Data storage

Enter the SlipChip: a SoC on the way to storing DNA data

A team of Chinese scientists from Southeastern University has developed a new way to store information in DNA. In a research paper published in Science, the team demonstrated a DNA synthesis and sequencing technique that uses a single electrode. This allowed scientists to avoid the longer, less stable chemical processes previously used for this purpose, greatly simplifying and speeding up the process.

The use of DNA as a storage medium is not new; Richard B. Feynman originally proposed it in 1959. What made DNA so attractive from the start was that it already functions as a storage device on its own – and with immense memory density. . DNA can store information at a density of 455 ExaBytes per gram. Roughly speaking: an average 720g, 20TB hard drive has a storage density of 0.027TB per gram. We therefore understand why it would be interesting to continue in this direction.

Southeastern University Materials

The SlipChip itself: automation of DNA synthesis and sequencing tasks. (Image credit: Southeastern University)
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Southeastern University Materials

Binary Code Encoding in DNA Synthesis and Sequencing with a Single Gold Electrode (Image credit: Southeastern 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 DNA-based data storage. (B) Schematic of electrochemically triggered phosphoramidite chemistry for DNA synthesis 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 bond. (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 next cycle addition. (VS) Schematic of same-electrode DNA sequencing method based on charge redistribution in sequencing-by-synthesis process. (IV) A known deoxyribonucleoside triphosphate (dNTP) and DNA polymerase are added. Then, the polymerase binds to the template DNA, which is complementary to a DNA primer. (V) A proton is removed in the coupling reaction, and proton scattering induces charge redistribution and hence 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 into the reservoirs. Wash solution and other reagents are introduced using the fluid channel. Liquid handling is done by sliding the top plate.

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Southeastern University Materials

A schematic for electrode-activated DNA sequencing. (Image credit: Southeastern University)

DNA sequencing on the electrode.

(A) Schematic illustration of the DNA synthesis sequencing process for 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 with the black arrow, including the polymerase and a complementary dNTP (black), the polymerase and a non-complementary dNTP (blue ), and a complementary polymerase-free dNTP (yellow), respectively. For the control experiment (green), there was no oligonucleotide on the Au electrode. A Gaussian fit of the black curve was also shown (red). (VS) Peak/load area (Q) transient signals in response to the addition of dNTPs. The colors correspond to those of the curves in (B). (D) Peak/load area (Q) measured for Oligo-2 sequencing. Sequencing was performed by sequential introduction of different dNTPs in the order A, T, C and G to the electrode, while measuring the current. The number of dNTPs paired each time was determined based on the magnitude of the peak area relative to Q0 and 2Q0, as indicated by the brown dotted lines in the figure. Error bars represent the SD of five replicate measurements.

To achieve this feat, the scientists developed a whole new way of handling DNA processing: they developed a “SlipChip”, as they call it. It is essentially a small exchange chamber with microfluidic pathways, traps, and chambers that allow controlled interactions between the various chemical compounds needed for DNA synthesis and sequencing. The top plate can be restructured, if necessary, to take the DNA manipulation process to the next step.

This is where the electrode technology comes into play: the SlipChip also contains a single gold electrode. It essentially defines two states: a state in the absence of contact with DNA (0) and a second state that 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 much-needed simplification and increased security to the entire process. As they put it, current DNA storage methods “usually involve complicated liquid manipulations at each step and manual operations in between. Adding a phosphoramidite nucleotide monomer in the synthesis step usually requires the introduction of at least four types of liquid solutions, not to mention the sequencing step, which limit the scalability of this technique and increase the probability of error.

With the new technique, several obstacles to DNA storage are now resolved. The equipment used in previous DNA processing methods (large and cumbersome) is no longer necessary; the steps are simplified; and they can now be performed without manual intervention, reducing errors. Additionally, the entire process is now condensed into the venerable SlipChip – an on-chip DNA synthesis storage and retrieval system. This is the industrial revolution equivalent of DNA data storage research.

Southeastern University Materials

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 upper PDMS plate as well as a 2 × 2 Au electrode array on the lower glass slide. Scale bar: 5mm. (B) Photographs showing the DNA synthesis process using the SlipChip device. The phosphoramidite coupling, washing, oxidation, and deprotection steps were performed by aligning the reagent reservoirs or the fluid channel with the electrodes, respectively. For electrochemical deprotection, a potential was applied to the electrodes using a CHI900D workstation. Scale bars: 5 mm. (VS) Surface densities of DNA synthesized on microfabricated electrodes of two sizes (d = 260 and 500 μm) and a commercial 2 mm disc electrode. (D) Current signals and corresponding peak area/charge (Q) for sequencing. (Image credit: Southeastern University)

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

If you’re wondering how fast this process actually was, well, it really wasn’t. The researchers were able to write and read at around 0.5 bytes/hour with a single electrode. That figure is ridiculously low for the overall digital footprint of even a minute of our lives, let alone significant storage space. However, the process is capable of scaling up as currently designed. By increasing the number of electrodes to four, the researchers found that it took about 14 hours to write and read 20 bytes of data, for an average of 1.43 bytes/hour – an imperfect scaling on a already slow process. But there are also scaling and improving techniques to be done from here – we have to remember that Intel’s Pentium started at 60MHz in 1993.

DNA-based storage is still far from having a significant capacity. Significant speed improvements are still needed, but that’s the custom across the board. If the Cambrian explosion of DNA storage is yet to come, it is another important step in this journey.