Team Talk – Dr Vijay Narayan, Head of Physics
When did you join Evonetix, and what attracted you to the Company?
I joined Evonetix in April of 2018, when the Company was a lot smaller than it is now. I was particularly struck by the ambition of the Company, its goals, and exciting vision. The opportunity to get involved in the pioneering field of synthetic biology at such an early stage really appealed to me.
What is the focus of your role at Evonetix?
I first joined the Company as a Senior Engineer. My role was to develop the layout of the DNA chip that lies at the heart of our technology. I also performed simulations of the thermal properties of the chip to check its performance and provide feedback to our manufacturing partners.
I took on the role of Head of Physics in October 2020, and my role has expanded along with the size of the team: we were initially a team of four, and now we are ten. The team’s activities are focused on the development of the chips, computational modelling, distribution of prototype chips to our Biology and Chemistry teams, cooling of the chip under operating conditions, and devising methods to transport DNA across the chip. We interact with all the other teams within Evonetix as well as with our external manufacturing partners, and therefore a significant aspect of my role now is to facilitate and maintain communication between the various parties. This ensures that everyone has a full understanding of the device requirements and that no information is lost.
What first ignited your interest in synthetic biology?
I have always been intrigued by interdisciplinary environments. This is what initially drew me to synthetic biology, as it combined aspects of physics and biology that I had previously enjoyed working in. When I first read about Evonetix, I could see the huge potential that the Company’s technology offered to the field, and its ambitious goals and vision really resonated with me. The opportunity to make a chip that would ultimately have applications in biology and chemistry seemed very unique and exciting.
We understand that a key challenge faced by your team was the need to design a heater only 100 μm across, and keep its heating effect completely separate from another, just 300 μm away. Please could you describe why this was needed, and the approach taken by your team?
The interesting thing about this heater is that it is just a mini version of a heater found in a kitchen hob. But there are challenges and complications working with something so small when such a lot of heat is generated in an area only 100 µm across. For instance, we get tiny ‘explosions’ if the thermal power is not properly optimised, and so it is important we manage the thermal behaviour of the system closely. Our customised chip design enables heat to “spread” out evenly across the heater area and ensures that the area outside the heater is kept cool. We did this by testing a combination of different design layouts and using simulations to assess potential failure points.
The challenge and complexity associated with the design of a single heater is only one element of the problem. In some of our chips, multiple heaters are packed into an area the size of a British one-pound coin, which generates a lot of heat. To manage this, we used simulations to help us develop a cooling system at the back of the chip to remove excess heat. Our method involves a combination of flowing coolant liquid, thermoelectric coolers, and a copper base plate stuck to the back of the chip which effectively conducts heat away.
How have Evonetix’ partnerships with ADI, LioniX International, IMEC, etc helped to drive forward your development work.
All our partners have been brilliant in helping us develop the Evonetix technology further. LioniX International supplied us with silicon-based chips that allowed us to prototype the technology in full. LioniX also created a simplified version of the chip out of glass, which does not have the full functionality, but nevertheless, has greatly helped us advance our technology due to its shorter turnaround time.
IMEC and ADI are helping us with the large-scale manufacturing of our chips. IMEC patterns the heater arrays while ADI designs the electronics, and the two are combined into an integrated chip. ADI is also supporting us with the packaging of the chips.
What are the main technical challenges your group has faced, and how you have approached them?
One of the biggest challenges in designing the chip was to ensure that within the array of closely spaced reaction sites, each heater acted independently, i.e., without heating its neighbours. Our team addressed this by placing each heater on a membrane over an air pocket embedded in the silicon chip. The chip itself is glued to a copper block which, in turn, is placed in contact with a bespoke, external cooling circuit. This ensures any heat that leaks outside the reaction site into the silicon is immediately sucked away. Interestingly, even finding the right glue to stick the chip to the copper cooling block was a challenge as it needed to be a good thermal conductor to stop heat from being trapped and building up within the glue itself.
Apart from the thermal functionality, the chip also needs to be able to transport DNA between individual reaction sites when it is released from the surface of the chip. The transport is achieved through the use of electric fields: DNA being charged can be attracted, repelled, and trapped using electric fields. The fields are applied by surface electrodes which we place in the regions between reaction sites.
We also faced some interesting manufacturing challenges – one of the most dramatic being when the silicon wafers were bonded together using heat and pressure. What happens is that unless the surfaces of the wafers are almost perfectly smooth, you get tiny air pockets at the interface between the wafers. These expand when heated (as is the case during subsequent steps in the manufacture flow) and cause the silicon wafers to explode, which is very frustrating! It is therefore very important that the roughness of the bonding surfaces is less than a few nanometres since tiny fluctuations can have such dramatic effects.
More generally, a key technical challenge we faced was designing a chip that would operate with active circuitry submerged in strong acids and bases, heated to near the boiling point of water. It took a lot of investigation, and some trial and error to find materials and coatings that were suitable for use. Our biggest asset here is having such a wealth of expertise within the company and through our excellent collaborators which has enabled us to find solutions to each of these challenges.
From a physics-focused perspective, what do you think are the main outstanding challenges facing the synthetic biology field?
In physics, we rely heavily on theoretical models to help us predict outcomes of certain events. However, these become difficult to apply to complex biological systems, where a multitude of factors can have significant effects. Therefore, I believe a major challenge facing synthetic biology is the ability to develop theoretical frameworks and detailed, predictive simulations that can help us to understand what happens under different conditions. This is especially true when working with a charged molecule like DNA in a range of solvents and buffers, subjected to electrical and temperature gradients.
Another challenge is understanding what materials to use. Because synthetic biology is such a novel field, we do not have the wealth of information that other industries (such as the semiconductor industry) have on what materials are optimal. Part of this challenge is finding a balance between the materials and biological systems. Some materials that may offer good functionality could be toxic to the biological components, whereas other materials may be degraded by the harsh environments necessary to support these components. We are still learning how to optimise our materials whilst ensuring compatibility with the biological systems.
Where do you see the future development of physics in synthetic biology and what new possibilities may be opened?
The whole field of synthetic biology is reliant on access to long and accurate DNA, so I think Evonetix provides endless opportunities. Being able to make accurate tailor-made sequences could revolutionise research from sectors such as agriculture by improving drought resistance in crops, to pharmaceuticals by producing synthetic microbes that act as drug delivery systems.
Which are the areas you see the greatest opportunity for Evonetix to support research?
Other than the opportunities in the field of synthetic biology, one idea would be to use DNA for memory storage in large data centers. The stability of DNA means data has the potential to be stored for hundreds of years, but the development of this field is being held back by a range of factors, one of which is the challenge in producing long and accurate sequences. Evonetix strives to provide the tools that render these opportunities to be within our grasp.
For more information about Evonetix, please visit: www.evonetix.com.