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ULTRA-SPEED ATOMIC FORCE MICROSCOPY FOR CRYSTALLISATION

Lead Research Organisation: University of Manchester
Department Name: Chemistry

Abstract

Crystals have provided fascination and utility to man since the dawn of time taking an important place in ancient civilisations with talismanic properties or as the functional quartz lens in the early Keplerian telescopes. The natural world utilises crystals for not dissimilar optical advantage with the eyes of trilobites consisting of calcite (calcium carbonate) lenses. Shells on the beach are also principally calcium carbonate, some parts calcite and other parts a different mineral aragonite (but still calcium carbonate). Indeed the beautiful iridescent mother-of-pearl often seen on the inside of a shell are crystals of aragonite that the organism has carefully controlled to be of a size about the same as the wavelength of light - and hence the light scattering. But crystals are also used in almost every aspect of our modern life, from the pharmaceuticals that improve our health to the catalysts that make our chemicals to the opto-electronic gadgets that enrich our lives. Crystals are organised matter, where molecules are arranged next to one another in a regular, infinitely repeating array. Mistakes in this organisation results in imperfections or defects in the crystal that can vastly alter the properties and use of the crystal. The crystals perform a clever trick by normally discarding mistakes back into solution as and when they occur and only ultimately accepting correctly positioned molecules. Nevertheless, defects do still occur. These solid crystals grow out of solutions or from the gas phase via the controlled precipitation of the molecules that make up the final structure and, because of the enormous importance of crystals, there has been interest over the past 100 years in how these crystals form. However, it is only in the past decade that modern microscopy tools that are able to monitor the growing crystals at the molecular scale have been available and deployed in such studies. This is providing a vast amount of new detailed information about the intricacies of the crystal-growth process that provides clues as to how Nature does - and scientists may - control these processes. Every crystal structure is different and every crystal shows peculiarities in the manner of growth, however, there are always some underlying rules that govern all crystal growth.

The objective of this work is to set up a state-of-the-art microscope facility that is able to observe crystals growing almost molecule-by-molecule so that the users can better understand how their crystals are growing. Armed with this knowledge they will be able to adjust how their crystals grow in order to produce crystals of the right size, shape and purity to perform the function of interest. Whether this is a medicine such as paracetamol, a material to go in your computer such as a battery or a material to capture carbon dioxide to improve climate change. The facility will be available to all those interested in crystallisation processes.
 
Description We have measured the first high speed AFM recorded on the important pharmaceutical paracetamol. This has reveled hithertoo unknown mechanisms for the incorporation of defects into the crystal structure
Exploitation Route These results will help pharmaceutical companies to control the quality of their crystalline products
Sectors Chemicals

Healthcare

Manufacturing

including Industrial Biotechology

 
Description The findings from the research have been used to understand the fundamental mechanisms of the crystallisation of pharmaceutical materials. This has resulted in the savings to pharmaceutical companies of £100k's owing to improved crystallisation workflows
First Year Of Impact 2023
Sector Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Control of Pharmaceutical Crystallisation 
Organisation Roche Pharmaceuticals
Country Global 
Sector Private 
PI Contribution We have helped Roche to understand the mechanism of their pharmaceutical crystallisations
Collaborator Contribution Roche has shared proprietary crystallisation details
Impact N/A
Start Year 2023
 
Description Control of Pharmaceutical Crystallisation 
Organisation Vertex Pharmaceuticals
Country United States 
Sector Private 
PI Contribution We have helped Vertex to understand the mechanism of their pharmaceutical crystallisations
Collaborator Contribution Vertex has shared their proprietary crysatlisation details
Impact N/A
Start Year 2022
 
Title CrystalGrower 
Description Monte Carlo Crystal Growth Software 
Type Of Technology Software 
Year Produced 2023 
Impact The software is the basis for the successful spin out CrystalGrower Ltd that has secured 10 major clients in the first year of trading 
URL https://crystalgrower.org/
 
Company Name CrystalGrower 
Description CrystalGrower develops simulation software that enables users to monitor and analyse the growth of crystals. 
Year Established 2021 
Impact Secured business from 10 major clients in first year of trading
Website http://crystalgrower.org