体装置中可获得的高温分辨率的潜力。
    Many biological systems have a narrow temperature range of operation, meaning high accuracy and spatial distribution level are needed to study these systems. Most temperature sensors cannot meet both the accuracy and spatial distribution required in the microfluidic systems that are often used to study these systems in isolation. This paper introduces a neural network called the Multi-Directional Fluorescent Temperature Long Short-Term Memory Network (MFTLSTM) that can accurately calculate the temperature at every pixel in a fluorescent image to improve upon the standard fitting practice and other machine learning methods use to relate fluorescent data to temperature. This network takes advantage of the nature of heat diffusion in the image to achieve an accuracy of ±0.0199 K RMSE within the temperature range of 298K to 308 K with simulated data. When applied to experimental data from a 3D printed microfluidic device with a temperature range of 290 K to 380 K, it achieved an accuracy of ±0.0684 K RMSE. These results have the potential to allow high temperature resolution in biological systems than is available in many microfluidic devices.
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  • 文章类型: Journal Article
    各种领域都需要对液体进行高灵敏度的定量分析。色谱等分析仪器和设备,光谱分析,DNA测序仪,免疫测定,质谱,和微流体装置用于此目的。通常,样品体积在毫升尺度上,而分析体积在微升规模。因此,大部分样本被丢弃。因此,需要通用的体积接口来定量浓缩从毫升到微升体积的样品。这项研究将液体定量函数引入到使用毫米尺度通道的旋风浓缩方法中,由于其对旋风流的高流体阻力,非常适合控制微升尺度的液体。该方法能够通过旋风流有效控制液体浓度。研究了最佳通道结构,并证明了33倍浓度的水溶液。最后,浓缩装置用于测量河流中的钼离子。
    Highly sensitive quantitative analysis of liquids is required in various fields. Analytical instruments and devices such as chromatography, spectroscopic analysis, DNA sequencers, immunoassay, mass spectrometry, and microfluidic devices are utilized for this purpose. Typically, the sample volume is at the milliliter scale, while the analysis volume is at the microliter scale. Consequently, most of the sample is discarded. Therefore, a universal volume interface is required to quantitatively concentrate samples from milliliter to microliter volume. This study introduces a liquid quantitative function to the cyclone concentration method using a millimeter-scale channel, which is highly suitable for controlling liquids at the microliter scale due to its high fluidic resistance against cyclone flow. This method enables the effective control of liquid concentration by cyclone flow. The optimum channel structure is investigated, and a 33-fold concentration of aqueous solutions is demonstrated. Finally, the concentration device is applied to measure molybdenum ions in a river.
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  • 文章类型: Journal Article
    芯片上器官(OOC)是一种多通道3D微流体细胞培养系统,包含在芯片中,可以刺激器官的行为。这项技术依赖于多学科科学,受益于包括微生物学在内的许多领域的进步,微流体,生物材料,和生物工程。本文综述了各种芯片上器官技术的进展和成果。它突出了该技术在减少动物试验和提供个性化医疗反应方面的显著优势。此外,本文展示了OOC如何成为药物研究中对抗疾病的有前途和强大的工具。它不仅可以预测药物对靶器官的影响,使用芯片上的身体系统,它可以提供对药物递送对其他器官的副作用的见解。同样,研究了用于构建各种芯片上器官的模型以及微流体设备的设计和材料。对于每个OOC,芯片内的集成监控设备(例如,传感器和生物传感器)进行了讨论。我们还讨论了FDA法规的演变以及在不久的将来将OOC整合到协议批准中的潜力,以支持和减少临床前和临床研究中的需求和失败率。
    Organ-On-a-Chip (OOC) is a multichannel 3D-microfluidic cell-culture system included in a chip that stimulates the behavior of an organ. This technology relies on a multidisciplinary science benefiting from and helping in the progress of many fields including microbiology, microfluidics, biomaterials, and bioengineering. This review article summarizes the progress and achievements of various organ-on-chip technologies. It highlights the significant advantages of this technology in terms of reducing animal testing and providing personalized medical responses. In addition, this paper demonstrates how OOC is becoming a promising and powerful tool in pharmaceutical research to combat diseases. It predicts not only the effects of drugs on the target organs but also, using body-on-a-chip systems, it may provide insights into the side effects of the drug delivery on the other organs. Likewise, the models used for the construction of various organ-on-a-chip are investigated along with the design and materials of microfluidic devices. For each OOC, the integrated monitoring devices within the chips (e.g., sensors and biosensors) are discussed. We also discussed the evolution of FDA regulations and the potential in the near future for integrating OOCs in protocols approval that support and reduce the need and the failure rates in preclinical and clinical studies.
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  • 文章类型: Journal Article
    轴突损伤是创伤性损伤和神经退行性疾病的共同特征。损伤后轴突再生和恢复功能的能力是一种在周围神经系统中很容易看到的现象。尤其是在啮齿动物模型中,但人类轴突再生是有限的,并不能导致功能的完全恢复。在这里,我们描述了一个系统,其中可以通过在微流体系统中培养的人诱导多能干细胞(hiPSC)衍生的神经元的实时成像来评估人轴突生长和再生的动力学。细胞体从轴突中分离出来。该系统可以帮助研究轴突生长动力学,并且可以用于测试促进神经系统再生和修复的潜在药物。
    Axonal damage is a common feature of traumatic injury and neurodegenerative disease. The capacity for axons to regenerate and to recover functionality after injury is a phenomenon that is seen readily in the peripheral nervous system, especially in rodent models, but human axonal regeneration is limited and does not lead to full functional recovery. Here we describe a system where dynamics of human axonal outgrowth and regeneration can be evaluated via live imaging of human-induced pluripotent stem cell (hiPSC)-derived neurons cultured in microfluidic systems, in which cell bodies are isolated from their axons. This system could aid in studying axonal outgrowth dynamics and could be useful for testing potential drugs that encourage regeneration and repair of the nervous system.
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  • 文章类型: Journal Article
    气味运输具有基础和应用重要性。使用计算模拟,我们在Hagfish(可能是Eptatretusstoutii)的鼻通道的解剖学精确模型中研究了气味运输。我们发现环境水被广泛采样,有明显的腹侧元素。此外,嗅觉流有双边元素,它进入两个狭窄的单个鼻孔,然后在鼻腔之前由中央嗅层的前缘分裂的层流。该薄片上的附属物将整个鼻流的一小部分(10-14%)引导到嗅觉感觉通道。剩余流的大部分通过两个外围通道从感觉通道转向。中央嗅层的前缘,连同喷射冲击机构,将流动分散在嗅觉表面上。感官通道的大表面积:体积比促进了气味剂从散装水到嗅觉表面的扩散,并通过基于阻力的流体动力学机制,导致在感觉通道中的长停留时间(高达4.5s)。随着体积流量的增加,气味转移到嗅觉表面的速率增加,但是气味吸收的效率降低了,落在2-6%的范围内。气味通量在嗅觉表面的尾随减少,表明在体内,嗅觉感觉神经元在每个嗅觉表面的前部占优势。我们得出的结论是,盲鱼具有复杂的解剖结构,可以定位和捕获气味分子。
    Odorant transport is of fundamental and applied importance. Using computational simulations, we studied odorant transport in an anatomically accurate model of the nasal passage of a hagfish (probably Eptatretus stoutii). We found that ambient water is sampled widely, with a significant ventral element. Additionally, there is a bilateral element to olfactory flow, which enters the single nostril in two narrow, laminar streams that are then split prior to the nasal chamber by the anterior edge of the central olfactory lamella. An appendage on this lamella directs a small portion (10-14%) of the overall nasal flow to the olfactory sensory channels. Much of the remaining flow is diverted away from the sensory channels by two peripheral channels. The anterior edge of the central olfactory lamella, together with a jet-impingement mechanism, disperses flow over the olfactory surfaces. Diffusion of odorant from bulk water to the olfactory surfaces is facilitated by the large surface area:volume ratio of the sensory channels, and by a resistance-based hydrodynamic mechanism that leads to long residence times (up to 4.5 s) in the sensory channels. With increasing volumetric flow rate, the rate of odorant transfer to the olfactory surfaces increases, but the efficiency of odorant uptake decreases, falling in the range 2-6%. Odorant flux decreases caudally across the olfactory surfaces, suggesting in vivo a preponderance of olfactory sensory neurons on the anterior part of each olfactory surface. We conclude that the hagfish has a subtle anatomy for locating and capturing odorant molecules.
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  • 文章类型: Journal Article
    实体肿瘤是人类最常见的癌症类型,分为肉瘤,淋巴瘤,和基于起源细胞的癌。其中,癌,它们来自身体组织的上皮细胞和腺细胞,是最普遍的。在世界各地,近年来,观察到实体瘤的发病率显着增加。在这种情况下,发现更有效的癌症治疗方法的努力使人们对肿瘤微环境及其成分有了更深入的了解。目前,癌细胞和肿瘤微环境的元素之间的相互作用正在被深入研究。研究取得了显著进展,主要是由于先进的体外模型的发展,例如芯片上肿瘤模型,有助于理解并最终发现针对特定类型癌症的新的有效治疗方法。本文的目的是对肿瘤微环境和癌细胞成分进行综述,随着设计用于模拟肿瘤的芯片上肿瘤模型的进步,提供了当前最先进的视角。最近使用这种微设备再现肿瘤微环境的研究使人们对癌症及其治疗有了更好的了解。然而,该技术的当前应用存在一些局限性,必须克服这些局限性,以便寻求更深入的癌症知识和改善当前疗法的新策略的研究人员能够广泛应用。
    Solid tumors represent the most common type of cancer in humans and are classified into sarcomas, lymphomas, and carcinomas based on the originating cells. Among these, carcinomas, which arise from epithelial and glandular cells lining the body\'s tissues, are the most prevalent. Around the world, a significant increase in the incidence of solid tumors is observed during recent years. In this context, efforts to discover more effective cancer treatments have led to a deeper understanding of the tumor microenvironment (TME) and its components. Currently, the interactions between cancer cells and elements of the TME are being intensely investigated. Remarkable progress in research is noted, largely owing to the development of advanced in vitro models, such as tumor-on-a-chip models that assist in understanding and ultimately discovering new effective treatments for a specific type of cancer. The purpose of this article is to provide a review of the TME and cancer cell components, along with the advances on tumor-on-a-chip models designed to mimic tumors, offering a perspective on the current state of the art. Recent studies using this kind of microdevices that reproduce the TME have allowed a better understanding of the cancer and its treatments. Nevertheless, current applications of this technology present some limitations that must be overcome to achieve a broad application by researchers looking for a deeper knowledge of cancer and new strategies to improve current therapies.
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  • 文章类型: Journal Article
    最近的进展使体外模拟人类小肠成为可能,但要完全概括它们的结构和功能特征仍然是一个挑战。我们怀疑肠道内的间质流,在胚胎器官发生过程中由循环血浆提供动力,成为一个重要因素。我们旨在通过将间质流纳入系统来构建体内多层小肠组织,反过来,通过在能够复制间质流的微流体装置上同时区分定形内胚层和中胚层细胞与人多能干细胞,开发了小肠系统。这种方法增强了细胞成熟,并导致了具有绒毛样上皮和对齐的间充质层的三维小肠样组织的发育。我们的小肠系统不仅克服了传统肠道模型的局限性,而且还提供了一个独特的机会来深入了解肠道组织发育的详细机制。
    Recent advances have made modeling human small intestines in vitro possible, but it remains a challenge to recapitulate fully their structural and functional characteristics. We suspected interstitial flow within the intestine, powered by circulating blood plasma during embryonic organogenesis, to be a vital factor. We aimed to construct an in vivo-like multilayered small intestinal tissue by incorporating interstitial flow into the system and, in turn, developed the micro-small intestine system by differentiating definitive endoderm and mesoderm cells from human pluripotent stem cells simultaneously on a microfluidic device capable of replicating interstitial flow. This approach enhanced cell maturation and led to the development of a three-dimensional small intestine-like tissue with villi-like epithelium and an aligned mesenchymal layer. Our micro-small intestine system not only overcomes the limitations of conventional intestine models but also offers a unique opportunity to gain insights into the detailed mechanisms underlying intestinal tissue development.
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  • 文章类型: Journal Article
    在无血管肿瘤内形成坏死区域的潜在机制是复杂的且知之甚少。在本文中,我们研究了微流体装置内3D肿瘤细胞培养物中坏死核心的形成,考虑到氧气,营养素,并通过计算数学模型对微环境酸化进行了研究。我们的目标是模拟细胞过程,包括微流体装置内的增殖和死亡,根据微环境条件。我们利用考虑葡萄糖的有限元模型进行近似,氧气,和氢离子扩散,消费和生产,以及细胞增殖,移民和死亡,解决肿瘤细胞在不同条件下如何进化。在不同的情况下检查了所得的数学模型,能够在不同的细胞浓度下复制细胞死亡和增殖,坏死核的形成,与文献中报道的实验数据非常吻合。这种方法不仅促进了我们对坏死核心形成的基本理解,而且还提供了一个强大的计算平台来研究个性化治疗策略。提供癌症研究和治疗设计的重要工具。
    The mechanisms underlying the formation of necrotic regions within avascular tumors are complex and poorly understood. In this paper, we investigate the formation of a necrotic core in a 3D tumor cell culture within a microfluidic device, considering oxygen, nutrients, and the microenvironment acidification by means of a computational-mathematical model. Our objective is to simulate cell processes, including proliferation and death inside a microfluidic device, according to the microenvironmental conditions. We employed approximation utilizing finite element models taking into account glucose, oxygen, and hydrogen ions diffusion, consumption and production, as well as cell proliferation, migration and death, addressing how tumor cells evolve under different conditions. The resulting mathematical model was examined under different scenarios, being capable of reproducing cell death and proliferation under different cell concentrations, and the formation of a necrotic core, in good agreement with experimental data reported in the literature. This approach not only advances our fundamental understanding of necrotic core formation but also provides a robust computational platform to study personalized therapeutic strategies, offering an important tool in cancer research and treatment design.
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  • 文章类型: Journal Article
    MEMS器件越来越普遍地用作传感器,执行器,以及电子等不同领域的微流体设备,光电,和生物医学工程。传统的制造技术无法满足不断增长的器件小型化和缩短制造时间的需求,特别是当定制的设备是必需的。这就是为什么增材制造技术越来越多地应用于MEMS。在这次审查中,注意力集中在意大利关于3D打印MEMS的情况上,研究用于制造的技术和材料。为了这个目标,进行了如下研究:第一,已经说明了MEMS制造中常用的3D打印技术,然后报道了一些3D打印MEMS的例子。之后,这些技术的典型材料已经被提出,最后,已经描述了它们在MEMS制造中的一些应用示例。总之,3D打印技术的应用,而不是传统工艺,在意大利是一个日益增长的趋势,在那里已经获得了一些令人兴奋和有希望的结果,由于这些新的选择技术和涉及的新材料。
    MEMS devices are more and more commonly used as sensors, actuators, and microfluidic devices in different fields like electronics, opto-electronics, and biomedical engineering. Traditional fabrication technologies cannot meet the growing demand for device miniaturisation and fabrication time reduction, especially when customised devices are required. That is why additive manufacturing technologies are increasingly applied to MEMS. In this review, attention is focused on the Italian scenario in regard to 3D-printed MEMS, studying the techniques and materials used for their fabrication. To this aim, research has been conducted as follows: first, the commonly applied 3D-printing technologies for MEMS manufacturing have been illustrated, then some examples of 3D-printed MEMS have been reported. After that, the typical materials for these technologies have been presented, and finally, some examples of their application in MEMS fabrication have been described. In conclusion, the application of 3D-printing techniques, instead of traditional processes, is a growing trend in Italy, where some exciting and promising results have already been obtained, due to these new selected technologies and the new materials involved.
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  • 文章类型: Journal Article
    镰刀菌在谷物和饲料中发现,并可能产生霉菌毒素,是次生代谢产物,例如T-2毒素(T-2)。在这项工作中,我们使用微流控3D肝培养探索T-2的肝毒性。目标是:(i)探索与市售常规3D培养物(Aggrewell平板)相比,微流体3D培养物的益处,(ii)建立肝细胞(HepG2)和星状细胞(LX2)的3D共培养,并评估该模型中的T-2暴露,(iii)表征代谢酶的诱导,和(iv)评估微流控肝培养物中T-2暴露后的炎症标志物。我们的研究结果表明,与商业(大容量)3D文化相比,球状体形成得更快,在微流体装置中功能更强。在单培养和共培养中,活力和肝功能随T-2浓度的增加而降低。RT-PCR分析显示,暴露于T-2会上调多种I期和II期肝酶的表达。此外,暴露于T-2后,共培养物中几种促炎和抗炎蛋白增加.
    The Fusarium fungi is found in cereals and feedstuffs and may produce mycotoxins, which are secondary metabolites, such as the T-2 toxin (T-2). In this work, we explored the hepatotoxicity of T-2 using microfluidic 3D hepatic cultures. The objectives were: (i) exploring the benefits of microfluidic 3D cultures compared to conventional 3D cultures available commercially (Aggrewell plates), (ii) establishing 3D co-cultures of hepatic cells (HepG2) and stellate cells (LX2) and assessing T-2 exposure in this model, (iii) characterizing the induction of metabolizing enzymes, and (iv) evaluating inflammatory markers upon T-2 exposure in microfluidic hepatic cultures. Our results demonstrated that, in comparison to commercial (large-volume) 3D cultures, spheroids formed faster and were more functional in microfluidic devices. The viability and hepatic function decreased with increasing T-2 concentrations in both monoculture and co-cultures. The RT-PCR analysis revealed that exposure to T-2 upregulates the expression of multiple Phase I and Phase II hepatic enzymes. In addition, several pro- and anti-inflammatory proteins were increased in co-cultures after exposure to T-2.
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