Enhanced single-cell encapsulation in microfluidic devices: From droplet generation to single-cell analysis

Ling, Si Da; Geng, Yuhao; An, Chen; Du, Yanan; Xu, Jianhong

doi:10.1063/5.0018785

Cited by 41 publications

(30 citation statements)

References 191 publications

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“…We encourage readers to refer to other reviews regarding microfluidic-based droplet generation and single-cell encapsulation for more extensive detail. [155,[157][158][159][160][161]…”

Section: Leveraging Microfluidics For Optimizing Monodispersity and Capture Efficiencymentioning

confidence: 99%

“…Typically, manual washing steps via centrifugation are slow and can expose cells to extended periods of stress, while on-chip isolation methods provide a faster and facile way of retrieving single-cell microgels from the continuous phase. [161] There are many dimensionless parameters that physically describe microfluidic-based droplet generation (e.g., Reynolds number, Weber number, and Bond number), but for simplicity we focus primarily on the capillary number (Ca). The capillary number is the ratio of viscous force to interfacial tension, Ca = μU/γ, where μ is the fluid dynamic viscosity, U is the fluid velocity, and γ is the interfacial tension between the two fluids.…”

Section: Microfluidic-based Droplet Generationmentioning

confidence: 99%

“…To make an informed decision on which microfluidic-based purification approach is appropriate for a specific application, the reader is referred to one of the many review articles discussing these microfluidic-based techniques in more detail. [161,193,[220][221][222]…”

Section: Downstream Purification and Processingmentioning

confidence: 99%

See 2 more Smart Citations

Single‐Cell Microgels for Diagnostics and Therapeutics

Dubay

Urban

Darling

2021

Adv Funct Materials

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Cell encapsulation within hydrogel droplets is transforming what is feasible in multiple fields of biomedical science such as tissue engineering and regenerative medicine, in vitro modeling, and cell-based therapies. Recent advances have allowed researchers to miniaturize material encapsulation complexes down to single-cell scales, where each complex, termed a singlecell microgel, contains only one cell surrounded by a hydrogel matrix while remaining <100 μm in size. With this achievement, studies requiring singlecell resolution are now possible, similar to those done using liquid droplet encapsulation. Of particular note, applications involving long-term in vitro cultures, modular bioinks, high-throughput screenings, and formation of 3D cellular microenvironments can be tuned independently to suit the needs of individual cells and experimental goals. In this progress report, an overview of established materials and techniques used to fabricate single-cell microgels, as well as insight into potential alternatives is provided. This focused review is concluded by discussing applications that have already benefited from single-cell microgel technologies, as well as prospective applications on the cusp of achieving important new capabilities.

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“…We encourage readers to refer to other reviews regarding microfluidic-based droplet generation and single-cell encapsulation for more extensive detail. [155,[157][158][159][160][161]…”

Section: Leveraging Microfluidics For Optimizing Monodispersity and Capture Efficiencymentioning

confidence: 99%

Section: Microfluidic-based Droplet Generationmentioning

confidence: 99%

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Single‐Cell Microgels for Diagnostics and Therapeutics

Dubay

Urban

Darling

2021

Adv Funct Materials

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“…This reduces the problem to a single Poisson statistic allowing the majority of cells to be captured, albeit necessitating lower droplet generation rates, ultimately producing equivalent throughput to solid bead systems. The general problem of single cell encapsulation has attracted great interest, resulting in a wide variety of passive (trapping, 12,13 deterministic 14 and inertial ordering [15][16][17] ) and active (electrical, [18][19][20] magnetic, 21 optical, 22 acoustic 23 and mechanical 24 ) droplet generation and encapsulation strategies that have recently been expertly reviewed by Ling et al 25 Passive approaches harness flow and channel properties, with the benefit of being easy to operate. In particular, inertial microfluidic formats [26][27][28] enable high throughput and can produce entrainment effects to offer the enticing possibility of the periodic delivery of cell and beads, allowing deterministic packaging into droplets to free assays from the limitations of the Poisson statistic.…”

Section: Introductionmentioning

confidence: 99%

Dual dean entrainment with volume ratio modulation for efficient droplet co-encapsulation: extreme single-cell indexing

et al. 2021

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“…Droplet microfluidics has recently emerged as a powerful technology for single-cell manipulation [ 5 , 6 , 7 , 8 ]. Aqueous droplets in oil provide small isolated volumes, engineered environments, controllable vessels, and reduced shear stress levels on the encapsulated cells.…”

Section: Introductionmentioning

confidence: 99%

Encapsulated Cell Dynamics in Droplet Microfluidic Devices with Sheath Flow

et al. 2021

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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.

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Enhanced single-cell encapsulation in microfluidic devices: From droplet generation to single-cell analysis

Cited by 41 publications

References 191 publications

Single‐Cell Microgels for Diagnostics and Therapeutics

Single‐Cell Microgels for Diagnostics and Therapeutics

Dual dean entrainment with volume ratio modulation for efficient droplet co-encapsulation: extreme single-cell indexing

Encapsulated Cell Dynamics in Droplet Microfluidic Devices with Sheath Flow

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