Materials and methods for droplet microfluidic device fabrication

Elvira, Katherine S.; Gielen, Fabrice; Tsai, Scott S. H.; Nightingale, Adrian M.

doi:10.1039/d1lc00836f

Cited by 62 publications

(30 citation statements)

References 119 publications

(159 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The microfluidic device used a flow focusing droplet generator and was fabricated using soft lithography from PDMS. PDMS microfluidic devices are optimal for water-in-oil (w/o) droplet formation due to the hydrophobic nature of PDMS. , As oil-in-water (o/w) droplets were required for the fabrication of PCL microparticles, a hydrophilic substrate and surface modification of the PDMS device were used. In other words, the PDMS devices were bonded directly to a glass slide, and the channels were treated with a 2% (w/v) PVA solution.…”

Section: Resultsmentioning

confidence: 99%

Microfluidic Generation of Therapeutically Relevant Polycaprolactone (PCL) Microparticles: Computational and Experimental Approaches

Forigua

Dalili

Kirsch

et al. 2022

ACS Appl. Polym. Mater.

Self Cite

View full text Add to dashboard Cite

Drug releasing microparticles play an important role in drug delivery as they can be used for site specific delivery as well as control over the release time of therapeutics. The use of microfluidic technologies for the fabrication of these particles is of increasing interest since they provide enhanced control over microparticle size and size distribution compared to bulk production methods. However, the use of microfluidic platforms in the production of drug releasing microparticles with therapeutically relevant cargo still requires optimization depending on their application, and the effect of the addition of cargo on the production process is still unexplored. Here we show the formation of therapeutically relevant (in terms of size and dose of cargo) polycaprolactone (PCL) microparticles using a microfluidic platform and analyze the effect of the addition of cargo in the microparticle size and size distribution. This microfluidic platform was designed with the aid of computational fluid dynamic simulations, allowing us to construct a polydimethylsiloxane (PDMS) microfluidic device capable of making microparticles in the range of 15 to 35 μm with low coefficient of variation (CV) both with and without cargo by varying the flow rate ratios of the phases used during droplet generation. Our data show the effect of the addition of cargo on the droplet and microparticle sizes and monodispersity. Our fabrication method allows the formation of spherical microparticles, optimal for biomedical applications. In addition, our microfluidic platform can maintain the generation of monodisperse droplets (with an average size of 52.5 μm) over extended periods of time, suggesting it has the capacity to be used for scaled-up production of PCL microparticles. This microfluidic device is a robust and reliable method for the fabrication of PCL microparticles with cargo, which can potentially be loaded with other relevant therapeutic molecules for biomedical applications.

show abstract

Section: Resultsmentioning

confidence: 99%

Microfluidic Generation of Therapeutically Relevant Polycaprolactone (PCL) Microparticles: Computational and Experimental Approaches

Forigua

Dalili

Kirsch

et al. 2022

ACS Appl. Polym. Mater.

Self Cite

View full text Add to dashboard Cite

show abstract

“…162,163 The silanization of the PDMS devices serves to reduce "wetting effects" or friction at the channel walls, 164 and various surface modifications for hydrophobic or hydrophilic coating are available to match the carrier phase, allowing choices of different oils. 15 So-called "2.5D" designs (i.e., varying channel depth within the device) can be created by patterning several layers on the master in an iterative process. In this way, areas of the mask can have an additional buildup of material, leading to varying channel depths within the device.…”

Section: Chip Devicesmentioning

confidence: 99%

“…PDMS can also absorb 286,287 or transport 288 small molecules, suggesting a change of the chip material. 287,289 Finally the coating of the chip, i.e., surface modification for hydrophobic or hydrophilic coating to match the carrier phase, choice of oil, 15 or silanization of the PDMS devices (to reduce wetting effects or friction at the channel walls), 164 can be considered.…”

Section: Challenges To the Integrity Of The Droplet Compartmentmentioning

confidence: 99%

Ultrahigh-Throughput Enzyme Engineering and Discovery in In Vitro Compartments

et al. 2023

View full text Add to dashboard Cite

Novel and improved biocatalysts are increasingly sourced from libraries via experimental screening. The success of such campaigns is crucially dependent on the number of candidates tested. Water-in-oil emulsion droplets can replace the classical test tube, to provide in vitro compartments as an alternative screening format, containing genotype and phenotype and enabling a readout of function. The scale-down to micrometer droplet diameters and picoliter volumes brings about a >10 7 -fold volume reduction compared to 96-well-plate screening. Droplets made in automated microfluidic devices can be integrated into modular workflows to set up multistep screening protocols involving various detection modes to sort >10 7 variants a day with kHz frequencies. The repertoire of assays available for droplet screening covers all seven enzyme commission (EC) number classes, setting the stage for widespread use of droplet microfluidics in everyday biochemical experiments. We review the practicalities of adapting droplet screening for enzyme discovery and for detailed kinetic characterization. These new ways of working will not just accelerate discovery experiments currently limited by screening capacity but profoundly change the paradigms we can probe. By interfacing the results of ultrahigh-throughput droplet screening with next-generation sequencing and deep learning, strategies for directed evolution can be implemented, examined, and evaluated. CONTENTSAA 11.6.2. Combining High-Throughput Selections with High-Throughput Analysis AB 12. Conclusions

show abstract

“…The wider use of DE techniques has been impeded by the increased complexity required to form water in oil in water emulsions. Typical DE generators use a 3-D nested channel geometry or step-wise emulsification which requires challenging alignment steps. , To simplify fabrication we established a single layer PDMS device and adapted easy-to-perform plasma treatment to spatially pattern the surface wetting . This approach eliminates all laborious fabrication and treatment steps.…”

Section: Introductionmentioning

confidence: 99%

Simplified, Shear Induced Generation of Double Emulsions for Robust Compartmentalization during Single Genome Analysis

Cowell

Dobria

Han

2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Drop microfluidics has driven innovations for high throughput, low input analysis techniques such as single-cell RNA-seq. However, the instability of single emulsion (SE) drops occasionally causes significant merging during drop processing, limiting most applications to single-step reactions in drops. Here, we show that double emulsion (DE) drops address this critical limitation and completely prevent drop contents from mixing. DEs show excellent stability during thermal cycling. More importantly, DEs undergo rupture into the continuous phase instead of merging, preventing content mixing and eliminating unstable drops from the downstream analysis. Due to the lack of drop merging, the monodispersity of drops is maintained throughout a workflow, enabling the deterministic manipulation of drops downstream. We also developed a simple, one-layer DE drop maker compatible with simple surface treatment using a plasma cleaner. The device allows for the robust production of single-core DEs at a wide range of flow rates and better control over the shell thickness, both of which have been significant limitations of conventional two-layer devices. This approach makes the fabrication of DE devices much more accessible, facilitating its broader adoption. Finally, we show that DE droplets eliminate content mixing and maintain compartmentalization of single virus genomes during PCR-based amplification and barcoding, while SEs mixed contents due to merging. With their resistance to content mixing, DE drops have key advantages for multistep reactions in drops, which is limited in SEs due to merging and content mixing.

show abstract

Materials and methods for droplet microfluidic device fabrication

Abstract: Since the first reports two decades ago, droplet-based systems have emerged as a compelling tool for microbiological and (bio)chemical science, with droplet flow providing multiple advantages over standard single-phase microfluidics...

Cited by 62 publications

References 119 publications

Microfluidic Generation of Therapeutically Relevant Polycaprolactone (PCL) Microparticles: Computational and Experimental Approaches

Microfluidic Generation of Therapeutically Relevant Polycaprolactone (PCL) Microparticles: Computational and Experimental Approaches

Ultrahigh-Throughput Enzyme Engineering and Discovery in In Vitro Compartments

Simplified, Shear Induced Generation of Double Emulsions for Robust Compartmentalization during Single Genome Analysis

Contact Info

Product

Resources

About