Magnetic DNA random access memory with nanopore readouts and exponentially-scaled combinatorial addressing

Abstract

The storage of data in DNA typically involves encoding and synthesizing data into short oligonucleotides, followed by reading with a sequencing instrument. Major challenges include the molecular consumption of synthesized DNA, issues with basecalling errors, and limitations with scaling up read access operations for individual data elements. Addressing these challenges, we describe a DNA storage system called MDRAM (Magnetic DNA-based Random Access Memory) that enables repetitive and efficient readouts of targeted files with nanopore-based sequencing. Through conjugation of synthesized DNA to magnetic beads, we enabled repeated readouts of data while preserving the original DNA analyte and maintaining data readout quality. MDRAM also utilizes an efficient convolutional coding scheme that leverages soft information in raw nanopore sequencing signals to achieve information reading costs comparable to Illumina sequencing despite substantially higher error rates. Finally, we demonstrate a proof-of-concept DNA-based proto-filesystem that enables an exponentially-scalable data address space using only small numbers of targeting primers for assembly and readout.

Combinatorial PCR Method for Efficient, Selective Oligo Retrieval from Complex Oligo Pools

“…In alternative, hierarchical addressing methods, having a nested primer architecture allows for more file labels with the same number of primers. ,, For example, in recent work, with a universal reverse primer and two nested forward primers, 10 primers can uniquely identify and retrieve 72 files; this work’s method can uniquely identify 25 files (Figure ), and in contrast, with 10 primers, the traditional “one unique primer at each end” method can uniquely identify only five files (Figure ). However, while the hierarchical primer design is the most primer efficient method to date, there are several key drawbacks.…”