Aerolysin nanopores decode digital information stored in tailored macromolecular analytes

Abstract

Digital data storage is a growing need for our society and finding alternative solutions than those based on silicon or magnetic tapes is a challenge in the era of “big data.” The recent development of polymers that can store information at the molecular level has opened up new opportunities for ultrahigh density data storage, long-term archival, anticounterfeiting systems, and molecular cryptography. However, synthetic informational polymers are so far only deciphered by tandem mass spectrometry. In comparison, nanopore technology can be faster, cheaper, nondestructive and provide detection at the single-molecule level; moreover, it can be massively parallelized and miniaturized in portable devices. Here, we demonstrate the ability of engineered aerolysin nanopores to accurately read, with single-bit resolution, the digital information encoded in tailored informational polymers alone and in mixed samples, without compromising information density. These findings open promising possibilities to develop writing-reading technologies to process digital data using a biological-inspired platform.

Efficient molecular encoding in multifunctional self-immolative urethanes

“…Most synthetic sequence-defined oligomers are characterized by tandem mass spectrometry (MS/MS) 10 - 12 , 14 - 17 , 26 , 31 , 34 or, more recently, with a mutated nanopore. 35 , 36 In both cases, detectable variations in the monomers become difficult to elucidate and, as a result, are often limited to binary or two unique monomers per information-containing oligomer. In fact, careful examination of some of the MS/MS methods reported in previous encoding/decoding schemes reveal that the code can be difficult to decipher without prior knowledge of the structures of the molecules being used.…”

Large Sequence-Defined Supramolecules Obtained by the DNA-Guided Assembly of Biohybrid Poly(phosphodiester)s

“…Abiotic digital poly(phosphodiester)s can be decoded using different sequencing techniques 39 such as tandem mass spectrometry 40 and nanopore sequencing. 41 Figure 1b shows the general molecular structure of the bio-hybrid polymers synthesized herein. Three different types of macromolecules were prepared: triblocks 5'-DNA-b-PPDE-b-DNA-3' and diblocks 5'-DNAb-PPDE-3' and 5'-PPDE-b-DNA-3'.…”

The NEOtrap – en route with a new single-molecule technique

“…A library of fingerprints can be collected (Figure 3B) and used as a training set for pattern recognition algorithms to facilitate the label-free identification of protein mixtures. Such machine-learningenhanced sensing approaches (Arima et al, 2018;Cao et al, 2020;Meyer et al, 2020) may provide a basis for single-cell proteomics in the future. In all this, the label-free aspect is a key advantage of the NEOtrap as that provides the option of direct measurements of scarce and nonpurified biological samples, such as lysate, blood, sweat, saliva (Galenkamp et al, 2018;Sze et al, 2017) without additional preprocessing.…”