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Two chemistries on a single lab-on-chip: Nitrate and orthophosphate sensing underwater with inlaid microfluidics 芯片上单个实验室的两种化学物质:嵌入微流体的水下硝酸盐和正磷酸盐传感
Pub Date : 2022-12-07 DOI: 10.3389/fsens.2022.1080020
Edward Luy, James Smith, Iain Grundke, C. Sonnichsen, A. Furlong, V. Sieben
Autonomous in situ sensors are required to monitor high-frequency nutrient fluctuations in marine environments on a mass-scale. We present a submersible, dual-chemistry sensor that performs multiple colourimetric assays simultaneously on a fluid sample for multi-parameter in situ analysis. Based on a highly configurable architecture that has been successfully deployed for several multi-month periods, the sensor utilizes 10 solenoid valves, 4 syringes, 3 stepper motors, 2 LEDs, 4 photodiodes, and “inlaid” microfluidics to permit optical measurements of microliter fluid volumes. Fluid pathways are machined into a modular two-layer microfluidic lab-on-chip (LOC) fabricated from poly (methyl methacrylate) (PMMA) with two parallel inlaid optical cells of 10.4 mm and 25.4 mm path lengths (1.7 µl and 4 μl, respectively). Different LOC designs can be used to implement a wide variety of colorimetric assays. We demonstrate application of our dual-chemistry sensor towards simultaneous measurement of nitrate and dissolved orthophosphate: two nutrients fundamental to primary production. The performance of the dual-species nitrate and phosphate “NP Sensor” is characterized first in a controlled laboratory environment. Combined nutrient standards containing nitrate and phosphate concentrations ranging from 2.5 µM–100 µM N O 3 − and 0.25 µM–10 µM P O 4 3 − were analyzed, reporting detection limits of 97 nM N O 3 − and 15 nM P O 4 3 − . Calibrations were repeated under 3 fixed temperature conditions, T = 5°C, 10°C, 15°C, to determine the temperature-dependent sensitivity relations for both species needed to calculate concentrations during field deployments. Finally, an 8-day field deployment in Fish Hatchery Park, NS, Canada followed, acquiring a total of 592 nitrate and dissolved orthophosphate measurements. An on-board combined nutrient standard was measured periodically to assess the in situ accuracy of the sensor, with an average relative uncertainty of 15% across the deployment. Measured nitrate and dissolved orthophosphate levels in the river reached as high as 10 µM and 3.6 µM, respectively. Fast Fourier transform analysis suggests a strong out-of-phase relationship between measured phosphate and water level, with a shared frequency peak in both data agreeing within a 3.2% difference. This trend is due to conventional mixing at the river mouth to neighboring Bedford Basin. A spike in the measured nitrate to phosphate (N:P) ratio was also observed, synchronized to a precipitation event and indicative of runoff. The novel sensor will enable high-frequency dual-nutrient monitoring in many aquatic environments. Graphical Abstract
需要自主的原位传感器来大规模监测海洋环境中的高频营养物质波动。我们提出了一种潜水式双化学传感器,它可以对流体样品同时进行多种色度测定,用于多参数原位分析。基于已成功部署数个月的高度可配置架构,该传感器利用10个电磁阀、4个注射器、3个步进电机、2个LED、4个光电二极管和“嵌入式”微流体,实现微升流体体积的光学测量。流体通道被加工成模块化的两层微流体芯片实验室(LOC),该实验室由聚甲基丙烯酸甲酯(PMMA)制成,具有两个平行镶嵌的光学单元,路径长度分别为10.4 mm和25.4 mm(分别为1.7µl和4μl)。不同的LOC设计可用于实施各种各样的比色测定。我们展示了我们的双化学传感器在同时测量硝酸盐和溶解的正磷酸盐方面的应用:这两种营养素是初级生产的基础。硝酸盐和磷酸盐双物种“NP传感器”的性能首先在受控的实验室环境中进行了表征。分析了硝酸盐和磷酸盐浓度范围为2.5µM–100µM N O 3−和0.25µM–10µM P O 4 3−的联合营养标准品,报告检测限为97 nM N O 3–和15 nM P O 3−。在T=5°C、10°C、15°C的3个固定温度条件下重复校准,以确定两种物种在野外部署期间计算浓度所需的温度相关灵敏度关系。最后,在加拿大NS的Fish Hatchery Park进行了为期8天的实地部署,共获得592份硝酸盐和溶解正磷酸盐测量结果。定期测量机载组合营养素标准,以评估传感器的原位精度,整个部署的平均相对不确定度为15%。河流中的硝酸盐和溶解正磷酸盐含量分别高达10µM和3.6µM。快速傅立叶变换分析表明,测得的磷酸盐和水位之间存在强烈的异相关系,两个数据中的共享频率峰值相差3.2%。这一趋势是由于河口到邻近贝德福德盆地的传统混合造成的。还观察到测得的硝酸盐与磷酸盐(N:P)的比值出现峰值,与降水事件同步,表明径流。这种新型传感器将能够在许多水生环境中进行高频双营养监测。图形摘要
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引用次数: 0
Three-dimensional ready-to-pick reservoir-based preconcentrator with a pillar-structured channel for miRNA applications 具有柱状结构通道的miRNA应用的三维蓄水池预选器
Pub Date : 2022-11-22 DOI: 10.3389/fsens.2022.1066974
Seungmin Lee, Jinhwan Kim, Nalae Lee, Kang-Hyeon Kim, Seong Jun Park, J. Park, Cheonjung Kim, Ji Hye Hong, D. Yoon, Y. Yoo, Jeong-Hoon Lee
A sample preconcentration technique that exceeds a microfluidic device’s limited processing volume (up to microliters) is critical for real sample pretreatment applications. Here, we have developed a 3D-printed preconcentrator with a pillar structure (3DP2) to enrich the biological samples up to hundreds of microliter scales (700 μL) within 20 min by utilizing ion concentration polarization (ICP). We designed three-dimensional ready-to-pick reservoirs serially connected with a pillar-structured channel to enable large-volume preconcentration by balancing the preconcentrating forces (depletion, electrophoretic, and electroosmotic force) generated by ICP. Using the I-t and I-V curves, we confirmed that ICP performance was enhanced due to a pillar structure’s suppression of the vortex. Finally, we preconcentrated bovine serum albumin (BSA) and micro ribonucleic acid-21 (miRNA-21) two-fold. Moreover, depending on their size and charge, these were concentrated at different locations and could be extracted easily using pipettes. We believe that this study provides a novel strategy for downstream applications.
超过微流体设备有限处理体积(高达微升)的样品预浓缩技术对于实际样品预处理应用至关重要。在这里,我们开发了一种具有柱状结构的3D打印预浓缩器(3DP2),通过利用离子浓度极化(ICP)在20分钟内富集数百微升级(700μL)的生物样品。我们设计了与柱状结构通道串联的三维即采储层,通过平衡ICP产生的预浓缩力(耗尽力、电泳力和电渗力)实现大体积预浓缩。使用I-t和I-V曲线,我们证实了由于柱状结构对涡流的抑制,ICP性能得到了增强。最后,我们将牛血清白蛋白(BSA)和微小核糖核酸-21(miRNA-21)预浓缩两倍。此外,根据它们的大小和电荷,这些物质被集中在不同的位置,可以使用移液管轻松提取。我们相信,这项研究为下游应用提供了一种新的策略。
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引用次数: 1
One-step on-chip microfluidic synthesis of the hybrid capsules using aqueous two-phase system 采用双水相体系一步芯片微流控合成杂化胶囊
Pub Date : 2022-11-18 DOI: 10.3389/fsens.2022.1040542
Sneha Daradmare, Jae Seong Kim, R. Ganguly, Chang-Soo Lee
Hydrogel capsules synthesized by conventional water-in-oil emulsion systems are the less preferred choice for biomedical applications due to the use of oils and surfactants. An aqueous two-phase system (ATPS), which allows the formation of water-in-water emulsion, is considered a green alternative and therefore has been explored a lot for its application in the biomedical field. Herein, we present the synthesis of hydrogel capsules using a set-up consisting of a pneumatic valve integrated with the ATPS microfluidic system. In this arrangement, at first, a pneumatic valve facilitates the generation of the droplets of one aqueous system i.e. sodium alginate (SA) containing dextran solution into another aqueous phase comprising polyethylene glycol solution. The present approach allows good control over droplet generation by tuning the pressure of the pneumatic valve and the flow rates of the core and middle phases. The synthesis of hybrid capsules within the microfluidic device is carried out mainly by using the interfacial complexation of oppositely charged polyelectrolytes, chitosan with SA via electrostatic interactions. The interfacial complexed SA and chitosan hydrogel capsules were collected via the settling collection method, which ensures the retaining of the shape of the hybrid capsules. The morphological properties of as-synthesized droplets and hybrid capsules were examined via optical microscopy. The hydrogel capsules show good encapsulation capability for the magnetic particles. Even though this study mainly focuses on the synthesis part, we anticipate that the proposed approach will enable the encapsulation of cells within the hybrid capsules as well as enhance the cell adhesion on the surface of the hydrogel capsules hence, these hydrogel capsules can find the potent application in the biomedical engineering.
由于使用油和表面活性剂,传统油包水乳液系统合成的水凝胶胶囊在生物医学应用中不太受欢迎。水两相体系(ATPS)可以形成水包水乳液,被认为是一种绿色的替代方案,因此在生物医学领域的应用得到了大量的探索。在这里,我们提出了水凝胶胶囊的合成使用的设置组成的气动阀集成的ATPS微流体系统。在这种安排中,首先,气动阀促进一个水系统的液滴的产生,即含有葡聚糖溶液的海藻酸钠(SA)进入另一个含有聚乙二醇溶液的水相。目前的方法允许通过调整气动阀的压力和核心和中间相的流量来很好地控制液滴的产生。微流控装置内杂化胶囊的合成主要是利用带相反电荷的聚电解质壳聚糖与SA通过静电相互作用进行界面络合。采用沉降收集法收集界面络合的SA和壳聚糖水凝胶胶囊,保证了杂化胶囊的形状不变。通过光学显微镜观察了合成的微滴和杂交胶囊的形态特征。水凝胶胶囊对磁性颗粒具有良好的包封能力。尽管本研究主要集中在合成部分,但我们预计所提出的方法将使细胞被封装在杂交胶囊内,并增强细胞在水凝胶胶囊表面的粘附,因此这些水凝胶胶囊可以在生物医学工程中找到强有力的应用。
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引用次数: 0
OLIA: An open-source digital lock-in amplifier OLIA:开源数字锁定放大器
Pub Date : 2022-11-16 DOI: 10.3389/fsens.2023.1102176
A. Harvie, J. D. de Mello
The Open Lock-In Amplifier (OLIA) is a microcontroller-based digital lock-in amplifier built from a small number of inexpensive and easily sourced electronic components. Despite its small credit card-sized form-factor and low build-cost of around US$35, OLIA is a capable instrument that offers many features associated with far costlier commercial devices. Key features include dual-phase lock-in detection at multiple harmonic frequencies up to 50 kHz, internal and external reference modes, adjustable levels of input gain, a choice between low-pass filtering and synchronous filtering, noise estimation, and a comprehensive programming interface for remote software control. OLIA comes with an optional optical breakout board that allows noise-tolerant optical detection down to the 40-pW level. OLIA and its breakout board are released here as open hardware, with technical diagrams, full parts-lists, and source-code for the firmware.
开放式锁定放大器(OLIA)是一种基于微控制器的数字锁定放大器,由少量廉价且易于采购的电子元件构建而成。尽管OLIA的外形尺寸较小,构建成本约为35美元,但它是一款功能强大的仪器,提供了许多与成本高得多的商业设备相关的功能。主要功能包括在高达50 kHz的多个谐波频率下进行双相位锁定检测、内部和外部参考模式、可调节的输入增益水平、低通滤波和同步滤波之间的选择、噪声估计以及用于远程软件控制的全面编程接口。OLIA配备了一个可选的光学转接板,允许低至40 pW级别的耐噪声光学检测。OLIA及其转接板作为开放式硬件在这里发布,提供了技术图、完整的零件列表和固件的源代码。
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引用次数: 1
Earthquake early warning systems based on low-cost ground motion sensors: A systematic literature review 基于低成本地震动传感器的地震预警系统:系统文献综述
Pub Date : 2022-11-03 DOI: 10.3389/fsens.2022.1020202
Chanthujan Chandrakumar, R. Prasanna, M. Stephens, M. L. Tan
Earthquake early warning system (EEWS) plays an important role in detecting ground shaking during an earthquake and alerting the public and authorities to take appropriate safety measures, reducing possible damages to lives and property. However, the cost of high-end ground motion sensors makes most earthquake-prone countries unable to afford an EEWS. Low-cost Microelectromechanical systems (MEMS)-based ground motion sensors are becoming a promising solution for constructing an affordable yet reliable and robust EEWS. This paper contributes to advancing Earthquake early warning (EEW) research by conducting a literature review investigating different methods and approaches to building a low-cost EEWS using MEMS-based sensors in different territories. The review of 59 articles found that low-cost MEMS-based EEWSs can become a feasible solution for generating reliable and accurate EEW, especially for developing countries and can serve as a support system for high-end EEWS in terms of increasing the density of the sensors. Also, this paper proposes a classification for EEWSs based on the warning type and the EEW algorithm adopted. Further, with the support of the proposed EEWS classification, it summarises the different approaches researchers attempted in developing an EEWS. Following that, this paper discusses the challenges and complexities in implementing and maintaining a low-cost MEMS-based EEWS and proposes future research areas to improve the performance of EEWSs mainly in 1) exploring node-level processing, 2) introducing multi-sensor support capability, and 3) adopting ground motion-based EEW algorithms for generating EEW.
地震预警系统(EEWS)在探测地震时的地面震动,提醒公众和当局采取适当的安全措施,减少可能造成的生命财产损失方面发挥着重要作用。然而,高端地面运动传感器的成本使得大多数地震易发国家无力负担EEWS。基于微机电系统(MEMS)的低成本地震动传感器正在成为一种有前途的解决方案,用于构建经济实惠、可靠且强大的EEWS。本文通过对不同地区使用mems传感器构建低成本地震预警系统的不同方法和途径进行文献综述,为推进地震预警(EEW)研究做出贡献。对59篇文章的回顾发现,低成本的基于mems的EEWS可以成为产生可靠和精确的EEWS的可行解决方案,特别是对于发展中国家,并且可以在增加传感器密度方面作为高端EEWS的支持系统。并根据预警类型和所采用的EEW算法对eews进行分类。此外,在拟议的EEWS分类的支持下,它总结了研究人员在开发EEWS时尝试的不同方法。接下来,本文讨论了实现和维护低成本mems EEWS的挑战和复杂性,并提出了未来提高EEWS性能的研究方向,主要包括1)探索节点级处理,2)引入多传感器支持能力,以及3)采用基于地震动的EEW算法生成EEW。
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引用次数: 1
AI-boosted CRISPR-Cas13a and total internal reflection fluorescence microscopy system for SARS-CoV-2 detection 人工智能增强CRISPR-Cas13a和全内反射荧光显微镜系统检测SARS-CoV-2
Pub Date : 2022-11-02 DOI: 10.3389/fsens.2022.1015223
Likun Zhang, Zhengyang Lei, Chufan Xiao, Zhicheng Du, Chenyao Jiang, Xi Yuan, Qiuyue Hu, Shiyao Zhai, Lulu Xu, Changyue Liu, Xiao-Yu Zhong, Haifei Guan, Muhammad Hassan, I. Gul, V. Pandey, Xinhui Xing, Canyang Zhang, Qian He, Peiwu Qin
Integrating artificial intelligence with SARS-CoV-2 diagnostics can help in the timely execution of pandemic control and monitoring plans. To improve the efficiency of the diagnostic process, this study aims to classify fluorescent images via traditional machine learning and deep learning-based transfer learning. A previous study reported a CRISPR-Cas13a system combined with total internal reflection fluorescence microscopy (TIRFM) to detect the existence and concentrations of SARS-CoV-2 by fluorescent images. However, the lack of professional software and excessive manual labor hinder the practicability of the system. Here, we construct a fluorescent image dataset and develop an AI-boosted CRISPR-Cas13a and total internal reflection fluorescence microscopy system for the rapid diagnosis of SARS-CoV-2. Our study proposes Fluorescent Images Classification Transfer learning based on DenseNet-121 (FICTransDense), an approach that uses TIRF images (before and after sample introduction, respectively) for preprocessing, including outlier exclusion and setting and division preprocessing (i.e., SDP). Classification results indicate that the FICTransDense and Decision Tree algorithms outperform other approaches on the SDP dataset. Most of the algorithms benefit from the proposed SDP technique in terms of Accuracy, Recall, F1 Score, and Precision. The use of AI-boosted CRISPR-Cas13a and TIRFM systems facilitates rapid monitoring and diagnosis of SARS-CoV-2.
将人工智能与严重急性呼吸系统综合征冠状病毒2型诊断相结合,有助于及时执行疫情控制和监测计划。为了提高诊断过程的效率,本研究旨在通过传统的机器学习和基于深度学习的迁移学习对荧光图像进行分类。先前的一项研究报道了CRISPR-Cas13a系统与全内反射荧光显微镜(TIRFM)相结合,通过荧光图像检测严重急性呼吸系统综合征冠状病毒2型的存在和浓度。然而,缺乏专业的软件和过多的体力劳动阻碍了该系统的实用性。在这里,我们构建了一个荧光图像数据集,并开发了一个AI增强的CRISPR-Cas13a和全内反射荧光显微镜系统,用于快速诊断严重急性呼吸系统综合征冠状病毒2型。我们的研究提出了基于DenseNet-121(FICTransDense)的荧光图像分类转移学习,这是一种使用TIRF图像(分别在样本引入之前和之后)进行预处理的方法,包括异常值排除、设置和划分预处理(即SDP)。分类结果表明,FICTransDense和决策树算法在SDP数据集上的性能优于其他方法。在准确性、召回率、F1分数和精度方面,大多数算法都受益于所提出的SDP技术。人工智能增强的CRISPR-Cas13a和TIRFM系统的使用有助于快速监测和诊断严重急性呼吸系统综合征冠状病毒2型。
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引用次数: 6
Development of a highly sensitive lateral flow strip device for nucleic acid detection using molecular beacons 利用分子信标进行核酸检测的高灵敏度横向流条装置的开发
Pub Date : 2022-10-28 DOI: 10.3389/fsens.2022.1012775
Youngkwang Moon, Hyeokgyun Moon, Junhyuck Chang, Harold D. Kim, Jung Heon Lee, Jinkee Lee
Extensive research is focused on the development of highly sensitive, rapid on-site diagnostic devices. The lateral flow strip (LFS) is a paper-based point-of-care diagnostic device, which is highly promising because of its ease of use and low cost. Despite these advantages, LFS device is still less popular than other methods such as enzyme-linked immunosorbent assay (ELISA) or real-time polymerase chain reaction (qPCR) due to its low sensitivity. Here, we have developed a fluorescence-based lateral flow strip (f-LFS) device for DNA detection using a molecular beacon (MB), a short hairpin-forming DNA strand tagged with a fluorophore-quencher pair. Each paper and membrane component of f-LFS device was carefully selected based on their physicochemical properties including porosity, surface functionality, and autofluorescence. The limit of detection (LOD) of this device was substantially improved to 2.1 fg/mL by adding MgCl2 to the reaction buffer and narrowing the test membrane dimension. Also, a portable fluorescence detection system for f-LFS was developed using a multi-pixel photon counter (MPPC), a sensitive detector detecting the signal on site. We anticipate that this highly sensitive paper-based diagnostic device can be utilized for on-site diagnosis of various diseases.
广泛的研究集中在开发高灵敏度、快速的现场诊断设备上。侧流条(LFS)是一种基于纸张的护理点诊断设备,由于其易于使用和低成本,因此极具前景。尽管有这些优点,LFS设备仍然不如酶联免疫吸附测定(ELISA)或实时聚合酶链式反应(qPCR)等其他方法受欢迎,因为其灵敏度较低。在这里,我们开发了一种基于荧光的横向流带(f-LFS)设备,用于使用分子信标(MB)进行DNA检测,分子信标是一种用荧光团猝灭剂对标记的形成短发夹的DNA链。f-LFS装置的每种纸张和膜组件都是根据其物理化学性质(包括孔隙率、表面功能性和自发荧光)仔细选择的。通过向反应缓冲液中加入MgCl2并缩小测试膜尺寸,该装置的检测限(LOD)显著提高至2.1 fg/mL。此外,使用多像素光子计数器(MPPC)开发了一种用于f-LFS的便携式荧光检测系统,MPPC是一种现场检测信号的灵敏检测器。我们预计这种高灵敏度的纸基诊断设备可以用于各种疾病的现场诊断。
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引用次数: 0
MXene-based flexible sensors: A review 基于mxene的柔性传感器:综述
Pub Date : 2022-10-27 DOI: 10.3389/fsens.2022.1006749
Sajjad Hajian, D. Maddipatla, B. B. Narakathu, M. Atashbar
MXenes are an emerging family of two-dimensional (2D) materials which exhibits unique characteristics such as metal-like thermal and electrical conductivity, huge surface area, biocompatibility, low toxicity, excellent electrochemical performance, remarkable chemical stability, antibacterial activity, and hydrophilicity. Initially, MXene materials were synthesized by selectively etching metal layers from MAX phases, layered transition metal carbides, and carbonitrides with hydrofluoric acid. Multiple novel synthesis methods have since been developed for the creation of MXenes with improved surface chemistries using non-aqueous etchants, molten salts, fluoride salts, and various acid halogens. Due to the promising potential of MXenes, they have emerged as attractive 2D materials with applications in various fields such as energy storage, sensing, and biomedical. This review provides a comprehensive overview of MXenes and discusses the synthesis and properties of MXenes, including the methods of etching, delamination, and modification/functionalization, as well as the electrical properties of MXenes. Following this, the recent advances in the development of various MXene-based sensors are presented. Finally, the challenges and opportunities for future research on the development of MXenes-based sensors are discussed.
MXenes是一个新兴的二维(2D)材料家族,具有类似金属的导热性和导电性、巨大的表面积、生物相容性、低毒性、优异的电化学性能、显著的化学稳定性、抗菌活性和亲水性等独特特性。最初,MXene材料是通过用氢氟酸选择性蚀刻MAX相的金属层、层状过渡金属碳化物和碳氮化物来合成的。此后,已经开发了多种新的合成方法,用于使用非水蚀刻剂、熔盐、氟化物盐和各种酸性卤素来产生具有改进的表面化学性质的MXenes。由于MXenes的潜在潜力,它们已成为一种有吸引力的二维材料,在储能、传感和生物医学等各个领域都有应用。这篇综述对MXenes进行了全面的综述,并讨论了MXenes的合成和性能,包括蚀刻、分层和改性/功能化的方法,以及MXenes。在此之后,介绍了各种基于MXene的传感器的最新发展。最后,讨论了未来研究基于MXenes的传感器的挑战和机遇。
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引用次数: 4
Numerical and experimental investigations of uniform fluid distribution for droplet formation in parallelized microfluidics 平行微流体中液滴形成均匀分布的数值与实验研究
Pub Date : 2022-10-21 DOI: 10.3389/fsens.2022.1014864
Adedamola D. Aladese, Heon-Ho Jeong
Droplet microfluidics, which is the manipulation and handling of fluid in microscale channels, has excellent applications in material science, chemical synthesis, genetic analysis, drug discovery and delivery, organ on chips, and tissue engineering. Consequently, this field has attracted significant attention from both academic institutions and industries. However, one of the major constraints is increasing the droplet production rate from a single generator to thousands of generators in order to move from a laboratory scale to industrial standards. Although the scale-up method (in this case, parallelization) of droplet production using theoretical calculations has been extensively investigated, it has been discovered to be occasionally unreliable during experiments. The use of computational fluid dynamics (CFD) simulation, which has recently been applied to droplet microfluidics, has helped to determine the exact factors and conditions required for uniform droplet formation in flow-focusing devices. Thus far, there has been limited study on the simulation of distribution structures that effectively supply fluids to microfluidic devices in parallel orientation. In this study, CFD is used to provide detailed insights into the conditions required to achieve uniform fluid distribution in the delivery and/or distribution channel of microfluidic devices, and experimental analysis is used to further validate the findings.
液滴微流体是一种在微尺度通道中对流体进行操纵和处理的技术,在材料科学、化学合成、基因分析、药物发现和传递、芯片器官和组织工程等领域都有很好的应用。因此,这一领域引起了学术界和工业界的极大关注。然而,主要的限制之一是为了从实验室规模转移到工业标准,将液滴的生产速度从单个发电机增加到数千个发电机。尽管使用理论计算的液滴生产的放大方法(在这种情况下,并行化)已被广泛研究,但在实验中发现它偶尔不可靠。计算流体动力学(CFD)模拟最近被应用于液滴微流体,它有助于确定流动聚焦装置中均匀液滴形成所需的确切因素和条件。到目前为止,对平行向微流控装置有效供液的分布结构的模拟研究还很有限。在本研究中,利用CFD详细了解了微流控装置输送和/或分配通道中流体均匀分布所需的条件,并通过实验分析进一步验证了研究结果。
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引用次数: 1
High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation 高通量生成用于大规模单细胞封装的微流控模板微凝胶
Pub Date : 2022-10-18 DOI: 10.3389/fsens.2022.1037723
Haoyue Zhang, Chengze Li, Yujie Zhang, Chuanfeng An, Hanting Li, Jiahui Yu, Yonghao Zhang, Wei He, Huanan Wang
Microfluidics-based fabrication of cell-laden microgels has shown great potential for applications in cell therapy and tissue engineering, however, the difficulty in chip operation and compromised cell viability due to cell sedimentation and channel blockage remain a major challenge for functional cell-laden microgels preparation. Herein, we presented the design and optimization of integrated microfluidic chip for large-scale preparation of cell-laden microgels with controllable size and complex microstructure. Specifically, to avoid severe cell sedimentation and uneven distribution in the parallelized microchannel, we simulated cell movement state using computational fluid dynamics simulation. It was found that higher laminar flow velocity gradient and higher precursor viscosity can significantly improve the uniform cell distribution in parallelized channels and reduce the product difference between channels. Moreover, we designed multiple-layered microfluidic chips allowing multiple inputting liquids for the fabrication of microgels with complex structures. This integrated chip facilitated cell encapsulation at a maximum production rate of 240 ml/h of cell suspension with retained cell viability and functionality. Therefore, our study provided a biocompatible and high-throughput strategy for large-scale preparation of cell-laden microgels, which can enable significant advances for clinical-relevant applications of cell-laden microgels, including cell therapy, tissue regeneration and 3D bioprinting.
基于微流体的载细胞微凝胶制备在细胞治疗和组织工程中显示出巨大的应用潜力,然而,由于细胞沉淀和通道堵塞,芯片操作困难和细胞活力受损仍然是制备功能性载细胞微胶的主要挑战。在此,我们提出了集成微流控芯片的设计和优化,用于大规模制备尺寸可控、微观结构复杂的载细胞微凝胶。具体来说,为了避免平行微通道中严重的细胞沉积和不均匀分布,我们使用计算流体动力学模拟来模拟细胞的运动状态。研究发现,较高的层流速度梯度和较高的前驱体粘度可以显著改善平行通道中细胞的均匀分布,并减少通道之间的产物差异。此外,我们设计了多层微流体芯片,允许多种输入液体用于制造具有复杂结构的微凝胶。这种集成芯片有助于以240ml/h的最大细胞悬浮液生产速率进行细胞封装,并保留了细胞活力和功能。因此,我们的研究为大规模制备载有细胞的微凝胶提供了一种生物相容性和高通量的策略,这可以使载有细胞的小凝胶的临床相关应用取得重大进展,包括细胞治疗、组织再生和3D生物打印。
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引用次数: 2
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Frontiers in sensors
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