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High throughput microfluidics

Sanne L N Brouns, Johanna P van Geffen, Johan W M Heemskerk
In recent years, considerable progress has been made in understanding the mechanisms involved in platelet activation during hemostasis and thrombosis. Parallel-plate flow chambers and other microfluidic devices have markedly contributed to this insight. Conversely, such flow devices are now increasingly used to monitor the combined processes of platelet aggregation, thrombus formation, and coagulation in human blood. Currently, by combining microspotting and multi-color fluorescence microscopy, this technology offers the capability of high-throughput measurement of platelet activation processes, even in small blood samples...
March 14, 2018: Platelets
Aynur Abdulla, Wenjia Liu, Azarmidokht Gholamipour-Shirazi, Jiahui Sun, Xianting Ding
Circulating tumor cells (CTCs) are rare cells that detach from primary or metastasis tumor and flow into the blood stream. Intact and viable tumor cells are needed for genetic characterization of CTCs, new drug development, and other research. Although separation of CTCs using spiral channel with two outlets has been reported, few literatures demonstrated simultaneous isolation of different types of CTCs from human blood using cascaded inertial focusing microfluidic channel. Herein, we introduce a cascaded microfluidic device consisting of two spiral channels and one zigzag channel designed with different fluid fields, including lift force, Dean drag force, and centrifugal force...
March 14, 2018: Analytical Chemistry
Lukas Valihrach, Peter Androvic, Mikael Kubista
Single-cell analysis has become an established method to study cell heterogeneity and for rare cell characterization. Despite the high cost and technical constraints, applications are increasing every year in all fields of biology. Following the trend, there is a tremendous development of tools for single-cell analysis, especially in the RNA sequencing field. Every improvement increases sensitivity and throughput. Collecting a large amount of data also stimulates the development of new approaches for bioinformatic analysis and interpretation...
March 11, 2018: International Journal of Molecular Sciences
Fuqiang Ma, Meng Ting Chung, Yuan Yao, Robert Nidetz, Lap Man Lee, Allen P Liu, Yan Feng, Katsuo Kurabayashi, Guang-Yu Yang
Directed evolution has long been a key strategy to generate enzymes with desired properties like high selectivity, but experimental barriers and analytical costs of screening enormous mutant libraries have limited such efforts. Here, we describe an ultrahigh-throughput dual-channel microfluidic droplet screening system that can be used to screen up to ~107 enzyme variants per day. As an example case, we use the system to engineer the enantioselectivity of an esterase to preferentially produce desired enantiomers of profens, an important class of anti-inflammatory drugs...
March 12, 2018: Nature Communications
Majid Malboubi, Asier Jayo, Maddy Parsons, Guillaume Charras
Cell migration plays a key role in many physiological and pathological conditions during which cells migrate primarily in the 3D environments formed by tissues. Microfluidics enables the design of simple devices that can mimic in a highly controlled manner the geometry and dimensions of the interstices encountered by cells in the body. Here we describe the design, fabrication, and implementation of an array of channels with a range of cross sections to investigate migration of cells and cell clusters through confined spaces...
2018: Methods in Molecular Biology
Ana C Fernandes, Daria Semenova, Peter Panjan, Adama M Sesay, Krist V Gernaey, Ulrich Krühne
The limited availability of metabolite-specific sensors for continuous sampling and monitoring is one of the main bottlenecks contributing to failures in bioprocess development. Furthermore, only a limited number of approaches exist to connect currently available measurement systems with high throughput reactor units. This is especially relevant in the biocatalyst screening and characterization stage of process development. In this work, a strategy for sensor integration in microfluidic platforms is demonstrated, to address the need for rapid, cost-effective and high-throughput screening in bioprocesses...
March 6, 2018: New Biotechnology
Adilya Dagkesamanskaya, Krzysztof Langer, Alexandra Tauzin, Catherine Rouzeau, Delphine Lestrade, Gabrielle Potocki-Veronese, Laurent Boitard, Jérôme Bibette, Jean Baudry, Denis Pompon, Véronique Anton-Leberre
Application of droplet-based microfluidics for the screening of microbial libraries is one of the important ongoing developments in functional genomics/metagenomics. In this article, we propose a new method that can be employed for high-throughput profiling of cell growth. It consists of light-driven labelling droplets that contain growing cells directly in a microfluidics observation chamber, followed by recovery of the labelled cells. This method is based on intracellular expression of green-to-red switchable fluorescent proteins...
March 5, 2018: Journal of Microbiological Methods
Tom Bongiorno, Jeremy Gura, Priyanka Talwar, Dwight Chambers, Katherine M Young, Dalia Arafat, Gonghao Wang, Emily L Jackson-Holmes, Peng Qiu, Todd C McDevitt, Todd Sulchek
The highly proliferative and pluripotent characteristics of embryonic stem cells engender great promise for tissue engineering and regenerative medicine, but the rapid identification and isolation of target cell phenotypes remains challenging. Therefore, the objectives of this study were to characterize cell mechanics as a function of differentiation and to employ differences in cell stiffness to select population subsets with distinct mechanical, morphological, and biological properties. Biomechanical analysis with atomic force microscopy revealed that embryonic stem cells stiffened within one day of differentiation induced by leukemia inhibitory factor removal, with a lagging but pronounced change from spherical to spindle-shaped cell morphology...
2018: PloS One
Roberto Molinaro, Michael Evangelopoulos, Jessica R Hoffman, Claudia Corbo, Francesca Taraballi, Jonathan O Martinez, Kelly A Hartman, Donato Cosco, Giosue' Costa, Isabella Romeo, Michael Sherman, Donatella Paolino, Stefano Alcaro, Ennio Tasciotti
The advancement of nanotechnology toward more sophisticated bioinspired approaches has highlighted the gap between the advantages of biomimetic and biohybrid platforms and the availability of manufacturing processes to scale up their production. Though the advantages of transferring biological features from cells to synthetic nanoparticles for drug delivery purposes have recently been reported, a standardizable, batch-to-batch consistent, scalable, and high-throughput assembly method is required to further develop these platforms...
March 7, 2018: Advanced Materials
Solmaz Karamikamkar, Ehsan Behzadfar, Karen C Cheung
Producing three-dimensional (3-D) multicellular tumor spheroids (TSs) is valuable for characterizing anticancer drugs since they provide a more representative model of the 3-D in vivo tumor than conventional two-dimensional (2-D) monolayer culture. The interaction of tumor cells with the extracellular matrix (ECM) in a 3-D culture environment is more similar to a tumor in vivo than in a 2-D environment; cell-cell and cell-ECM interaction can influence cell behaviour, such as in response to drug treatment. In vitro tumor spheroid models have been developed using microfluidic systems to generate 3-D hydrogel beads containing components of alginate and ECM protein, such as collagen, with high uniformity and throughput...
March 6, 2018: Biomedical Microdevices
Hongmei Chen
Inertial and deformability- based particles separations gradually attract more significant attentions. In this work, we present a hybrid chip by combining the advantages of inertial and deformability -based principle. The chip is a triplet parallelizing spiral inertial microfluidic chip interconnected with numerable tilted slits (Spiral-Slits Chip) for continuous separation of circulating tumor cells. Utilizing the inertial lift and viscous drag forces, different sized particles achieve different equilibrium at distinct streamlines of the spiral microchannel...
March 6, 2018: Scientific Reports
Ziqiu Tong, Gayathri Rajeev, Keying Guo, Angela Ivask, Scott McCormick, Enzo Lombi, Craig Priest, Nicolas H Voelcker
With the advances in nanotechnology, particles with various size, shape, surface chemistry and composition can be easily produced. Nano- and microparticles have been extensively explored in many industrial and clinical applications. Ensuring that the particles themselves are not possessing any toxic effects to the biological system is of paramount importance. This paper describes a proof of concept method in which a microfluidic system is used in conjunction with a cell microarray technique aiming to streamline the analysis of particle-cell interaction in a high throughput manner...
March 2, 2018: Analytical Chemistry
Xinjie Zhang, Zhixian Zhu, Nan Xiang, Feifei Long, Zhonghua Ni
Microfluidic technologies for cell separation were reported frequently in recent years. However, compact microfluidic instrument enabling thoroughly automated cell separation is still rarely reported until today due to difficult hybrid between macro-sized fluidic control system and micro-sized microfluidic device. In this work, we propose a novel and automated microfluidic instrument to realize size-based separation of cancer cells in label-free and high-throughput manner. Briefly, the instrument is equipped with a fully integrated microfluidic device and a set of robust fluid-driven and control units, and the instrument functions of precise fluid infusion and high-throughput cell separation are guaranteed by a flow regulatory chip and two cell separation chips which are the key components of the microfluidic device...
March 1, 2018: Analytical Chemistry
Rogier M Schoeman, Wesley T E van den Beld, Evelien W M Kemna, Floor Wolbers, Jan C T Eijkel, Albert van den Berg
We present a microfluidic chip that enables electrofusion of cells in microdroplets, with exchange of nuclear components. It is shown, to our knowledge for the first time, electrofusion of two HL60 cells, inside a microdroplet. This is the crucial intermediate step for controlled hybridoma formation where a B cell is electrofused with a myeloma cell. We use a microfluidic device consisting of a microchannel structure in PDMS bonded to a glass substrate through which droplets with two differently stained HL60 cells are transported...
February 27, 2018: Scientific Reports
Sung Hwa Hong, Twinkal Patel, Shell Ip, Shyam Garg, Jung Kwon Oh
Controlling the size and narrow size distribution of polymer-based nanocarriers for targeted drug delivery is an important parameter that significantly influences their colloidal stability, biodistribution, and targeting ability. Herein, we report a high-throughput microfluidic process to fabricate colloidally-stable aqueous nanoparticulate colloids with tunable sizes at 50-150 nm and narrow size distribution. The nanoparticulates are designed with different molecular weight polyesters having both ester bonds (responsive to esterase enzyme) and sulfide linkages (to oxidative reaction) on the backbones, thus exhibiting dual enzyme/oxidation responses, causing the destabilization of the nanoparticulates to lead to the controlled release of encapsulated therapeutics...
February 27, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Shuli Wang, Yongshun Liu, Peng Ge, Qiqi Kan, Nianzuo Yu, Jing Wang, Jingjie Nan, Shunsheng Ye, Junhu Zhang, Weiqing Xu, Bai Yang
This article shows a new strategy for the fabrication of nanofluidics based on nanoscale gaps in nanopillar arrays. Silicon nanopillar arrays are prepared in a designed position by combining conventional photolithography with colloidal lithography. The nanogaps between the pillars are used as nanochannels for the connection of two polydimethylsiloxane-based microchannels in microfluidics. The gap between neighbouring nanopillars can be accurately controlled by changing the size of initial colloidal spheres and by an etching process, which further determines the dimensions of the nanochannels...
February 27, 2018: Lab on a Chip
Bongseop Kwak, Yoohwan Lee, Jaehun Lee, Sungwon Lee, Jiseok Lim
In vivo tumors develop in a three-dimensional manner and have unique and complex characteristics. Physico-biochemical barriers on tumors cause drug resistance and limit drug delivery efficiency. Currently, 2D cancer cell monolayer platforms are frequently used to test the efficiency of new drug materials. However, the monolayer platform generally overestimates drug efficiency because of the absence of physico-biochemical barriers. Many literatures indicated that a 3D tumor spheroid model has very similar characteristics to in vivo tumor models, and studies demonstrated the accurate prediction of drug efficiency using this model...
February 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Lalit Bansal, Apratim Sanyal, Prasenjit Kabi, Binita Pathak, Saptarshi Basu
Evaporating sessile functional droplets act as the fundamental building block that control the cumulative outcome of many industrial and biological applications such as surface patterning, 3D printing, photonic crystals, DNA sequencing, to name a few. Additionally, a drying single sessile droplet forms a high throughput processing technique using low material volume which is especially suitable for medical diagnosis. Sessile droplet also provides an elementary platform to study and analyze fundamental interfacial processes at various lengthscale ranging from macroscopically observable wetting and evaporation to microfluidic transport to interparticle forces operating at a nanometric lengthscale...
February 22, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Jared L Wilmoth, Peter W Doak, Andrea Timm, Michelle Halsted, John D Anderson, Marta Ginovart, Clara Prats, Xavier Portell, Scott T Retterer, Miguel Fuentes-Cabrera
The factors leading to changes in the organization of microbial assemblages at fine spatial scales are not well characterized or understood. However, they are expected to guide the succession of community development and function toward specific outcomes that could impact human health and the environment. In this study, we put forward a combined experimental and agent-based modeling framework and use it to interpret unique spatial organization patterns of H1-Type VI secretion system (T6SS) mutants of P . aeruginosa under spatial confinement...
2018: Frontiers in Microbiology
Nachiket Shembekar, Hongxing Hu, David Eustace, Christoph A Merten
Monoclonal antibodies are a main player in modern drug discovery. Many antibody screening formats exist, each with specific advantages and limitations. Nonetheless, it remains challenging to screen antibodies for the binding of cell-surface receptors (the most important class of all drug targets) or for the binding to target cells rather than purified proteins. Here, we present a high-throughput droplet microfluidics approach employing dual-color normalized fluorescence readout to detect antibody binding. This enables us to obtain quantitative data on target cell recognition, using as little as 33 fg of IgG per assay...
February 20, 2018: Cell Reports
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