Microfluidic magnetic detection system combined with a DNA framework-mediated immune-sandwich assay for rapid and sensitive detection of tumor-derived exosomes

Qiuling Qian; Yutong Wei; Yi Xu; Mengmeng Zheng; Chenguang Wang; Shulin Zhang; Xiaoming Xie; Chaofeng Ye; Xianqiang Mi

doi:10.1038/s41378-023-00617-w

Microfluidic magnetic detection system combined with a DNA framework-mediated immune-sandwich assay for rapid and sensitive detection of tumor-derived exosomes

Microsyst Nanoeng. 2023 Nov 7:9:139. doi: 10.1038/s41378-023-00617-w. eCollection 2023.

Authors

Qiuling Qian^#^{1

2

3}, Yutong Wei^#^{1

3

4}, Yi Xu^#^{1

2}, Mengmeng Zheng^{2

5}, Chenguang Wang^{2

3}, Shulin Zhang¹, Xiaoming Xie¹, Chaofeng Ye⁴, Xianqiang Mi^{1

2

3

6}

Affiliations

¹ National Key Laboratory of Materials for Integrated Circuits, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, 865 Changning Road, Shanghai, 200050 China.
² Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210 China.
³ University of Chinese Academy of Sciences, Beijing, 100049 China.
⁴ School of Information Science and Technology, Shanghai Tech University, Shanghai, 201210 China.
⁵ School of Life Sciences, Shanghai University, Shanghai, 200444 China.
⁶ School of Physics and Optoelectronic Engineering Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024 China.

^# Contributed equally.

Abstract

Tumor-derived circulating exosomes (TDEs) are being pursued as informative and noninvasive biomarkers. However, quantitatively detecting TDEs is still challenging. Herein, we constructed a DNA tetrahedral-structured probe (TSP)-mediated microfluidic magnetic detection system (μFMS) to provide a rapid and sensitive platform for analyzing TDEs. CD63 aptamer-modified Fe₃O₄ magnetic nanoparticles (MNPs) were constructed to form magnetic nano-report probes (MNRs). The microfluidic chips were fabricated from glass functionalized with DNA TSP-modified aldehyde groups and a PDMS layer designed with serpentine microchannels. An induction coil-based magnetic detector was used to measure the magnetic signal. The linear dynamic range of the μFMS system for TDE assays was 1.98 × 10³-1.98 × 10⁷ particles/mL with a limit of detection of 1.98 × 10³ particles/mL in PBS. There was no significant difference in TDE detection between the simulated serum and PBS, which indicated the feasibility of the constructed μFMS system for TDE analysis in complex biological systems. In terms of cost, reaction time and operation procedure, this μFMS has the potential to be developed as a clinical point-of-care testing tool for cancer diagnosis and therapeutics.

Keywords: Biosensors; Microfluidics.