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2 pages, 147 KiB

Open AccessEditorial

Editorial for the Special Issue on Droplet Microfluidics

by Eric Brouzes and Siran Li

Micromachines 2020, 11(12), 1086; https://doi.org/10.3390/mi11121086 - 8 Dec 2020

Viewed by 1789

Abstract

Emulsions, which are collections of immiscible droplets, have elicited scientific and commercial interests for decades [...] Full article

(This article belongs to the Special Issue Droplet Microfluidics)

Research

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12 pages, 11278 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Method for Passive Droplet Sorting after Photo-Tagging

by Chandler Dobson, Claudia Zielke, Ching W. Pan, Cameron Feit and Paul Abbyad

Micromachines 2020, 11(11), 964; https://doi.org/10.3390/mi11110964 - 28 Oct 2020

Cited by 5 | Viewed by 4127

Abstract

We present a method to photo-tag individual microfluidic droplets for latter selection by passive sorting. The use of a specific surfactant leads to the interfacial tension to be very sensitive to droplet pH. The photoexcitation of droplets containing a photoacid, pyranine, leads to [...] Read more.

We present a method to photo-tag individual microfluidic droplets for latter selection by passive sorting. The use of a specific surfactant leads to the interfacial tension to be very sensitive to droplet pH. The photoexcitation of droplets containing a photoacid, pyranine, leads to a decrease in droplet pH. The concurrent increase in droplet interfacial tension enables the passive selection of irradiated droplets. The technique is used to select individual droplets within a droplet array as illuminated droplets remain in the wells while other droplets are eluted by the flow of the external oil. This method was used to select droplets in an array containing cells at a specific stage of apoptosis. The technique is also adaptable to continuous-flow sorting. By passing confined droplets over a microfabricated trench positioned diagonally in relation to the direction of flow, photo-tagged droplets were directed toward a different chip exit based on their lateral movement. The technique can be performed on a conventional fluorescence microscope and uncouples the observation and selection of droplets, thus enabling the selection on a large variety of signals, or based on qualitative user-defined features. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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10 pages, 3373 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations

by Mark Davies, Mannthalah Abubaker and Lorraine Bible

Micromachines 2020, 11(10), 943; https://doi.org/10.3390/mi11100943 - 18 Oct 2020

Cited by 4 | Viewed by 3093

Abstract

It is known that in many cases a combination of drugs is more effective than single-drug treatments both for reducing toxicity and increasing efficacy. With the advent of organoid screens, personalised medicine has become possible for many diseases. Automated pipetting to well plates [...] Read more.

It is known that in many cases a combination of drugs is more effective than single-drug treatments both for reducing toxicity and increasing efficacy. With the advent of organoid screens, personalised medicine has become possible for many diseases. Automated pipetting to well plates is the pharmaceutical industry standard for drug screening, but this is relatively expensive and slow. Here, a rotary microfluidic system is presented that can test all possible drug combinations at speed with the use of droplets. For large numbers of combinations, it is shown how the experimental scale is reduced by considering drug dilutions and machine learning. As an example, two cases are considered; the first is a three-ring and three radii configuration and the second is a four ring and forty-eight radii configuration. Between these two, all other cases are shown to be possible. The proposed commercial instrument is shown to be flexible, the user choosing which wells to fill and which driver-computational sub-routine to select. The major issues addressed here are the programming theory of the instrument and the reduction of droplets to be generated by drug dilutions and machine learning. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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12 pages, 3788 KiB

Open AccessArticle

Programmable µChopper Device with On-Chip Droplet Mergers for Continuous Assay Calibration

by Nan Shi and Christopher J. Easley

Micromachines 2020, 11(6), 620; https://doi.org/10.3390/mi11060620 - 25 Jun 2020

Cited by 11 | Viewed by 3976

Abstract

While droplet-based microfluidics is a powerful technique with transformative applications, most devices are passively operated and thus have limited real-time control over droplet contents. In this report, an automated droplet-based microfluidic device with pneumatic pumps and salt water electrodes was developed to generate [...] Read more.

While droplet-based microfluidics is a powerful technique with transformative applications, most devices are passively operated and thus have limited real-time control over droplet contents. In this report, an automated droplet-based microfluidic device with pneumatic pumps and salt water electrodes was developed to generate and coalesce up to six aqueous-in-oil droplets (2.77 nL each). Custom control software combined six droplets drawn from any of four inlet reservoirs. Using our μChopper method for lock-in fluorescence detection, we first accomplished continuous linear calibration and quantified an unknown sample. Analyte-independent signal drifts and even an abrupt decrease in excitation light intensity were corrected in real-time. The system was then validated with homogeneous insulin immunoassays that showed a nonlinear response. On-chip droplet merging with antibody-oligonucleotide (Ab-oligo) probes, insulin standards, and buffer permitted the real-time calibration and correction of large signal drifts. Full calibrations (LOD_conc = 2 ng mL⁻¹ = 300 pM; LOD_amt = 5 amol) required <1 min with merely 13.85 nL of Ab-oligo reagents, giving cost-savings 160-fold over the standard well-plate format while also automating the workflow. This proof-of-concept device—effectively a microfluidic digital-to-analog converter—is readily scalable to more droplets, and it is well-suited for the real-time automation of bioassays that call for expensive reagents. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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12 pages, 6083 KiB

Open AccessArticle

Microfluidic Droplet-Storage Array

by Hoon Suk Rho and Han Gardeniers

Micromachines 2020, 11(6), 608; https://doi.org/10.3390/mi11060608 - 23 Jun 2020

Cited by 6 | Viewed by 4097

Abstract

A microfluidic droplet-storage array that is capable of the continuous operation of droplet formation, storing, repositioning, retrieving, injecting and restoring is demonstrated. The microfluidic chip comprised four valve-assisted droplet generators and a 3 × 16 droplet-storage array. The integrated pneumatically actuated microvalves enable [...] Read more.

A microfluidic droplet-storage array that is capable of the continuous operation of droplet formation, storing, repositioning, retrieving, injecting and restoring is demonstrated. The microfluidic chip comprised four valve-assisted droplet generators and a 3 × 16 droplet-storage array. The integrated pneumatically actuated microvalves enable the precise control of aqueous phase dispensing, as well as carrier fluid flow path and direction for flexible manipulating water-in-oil droplets in the chip. The size of droplets formed by the valve-assisted droplet generators was validated under various operating conditions such as pressures for introducing solutions and dispensing time. In addition, flexible droplet addressing in the storage array was demonstrated by storing droplets with various numbers and compositions in different storage units as well as rearranging their stored positions. Moreover, serial injections of new droplets into a retrieved droplet from a storage unit was performed to show the potential of the platform in sequential dosing on incubated droplet-based reactors at the desired timeline. The droplet-storage array with great freedom and flexibility in droplet handling could be applied for performing complex chemical and biologic reactions, especially in which incubation and dosing steps are necessary. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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10 pages, 2581 KiB

Open AccessArticle

Generation of Ultra-Thin-Shell Microcapsules Using Osmolarity-Controlled Swelling Method

by Jianhua Guo, Lihua Hou, Junpeng Hou, Jiali Yu and Qingming Hu

Micromachines 2020, 11(4), 444; https://doi.org/10.3390/mi11040444 - 23 Apr 2020

Cited by 12 | Viewed by 4390

Abstract

Microcapsules are attractive core-shell configurations for studies of controlled release, biomolecular sensing, artificial microbial environments, and spherical film buckling. However, the production of microcapsules with ultra-thin shells remains a challenge. Here we develop a simple and practical osmolarity-controlled swelling method for the mass [...] Read more.

Microcapsules are attractive core-shell configurations for studies of controlled release, biomolecular sensing, artificial microbial environments, and spherical film buckling. However, the production of microcapsules with ultra-thin shells remains a challenge. Here we develop a simple and practical osmolarity-controlled swelling method for the mass production of monodisperse microcapsules with ultra-thin shells via water-in-oil-in-water (W/O/W) double-emulsion drops templating. The size and shell thickness of the double-emulsion drops are precisely tuned by changing the osmotic pressure between the inner cores and the suspending medium, indicating the practicability and effectiveness of this swelling method in tuning the shell thickness of double-emulsion drops and the resultant microcapsules. This method enables the production of microcapsules even with an ultra-thin shell less than hundreds of nanometers, which overcomes the difficulty in producing ultra-thin-shell microcapsules using the classic microfluidic emulsion technologies. In addition, the ultra-thin-shell microcapsules can maintain their intact spherical shape for up to 1 year without rupturing in our long-term observation. We believe that the osmolarity-controlled swelling method will be useful in generating ultra-thin-shell polydimethylsiloxane (PDMS) microcapsules for long-term encapsulation, and for thin film folding, buckling and rupturing investigation. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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9 pages, 2277 KiB

Open AccessCommunication

Air-Bubble Induced Mixing: A Fluidic Mixer Chip

by Xiaoyu Jia, Bingchen Che, Guangyin Jing and Ce Zhang

Micromachines 2020, 11(2), 195; https://doi.org/10.3390/mi11020195 - 14 Feb 2020

Cited by 5 | Viewed by 3593

Abstract

In this study, we report the design and fabrication of a novel fluidic mixer. As proof-of-concept, the laminar flow in the main channel is firstly filled with small air-bubbles, which act as active stirrers inducing chaotic convective turbulent flow, and thus enhance the [...] Read more.

In this study, we report the design and fabrication of a novel fluidic mixer. As proof-of-concept, the laminar flow in the main channel is firstly filled with small air-bubbles, which act as active stirrers inducing chaotic convective turbulent flow, and thus enhance the solutes mixing even at a low input flow rate. To further increase mixing efficiency, a design of neck constriction is included, which changes the relative positions of the inclusion bubbles significantly. The redistribution of liquid volume among bubbles then causes complex flow profile, which further enhances mixing. This work demonstrates a unique approach of utilizing air bubbles to facilitate mixing in bulk solution, which can find the potential applications in microfluidics, fast medical analysis, and biochemical synthesis. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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14 pages, 3244 KiB

Open AccessFeature PaperArticle

Numerical Simulation and Experimental Validation of Liquid Metal Droplet Formation in a Co-Flowing Capillary Microfluidic Device

by Qingming Hu, Tianyi Jiang and Hongyuan Jiang

Micromachines 2020, 11(2), 169; https://doi.org/10.3390/mi11020169 - 5 Feb 2020

Cited by 18 | Viewed by 6291

Abstract

A two-phase flow axisymmetric numerical model was proposed to understand liquid metal droplet formation in a co-flowing capillary microfluidics device based on a phase field model. The droplet detachment processes were observed in the experiment and are in good agreement with the simulation [...] Read more.

A two-phase flow axisymmetric numerical model was proposed to understand liquid metal droplet formation in a co-flowing capillary microfluidics device based on a phase field model. The droplet detachment processes were observed in the experiment and are in good agreement with the simulation method. The effects of the viscosities and flowrates of the continuous phase fluid, interfacial tension as well as the wetting property of the metallic needle against the bulk liquid metal on the droplet formation and production rate were numerically investigated. It was found that the droplet diameter decreased with the increment of the viscosities and flowrates of the outer phase carrier fluid. The dispersed phase fluid with high interfacial tension tended to prolong the time for equilibrium between the viscous drag force and interfacial tension on the liquid–liquid fluid surface, delaying the droplet to be pinched off from the capillary orifice and causing large droplet diameter. Finally, the wetting performance of the metallic needle against the liquid metal was explored. The result indicate that the droplet diameter became less dependent on the contact angle while the size distribution of the liquid metal droplet was affected by their wetting performance. A more hydrophilic wetting performance were expected to prepare liquid metal droplet with more monodispersity. The numerical model and simulation results provide the feasibility of predicting the droplet formation with a high surface tension in a glass capillary microfluidic device. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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Review

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21 pages, 2512 KiB

Open AccessReview

Droplet Microfluidics-Enabled High-Throughput Screening for Protein Engineering

by Lindong Weng and James E. Spoonamore

Micromachines 2019, 10(11), 734; https://doi.org/10.3390/mi10110734 - 29 Oct 2019

Cited by 52 | Viewed by 10180

Abstract

Protein engineering—the process of developing useful or valuable proteins—has successfully created a wide range of proteins tailored to specific agricultural, industrial, and biomedical applications. Protein engineering may rely on rational techniques informed by structural models, phylogenic information, or computational methods or it may [...] Read more.

Protein engineering—the process of developing useful or valuable proteins—has successfully created a wide range of proteins tailored to specific agricultural, industrial, and biomedical applications. Protein engineering may rely on rational techniques informed by structural models, phylogenic information, or computational methods or it may rely upon random techniques such as chemical mutation, DNA shuffling, error prone polymerase chain reaction (PCR), etc. The increasing capabilities of rational protein design coupled to the rapid production of large variant libraries have seriously challenged the capacity of traditional screening and selection techniques. Similarly, random approaches based on directed evolution, which relies on the Darwinian principles of mutation and selection to steer proteins toward desired traits, also requires the screening of very large libraries of mutants to be truly effective. For either rational or random approaches, the highest possible screening throughput facilitates efficient protein engineering strategies. In the last decade, high-throughput screening (HTS) for protein engineering has been leveraging the emerging technologies of droplet microfluidics. Droplet microfluidics, featuring controlled formation and manipulation of nano- to femtoliter droplets of one fluid phase in another, has presented a new paradigm for screening, providing increased throughput, reduced reagent volume, and scalability. We review here the recent droplet microfluidics-based HTS systems developed for protein engineering, particularly directed evolution. The current review can also serve as a tutorial guide for protein engineers and molecular biologists who need a droplet microfluidics-based HTS system for their specific applications but may not have prior knowledge about microfluidics. In the end, several challenges and opportunities are identified to motivate the continued innovation of microfluidics with implications for protein engineering. Full article

(This article belongs to the Special Issue Droplet Microfluidics)

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