microfluidic technology

微流控技术
  • 文章类型: Journal Article
    尽管有许多关于软骨形成的研究,软骨的修复-特别是通过一体化先进的药物递送系统重建软骨空洞仍然有限。在这项研究中,我们开发了一种软骨腔隙状水凝胶微球系统,具有整合的生物信号,实现顺序免疫调节和内源性关节软骨再生。我们首先将软骨形成生长因子转化生长因子-β3(TGF-β3)整合到介孔二氧化硅纳米颗粒(MSN)中。然后,将TGF-β3@MSN和胰岛素样生长因子1(IGF-1)封装在聚多巴胺(pDA)制成的微球中。在最后一步,将负载生长因子的MSN@pDA和含有血小板衍生生长因子-BB(PDGF-BB)的壳聚糖(CS)水凝胶混合,以使用微流体技术生产负载生长因子的复合微球(GFs@μS)。pDA的存在减少了最初的急性炎症反应,早期,PDGF-BB的强力释放有助于吸引内源性干细胞。在接下来的几周里,IGF-1和TGF-β3的持续释放增强了软骨形成和基质形成。μS掺入无细胞软骨细胞外基质(ACECM),并与聚多巴胺修饰的聚己内酯(PCL)结构结合产生组织工程支架,该支架模仿了软骨基质中均匀分布的软骨空洞的结构,从而增强软骨修复和髌骨软骨保护。本研究为优化生长因子递送和确保延长微环境重塑提供了战略途径。导致有效的关节软骨再生。
    Despite numerous studies on chondrogenesis, the repair of cartilage-particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-β3 (TGF-β3) into mesoporous silica nanoparticles (MSNs). Then, TGF-β3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@μS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation. μS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.
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  • 文章类型: Journal Article
    细胞共培养技术旨在研究细胞间的通讯机制,更好地揭示细胞生长等过程中所涉及的相互作用和调控机制,分化,凋亡,和其他细胞活动。这是通过模拟复杂的生物环境来实现的。此类研究对于理解多细胞生物的生理和病理过程具有重要意义。作为一种新兴的细胞培养技术,3D细胞共培养技术,基于微流控芯片,可以有效地,迅速,并准确实现细胞共培养。这是通过利用微流体芯片的独特微通道结构和流动特性来实现的。该技术可以模拟细胞生长的天然微环境,为研究细胞间通信提供了新的技术平台。它已被广泛应用于肿瘤学的研究,免疫学,神经科学,和其他领域。在这次审查中,我们总结并提供了对微流控芯片上细胞共培养系统设计的见解,共培养系统中使用的检测方法,以及这些模型的应用。
    Cell co-culture technology aims to study the communication mechanism between cells and to better reveal the interactions and regulatory mechanisms involved in processes such as cell growth, differentiation, apoptosis, and other cellular activities. This is achieved by simulating the complex organismic environment. Such studies are of great significance for understanding the physiological and pathological processes of multicellular organisms. As an emerging cell cultivation technology, 3D cell co-culture technology, based on microfluidic chips, can efficiently, rapidly, and accurately achieve cell co-culture. This is accomplished by leveraging the unique microchannel structures and flow characteristics of microfluidic chips. The technology can simulate the native microenvironment of cell growth, providing a new technical platform for studying intercellular communication. It has been widely used in the research of oncology, immunology, neuroscience, and other fields. In this review, we summarize and provide insights into the design of cell co-culture systems on microfluidic chips, the detection methods employed in co-culture systems, and the applications of these models.
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  • 文章类型: Journal Article
    神经系统结构和功能的复杂性,以及其缓慢的再生速度,与其他组织相比,治疗起来更加困难。神经组织工程旨在为神经细胞增殖和分化创造合适的环境。具有合适的形态和形貌以及更好的细胞外基质模拟的纤维支架有望用于神经细胞的排列和迁移。在这个前提下,为了改善脚手架的性能,我们将蒙脱石(MMT)与壳聚糖(CS)聚合物结合,并使用微流体技术创建了具有可变直径和不同浓度的MMT的微纤维,并测试了其对大鼠嗜铬细胞瘤细胞系(PC12)的适用性。根据调查结果,CS/MMT0.1%与CS/MMT0%相比,微纤维的杨氏模量增加了201MPa,电导率增加68mS/m,输出电压增加1.4倍。细胞线粒体活性分析验证了无毒性,导致良好的细胞形态与沿微纤维的方向。总的来说,该项目的结果表明,在低浓度的MMT中,可以显著改善微纤维的性能,并设计合适的支架用于神经组织工程。
    The complexity in structure and function of the nervous system, as well as its slow rate of regeneration, makes it more difficult to treat it compared to other tissues. Neural tissue engineering aims to create an appropriate environment for nerve cell proliferation and differentiation. Fibrous scaffolds with suitable morphology and topography and better mimicry of the extracellular matrix have been promising for the alignment and migration of neural cells. On this premise, to improve the properties of the scaffold, we combined montmorillonite (MMT) with chitosan (CS) polymer and created microfibers with variable diameters and varied concentrations of MMT using microfluidic technology and tested its suitability for the rat pheochromocytoma cell line (PC12). According to the findings, CS/MMT 0.1 % compared to CS/MMT 0 % microfibers showed a 201 MPa increase in Young\'s modulus, a 68 mS/m increase in conductivity, and a 1.4-fold increase in output voltage. Analysis of cell mitochondrial activity verified the non-toxicity, resulting in good cell morphology with orientation along the microfiber. Overall, the results of this project showed that with a low concentration of MMT, the properties of microfibers can be significantly improved and a suitable scaffold can be designed for neural tissue engineering.
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  • 文章类型: Journal Article
    干细胞在组织工程中至关重要,他们的微环境极大地影响了他们的行为。在各种牙齿干细胞类型中,根尖乳头(SCAP)的干细胞显示出再生牙髓-牙本质复合体的巨大潜力。影响SCAP的微环境线索包括物理和生化因素。为了研究牙髓-牙本质复合物的最佳再生,研究人员开发了几种受控的仿生微环境模型,从体内动物模型到体外模型,包括二维文化和三维设备。在这些模型中,最强大的工具是微流体设备,具有高微结构空间分辨率和精确微环境控制的芯片牙齿。在这次审查中,我们从牙髓-牙本质复合物再生中的SCAP微环境开始,讨论了与生物过程相关的研究模型和研究。
    Stem cells are crucial in tissue engineering, and their microenvironment greatly influences their behavior. Among the various dental stem cell types, stem cells from the apical papilla (SCAPs) have shown great potential for regenerating the pulp-dentin complex. Microenvironmental cues that affect SCAPs include physical and biochemical factors. To research optimal pulp-dentin complex regeneration, researchers have developed several models of controlled biomimetic microenvironments, ranging from in vivo animal models to in vitro models, including two-dimensional cultures and three-dimensional devices. Among these models, the most powerful tool is a microfluidic microdevice, a tooth-on-a-chip with high spatial resolution of microstructures and precise microenvironment control. In this review, we start with the SCAP microenvironment in the regeneration of pulp-dentin complexes and discuss research models and studies related to the biological process.
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  • 文章类型: Journal Article
    性传播感染(STIs)是全球最常见的传染病之一,经常导致合并感染。在高危人群中及时检测生殖道病原体对于预防性传播感染至关重要。我们评估了NAP-Fluo循环系统,创新的微流控核酸检测平台,具有同时识别沙眼衣原体(CT)的能力,淋病奈瑟菌(NG),解脲脲原体(UU),生殖支原体(MG),尿道或宫颈分泌物中的人型支原体(MH)。
    检测限(LODs),重复性,特异性,使用标准菌株评估系统的抗干扰性,由24种病原体组成的小组,和七个干扰物。我们使用该系统分析了302个临床样本,并将结果与五个已批准的商业参考试剂盒的结果进行了比较。
    系统达到500IFU/mL的LOD,500CFU/mL,和500CCU/mL的CT,NG,和UU/MG/MH,分别,表现出高稳定性(变异系数<1.1%),特异性,和抗干扰。在302个临床样本中,237单检测呈阳性,双重,三联感染率为35.6%,16.2%,和3.0%,分别。参考试剂盒检测到138个阳性样品。UU与商业参考试剂盒的一致率为100%,NG,MH;CT为94.85%;MG为80.00%。
    该系统提供了一个简化的,快速,和多路检测方法,减少了测试时间和复杂性。尽管它在纯菌株中表现良好,当使用CT和MG的临床样本时,它有局限性,建议在临床广泛使用之前需要进一步改进。
    UNASSIGNED: Sexually transmitted infections (STIs) are among the most common infectious diseases worldwide, often leading to coinfections. Timely detection of genital tract pathogens in at-risk populations is crucial for preventing STIs. We evaluated the NAP-Fluo Cycler System, an innovative microfluidic nucleic acid detection platform, for its ability to simultaneously identify Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Ureaplasma urealyticum (UU), Mycoplasma genitalium (MG), and Mycoplasma hominis (MH) in urethral or cervical secretions.
    UNASSIGNED: The limits of detection (LODs), repeatability, specificity, and interference resistance of the system were evaluated using standard strains, a panel of 24 pathogens, and seven interferents. We used the system to analyze 302 clinical samples and compared the results with those of five approved commercial reference kits.
    UNASSIGNED: The system achieved LODs of 500 IFU/mL, 500 CFU/mL, and 500 CCU/mL for CT, NG, and UU/MG/MH, respectively, demonstrating high stability (coefficient of variation <1.1 %), specificity, and resistance to interference. Among 302 clinical samples, 237 tested positive with single, dual, and triple infection rates of 35.6 %, 16.2 %, and 3.0 %, respectively. The reference kits detected 138 positive samples. The concordance rates with commercial reference kits were 100 % for UU, NG, and MH; 94.85 % for CT; and 80.00 % for MG.
    UNASSIGNED: This system offers a streamlined, rapid, and multiplex detection method that reduces testing time and complexity. Although it performs well with pure strains, it has limitations when using clinical samples of CT and MG, suggesting the need for further refinement before its widespread use in the clinic.
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  • 文章类型: Journal Article
    基于光学诱导介电泳(ODEP)的微粒分选和分离被认为是有前途的。然而,目前的方法通常缺乏运输和收集分离的微粒的下游过程,这可能会限制其应用。为了解决这个问题,ODEP微流体芯片包含三个微通道,这些微通道仅在微通道的中心部分连接(即,工作区)的设计。操作过程中,该区域产生了三个层流,其中两个动态光条阵列被设计用于以连续方式分选和分离不同尺寸的PS(聚苯乙烯)微珠。然后将分离的PS微珠以分隔方式在层流中连续运输以进行最终收集。结果表明,该方法能够以高纯度的方式分选和分离PS微珠(例如,收集的5.8、10.8和15.8μm微珠的微珠纯度值分别为89.9±3.7、88.0±2.5和92.8±6.5%,分别)。总的来说,这项研究证明了使用层流和ODEP来实现基于大小的分选,分离,以及以连续和高性能的方式收集微粒。除了示威,该方法还可用于基于大小的分选和其他生物或非生物微粒的分离。
    Optically induced dielectrophoresis (ODEP)-based microparticle sorting and separation is regarded as promising. However, current methods normally lack the downstream process for the transportation and collection of separated microparticles, which could limit its applications. To address this issue, an ODEP microfluidic chip encompassing three microchannels that join only at the central part of the microchannels (i.e., the working zone) was designed. During operation, three laminar flows were generated in the zone, where two dynamic light bar arrays were designed to sort and separate PS (polystyrene) microbeads of different sizes in a continuous manner. The separated PS microbeads were then continuously transported in laminar flows in a partition manner for the final collection. The results revealed that the method was capable of sorting and separating PS microbeads in a high-purity manner (e.g., the microbead purity values were 89.9 ± 3.7, 88.0 ± 2.5, and 92.8 ± 6.5% for the 5.8, 10.8, and 15.8 μm microbeads harvested, respectively). Overall, this study demonstrated the use of laminar flow and ODEP to achieve size-based sorting, separation, and collection of microparticles in a continuous and high-performance manner. Apart from the demonstration, this method can also be utilized for size-based sorting and the separation of other biological or nonbiological microparticles.
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  • 文章类型: Journal Article
    微流体技术,作为纳米粒子的连续和大量制备方法,近年来备受关注。在这项研究中,通过将微流体平台与反溶剂方法相结合,以高度受控的方式连续制造玉米醇溶蛋白纳米颗粒(ZNP)。乙醇含量的影响(60~95%,v/v)以及微流体平台中内部和外部相的流速对颗粒性质的影响。在所有ZNPS中,90%-ZNPs具有最高的溶解度(32.83%)和最低的疏水性(90.43),这是ZNP疏水性的反向点。此外,当内相流速为1.5mL/h时,随着外相流速从10mL/h增加到50mL/h,粒径从182.81nm显着降低到133.13nm。结果表明,乙醇含量对ZNP的亲水-疏水性能有显著影响。微流体平台中乙醇-水溶液和去离子水(溶剂和反溶剂)的流速显着影响ZNP的粒径。这些发现表明,微流体平台和反溶剂方法的组合应用可能是精确控制蛋白质纳米颗粒制造过程并调节其物理化学性质的有效途径。
    Microfluidic technology, as a continuous and mass preparation method of nanoparticles, has attracted much attention in recent years. In this study, zein nanoparticles (ZNPs) were continuously fabricated in a highly controlled manner by combining a microfluidics platform with the antisolvent method. The impact of ethanol content (60~95%, v/v) and flow rates of inner and outer phases in the microfluidics platform on particle properties were examined. Among all ZNPS, 90%-ZNPs have the highest solubility (32.83%) and the lowest hydrophobicity (90.43), which is the reverse point of the hydrophobicity of ZNPs. Moreover, when the inner phase flow rate was 1.5 mL/h, the particle size decreased significantly from 182.81 nm to 133.13 nm as the outer phase flow rate increased from 10 mL/h to 50 mL/h. The results revealed that ethanol content had significant impacts on hydrophilic-hydrophobic properties of ZNPs. The flow rates of ethanol-water solutions and deionized water (solvent and antisolvent) in the microfluidics platform significantly affected the particle size of ZNPs. These findings demonstrated that the combined application of a microfluidics platform and an antisolvent method could be an effective pathway for precisely controlling the fabrication process of protein nanoparticles and modulating their physicochemical properties.
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  • 文章类型: Journal Article
    本研究的主要目的是制造一种创新的三维微流体平台,适用于生产微调纳米结构材料所需的良好控制的化学合成。这项工作提出了使用限制在3D多层微反应器中的涡旋混合原理来合成具有定制尺寸和多分散性的磁性核壳纳米颗粒。新设计的微流体平台允许在短的反应时间和高流速下同时获得Fe3O4核及其与水杨酸壳的官能化。还进行了合成优化,利用试剂比例的变化来突出磁铁矿主要产生的浓度域,形成不同直径和低多分散性的纳米颗粒,以及胶体分散体在水中的稳定性。通过X射线衍射(XRD)对所得材料进行了进一步的表征,傅里叶变换红外(FT-IR)光谱,动态光散射(DLS),和透射电子显微镜(TEM),实验结果证实了水杨酸官能化氧化铁(Fe3O4-SA)纳米颗粒的生产,适用于不同的进一步应用。
    This study\'s main objective was to fabricate an innovative three-dimensional microfluidic platform suitable for well-controlled chemical syntheses required for producing fine-tuned nanostructured materials. This work proposes using vortex mixing principles confined within a 3D multilayered microreactor to synthesize magnetic core-shell nanoparticles with tailored dimensions and polydispersity. The newly designed microfluidic platform allowed the simultaneous obtainment of Fe3O4 cores and their functionalization with a salicylic acid shell in a short reaction time and under a high flow rate. Synthesis optimization was also performed, employing the variation in the reagents ratio to highlight the concentration domains in which magnetite is mainly produced, the formation of nanoparticles with different diameters and low polydispersity, and the stability of colloidal dispersions in water. The obtained materials were further characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM), with the experimental results confirming the production of salicylic acid-functionalized iron oxide (Fe3O4-SA) nanoparticles adapted for different further applications.
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  • 文章类型: Journal Article
    芯片上器官是一种创新技术,从组织工程和微流体技术中出现。预计芯片上器官设备(OoC)将提供有效的解决方案,以应对药物进步和个性化疾病治疗方面的挑战。芯片上器官是一种先进的方法,可以在小芯片上复制人体器官的生理条件和功能。它具有通过实现疾病模拟和药物测试来极大地改变药物开发过程的能力。这种先进的技术平台与常见的制药和医疗环境的有效整合仍然是一个挑战。微流体技术,一种微观层面的技术,已经成为生物医学工程研究的有力工具。因此,它彻底改变了包括生理材料解释在内的学科,化合物检测,基于细胞的测定,组织工程,生物诊断,和药物鉴定。本文旨在概述新开发的芯片上器官系统。它包括单器官平台,强调研究最多的器官,包括心脏,肝脏,动脉,还有肺.随后,它简要概述了芯片上肿瘤系统,并强调了它们在抗癌药物评估中的应用。
    Organ-on-chip is an innovative technique that emerged from tissue engineering and microfluidic technologies. Organ-on-chip devices (OoCs) are anticipated to provide efficient resolutions to dealing with challenges in pharmaceutical advancement and individualized illness therapies. Organ-on-chip is an advanced method that can replicate human organs\' physiological conditions and functions on a small chip. It possesses the capacity to greatly transform the drug development process by enabling the simulation of diseases and the testing of drugs. Effective integration of this advanced technical platform with common pharmaceutical and medical contexts is still a challenge. Microfluidic technology, a micro-level technique, has become a potent tool for biomedical engineering research. As a result, it has revolutionized disciplines including physiological material interpreting, compound detection, cell-based assay, tissue engineering, biological diagnostics, and pharmaceutical identification. This article aims to offer an overview of newly developed organ-on-a-chip systems. It includes single-organ platforms, emphasizing the most researched organs, including the heart, liver, blood arteries, and lungs. Subsequently, it provides a concise overview of tumour-on-a-chip systems and emphasizes their use in the evaluation of anti-cancer medications.
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  • 文章类型: Journal Article
    商业多西他赛(DTX)制剂由于聚山梨酯80和乙醇而引起严重的副作用。需要新型的不含表面活性剂的纳米颗粒(NP)系统来提高生物利用度并减少副作用。然而,控制NPs的粒度和稳定性以及改善批次间的变化是主要挑战。
    通过新型热驱动自组装/微流体技术制备了负载DTX的牛血清白蛋白纳米颗粒(DTX-BSA-NP)。通过单因素分析和正交试验,得到DTX-BSA-NP的最佳配方,封装效率(EE),和载药量(DL)。油/水流量和泵压力对颗粒尺寸的影响,EE,对DTX-BSA-NP的制备工艺进行了优化。药物释放,物理化学性质,稳定性,并对NPs的药代动力学进行了评价。
    优化的DTX-BSA-NP是均匀的,粒径为118.30nm,EE为89.04%,DL为8.27%。它们在96小时内表现出70%的持续释放和增加的稳定性。DTX-BSA-NP中的药物和赋形剂之间存在一些相互作用。半衰期,平均停留时间,DTX-BSA-NP的曲线下面积(AUC)增加,但与DTX相比,血浆清除率下降。
    热驱动自组装/微流体组合方法有效地产生了基于BSA的NPs,该NPs提高了DTX的生物利用度和稳定性,为传统配方提供了一个有希望的替代品。
    UNASSIGNED: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges.
    UNASSIGNED: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated.
    UNASSIGNED: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX.
    UNASSIGNED: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.
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