An interview with Professor Mervyn Miles

In this month’s blog I caught up with NuNano co-founder and director Professor Mervyn Miles to discover not only where his fascination with microscopy and high-speed imaging came from, but also where he thinks the next exciting areas of research are to be found...

 
Mervyn Miles is Professor of Physics at the University of Bristol, as well as Chief Scientific Advisor to the Institute of Physics Publishing and a Fellow of the Royal Society.

Mervyn Miles is Professor of Physics at the University of Bristol, as well as Chief Scientific Advisor to the Institute of Physics Publishing and a Fellow of the Royal Society.

 

How did you get involved in microscopy?

It’s funny because I never set out to work with microscopes. My PhD actually focused on understanding polymer samples and for the first part of my career, understanding and predicting the structure of polymer samples remained my main point of study.

During my time at Birmingham University, I was granted access to a million electron volt (MeV) electron microscope.

Now in the normal course of things polymer samples tended to get destroyed after a couple of seconds in electron microscopes operating in the 100 keV range. Not with this one though!

Using the mega-volt microscope, I could see all sorts of pretty diffraction patterns. My sample looked almost as though it was on fire in dark-field imaging. I couldn’t believe what I was seeing, that it was possible to see this much detail without killing the sample.

From that point on I was hooked on microscopy and imaging - though at that stage only because it was a fascinating tool to facilitate my polymer research.

So a key part of your polymer research was around accessing the best possible imaging equipment?

Yes, you could say that. I went to Germany to do my post-doc in synthetic polymer physics studying under Herbert Gleiter[1]. He had a whole new way of looking at polymers, again using electron microscopes[2].

He was an amazing guy to work with, really inspirational. He had a constant stream of ideas and treated everyone as an equal despite the fact he was working on some complex stuff and cutting edge ideas. In many ways I internally absorbed his way and pattern of working.

During this time I obtained some pretty interesting images, showing the nanoscale structures of polymer fibres produced under elongational flow stretched single molecules[3].  I showed these some years later at a conference which was attended by Andrew Keller, a polymer physicist working at the University of Bristol.  Keller was pretty impressed with what we'd achieved, which sorts of shows that it was ground-breaking stuff we were working on.

After I completed my post-doc in Germany I went to Case Western Reserve University, Cleveland, Ohio, which at the time had the best polymer department in the U.S.  That was a totally different experience to working with Professor Gleiter.  The guy I worked with in the Department of Macromolecular Science had great drive, but his focus and strength was in co-founding and building this department from the ground up, rather than the science.  He pretty much delegated the running of his quite substantial research group to me.  So I learned a lot quickly - many different projects needed data interpreting and new ideas and new directions.

After just one year in the U.S., I started my first period in Bristol.  Prof Andrew Keller, who founded the field of polymer physics, had told me that if I ever wanted a job to contact him.  It was time to cash in this offer! In that move, I did two very different jobs: transmission electron microscopy of polymers and elongational flow of polymer solutions to understand the nature of individual molecules in solution and what happen when they were stretched out by the flow field.  This all went very well, but after three years it was time to find a ‘proper job’ rather than another post-doc position.

My next move, still focusing on polymer research, was to Norwich, to work – rather bizarrely – for the Institute of Food Research. They had loads of money to do basic science which in turn meant we weren’t constrained in the science we could do. Though ideally the sample should be edible!

Our head of division was a fascinating enigmatic guy called Henry Chan. He moved so quietly around the place he would suddenly appear at your shoulder whilst you were working and say, ‘you’re in trouble Miles, …. Big trouble’.  I never found out if I really was or not. But brilliant. He was the person who first introduced me to and encouraged me to work with the new science of scanning tunnelling microscopy (STM).

Nobody really knew what it was about of course. Even at the European Bioscience Physical Congress, held in Bristol in 1984 – a huge conference with many parallel sessions including one on x-ray microscopy. I found myself making small talk with a chap needing help to find the building for the next session, I asked him was his area of research was. He told me about this esoteric technique where a sharp piece of wire is brought within an Angstrom or so of the sample surface and the quantum mechanical tunnelling current is measured as it is raster scanned over the sample. I thought this would never work because of the mechanical stability and control precision that would be needed. This was of course scanning tunnelling microscopy for which he, Heini Rohrer, and his colleague Gerd Binnig would be awarded the Nobel Prize in Physics two years later, and with the help of Prof. Sir Mark Welland in Cambridge, I began the change in direction in my career to this technique.

Through Dr. Chan’s and Dr. Morris’s encouragement I took one of the protein molecules I had been studying with small-angle x-ray scattering (SAXS) and deposited on an x-ray mirror’s surface, amorphous carbon, and looked at it via the STM with Mark Welland. It was pretty amazing. Through the images we obtained, we discovered the 3D structure the STM was showing us of individual molecules was as I had predicted from SAXS - we got one of the first pictures of a single protein molecule[4].

When did you start getting involved in the development of instrumentation?

By this point I was increasingly interested in the latest and best developments in microscopy.  My focus was on improving the substrate for immobilising biomolecules rather than the tool itself though.  I was always looking for the best substrate materials.

In 1989 I moved back to the University of Bristol, again working with Prof. Andrew Keller.  I was supposed to be working on x-ray diffraction and scattering, but clearly STM was going to be huge, so I applied for an STM grant immediately I arrived in Bristol and we were awarded it in April 1990. This meant we finally had our own STM to play with!

Around this time one of my undergraduate project students built a scanning near-field optical microscope (SNOM) which achieved the best resolution of anywhere in the world and this is really where developing instruments came in for me, from around 1990. This is the photon analogue of STM.

Shortly after that, I put in for a grant and got an Atomic Force Microscope (AFM). I recruited a post-doc, Terry McMaster, from Norwich, and we began work on AFM of biomolecules.

One from the archive... The Bristol SPM group in 2000, celebrating Mervyn's inaugural lecture.

One from the archive... The Bristol SPM group in 2000, celebrating Mervyn's inaugural lecture.

So when did you start your first company?

When I was awarded a personal chair, that is, promoted to professor at Bristol, I decided to do something different. I began work on developing holographic tweezers and also started a company: Infinitesima.

We produced and sold a product called Activ Q which helps to control the quality of factor of the cantilever and is very important in liquid for improving image quality in liquid. We sold quite a few which was encouraging. One of the key issues for a while had been around improving imaging quality and stability in liquids.

We started trying out ideas to increase the speed of imaging, initially in SNOM, where we managed to increase the frame rate 100,000 times.  We then wanted to try this for AFM, which would have far more applications.

Amazingly it worked – and even more amazingly the speed was critical to it being able to produce great images in liquid (see figure below for a recent example of our high-speed AFM imaging). If we had turned the speed up slowly we probably wouldn’t have continued along this route because it turns out that at a slower speed the sample continues to be destroyed! Another one of those, ‘let’s give it a go and see what happens’ instincts that turned out well!

So where did the idea to set up NuNano come from?

It was about ten years after I’d started Infinitesima. Frustrated by the varying quality of existing AFM probes, we thought maybe there was an opportunity to make improvements. It was the brain child of my colleague and co-founder Heinrich Hoerber. The mix of what seemed to me to be a great idea with the enthusiasm and drive of former PhD student and post-doc James Vicary made setting up the company a no-brainer.

James has done a brilliant job of implementing the idea and turning it into a successful product.  And, importantly developing out from that original idea to produce the kind of game-changing probes that no-one else is working on yet, such as the ultra-soft high-speed vertically-oriented probes (VOPs).

What excites you about the future of nanotechnology and what’s the next area of research you’re most interested in?

I think the use of high speed VOP force microscopy in true non-contact mode, with zero normal force, on living cells will make a major impact.  The ability to see signalling, transport and whole changes in structure at the cell membrane will give exciting new information.

Using the high speed vertical probes for example, as I have done lately with work I’ve been doing around Alzheimer’s, just makes you realise how much more there still is to be explored in the world of force microscopy.

Imaging membranes at high speed means you don’t end up making holes in the lipid (and thus destroying the sample). We’ve produced the most amazing images of membrane samples where you can actually see the Amyloid proteins destroying the membranes.

It's exciting and important work and we're looking at ways to go beyond just imaging.

High-speed (left) and normal speed (right) AFM images of the same area of a model multi- lipid component neuronal membrane. The contrast corresponds to the slightly different height of each lipid.  Such membranes are very soft, almost liquid-crystal-like, yet the disruption by the high-speed tip is surprisingly almost non-existent.  Image courtesy of Morgan Robinson & Zoya Leonenko (University of Waterloo, Canada) and Loren Picco, Ravi Sharma & Mervyn Miles (University of Bristol, UK).

High-speed (left) and normal speed (right) AFM images of the same area of a model multi- lipid component neuronal membrane. The contrast corresponds to the slightly different height of each lipid.  Such membranes are very soft, almost liquid-crystal-like, yet the disruption by the high-speed tip is surprisingly almost non-existent.  Image courtesy of Morgan Robinson & Zoya Leonenko (University of Waterloo, Canada) and Loren Picco, Ravi Sharma & Mervyn Miles (University of Bristol, UK).

[1] H Gleiter, “Nanoglasses: A new kind of Noncrystalline Material and Way to an Age of New Technologies?” Small 12 (2016) 2225–2233

[2] J Petermann and H Gleiter, “Direct Observation of Amorphous And Crystalline Regions in Polymers by Defocus Imaging”, Philosophical Magazine 31 (1975) 929-934

[3] MJ Miles,  J Petermann & H Gleiter, “Deformation Mechanism of ‘Hard’ Elastic Fibres’, Colloid & Polymer Science, 62 (1977) 6-8.

[4] ME Welland et al., "The Structure of the Globular Protein Vicilin revealed by Scanning Tunnelling Microscopy", International Journal of Biological Macromolecules, 11 (1989) 29-32.

Building a world class team: What NuNano can learn from Le Tour

As many of you are aware my passion (aside from AFM probes of course!) is cycling.

July is the big month in the professional cycling calendar, as the sports' top athletes take part in the Tour de France.

It's always the wearer of the famous maillot jaune or yellow jersey who grabs the headlines.  As the rider with the lowest cumulative finishing times, they are the overall race winner at the end of the gruelling 2,200 mile mountainous ride.

Team Sky at the Tour de France

Team Sky at the Tour de France

But the yellow jersey winner is heavily dependent on the performances of the other eight people in their team.  Interestingly, each of those team members has a specific role to play in making that win happen - be that as team road captain, sprinter, climber or domestiques (the guys who give up their wheels when team-mates puncture or collect food and bottles to distribute to other team members).

What's fascinating is that each of these riders, generally speaking, have psychological profiles that match the roles they play.  Sprinters and team captains tend to be extroverted, whereas climbers and time-trialists are likely to be more internally driven and introverted.  Sprinters and time-trialists are more motivated by the desire to win, whereas road captains and domestiques are motivated by the effectiveness with which they can support the team.

It's much the same in any team building situation of course.  But maybe I'm more focused on this aspect of Le Tour this year because NuNano is in a state of growth - I'm in the process of building our world-class team!

 
Our expanding process engineering team

Our expanding process engineering team

 

It's quite a different challenge for me and for the company as a whole.  We've brought an academic idea out into the world of commerce and in doing so have had to learn an enormous amount about how a business functions.

That's required me to develop 'all-rounder' skills - perhaps the equivalent of being Chris Froome in Team Sky (?!).  But like Chris, I need a team around me.  So now it's all about making sure NuNano is made up of the right mix of roles and personalities, and that I have a good understanding of the difference ways in which each type of person is likely to be motivated.

Process engineers for example are more like the hill climbers.  They need longer extended energy for those mountainous ascents/long periods of time working to develop robust fabrication processes.  Here pacing rather than speed is the key and their ability to internalise their motivation and maintain their patience and dedication right through to the summit/the completed fabrication of a batch of probes is critical.

Conversely, sales managers are more like the sprinters in the team.  They work in short bursts of energy and are hidden away for most of the racing day/probe fabrication process, only really seen at the crucial point where focus is on crossing the finishing line first/winning the business.

Obviously, each person is individual and such generalisations are only useful up to a point.  But what is really exciting however is that we're starting to fill out these desks around me, a process through which I get to learn more about the people, their passions, and the skills they can bring to NuNano, to continue our ongoing success and growth.

NuNano joins new Bristol hub for science start-ups

We’re delighted to announce that this month NuNano has moved into Bristol’s newly launched centre for scientific enterprise, Unit DX.

 
 

Much like SETsquared, the ‘home’ we’ve just come from, Unit DX is a business incubator. But whereas SETsquared caters for high-tech start-ups in general, Unit DX’s mission is to encourage more scientists to join the entrepreneurial ecosystem in Bristol.

In addition to the office space, meeting rooms and event spaces you’d expect to find in any business incubator, the majority of Unit DX premises are given over to high-spec lab space and facilities.

It couldn’t be closer to my own belief in the importance of academic entrepreneurs and the value we can bring by drawing research and business closer together.

What is also inspiring is being part of a facility that is frankly unique outside of the London, Cambridge, Oxford triangle.

I chose to set up NuNano in Bristol and have felt as frustrated as Unit DX founder, Dr Harry Destecroix, at the brain drain of scientific talent from the city.

Many of my colleagues who have moved away have done so because the opportunities simply weren’t here, despite them often wanting to stay in the area and do something innovative and challenging with their research and ideas.

Harry is having numerous conversations with companies and individuals about taking up residence in Unit DX and I have to say if you’re even half thinking about setting up a science-based business get in touch with him as soon as.

Whilst it’s a bit echoey in here at the moment with ourselves and Ziylo as the first two residents it isn’t going to be this way for long. There’s a real sense of anticipation of what Unit DX will become over the next few months (and the bonus is we got to pick the best desks!).

 
unitdx02.jpg
 

It’s going to be fascinating to see the businesses as they start to come through. NuNano is already established and we’ve learned such a lot along our journey to the growth stage we find ourselves at now. I’m hopeful that we may be able to offer helpful suggestions and pointers to some of the newer companies just in the natural course of being in the same building.

Engaging with fellow academic entrepreneurs, sharing our enthusiasm and our experiences of the worlds of academia and business can only serve to expand our knowledge and understanding of both.

Now, where's the coffee machine in this place...?

 

If Carlsberg made AFM probes...

When you drink a pint of Carlsberg you know precisely what to expect in terms of taste and flavour.

Carlsberg’s best known beer, Carlsberg Export, is allegedly still brewed to the original recipe that Danish brewery founder J.C Jacobsen created in 1847.

Jacobsen claimed that “develop[ing] the art of making beer to the highest possible degree of perfection” was his central and constant purpose.

For the company, as for the founder, repeatability of their lager recipes to the same standard every time continues to be central to this pursuit for (and some might say achievement of) excellence.

 
Carlsberg-Bottle-Neck.jpeg
 

Reliability and repeatability are values that we hold pretty dear at NuNano too.

The experience of working with AFM probes as a doctoral student has informed my own “pursuit of perfection” in the art of making AFM tips to a consistently high quality of sharpness.

Few things were more frustrating than going through the rigmarole of preparing my precious sample, setting up the system, carefully scanning the sample and then not getting the image or image clarity that I expected.

Checking off the different reasons for this and adjusting various imaging parameters, only to discover that simply changing the probe made all the difference in the world was a good outcome, but very time consuming, and sometime required the preparation of yet another sample...

It wasn’t just the cost of the probes or the associated time wasted in this way that I found frustrating, it was also the break in momentum. I know from other colleagues then and now that poor tip sharpness can stall a good day’s science.

For some it’s costly in different ways, for example when they are dealing samples that are particularly sensitive or could degrade quickly. There simply isn’t time to faff around changing AFM probes.

 
Quality Control @ NuNano

Quality Control @ NuNano

 

For this reason I’ve ensured a market leading level of quality checking in our AFM probe manufacturing process.

Specifically, during and after production we inspect every single probe.

Using scanning electron microscope (SEM), we check each probe for tip sharpness, cantilever thickness and uniformity, measuring the radius of the curvature of the tip to ensure it is sub-10 nanometres.

Our strict quality control (QC) process during fabrication safeguards the tips from contamination during these checks. The follow up post-production QC confirms that each tip meets the requisite sharpness, and if it doesn’t, the probe simply doesn’t get shipped.

As founder of NuNano, this is my central and constant purpose: ensuring that we provide a level of quality that guarantees reliable and accurate imaging from every probe in every box we ship. It gives our customers peace of mind and saves them time as every probe works.

And this of course is precisely what makes our AFM probes the best in the world. Probably.

Pint anyone?

Why growing your start-up business inside an incubator is a good idea – an outsider-insider perspective

This month’s blog is written by our non-exec Chairman Rick Chapman who reflects on his journey with NuNano and what it takes to raise a company from start-up to scale-up…

Rick has over 30 years of experience working in high tech industries (including corporates such as Marconi and STMicroelectronics) but since 2001 he has worked predominantly with start-ups, successfully helping four grow himself – two hardware and two software businesses.

 
Rick Chapman, Non-exec Chairman, Nu Nano Ltd

Rick Chapman, Non-exec Chairman, Nu Nano Ltd

 

We’re experiencing exciting times at NuNano. As a company we no longer really fit the descriptor of ‘start-up’, having graduated into a growth-stage company.

You’ll be hearing more about this in the coming weeks, but I want to share with you some of key factors that helped move us from a position of having cutting edge tech, grounded in academic research, that we’ve now turned into a viable, expanding and scalable business.

Central to our success has been the fact that, since our inception, we have been housed within SETsquared, the University of Bristol’s business incubator.

The SETsquared Partnership was formed in 2003 through a collaboration between five leading research-intensive universities: Bath, Bristol, Exeter, Southampton and Surrey. SETsquared is a focus for enterprise activity and new business creation for the five university partners, including incubating start-ups.

Whilst an incubator isn’t the right thing for all start-ups, a young business, like a young child, needs support, guidance and to be part of a community. For us SETsquared was the perfect environment for this nurturing growth approach, but any incubation hub is good, at the right time.

 
Inside SETsquared Bristol - © Candour Creative Photography

Inside SETsquared Bristol - © Candour Creative Photography

 

Here are three ways that being part of SETsquared really moved our business on.

1)  Business Review Panels – Roughly every 6 – 12 months SETsquared invites the companies it is incubating to present to a panel of 5 – 6 business people. This is a mix of people from within SETsquared, within industry and from services such as legal and finance. It’s effectively a cross between Dragon’s Den and a therapy session! The CEO presents the current business plan to the panel which is followed by a 2 – 3 hour discussion about the business, approach and next steps. Knowledge and insight is shared with the start-up and a robust plan of next steps is formulated with the CEO.

2)  Coaching and mentoring – SETsquared have ‘Entrepreneurs-in-Residence’, these are people like myself who have a significant amount of industry and start-up experience who are able to provide structured and ad-hoc support, advice and guidance to the CEO as they navigate the first few months and years of the business, implementing their plans and responding to challenges.

3)  Learning and development – SETsquared annually organise a number of workshops from the basics of setting up a company to company finances, writing grant applications, presentation skills and so on. What works really well for companies within the hub is that they can attend these workshops at the point in time that it is most relevant and helpful for their company development.

Fundamentally this combination of support methods means that the incubator is able to provide a bespoke programme tailored to the real-time needs of the developing company.

There is of course a fourth way that incubators can help – they can put a business like NuNano in touch with someone like me – people looking to get actively involved with young companies and assist their growth in a hands-on fashion. This combination of solid technical and academic credentials with strong business background and knowledge of developing start-ups makes for a powerful relationship. Ultimately having the right mix of great product and great business skills is what can really help to take your business onto that next level.

Now not all such connections necessarily progress as ours did with me becoming non-exec chair of NuNano. However if you speak to any of my fellow ‘Entrepreneurs-in-Residence’ at SETsquared they would agree that one of the challenges of working in an incubator is holding yourself back from wanting to get too involved in a hands-on way with all the great companies that you meet.

 
Rick Chapman, Non-exec Chairman, Nu Nano Ltd
 

In the main, we simply don’t. But with NuNano it was different. I was impressed from that first Business Review Panel – here was a company with a great product, being led and run by one person, James Vicary, but with a vision from the get-go of being something much bigger.

One indicator of this was the fact that the company had a board in place – something that many might consider overkill for a company with, as it was then, just one employee. But having that structure in place set out a clear stall in terms of future ambition and, as that future starts to unfold before us now, puts us in a strong place with new investors as we’re already set up and familiar with boardroom landscape.

I can’t speak highly or strongly enough of the importance of the level of guidance and support for new businesses provided by innovation hubs such as SETsquared. You can’t put a price on the value of having the ability to run out and test ideas and strategies and come back into the relative safety of the hub to discuss how things went, what could be done differently and what needs to be done next.

I feel privileged to have accompanied James and NuNano on the journey from that first Business Review Panel - very much as a company outsider - to most recently helping to drive the business into our latest stage of growth from the inside.  Whilst the time with the incubator is coming to a natural close as we move into the next phase of development, I would certainly recommend other fledgling companies to consider joining an incubator program to help grow their acorn idea into something that is built to last.