Reading mixtures of uniform sequence-defined macromolecules to increase data storage capacity

Abstract

In recent years, the field of molecular data storage has emerged from a niche to a vibrant research topic. Herein, we describe a simultaneous and automated read-out of data stored in mixtures of sequence-defined oligomers. Therefore, twelve different sequence-defined tetramers and three hexamers with different mass markers and side chains are successfully synthesised via iterative Passerini three-component reactions and subsequent deprotection steps. By programming a straightforward python script for ESI-MS/MS analysis, it is possible to automatically sequence and thus read-out the information stored in these oligomers within one second. Most importantly, we demonstrate that the use of mass-markers as starting compounds eases MS/MS data interpretation and furthermore allows the unambiguous reading of sequences of mixtures of sequence-defined oligomers. Thus, high data storage capacity considering the field of synthetic macromolecules (up to 64.5 bit in our examples) can be obtained without the need of synthesizing long sequences, but by mixing and simultaneously analysing shorter sequence-defined oligomers.

Molecular data storage with zero synthetic effort and simple read-out

“…Further methods to increase the complexity of the repeating units rely on dual side chain 52 , 53 , backbone and side chain 54 , 55 , dual side chain and backbone 56 or dual side chain and dual backbone 57 control and were successfully decoded applying tandem MS analysis. The read-out of mixtures of sequence defined oligomers (three hexamers, up to 64 bits in total), avoiding the synthesis of longer sequences, was recently reported by our working group 58 .…”

“…Thus, writing the data and the subsequent manual decoding reach their limits. For writing, increasingly automated synthesis and chemical printers are used, and software is being developed for processing the amount of data and reading out the original information 47 , 58 , 69 .…”

Fabrication and Decryption of a Microarray of Digital Dithiosuccinimide Oligomers

“…Therefore, a large amount of data can be encoded into DNA strings and decoded by DNA sequencing with the development of the high throughput microarray techniques ( Scheme a). [ 4–18 ] Inspired by this, chemists demonstrated sequence‐defined synthetic polymer can be used as an alternative data recorder, termed as digital polymer by Lutz et al [ 19–21 ] By employing two different monomers regarded as binary codes “0” and “1,” binary digital message can be encoded in the polymer chain through iterative synthetic strategies [ 22–35 ] and retrieved by tandem mass spectrometry (MS/MS) [ 36–46 ] as well as nanopore‐sequencing technique. [ 47,48 ] Compared to DNA, digital polymer displays higher chemical stability, better compatibility, and broader structural designability, [ 24,34,49,50 ] which improve the storage capacity [ 28,29,51–56 ] and facilitate decoding process [ 34,43,57–61 ] as well as applications.…”

“…[ 4–18 ] Inspired by this, chemists demonstrated sequence‐defined synthetic polymer can be used as an alternative data recorder, termed as digital polymer by Lutz et al [ 19–21 ] By employing two different monomers regarded as binary codes “0” and “1,” binary digital message can be encoded in the polymer chain through iterative synthetic strategies [ 22–35 ] and retrieved by tandem mass spectrometry (MS/MS) [ 36–46 ] as well as nanopore‐sequencing technique. [ 47,48 ] Compared to DNA, digital polymer displays higher chemical stability, better compatibility, and broader structural designability, [ 24,34,49,50 ] which improve the storage capacity [ 28,29,51–56 ] and facilitate decoding process [ 34,43,57–61 ] as well as applications. [ 44,53,62–66 ] While most of the efforts have been spent on novel structure and application design of digital polymers, few attentions were paid to implement the basic function of digital polymers, that is, designing a practical storing device or carrier of digital polymers for arbitrary writing and reading information in a reliable manner.…”

“…Therefore, a large amount of data can be encoded into DNA strings and decoded by DNA sequencing with the development of the high throughput microarray techniques (Scheme 1a). [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Inspired by this, chemists demonstrated sequence-defined synthetic polymer can be used as an alternative data recorder, termed as digital polymer by Lutz et al [19][20][21] By employing two different monomers regarded as binary codes "0" and "1," binary digital message can be encoded in the polymer chain through iterative synthetic strategies [22][23][24][25][26][27][28][29][30][31][32][33][34][35] and retrieved by tandem mass spectrometry (MS/MS) [36][37][38][39][40][41][42][43][44][45][46] as well as nanopore-sequencing technique. [47,48] Compared to DNA, digital polymer displays higher chemical stability, better compat...…”