Cited by 235DNA and Biological ComputingAdvanced biosensing and bioanalysis techniquesNanopore and Nanochannel Transport Studies

Emerging Approaches to DNA Data Storage: Challenges and Prospects

Open access
Doricchi, Andrea, Platnich, Casey M., Gimpel, Andreas, Horn, Friederikee, Earle, Max, Lanzavecchia, German, Cortajarena, Aitziber L., Liz-Marzán, Luis M. +6 more·2022·ACS Nano

Abstract

. As such, data production will far exceed the capacity of currently available storage methods. The costs of maintaining and transferring data, as well as the limited lifespans and significant data losses associated with current technologies also demand advanced solutions for information storage. Nature offers a powerful alternative through the storage of information that defines living organisms in unique orders of four bases (A, T, C, G) located in molecules called deoxyribonucleic acid (DNA). DNA molecules as information carriers have many advantages over traditional storage media. Their high storage density, potentially low maintenance cost, ease of synthesis, and chemical modification make them an ideal alternative for information storage. To this end, rapid progress has been made over the past decade by exploiting user-defined DNA materials to encode information. In this review, we discuss the most recent advances of DNA-based data storage with a major focus on the challenges that remain in this promising field, including the current intrinsic low speed in data writing and reading and the high cost per byte stored. Alternatively, data storage relying on DNA nanostructures (as opposed to DNA sequence) as well as on other combinations of nanomaterials and biomolecules are proposed with promising technological and economic advantages. In summarizing the advances that have been made and underlining the challenges that remain, we provide a roadmap for the ongoing research in this rapidly growing field, which will enable the development of technological solutions to the global demand for superior storage methodologies.

AI snapshot

Written from the paper’s full text.

TL;DR

This review surveys sequence-based and structure-based DNA data storage, arguing that DNA offers exceptional density and longevity but remains noncompetitive because of slow writing/reading and high cost. It outlines advances in synthesis, storage, random access, sequencing, error correction, and DNA nanotechnology, and proposes hybrid approaches for archival storage.

Key findings

  • Global data storage demand is predicted to reach 1.75 × 10^14 GB by 2025, while current storage media have a maximum density of 10^3 GB/mm^3; DNA has a theoretical density of 6 bits per 1 nm of polymer, or ∼4.5 × 10^7 GB/g.
  • Sequence-based DNA storage is estimated at 800 million USD per terabyte versus about 15–16 USD/TB for tape; current writing speed is on the order of kilobytes/second, with a need for gigabytes/second, leaving gaps of 6 orders of magnitude in writing and 2–3 orders in reading.
  • Storage protection trades longevity against density: Table 1 reports dried DNA at 17,000 PB/g with a 7-year half-life at 10 °C, DNAshell at >100,000 years but only 0.0034 PB/g, silica particles at 580 PB/g and 540 years, and salt matrices at 3400 PB/g and 750 years; random access has been demonstrated at a 5.5 TB pool size.
  • Structure-based DNA storage can be erased and rewritten via self-assembly but requires ∼100 base pairs per bit, still about 3 orders of magnitude denser than current hard drives; nanopore readout can read a DNA hard drive on the millisecond time scale, with a 3-bit barcode assigned at 94% accuracy and up to 10 structural colors.

Methods

  • This is a review article comparing “sequence-based” and “structure-based” DNA data storage across encoding, writing, storage, random access, reading, decoding, and DNA nanotechnology/computation.
  • It synthesizes prior literature and tabulated data; no new experimental samples or primary data are reported. The main analysis is qualitative and comparative, using metrics from cited studies.

Limitations

  • Stated: DNA data storage is currently limited by low writing and reading speed, high cost per byte, storage degradation, random-access constraints, and unresolved optimal error correction for high insertion/deletion error rates; structure-based methods have lower density because they require ∼100 base pairs per bit.
  • Stated: long-term stability of noncovalently assembled DNA nanostructures, encapsulation/retrieval in matrices, and readability after prolonged freezing need further study, and systematic decay studies are missing.
  • Evident: as a review, it does not present original experiments, and its cost/speed figures are drawn from cited works and may not reflect later developments.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1021/acsnano.2c06748

Cites

155 of 155 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 220 cited sources checked · 0 supported · 0 flagged

  • Findingreasoning

    Generally, all storage approaches trade long-term stability with a decrease in storage density by 1-3 orders of magnitude, caused by the low loading ratio between DNA and carrier.

    “Generally, all storage approaches trade long-term stability with a decrease in storage density by 1–3 orders of magnitude, caused by the low loading ratio between DNA and carrier (see Table 1).”
    Quote in the paperNot a substantial claim
  • Premisecitation

    DNA molecules are stable for thousands of years under suitable storage conditions.

    “these molecules are stable for thousands of years under suitable storage conditions;4”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Premisecitation

    The global data storage demand is predicted to grow to 1.75 × 10^14 GB by 2025.

    “the global data storage demand is predicted to grow to 1.75 × 1014 GB by 2025.”
    • Also stated in: § Introduction · hedged
      “the global demand for data storage expected to grow up to 1.75 × 1014 GB by 2025”
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  • Premisecitation

    DNA nanotechnology can create arbitrary two- and three-dimensional shapes using the specific base-pairing properties of the nitrogenous bases.

    “DNA nanotechnology harnesses the specific base-pairing properties of the nitrogenous bases to create arbitrary two- and three-dimensional shapes.24”
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  • Interpretationreasoning

    One potential strategy to circumvent the pitfalls of sequence-based DNA data storage is to rely on the programmable three-dimensional structure of DNA as opposed to its primary sequence.

    “One potential strategy to circumvent these pitfalls is to rely on the programmable three-dimensional structure of DNA as opposed to its primary sequence (Figure 2c,d).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 45
  • May combine two claims. 99
  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Findingnone given

    Currently, long-term storage is only feasible within a protective material and at DNA loadings of only a few percent.

    “Currently, long-term storage is only feasible within a protective material and at DNA loadings of only a few percent.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    DNA has a theoretical data density of 6 bits for every 1 nm of polymer, or ∼4.5 × 10^7 GB/g, which is orders of magnitude higher than the densities achievable using traditional devices.

    “On the basis of its physical dimensions, DNA has a theoretical data density of 6 bits for every 1 nm of polymer, or ∼4.5 × 107 GB/g,6 which is orders of magnitude higher than the densities achievable using traditional devices.7,8”
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    Premisecitation

    Current storage technologies, including optical and magnetic devices, are reaching their information density limits and are not suitable for long-term (>50 years) storage.

    “Current storage technologies, including optical and magnetic devices, are reaching their information density limits and are thus not suitable for long-term (>50 years) storage”
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    Interpretationcitation

    The dynamic nature of DNA nanostructure assemblies can be exploited to perform data operations, allowing DNA data storage to integrate directly into DNA computation.

    “Moreover, the dynamic nature of these assemblies can be exploited to perform data operations,13,27 which allows DNA data storage to integrate directly into the field of DNA computation.”
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    Premisecitation

    De novo synthesis of long sequences of DNA remains challenging, so sequences must be broken into smaller fragments of ∼200 bases, requiring massive numbers of unique DNA sequences.

    “Because the de novo synthesis of long sequences of DNA remains challenging,20 these sequences must be broken into smaller fragments (∼200 bases), which requires massive numbers of unique DNA sequences to be made.”
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    Premisenone given

    Phosphoramidite synthesis requires the use of anhydrous solvents, which produce toxic waste.

    “While there are many advantages to phosphoramidite synthesis, it is worth noting that it requires the use of anhydrous solvents, which produce toxic waste.”
    Quote in the paperNot a substantial claim
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    Premisecitation

    With current technologies, DNA storage is estimated to cost 800 million USD per terabyte of data, whereas tape storage costs approximately 15 USD per terabyte.

    “With the use of current technologies, DNA storage is estimated to cost 800 million USD per one terabyte of data (by contrast, tape storage costs approximately 15 USD per terabyte).12”
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    Interpretationcitation

    Because DNA nanotechnology-based approaches capitalize on self-assembly, the resulting structures are inherently reconfigurable, enabling data erasing and rewriting without further synthesis.

    “Because DNA nanotechnology-based approaches capitalize on the self-assembly of DNA sequences, the resulting structures are inherently reconfigurable, which enables data erasing and rewriting without further synthesis.26”
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    Premisenone given

    DNA sequencing readout often relies on fluorescence outputs, which require expensive fluorophores, optical equipment, trained personnel, substantial amounts of DNA, and long reading times.

    “Sequencing often relies on fluorescence outputs, which require expensive fluorophores, optical equipment, and trained personnel, as well as substantial amounts of DNA and long reading times (Figure 2a,b).”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    DNA will never become obsolete as a data storage medium.

    “As such, DNA will never become obsolete as a data storage medium.”
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    Premisecitation

    Photomask arrays have proven to generate high oligonucleotide densities but rely on a series of bespoke photolithographic masks for each set of desired sequences.

    “To this end, photomask arrays have proven to generate high oligonucleotide densities;34 however, this technique relies on a series of bespoke photolithographic masks to synthesize a defined set of sequences, that is, masks must be created for each set of desired sequences.”
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    Interpretationreasoning

    Structure-based methods eliminate the need for next-generation sequencing, which remains among the most time-consuming aspects of DNA data storage.

    “These structure-based methods also eliminate the need for next-generation sequencing, which remains among the most time-consuming aspects of DNA data storage.”
    Quote in the paperSubstantial claim
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    Interpretationcitation

    Enzymatic DNA synthesis is expected to become both cheaper and faster than phosphoramidite synthesis for data storage applications.

    “this approach is expected to become both cheaper and faster than phosphoramidite synthesis for data storage applications.40”
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    Premisenone given

    So far, only tiny amounts of data (hundreds of bits) have been stored using enzymatic synthesis versus data consisting of billions of bits using phosphoramidite synthesis.

    “So far, only tiny amounts of data (hundreds of bits) have been stored using enzymatic synthesis versus data consisting of billions of bits using phosphoramidite synthesis.”
    Quote in the paperNot a substantial claim
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    Premisecitation

    Nguyen et al. produced an electrode array and demonstrated independent electrode-specific control of DNA synthesis with electrode sizes and pitches that enabled a synthesis density of 25 million oligonucleotides/cm2.

    “For example, Nguyen et al.35 produced an electrode array and demonstrated independent electrode-specific control of DNA synthesis with electrode sizes and pitches that enabled a synthesis density of 25 million oligonucleotides/cm2 (Figure 3C).”
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    Interpretationreasoning

    Information can be stored in the 3D structures of DNA assemblies instead of in the sequence, with readout relying on imaging techniques or single-molecule nanopore measurements.

    “Information can thus be stored in the 3D structures of these assemblies instead of in the sequence, with readout relying on imaging techniques, such as super resolution imaging,22 or using single-molecule nanopore measurements.23,25”
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    Premisenone given

    PCR-based addressing is incompatible with common storage approaches, necessitating removal and re-embedding of the encoding DNA into the storage matrix for each random-access operation.

    “Lastly, PCR-based addressing is incompatible with common storage approaches, thus necessitating the removal and re-embedding of the encoding DNA into the storage matrix for each random-access operation.”
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    Premisecitation

    DNA decay by hydrolysis scales with the number of nucleotides per oligo, so a proportional increase in the expected number of errors is anticipated for longer oligos.

    “While both micro- and macroscopic storage systems are independent of sequence length, DNA decay by hydrolysis scales with the number of nucleotides per oligo and, thus, a proportional increase in the expected number of errors is anticipated.73”
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  • May combine two claims.

    Interpretationcitation

    The use of a physical substrate on which DNA can be arrayed may solve random access, but this approach and similar solutions relying on physical separation of individual oligos or oligo pools render DNA's density advantage obsolete.

    “Whereas the use of a physical substrate on which DNA can be arrayed may solve this problem,31 this approach and similar solutions relying on the physical separation of individual oligos or oligo pools render DNA’s density advantage obsolete.”
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    Premisereasoning

    Physical redundancy is achieved by creating many, sometimes inaccurate, copies of each sequence, which enables a consensus to be reached when the data is read.

    “Physical redundancy is achieved by creating many, sometimes inaccurate, copies of each sequence, which enables a consensus to be reached when the data is read.”
    Quote in the paperNot a substantial claim
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    Premisecitation

    PCR-based random access irreversibly removes oligos from the pool, which necessitates potentially lossy reamplification of the entire pool after repeated data retrieval.

    “Second, PCR-based random access irreversibly removes oligos from the pool, which necessitates potentially lossy reamplification of the entire pool after repeated data retrieval.75,76”
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    Interpretationnone given

    DNA barcodes on silica particles would likely decay much faster than the data-encoding DNA within, so random access would cease to function even if the data itself may still be intact.

    “While this represents a scalable random access scheme compatible with long-term storage, it is likely that the DNA barcodes on silica particles would decay much faster than the data-encoding DNA within so that random access ceases to function even if the data itself may still be intact.”
    Quote in the paperNot a substantial claim
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    Premisecitation

    Two key constraints of nanopore sequencing are its high error rate and the required sequence length.

    “two key constraints of the technology are its high error rate and the required sequence length.”
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    Premisecitation

    Beyond random access, other file operations such as encryption with genomic keys, erasure on the basis of obfuscation, and rewriting by chemical modification or PCR are also supported by sequence-based DNA data storage.

    “Beyond random access, other file operations such as encryption with genomic keys,79 erasure on the basis of obfuscation,80 and rewriting by chemical modification or PCR81,82 are also supported by sequence-based DNA data storage.”
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    Premisecitation

    Contrary to SBS, nanopore sequencing is able to identify modified and unnatural nucleotides such that readout of data encoded using an expanded molecular alphabet is possible.

    “Contrary to SBS, it is therefore also able to identify modified and unnatural nucleotides such that the readout of data encoded using an expanded molecular alphabet is possible.”
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  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    Complete and error-free retrieval of stored data must be guaranteed within a defined set of storage and sequencing conditions for DNA data storage to have commercial relevance.

    “the complete and error-free retrieval of stored data must be guaranteed within a defined set of storage and sequencing conditions in order for DNA data storage to have any commercial relevance.”
    Quote in the paperNot a substantial claim
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    Premisecitation

    The biotin-based physical separation approach allows the sample to be reused for subsequent retrievals and circumvents nonspecific binding and PCR-induced biases.

    “This approach has two key advantages: the sample can be reused for subsequent retrievals and nonspecific binding and PCR-induced biases are circumvented.78”
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    Premisecitation

    Storage mainly contributes to shifts in the copy number distribution of sequences, leading to unrecoverable loss of individual sequences over time, e.g., 8% after 94% of the DNA has decayed (four half-lives).

    “storage mainly contributes to shifts in the copy number distribution of the sequences, which leads to the unrecoverable loss of individual sequences over time, e.g., 8% after 94% of the DNA has decayed (i.e., four half-lives).”
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    Interpretationreasoning

    These constraints currently render nanopore sequencing more challenging and slower than SBS.

    “These constraints currently render nanopore sequencing more challenging and slower than SBS.”
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  • May combine two claims.

    Interpretationreasoning

    The process of combining oligo libraries via Gibson assembly or overlap extension PCR reintroduces difficult-to-automatize steps into the sequencing workflow, calling into question nanopore sequencing's claims of improved portability and ease of automation over SBS.

    “This process, usually performed via Gibson assembly or overlap extension PCR,70,81,86 reintroduces several difficult-to-automatize steps into the sequencing workflow, which calls the approach’s claims of improved portability and ease of automation over SBS into question.”
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  • May combine two claims.

    Interpretationreasoning

    The high error rate of nanopore sequencing necessitates clustering of sequence information, higher sequencing coverage, and additional postprocessing of sequencing data.

    “necessitates the clustering of sequence information, and thus, higher sequencing coverage and additional postprocessing of sequencing data.”
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    Premisecitation

    Insertions are uncommon and usually occur at less than 0.1% per nucleotide, mainly because of synthesis.

    “Insertions (addition of extra bases) are uncommon and usually occur at less than 0.1% per nt, mainly because of synthesis.”
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    Premisecitation

    The largest data size retrieved using nanopore sequencing is currently about 1.67 MB, compared with around 200 MB for SBS.

    “the largest data size retrieved using the technology is currently about 1.67 MB, compared with around 200 MB for SBS.”
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  • May combine two claims.

    Interpretationreasoning

    The use of SBS and nanopore sequencing for DNA data storage highlights a current trade-off between sequencing accuracy and cost, with implications for future scalability.

    “The use of both state-of-the-art SBS and rapidly developing nanopore sequencing for DNA data storage highlights the current trade-off between sequencing accuracy and cost, as well as implications for future scalability.”
    Quote in the paperSubstantial claim
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    Premisecitation

    Grass et al.'s encoding/decoding algorithm uses an outer code that can correct for loss of sequences, adds an index for each sequence to retrieve order, and uses an inner error-correcting code that can correct nucleotide errors within sequences.

    “It uses an outer code that can correct for the loss of sequences, adds an index for each sequence to be able to retrieve the order of the sequences that are lost during storage, and uses an inner error-correcting code that can correct nucleotide errors within sequences.”
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    Premisecitation

    The maximal information rate that an error-correcting code can achieve is theoretically bounded by the channel capacity, which depends on the characteristics of the noisy channel.

    “The maximal information rate that an error-correcting code can achieve is theoretically bounded.89 This bound is known as the channel capacity and depends on the characteristics of the noisy channel.”
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    Premisecitation

    Reed-Solomon code, Fountain codes, and LDPC code were used as an outer code.

    “A Reed–Solomon code,4,44,70 Fountain codes,14 and LDPC (low-density parity check) code were used as an outer code.91”
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    Premisecitation

    Goldman et al. used an error-correction code where each part of the information was written on four subsequent DNA sequences, so loss of sequences could be corrected if fewer than four subsequent sequences were lost.

    “A simple example of an error-correction code was used by Goldman et al.,9 where each part of the information was written on four subsequent DNA sequences. Thus, the loss of sequences could be corrected if fewer than four subsequent sequences were lost.”
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    Premisecitation

    Goldman et al.'s coding scheme was ill-suited for the used DNA channel because it had a low effective information rate and did not recover the whole message.

    “This coding scheme, however, was ill-suited for the used DNA channel because it had a low effective information rate, i.e., number of information bits per total number of encoded bits, and did not recover the whole message.”
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    Premisecitation

    Increasing physical redundancy to cluster sequence information alleviates the problem of sequence loss and errors but is undesirable and inefficient because it drastically lowers information density.

    “While an increase of physical redundancy to cluster sequence information alleviates this problem, doing so is undesirable and inefficient because it drastically lowers the information density.”
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    Premisereasoning

    In general, the outer code applies on the level of the original information, whereas the inner code protects single sequences or indices.

    “In general, the outer code applies on the level of the original information, whereas the inner code protects single sequences or indices.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Reed-Solomon code can correct up to e erasures and s substitutions with 2s + e additional symbols.

    “For example, the Reed–Solomon code can correct up to e erasures and s substitutions with 2s + e additional symbols.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    Different codes were used for the outer and inner codes.

    “However, different codes were used for the outer and inner codes.”
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    Premisecitation

    The inner-outer coding scheme cannot correct large error rates dominated by insertions and deletions because no inner codes exist that work sufficiently well on short sequences in these noisy setups.

    “However, it cannot correct large error rates that are dominated by insertions and deletions. This is because no inner codes exist that work sufficiently well on short sequences in these noisy setups.92”
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    The synthesis of DNA oligos for data storage was column-based and developed in the 1980s; since then, this process has been fully automated and now allows synthesis of 96-384 oligos simultaneously.

    “The synthesis of DNA oligos for data storage was column-based and was developed in the 1980s. Since then, this process has been fully automated, and now it allows the synthesis of 96–384 oligos simultaneously.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Blawat et al. proposed to protect the index separately with a bit-correcting code (BCH) as the inner code.

    “Blawat et al. proposed to protect the index separately with a bit-correcting code (BCH) as the inner code.”
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    Premisecitation

    DNA has become a promising tool for next-generation data storage since it provides high data capacity and storage density and can be stored in multiple ways over significant time periods.

    “DNA has become a promising tool for next-generation data storage since it provides high data capacity and storage density78 and it is possible to store it in multiple ways37 over significant time periods.4”
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    Interpretationnone given

    To make DNA data storage standard, some limitations must be overcome.

    “However, in order to make DNA data storage standard, some limitations must be overcome.”
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    Interpretationnone given

    Different synthesis and sequencing techniques might motivate different approaches.

    “Furthermore, different synthesis and sequencing techniques might motivate different approaches.”
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    Premisecitation

    Recent works have explored efficient clustering methods tailored to DNA data storage and efficient encoding schemes that allow recovery of a sequence from multiple noisy reads.

    “Recent works have explored the development of efficient clustering methods tailored to DNA data storage, as well as efficient encoding schemes that allow the recovery of a sequence from multiple noisy reads.93−96”
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    Premisenone given

    The capacity of deletion and insertion channels or reconstruction from multiple reads with the combination of different errors are not fully understood yet.

    “For example, the capacity of deletion and insertion channels or reconstruction from multiple reads with the combination of different errors are not fully understood yet.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Such codes could be used as an inner code.

    “Such codes could then be used as an inner code.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisereasoning

    Array-based synthesis processes were developed in the 1990s and lowered costs because of their high-throughput nature, with an average price per nucleotide down to 10-4 USD.

    “Array-based synthesis processes were developed in the 1990s. They lowered the costs because of their high-throughput nature, with an average price per nucleotide down to 10–4 USD.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In Antkowiak et al., noisy sequences were first clustered by similarity, then information on multiple erroneous copies was combined to construct a sequence with fewer errors via alignment and majority voting.

    “For example, in Antkowiak et al.,42 the noisy sequences were first clustered by similarity, then the information on multiple erroneous copies was combined to construct a sequence with fewer errors. This was achieved by an alignment step within the clusters and subsequent majority voting.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The total costs of synthesizing 1000 strands of 1000 nucleotide length would be 136 USD with recycled TdT, 2700 USD by phosphoramidite technique, and 136,000 USD if a fresh stock of TdT was introduced at every cycle.

    “The total costs of synthesizing 1000 strands of 1000 nucleotide length would be 136 USD with recycled TdT, 2700 USD by phosphoramidite technique, and 136 000 USD if a fresh stock of TdT was introduced at every cycle.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [100] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tape storage costs 7-8 orders of magnitude less than DNA data storage, about 16 USD/TB, with prices decreasing by 10% every year.

    “In comparison, tape storage costs 7–8 orders of magnitude less, i.e., about 16 USD/TB of data, with prices decreasing by 10% every year”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] source

      Not checked in the free run.

    • cites [98] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tang et al.'s strategy allowed the enhancement of the coding rate to more than log2 3 per unit time and avoidance of deletions.

    “This strategy allowed the enhancement of the coding rate to more than log23 per unit time and avoidance of deletions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Tang Y., 2021

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Automation could possibly lead to a reduction of the time costs for DNA data storage.

    “Besides economic costs, automation could possibly lead to a reduction of the time costs for DNA data storage, as well.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisenone given

    Enzymatic synthesis occurs in aqueous environments and yields longer strands; however, error rates need to be assessed.

    “It occurs in aqueous environments and it yields longer strands; however, error rates need to be assessed.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    This could be detrimental, especially when the only possible alternative to retrieve a file would be to read the entire database: it would be a very slow process.

    “This could be detrimental, especially when the only possible alternative to retrieve a file would be to read the entire database: it would be a very slow process.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationcitation

    In the 0.1% chemical yield case, the cost of photolithographic DNA storage would be ∼10 USD/TB, and synthesis conditions would be similar to surface chemistry (1000× reagent excess), demonstrating that optimization of chemical DNA synthesis processes is compatible with DNA data storage applications.

    “In the latter case, the cost of photolithographic DNA storage would be ∼10 USD/TB, and synthesis conditions would be similar to the one used in surface chemistry (1000× reagent excess), which demonstrates that an optimization of chemical DNA synthesis processes is compatible with DNA data storage applications.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In 2020, Antkowiak et al. proposed that synthesis costs will drop to around 10^6 USD/TB (2-3 orders of magnitude reduction) as a result of improved synthesis strategies, including large parallelization, optimization of reagents, and combination of nonvolatile DNA-based memories with logical operations.

    “In 2020, Antkowiak et al. proposed that synthesis costs will drop to around 106 USD/TB (i.e., 2–3 orders of magnitude reduction) as a result of improved synthesis strategies, including large parallelization, optimization of reagents, and combination of nonvolatile DNA-based memories with logical operations”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The combination of advanced error-correcting codes and synchronization algorithms could possibly achieve lower costs of enzymatic DNA synthesis, as recently reported by Tang et al.

    “The combination of advanced error-correcting codes and synchronization algorithms could possibly achieve lower costs of enzymatic DNA synthesis, as recently reported by Tang et al.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tang et al.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Antkowiak et al. estimated that with photolithography to synthesize 10,000 copies of each oligo, a nucleotide reagent cost of 100 USD/g, and a logical density equal to 1 bit/nucleotide, the cost of 1 TB of data stored in DNA would be ∼10-2 USD, with a chemical yield of 100%.

    “With the use of photolithography to synthesize 10 000 copies of each oligo, with a nucleotide reagent cost of 100 USD/g and a logical density equal to 1 bit/nucleotide, the cost of 1 TB of data stored in DNA would be ∼10–2 USD, with a chemical yield of 100%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    This is another pivotal reason for investigations about synthetic polymers as data storage tools, together with the mentioned high cost of DNA.

    “This is another pivotal reason for the investigations about synthetic polymers as data storage tools, together with the mentioned high cost of DNA.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The current writing speed for DNA archives is in the order of kilobytes/second, thus a reading/writing cycle has a significant cost in terms of time.

    “The current writing speed for DNA archives is in the order of kilobytes/second, thus a reading/writing cycle has a significant cost in terms of time.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    The maximum preservation time of information is 50 years for digital memories and 500 years for paper, while it is millennia for inorganic matrix-encapsulated DNA.

    “Indeed, the maximum preservation time of information is 50 years for digital memories and 500 years for paper, while it is millennia for inorganic matrix-encapsulated DNA.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Interpretationreasoning

    DNA data storage presents both advantages and disadvantages with respect to traditional storage methods regarding costs.

    “In conclusion, DNA data storage presents both advantages and disadvantages with respect to traditional storage methods regarding costs.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Considering the advantages of encoding information into the secondary structure-including ease of readout, synthetic simplicity, and reconfigurability-this is a minor obstacle and one that may be mitigated through the careful design of DNA nanostructures.

    “Considering the advantages of encoding information into the secondary structure—including ease of readout, synthetic simplicity, and reconfigurability—this is a minor obstacle and one that may be mitigated through the careful design of DNA nanostructures.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    Because of the self-assembled nature of DNA nanostructures, it is possible to significantly reduce the synthetic demand and to eliminate the need for next-generation sequencing for DNA data storage.

    “Because of the self-assembled nature of DNA nanostructures (Figure 8), it is possible to significantly reduce the synthetic demand and to eliminate the need for next-generation sequencing for DNA data storage.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Premisereasoning

    Through careful design of the sequences of these strands, exquisite control over their final assembly can be realized, enabling construction of nanoscale shapes and patterns.

    “Through careful design of the sequences of these strands, which can be easily synthesized in an automated manner or even purchased from commercial vendors, exquisite control over their final assembly can be realized, thereby enabling the construction of nanoscale shapes and patterns.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    DNA data storage must fulfill a gap of 6 orders of magnitude in regard to writing (synthesis) and a gap of 2-3 orders of magnitude in regard to reading (sequencing).

    “This means DNA data storage must fulfill a gap of 6 orders of magnitude in regard to the writing (i.e., synthesis) and a gap of 2–3 orders of magnitude in regard to the reading (i.e., sequencing).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    DNA origami is the most widely used method for the construction of DNA-based data storage structures at the nanoscale.

    “Among these, DNA origami is the most widely used method for the construction of DNA-based data storage structures at the nanoscale.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The main approaches in structural DNA nanotechnology can be divided into three groups: DNA origami, DNA tile assembly, and wireframe DNA structures.

    “The main approaches in structural DNA nanotechnology can be divided into three groups: DNA origami, DNA tile assembly, and wireframe DNA structures,104”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [104] source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    This density is still approximately 3 orders of magnitude higher than current hard drive technologies, with further improvements conceivable through the optimization of the 3D DNA structure.

    “That being said, this density is still approximately 3 orders of magnitude higher than current hard drive technologies, with further improvements conceivable through the optimization of the 3D DNA structure.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationcitation

    Reversible Watson-Crick base pairing means that data storage platforms based on DNA nanostructures can be erased and rewritten multiple times without requiring laborious chemical synthesis, which decreases the synthetic demand and cost associated with these methods.

    “The reversible Watson–Crick base pairing means that, unlike data encoded directly into the primary DNA sequence, data storage platforms based on DNA nanostructures can be “erased” and “rewritten” multiple times without requiring any laborious chemical synthesis, which decreases the synthetic demand and cost associated with these methods.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    All of these bottom-up approaches enable the production of asymmetric patterns, which is a key criterion for data storage applications: instead of encoding information directly into the sequence of bases, data may be stored in the three-dimensional shape of these assemblies.

    “Importantly, all of these bottom-up approaches enable the production of asymmetric patterns, which is a key criterion for data storage applications: instead of encoding information directly into the sequence of bases, data may be stored in the three-dimensional shape of these assemblies.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Standard DNA data storage requires slow and costly DNA synthesis, while DNA nanostructures already store molecular data in two- and three-dimensional objects.

    “In particular, standard DNA data storage requires slow and costly DNA synthesis, while DNA nanostructures already store molecular data in two- and three-dimensional objects.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The switch between two possible intensity values provides the binary logic in polychromic address multiplexing.

    “The switch between two possible intensity values provides the binary logic in this system.119”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [119] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In an alternative approach, five single-stranded nucleotides were annealed together to form an assembly with three addressable overhangs; when complementary strands to each of these overhangs were introduced, the site changed from a "0" (single-stranded) to a "1" (double-stranded) state, which could then be reversed using strand displacement.

    “In an alternative approach, five single-stranded nucleotides were annealed together to form an assembly with three addressable overhangs; when complementary strands to each of these overhangs were introduced, the site changed from a “0” (single-stranded) to a “1” (double-stranded) state, which could then be reversed using strand displacement.115”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Because the molecular memory process is performed in solution, the whole memory is erased simultaneously, highlighting the need for alternative strategies that enable spatial addressability.

    “Unfortunately, because this process is performed in solution, the whole memory is erased simultaneously, which highlights the need for alternative strategies that enable spatial addressability.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    These examples highlight the simple and inexpensive nature of gel electrophoresis as a readout platform, especially when compared with optical, electrochemical, and AFM-based methods.

    “These examples highlight the simple and inexpensive nature of gel electrophoresis as a readout platform, especially when compared with optical, electrochemical, and AFM-based methods.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Halvorsen and Wong used electrophoresis to demonstrate the readout of an 11 byte ASCII message.

    “The authors used electrophoresis to demonstrate the readout of an 11 byte ASCII message.113”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [113] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Because the single-molecule readout methods used for the assessment of DNA nanostructures are also used in DNA sequencing, these techniques are constantly improving; in this way, the advancement of sequence-based DNA data storage also supports the growth of alternative, structure-based approaches.

    “Additionally, because the single-molecule readout methods used for the assessment of DNA nanostructures are also used in DNA sequencing, these techniques are constantly improving: in this way, the advancement of sequence-based DNA data storage also supports the growth of alternative, structure-based approaches.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    Use of this suite of techniques has the advantage that, depending on the design and physical attributes of the data storage structure, it may be possible to perform more than one type of characterization; comparing results of different readout methodologies may allow identification of systematic biases in each modality, generating a feedback cycle wherein structures may be improved upon and re-

    “Depending on the design and the physical attributes of the data storage structure, it may be possible to perform more than one type of characterization. Comparing the results of different readout methodologies may allow for the identification of systematic biases in each modality, which generates a feedback cycle wherein structures may be improved upon and recharacterized.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    The relatively long read times and low data capacity of these methodologies limit their applicability.

    “However, the relatively long read times and low data capacity of these methodologies limit their applicability.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisenone given

    Nanopore methods require no labeling for readout, making them an attractive alternative to fluorescence.

    “Nanopore methods require no labeling for readout, which makes them an attractive alternative to fluorescence.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fan et al. used AFM to decode information stored in DNA domino arrays.

    “Similarly, Fan et al. used AFM to decode information stored in DNA domino arrays.127”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Quartz nanopores can read out DNA hairpins along a carrier strand with a density of approximately 1 bit per 30 nm, about 3 times the data density of conventional hard drives.

    “Now, these quartz nanopores can read out DNA hairpins along a carrier strand with a density of approximately 1 bit per 30 nm—ca. 3 times the data density of conventional hard drives.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    In nanopore measurements, an electric field causes molecules to translocate through a nanoscale hole, and the analyte modulates the ionic current by blocking the pore, translating the DNA nanostructure into an electrical signal.

    “Briefly, an electric field is applied across a nanoscale hole (made from glass or Si3N4, for example), which causes molecules to translocate through this nanopore. As the analyte passes, it modulates the ionic current signal because of its 3D shape blocking the pore—in this way, the structure of the DNA nanoconstruct is translated directly into an electrical signal (Figure 10).”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    DNA is difficult to visualize using EM because of insufficient electron density-related contrast, and therefore often requires staining.

    “DNA itself can be difficult to visualize using EM because of insufficient electron density-related contrast, and therefore, often requires staining.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    AFM measurements detect differences in height over a sample surface without affecting the sample, making AFM ideally suited to reading out three-dimensional patterns on DNA origami.

    “AFM measurements detect differences in height over a sample surface, without affecting the sample, thus rendering this method ideally suited to reading out three-dimensional patterns on DNA origami.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Premisecitation

    In the DNA braille system, the data are encrypted; only when streptavidin is added and binds to biotin does the pattern become readable by AFM.

    “The data in this system are encrypted; only when streptavidin is added and binds to biotin does the pattern become readable by AFM.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    EM allows high-resolution two- and three-dimensional images of DNA nanostructures but is time-consuming, expensive, and relatively low-throughput.

    “EM exhibits some of the same advantages and pitfalls of AFM: while these techniques allow for high-resolution two- and three-dimensional images to be formed of DNA nanostructures, they are time-consuming and expensive, as well as relatively low-throughput.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    Unlike DNA sequencing, which requires multiple reads to reach a consensus, the DNA origami breadboard tactic can read 750 origami to reach a 100% probability of full data retrieval.

    “Unlike DNA sequencing, which requires multiple reads to reach a consensus, this tactic can read 750 origami to reach a 100% probability of full data retrieval, which means that only femtomoles of material are needed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Atomic force microscopy (AFM) was used to read out images formed by DNA origami and remains a key technique for the study of DNA-based nanomaterials.

    “Atomic force microscopy (AFM) was used to “read-out” images formed by DNA origami, and this remains a key technique for the study of DNA-based nanomaterials.126”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [126] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In DNA punch cards, a pattern of nicking positions is realized on the backbone of native dsDNA, and information is encoded by absence (0) or presence (1) of nicks.

    “Indeed, a pattern of nicking positions was precisely realized on the backbone of native dsDNA, and here, information was encoded by means of absence (i.e., 0) or presence (i.e., 1) of nicks.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [72] source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    In a DNA computer, each DNA molecule plays the part of a separate processor, enabling many parallel operations to be carried out in a small reaction volume.

    “In a DNA computer, however, each DNA molecule plays the part of a separate processor, which enables many parallel operations to be carried out in a small reaction volume.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    Cao et al. used informational biopolymers composed of a backbone of poly(phosphodiesters) with dideoxyadenosine at both ends, and engineered-aerolysin nanopores.

    “As an example, Cao et al. used informational biopolymers composed of a backbone of poly(phosphodiesters) with dideoxyadenosine at both ends, and engineered-aerolysin nanopores.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Apart from DNA, other organic molecules have been proposed for data storage, including peptide sequences and urethanes.

    “Apart from DNA, other organic molecules have been recently proposed.133,134 Two interesting examples are the use of peptide sequences for data storage, as reported by Ng et al.133 and the use of urethanes as reported by Dahlhauser et al.134”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [133] source

      Not checked in the free run.

    • cites [134] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Adleman developed a working prototype for a DNA computer in 1994, using a separation-based approach to calculate a Hamiltonian path in a graph with seven summits.

    “A working prototype for a DNA computer was developed by Adleman in 1994,136 wherein he used a separation-based approach to calculate a Hamiltonian path in a graph with seven summits.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [136] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Adleman experiment acted as a proof of concept, but in practice the process was more time- and labor-intensive than a conventional digital approach.

    “The Adleman experiment acted as a proof of concept: in practice, the process was more time- and labor-intensive than a conventional digital approach.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [136] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    This DNA computing strategy greatly accelerates the initial path search, as statistics predict that DNA constructs corresponding to every possible path should be produced upon mixing.

    “This strategy greatly accelerates the initial path search, as statistics predict that DNA constructs corresponding to every possible path should be produced upon mixing.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    Su et al. produced DNA logic cascades that allow the buildup of a full adder, a 4:1 multiplexer, and, combined with other logic circuits, a DNA arithmetic logic unit (ALU), the foundation of general-purpose processors.

    “Su et al. produced DNA logic cascades, which allows the buildup of a full adder, a 4:1 multiplexer, and then, they combined these with other logic circuits to produce a DNA arithmetic logic unit (ALU): the foundation of general-purpose processors.139”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [139] source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Synthetic polymers can be used to increase stability against chemical degradation while offering a wide range of base modifications.

    “Synthetic polymers can be used to increase stability against chemical degradation while offering a wide range of base modifications.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In those structures, DNA nicks were ligated to favor the copy of the barcode by PCR.

    “In these structures, DNA nicks were ligated to favor the copy of the barcode by PCR.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [101] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The results of Cao et al. suggest a path to single-bit resolution at least in short polymers, but machine learning and training are needed for successful readout.

    “The results suggest a path to single-bit resolution at least in short polymers, however machine learning and training are needed for the successful readout.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Because DNA nanostructures are noncovalent, these materials are primed for use in molecular computation.

    “Because of the noncovalent nature of DNA nanostructures, these materials are primed for use in molecular computation.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisenone given

    Compared with fluorescence, sequencing, or gel electrophoresis-based strategies, single-molecule nanopore measurements require less material and enable faster data reading.

    “Compared with fluorescence, sequencing, or gel electrophoresis-based strategies, single-molecule nanopore measurements require less material and enable faster data reading; through a combination of this technology with deep learning methods,131 real-time nanopore data analysis is attainable.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    In both peptide and urethane data storage cases, reading required the use of mass spectroscopy, with consequent limitations in costs and speed.

    “Unfortunately in both these cases, reading required the use of mass spectroscopy, with the consequent limitation in terms of costs and speed.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [133] source

      Not checked in the free run.

    • cites [134] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These chemistries widen the breadth of materials that can be produced and may further extend the lifetime of DNA sequences, as these modifications render DNA less recognizable to enzymes.

    “Importantly, these chemistries not only widen the breadth of materials that can be produced, but also may further extend the lifetime of DNA sequences, as these modifications render DNA less recognizable to enzymes.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    In terms of synthesis, DNA nanotechnology greatly simplifies assembly procedures and produces structures that can easily be reconfigured.

    “In terms of synthesis, DNA nanotechnology greatly simplifies assembly procedures and produces structures that can easily be reconfigured.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    The current record for DNA digital data storage is still around 200 MB, with single synthesis runs lasting about 24 h.

    “While stored data size has been markedly increased, the current record for DNA digital data storage is still around 200 MB, with single synthesis runs lasting about 24 h.8,12”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] source

      Not checked in the free run.

    • cites [12] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationcitation

    There is potentially important synergy between in vitro/in vivo DNA nanotechnology and data storage, which remains unexplored.

    “As three-dimensional nucleic acid nanostructures have also successfully been produced inside cells,154 there is potentially important synergy between in vitro/in vivo DNA nanotechnology and data storage, which remains, as of yet, unexplored.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [154] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Robust, rigid DNA tiles with programmable "sticky ends" have been made using double-crossover (DX), triple-crossover (TX), and single-stranded tile (SST) motifs and used for algorithmic self-assembly experiments.

    “Robust, rigid DNA tiles with programmable “sticky ends” have been made using double-crossover (DX),141 triple-crossover (TX),142 and single-stranded tile (SST)143 motifs and used for a variety of algorithmic self-assembly experiments.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [141] source

      Not checked in the free run.

    • cites [142] source

      Not checked in the free run.

    • cites [143] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Past applications of DNA tile self-assembly include TX tiles carrying out a cumulative XOR operation, DX tiles self-assembling into a Sierpinski triangle, and 355 SSTs producing cellular automata capable of computational tasks.

    “Past applications of this idea include the design of a set of TX tiles that carry out a cumulative XOR operation, a set of DX tiles that self-assemble into a Sierpinski triangle, and impressively, a set of 355 SSTs that can be used to produce a variety of cellular automata capable of carrying out a number of computational tasks (Figure 11).144”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [144] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    DNA data storage-both the sequence- and structure-based versions-offers the possibility of storing digital information at very high data density.

    “DNA data storage—both the sequence- and structure-based versions—offers the possibility of storing digital information at very high data density.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    DNA nanostructures may present advantages over traditional sequence-based storage methods for dynamic properties, as the reconfiguration of these supramolecular moieties is firmly established, though rarely in the context of information storage.

    “In this area, DNA nanostructures may present advantages over traditional sequence-based storage methods, as the reconfiguration of these supramolecular moieties is firmly established, though rarely in the context of information storage.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The reconfiguration of DNA supramolecular moieties is firmly established.
  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    A DNA database would benefit greatly from dynamic properties that allow data to be erased, rewritten, and updated.

    “Even in the context of archival storage, a DNA database, like its electronic analogues, would benefit greatly from dynamic properties that allow data to be erased, rewritten, and updated.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    In-storage file operations and computations, as well as the ability to repeatedly access DNA databases, would reduce DNA synthesis costs and abrogate the need to store multiple copies of archives.

    “For example, in-storage file operations and computations, as well as the ability to repeatedly access DNA databases, would reduce DNA synthesis costs and abrogate the need to store multiple copies of archives.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    All current DNA sequencing techniques require molecular machines like polymerases, which set fundamental limits for the throughput per enzyme, meaning there is an upper threshold on the rate of sequencing even with massive parallelization.

    “Furthermore, all current DNA sequencing techniques require molecular machines like polymerases, which set fundamental limits for the throughput per enzyme, thereby meaning there is an upper threshold on the rate of sequencing even with massive parallelization.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisereasoning

    The logical equivalence of these DNA tiles with Wang tiles facilitates their use; Wang tiles are theoretical constructs with specified interactions that can simulate a Turing machine.

    “This is facilitated by the logical equivalence of these tiles with Wang tiles, which are theoretical constructs with specified interactions that can simulate a Turing machine.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    As the chemical and enzymatic processes for making sequence-defined nucleic acids continue to improve, the cost and time associated with writing DNA-based information is continually decreasing.

    “As the chemical and enzymatic processes for making sequence-defined nucleic acids continue to improve, the cost and time associated with writing DNA-based information is continually decreasing.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationnone given

    Both natural and chemically modified oligonucleotides, as well as hybrid nanostructures involving DNA and quantum dots or nanoparticles, may be read out using solid-state nanopores.

    “Both natural and chemically modified oligonucleotides, as well as hybrid nanostructures involving DNA and quantum dots or nanoparticles, may be read out using solid-state nanopores.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationreasoning

    These improvements are particularly important for sequence-based storage but also reduce costs for structure-based approaches.

    “These improvements are particularly important for sequence-based storage, but they importantly reduce costs for structure-based approaches, as well.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    A combination of sequence- and structure-based approaches could represent a significant advancement to overcome the various hurdles associated with DNA data storage.

    “A combination of sequence- and structure-based approaches could represent a significant advancement to overcome the various hurdles associated with DNA data storage.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    Long-term archival storage operates over long time scales-decades, centuries, and possibly millennia-and requires only infrequent access, which substantially reduces the impact of reading costs and long read times associated with DNA data storage.

    “Considering that long-term, archival storage97 operates over long time scales—decades, centuries, and possibly millennia—this application requires only infrequent access to the stored information, which substantially reduces the impact of reading costs and long read times associated with DNA data storage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [97] source

      Not checked in the free run.

127 of 127
  • The authors state this as an assumption.

    Any synthetic errors introduced by cheaper, less reliable synthesis processes can be identified and corrected for upon readout.

    “if it is assumed that any synthetic errors can be identified and corrected for upon readout”
  • The paper relies on this without support.

    DNA has long-term stability under appropriate storage conditions.

    “While the long-term stability of DNA, itself, is firmly established, further studies on the lifetimes of noncovalently assembled DNA nanostructures will need to be conducted to ensure that data stored in these formats are not compromised over time.”
  • The paper relies on this without support.

    The reconfiguration of DNA supramolecular moieties is firmly established.

    “In this area, DNA nanostructures may present advantages over traditional sequence-based storage methods, as the reconfiguration of these supramolecular moieties is firmly established, though rarely in the context of information storage.”
  • The paper relies on this without support.

    Current DNA sequencing techniques require molecular machines like polymerases, which set fundamental limits on throughput per enzyme.

    “Furthermore, all current DNA sequencing techniques require molecular machines like polymerases, which set fundamental limits for the throughput per enzyme, thereby meaning there is an upper threshold on the rate of sequencing even with massive parallelization.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Current research focuses on increasing DNA data storage density and preservation time by protecting DNA from high humidity and oxygen.

    “Therefore, current research focuses on increasing the DNA data storage density and the time of its preservation by protecting DNA from the influence of high humidity and the presence of oxygen [37].”

    From DNA Data Storage. (2023) · cites this paper as [37]

    The “Storage and Degradation Issues” section says DNA storage approaches protect against moisture and oxygen to enable long-term preservation, and it identifies a need for systems closer to DNA’s true storage density. But it says protective materials currently reduce storage density by 1–3 orders of magnitude; it does not support the claim that protection itself increases density. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • The most commonly used platforms for sequencing data-encoding DNA are Next-Generation Sequencing by Illumina and Third Generation Sequencing by Oxford Nanopore Technology.

    “Currently, the most commonly used platforms for the sequencing of data-encoding DNA are Next-Generation Sequencing by Illumina sequencing and Third Generation Sequencing by Oxford Nanopore Technology [37].”

    From DNA Data Storage. (2023) · cites this paper as [37]

  • At the moment, for DNA data storage purposes, the most commonly used sequencing method is Illumina.

    “Therefore, at the moment, for DNA data storage purposes, the most commonly used is Illumina sequencing [37].”

    From DNA Data Storage. (2023) · cites this paper as [37]

  • Nanopore has lower accuracy compared to Illumina; error rates are ∼10% per nucleotide in single read-out for Nanopore and ∼0.5% per nucleotide for Illumina, making Nanopore approximately 20 times less accurate.

    “However, Nanopore also has some limitations, for instance, lower accuracy compared to Illumina. In fact, a direct comparison of the error rates of Nanopore (∼10% per nucleotide in single read-out) and of Illumina (∼0.5% per nucleotide) shows that Nanopore technology is approximately 20 times less accurate.”

    From DNA Data Storage. (2023) · cites this paper as [37]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure 3C is assigned two different synthesis methods

    Minor

    The text points to Figure 3C for an electrode array, but the figure caption identifies panel C as enzymatic synthesis.

  • Long-term storage is said to require only a few percent DNA loading

    Minor

    The statement conflicts with Table 1's salt-matrix approach, which lists a 750-year half-life at 10 °C and 20% DNA loading.

  • Stated 1-3-order storage-density loss conflicts with Table 1

    Minor

    The text describes a 1-3-order-of-magnitude density loss for storage approaches, but Table 1 gives 17,000 PB/g for dried DNA and 0.0034 PB/g for a DNAshell-a five-million-fold loss.

  • Nanopore sequencing is assigned to the wrong Figure 5 panel

    Minor

    The text directs readers to Figure 5C for nanopore sequencing, while the caption identifies the Oxford Nanopore panel as Figure 5B.

  • Table assumes a DNA information density above the stated theoretical density

    Minor

    The introduction gives a theoretical density of about 4.5 × 107 GB/g (45 PB/g), while Table 1 assumes 17 EB/g (17,000 PB/g) for DNA. The table's assumed density is roughly 378 times the stated theoretical density.

  • Unnatural-nucleotide sequencing is both possible and incompatible

    Minor

    The reading section says nanopore sequencing can identify modified and unnatural nucleotides, whereas the conclusion says current sequencing methods are incompatible with unnatural monomer units.

6 of 6

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. 10.1063/1.5007621 · DOI · Paper page

Cited by

Sorted by citations

Authors
Doricchi, A., Platnich, C. M., Gimpel, A., Horn, F., Earle, M., Lanzavecchia, G., Cortajarena, A. L., Liz-Marzán, L. M., Liu, N., Heckel, R., Grass, R. N., Krahne, R., Keyser, U. F., & Garoli, D.
Affiliations
  • Italian Institute of Technology (IT)
  • University of Cambridge (GB)
  • ETH Zurich (CH)
  • Technical University of Munich (DE)
  • Istituto Italiano di Tecnologia, via Morego 30, I-16163 Genova, Italy
  • Ikerbasque (ES)
  • Center for Cooperative Research in Biomaterials (CICbiomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramón 194, 20014 Donostia-San Sebastián, Spain
  • University of Stuttgart (DE)
Corresponding author
  • Keyser, Ulrich F.
  • Garoli, Denis
Venue
ACS Nano
Published
2022-10-18
Volume
16
Issue
11
Pages
17552-17571
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
OpenAlex
W4306750370
Cited by
235
References
155
Citations by year
2026: 58 · 2025: 74 · 2024: 62 · 2023: 38 · 2022: 3
FWCI
4.63
Type
journal article
Language
en
Open access
Locations
  • ACS Nano (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection
Funders
H2020 Future and Emerging Technologies (964995)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Biological Computing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
  • Physical Sciences › Engineering › Biomedical Engineering › Nanopore and Nanochannel Transport Studies
Keywords
DNA data storage, DNA nanostructures, DNA sequence encoding, storage density
MeSH terms
DNA, Information Storage and Retrieval, Sequence Analysis, DNA

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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