High-throughput generation of aqueous two-phase microcapsules using microfluidic bubble triggering

Sixiang Rao , Weiliang Zhi , Chengkai Hong , Yanan Du , Long Chen , Yuan Luo , Yifan Liu

Droplet ›› 2026, Vol. 5 ›› Issue (1) : e70034

PDF
Droplet ›› 2026, Vol. 5 ›› Issue (1) :e70034 DOI: 10.1002/dro2.70034
RESEARCH ARTICLE
High-throughput generation of aqueous two-phase microcapsules using microfluidic bubble triggering
Author information +
History +
PDF

Abstract

Hydrogel microcapsules are powerful microreactor vessels that have attracted widespread attention and research. Among the various methods for their generation, the aqueous two-phase system (ATPS) is by far the most straightforward approach. However, the high viscosity of ATPS solutions significantly limits the generation throughput of hydrogel microcapsule. In this study, we developed a novel high-throughput approach for generating hydrogel microcapsules using a microfluidic bubble-triggering strategy. By integrating constant-pressure air flow with droplet microfluidics devices, we efficiently manipulated the formation of ATPS droplet through bubble-induced Rayleigh-Plateau instability, enabling the production of uniform, monodisperse microcapsules. Additionally, the droplet generation frequency in the bubble-triggering method exceeded 36 kHz. We further demonstrated the encapsulation of genetically engineered Escherichia coli strains, which acted as biosensors for arsenic ions and caprolactam, highlighting the potential of these microcapsules for biosensing applications. This advancement in hydrogel microcapsule generation offers promising implications for scalable applications in biosensing, organoid culture, and high-throughput screening.

Cite this article

Download citation ▾
Sixiang Rao, Weiliang Zhi, Chengkai Hong, Yanan Du, Long Chen, Yuan Luo, Yifan Liu. High-throughput generation of aqueous two-phase microcapsules using microfluidic bubble triggering. Droplet, 2026, 5(1): e70034 DOI:10.1002/dro2.70034

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Whitesides GM. The origins and the future of microfluidics. Nature. 2006; 442: 368-373.

[2]

Nan L, Lai MYA, Tang MYH, Chan YK, Poon LLM, Shum HC. On-demand droplet collection for capturing single cells. Small. 2020; 16:e1902889.

[3]

Zhang M, Ettelaie R, Dong L, et al. Pickering emulsion droplet-based biomimetic microreactors for continuous flow cascade reactions. Nat Commun. 2022; 13: 475.

[4]

Song W, Lin G, Ge J, Fassbender J, Makarov D. Encoding microreactors with droplet chains in microfluidics. ACS Sens. 2017; 2: 1839-1846.

[5]

Vegas AJ, Veiseh O, Doloff JC, et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol. 2016; 34: 345-352.

[6]

van Loo B, Ten Den SA, Araújo-Gomes N, et al. Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules. Nat Commun. 2023; 14: 6685.

[7]

Fattahi P, Rahimian A, Slama MQ, et al. Core‒shell hydrogel microcapsules enable formation of human pluripotent stem cell spheroids and their cultivation in a stirred bioreactor. Sci Rep. 2021; 11: 7177.

[8]

Zhou C, Zhu P, Han X, Shi R, Tian Y, Wang L. Microfluidic generation of ATPS droplets by transient double emulsion technique. Lab Chip. 2021; 21: 2684-2690.

[9]

Zhou C, Zhu P, Tian Y, Tang X, Shi R, Wang L. Microfluidic generation of aqueous two-phase-system (ATPS) droplets by oil-droplet choppers. Lab Chip. 2017; 17: 3310-3317.

[10]

Teixeira AG, Agarwal R, Ko KR, Grant-Burt J, Leung BM, Frampton JP. Emerging biotechnology applications of aqueous two-phase systems. Adv Healthc Mater. 2018; 7:e1701036.

[11]

Chao Y, Shum HC. Emerging aqueous two-phase systems: from fundamentals of interfaces to biomedical applications. Chem Soc Rev. 2020; 49: 114-142.

[12]

Albertsson PA. Partition of cell particles and macromolecules in polymer two-phase systems. Adv Protein Chem. 1970; 24: 309-341.

[13]

Seo H, Nam C, Kim E, Son J, Lee H. Aqueous two-phase system (ATPS)-based polymersomes for particle isolation and separation. ACS Appl Mater Interfaces. 2020; 12: 55467-55475.

[14]

Jeyhani M, Thevakumaran R, Abbasi N, Hwang DK, Tsai SSH. Microfluidic generation of all-aqueous double and triple emulsions. Small. 2020; 16:e1906565.

[15]

Zhang Y, Luo Y, Zhao J, et al. Emerging delivery systems based on aqueous two-phase systems: a review. Acta Pharm Sin B. 2024; 14: 110-132.

[16]

Shi H, Wang Y, Zhang Z, et al. Recent advances of integrated microfluidic systems for fungal and bacterial analysis. TrAC, Trends Anal Chem. 2023; 158:116850.

[17]

Abate AR, Weitz DA. Air-bubble-triggered drop formation in microfluidics. Lab Chip. 2011; 11: 1713-1716.

[18]

Li L, Zhang R, Chen L, et al. Permeability-engineered compartmentalization enables in vitro reconstitution of sustained synthetic biology systems. Adv Sci (Weinh). 2022; 9:e2203652.

[19]

Nan L, Cao Y, Yuan S, Shum HC. Oil-mediated high-throughput generation and sorting of water-in-water droplets. Microsyst Nanoeng. 2020; 6: 70.

[20]

Leonaviciene G, Leonavicius K, Meskys R, Mazutis L. Multi-step processing of single cells using semi-permeable capsules. Lab Chip. 2020; 20: 4052-4062.

[21]

Wan X, Volpetti F, Petrova E, French C, Maerkl SJ, Wang B. Cascaded amplifying circuits enable ultrasensitive cellular sensors for toxic metals. Nat Chem Biol. 2019; 15: 540-548.

[22]

Zhao C-X, Liu J-N, Li B-Q, et al. Multiscale construction of bifunctional electrocatalysts for long-lifespan rechargeable zinc-air batteries. Adv Funct Mater. 2020; 30:2003619.

[23]

Ma C, Li J, Zhang B, Liu C, Zhang J, Liu Y. Hydrogel microparticles functionalized with engineered Escherichia coli as living lactam biosensors. Sensors (Basel). 2019; 19: 5556.

[24]

Tang T-C, Tham E, Liu X, et al. Hydrogel-based biocontainment of bacteria for continuous sensing and computation. Nat Chem Biol. 2021; 17: 724-731.

RIGHTS & PERMISSIONS

2026 The Author(s). Droplet published by Jilin University and John Wiley & Sons Australia, Ltd.

PDF

8

Accesses

0

Citation

Detail

Sections
Recommended

/