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The Evolution of LR White

Written by Dr Brian Causton, founder of London Resin

The formulation now known as LR White first saw the light of day in 1968. I was studying corrosion in submarine battery grids and needed to prepare metallurgical samples that preserved the fluffy structure of the corrosion product in exact register to the corroding alloy beneath. The existing embedding material was too viscous, and because I was using an early surface analyser called the Cambridge Geoscan the electron beam was ablating my old embedding resin, causing the specimen to disintegrate. So, instead I made a very low viscosity embedding material with a good electron beam stability. In those days we tended to synthesise our own resin components and I based my formula on acrylics because they were less sensitising than epoxies and urethanes. The formulation worked perfectly and I was able to prove the corrosion originated as a result of segregation in the battery grid alloy.

A year later I had seized the opportunity to work with Mike Braden at the London Hospital Medical College in the rapidly growing field of Biomaterials. ‘The London’ was a very inclusive place to work and quickly I was being helped in my research by the advice and sharing of resources of the schools many departments. Foremost among them was Professor ‘Loma’ Miles’ Oral Pathology department. John Linder (JL) was head of the Oral Pathology Laboratory.  

It was JL that opened my eyes to the complexity of biological tissue. He greatly increased my knowledge of Light microscopy and would let me use his precious interference microscope to study the propagation of cracks in implants and bio-adhesives. JL was a magnet for struggling young researchers and as a result I met many people in need of solutions to difficult embedding problems. 

As the only polymer chemist in the room I was for ever making novel resin system for my colleagues to try as they investigated tissues as diverse as healing burns to old stab wounds to failed hip protheses. However, as a junior academic in the early seventies my most popular formulation was a rust stabiliser, an essential aid when getting ones car through the MOT!

Kidney, Jones Hexamine Silver. Total mag x 560. Section thickness 1 um

I began to investigate the biofilms that form on implants in the early 70’s. To do this I resurrected my old embedding resin from ’68. The reason being that I needed the help of Wally Goss and his electron microscope to understand the fine detail of the process and didn’t want to use the far more toxic low viscosity epoxy resins on offer at the time. I had joined the RMS by then and had started to try and persuade microscopists to use acrylics as opposed to epoxies for reasons of health and safety. I would slip people bottles of my resin at conferences and RMS regional meetings. Soon I was taking my resin to conferences abroad, I knew no shame in my missionary zeal to convert the microscopy world to acrylics. I was still synthesising more than half the components of the resin, though the growth of soft contact lenses, plastic dental fillings and false nails had made some of the components more available. 

At this time, I was starting to get useful feedback on my formulation. It’s use embedding seed coatings and other highly fibrous tissue was proving particularly advantageous.   This was to be expected because the formula was designed to enhance the diffusion coefficient of the tissue to the large crosslinking components of the resin by the smaller more agile components of the mix heading the diffusion front and lowering the glass transition temperature of the fibre bundles. The light microscopists, with their large specimen blocks were reporting instances of chattering when cutting thin sections and the electron microscopists with their small blocks reported very little. The cause was the nature of the exothermic curing reaction of acrylics. If the exothermic reaction is allowed to run away this results in a much higher degree of crosslinking in the cured resin.  When the resin is cut the crack that grows ahead of the knife blade accelerates away from the blade edge, quickly reaching its terminal velocity in the cured resin. At this point the crack bifurcates and accelerates even more quickly, bifurcating again and again. This is the cause of the chattered surface. 

I mention this because I learnt a great deal from this feedback, I learnt that size matters. When using radical polymerised embedding material tailor, the curing instructions to suit the size of your specimen, the larger the specimen the slower the cure should be; lower the oven temperature, reduce the accelerator a little, be watchful of the intensity of light source used in the light-curing of the resin. At this time the other useful feedback evolved around the infiltration of the resin into the block.  I mentioned that the resin formula consists of large bulky components and fast diffusing small components. The small components have to be given time to lower the mechanical glass transition temperature of the biomass it is diffusing through. The difference in diffusion coefficient between a mass below it glass transition temperature and one that is above is 1000 times. If the infiltration is rushed and the curing started prior to equilibration, parts of the specimen will only have the smaller components of the resin present, leading to heterogeneous crack propagation during sectioning. 

Human Oral Epithelium. Section stained with aqueous Uranyl Acetate and Lead Citrate. 120kV x 36,000

For ten years I gave out small bottles of the resin and built up a feel for how best to use the resin in a wide variety of circumstances. However, during this time there had been an increase in the use of immuno-chemistry in both light and electron microscopy.  At the time one of my main fields of study had been the formation of biofilms, and the bodies response to implants. My approach to biofilm formation was to make implant coating that had the structural and charge characteristics of both free and surface perturbed water.  At the time I was privileged to give small chats at Julia Polak’s immuno-histology summer school at the Royal Postgraduate Medical School. I immediately saw a link between the need to embed the tissue in such a way that the labelled antibodies could interact with their targets, and my own work on implant biofilm progenesis.  So I started slipping bottles of my resin to immuno-cytochemists, modifying the formula to allow the resin to be cured at low temperatures with blue light using Benzil as an initiator. This later became known as LR Gold.

It was Tony Robarts from York that suggested I made the resin in commercial quantities. Ironically, I asked Alan Agar, who had founded a company called Agar Aids if he would like to manufacture the resin, but he said no at the time. So I approached the trustees of the London Hospital.  

Back in 1919 an improved form of resorbable catgut suture had been invented in the surgical department. A company had been set up to manufacture the sutures and was known as The London Catgut Company. Little did I know that the company had recently gone into liquidation and my suggestion of founding a new company called The London Resin Company, only raised painful memories in the minds of the trustees. However, they said that if I wanted to use the name that was fine by them. JL and Wally Goss had retired by then so I invited their successors, Jocelyn Germain and Roy Gillette, to join me in the venture.  

Human Lymph Node. Gordon & Sweet’s Reticulin stained x25 objective

I was to make the resin in my garage in Basingstoke, what could be simpler. Well for a start, commercial resins and monomers are sold in 200kg barrels, not handy Winchesters, also the barrels were delivered by juggernauts from Rotterdam at 6:00 in the morning to my house in a twee new development with narrow roads.  I heard the juggernaut reversing down the road and groaned as I saw it missing neighbours’ cars by inches.  The friendly Dutch driver asked me where the factory and my forklift truck were, after he stopped laughing, we had to come up with a cunning plan. We took the mattresses of the beds and placed them next to the lorry in a pile, he rolled the 200kg barrel off the lorry and onto the mattresses and I stopped it from flattening my neighbours’ roses. As he drove of down a sea of twitching curtains, it dawned on me that three more barrels were on their way.  By the time they arrived I had made a ramp and winch mechanism.  However, I was at The London when the next barrels arrived so my wife Chris got the other barrels off the lorries.  

At this time a search of the liner the QE ll at Southampton docks had revealed bomb making equipment and the local TV that night were appealing for the public to report any strange deliveries of bulk chemicals. No one snitched! 

Forty years on and two factories later, Agar Scientific has taken over the manufacture of the LR White and LR Gold resins in their new resin manufacturing facility at Stansted. I quite miss my old factory in Berkshire, but I miss the chance to answer customer queries more. 

The introduction of uncatalysed LR White arose from just such an exchange. Soon after the launch of LR White I got a letter from the Clove Diseases Research Centre in Madagascar asking if we shipped to the tropics, the only way to find out was to send them a free bottle, which duly arrived pre-polymerised, not a great start. So, I made up a special batch with no catalyst, sent it off with the catalyst in a separate bottle and the diseased cloves were embedded without further ado. Uncatalysed LR White is still in production today.  

For more information on the London Resin range at Agar Scientific, please visit www.agarscientific.com/londonresin

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