biostudies-literatureBanal JLUnited States Department of Defense | United States Navy | Office of Naval ResearchUnited States Department of Defense | United States Army | U.S. Army Research, Development and Engineering Command | Army Research OfficeBurroughs Wellcome FundNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of HealthNational Science Foundation1272-1280https://www.ebi.ac.uk/biostudies/studies/S-EPMC8564878biostudies-literatureUnknown20(9)DNA is an ultrahigh-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and if random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible. Here, we demonstrate a path to overcome the second barrier by encapsulating data-encoding DNA file sequences within impervious silica capsules that are surface labelled with single-stranded DNA barcodes. Barcodes are chosen to represent file metadata, enabling selection of sets of files with Boolean logic directly, without use of amplification. We demonstrate random access of image files from a prototypical 2-kilobyte image database using fluorescence sorting with selection sensitivity of one in 10⁶ files, which thereby Nature materialsRandom access DNA memory using Boolean search in an archival file storage system.PMC8564878N00014-12-1-0621Grant # 1122374N00014-17-1-2609F32CA236425CBET-1729397CCF-1956054CCF-1564025F32 CA236425N00014-18-1-2290W911NF-19-2-0026Reyes MBerleant JHuang HBlainey PCShepherd TRBathe MBanal JLAckerman CMfalseRandom access DNA memory using Boolean search in an archival file storage system.DNA is an ultrahigh-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and if random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible. Here, we demonstrate a path to overcome the second barrier by encapsulating data-encoding DNA file sequences within impervious silica capsules that are surface labelled with single-stranded DNA barcodes. Barcodes are chosen to represent file metadata, enabling selection of sets of files with Boolean logic directly, without use of amplification. We demonstrate random access of image files from a prototypical 2-kilobyte image database using fluorescence sorting with selection sensitivity of one in 10⁶ files, which thereby 2021-01-01T00:00:00Z2021 Sep2025-04-22T09:15:09.44Z2025-04-05T22:56:48.426ZS-EPMC85648783411297510.1038/s41563-021-01021-3