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. He had a whole new way of looking at polymers, again using electron microscopes.
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. 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.
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.