Interview with Dr Matthew Hayes, Chief Technology Officer

Dr Matthew Hayes is the Chief Technology Officer of Evonetix and was a founding member of the team that established the Company in 2015.

Before joining Evonetix, Matthew was Head of Technology for the Global Medtech Division of Cambridge Consultants. He joined Cambridge Consultants in 2001 and was responsible for the leadership of many of their largest and most technically challenging projects.

Matthew specialises in multi-disciplinary system design, medical device development, ASIC design and opto-electronics. He holds a PhD and MEng in Electronic Engineering, both from Loughborough University.

Before starting Evonetix, I had been working on a thermocycling technology for medical diagnostics systems and had been looking at the potential for heat control in DNA synthesis. I began exploring array-based technology for highly parallel DNA synthesis and whether this could be achieved using multiple heater/cooler synthesis sites to overcome some of the challenges faced by traditional array-based DNA synthesis platforms. After some calculations on a whiteboard, I realised that it is eminently controllable and within the laws of Physics – it was just an engineering challenge.

I’d had experience in semiconductor technology and chip design from my work with Cambridge Consultants and could see how the scalability of silicon chip manufacture would allow DNA synthesis, only currently available from dedicated service centres, to be available in a benchtop system. This inspired the core idea and we started the early stage of the Company with seed money from Hermann Hauser and Cambridge Consultants. With a team of around six engineers and six chemists, we then spent the next 18 months developing the first chips.

Since then, we’ve raised series A and B funding, expanded the team to over 100 people, and have been working to combine all the separate elements of our technology to synthesise DNA on the surface of our chips.

We have designed our platform from the ground up to be a benchtop DNA synthesis system with the intention of breaking dependence on the service provider approach and giving users the power to prepare gene sequences rapidly in their own laboratories.

There are three core elements to our technology that make this possible. Firstly, our chip technology, which facilitates an extremely high-throughput, highly parallel synthesis platform. Secondly, there is the synthesis chemistry, which has been re-engineered to be thermally controlled and therefore directly controllable by our chips. And lastly, there is the error-removing assembly process, which is made possible by the combination of our novel chips and synthesis chemistry.

What makes our approach unique is that by integrating these elements we’re able to combine overlapping single-stranded DNA into double-stranded sequences in a way that removes synthesis errors. In addition to this, we’re miniaturising the process and achieving highly parallel synthesis within a machine small enough to sit on a laboratory bench top.

The ultimate end goal is to have a desktop synthesiser in every lab, putting DNA synthesis in the hands of every researcher.

In terms of other goals on our roadmap, we will continue scaling up the number of reaction sites on the chips, perfecting the assembly process, and then integrating the assembly technology with the synthesis technology. This will come as result of combining the three elements that underpin our technology and will bring us closer to building the full product.

There are a number of companies trying different approaches. One approach that is gaining traction is enzymatic synthesis, which is looking to replace the conventional chemical method as it is more convenient for general lab use. Developers are working to engineer their enzymes in the hope of providing lower error rates, however, this improvement is limited, because as the length of the DNA strand increases, the error rate also increases exponentially.

Our approach aims to address this fundamental problem, which most other companies are failing to do. Our assembly process removes errors, meaning we can accurately build long strands of DNA despite inevitable errors from the synthesis process.

Other companies working on benchtop synthesis tend to focus on either synthesis or assembly. There are some that use pre-synthesised short strands of DNA, and assemble them together, delivering the final long strands to their customers, while others use relatively low throughput instruments to deliver oligonucleotides but without the assembly capability.

Most DNA, however, is still made by service providers, who use instruments that cannot be miniaturised into viable benchtop platforms. We aim to address both sides of the process, through miniaturised benchtop synthesis and gene assembly in a single platform.

The main use for our technology will be to reduce the time it takes to iterate researchers’ designs and extend the complexity of the designs that are possible. Currently, the design-build-test cycle is restrained by the lengthy timescales of the ‘build’ process. By putting DNA synthesis directly in the hands of the researcher, we give them the opportunity to move through the cycle much faster, which in turn will greatly impact research in general.

There has been a lot of interest in synthetic biology recently, with large amounts of funding being raised by companies working in the field. However, there is a major divide between the companies that are developing the end use applications, and the companies developing the tools that are enabling them.

For more information about Evonetix, please visit: www.evonetix.com.