For more than three decades DNA has been synthesised by constructing individual strands through sequential chemical addition of bases and then combining them to create longer, double-stranded DNA.
Despite various improvements in the approach, there remain numerous problems in the synthesis of longer DNA. Current techniques are typically provided as a service, are slow, cannot synthesise all sequences and often incorporate random errors, requiring cloning time-consuming further analysis and sequencing to ensure acceptable quality. In addition, synthesis of error-free DNA becomes increasingly difficult as the length increases, creating challenges for its use in synthetic biology where the ability to access high-fidelity DNA at scale is an important requirement.
Our proprietary approach utilises a silicon chip, made by MEMS processing, that integrates physics with biology, and controls the synthesis of DNA at many thousands of independently controlled reaction sites or ‘pixels’ on the chip surface in a highly parallel fashion. Our approach is compatible with both chemical and enzymatic DNA synthesis. Following synthesis, strands are assembled on-chip into double-stranded DNA in a process that identifies and removes errors, providing accuracy that is several orders of magnitude better than the conventional approach.
We have developed a unique silicon chip that allows large-scale DNA synthesis to occur in parallel. Rather than creating different strands in physically separated wells, we use thermal engineering to independently control the sequence of strands synthesised at each reaction site.
By controlling the temperature of each reaction site, the growing strands of DNA are selectively deprotected, preparing them for new bases to be added according to the planned DNA sequence.
As reagents for each of the four bases (A, C, G, T) are introduced sequentially, the timing of thermal deprotection enables a different sequence to be synthesised at each of the reaction sites.
With the silicon chip’s ability to precisely and independently control the temperature of individual reaction sites, we can detect and remove any strands with errors before they are incorporated into double-stranded DNA. We achieve this by understanding the melt temperature of annealing DNA strands and the shift in this temperature that a sequence error causes. This saves the laborious, time-consuming work that would otherwise be required to search for and assemble error-free DNA.
By assembling long, double-stranded DNA from short strands, we are able to test for accuracy at each step of the assembly process and thus prevent errors from contaminating the final product.
Our binary assembly process is unique and is central to revolutionising the established methods of making DNA.
Our desktop device
Our DNA writer will be a ‘plug and play’ desktop instrument, easy to acquire and use.
It will support multiple functionalities and applications through single-use, application-specific cartridges that contain the bulk of complexity and enable highly parallel synthesis.
The user interface, design algorithms, partnering and community portals will all be implemented in the cloud enabling, among other things, tight control of the biosecurity aspects of gene synthesis.
Advantages of our approach
An integrated desktop platform
High-fidelity DNA at scale and in the hands of every researcher
Rapid prototyping to accelerate the evolution of new genes and pathways
Third-generation gene synthesis