A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles

Hao Zhong; Zeyin Mao; Xuwen Li; Anni Deng; Yihao Zhu; Shihong Wang; Leyang Huang; Jianxin Zhao; Wenqi Lv; Yixuan Shi; Qin Huang; Yabo Zhai; Chenzhou Hui; Xianbo Luo; Li Ma; Rongxin Fu; Xiongjun Ye; Guoliang Huang

doi:10.1016/j.snb.2025.138898

A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles

Hao Zhong, Zeyin Mao, Xuwen Li, Anni Deng, Yihao Zhu, Shihong Wang, Leyang Huang, Jianxin Zhao, Wenqi Lv, Yixuan Shi, Qin Huang, Yabo Zhai, Chenzhou Hui, Xianbo Luo, Li Ma, Rongxin Fu, Xiongjun Ye^*, Guoliang Huang^*

^*Corresponding author for this work

School of Medical and Technology

Research output: Contribution to journal › Article › peer-review

Abstract

Small extracellular vesicles (sEVs), which are ubiquitously present in bodily fluids, hold significant promise as biomarkers for disease diagnosis and targeted therapy. However, their isolation remains challenging due to their small size (typically < 200 nm) and the complexity of biological fluids. This study presents a novel microfluidic strategy integrating Magnetic Stirring with Tangential Flow Filtration (MS-TFF). The automated, portable device (palm-sized, 12.5 cm × 11.1 cm × 6.25 cm) features user-friendly operation: inserting the chip into a slot and closing the lid initiates automated sEV extraction. The system processes 10 mL of morning urine or cell culture supernatant within ∼40 min. Compared to ultracentrifugation (UC), MS-TFF reduces processing time from ∼4 h to ∼40 min while achieving a 6-fold higher sEV yield. Clinical validation using urine from 16 subjects (6 healthy/10 prostate cancer patients) enabled quantitative *KLK3/PCA3* RNA biomarker detection, achieving AUC = 0.93 for cancer diagnosis, confirming its diagnostic potential.

Original language	English
Article number	138898
Journal	Sensors and Actuators, B: Chemical
Volume	447
DOIs	http://doi.org/10.1016/j.snb.2025.138898
Publication status	Published - 15 Jan 2026

Keywords

Cancer diagnosis
Magnetic stirring
Microfluidic chip
SEVs
Tangential flow filtration

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10.1016/j.snb.2025.138898

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Zhong, H., Mao, Z., Li, X., Deng, A., Zhu, Y., Wang, S., Huang, L., Zhao, J., Lv, W., Shi, Y., Huang, Q., Zhai, Y., Hui, C., Luo, X., Ma, L., Fu, R., Ye, X., & Huang, G. (2026). A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles. Sensors and Actuators, B: Chemical, 447, Article 138898. http://doi.org/10.1016/j.snb.2025.138898

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title = "A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles",

abstract = "Small extracellular vesicles (sEVs), which are ubiquitously present in bodily fluids, hold significant promise as biomarkers for disease diagnosis and targeted therapy. However, their isolation remains challenging due to their small size (typically < 200 nm) and the complexity of biological fluids. This study presents a novel microfluidic strategy integrating Magnetic Stirring with Tangential Flow Filtration (MS-TFF). The automated, portable device (palm-sized, 12.5 cm × 11.1 cm × 6.25 cm) features user-friendly operation: inserting the chip into a slot and closing the lid initiates automated sEV extraction. The system processes 10 mL of morning urine or cell culture supernatant within ∼40 min. Compared to ultracentrifugation (UC), MS-TFF reduces processing time from ∼4 h to ∼40 min while achieving a 6-fold higher sEV yield. Clinical validation using urine from 16 subjects (6 healthy/10 prostate cancer patients) enabled quantitative *KLK3/PCA3* RNA biomarker detection, achieving AUC = 0.93 for cancer diagnosis, confirming its diagnostic potential.",

keywords = "Cancer diagnosis, Magnetic stirring, Microfluidic chip, SEVs, Tangential flow filtration",

author = "Hao Zhong and Zeyin Mao and Xuwen Li and Anni Deng and Yihao Zhu and Shihong Wang and Leyang Huang and Jianxin Zhao and Wenqi Lv and Yixuan Shi and Qin Huang and Yabo Zhai and Chenzhou Hui and Xianbo Luo and Li Ma and Rongxin Fu and Xiongjun Ye and Guoliang Huang",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier B.V.",

year = "2026",

month = jan,

day = "15",

doi = "10.1016/j.snb.2025.138898",

language = "English",

volume = "447",

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Zhong, H, Mao, Z, Li, X, Deng, A, Zhu, Y, Wang, S, Huang, L, Zhao, J, Lv, W, Shi, Y, Huang, Q, Zhai, Y, Hui, C, Luo, X, Ma, L, Fu, R, Ye, X & Huang, G 2026, 'A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles', Sensors and Actuators, B: Chemical, vol. 447, 138898. http://doi.org/10.1016/j.snb.2025.138898

TY - JOUR

T1 - A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles

AU - Zhong, Hao

AU - Mao, Zeyin

AU - Li, Xuwen

AU - Deng, Anni

AU - Zhu, Yihao

AU - Wang, Shihong

AU - Huang, Leyang

AU - Zhao, Jianxin

AU - Lv, Wenqi

AU - Shi, Yixuan

AU - Huang, Qin

AU - Zhai, Yabo

AU - Hui, Chenzhou

AU - Luo, Xianbo

AU - Ma, Li

AU - Fu, Rongxin

AU - Ye, Xiongjun

AU - Huang, Guoliang

PY - 2026/1/15

Y1 - 2026/1/15

N2 - Small extracellular vesicles (sEVs), which are ubiquitously present in bodily fluids, hold significant promise as biomarkers for disease diagnosis and targeted therapy. However, their isolation remains challenging due to their small size (typically < 200 nm) and the complexity of biological fluids. This study presents a novel microfluidic strategy integrating Magnetic Stirring with Tangential Flow Filtration (MS-TFF). The automated, portable device (palm-sized, 12.5 cm × 11.1 cm × 6.25 cm) features user-friendly operation: inserting the chip into a slot and closing the lid initiates automated sEV extraction. The system processes 10 mL of morning urine or cell culture supernatant within ∼40 min. Compared to ultracentrifugation (UC), MS-TFF reduces processing time from ∼4 h to ∼40 min while achieving a 6-fold higher sEV yield. Clinical validation using urine from 16 subjects (6 healthy/10 prostate cancer patients) enabled quantitative *KLK3/PCA3* RNA biomarker detection, achieving AUC = 0.93 for cancer diagnosis, confirming its diagnostic potential.

AB - Small extracellular vesicles (sEVs), which are ubiquitously present in bodily fluids, hold significant promise as biomarkers for disease diagnosis and targeted therapy. However, their isolation remains challenging due to their small size (typically < 200 nm) and the complexity of biological fluids. This study presents a novel microfluidic strategy integrating Magnetic Stirring with Tangential Flow Filtration (MS-TFF). The automated, portable device (palm-sized, 12.5 cm × 11.1 cm × 6.25 cm) features user-friendly operation: inserting the chip into a slot and closing the lid initiates automated sEV extraction. The system processes 10 mL of morning urine or cell culture supernatant within ∼40 min. Compared to ultracentrifugation (UC), MS-TFF reduces processing time from ∼4 h to ∼40 min while achieving a 6-fold higher sEV yield. Clinical validation using urine from 16 subjects (6 healthy/10 prostate cancer patients) enabled quantitative *KLK3/PCA3* RNA biomarker detection, achieving AUC = 0.93 for cancer diagnosis, confirming its diagnostic potential.

KW - Cancer diagnosis

KW - Magnetic stirring

KW - Microfluidic chip

KW - SEVs

KW - Tangential flow filtration

UR - http://www.scopus.com/pages/publications/105017840983

U2 - 10.1016/j.snb.2025.138898

DO - 10.1016/j.snb.2025.138898

M3 - Article

AN - SCOPUS:105017840983

SN - 0925-4005

VL - 447

JO - Sensors and Actuators, B: Chemical

JF - Sensors and Actuators, B: Chemical

M1 - 138898

ER -

A microfluidic device integrating magnetic stirring with tangential flow for high-efficiency isolation of small extracellular vesicles

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Keywords

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