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13 pages, 9121 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

From Microtiter Plates to Droplets—There and Back Again

by Thomas Henkel, Günter Mayer, Jörg Hampl, Jialan Cao, Linda Ehrhardt, Andreas Schober and Gregor Alexander Groß

Micromachines 2022, 13(7), 1022; https://doi.org/10.3390/mi13071022 - 28 Jun 2022

Cited by 2 | Viewed by 2555

Abstract

Droplet-based microfluidic screening techniques can benefit from interfacing established microtiter plate-based screening and sample management workflows. Interfacing tools are required both for loading preconfigured microtiter-plate (MTP)-based sample collections into droplets and for dispensing the used droplets samples back into MTPs for subsequent storage [...] Read more.

Droplet-based microfluidic screening techniques can benefit from interfacing established microtiter plate-based screening and sample management workflows. Interfacing tools are required both for loading preconfigured microtiter-plate (MTP)-based sample collections into droplets and for dispensing the used droplets samples back into MTPs for subsequent storage or further processing. Here, we present a collection of Digital Microfluidic Pipetting Tips (DMPTs) with integrated facilities for droplet generation and manipulation together with a robotic system for its operation. This combination serves as a bidirectional sampling interface for sample transfer from wells into droplets (w2d) and vice versa droplets into wells (d2w). The DMPT were designed to fit into 96-deep-well MTPs and prepared from glass by means of microsystems technology. The aspirated samples are converted into the channel-confined droplets’ sequences separated by an immiscible carrier medium. To comply with the demands of dose-response assays, up to three additional assay compound solutions can be added to the sample droplets. To enable different procedural assay protocols, four different DMPT variants were made. In this way, droplet series with gradually changing composition can be generated for, e.g., 2D screening purposes. The developed DMPT and their common fluidic connector are described here. To handle the opposite transfer d2w, a robotic transfer system was set up and is described briefly. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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11 pages, 4404 KiB

Open AccessArticle

Single Microdroplet Breakup-Assisted Viscosity Measurement

by Yeongseok Jang, Hwabok Wee, Jonghyun Oh and Jinmu Jung

Micromachines 2022, 13(4), 558; https://doi.org/10.3390/mi13040558 - 31 Mar 2022

Cited by 1 | Viewed by 1772

Abstract

Recently, with the development of biomedical fields, the viscosity of prepolymer fluids, such as hydrogels, has played an important role in determining the mechanical properties of the extracellular matrix (ECM) or being closely related to cell viability in ECM. The technology for measuring [...] Read more.

Recently, with the development of biomedical fields, the viscosity of prepolymer fluids, such as hydrogels, has played an important role in determining the mechanical properties of the extracellular matrix (ECM) or being closely related to cell viability in ECM. The technology for measuring viscosity is also developing. Here, we describe a method that can measure the viscosity of a fluid with trace amounts of prepolymers based on a simple flow-focused microdroplet generator. We also propose an equation that could predict the viscosity of a fluid. The viscosity of the prepolymer was predicted by measuring and calculating various lengths of the disperse phase at the cross junction of two continuous-phase channels and one disperse-phase channel. Bioprepolymer alginates and gelatin methacryloyl (GelMA) were used to measure the viscosity at different concentrations in a microdroplet generator. The break-up length of the dispersed phase at the cross junction of the channel gradually increased with increasing flow rate and viscosity. Additional viscosity analysis was performed to validate the standard viscosity calculation formula depending on the measured length. The viscosity formula derived based on the length of the alginate prepolymer was applied to GelMA. At a continuous phase flow rate of 400 uL/h, the empirical formula of alginate showed an error within about 2%, which was shown to predict the viscosity very well in the viscometer. Results of this study are expected to be very useful for hydrogel tuning in biomedical and tissue regeneration fields by providing a technology that can measure the dynamic viscosity of various prepolymers in a microchannel with small amounts of sample. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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17 pages, 3769 KiB

Open AccessArticle

Encapsulated Cell Dynamics in Droplet Microfluidic Devices with Sheath Flow

by Peter E. Beshay, Ali M. Ibrahim, Stefanie S. Jeffrey, Roger T. Howe and Yasser H. Anis

Micromachines 2021, 12(7), 839; https://doi.org/10.3390/mi12070839 - 19 Jul 2021

Cited by 1 | Viewed by 3952

Abstract

In this paper we study the dynamics of single cells encapsulated in water-in-oil emulsions in a microchannel. The flow field of a microfluidic channel is coupled to the internal flow field of a droplet through viscous traction at the interface, resulting in a [...] Read more.

In this paper we study the dynamics of single cells encapsulated in water-in-oil emulsions in a microchannel. The flow field of a microfluidic channel is coupled to the internal flow field of a droplet through viscous traction at the interface, resulting in a rotational flow field inside the droplet. An encapsulated single cell being subjected to this flow field responds by undergoing multiple orbits, spins, and deformations that depend on its physical properties. Monitoring the cell dynamics, using a high-speed camera, can lead to the development of new label-free methods for the detection of rare cells, based on their biomechanical properties. A sheath flow microchannel was proposed to strengthen the rotational flow field inside droplets flowing in Poiseuille flow conditions. A numerical model was developed to investigate the effect of various parameters on the rotational flow field inside a droplet. The multi-phase flow model required the tracking of the fluid–fluid interface, which deforms over time due to the applied shear stresses. Experiments confirmed the significant effect of the sheath flow rate on the cell dynamics, where the speed of cell orbiting was doubled. Doubling the cell speed can double the amount of extracted biomechanical information from the encapsulated cell, while it remains within the field of view of the camera used. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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13 pages, 3283 KiB

Open AccessArticle

Fabrication of Multi-Layered Microspheres Based on Phase Separation for Drug Delivery

by He Xia, Ang Li, Jia Man, Jianyong Li and Jianfeng Li

Micromachines 2021, 12(6), 723; https://doi.org/10.3390/mi12060723 - 19 Jun 2021

Cited by 8 | Viewed by 3996

Abstract

In this work, we used a co-flow microfluidic device with an injection and a collection tube to generate droplets with different layers due to phase separation. The phase separation system consisted of poly(ethylene glycol) diacrylate 700 (PEGDA 700), PEGDA 250, and sodium alginate [...] Read more.

In this work, we used a co-flow microfluidic device with an injection and a collection tube to generate droplets with different layers due to phase separation. The phase separation system consisted of poly(ethylene glycol) diacrylate 700 (PEGDA 700), PEGDA 250, and sodium alginate aqueous solution. When the mixture droplets formed in the outer phase, PEGDA 700 in the droplets would transfer into the outer aqueous solution, while PEGDA 250 still stayed in the initial droplet, breaking the miscibility equilibrium of the mixture and triggering the phase separation. As the phase separation proceeded, new cores emerged in the droplets, gradually forming the second and third layers. Emulsion droplets with different layers were polymerized under ultraviolet (UV) irradiation at different stages of phase separation to obtain microspheres. Microspheres with different layers showed various release behaviors in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The release rate decreased with the increase in the number of layers, which showed a potential application in sustained drug release. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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11 pages, 910 KiB

Open AccessArticle

Modeling of Droplet Generation in a Microfluidic Flow-Focusing Junction for Droplet Size Control

by Ali M. Ibrahim, Jose I. Padovani, Roger T. Howe and Yasser H. Anis

Micromachines 2021, 12(6), 590; https://doi.org/10.3390/mi12060590 - 21 May 2021

Cited by 22 | Viewed by 5910

Abstract

In this paper, we study the parameters that affect the generation of droplets in a microfluidic flow-focusing junction. Droplets are evaluated based on the size and frequency of generation. Droplet size control is essential for microfluidic lab-on-a-chip applications in biology, chemistry, and medicine. [...] Read more.

In this paper, we study the parameters that affect the generation of droplets in a microfluidic flow-focusing junction. Droplets are evaluated based on the size and frequency of generation. Droplet size control is essential for microfluidic lab-on-a-chip applications in biology, chemistry, and medicine. We developed a three-dimensional numerical model that can emulate the performance of the physical system. A numerical model can help design droplet-generation chips with new junction geometries, different dispersed and continuous phase types, and different flow rates. Our model uses a conservative level-set method (LSM) to track the interface between two immiscible fluids using a fixed mesh. Water was used for the dispersed phase and mineral oil for the continuous phase. The effects of the continuous-to-dispersed flow rate ratio (

Q_{o} / Q_{w}

) and the surfactant concentration on the droplet generation were studied both using the numerical model and experimentally. The numerical model was found to render results that are in good agreement with the experimental ones, which validates the LSM model. The validated numerical model was used to study the time effect of changing

Q_{o} / Q_{w}

on the generated droplet size. Properly timing when the flow rates are changed enables control over the size of the next generated droplet, which is useful for single-droplet size modulation applications. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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13 pages, 5945 KiB

Open AccessArticle

3D-Printed Microfluidic Droplet Generator with Hydrophilic and Hydrophobic Polymers

by Chandler A. Warr, Hunter S. Hinnen, Saroya Avery, Rebecca J. Cate, Gregory P. Nordin and William G. Pitt

Micromachines 2021, 12(1), 91; https://doi.org/10.3390/mi12010091 - 16 Jan 2021

Cited by 21 | Viewed by 4433

Abstract

Droplet generation has been widely used in conventional two-dimensional (2D) microfluidic devices, and has recently begun to be explored for 3D-printed droplet generators. A major challenge for 3D-printed devices is preventing water-in-oil droplets from sticking to the interior surfaces of the droplet generator [...] Read more.

Droplet generation has been widely used in conventional two-dimensional (2D) microfluidic devices, and has recently begun to be explored for 3D-printed droplet generators. A major challenge for 3D-printed devices is preventing water-in-oil droplets from sticking to the interior surfaces of the droplet generator when the device is not made from hydrophobic materials. In this study, two approaches were investigated and shown to successfully form droplets in 3D-printed microfluidic devices. First, several printing resin candidates were tested to evaluate their suitability for droplet formation and material properties. We determined that a hexanediol diacrylate/lauryl acrylate (HDDA/LA) resin forms a solid polymer that is sufficiently hydrophobic to prevent aqueous droplets (in a continuous oil flow) from attaching to the device walls. The second approach uses a fully 3D annular channel-in-channel geometry to form microfluidic droplets that do not contact channel walls, and thus, this geometry can be used with hydrophilic resins. Stable droplets were shown to form using the channel-in-channel geometry, and the droplet size and generation frequency for this geometry were explored for various flow rates for the continuous and dispersed phases. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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11 pages, 2981 KiB

Open AccessArticle

Electrowetting-on-Dielectric Based Economical Digital Microfluidic Chip on Flexible Substrate by Inkjet Printing

by He Wang and Liguo Chen

Micromachines 2020, 11(12), 1113; https://doi.org/10.3390/mi11121113 - 16 Dec 2020

Cited by 11 | Viewed by 3923

Abstract

In order to get rid of the dependence on expensive photolithography technology and related facilities, an economic and simple design and fabrication technology for digital microfluidics (DMF) is proposed. The electrodes pattern was generated by inkjet printing nanosilver conductive ink on the flexible [...] Read more.

In order to get rid of the dependence on expensive photolithography technology and related facilities, an economic and simple design and fabrication technology for digital microfluidics (DMF) is proposed. The electrodes pattern was generated by inkjet printing nanosilver conductive ink on the flexible Polyethylene terephthalate (PET) substrate with a 3D circuit board printer, food wrap film was attached to the electrode array to act as the dielectric layer and Teflon^® AF was sprayed to form a hydrophobic layer. The PET substrate and food wrap film are low cost and accessible to general users. The proposed flexible DMF chips can be reused for a long time by replacing the dielectric film coated with hydrophobic layer. The resolution and conductivity of silver traces and the contact angle and velocity of the droplets were evaluated to demonstrate that the proposed technology is comparable to the traditional DMF fabrication process. As far as the rapid prototyping of DMF is concerned, this technology has shown very attractive advantages in many aspects, such as fabrication cost, fabrication time, material selection and mass production capacity, without sacrificing the performance of DMF. The flexible DMF chips have successfully implemented basic droplet operations on a square and hexagon electrode array. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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12 pages, 3470 KiB

Open AccessArticle

Designing Splicing Digital Microfluidics Chips Based on Polytetrafluoroethylene Membrane

by Haoqiang Feng, Zichuan Yi, Ruizhi Yang, Xiaofeng Qin, Shitao Shen, Wenjun Zeng, Lingling Shui, Guofu Zhou and Chongfu Zhang

Micromachines 2020, 11(12), 1067; https://doi.org/10.3390/mi11121067 - 30 Nov 2020

Cited by 16 | Viewed by 3222

Abstract

As a laboratory-on-a-chip application tool, digital microfluidics (DMF) technology is widely used in DNA-based applications, clinical diagnosis, chemical synthesis, and other fields. Additional components (such as heaters, centrifuges, mixers, etc.) are required in practical applications on DMF devices. In this paper, a DMF [...] Read more.

As a laboratory-on-a-chip application tool, digital microfluidics (DMF) technology is widely used in DNA-based applications, clinical diagnosis, chemical synthesis, and other fields. Additional components (such as heaters, centrifuges, mixers, etc.) are required in practical applications on DMF devices. In this paper, a DMF chip interconnection method based on electrowetting-on-dielectric (EWOD) was proposed. An open modified slippery liquid-infused porous surface (SLIPS) membrane was used as the dielectric-hydrophobic layer material, which consisted of polytetrafluoroethylene (PTFE) membrane and silicone oil. Indium tin oxide (ITO) glass was used to manufacture the DMF chip. In order to test the relationship between the splicing gap and droplet moving, the effect of the different electrodes on/off time on the minimum driving voltage when the droplet crossed a splicing gap was investigated. Then, the effects of splicing gaps of different widths, splicing heights, and electrode misalignments were investigated, respectively. The experimental results showed that a driving voltage of 119 V was required for a droplet to cross a splicing gap width of 300 μm when the droplet volume was 10 μL and the electrode on/off time was 600 ms. At the same time, the droplet could climb a height difference of 150 μm with 145 V, and 141 V was required when the electrode misalignment was 1000 μm. Finally, the minimum voltage was not obviously changed, when the same volume droplet with different aqueous solutions crossed the splicing gap, and the droplet could cross different chip types. These splicing solutions show high potential for simultaneous detection of multiple components in human body fluids. Full article

(This article belongs to the Special Issue Droplet-Based Microfluidic Devices)

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