Droplet Microfluidics

Droplet microfluidics has dramatically developed in the past decade and has been established as a microfluidic technology that can translate into commercial products. Its rapid development and adoption have relied not only on an efficient stabilizing system (oil and surfactant), but also on a library of modules that can manipulate droplets at a high-throughput. Droplet microfluidics is a vibrant field that keeps evolving, with advances that span technology development and applications. Recent examples include innovative methods to generate droplets, to perform single-cell encapsulation, magnetic extraction, or sorting at an even higher throughput. The trend consists of improving parameters such as robustness, throughput, or ease of use. These developments rely on a firm understanding of the physics and chemistry involved in hydrodynamic flow at a small scale. Finally, droplet microfluidics has played a pivotal role in biological applications, such as single-cell genomics or high-throughput microbial screening, and chemical applications. This Special Issue will showcase all aspects of the exciting field of droplet microfluidics, including, but not limited to, technology development, applications, and open-source systems

Epoxy resin mold and PDMS microfluidic devices through photopolymer flexographic printing plate

Photopolymer flexographic printing plate is a new photopolymeric material used for microdevices fabrication. This work demonstrates that a photopolymer flexographic master mold can be used for the fabrication of PDMS (polydimethylsiloxane) microdevices by a multi-step manufacturing process. The methodology entails three main fabrication steps: (1) a photopolymer flexographic printing plate mold (FMold) is generated by UV exposure through a transparent film, (2) an epoxy resin mold (ERmold) is fabricated by transferring the features of the photopolymer mold and (3) a PDMS microdevice is manufactured from the epoxy resin mold. The characterization of the manufactured PDMS microdevices was performed using scanning electron microscopy (SEM) and profilometry. Results showed high accuracy in the replication of the profiles. To show the feasibility of the fabrication process a microdevice for microdroplet generation was designed, manufactured and tested. Hence, the manufacturing process described in this work provides an easy, robust, and low-cost strategy that facilitates the scaling-up of microfluidic devices without requiring any sophisticated equipment.Fil: Olmos Carreno, Carol Maritza. Universidad Tecnológica Nacional. Facultad Regional Haedo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vaca Mora, Andrea Vanessa. Universidad Tecnológica Nacional. Facultad Regional Haedo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rosero, Gustavo. Universidad Tecnológica Nacional. Facultad Regional Haedo; ArgentinaFil: Peñaherrera Pazmiño, Ana Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Haedo; ArgentinaFil: Pérez Sosa, Camilo José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Haedo; ArgentinaFil: de Sá Carneiro, Igor. Universidad Tecnológica Nacional. Facultad Regional Haedo; ArgentinaFil: Vizuete, Karla. Universidad de Las Fuerzas Armadas Espe; EcuadorFil: Arroyo, Carlos R.. Universidad de Las Fuerzas Armadas; EcuadorFil: Debut, Alexis. Universidad de Las Fuerzas Armadas; EcuadorFil: Perez, Maximiliano Sebastian. Universidad Tecnológica Nacional. Facultad Regional Haedo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; ArgentinaFil: Cumbal, Luis. Universidad de Las Fuerzas Armadas; EcuadorFil: Lerner, Betiana. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Haedo; Argentin

Design and Fabrication of Flow-Focusing Devices for Tissue Engineering Applications

While the lifespan of humans has increased, the durability of cartilage has not, leading to increasing rates of arthritis in aging humans. As both natural and surgical methods for repairing osteochondral defects tend to fall short, UVM’s Engineered Biomaterials Research Laboratory (EBRL) is working towards a solution where biomimetic, polymeric, and porous engineered tissue scaffolds are seeded with drugs and human mesenchymal stem cells (hMSCs). The seeded scaffold is then implanted or injected into the patient’s osteochondral defect, where the hMSCs differentiate and grow a new cartilaginous extracellular matrix to heal the defect as the artificial scaffold breaks down. Microspheres in three distinct size ranges are required to create pores and embed drugs and cells in the scaffold. In order to produce these microspheres, we turn to the field of microfluidics, which examines fluid interactions at micro-scale geometries and flow rates. A microfluidic flow-focusing device (MFFD) leverages the low Reynolds numbers and pronounced effects of surface tension in such flows to create highly monodisperse droplets of one fluid in a second. This project investigates the design and fabrication of MFFDs for the production of homogeneous microspheres. A MFFD must be consistently reproducible, readily characterized, and easy to test and use. MFFDs show great potential to successfully play a role in the EBRL’s investigation of engineered tissue scaffolds

Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery

Microfluidics is an emerging and promising interdisciplinary technology which offers powerful platforms for precise production of novel functional materials (e.g., emulsion droplets, microcapsules, and nanoparticles as drug delivery vehicles- and drug molecules) as well as high-throughput analyses (e.g., bioassays, detection, and diagnostics). In particular, multiphase microfluidics is a rapidly growing technology and has beneficial applications in various fields including biomedicals, chemicals, and foods. In this review, we first describe the fundamentals and latest developments in multiphase microfluidics for producing biocompatible materials that are precisely controlled in size, shape, internal morphology and composition. We next describe some microfluidic applications that synthesize drug molecules, handle biological substances and biological units, and imitate biological organs. We also highlight and discuss design, applications and scale up of droplet- and flow-based microfluidic devices used for drug discovery and delivery. © 2013 Elsevier B.V. All rights reserved

System Integration - A Major Step toward Lab on a Chip

Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications

A fluorescent oil detection device

On April 20th 2010, the largest offshore oil spill in U.S. history happened in the Gulf of Mexico. It is estimated total more than 4 million barrels oil spilled to Gulf of Mexico. More than two million gallons had been used. This had made the threat to coastal and sea ecosystem even greater and long term. Real-time monitoring is also a critical topic for oil spill response. In-situ monitoring devices are needed for rapid collection of real-time data. A new generation of instruments for spilled oil detection is reported in this paper. The main hypothesis in this research is that the sensitivity of the new instrument based on a micro-fluidic-optic chip can be higher than its conventional sized counterparts. The adoption of the micro-fluidic-optic chip helped to miniaturize the sample extraction unit and also to integrate the optical detection on the same chip substrate. Only the monitoring and displaying unit and the power supply were external to the micro-fluidic-optic chip. In this way, the micro-fluidic-optic chip is replaceable and can be disposable. This also helps to eliminate the need for cleaning the fluidic components, which may be very difficult in micro-scales because of surface tension and flow resistances. Liquid-Liquid extraction unit for sample pre-concentration and micro-optic components for fluorescence detection are the key microfluidic components and have been designed and fabricated on a single disposable chip. In the Liquid-Liquid extraction system, different designs are compared and electromagnetically actuated micro-valves and peristaltic pumps have been designed and fabricated to control the aqueous sample fluid and the organic phase solution. In the micro-optic detection system, different designs are compared and an out-of-plane lens was designed, fabricated, and integrated to enhance the measurement sensitivity. The experimental results of the integrated system have proved that the liquid-liquid extraction functioned very well and the overall measurement sensitivity of the system has been increased more than six hundred percent. An overall oil detection sensitivity blow 1ppm has been achieved. The research work presented in this dissertation has proved the feasibility of this novel oil detection instrument based on micro-fluidic-optic chip. This detection system may also be used for detection of other samples that can be measured based on fluoresce principles

Design and fabrication of novel microfluidic systems for microsphere generation

In this thesis, a study of the rational design and fabrication of microfluidic systems for microsphere generation is presented. The required function of microfluidic systems is to produce microspheres with the following attributes: (i) the microsphere size being around one micron or less, (ii) the size uniformity (in particular coefficient of variation (CV)) being less than 5%, and (iii) the size range being adjustable as widely as possible. Micro-electro-mechanical system (MEMS) technology, largely referring to various micro-fabrication techniques in the context of this thesis, has been applied for decades to develop microfluidic systems that can fulfill the foregoing required function of microsphere generation; however, this goal has yet to be achieved. To change this situation was a motivation of the study presented in this thesis. The philosophy behind this study stands on combining an effective design theory and methodology called Axiomatic Design Theory (ADT) with advanced micro-fabrication techniques for the microfluidic systems development. Both theoretical developments and experimental validations were carried out in this study. Consequently, the study has led to the following conclusions: (i) Existing micro-fluidic systems are coupled designs according to ADT, which is responsible for a limited achievement of the required function; (ii) Existing micro-fabrication techniques, especially for pattern transfer, have difficulty in producing a typical feature of micro-fluidic systems - that is, a large overall size (~ mm) of the device but a small channel size (~nm); and (iii) Contemporary micro-fabrication techniques to the silicon-based microfluidic system may have reached a size limit for microspheres, i.e., ~1 micron. Through this study, the following contributions to the field of the microfluidic system technology have been made: (i) Producing three rational designs of microfluidic systems, device 1 (perforated silicon membrane), device 2 (integration of hydrodynamic flow focusing and crossflow principles), and device 3 (liquid chopper using a piezoelectric actuator), with each having a distinct advantage over the others and together having achieved the requirements, size uniformity (CV ≤ 5%) and size controllability (1-186 µm); (ii) Proposing a new pattern transfer technique which combines a photolithography process with a direct writing lithography process (e.g., focused ion beam process); (iii) Proposing a decoupled design principle for micro-fluidic systems, which is effective in improving microfluidic systems for microsphere generation and is likely applicable to microfluidic systems for other applications; and (iv) Developing the mathematical models for the foregoing three devices, which can be used to further optimize the design and the microsphere generation process

Design, Fabrication and Characterization

Funding Information: This work was financed by national funds from FCT, Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020, UIDP/50025/2020, and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication, i3N, and also under project dPCR4FreeDNA of the same research unit, PTDC/BTM-SAL/31201/2017. Furthermore, the work received funding from FCT in the scope of projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences, UCIBIO, and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy, i4HB. B. J. Coelho acknowledges FCT for the attribution of grant SFRH/BD/132904/2017 and grant COVID/BD/152453/2022. Publisher Copyright: © 2023 by the authors.Microfluidic-based platforms have become a hallmark for chemical and biological assays, empowering micro- and nano-reaction vessels. The fusion of microfluidic technologies (digital microfluidics, continuous-flow microfluidics, and droplet microfluidics, just to name a few) presents great potential for overcoming the inherent limitations of each approach, while also elevating their respective strengths. This work exploits the combination of digital microfluidics (DMF) and droplet microfluidics (DrMF) on a single substrate, where DMF enables droplet mixing and further acts as a controlled liquid supplier for a high-throughput nano-liter droplet generator. Droplet generation is performed at a flow-focusing region, operating on dual pressure: negative pressure applied to the aqueous phase and positive pressure applied to the oil phase. We evaluate the droplets produced with our hybrid DMF–DrMF devices in terms of droplet volume, speed, and production frequency and further compare them with standalone DrMF devices. Both types of devices enable customizable droplet production (various volumes and circulation speeds), yet hybrid DMF–DrMF devices yield more controlled droplet production while achieving throughputs that are similar to standalone DrMF devices. These hybrid devices enable the production of up to four droplets per second, which reach a maximum circulation speed close to 1540 µm/s and volumes as low as 0.5 nL.publishersversionpublishe