Self-assembly of long ssDNA scaffolds (M13mp18, ~7249nt) into DNA origami structures has been recognized as versatile programmable platform with applications across many fields. From drug delivery to molecular machinery, templated material synthesis, and breadboards for nanolithography, etc. they are desirable for their ability to spatially organize molecules on the nanometer scale in various user-defined shapes due to their unique addressability. However, characterization of these structures has hitherto been limited to qualitative analytical techniques which precludes the acquisition of robust information such as yield, size, and nature of the intermediates in the assembly process which are useful for downstream applications such as drug delivery and molecular machinery. Conventional quantitative techniques such as mass spectrometry fail owing to inherent sample heterogeneity and the megadalton sizes of these structures. Here, we demonstrate charge detection mass spectrometry (CDMS) as a viable quantitative technique for characterizing DNA origami. CDMS, a single particle technique that simultaneously measures the mass to charge ratio and charge on each ion, was used to analyze DNA origami gear structures. Data obtained indicated the presence of complete structures, incomplete structural intermediates, and the release of bound oligonucleotides. These findings not only demonstrate CDMS’ ability to characterize DNA origamis, but it also reveals its viability as an imperative tool for probing the efficacy of downstream applications involving DNA origami, such as DNA origami-based enzyme replacement therapy or gene therapy.

Quantitative characterization of DNA origami structures using charge detection mass spectrometry

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