Label-free electrical monitoring of nucleic acid amplification with integrated hydrogel ionic diodes

Chenwei Xiong; Jie Li; Luyao Li; Long Chen; Rong Zhang; Xianqiang Mi; Yifan Liu

doi:10.1016/j.mtbio.2022.100281

Label-free electrical monitoring of nucleic acid amplification with integrated hydrogel ionic diodes

Mater Today Bio. 2022 May 11:15:100281. doi: 10.1016/j.mtbio.2022.100281. eCollection 2022 Jun.

Authors

Chenwei Xiong¹, Jie Li¹, Luyao Li¹, Long Chen^{1

2

3}, Rong Zhang¹, Xianqiang Mi^{2

3

4

5

6}, Yifan Liu¹

Affiliations

¹ Division of Chemistry and Physical Biology, School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
² Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China.
³ University of Chinese Academy of Sciences, Beijing, 100049, China.
⁴ Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
⁵ Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, 310024, China.
⁶ Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.

Abstract

We demonstrate here for the first time the utility of a monolithically integrated hydrogel ionic diode for label-free quantitative DNA detection and real-time monitoring of nucleic acid amplification. The hydrogel ionic diode presented herein, unlike nanomaterial-based field-effect biosensors, features high cost-effectiveness and convenient fabrication. This is realized by patterning a micrometer-sized heterojunction consisting of adjacent segments of polycationic and polyanionic hydrogels on a microfluidic chip through simple photocuring steps. The integrated diode rectifies ionic currents being sensitive to the charge of DNA adsorbed onto the polycationic chains through electrostatic associations. Based on the mechanism, we show that the ionic biosensor can electrically quantify DNA in a dynamic range relevant to typical nucleic acid amplification assays. Utilizing the device, we demonstrate the evaluation of a PCR assay amplifying a 500-bp DNA fragment of E. coli, an infection-causing pathogen, and real-time in situ monitoring of an isothermal assay amplifying E. coli whole genome. We anticipate that the device could potentially pave the way for miniaturized optics-free platforms for quantifying nucleic acid amplification at point-of-care.

Keywords: Electrical biosensor; Hydrogel; Ionic diode; Nucleic acid; Point-of-care.