Scientists have created a molecular tagging system that utilizes synthetic DNA strands to create a "molbit" barcode that is readable within seconds.
We've all found ourselves in the middle of a changing room, panting and desperately trying to untangle ourselves from the wrath of a top – which upon reflection, maybe is a size too small – all the while being prodded and scratched by the price tag.
After the ordeal, perhaps you decide to purchase the top anyway, in which case the price tag becomes a central part of the transaction. By scanning the barcode at the till, the cashier is alerted to exactly how much you are required to pay for the item and informs the store's supply system that stock needs replenishing.
It is possible that you do not give this process much thought at all once you leave the store, bag in hand. After all, we see barcodes printed everywhere, from the aisles in the grocery shop to our Amazon parcel that we track on our phones as soon as it leaves the warehouse. In the smartphone era, we have even seen the traditional black and white barcode receive an upgrade to the modernistic QR code. But scientists have been working on novel methods to improve these object tagging systems, which can have several limitations, depending on the context in which they are being used.
Thanks to advances in the field of synthetic biology, scientists can now store data in the form of DNA code. As such, the utility of DNA as part of a "molecular" tagging system has been explored. DNA is incredibly small, and thus offers the potential for an incredibly compact tagging system, compared to conventional approaches.
“Molecular tagging is not a new idea, but existing methods are still complicated and require access to a lab, which rules out many real-world scenarios,” said Kathryn Doroshack, a PhD student in the Molecular Information Systems Laboratory (MISL) at the University of Washington. Doroshack is the lead author on a paper published in Nature Communications, outlining the MISL teams' creation of a novel molecular tagging system, known as Porcupine.1
“We designed the first portable, end-to-end molecular tagging system that enables rapid, on-demand encoding and decoding at scale, and which is more accessible than existing molecular tagging methods,” added Doroshack. Porcupine, developed in collaboration with Microsoft, uses synthetic DNA-based tags and nanopore-based readouts.
How does Porcupine work?
The scientists first created 96 unique synthetic strands of DNA which they called molecular bits, or "molbits". The 0s and 1s of a digital tag are represented by the absence or presence of each of the 96 molbits. Why 96? MISL co-director Karin Strauss noted that this was to provide initial proof-of-concept that the system works.
"A user first defines a digital tag as a binary 96-bit number, and pipettes 1-bits into the molecular tag. The tag is applied to an object, which is then shipped or stored," the authors write in the paper. For a user to then read the tag, they must rehydrate it and load it onto a ONT MinION device – a portable system from which software decodes it without any prior information regarding the original digital tag. A visual shared by MISL summarizes this process.
After designing the original 96 molbit barcodes, Doroshak and colleagues wanted to increase the number of molbits without having to physically synthesize more of them. To do this, they inserted a DNA fragment in between the barcode regions in the molbit as a spacer, the length of which can be modified. Therefore, each molbit consists of a unique barcode and a spacer sequence of a specific length. " Length works as an additional encoding channel because even without basecalling, the length of nanopore signals can be easily distinguished; the signal length is roughly proportional to the DNA fragment length," they write in the paper.
For a molecular data storage novice, this approach may sound slightly more complex than the conventional black and white striped barcode. But it holds numerous advantages, the developers emphasize. "Unlike existing inventory control methods, DNA tags can’t be detected by sight or touch. Practically speaking, this means they are difficult to tamper with,” said co-author Jeff Nivala. “This makes them ideal for tracking high-value items and separating legitimate goods from forgeries. A system like Porcupine could also be used to track important documents. For example, you could envision molecular tagging being used to track voters’ ballots and prevent tampering in future elections.”
Furthermore, whilst DNA is renowned for being expensive to both read and write, the Porcupine system overcomes this issue by pre-synthesizing the DNA fragments, which lowers costs and enables the rapid creation of new tags by mixing existing strands.
Molbits – the future?
Will we be seeing DNA-tagged clothes in stores any time soon? Perhaps not for some time, as this is one of the more novel applications of synthetic biology. But, the authors are certainly enthused about the applications a system such as Porcupine could have. "Porcupine is one more exciting example of a hybrid molecular-electronic system, combining molecular engineering, new sensing technology and machine learning to enable new applications.” MISL co-director Luis Ceze concluded.
1. Doroschak K, Zhang K, Queen M, et al. Rapid and robust assembly and decoding of molecular tags with DNA-based nanopore signatures. Nat Communications. 2020;11(1):5454. doi:10.1038/s41467-020-19151-8.