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12 pages, 5195 KiB

Open AccessArticle

Mode Transition of Droplet Formation in a Semi-3D Flow-Focusing Microfluidic Droplet System

by Yan Wu, Xiang Qian, Min Zhang, Ying Dong, Shuqing Sun and Xiaohao Wang

Micromachines 2018, 9(4), 139; https://doi.org/10.3390/mi9040139 - 21 Mar 2018

Cited by 6 | Viewed by 4391

Abstract

Uniform droplets have significant potential in many biological applications due to their higher surface area to volume ratio. This paper proposed a semi-three-dimensional (sime-3D) flow-focusing microfluidic system, which was fabricated using the multi-layer soft lithography method. Based on the semi-3D structure, we focus [...] Read more.

Uniform droplets have significant potential in many biological applications due to their higher surface area to volume ratio. This paper proposed a semi-three-dimensional (sime-3D) flow-focusing microfluidic system, which was fabricated using the multi-layer soft lithography method. Based on the semi-3D structure, we focus on droplets formation modes and droplet uniformity at different bulk concentration of surfactant. The relationships between droplets uniformity, droplets breakup processes (jetting mode, dripping mode and tip-streaming mode) and surfactant concentration was investigated. It was found that three droplet generation modes occur through adjusting the pressure ratio in two inlet channels and the concentration of surfactant in continuous phase liquid. The jetting mode would transform to the dripping mode or the tip-streaming mode as the pressure ratio in different surfactant concentrations increased. Furthermore, the uniformity of droplets could be improved through the transition of jetting to dripping mode. We assumed that the uniformity declined through the transition of jetting to tip-streaming, and explored the specific transitions from jetting to dripping mode and tip-streaming mode. Dripping mode leads to high droplet uniformity, and generation frequency decreases with increasing pressure ratio. Tip-streaming mode is considered as an extreme state of jetting mode, leading to higher formation frequency and smaller droplet size at low uniformity. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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2951 KiB

Open AccessArticle

An Automated Microfluidic System for the Generation of Droplet Interface Bilayer Networks

by Magdalena A. Czekalska, Tomasz S. Kaminski, Michal Horka, Slawomir Jakiela and Piotr Garstecki

Micromachines 2017, 8(3), 93; https://doi.org/10.3390/mi8030093 - 21 Mar 2017

Cited by 12 | Viewed by 5980

Abstract

Networks of droplets, in which aqueous compartments are separated by lipid bilayers, have shown great potential as a model for biological transmembrane communication. We present a microfluidic system which allows for on-demand generation of droplets that are hydrodynamically locked in a trapping structure. [...] Read more.

Networks of droplets, in which aqueous compartments are separated by lipid bilayers, have shown great potential as a model for biological transmembrane communication. We present a microfluidic system which allows for on-demand generation of droplets that are hydrodynamically locked in a trapping structure. As a result, the system enables the formation of a network of four droplets connected via lipid bilayers and the positions of each droplet in the network can be controlled thanks to automation of microfluidic operations. We perform electrophysiological measurements of ionic currents indicating interactions between nanopores and small molecules to prove the potential of the device in screening of the inhibitors acting on membrane proteins. We also demonstrate, for the first time, a microfluidic droplet interface bilayer (DIB) system in which the testing of inhibitors can be performed without direct contact between the tested sample and the electrodes recording picoampere currents. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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14127 KiB

Open AccessArticle

Droplet Microfluidics Approach for Single-DNA Molecule Amplification and Condensation into DNA-Magnesium-Pyrophosphate Particles

by Greta Zubaite, Karolis Simutis, Robertas Galinis, Valdemaras Milkus, Vaidotas Kiseliovas and Linas Mazutis

Micromachines 2017, 8(2), 62; https://doi.org/10.3390/mi8020062 - 20 Feb 2017

Cited by 14 | Viewed by 10347

Abstract

Protein expression in vitro has broad applications in directed evolution, synthetic biology, proteomics and drug screening. However, most of the in vitro expression systems rely on relatively high DNA template concentrations to obtain sufficient amounts of proteins, making it harder to perform in [...] Read more.

Protein expression in vitro has broad applications in directed evolution, synthetic biology, proteomics and drug screening. However, most of the in vitro expression systems rely on relatively high DNA template concentrations to obtain sufficient amounts of proteins, making it harder to perform in vitro screens on gene libraries. Here, we report a technique for the generation of condensed DNA particles that can serve as efficient templates for in vitro gene expression. We apply droplet microfluidics to encapsulate single-DNA molecules in 3-picoliter (pL) volume droplets and convert them into 1 μm-sized DNA particles by the multiple displacement amplification reaction driven by phi29 DNA polymerase. In the presence of magnesium ions and inorganic pyrophosphate, the amplified DNA condensed into the crystalline-like particles, making it possible to purify them from the reaction mix by simple centrifugation. Using purified DNA particles, we performed an in vitro transcription-translation reaction and successfully expressed complex enzyme β-galactosidase in droplets and in the 384-well format. The yield of protein obtained from DNA particles was significantly higher than from the corresponding amount of free DNA templates, thus opening new possibilities for high throughput screening applications. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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2853 KiB

Open AccessArticle

Optical Flow Cell for Measuring Size, Velocity and Composition of Flowing Droplets

by Sammer-ul Hassan, Adrian M. Nightingale and Xize Niu

Micromachines 2017, 8(2), 58; https://doi.org/10.3390/mi8020058 - 16 Feb 2017

Cited by 17 | Viewed by 6959

Abstract

Here an optical flow cell with two light paths is reported that can accurately quantify the size and velocity of droplets flowing through a microchannel. The flow cell can measure the time taken for droplets to pass between and through two conjoined light [...] Read more.

Here an optical flow cell with two light paths is reported that can accurately quantify the size and velocity of droplets flowing through a microchannel. The flow cell can measure the time taken for droplets to pass between and through two conjoined light paths, and thereby is capable of measuring the velocities (0.2–5.45 mm/s) and sizes of droplets (length > 0.8 mm). The composition of the droplet can also be accurately quantified via optical absorption measurements. The device has a small footprint and uses low-powered, low-cost components, which make it ideally suited for use in field-deployable and portable analytical devices. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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4513 KiB

Open AccessArticle

Droplet Dynamics of Newtonian and Inelastic Non-Newtonian Fluids in Conﬁnement

by Nikolaos Ioannou, Haihu Liu, Mónica S. N. Oliveira and Yonghao Zhang

Micromachines 2017, 8(2), 57; https://doi.org/10.3390/mi8020057 - 15 Feb 2017

Cited by 10 | Viewed by 4977

Abstract

Microﬂuidic droplet technology has been developing rapidly. However, precise control of dynamical behaviour of droplets remains a major hurdle for new designs. This study is to understand droplet deformation and breakup under simple shear ﬂow in conﬁned environment as typically found in microﬂuidic [...] Read more.

Microﬂuidic droplet technology has been developing rapidly. However, precise control of dynamical behaviour of droplets remains a major hurdle for new designs. This study is to understand droplet deformation and breakup under simple shear ﬂow in conﬁned environment as typically found in microﬂuidic applications. In addition to the Newtonian–Newtonian system, we consider also both a Newtonian droplet in a non-Newtonian matrix ﬂuid and a non-Newtonian droplet in a Newtonian matrix. The lattice Boltzmann method is adopted to systematically investigate droplet deformation and breakup under a broad range of capillary numbers, viscosity ratios of the ﬂuids, and conﬁnement ratios considering shear-thinning and shear-thickening ﬂuids. Conﬁnement is found to enhance deformation, and the maximum deformation occurs at the viscosity ratio of unity. The droplet orients more towards the ﬂow direction with increasing viscosity ratio or conﬁnement ratio. In addition, it is noticed that the wall effect becomes more signiﬁcant for conﬁnement ratios larger than 0.4. Finally, for the whole range of Newtonian carrier ﬂuids tested, the critical capillary number above which droplet breakup occurs is only slightly affected by the conﬁnement ratio for a viscosity ratio of unity. Upon increasing the conﬁnement ratio, the critical capillary number increases for the viscosity ratios less than unity, but decreases for the viscosity ratios more than unity. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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6249 KiB

Open AccessArticle

A Study on the Influence of the Nozzle Lead Angle on the Performance of Liquid Metal Electromagnetic Micro-Jetting

by Zhiwei Luo, Gaofeng Zheng and Lingyun Wang

Micromachines 2016, 7(12), 220; https://doi.org/10.3390/mi7120220 - 5 Dec 2016

Cited by 3 | Viewed by 5205

Abstract

To improve the jetting performance of liquid metals, an electromagnetic micro-jetting (EMJ) valve that realizes drop-on-demand (DOD) jetting while not involving any valve core or moving parts was designed. The influence of the lead angle of the nozzle on the jetting of liquid [...] Read more.

To improve the jetting performance of liquid metals, an electromagnetic micro-jetting (EMJ) valve that realizes drop-on-demand (DOD) jetting while not involving any valve core or moving parts was designed. The influence of the lead angle of the nozzle on the jetting of liquid metal gallium (Ga) was investigated. It was found that the Lorentz force component parallel to the nozzle that jets the electrified liquid Ga is always larger than its internal friction; thus, jet can be generated with any lead angle but with different kinetic energies. Experimental results show that the mass of the jetting liquid, the jetting distance, the initial velocity of the jet, and the resulting kinetic energy of the jet increase first and then decrease. When the lead angle is 90°, the mass of the jetting liquid and the kinetic energy are at their maximum. When the angle is 80°, the initial velocity achieves its maximum, with a calculated value of 0.042 m/s. Moreover, very close and comparatively high kinetic energies are obtained at 80° and 90°, indicating that angles in between this range can produce a preferable performance. This work provides an important theoretical basis for the design of the EMJ valve, and may promote the development and application of micro electromagnetic jetting technology. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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2336 KiB

Open AccessArticle

Operation of Droplet-Microfluidic Devices with a Lab Centrifuge

by Noorsher Ahmed, David Sukovich and Adam R. Abate

Micromachines 2016, 7(9), 161; https://doi.org/10.3390/mi7090161 - 6 Sep 2016

Cited by 14 | Viewed by 7495

Abstract

Microfluidic devices are valuable for a variety of biotechnology applications, such as synthesizing biochemical libraries, screening enzymes, and analyzing single cells. However, normally, the devices are controlled using specialized pumps, which require expert knowledge to operate. Here, we demonstrate operation of poly(dimethylsiloxane) devices [...] Read more.

Microfluidic devices are valuable for a variety of biotechnology applications, such as synthesizing biochemical libraries, screening enzymes, and analyzing single cells. However, normally, the devices are controlled using specialized pumps, which require expert knowledge to operate. Here, we demonstrate operation of poly(dimethylsiloxane) devices without pumps. We build a scaffold that holds the device and reagents to be infused in a format that can be inserted into a 50 mL falcon tube and spun in a common lab centrifuge. By controlling the device design and centrifuge spin speed, we infuse the reagents at controlled flow rates. We demonstrate the encapsulation and culture of clonal colonies of red and green Escherichia coli in droplets seeded from single cells. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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4918 KiB

Open AccessFeature PaperArticle

Integration of a Droplet-Based Microfluidic System and Silicon Nanoribbon FET Sensor

by Roodabeh Afrasiabi, Lovisa M. Soderberg, Haakan N. Joensson, Per Björk, Helene Andersson Svahn and Jan Linnros

Micromachines 2016, 7(8), 134; https://doi.org/10.3390/mi7080134 - 5 Aug 2016

Cited by 7 | Viewed by 7247

Abstract

We present a novel microfluidic system that integrates droplet microfluidics with a silicon nanoribbon field-effect transistor (SiNR FET), and utilize this integrated system to sense differences in pH. The device allows for selective droplet transfer to a continuous water phase, actuated by dielectrophoresis, [...] Read more.

We present a novel microfluidic system that integrates droplet microfluidics with a silicon nanoribbon field-effect transistor (SiNR FET), and utilize this integrated system to sense differences in pH. The device allows for selective droplet transfer to a continuous water phase, actuated by dielectrophoresis, and subsequent detection of the pH level in the retrieved droplets by SiNR FETs on an electrical sensor chip. The integrated microfluidic system demonstrates a label-free detection method for droplet microfluidics, presenting an alternative to optical fluorescence detection. In this work, we were able to differentiate between droplet trains of one pH-unit difference. The pH-based detection method in our integrated system has the potential to be utilized in the detection of biochemical reactions that induce a pH-shift in the droplets. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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15746 KiB

Open AccessArticle

Droplet Velocity in an Electrowetting on Dielectric Digital Microfluidic Device

by Mun Mun Nahar, Jagath B. Nikapitiya, Seung M. You and Hyejin Moon

Micromachines 2016, 7(4), 71; https://doi.org/10.3390/mi7040071 - 20 Apr 2016

Cited by 29 | Viewed by 8891

Abstract

In many electrowetting on dielectric (EWOD) based microfluidics devices, droplet actuation speed is a crucial performance-controlling parameter. Our present study aims to characterize and study droplet speed in a typical EWOD device. First, a practical droplet speed measurement method has been methodically demonstrated [...] Read more.

In many electrowetting on dielectric (EWOD) based microfluidics devices, droplet actuation speed is a crucial performance-controlling parameter. Our present study aims to characterize and study droplet speed in a typical EWOD device. First, a practical droplet speed measurement method has been methodically demonstrated and some related velocity terms have been introduced. Next, influence of electrode shape on droplet speed has been studied and a new design to enhance droplet speed has been proposed and experimentally demonstrated. Instead of using square shaped electrodes, rectangular electrodes with smaller widths are used to actuate droplets. Additionally, different schemes of activating electrodes are studied and compared for the same applied voltage. The experiments show that a particular scheme of activating the array of rectangular electrodes enhances the droplet speed up to 100% in comparison to the droplet speed in a conventional device with square shaped electrodes. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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Review

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6098 KiB

Open AccessReview

Coalescence Processes of Droplets and Liquid Marbles

by Jing Jin, Chin Hong Ooi, Dzung Viet Dao and Nam-Trung Nguyen

Micromachines 2017, 8(11), 336; https://doi.org/10.3390/mi8110336 - 20 Nov 2017

Cited by 53 | Viewed by 9784

Abstract

The coalescence process of droplets and, more recently, of liquid marbles, has become one of the most essential manipulation schemes in digital microfluidics. This process is indispensable for realising microfluidic functions such as mixing and reactions at microscale. This paper reviews previous studies [...] Read more.

The coalescence process of droplets and, more recently, of liquid marbles, has become one of the most essential manipulation schemes in digital microfluidics. This process is indispensable for realising microfluidic functions such as mixing and reactions at microscale. This paper reviews previous studies on droplet coalescence, paying particular attention to the coalescence of liquid marbles. Four coalescence systems have been reviewed, namely, the coalescence of two droplets freely suspended in a fluid; the coalescence of two sessile droplets on a solid substrate; the coalescence of a falling droplet and a sessile droplet on a solid substrate; and liquid marble coalescence. The review is presented according to the dynamic behaviors, physical mechanisms and experimental parameters of the coalescence process. It also provides a systematic overview of how the coalescence process of droplets and liquid marbles could be induced and manipulated using external energy. In addition, the practical applications of liquid marble coalescence as a novel microreactor are highlighted. Finally, future perspectives on the investigation of the coalescence process of liquid marbles are proposed. This review aims to facilitate better understanding of the coalescence of droplets and of liquid marbles as well as to shed new insight on future studies. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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2385 KiB

Open AccessReview

Ultrahigh-Throughput Improvement and Discovery of Enzymes Using Droplet-Based Microfluidic Screening

by Alexis Autour and Michael Ryckelynck

Micromachines 2017, 8(4), 128; https://doi.org/10.3390/mi8040128 - 18 Apr 2017

Cited by 51 | Viewed by 13140

Abstract

Enzymes are extremely valuable tools for industrial, environmental, and biotechnological applications and there is a constant need for improving existing biological catalysts and for discovering new ones. Screening microbe or gene libraries is an efficient way of identifying new enzymes. In this view, [...] Read more.

Enzymes are extremely valuable tools for industrial, environmental, and biotechnological applications and there is a constant need for improving existing biological catalysts and for discovering new ones. Screening microbe or gene libraries is an efficient way of identifying new enzymes. In this view, droplet-based microfluidics appears to be one of the most powerful approaches as it allows inexpensive screenings in well-controlled conditions and an ultrahigh-throughput regime. This review aims to introduce the main microfluidic devices and concepts to be considered for such screening before presenting and discussing the latest successful applications of the technology for enzyme discovery. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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20375 KiB

Open AccessReview

Microfluidic Production of Multiple Emulsions

by Goran T. Vladisavljević, Ruqaya Al Nuumani and Seyed Ali Nabavi

Micromachines 2017, 8(3), 75; https://doi.org/10.3390/mi8030075 - 2 Mar 2017

Cited by 129 | Viewed by 19515

Abstract

Microfluidic devices are promising tools for the production of monodispersed tuneable complex emulsions. This review highlights the advantages of microfluidics for the fabrication of emulsions and presents an overview of the microfluidic emulsification methods including two-step and single-step methods for the fabrication of [...] Read more.

Microfluidic devices are promising tools for the production of monodispersed tuneable complex emulsions. This review highlights the advantages of microfluidics for the fabrication of emulsions and presents an overview of the microfluidic emulsification methods including two-step and single-step methods for the fabrication of high-order multiple emulsions (double, triple, quadruple and quintuple) and emulsions with multiple and/or multi-distinct inner cores. The microfluidic methods for the formation of multiple emulsion drops with ultra-thin middle phase, multi-compartment jets, and Janus and ternary drops composed of two or three distinct surface regions are also presented. Different configurations of microfluidic drop makers are covered, such as co-flow, T-junctions and flow focusing (both planar and three-dimensional (3D)). Furthermore, surface modifications of microfluidic channels and different modes of droplet generation are summarized. Non-confined microfluidic geometries used for buoyancy-driven drop generation and membrane integrated microfluidics are also discussed. The review includes parallelization and drop splitting strategies for scaling up microfluidic emulsification. The productivity of a single drop maker is typically <1 mL/h; thus, more than 1000 drop makers are needed to achieve commercially relevant droplet throughputs of >1 L/h, which requires combining drop makers into twodimensional (2D) and 3D assemblies fed from a single set of inlet ports through a network of distribution and collection channels. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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5982 KiB

Open AccessFeature PaperReview

Faraday Waves-Based Integrated Ultrasonic Micro-Droplet Generator and Applications

by Chen S. Tsai, Rong W. Mao, Shirley C. Tsai, Kaveh Shahverdi, Yun Zhu, Shih K. Lin, Yu-Hsiang Hsu, Gerry Boss, Matt Brenner, Sari Mahon and Gerald C. Smaldone

Micromachines 2017, 8(2), 56; https://doi.org/10.3390/mi8020056 - 14 Feb 2017

Cited by 13 | Viewed by 7869

Abstract

An in-depth review on a new ultrasonic micro-droplet generator which utilizes megahertz (MHz) Faraday waves excited by silicon-based multiple Fourier horn ultrasonic nozzles (MFHUNs) and its potential applications is presented. The new droplet generator has demonstrated capability for producing micro droplets of controllable [...] Read more.

An in-depth review on a new ultrasonic micro-droplet generator which utilizes megahertz (MHz) Faraday waves excited by silicon-based multiple Fourier horn ultrasonic nozzles (MFHUNs) and its potential applications is presented. The new droplet generator has demonstrated capability for producing micro droplets of controllable size and size distribution and desirable throughput at very low electrical drive power. For comparison, the serious deficiencies of current commercial droplet generators (nebulizers) and the other ultrasonic droplet generators explored in recent years are first discussed. The architecture, working principle, simulation, and design of the multiple Fourier horns (MFH) in resonance aimed at the amplified longitudinal vibration amplitude on the end face of nozzle tip, and the fabrication and characterization of the nozzles are then described in detail. Subsequently, a linear theory on the temporal instability of Faraday waves on a liquid layer resting on the planar end face of the MFHUN and the detailed experimental verifications are presented. The linear theory serves to elucidate the dynamics of droplet ejection from the free liquid surface and predict the vibration amplitude onset threshold for droplet ejection and the droplet diameters. A battery-run pocket-size clogging-free integrated micro droplet generator realized using the MFHUN is then described. The subsequent report on the successful nebulization of a variety of commercial pulmonary medicines against common diseases and on the experimental antidote solutions to cyanide poisoning using the new droplet generator serves to support its imminent application to inhalation drug delivery. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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Other

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218 KiB

Open AccessOpinion

Commercial Value and Challenges of Drop-Based Microfluidic Screening Platforms–An Opinion

by Christian Holtze, Sebastian A. Weisse and Marcel Vranceanu

Micromachines 2017, 8(6), 193; https://doi.org/10.3390/mi8060193 - 20 Jun 2017

Cited by 15 | Viewed by 5632

Abstract

Developments in High Throughput Screening aim at maximizing the number of samples per time and reducing the cost per sample, e.g., by applying very small sample volumes. The ultimate technological step in miniaturization is moving from microtiter plate wells to droplets, and from [...] Read more.

Developments in High Throughput Screening aim at maximizing the number of samples per time and reducing the cost per sample, e.g., by applying very small sample volumes. The ultimate technological step in miniaturization is moving from microtiter plate wells to droplets, and from batch-wise characterization to the continuous preparation and analysis of samples. A range of drop-based microfluidic screening platforms has emerged that benefit from drop-formation rates of thousands per second, perfect drop size uniformity, plug-flow and compartmentalization, and the possibility of continuously analyzing a train of drops. However, after many years of intensive research, only few commercial applications have been developed and substantial development in the field is still required to make them reliable and broadly applicable. Can academic research achieve this, given that most of the fundamental concepts have been described already, making it hard to publish a big story? Can start-up companies raise enough money to overcome the technical issues of drop-based screening platforms? This contribution addresses the question, focusing on how the different stakeholders in the field should interact so that disillusionment will not put a premature end to the development of drop-based screening technologies. Full article

(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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