Bead‐Based DNA Synthesis and Sequencing for Integrated Data Storage Using Digital Microfluidics

Abstract DNA is considered as a prospective candidate for the next‐generation data storage medium, due to its high coding density, long cold‐storage lifespan, and low energy consumption. Despite these advantages, challenges remain in achieving high‐fidelity, fully integrated, and cost‐efficient DNA storage system. In this study, a homemade digital microfluidic (DMF)‐based compact DNA data storing pipeline is orchestrated to complete the entire process from the synthesis to the sequencing. The synthetic half employs phosphoramidite chemistry on 200 nm magnetic beads (MBs), where the dimethyltrityl protecting group is removed by droplet manipulation of trichloroacetic acid. The sequencing counterpart relies on pyrophosphate releasing originated from polymerase‐catalyzed primer extension, which leads to photon‐countable chemiluminescence (CL) signal in 2.5‐μL drops of trienzyme cascading reactions. Further by DNA denaturation, repeated pyrosequencing plus plurality voting can improve the nucleobase accuracy beyond 95 %. As a proof‐of‐concept trial, semantic information is saved in DNA via the Huffman coding algorithm plus the Reed‐Solomon error‐correction, and then robustly retrieved from this streamlined platform. As a result, it took a net total of approximately 6.5 h to writing and reading 8 bytes of data, that equal to a storaging speed of 49 min/byte, much quicker than the previously reported 2.8–4.2 h/byte. This bead‐based miniaturized device promises an unattended protocol for achieving high‐throughput, full‐packaged, and above all, neatly precision DNA storage.