DNA storage in thermoresponsive microcapsules for repeated random multiplexed data access

DNA has emerged as an attractive medium for archival data storage due to its durability and high information density. Scalable parallel random access to information is a desirable property of any storage system. For DNA-based storage systems, however, this still needs to be robustly established. Here we report on a thermoconfined polymerase chain reaction, which enables multiplexed, repeated random access to compartmentalized DNA files. The strategy is based on localizing biotin-functionalized oligonucleotides inside thermoresponsive, semipermeable microcapsules. At low temperatures, microcapsules are permeable to enzymes, primers and amplified products, whereas at high temperatures, membrane collapse prevents molecular crosstalk during amplification. Our data show that the platform outperforms non-compartmentalized DNA storage compared with repeated random access and reduces amplification bias tenfold during multiplex polymerase chain reaction. Using fluorescent sorting, we also demonstrate sample pooling and data retrieval by microcapsule barcoding. Therefore, the thermoresponsive microcapsule technology offers a scalable, sequence-agnostic approach for repeated random access to archival DNA files. Microcompartments with a temperature-responsive membrane are used to stably localize DNA-encoded files, which enables parallel, repeated polymerase-chain-reaction-based random access and DNA file sorting using fluorescent barcodes.

Automated summary

DNA, as a data storage medium, has the advantages of durability and high information density. This study proposes a thermoconfined polymerase chain reaction technology that enables multiplexed, repeated random access to DNA files within microcapsules. The technology utilizes biotin-functionalized oligonucleotides localized inside thermoresponsive, semipermeable microcapsules, which are permeable at low temperatures and prevent molecular crosstalk during amplification at high temperatures. The results show that this technology outperforms non-compartmentalized DNA storage, reducing amplification bias and enabling sample pooling and data retrieval by microcapsule barcoding. Therefore, the thermoresponsive microcapsule technology provides a scalable, sequence-agnostic approach for repeated random access to archival DNA files.