Scalable Nucleic Acid Storage and Retrieval Using Barcoded Microcapsules

Rapid advances in nucleic acid sequencing and synthesis technologies have spurred a major need to collect, store, and sequence the DNA and RNA from viral, bacterial, and mammalian sources and organisms. However, current approaches to storing nucleic acids rely on a low-temperature environment and require robotics for access, posing challenges for scalable and low-cost nucleic acid storage. Here, we present an alternative method for storing nucleic acids, termed Preservation and Access of Nucleic aciDs using barcOded micRocApsules (PANDORA). Nucleic acids spanning kilobases to gigabases and from different sources, including animals, bacteria, and viruses, are encapsulated into silica microcapsules to protect them from environmental denaturants at room temperature. Molecular barcodes attached to each microcapsule enable sample pooling and subsequent identification and retrieval using fluorescence-activated sorting. We demonstrate quantitative storage and rapid access to targeted nucleic acids from a pool emulating standard retrieval operations implemented in conventional storage systems, including recovery of 100,000-200,000 samples and Boolean logic selection using four unique barcodes. Quantitative polymerase chain reaction and short-read sequencing of the retrieved samples validated the sorting experiments and the integrity of the released nucleic acids. Our proposed approach offers a scalable long-term, room-temperature storage and retrieval of nucleic acids with high sample fidelity.