Fabrication of monodisperse alginate microgel beads by microfluidic picoinjection: a chelate free approach

Ahmed, Husnain; Stokke, Bjørn Torger

doi:10.1039/d1lc00111f

Cited by 32 publications

(27 citation statements)

References 49 publications

(42 reference statements)

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“…Single-cell research is commonly used to deprive cells from cell-cell interactions and discover their innate capabilities and potential for responding to (Martinez et al, 2012). (C) Microfluidic design utilizing pico-injection of CaCl 2 after droplet formation point to prevent premature gelation of alginate solution (Ahmed et al, 2021). specific stimuli.…”

Section: Microfluidicsmentioning

confidence: 99%

“…Therefore, the type of crosslinking dictates droplet formation and adjustments that need to be made to device design. Commonly used types are ionic cross-linking (Choi et al, 2007;Workman et al, 2007;Utech et al, 2015;Ahmed and Stokke, 2021), photo-cross-linking (Zhao et al, 2016;Mohamed et al, 2019;Nan et al, 2019), and thermoresponsive cross-linking (Dolega et al, 2015;Yanakieva et al, 2020;Tiemeijer et al, 2021;Zhang et al, 2021). By design, the latter two do not require on-chip mixing of different aqueous phases and can still be used in conventional device designs.…”

Section: Microfluidicsmentioning

confidence: 99%

“…Therefore, other strategies can be needed for on-chip droplet formation to ensure constant low viscosity during droplet production. Recently, Ahmed et al demonstrated a unique device design which produced alginate droplets following a conventional approach but used on-chip pico-injection of CaCl 2 solution to prevent problems with premature gelation and obtain monodisperse hydrogel droplets (Figure 2C) (Ahmed and Stokke, 2021). Alternatives to CaCl 2 are partially soluble or insoluble calcium salts such as calcium sulfate (Kong et al, 2003) and calcium carbonate (Tan and Takeuchi, 2007;Workman et al, 2007), respectively.…”

Section: Natural Hydrogelsmentioning

confidence: 99%

“…(B) Transfer of alginate solution from a double-emulsion toward a CaCl 2 solution causes gelation within 100 ms(Martinez et al, 2012). (C) Microfluidic design utilizing pico-injection of CaCl 2 after droplet formation point to prevent premature gelation of alginate solution(Ahmed et al, 2021).…”

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confidence: 99%

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Hydrogels for Single-Cell Microgel Production: Recent Advances and Applications

Tiemeijer

Tel

2022

Front. Bioeng. Biotechnol.

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Single-cell techniques have become more and more incorporated in cell biological research over the past decades. Various approaches have been proposed to isolate, culture, sort, and analyze individual cells to understand cellular heterogeneity, which is at the foundation of every systematic cellular response in the human body. Microfluidics is undoubtedly the most suitable method of manipulating cells, due to its small scale, high degree of control, and gentle nature toward vulnerable cells. More specifically, the technique of microfluidic droplet production has proven to provide reproducible single-cell encapsulation with high throughput. Various in-droplet applications have been explored, ranging from immunoassays, cytotoxicity assays, and single-cell sequencing. All rely on the theoretically unlimited throughput that can be achieved and the monodispersity of each individual droplet. To make these platforms more suitable for adherent cells or to maintain spatial control after de-emulsification, hydrogels can be included during droplet production to obtain “microgels.” Over the past years, a multitude of research has focused on the possibilities these can provide. Also, as the technique matures, it is becoming clear that it will result in advantages over conventional droplet approaches. In this review, we provide a comprehensive overview on how various types of hydrogels can be incorporated into different droplet-based approaches and provide novel and more robust analytic and screening applications. We will further focus on a wide range of recently published applications for microgels and how these can be applied in cell biological research at the single- to multicell scale.

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Section: Microfluidicsmentioning

confidence: 99%

Section: Microfluidicsmentioning

confidence: 99%

Section: Natural Hydrogelsmentioning

confidence: 99%

mentioning

confidence: 99%

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Hydrogels for Single-Cell Microgel Production: Recent Advances and Applications

Tiemeijer

Tel

2022

Front. Bioeng. Biotechnol.

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“…Literature includes several examples presenting the use of microfluidics in the fabrication of different-sized particles. Among those examples are microparticles like micron-sized beads as alginate microgel (8–28 μm in diameter) (Ahmed & Stokke, 2021 ), PLGA magnetic beads (≈ 60 μm in diameter), hybrid microgels (70–90 μm in diameter) (de Carvalho et al., 2021 ), and nanoparticles as gold nanoparticles (2–4 nm) (Al-Ahmady et al., 2019 ), citric acid-modified gold nanoparticles (≈15 nm in diameter) (Wang et al., 2019 ) and American ginseng polysaccharide nanoparticles (≈20 nm in diameter) (Akhter et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects

et al. 2022

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Microfluidics is used to manipulate fluid flow in micro-channels to fabricate drug delivery vesicles in a uniform tunable size. Thanks to their designs, microfluidic technology provides an alternative and versatile platform over traditional formulation methods of nanoparticles. Understanding the factors that affect the formulation of nanoparticles can guide the proper selection of microfluidic design and the operating parameters aiming at producing nanoparticles with reproducible properties. This review introduces the microfluidic systems’ continuous flow (single-phase) and segmented flow (multiphase) and their different mixing parameters and mechanisms. Furthermore, microfluidic approaches for efficient production of nanoparticles as surface modification, anti-fouling, and post-microfluidic treatment are summarized. The review sheds light on the used microfluidic systems and operation parameters applied to prepare and fine-tune nanoparticles like lipid, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles as well as cross-linked nanoparticles. The approaches for scale-up production using microfluidics for clinical or industrial use are also highlighted. Furthermore, the use of microfluidics in preparing novel micro/nanofluidic drug delivery systems is presented. In conclusion, the characteristic vital features of microfluidics offer the ability to develop precise and efficient drug delivery nanoparticles.

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Effect of preparation method on alginate wafer properties

Man

Oluwasanmi

Lamprou

et al. 2022

J of Applied Polymer Sci

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The utilization of alginate polymers for wound healing is well explored; however, little attention is paid toward the optimization of the manufacturing process, especially in regards to the final morphological and rheological properties that are imparted to the alginate matrix. This is important as it helps to establish a set of guidelines for the consistent fabrication of mechanically strong polymer wafers, which in the context of manufacturing and production contributes to the reduction in research and development time required. In this study, the order of application with respect to cross-linking and freezedrying parameters has been investigated, which showed to result in distinct differences in terms of their overall morphology and mechanical strength. The application of freeze-drying before cross-linking results in the uniform distribution of cross-links throughout the alginate wafer, thereby producing a mechanically strong polymer wafer that retains the dehydrated matrices original thickness and architecture. Based on the observed data, freeze-drying prior to cross-linking facilitates the increased permeation and distribution of the cross-linker solution into the polymer matrix, thus resulting in the uniform distribution of ionic cross-links, which is necessary to produce a more mechanically superior polymer matrix.

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Fabrication of monodisperse alginate microgel beads by microfluidic picoinjection: a chelate free approach

Abstract: Micron-sized alginate hydrogel beads are extensively employed as an encapsulation medium for biochemical and biomedical applications. Here we report on the microfluidic assisted fabrication of calcium alginate (Ca-alginate) beads by...

Cited by 32 publications

References 49 publications

Hydrogels for Single-Cell Microgel Production: Recent Advances and Applications

Hydrogels for Single-Cell Microgel Production: Recent Advances and Applications

Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects

Effect of preparation method on alginate wafer properties

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