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Enter the SlipChip: An SoC on the Road to DNA Data Storage

The SlipChip itself
(Image credit: Northeast University)

A team of Chinese scientists from Southeast University developed a novel way to store information in DNA. In a research article published in Science, the team demonstrated a DNA synthesis and sequencing technique that uses a single electrode. This enabled the scientists to skip the longer and less stable chemical processes previously used for that purpose, simplifying and accelerating the process immensely. 

Using DNA as a storage medium isn't new; Richard B. Feynman initially proposed it in 1959. What made DNA so attractive from the get-go is that it already functions as a storage device by itself - and one with an immense memory density. DNA can store information at a density of 455 ExaBytes per gram. Crudely put: an average 720g, 20 TB HDD comes in at a storage density of 0,027 TB per gram. So it becomes clear why it'd be interesting to pursue this road. 

Materials from Southeast university

The SlipChip itself: automating DNA synthesis and sequencing tasks. (Image credit: Southeast University)
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Materials from Southeast university

Encoding binary code in DNA synthesis and sequencing with a single gold electrode (Image credit: Southeast University)

Schematic illustration of a data storage system based on DNA synthesis and sequencing on the same Au electrode.

(A) Schematic showing the generation procedure for the DNA-based data storage. (B) Schematic of the electrochemically triggered phosphoramidite chemistry for the synthesis of DNA on the electrode. (I) A phosphoramidite nucleotide monomer with a dimethyltrityl (DMT) protecting group reacts with the free-hydroxyl group on the electrode/DNA molecule, forming a phosphite linkage. (II) The phosphite bond is oxidized by iodine to a more stable phosphate bond. (III) A positive potential is then applied to the electrode to generate protons. The acid-labile DMT protecting group on the nucleotide is removed to expose another free hydroxyl group for the addition of the next cycle. (C) Schematic of the DNA sequencing method on the same electrode based on charge redistribution in the sequencing-by-synthesis process. (IV) A known deoxyribonucleoside triphosphate (dNTP) and the DNA polymerase are added. Then, the polymerase binds to the template DNA, which is complementary with a primer DNA. (V) A proton is removed in the coupling reaction, and diffusion of the proton induces a charge redistribution and thus a transient current signal for base identification. (D) Schematic illustration of the principle of the SlipChip device for integrated DNA synthesis and sequencing. Four phosphoramidite nucleotide monomers for synthesis (or four dNTPs for sequencing) are preloaded in the reservoirs. A washing solution and other reagents are introduced using the fluidic channel. Liquid manipulation is accomplished by sliding the top plate.

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Materials from Southeast university

A schematic for DNA sequencing as enabled via the electrode. (Image credit: Southeast University)

DNA sequencing on the electrode.

(A) Schematic illustration of the DNA sequencing-by-synthesis process for the self-priming Oligo-2. (B) Current as a function of time measured in the sequencing-by-synthesis process. Different reagents were introduced to electrodes having the self-priming Oligo-2 at the time marked using the black arrow, including polymerase and a complementary dNTP (black), polymerase and a noncomplementary dNTP (blue), and a complementary dNTP without polymerase (yellow), respectively. For the control experiment (green), there was no oligonucleotide on the Au electrode. A Gaussian fitting of the black curve was also shown (red). (C) Peak area/charge (Q) of the transient signals in response to the dNTP addition. The colors correspond to those of curves in (B). (D) Peak area/charge (Q) measured for sequencing of the Oligo-2. The sequencing was carried out by sequential introduction of different dNTPs in the order of A, T, C, and G to the electrode, while measuring the current. The number of dNTPs coupled for each time was determined on the basis of the magnitude of the peak area relative to Q0 and 2Q0, as indicated by the brown dash lines in the figure. Error bars represent the SD of five replicated measurements.

To achieve this feat, the scientists developed an entirely new way to handle DNA processing: they developed a "SlipChip," as they call it. Essentially, it's a small exchange chamber with microfluidic pathways, traps, and chambers that allow for controlled interactions between the various chemical compounds required for DNA synthesis and sequencing. The top plate can be restructured, when necessary, to move the DNA manipulation process to its next step.

It's here that the electrode bit of the technique enters: the SlipChip also encases a single gold electrode. It essentially defines two states: one state in the absence of DNA contact (0), and a second state which simply identifies the presence of DNA sequences (1) born from the latent electrical current that spikes during the process.

According to the researchers, this brings about much-needed simplification and increased security for the entire process. As they put it, current DNA storage 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."

With the new technique, several roadblocks to DNA storage are now resolved. Equipment used in previous DNA processing methods (large and impractical) is no longer required; steps are simplified; and they can now be done without manual intervention, thus reducing errors. In addition, the entire process is now condensed into the venerable SlipChip - a DNA synthesis storage and retrieval System-On-a-Chip. It's the industrial revolution equivalent of DNA data storage research.

Materials from Southeast university

Integrated data storage based on an electrode array. (A) Photograph of the SlipChip device with a fluidic channel (orange) and reagent reservoirs (blue) on the top PDMS plate as well as a 2×2 Au electrode array on the bottom glass slide. Scale bar: 5mm. (B) Photographs showing the DNA synthesis process using the SlipChip device. Phosphoramidite coupling, washing, oxidation, and deprotection steps were performed by aligning the reagent reservoirs or fluidic channel with the electrodes, respectively. For electrochemical deprotection, a potential was applied to the electrodes using a CHI900D workstation. Scale bars: 5mm. (C) Surface densities of the synthesized DNA on microfabricated electrodes of two sizes (d = 260 and 500μm) and a commercial 2mm disk electrode. (D) Current signals and corresponding peak area/charge (Q) for sequencing. (Image credit: Southeast University)

For the experiment, the researchers wrote the motto for the Southeastern University ("Rest in the highest excellence!") in binary data, which was encoded into the ATCG (quaternary) DNA base sequences. These are synthesized into DNA in the process. Sequencing (reading) the resulting DNA, the team first achieved a respectable 87.22% accuracy. Adding error correction capabilities via data redundancy in the encoding step unlocked the coveted 100% accuracy.

If you're wondering how fast that process actually was, well, it really wasn't. The researchers managed to write and read at around 0.5 bytes/hour with a single electrode. That figure is ridiculously slow for the overall digital footprint of even a minute of our lives, let alone for meaningful storage space. However, the process is capable of scaling up, as currently designed. Increasing the number of electrodes to four, the researchers found it took about 14 hours to write and read 20 bytes of data, for an average of 1.43 bytes/hour — imperfect scaling on an already slow process. But there are scaling and improvement techniques to do from here as well - we must remember that Intel's Pentium started at 60 MHz back in 1993.

DNA-based storage is still a long way off in any significant capacity. Significant speed improvements are still required, but that is customary in every field. If the Cambrian explosion of DNA storage is yet to come, this is one more important step on that journey.