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Cited by 80DNA and Biological ComputingAdvanced biosensing and bioanalysis techniquesElectrochemical sensors and biosensors

Electrochemical DNA synthesis and sequencing on a single electrode with scalability for integrated data storage

Open access
Xu, Chengtao, Ma, Biao, Gao, Zhongli, Dong, Xing, Zhao, Chao, Liu, Hong·2021·Science Advances
DOI 10.1126/sciadv.abk0100PMC PMC8589306
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Abstract

DNA synthesis and sequencing on a single electrode enables integrated data storage using a sliding microarray chip.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper demonstrates a fully integrated DNA data storage proof-of-concept in which electrochemical DNA synthesis and sequencing occur on the same Au electrode, with liquid handling by a SlipChip device. It shows writing/reading of small text files and scalability using a 2 × 2 electrode array.

Key findings

  • Electrochemical phosphoramidite synthesis on Au electrodes gave an averaged stepwise yield of ~97.1%; Au NP modification increased Syn-10nt surface density from 1.644 × 10^13 to 4.062 × 10^13 molecules cm−2.
  • Sequencing-by-synthesis on the same electrode detected complementary dNTP addition as a transient current of ~20 nA within 300 ms, with an averaged valid charge of ~2.87 nC corresponding to 5.7 × 10^11 DNA molecules cm−2.
  • Sequencing accuracy was 84.21% (16 of 19 sites matched); integrated synthesis-and-sequencing accuracy was 75.56%, from which synthesis accuracy was roughly estimated as 89.73%. After three repeated readings and plurality voting, data recovery accuracy improved to ~87.22% on average, and Reed-Solomon redundancy (6/15 = 40%) corrected remaining errors to achieve 100% recovery.
  • A SlipChip-based 2 × 2 Au electrode array stored “DNAStoresFutureWorld” with ~89.17% accuracy after three replicated sequencing and plurality voting, then recovered the original data after error correction; writing/reading took ~9 hours for 4.5 bytes on a single electrode and ~14 hours for 20 bytes on the four-electrode array.

Methods

  • The system used a Au electrode modified with bis-aniline–cross-linked Au nanoparticles and 6-mercapto-1-hexanol; DNA synthesis used phosphoramidite chemistry with electrochemical acid deprotection at an optimized 1.4 V, and sequencing used polymerase-catalyzed primer extension detected by charge redistribution/transient current.
  • Data were encoded into DNA using Reed-Solomon codes, synthesized on electrodes, sequenced on the same electrodes, and decoded; repeated sequencing was enabled by electrode regeneration with 0.20 M NaOH and plurality voting.
  • Characterization included fluorescence hybridization, chronocoulometry with RuHex, current/charge measurements, Needleman-Wunsch alignment, and a SlipChip microfluidic device with a 2 × 2 Au electrode array for integrated liquid manipulation.

Limitations

  • Stated: the synthesis accuracy estimate is rough and accuracy depends on specific sequence and length; homopolymer regions, especially G and C, cause synthesis and sequencing errors; excessive sequencing increases cost/time and accuracy decreased with increasing cycles, estimated to fall to 50% after ~21 cycles.
  • Stated: slipping operations slightly decreased surface densities on microfabricated electrodes, though they remained sufficient for sequencing.
  • Evident: the demonstration is small-scale proof-of-concept (4.5 bytes on one electrode; 20 bytes on four electrodes), with relatively low raw accuracy requiring repeated sequencing, plurality voting, and substantial error-correction redundancy; large-scale high-density arrays are proposed as future work rather than demonstrated.

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

Integrity signals

Registry

Crossref · 10.1126/sciadv.abk0100

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 29 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The Au electrode surface area increased after modification with bis-aniline-cross-linked Au NPs, confirmed by a ~4.2-fold increased characteristic Au peak at ~0.97 V versus AgCl/Ag in cyclic voltammogram in 0.50 M H2SO4.

    “The surface area of the electrode increased after the modification, which was confirmed by the increased characteristic Au peak (~4.2 times of a naked electrode) at ~0.97 V (versus AgCl/Ag) in the cyclic voltammogram in 0.50 M H2SO4 (fig. S2B).”
    Quote in the paperSubstantial claim
  • Findingreasoning

    Average surface density of Syn-10nt on a bare Au electrode was 1.644 × 10^13 molecules cm−2.

    “By calculation, the average surface density of the Syn-10nt on a bare Au electrode was 1.644 × 1013 molecules cm−2.”
    Quote in the paperNot a substantial claim
  • Findingown data

    With bis-aniline-cross-linked Au NPs on the surface, a larger anodic current for proton generation was observed than for a bare Au electrode.

    “Besides, with the bis-aniline–cross-linked Au NPs on the surface, a larger anodic current for the proton generation was observed than that for a bare Au electrode, as shown in fig. S4B.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Chronocoulometric measurements showed that electric charge attributed to RuHex reduction correlated with the length of oligonucleotides synthesized on the electrode.

    “The charge exhibited a correlation with the length of the oligonucleotides synthesized [in nucleotides (nt)] on the electrode (Syn-5nt, 3′-TGACT-5′; Syn-10nt, 3′-TGACTGACTG-5′; Syn-15nt, 3′-TGACTGACTGACTGA-5′; Syn-20nt, 3’-TGACTGACTGACTGACTGAC-5′), as shown in Fig. 2E.”
    Quote in the paperSubstantial claim
  • Findingown data

    A potential of 1.4 V was optimal for the electrochemical deprotection step for DNA synthesis.

    “The result indicated that a potential of 1.4 V was the optimal potential for the electrochemical deprotection step for DNA synthesis, which was used for future experiments.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 2
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 12

  • The quote only partly states this claim.

    Findingnone given

    The bis-aniline units used to cross-link Au NPs on the electrode exhibited redox properties similar to proton-coupled redox reactions.

    “In this work, the bis-aniline units used to cross-link the Au NPs on the electrode exhibited similar redox properties.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The anodic current monotonically increased with increasing potentials from 1.2 to 1.7 V, but the resulting oligonucleotide density of Syn-10nt on the electrode first increased and then decreased with increasing potentials.

    “As shown in the Supplementary Materials, the anodic current monotonically increased with increasing potentials from 1.2 to 1.7 V (fig. S5A), but the resulting oligonucleotide density of Syn-10nt on the electrode first increased and then decreased with increasing potentials (fig. S5B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A self-priming single-stranded oligonucleotide (Oligo-2) was immobilized on the electrode as target for sequencing; it spontaneously formed a hairpin secondary structure after incubation so DNA polymerase could directly bind to its 3′ end without additional primer.

    “The self-priming Oligo-2 spontaneously formed a hairpin secondary structure after incubation so that a DNA polymerase could directly bind to its 3′ end without an additional primer (Fig. 3A and fig. S6).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Without either polymerase or Oligo-2, only background current was observed, indicating perturbation of the interface from fluid introduction was negligible.

    “For the experiments without either the polymerase or Oligo-2, only background current was observed, which indicated that the perturbation of the interface owing to the fluid introduction was negligible.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After cross-linking Au NPs on the electrode, surface density increased to 4.062 × 10^13 molecules cm−2, higher than conventional surface-immobilized DNA (~6 × 10^12 molecules cm−2).

    “After cross-linking Au NPs on the electrode to increase the surface area, the surface density increased to 4.062 × 1013 molecules cm−2, as shown in fig. S4A, which was higher than that reported for conventional surface-immobilized DNA (~6 × 1012 molecules cm−2) (38, 43).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [38] J. Zhang, S. Song, L. Zhang, L. Wang, H. Wu, D. Pan, C. Fan, Sequence-specific detection of femtomolar DNA via a chronocoulometric DNA sensor (CDS): Effects of nanoparticle-mediated amplification and nanoscale control of DNA assembly at electrodes. J. Am. Chem. Soc. 128, 8575– 8580 (2006). 16802824 source

      Not checked in the free run.

    • cites [43] J. Zhang, S. Song, L. Wang, D. Pan, C. Fan, A gold nanoparticle-based chronocoulometric DNA sensor for amplified detection of DNA. Nat. Protoc. 2, 2888– 2895 (2007). 18007624 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    An exponential attenuation model fit to the data gave an averaged stepwise yield of ~97.1%, acceptable compared with previously reported chemical synthesis yields (90 to 98%) and enzymatic synthesis (~97.7%).

    “An exponential attenuation model was used to fit the data points in Fig. 2E so that an averaged stepwise yield of ~97.1% was obtained from the equation, which was acceptable compared with previously reported yields for chemical synthesis (90 to 98%) (40, 41) and enzymatic synthesis (~97.7%) (42).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [40] G. H. McGall, A. D. Barone, M. Diggelmann, S. P. Fodor, E. Gentalen, N. Ngo, The efficiency of light-directed synthesis of DNA arrays on glass substrates. J. Am. Chem. Soc. 119, 5081– 5090 (1997). source

      Not checked in the free run.

    • cites [41] B. Y. Chow, C. J. Emig, J. M. Jacobson, Photoelectrochemical synthesis of DNA microarrays. Proc. Natl. Acad. Sci. U.S.A. 106, 15219– 15224 (2009). 19706433 PMC2741231 source

      Not checked in the free run.

    • cites [42] S. Palluk, D. H. Arlow, T. de Rond, S. Barthel, J. S. Kang, R. Bector, H. M. Baghdassarian, A. N. Truong, P. W. Kim, A. K. Singh, N. J. Hillson, J. D. Keasling, De novo DNA synthesis using polymerase-nucleotide conjugates. Nat. Biotechnol. 36, 645– 650 (2018). 29912208 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Fluorescence measurements showed higher signal for complementary probe Oligo-c1 than mismatched probe Oligo-mis1, indicating the predetermined oligonucleotide sequence was available on the electrode.

    “After washing to remove the nonspecifically adsorbed oligonucleotide, the fluorescence measured for Oligo-c1 was higher than that for Oligo-mis1, as shown in Fig. 2B, which indicated that the oligonucleotide with the predetermined sequence was available on the electrode.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Accuracy for data recovery improved to ~87.22% on average after three repeated reading and plurality voting, and errors were usually correlated to synthesis and sequencing of homopolymer regions.

    “It was found that the accuracy for data recovery was improved to ~87.22% on average after three repeated reading and plurality voting, and errors were usually correlated to the synthesis and sequencing of homopolymer regions, as shown in table S2.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    The length of oligonucleotides (43 nt) was much greater than previously synthesized (10 nt), so surface density measured (3.2 × 10^11 DNA molecules cm−2) was much lower, reasonable considering nonideal yield.

    “The length of the oligonucleotides (43 nt) was much greater than that we have previously synthesized (10 nt), so the surface density of the oligonucleotides we measured (3.2 × 1011 DNA molecules cm−2) was much lower, which was reasonable considering the nonideal yield of the DNA synthesis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The self-priming Oligo-2 included sequence 5′-GCTGGAATTCGTTGTGAGG-3′, which was sequenced multiple times.

    “The self-priming Oligo-2 included a sequence of 5′-GCTGGAATTCGTTGTGAGG-3′, which was sequenced multiple times using our method, and the resulting data were shown in Fig. 3D and fig. S8.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    With increasing cycles of DNA sequencing, accuracy decreased gradually, probably because of incomplete electrode regeneration and DNA degradation.

    “As shown in fig. S9, with increasing cycles of DNA sequencing, the accuracy decreased gradually, which was probably because of incomplete electrode regeneration and DNA degradation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For a valid signal of dNTP addition, averaged charge was approximately 2.87 nC, corresponding to a surface density of 5.7 × 10^11 DNA molecules cm−2.

    “It was found that for a valid signal of a dNTP addition, the averaged charge was approximately 2.87 nC, which corresponded to a surface density of 5.7 × 1011 DNA molecules cm−2.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Needleman-Wunsch alignment of sequencing result with actual sequence showed 16 of 19 sites matched, indicating accuracy of 84.21%.

    “To evaluate the sequencing accuracy, we used the Needleman-Wunsch alignment in DNAMAN software to compare the sequencing result with the actual sequence (46, 47). Sixteen of 19 sites were matched in the final alignment, which indicated that an accuracy of 84.21% was achieved.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [46] B. Morgenstern, DIALIGN 2: Improvement of the segment-to-segment approach to multiple sequence alignment. Bioinformatics 15, 211– 218 (1999). 10222408 source

      Not checked in the free run.

    • cites [47] W. J. Wilbur, D. J. Lipman, Rapid similarity searches of nucleic acid and protein data banks. Proc. Natl. Acad. Sci. U.S.A. 80, 726– 730 (1983). 6572363 PMC393452 source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    Alkaline solution denaturized double-stranded DNA and removed extended primer so original DNA was able to bind another primer for sequencing.

    “The alkaline solution denaturized the double-stranded DNA and removed the extended primer so that the original DNA was able to bind with another primer for sequencing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Oligonucleotide strands of 43 nt (Motto sequences) were synthesized on different Au electrodes, subsequently sequenced using the same electrode, and decoded to obtain encoded data.

    “Oligonucleotide strands of these sequences (43 nt) were synthesized on different Au electrodes, respectively, which were subsequently sequenced using the same electrode and decoded to obtain the encoded data.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    Correcting data errors requires considerable data redundancy, which restricts the efficiency of DNA data storage.

    “Correcting data errors requires a considerable amount of data redundancy, which restricts the efficiency of data storage.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    All liquid manipulations for synthesis and sequencing were accomplished based on SlipChip, which can be fully integrated for scale-up of the database.

    “All of the liquid manipulations for the synthesis and sequencing are accomplished on the basis of the principle of SlipChip, which can be fully integrated for the scale-up of the database (Fig. 1D).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Conventional phosphoramidite DNA synthesis relies on an acidic reagent such as trichloroacetic acid to remove the DMT protecting group at the 5′ end to activate the nucleotide monomer.

    “Conventional DNA synthesis based on the phosphoramidite chemistry relies on an acidic reagent (e.g., trichloroacetic acid) to remove the protecting group [e.g., dimethyltrityl (DMT)] at the 5′ end to activate the nucleotide monomer (34).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] E. M. LeProust, B. J. Peck, K. Spirin, H. B. McCuen, B. Moore, E. Namsaraev, M. H. Caruthers, Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process. Nucleic Acids Res. 38, 2522– 2540 (2010). 20308161 PMC2860131 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Writing and reading data on a single electrode does not require an address sequence, so data volume is limited only by the number of electrodes.

    “By writing and reading data on a single electrode, an address sequence is not required so that the data volume is only limited by the number of electrodes.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The strategy can eliminate some random errors by multiple sequencing and base identification using plurality voting.

    “The strategy can also eliminate some random errors by multiple sequencing and base identification using the principle of plurality voting.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The larger surface area after Au NP modification can provide more active sites for DNA synthesis, enhancing current signals for subsequent DNA sequencing.

    “The larger surface area can provide more active sites for DNA synthesis so as to enhance the current signals for the subsequent DNA sequencing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Current DNA data storage methods based on commercial instrumentation involve complicated liquid manipulations and manual operations, limiting scale-up and increasing error probability.

    “For example, current methods usually involve complicated liquid manipulations in each step and manual operations in between. Adding one phosphoramidite nucleotide monomer in the synthesis step generally requires the introduction of at least four kinds of liquid solutions, not to mention the sequencing step. These limit the scale-up capability of this technique and increase the error probability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because the electrochemical reaction was reversible, the electrode could quickly switch between ON and OFF states to increase the speed of DNA synthesis.

    “As the electrochemical reaction was reversible, the electrode could quickly switch between the ON and OFF states to increase the speed of the DNA synthesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because redox groups were tethered on the electrode surface, deprotection was more localized, which could help avoid cross-talk in a microelectrode array.

    “Furthermore, as the redox groups were tethered on the electrode surface, the deprotection was more localized, which could help to avoid cross-talk in a microelectrode array.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The charge and oligonucleotide length were not linearly correlated, which is reasonable because the stepwise yield for chemical DNA synthesis was less than 100%.

    “However, the charge and the oligonucleotide length were not linearly correlated, and this is reasonable because the stepwise yield for the chemical DNA synthesis was less than 100%.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Electric charges were used instead of current signals because charges directly reflected the number of protons released during the polymerase-catalyzed reaction, and measurement of charges was more reproducible than current for the transient process.

    “For quantitative analysis, the electric charges (the integral of current over time) were used instead of current signals (fig. S7), because the charges directly reflected the number of protons released during the polymerase-catalyzed reaction, and measurement of charges was more reproducible than current for the transient process.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The accuracy of the sequencing step was 84.21%, which can be representative of the sequencing accuracy of the method.

    “The accuracy of the sequencing step was found to be 84.21% (Fig. 3), which can be representative of the sequencing accuracy of our method.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The sequencing accuracy measured from one Oligo-2 sequence (84.21%) is representative of the sequencing accuracy of the method generally.

  • The quote only partly states this claim.

    Interpretationcitation

    The sequencing accuracy of 84.21% was acceptable compared with previously reported results.

    “The accuracy was acceptable compared with the previously reported results (48–50).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [48] O. Harismendy, P. C. Ng, R. L. Strausberg, X. Wang, T. B. Stockwell, K. Y. Beeson, N. J. Schork, S. S. Murray, E. J. Topol, S. Levy, K. A. Frazer, Evaluation of next generation sequencing platforms for population targeted sequencing studies. Genome Biol. 10, R32 (2009). 19327155 PMC2691003 source

      Not checked in the free run.

    • cites [49] R. R. Wick, L. M. Judd, K. E. Holt, Performance of neural network basecalling tools for Oxford Nanopore sequencing. Genome Biol. 20, 129 (2019). 31234903 PMC6591954 source

      Not checked in the free run.

    • cites [50] E. J. Fox, K. S. Reid-Bayliss, M. J. Emond, L. A. Loeb, Accuracy of next generation sequencing platforms. Next Gener. Seq. Appl. 1, 1000106 (2014). 25699289 PMC4331009

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Excessive sequencing would increase cost and time notably and would not necessarily further improve accuracy.

    “However, excessive sequencing would increase the cost and time notably and would not necessarily further improve the accuracy.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    This synthesis accuracy estimate is rough and accuracy also depends on specific sequence and length.

    “Note that this is a rough estimation. The accuracy also depends on specific sequence and length.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Homopolymer can lead to low coupling efficiency in DNA synthesis, especially for G and C, and quantification of the number of identical nucleotides in DNA sequencing can also be problematic.

    “The homopolymer can lead to low coupling efficiency in DNA synthesis (especially for G and C), and quantification of the number of identical nucleotides in DNA sequencing can also be problematic (39, 53).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] R. Heckel, G. Mikutis, R. N. Grass, A characterization of the DNA data storage channel. Sci. Rep. 9, 9663 (2019). 31273225 PMC6609604 source

      Not checked in the free run.

    • cites [53] M. G. Ross, C. Russ, M. Costello, A. Hollinger, N. J. Lennon, R. Hegarty, C. Nusbaum, D. B. Jaffe, Characterizing and measuring bias in sequence data. Genome Biol. 14, R51 (2013). 23718773 PMC4053816 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SlipChip is especially appropriate for integrated DNA-based data storage because all microdroplets can be moved simultaneously by sliding, so no valves, pumps, or tubes are required.

    “As a microfluidic device for handling a large array of microdroplets, SlipChip is a platform that is especially appropriate for the development of an integrated DNA-based data storage system. All the microdroplets can be moved simultaneously on a SlipChip by simply sliding the device, so no valves, pumps, or tubes are required (54–56).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [54] F. Shen, E. K. Davydova, W. Du, J. E. Kreutz, O. Piepenburg, R. F. Ismagilov, Digital isothermal quantification of nucleic acids via simultaneous chemical initiation of recombinase polymerase amplification reactions on SlipChip. Anal. Chem. 83, 3533– 3540 (2011). 21476587 PMC3101872 source

      Not checked in the free run.

    • cites [55] W. Du, L. Li, K. P. Nichols, R. F. Ismagilov, SlipChip. Lab Chip 9, 2286– 2292 (2009). 19636458 PMC2719824 source

      Not checked in the free run.

    • cites [56] F. Shen, W. Du, J. E. Kreutz, A. Fok, R. F. Ismagilov, Digital PCR on a SlipChip. Lab Chip 10, 2666– 2672 (2010). 20596567 PMC2948063 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    This is beneficial for developing a fully integrated DNA-based database with low reagent consumption and cost.

    “This is beneficial for developing a fully integrated DNA-based database with low reagent consumption and cost.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    The increased electrode surface by Au NP modification can enhance the charge redistribution signal in the sequencing process.

    “which can enhance the charge redistribution signal in the sequencing process.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The time can be further improved by scaling up using an electrode array.

    “It took about 9 hours to write and read 4.5 bytes of data on the single electrode, which can be further improved by scaling up using an electrode array as shown below.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Amphiphobic fluorinated fluid FC-40 was used to seal reagent droplets in reservoirs and avoid cross-contamination.

    “To seal the reagent droplets in reservoirs and avoid cross-contamination, we used amphiphobic fluorinated fluid FC-40.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    By regeneration of the electrode after the synthesis-by-sequencing process, the electrode can be sequenced multiple times.

    “Last, by regeneration of the electrode after the synthesis-by-sequencing process, the electrode can be sequenced multiple times”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Because of the small size of the microfluidic channels, reservoirs, and microelectrodes, mass transfer can be accelerated to improve the reaction kinetics.

    “Besides, because of the small size of the microfluidic channels, reservoirs, and the microelectrodes, mass transfer can be accelerated to improve the reaction kinetics”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The overall sequencing accuracy was determined using three replicated sequencing runs and plurality voting.

    “after three replicated sequencing and plurality voting (table S2).”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    The high-density microelectrode array is fully compatible with the paralleled liquid manipulation technique based on SlipChip demonstrated in this work.

    “The microelectrode array of high density is also fully compatible with the paralleled liquid manipulation technique based on SlipChip demonstrated in this work.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Fabrication of a high-density microelectrode array is technically feasible.
40 of 40

  • The paper relies on this without support.

    The sequencing accuracy measured from one Oligo-2 sequence (84.21%) is representative of the sequencing accuracy of the method generally.

    “The accuracy of the sequencing step was found to be 84.21% (Fig. 3), which can be representative of the sequencing accuracy of our method.”

  • The paper relies on this without support.

    The integrated DNA synthesis and sequencing accuracy equals the product of synthesis accuracy and sequencing accuracy, allowing synthesis accuracy to be estimated by dividing integrated accuracy by sequencing accuracy.

    “So the accuracy of the synthesis could be estimated by 75.56/84.21% = 89.73%.”

  • The paper relies on this without support.

    Fabrication of a high-density microelectrode array is technically feasible.

    “Fabrication of a microelectrode array of high-density is technically feasible, which we are working on now for practically applicable large-scale data storage.”
3 of 3

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?

  • 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.”

    From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [31]

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Authors
Xu, C., Ma, B., Gao, Z., Dong, X., Zhao, C., & Liu, H.
Affiliations
  • State Key Laboratory of Digital Medical Engineering (CN)
  • State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University, 2# Sipailou, Nanjing, Jiangsu 210096, China.
Corresponding author
Liu, Hong
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2021-11-12
Volume
7
Issue
46
Pages
eabk0100-eabk0100
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.abk0100
PMC
PMC8589306
OpenAlex
W3214254250
Semantic Scholar
82663577cf1d08235bb56ad648c9dad36343ccfb
Cited by
79
References
58
Citations by year
2026: 11 · 2025: 25 · 2024: 21 · 2023: 15 · 2022: 7
FWCI
3.37
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
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 › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
Keywords
DNA data storage, DNA sequencing, single electrode, phosphoramidite chemistry, charge redistribution, electrode regeneration, SlipChip, scalability

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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