Isotope Dilution DNA Logic Circuits for Multiple Output and Absolute Quantification

• Published in: Analytical chemistry (Washington) Vol. 97; no. 12; pp. 6670 - 6677
• Main Authors: Zhu, Yiyan, Wei, Chao, Li, Ziyan, Li, Yan, Liu, Rui, Lv, Yi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.04.2025
• Subjects: analytical chemistry; Biomarkers; Circuits; Computation; Computers, Molecular; Deoxyribonucleic acid; Dilution; DNA; DNA - chemistry; DNA probes; Gadolinium isotopes; Humans; International System of Units; isotope dilution technique; Isotopes; Isotopes - chemistry; lanthanides; Lanthanoid Series Elements - chemistry; Logic circuits; Mass Spectrometry; Mass spectroscopy; microRNA; MicroRNAs - analysis; miRNA
• ISSN: 0003-2700; 1520-6882; 1520-6882
• DOI: 10.1021/acs.analchem.4c06637

DNA logic circuits have gained great success in the past, thanks to their distinct performance regarding the scalability and correctness of computation. However, there are still two challenges often considered for DNA logic circuit-based computation. First, the mainstream optical probes are often subject to spectral overlapping interference for complex multitask analysis and outputs. Second, absolute quantification results traceable to the primary international system of units are mission impossible, especially for interlaboratory comparisons and quality assurances. Herein, we constructed DNA logic circuits encoded with lanthanide isotopes and decoded by elemental mass spectrometry. The 155Gd-enriched isotope and 145Nd-enriched isotope were incorporated in the DNA logic circuits for the isotope dilution-based absolute quantification of microRNAs. The proposed isotopic DNA logic circuits greatly enhance the multiplexity and computation accuracy, which poses a great potential for cancer biomarker-related diagnosis.