Ratiometric detection of lithium ions in serum and living cells using DNAzyme-assisted hybridization chain reaction

Lithium, a first-line mood stabilizer for bipolar disorder (BD), presents challenges due to its narrow therapeutic window (0.6–1.2 mM) and potential side effects in overdose. Hence, it is crucial to accurately and sensitively detect lithium ions (Li+) in serum and living cells for timely monitoring of BD progression and gaining mechanistic insight into lithium-based therapy. In this study, we design a Li+-responsive DNAzyme-HCR amplifier by combining hybridization chain reaction (HCR) and the Li+-specific DNAzyme. The presence of Li+ catalytically cleaves the DNAzyme, releasing the embedded HCR DNA trigger and generating numerous DNAzyme-assisted HCR products, ultimately activating the fluorescence resonance energy transfer response. Our results demonstrate that the DNAzyme-HCR amplifier enables amplified Li+ detection in serum, which are consistent with the results obtained using the inductively coupled plasma optical emission spectroscopy (ICP-OES) method. Furthermore, the DNAzyme-HCR amplifier allows for Li+ imaging in living cells, showing promising potential in monitoring treatment effects against BD.