Development of ratiometric electrochemical molecular switches to assay endogenous formaldehyde in live cells, whole blood and creatinine in saliva

Sakthivel Kumaravel, Shao Hsuan Wu, Guan Zhang Chen, Sheng Tung Huang, Chun Mao Lin, Yu Chieh Lee, Ching Hui Chen

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Formaldehyde is a reactive carbonyl species (RCS) that is produced naturally in the human body via metabolic and epigenetic biochemical processes, yet in high concentrations is highly toxic to the environment as well as to living organisms. Therefore, we designed two ratiometric electrochemical molecular redox probes, Formaldehyde oxidative latent probe (FOLP) and dihydroxy-formaldehyde oxidative latent probe (HFOLP), for the selective profiling of endogenous formaldehyde. FOLP and HFOLP each underwent the aza-Cope reaction with formaldehyde followed by hydrolysis to eliminate unmask redox reporter N-alkylated aminoferrocene (AAF) to monitor their response current. The FOLP and HFOLP sensors showed broad dynamic ranges of 0.12–1000 μM and 0.09–3 mM for formaldehyde with detection limits of 48.2 nM and 31.6 μM, respectively. Also, since formaldehyde is the byproduct of biochemical reactions for detecting creatinine and creatinine is an important biomarker for chronic kidney disease (CKD), we tested the FOLP probe for its ability to monitor creatinine. It successfully did so, and this ability was used to develop an electrochemical platform for the quantification of creatinine; it showed a dynamic range of 3.25–200 μM and a limit of detection (1.3 μM). In addition, the FOLP-based assay platform delivered a reliable analytical performance for the quantification of formaldehyde in human whole blood and of creatinine in saliva, and also for the real-time monitoring of endogenous formaldehyde secretion in HeLa cells. Moreover, the concentrations determined using our method were found to be consistent with those determined using formaldehyde and creatinine fluorometric assay kits.

Original languageEnglish
Article number112720
JournalBiosensors and Bioelectronics
Publication statusPublished - Jan 1 2021


  • Creatinine detection
  • Electrochemical probes
  • Formaldehyde
  • Real-time profiling
  • Salivary creatinine
  • Whole blood assay

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biomedical Engineering
  • Electrochemistry


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