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Biological Sciences

Publication

Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes

Authors: Mubashir Ahmad, Shahzeb Khan, Syed Muhammad Hassan Shah, Muhammad Zahoor, Zahid Hussain, Haya Hussain, Syed Wadood Ali Shah, Riaz Ullah and Amal Alotaibi

Published year: 2023

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Produce nanocrystals to improve bioavailability of an antihyperglycaemic drug. Nanocrytals had a much lower IC50 than the tablet form, and higher efficacy than other drugs

Publication

FACS-Based Functional Protein Screening via Microfluidic Co-encapsulation of Yeast Secretor and Mammalian Reporter Cells

Authors: Desislava Yanakieva, Adrian Elter, Jens Bratsch, Karlheinz Friedrich, Stefan Becker & Harald Kolmar

Published year: 2020

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Successfully enriched 1:10000 dilution of secreting yeast cells. Used 2 rounds of encapsulation of agarose (water) in oil, FACS sorting after emulsion breaking

Publication

Xdrop: Targeted sequencing of long DNA molecules from low input samples using droplet sorting

Authors: Esben B. Madsen, Ida Höijer, Thomas Kvist, Adam Ameur, Marie J. Mikkelsen

Published year: 2020

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Introducing Xdrop technology, a novel microfluidic-based workflow for targeted enrichment of long DNA molecules

Publication

Cyclin B1 is essential for mitosis in mouse embryos, and its nuclear export sets the time for mitosis 

Authors: Bernhard Strauss, Andrew Harrison, Paula Almeida Coelho, Keiko Yata, Magdalena Zernicka-Goetz, Jonathon Pines

Published year: 2018

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Cyclin B1 is essential for embryo development, but its role in mitosis was unclear. In this study, large numbers of mouse embryos were cultured in a custom microfluidic chip, and imaged before recovering for genotyping. They found that Cyclin B1 is an essential regulator of the cell cycle

Publication

A monolithic glass chip for active single-cell sorting based on mechanical phenotyping

Authors: Christoph Faigle, Franziska Lautenschläger, Graeme Whyte, Philip Homewood, Estela Martín-Badosa and Jochen Guck

Published year: 2015

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Showing the utility of a custom glass-stretcher chip through measuring and and sorting single cells by their mechanical properties in a heterogenous population

Publication

Microencapsulation of growth factors by microfluidic system

Authors: Lilith M. Caballero-Aguilar, Serena Duchi, Anita Quigley, Carmine Onofrillo, Claudia Di Bella, Simon E. Moulton

Published year: 2021

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The encapsulation of growth factors is an important component of tissue engineer- ing. Using microspheres is a convenient approach in which the dose of factors can be regulated by increasing or decreasing the number of encapsulated microspheres. Moreover, microspheres offer the possibility of delivering the growth factors directly to the target site. However, the fabrication of microspheres by traditional emulsion methods is largely variable due to the experimental procedure. We have developed a protocol using a commercially available microfluidic system that allows formation of tunable particle-size droplets loaded with growth factors. The methodology includes a guide for preparing an alginate-growth factors solution followed by the specific set-up needed for using the microfluidic system to form the microspheres. The procedure also includes a unique post-crosslinking process without pH modification. These methods allow the preservation of integrity and bioactivity of the growth factors tested (BMP-6 and TGFβ -3) and their subsequent sustained delivery.

  • The protocol can be tuned to form particles of various sizes.
  • The gentle post-crosslinking process allows conformational integrity of various bioactive molecules.

Publication

Formation of alginate microspheres prepared by optimized microfluidics parameters for high encapsulation of bioactive molecules

Authors: Lilith M. Caballero Aguilar, Serena Duchi, Carmine Onofrillo, Cathal D. O’Connell, Claudia Di Bella, Simon E. Moulton

Published year: 2020

Field: BioScience

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Publication

Ultra-precise quantification of mRNA targets across a broad dynamic range with nanoreactor beads

Authors: Ivan Francisco Loncarevic, Susanne Toepfer, Stephan Hubold, Susanne Klingner,Lea Kanitz, Thomas Ellinger,Katrin Steinmetzer, Thomas Ernst, Andreas Hochhaus, Eugen Ermantraut

Published year: 2021

Field: BioScience

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Precise quantification of molecular targets in a biological sample across a wide dynamic range is a key requirement in many diagnostic procedures, such as monitoring response to therapy or detection of measurable residual disease. State of the art digital PCR assays provide for a dynamic range of four orders of magnitude. However digital assays are complex and require sophisticated microfluidic tools. Here we present an assay format that enables ultra-precise quantification of RNA targets in a single measurement across a dynamic range of more than six orders of magnitude. The approach is based on hydrogel beads that provide for microfluidic free compartmentalization of the sample as they are used as nanoreactors for reverse transcription, PCR amplification and combined real time and digital detection of gene transcripts. We have applied these nanoreactor beads for establishing an assay for the detection and quantification of BCR-ABL1 fusion transcripts. The assay has been characterized for its precision and linear dynamic range. A comparison of the new method against conventional real time RT-PCR analysis (reference method) with clinical samples from patients with chronic myeloid leukemia (CML) revealed excellent concordance with Pearsons correlation coefficient of 0.983 and slope of 1.08.

Chemistry

Publication

Microfluidic Systems For Manufacturing of Microparticle-Based Drug-Delivery Systems: Design, Construction, and Operation

Authors: Nihan Yonet-Tanyeri, Maher Amer, Stephen C. Balmert, Emrullah Korkmaz, Louis D. Falo Jr., and Steven R. Little

Published year: 2022

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Particles synthesized from biodegradable polymers hold great potential as controlled drug delivery systems. Continuous flow platforms based on microfluidics offer attractive advantages over conventional batch-emulsification techniques for the scalable fabrication of drug-loaded particles with controlled physicochemical properties. However, widespread utilization of microfluidic technologies for the manufacturing of drug-loaded particles has been hindered largely by the lack of practical guidelines toward cost-effective development and reliable operation of microfluidic systems. Here, we present a framework for rational design and construction of microfluidic systems using commercially available components for high-throughput production of uniform biodegradable particles encapsulating drugs. We also demonstrate successful implementation of this framework to devise a robust microfluidic system that is capable of producing drug-carrying particles with desired characteristics. The guidelines provided in this study will likely help broaden the applicability of microfluidic technologies for the synthesis of high-quality, drug-loaded biodegradable particles.

Publication

Scaled-up droplet generation in parallelised 3D flow focusing junctions

Authors: Tymele Deydier, Guido Bolognesi,Goran T. Vladisavljević

Published year: 2022

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Monodispersed organic phase droplets with an average diameter from 20 to 200 µm were produced at the rate of up to 20,000 droplets per second in a glass microfluidic chip composed of 7 parallel 3D flow focusing junctions with 100 µm-deep channels. The continuous phase was 2 wt% polyvinyl alcohol solution, while the dispersed phase was dichloromethane, n-dodecane, and polydimethylsiloxane 10 cSt fluid corresponding to the dispersed-to-continuous-phase viscosity ratio of 0.2, 0.8 and 6.1, respectively. Four different droplet generation regimes were observed, dripping, squeezing, jetting, and threading. The regions where each of these regimes was stable were mapped using Weber number of the dispersed phase and capillary number of the continuous phase. The transitions between the droplet formation regimes were governed by the Weber number of the dispersed phase, indicating that inertial forces in the dispersed phase were more relevant than viscous forces in controlling the transition. Stable droplet generation in dripping regime in each junction was maintained for at least 6 h. The coefficient of variation of droplet sizes from individual junctions and all junctions combined was < 3% under optimal conditions. The droplet size variations between different junctions were greater than those within each junction. Liquid plugs were produced in the squeezing regime at the dispersed-to-continuous phase flow rate ratio greater than one. This study is the first investigation of droplet generation in multiple 3D flow-focusing junctions with potential applications for the production of drug microcarriers using emulsification solvent evaporation, especially for the encapsulation and controlled delivery of lipophilic drugs.

Publication

Microfluidic Study of Oil Droplet Stability in Produced Water with Combinations of Production Chemicals

Authors: Liridon Aliti, Alexander Shapiro, Simon Ivar Andersen

Published year: 2023

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Discharged produced water contains traces of hydrocarbons after separation that might affect the eco-toxicity. These hydrocarbons can be oil droplets that are stabilized by added production chemicals and their combinations. The chemicals highly affect the treatment of the produced water before either reinjection or discharge to the sea. We apply microfluidic droplet generation for rapid evaluation of the synergistic effects of the combinations of production chemicals on the oil droplet stability. The coalescence frequency of dispersed droplets is calculated on the basis of high-speed camera video acquisition. The dispersed phase is either a model oil or a bottomhole crude oil sample, both in an aqueous medium. The individual and combined effects of a commercial demulsifier and a corrosion inhibitor are evaluated on the basis of the hydrophilic–lipophilic deviation theory. The presence of as low as 4 ppm of the water-in-oil demulsifier is demonstrated to stabilize oil-in-water droplets, while the corrosion inhibitor creates droplets in oil–water slug flow fashion. The presence of the corrosion inhibitor in conjunction with the demulsifier results in the droplet adherence to the channel surface. The importance of the right dosage and the right combination of production chemicals is demonstrated. The microfluidic droplet generation technique is a valuable tool for assessing the effects of production chemicals on oil droplet stability.

Publication

Autonomous electrochemical system for ammonia oxidation reaction measurements at the International Space Station

Authors: Camila Morales-Navas, Roberto A. Martínez-Rodríguez, Francisco J. Vidal-Iglesias, Armando Peña, Joesene J. Soto-Pérez, Pedro Trinidad, José Solla-Gullón, Toshko Tzvetkov, Jonathan Doan, Eugene S. Smotkin, Eduardo Nicolau, Juan M. Feliu & Carlos R. Cabrera

Published year: 2023

Field: Chemistry

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Ammonia has potential in in-situ resource utilization for NASA space missions, as it is a high energy molecule that can be converted to nitrogen and electrical energy via the ammonia oxidation reaction. In this proof of concept, a small scale AOR setup was taken to the ISS, and achieved positive results, opening the door to future scaled-up experiments

Publication

Freezing of micro-droplets driven by power ultrasound

Authors: Shaolei Gai, Zhengbiao Peng, Behdad Moghtaderi, Jianglong Yu, Elham Doroodchi

Published year: 2022

Field: Chemical engineering

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Studying the effects of system parameters on the freezing of droplets. The study revealed important data for the formation of small spherical ice droplets

Publication

Application of microfluidics to control product selectivity during non-catalytic oxidation of naphthenic-aromatic hydrocarbons

Authors: M. N. Siddiquee A. de Klerk and N. Nazemifard 

Published year: 2016

Field: Organic chemistry – petrochemicals

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Analysis of the liquid phase oxidation behavior of a simple naphthenic-aromatic hydrocarbon. Increasing oxygen availability in the microreactor. Ketone-to-alcohol sensitivity increased with oxygen availability.

Publication

Drop formation in microfluidic cross-junction: jetting to dripping to jetting transition

Authors: Nina M. Kovalchuk, Masanobu Sagisaka, Kasparas Steponavicius, Daniele Vigolo & Mark J. H. Simmons

Published year: 2019

Field: Chemical engineering

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The study examined drop generation in a Dolomite microfluidic device, focusing on transitions between dripping and jetting regimes. It found that these transitions are governed by the capillary numbers of the dispersed and continuous phases. At high dispersed-phase capillary numbers, only jetting occurred, while lower values showed a jetting→dripping→jetting transition as the continuous-phase capillary number increased. Drop volume scaled with the flow rate ratio, independent of interfacial tension.

Material Science

Publication

High-throughput production of microcapsules using microfluidics for self-healing of cementitious materials

Authors: Lívia Ribeiro de Souza and Abir Al-Tabbaa

Published year: 2021

Field: Engineering

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Capsules with a liquid core present a promising solution for self-healing cementitious materials. Microfluidics allow for precise control over size and thickness using double emulsions. Here, production was scaled up with a high-throughput microfluidic system