Grooved step emulsification systems optimize the throughput of passive generation of monodisperse emulsions

Opalski, Adam S.; Makuch, Karol; Lai, Yu-Kai; Derzsi, Ladislav; Garstecki, Piotr

doi:10.1039/c8lc01096j

Cited by 20 publications

(15 citation statements)

References 43 publications

(66 reference statements)

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“… 25 , 26 Although the mechanism was discovered in the mid-1990s, 27 it was largely ignored until recent years. 28 , 29 The droplet size in step emulsification devices can be tuned solely by the geometry of shallow channels. The effect of fluid flow rates is negligible, which allows for easy multiplication of individual channels.…”

Section: Introductionmentioning

confidence: 99%

Monodispersed Sirolimus-Loaded PLGA Microspheres with a Controlled Degree of Drug–Polymer Phase Separation for Drug-Coated Implantable Medical Devices and Subcutaneous Injection

Zhang

Ekanem

Nakajima

et al. 2022

ACS Appl. Bio Mater.

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Monodispersed sirolimus (SRL)-loaded poly(lacticco-glycolic acid) microspheres with a diameter of 1.8, 3.8, and 8.5 μm were produced by high-throughput microfluidic step emulsification�solvent evaporation using single crystal silicon chips consisted of 540−1710 terraced microchannels with a depth of 2, 4, or 5 μm arranged in 10 parallel arrays. Uniform sized droplets were generated over 25 h across all channels. Nearly 15% of the total drug was released by the initial burst release during an accelerated drug release testing performed at 37 °C using a hydrotropic solution containing 5.8 M N,N-diethylnicotinamide. After 24 h, 71% of the drug was still entrapped in the particles. The internal morphology of microspheres was investigated by fluorescence microscopy using Nile red as a selective fluorescent stain with higher binding affinity toward SRL. By increasing the drug loading from 33 to 50 wt %, the particle morphology evolved from homogeneous microspheres, in which the drug and polymer were perfectly mixed, to patchy particles, with amorphous drug patches embedded within a polymer matrix to anisotropic patchy Janus particles. Janus particles with fully segregated drug and polymer regions were achieved by pre-saturating the aqueous phase with the organic solvent, which decreased the rate of solvent evaporation and allowed enough time for complete phase separation. This approach to manufacturing drug-loaded monodisperse microparticles can enable the development of more effective implantable drug-delivery devices and improved methods for subcutaneous drug administration, which can lead to better therapeutic treatments.

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Section: Introductionmentioning

confidence: 99%

Monodispersed Sirolimus-Loaded PLGA Microspheres with a Controlled Degree of Drug–Polymer Phase Separation for Drug-Coated Implantable Medical Devices and Subcutaneous Injection

Zhang

Ekanem

Nakajima

et al. 2022

ACS Appl. Bio Mater.

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“…Here, the droplet is formed spontaneously, and the droplet diameter is only defined by surface forces and geometry. Published systems such as “microchannel emulsification”, the “millipede device”, and step, groove, or gradient-based emulsifiers − show that the droplet diameter is constant with a CV of <5% in droplet diameter in a defined range of operation. A major disadvantage of geometry and surface tension-based technologies is a limited droplet generation rate dependent on modus of operation and droplet size.…”

Section: Introductionmentioning

confidence: 99%

Centrifugal Step Emulsification: How Buoyancy Enables High Generation Rates of Monodisperse Droplets

et al. 2019

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We demonstrate that buoyancy in centrifugal step emulsification enables substantially higher generation rates of monodisperse droplets compared to pressure driven set-ups. Step emulsification in general can produce droplets in comparatively simple systems (only one moving liquid) with a low CV of <5% in droplet diameter and with a minimum dead volume. If operated below a critical capillary number, the droplet diameter is defined by geometry and surface forces only. Above that critical capillary number, however, jetting occurs, leading to an increased droplet diameter and CV. Consequently, generation rates of monodisperse droplets are limited in pressure-driven systems. In this paper, we show that centrifugal step emulsification can overcome this limitation by applying sufficient buoyancy to the system. The buoyancy, induced by the centrifugal field and a density difference of the continuous and disperse phase, supports droplet necking by pulling the forming droplet away from the nozzle. The influence of buoyancy is studied using specific microfluidic designs that allow for supplying different buoyancies to the same droplet generation rates. For a droplet diameter of 100 μm, droplet generation at rates above 2.8k droplets per second and nozzle were reached, which is an increase of more than a factor of 8 in comparison to pressure-driven systems.

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“…Such surface roughness is actually known to improve the effectiveness of the fluorophilic coating of polycarbonate with Novec 1720. 28 In order to avoid even partial wetting of channel walls by the dispersed phases, first we filled our devices with the outer phase and only then introduced the to-be dispersed phases.…”

Section: Methodsmentioning

confidence: 99%

A double-step emulsification device for direct generation of double emulsions

et al. 2022

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Grooved step emulsification systems optimize the throughput of passive generation of monodisperse emulsions

Abstract: A novel step emulsifier allows high throughput production of monodisperse emulsions. Additionally, different modes of droplet production are investigated.

Cited by 20 publications

References 43 publications

Monodispersed Sirolimus-Loaded PLGA Microspheres with a Controlled Degree of Drug–Polymer Phase Separation for Drug-Coated Implantable Medical Devices and Subcutaneous Injection

Monodispersed Sirolimus-Loaded PLGA Microspheres with a Controlled Degree of Drug–Polymer Phase Separation for Drug-Coated Implantable Medical Devices and Subcutaneous Injection

Centrifugal Step Emulsification: How Buoyancy Enables High Generation Rates of Monodisperse Droplets

A double-step emulsification device for direct generation of double emulsions

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