pH calibration allows accurate glucose detection in interstitial fluid via reverse iontophoresis

Wangwang Zhu, Haixia Yu, Wenjun Li, Xi Li, Hao Zheng, Chengcheng Li, Xingguo Zhang, Chenxi Jin, Mutian Wang, Jiaqi Hou, Youhao Liu, Yuxiao Ma, Zhongxu Zhou, Miao Deng, Peng Guo, Mingzhen Li, Zhenqiang Song, Zhihua Pu () and Dachao Li ()
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Wangwang Zhu: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Haixia Yu: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Wenjun Li: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Xi Li: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Hao Zheng: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Chengcheng Li: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Xingguo Zhang: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Chenxi Jin: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Mutian Wang: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Jiaqi Hou: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Youhao Liu: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Yuxiao Ma: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Zhongxu Zhou: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Miao Deng: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Peng Guo: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Mingzhen Li: Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases
Zhenqiang Song: Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases
Zhihua Pu: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments
Dachao Li: Tianjin University, State Key Laboratory of Precision Measurement Technology and Instruments

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Reverse iontophoresis (RI) is a promising non-invasive, wearable technology for the transdermal extraction of interstitial fluid (ISF), which contains rich biomarkers relevant to health status. Despite the advancement of wearable sensors, this technology is still restricted for accurate non-invasive biomarkers detection. The main challenge lies in the instability of ISF extraction during RI. We found that this instability is primarily caused by the skin surface pH variations because of the interaction between the RI-induced H+ movement and the skin recovery ability. Here, we investigated how the skin surface pH affected RI, theoretically and experimentally; and developed a wearable device and a calibration method to enable accurate non-invasive ISF glucose detection, accordingly. The result showed that glucose prediction accuracy was markedly improved, with mean absolute relative difference (MARD) decreased from 34.44% to 14.78% across both healthy and diabetic volunteers.

Date: 2025
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DOI: 10.1038/s41467-025-65453-0

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