Consider the explosion Nanomedicine where huge advances are being made daily. Under the veneer of global acceptance is the growth of a few giants whose products were perfectly matched to the emerging needs of the pandemic. Their juggernaut continues with little indication it will slow. A key driver is the Pandora’s box of opportunities now possible to address a multitude of diseases currently untreatable. 

When a cognisant few identify, recognise and act to make material change to the accepted paradigm it echoes the sentiment of Paul Kelly’s classic song ”From Little Things Big Things Grow”.

What is needed is an elegant disruptor to influence the market, something to resolve what seems to be the only choice in Nanoparticle production, something that can encapsulate the RNA and other molecules not only in the lab scale, but do so seamlessly and efficiently for global population volumes. Imagine 1,500 Litres an hour, translating to 58,000 doses of vaccine every minute – from something that can fit into a small briefcase!

What is Micropore Technologies?

Micropore Technologies is a UK based company with its roots in micro-mixing and emulsions expanding developments in the fundamental understanding of crossflow mixing technology research at Loughborough University. Far from the glitz and glamourous archetypal corporate we imagine but a collection of clever engineers, scientists and pharma process control experts designing a new way to solve the puzzle. Tucked away in a former chemical company’s site on the Tees, near Middlesbrough is a rich history of scientific endeavour that has served the UK and indeed the world well. Fitting yet another discovery emanates from here.

Advanced crossflow (AXF™) mixing has solved the problem of how to create micro and nano-spheres, emulsions and crystals with a very narrow size distribution around a chosen size with a robust, cost-effective manufacturing-scale technology. Whilst firmly rooted in micro-emulsions the team at Micropore answered the call of the pandemic tweaking the technology to produce Lipid Nano Particles (LNP) that encapsulate genetic material with efficiencies over 95%, peptides and small molecules. Micropore’s precision engineered, crossflow micromixing equipment allows for thorough, reproducible nano-formulation at scales ranging from microlitres up to hundreds of litres using gentle laminar flows. The intuitive design and stainless-steel construction make GMP production of narrowly dispersed, accurately sized nanomedicines easier than ever before.

Given such a small footprint required and the simplicity of design, this will likely be the future of production; no need to build a factory even if it is a Flex Factory! This technology makes a deal of sense, in a GMP setting it is Clean In Place (CIP) or Steam In Place (SIP) – making it possible to achieve without the need to continuously buy consumables at exorbitant prices of hundreds of thousands of dollars just to run a single batch.

Global Leaders In Lipid Nanoparticle Production

Recognising global leaders in LNP creation and research were close by, they collaborated with The University of Strathclyde and a giant in this field Prof Yvonne Perrie. Yvonne stated the AXF has “A true workhorse capability. Easy to operate and very stable in operation”. Her research also found there was “No mRNA degradation in LNP production using AXF™ advanced crossflow mixing”. It is ticking fundamental boxes, but what about scaling up?

There are a few platforms that create excellent lab scale LNPs that may be parallelised to create higher volumes. Some alter the dimensions to achieve higher volumes, much like increasing the diameter in microfluidic channels. Others stack a multitude of lab scale systems to attain the desired outcome. Essentially, they all experience the ‘microfluidic roadblock’, not purposefully, but as a result of a few laws in fluid dynamics and the desire to expand capacity using the same conditions employed to create lab scale batches. I recall seeing a program during the pandemic exploring a Pfizer facility where their vaccine was produced, starkly, I recall what could be described as a warehouse with enormous racks and rows of hundreds of pumps and Impinging Jet Mixers. I pondered how on earth are they controlling size, PDI, encapsulation amongst a myriad of other parameters? The enormity of this project was astounding and a feat of intent. The world certainly gained from this endeavour. I can’t help but admit I also felt there must me a more efficient way. 

When we discovered Micropore serendipitously, I knew they were an answer.
Micropore differs from all the other technologies, consider they started with volume and worked backwards to lab scale. Envisage a 316 stainless steel pipe with another pipe with 100s of 1000s of electropolished holes inside (called a membrane), attach 2 fluid streams, one as a continuous phase through the pipes and one at 90 degrees – forcing the second stream through the membrane into the continuous phase. Brilliantly engineered, so simply by design. You can put several together to achieve 1,500 L/hour, or you can make a Mini version and run from 600 µl up. Therefore, lab scale and population scale in something that as noted previously, can fit into a small briefcase!

To develop nanomedicines requires a deal of research, countless formulations and tweaking to fine tune not only the drug but the carrier such as a lipid encapsulating it. Each iteration will need to be produced and analysed. This likely equates to 100’s of runs and in microfluidic systems this may be tens of thousands of dollars in consumables such as cartridges to achieve the candidate for further development. There are no consumables in the Micropore system aside from a few PTFE ‘O’ rings. And the membrane is used over and over, it lasts for years – it is stainless steel after all. Micropore Technologies recognised the need to build a system that will not only direct LNPs created into a test tube but assist in the development of the formulation. The result is aptly named, the Pathfinder. Imagine you can ramp up through a range of flow rates collecting samples into a 96 well plate as you go, effectively running over 90 experiments in less than a minute! Now that is accelerating research and development!

Perhaps we should understand the Micropore Technologies’ corporate culture as this is incredibly important when accessing the organisation and investing in their technology. The CEO received an MBE from the newly minted King of England – the MBE was awarded by the Queen, but COVID got in the way of the ceremony. Notably the Chairman of their board also has an MBE- I understand you don’t find these in a cereal box. From what I have observed, their actions match their ethos to ‘improve life by delivering innovative technical solutions for better & more affordable products’.

The Micropore AXF system is promising to be a true in country manufacturing option- think Island nations – poor countries – lets democratise medicine … Again. With this in mind, it is fitting to use the Paul Kelly protest song, we can stand up against a few global giants trying to control what it will cost to produce medicines.

For further information call Peter Davis, Applications Specialist, T: 02 9541 3500 or email pdavis@atascientific.com.au

Reference:
https://microporetech.com/making-products-better/scientific-papers/fast-controlled-and-consistent-an-exploration-of-current-mrna-vaccine-production-technologies

A common challenge found in the world of scientific research is achieving recognition for topics not typically trending among influencers for the importance of fundamental research. Dr Georgia Atkin-Smith, a researcher at the Walter and Eliza Hall Institute and founder of the “Some Blonde Scientist” website noted in a recent post “most people think we should just fund the research that makes the drugs. But we obviously need to fund the research that makes the knowledge come to fruition before we can make the drugs.” Lipid Nanoparticles (LNPs) encapsulating mRNA have quickly gained popularity since used successfully during the COVID-19 pandemicby Pfizer and Moderna. However, the speed of vaccine development was only made possible because scientists had previously been working with this technology since the 1990s as drug delivery vectors for nucleic acid-based drugs and vaccines. The pandemic has demonstrated the need for developing fundamental knowledge that can be drawn upon in times of need. By using the right analytical tools and strategies we can ensure tomorrow’s therapeutic drugs and vaccines will be possible with today’s scientific breakthroughs. 

Shining a light on the drug development journey

The first step in the drug discovery and development journey involves identifying the molecules or compounds that bind to target proteins with the desired characteristics. This process however, comes with a high risk of failure -compounds may not behave as expected, lack the required activity, or show issues during development. Access to the best possible data can help researchers to make informed decisions about how the characteristics of the molecules and materials they are working with impact on their behaviour. In this way, a more complete picture of the interaction between lead molecules and target protein in terms of structure activity relationship and underlying interactions can be revealed. 

Advantage of using multiple analysis methods 

While proven analytical technologies can monitor a range of attributes, no one single biophysical characterisation technique can provide a complete picture, in the same way that no one single drug can be used to cure all types of diseases. Physicochemical characteristics like molecular size, composition, aggregation, surface charge, and structure can all have significant effects on the therapeutic molecule’s success. In addition, optimising one property may come at the detriment of another. These interdependent characteristics can impact stability during production, transport, storage, or affect the delivery of the drug in the body. From early drug discovery phases in the lab through to clinical, manufacturing and ultimately to the patient, adopting the power of orthogonal approaches of cutting-edge analytical solutions can ensure a more comprehensive understanding of the critical parameters needed that define the behaviour of a drug.

Analytical techniques are being increasingly implemented by biotech organisations

Access to accurate, robust, repeatable data is paramount to enable the rapid identification of optimal compounds that meet safety, bioavailability and likely processability requirements. 

For example, when formulating lipid nanoparticles (LNPs) as drug delivery vehicles, both the ratios of the ingredients and mixing technique must be optimised to ensure product consistency. The components of LNPs (cationic lipids, helper lipids such as distearoylphosphatidylcholine (DSPC), sterols such as cholesterol, and polyethylene glycol-containing (i.e., PEGylated) lipids) self-assemble during mixing so any small batch-to-batch variations like changes in flow rates can result in different compositions or LNP size. If the particles are too small they may be cleared from the body before they have a chance to take effect. On the other hand, larger particles can form aggregates and may fail to penetrate cells or induce unwanted side effects. Surface charge is also important as it can influence the uptake of LNPs to different cell types. 

Table 1 below lists a toolset of proven physicochemical analysis solutions helping researchers to make informed decisions about how the characteristics of the molecules and materials they are working with impact on their behaviour.

Table 1: Advanced physicochemical analysis solutions

	Particle size	Polydispersity	Particle concentration	Surface charge	Thermal stability	Higher order structure	Binding interaction	Particle composition
DLS	✔	✔			✔
MADLS	✔	✔	✔
NTA	✔	✔	✔
ELS		✔		✔
Multi detection SEC	✔	✔	✔					✔
DSC					✔	✔	✔
ITC					✔		✔
GCI							✔

MONITOR PARTICLE SIZE

Particle size can influence dissolution, solubility, bioavailability and stability. The Mastersizer 3000 uses laser diffraction, one of the most widely used techniques for particle size distribution analysis. Suitable for both wet and dry samples, this highly repeatable (+/-1%) particle sizing technique delivers volume-based distributions in the size range 0.01 to 3500 microns and allows a specification developed in the laboratory to be transferred during scale-up. 

Two other well-established techniques used to monitor particle size and polydispersity include Dynamic Light Scattering (DLS) using the Malvern Zetasizerrange and NanoParticle tracking analysis (NTA) using the Malvern NanoSight range. Typically, DLS is used for rapid screening and tracking changes in size distribution. NTA provides high resolution size distribution and concentration measurements for individual nanoparticles while a fluorescence mode allows differentiation of fluorescing particles. Both methods measure changes in the scattering pattern of particles in suspension which is translated into size with larger particles diffusing more slowly than smaller particles.

Malvern Zetasizer Ultra is the most advanced system for the measurement of particle and molecular size, particle charge and particle concentration. Alongside the patented Non-Invasive Back-Scatter (NIBS) technology ideal for concentrated samples, the Zetasizer Ultra offers Multi-Angle Dynamic Light Scattering (MADLS®). Using back, side, and forward detection angles, MADLS offers a higher resolution than DLS, allowing it to identify additional populations of particles. It also enables calibration-free particle concentration analysis, resolving the individual concentrations of different size populations to provide even greater insight into samples. NTA offers even higher resolution but often requires sample dilution which can impact stability. The choice between these complementary techniques depends on factors, such as size and polydispersity, sample heterogeneity, and the product specifications.

Solubility issues during formulation can form undesirable aggregates which reduce the amount of active ingredient in the sample, thereby reducing efficacy, and they can stimulate immunogenic responses. Size Exclusion Chromatography (SEC) is a method commonly used to separate and measure the amount of different protein aggregate components and identify and characterise each of them by their molecular weight. But many proteins do not have globular structures making their measured molecular weights inaccurate using conventional SEC. 

The OMNISEC Multi-detection SECis a technique that combines the resolving power of chromatography with the revealing power of light scattering detectors and a viscometer. In a multi-detection SEC system, the light scattering detectors measure absolute molecular weight (as opposed to a column calibration system that can only provide a relative measurement) and the differential viscometer provides information about the molecular structure. This wider range of accurate data provides a more complete characterisation of the protein mixtures.

STABILITY & INTERACTION

Differential Scanning Calorimetry (DSC) is a well-established label-free technique for structural characterisation and stability profiling of biomolecules and viruses in solution. DSC can analyse the effects of different storage conditions on the higher-order structure. It works by measuring the enthalpy (ΔH), temperature (Tm) and thermal stability of a vaccine. The MicroCal PEAQ-DSC system is the Gold standard stability assay platform which can be automated to support the generation of high integrity thermal stability data and deliver compliance with regulatory requirements.

Electrophoretic light scattering (ELS) is used in the characterisation and formulation development of products such as vaccines that use LNPs, liposomes and other nanoparticles as carriers, to determine size and colloidal stability. This method is useful in understanding what happens when a drug enters different cellular environments. The Malvern Zetasizer measures the zeta potential or apparent surface charge of particles and molecules, indicating sample stability and/or propensity to aggregate. The apparent surface charge can be used to detect formulation condition differences.

BINDING AFFINITY

Understanding the binding affinity, or the interaction between biomolecules, is key for the design of drugs that bind their targets selectively and specifically. Grating-Coupled Interferometry (GCI)and Isothermal Titration Calorimetry (ITC) can be used together to provide highly quantitative affinity (KD) values. Both are label-free quantification techniques, allowing the use of native molecules. GCI is an optical method that measures the change in refractive index on a sensor surface caused by the binding event and is used to study the affinity and kinetics of an interaction. The Creoptix WAVE biosensor with proprietary GCI technology measures KD values in the millimolar to picomolar range and additionally determines the kinetics of an interaction, more specifically, the on (ka) and off (kd) rates. It an aid screening for real-time label-free binding kineticsusing low sample volumes, even from unpurified material. The MicroCal ITC range measures the heat change associated with the binding event. It measures KD values in the millimolar to nanomolar range and determines the binding stoichiometry and binding thermodynamics of the interaction. Both kinetics and thermodynamics are important in the characterisation of intermolecular interactions.

At ATA Scientific, we’re proud to enable scientists to accelerate Drug Discovery by providing cutting-edge tools for molecular interaction analysis. If you need assistance in determining if your application is possible, contact us.

For further details contact 
ATA Scientific Pty Ltd
+61 2 9541 3500

enquiries@atascientific.com.au
www.atascientific.com.au

References: 

• Bad breath and garbage cells net female scientists $25,000 research prizes (smh.com.au)
• https://www.malvernpanalytical.com/en/learn/events-and-training/webinars/W220922-VV-vector-panel
• https://www.e-digitaleditions.com/i/1478917-biopharm-international-september-2022/22?
• Optimizing Pharmaceutical Formulations: The Role of Physicochemical Analysis | Malvern Panalytical
• Drug Discovery & Analytical Research Solutions | Malvern Panalytical

This is a story of the origin of a key analytical technology and how this led to the Australian distributor ATA Scientific, analytical instruments supplier.

The story starts in the early years of the second world war at RSRE (Royal Signals and Radar Establishment) located in the town of Malvern in the UK. Steve Trudgill started there as an Apprentice and graduated to become a Senior Experimental Officer working with some of the top engineers in the country who were brought together to develop radar. They worked long, gruelling hours, often flying at night to carry out tests. The development of radar made a significant contribution to the winning of the war.

Apart from electronic engineering Steve also had a natural business ability. He installed a new garden shed and started up Lawson Tubes, purchasing old televisions and repairing them which developed into a television tube business.

In the late 1950’s, in parallel with his tube activity, he worked with Bill Woodley, a Scientific Officer within RSRE, who had been tasked to reduce the focussed spot size of magnetically focussed and deflected cathode ray tubes for Radar displays. A cottage industry sprang up from this research, becoming their own company in 1961, Precision Display Systems (PDS).

The Company continued innovative research and as it expanded the name was changed to Malvern Instruments Ltd. The first innovation was the Malvern correlator. The concept for the Malvern Correlator originated from work carried out in the mid to late 1960s at RSRE and Malvern on the fundamental properties of light. Roy Pike with his colleague Eric Jakeman conceived an idea relating to the temporal correlation of photon events, the aim being to create a novel type of ultra-high-resolution spectroscopy. 

The Malvern K7023 Correlator

A correlator is a signal analysis device which can be used to look at the correlation in a signal with a delayed version of the same signal. By averaging and multiplication of the signal with a delayed version of itself it is possible to extract periodicities or characteristic decay times present in the signal.

The Malvern Instruments’ High Speed Digital Correlator and Probability Analyser System Type K7023 was patented and launched in 1971. Steve Trudgill named the correlator after one of his daughters (Katherine) and the reference number of a Great Western railway steam locomotive (7023) of which he was a fan!

The Malvern correlator was used in combination with a photomultiplier to study the fluctuations in the intensity of scattered light over short time periods from microseconds to milliseconds. This was referred to as Photon Correlation Spectroscopy (PCS) and could be used to determine the translational diffusion coefficient of colloidal particles or molecules undergoing random Brownian motion in a liquid.

The key application was the ability to measure the size distribution of particles or macromolecules in suspension by measuring the diffusion coefficient of the scattering entities. For particle sizing the electronics had to be paired up with a laser-scattering goniometer, such as the Type 4300, and in such a configuration the Malvern Correlator became the world’s firstcommercial laser-based, particle size analyser.

This correlator technology found another early application in laser Doppler velocimetry (LDV), which could be used to measure the flow pattern of air over a wing or around an aeroplane engine or to measure the flow rate of blood in the retina of the human eye.

Since then, the technique of Photon Correlation Spectroscopy (PCS), now more commonly known as Dynamic Light Scattering (DLS), has continued to evolve with Malvern’s first integrated measurement system, the Autosizer, appearing on the market in the late 1970s. The subsequent development of Electrophoretic Light Scattering (ELS) in the early 1980s resulted in the first integrated size and zeta potential measurement system, the Zetasizer.

The latest iteration of the Zetasizer series employs the basic principles proposed by Roy Pike and his colleagues over 50 years ago but utilizing the latest advances in technology to greatly improve measurement quality, versatility, robustness, and ease of use.

The innovations continue

The next innovation based on the original opto-electronic research by Steve and his colleagues was Laser Diffraction particle sizing. Malvern was one of the pioneers in Laser Diffraction instrumentation with the release of the first instrument in 1976. Since then, a succession of ever improving instruments has culminated in the Mastersizer 3000 Series, now the market leader in Laser Diffraction particle sizing.

Malvern was merged with its sister company and is now a world-leading analytical instrument company, re-named Malvern Panalytical, and is still based in Malvern town in the UK. They continue to develop technically innovative products and now offer an extensive range of instruments applicable across many Science disciplines and many industries.

So, starting in a garden shed, Steve Trudgill with his commercial acumen and the foresight, knowledge and innovation provided by Roy Pike and his team, were the creators of Malvern Panalytical which has made such a global impact in the field of analytical instrumentation.

Over the years, Malvern’s innovative products gained the Queen’s Award for Technological Achievement in in 1977, 1981 and 1988. Malvern was also awarded the “Analytical and Scientific Instrument Heritage Certification” for the High Speed Digital Correlator and Probability Analyser System Type K7023.

ATA Scientific – another success story that started in a home garage

Resembling a similar humble beginning, ATA Scientific, established over 30 years ago can be traced back not in a garden shed but instead to what is known as the Bundeena Bunker – the old home garage of the company’s founders,located in the Royal National Park. 

Since it’s early days, ATA Scientific has continued to evolve as a business focused on Particle, Surface/Material, Biomolecular Sciences and high resolution Imaging meeting the everchanging needs of the scientific community. Sourcing the latest technologies from around the world the company has supported a diverse range of companies throughout Australia and New Zealand particularly in the pharmaceutical, polymer, chemical and mining industries, in addition to all major universities and government research institutes like CSIRO.

At ATA Scientific, we don’t just sell our instruments

Through collaboration with a broad range of industries and academic institutions, we play a key role in optimising product development and manufacturing processes. We support our customers by providing optimal material characterisation techniques used in a wide range of industries together with key insights into the application, measurements and analysis to fully understand material behaviour. 

As the company grew in people and capability we moved to rented premises, including many years at the ANSTO Technology Park. We are now fortunate enough to move into our own building, at 47 Cawarra Rd Caringbah, Sydney.

This new facility affords purpose-built areas for service work, customer training and a demonstration suite with an array of operating instruments. 

We have built our product range over the years and expanded our customer support capacity. Apart from our long-established Particle Characterisation instruments we now also have an exciting portfolio of Life Science products. This sector is likely to be a future powerhouse given the global focus on genetic medicines, vaccine development etc. We are now well positioned to enhance our ability to support and service the Life Scientific community. We will continue to invest in scientific endeavours such as our Young Scientists Encouragement Awards and conference sponsorships.

We are pleased to be able to share some of the review comments from our customers over the years. Click here to take a look

Contact us for more information today!

The measurement of particle size distribution is important in many fields of science. Most notably materials testing, life sciences, food testing, and pharmaceutical companies all use it to understand how size affects the performance of their final product. For solids like cement, the surface area of the particle is critical in determining the rate of chemical reaction which affects the final product strength. For metal production processes, a distribution of finer particles are preferred to offer high packing density and improve quality. Fines are more likely to dissolve quicker which is extremely important for the pharmaceutical industry. Particle size affects the flavours released in the coffee brewing process and similarly for chocolate, the size effects the taste and mouth feel.

So, how do we measure particle size? 

If we consider how particle characterisation tools have progressed over the last 30 years, we can see a distinct trend towards more sophisticated technologies providing an ever more detailed knowledge of particle properties. At a basic level, traditional mechanical particle size measurement techniques, such as sieving and sedimentation, combine low cost technology and simple, ‘easy to interpret’ results. However, the trade-off for this level of simplicity is the limited applicability to different types of sample and the limited information provided by such techniques.

All particle size analysis techniques measure some property of a particle and reports results as the equivalent spherical diameter based on this measured parameter. Whatever method we choose we need to be aware that different techniques will give different results. This is because we are measuring a different property of the particle (e.g. Length, Stokes’ diameter or a volume).

In aggressive fast-changing markets, investment in more sophisticated, optical data collection tools can provide a significant competitive advantage. The development of light scattering-based technologies such as laser diffraction, have forever changed particle size measurement, delivering robust, reliable particle size distributions and rapid, easy analysis for an extremely wide range of types of sample, ranging from granules (>1mm) to sub-micron fines (100nm and below). Easy to integrate either on-line or off-line, laser diffraction supports every stage of the product development cycle, as well as production efficiency and quality control of the final product. 

Malvern Panalytical is the world’s leading supplier of particle size analysers and has been since first inventing the technology dating back as far as 1950s with RADAR used in WWII!

Some interesting facts about particle size analysers: 

• 19 out of 20 of the world’s leading University’s use Malvern Panalytical particle size analysers
• 19 out of 20 of the world’s largest chemical companies use Malvern Panalytical particle size analysers
• All the top 20 pharmaceutical companies use Malvern Panalytical particle size analysers

Where it all began for particle science

Originating in 1953, The Radars and Signals Research Establishment (RSRE), now Qinetiq, was a research centre for the British army located in Malvern, Worcestershire, UK. It had a long history of inventive discovery involving RADAR, satellite communications, thermography, liquid crystal displays, speech synthesis and the Touchscreen. The future founder of Malvern Instruments, Steve Trudgill worked at RSRE as a Senior Experimental Officer during the early years of WWII, with some of the top engineers in the country to develop RADAR, which made a significant contribution to the winning of the war!

In the late 1950’s Steve started a new business repairing TV tubes which expanded when he partnered with colleagues from RSRE to supply cathode ray tubes for radar displays and eventually correlators in 1971. The company ‘Precision devices and systems UK Ltd’ then changed its name to Malvern Instruments in 1980 and further development of innovative products continued. Correlator technologies developed by Malvern Instruments proved useful for a wide range of applications and eventually led to particle sizing using PCS (Photon Correlation Spectroscopy), now more commonly called DLS (Dynamic Light Scattering). Parallel development of laser diffraction technologies resulted in commercial instrumentation received multiple Queen’s Awards for Technological Achievement between 1981 and 1988.

Now a world-leading company Malvern-Panalytical is committed to harnessing the power of precision measurement to allow for a cleaner, healthier and more productive world and continues to develop technically innovative products, building on Steve Trudgill’s founding innovation and leadership.

Some milestone instruments developed by Malvern are discussed below.

1972

The first Malvern correlator, known as ‘The Malvern’ was the world’s first commercial laser-based, particle-size analyser. It was developed with the aim to create a novel type of ultra-high resolution spectroscopy. In 1977 it received the coveted MacRobert Award – a well-deserved award for an instrument which was pivotal in the analysis of particle size and particle size distribution.

MacRobert Award is UK’s longest running and most prestigious national prize for engineering innovation. Other past winners include engineers behind innovations such as the Pegasus jet engine, catalytic converters, the roof of the Millennium Dome and intelligent prosthetic limbs. The Malvern correlator had applications in areas including: Aeronautics for plotting aerodynamic flow fields in aero-engine development; Marine engineering for measuring velocity and turbulence fields around ship models; Fuel and gas to assess the performance of burners from the velocity and turbulence levels of reactive gases; and Medical science to study blood flow in the retina used to diagnose diseases and defects. The key application, as it turned out, was the ability to measure the size distribution of particles in suspension or macromolecules in solution by measuring the diffusion coefficient of the scattering particles.

1972-1980

The Malvern Type 4300 was the first nano particle sizing system, combining the Malvern Correlator with the Photon Correlation Spectroscopy (PCS), more commonly known as Dynamic Light Scattering (DLS). Developed with input from the RSRE and Loughborough University, this technology is used to determine the velocity of nanoparticles undergoing electrophoresis in an electric field and to calculate their zeta potential, and in practice forms the basis of the Malvern Zetasizer series of instruments in use today.

50 years of laser diffraction and the evolution of the Mastersizer 3000.

1976-1980

Malvern ST1800 was the first Particle and Droplet Size Distribution Analyser that used the principle of Fraunhofer to measure particle size. It was the first Malvern laser diffraction system developed based on research at the University of Sheffield and was built for spray applications. 

With the Malvern ST1800, the spray was fired through a parallel laser beam of monochromatic (red) light. The light, on hitting a droplet, was deflected by an angle which is a function of the size of the droplet. After passing through a lens the light hit a multi-element detector, the output from which passed through a small computer (PDP8 with a Teletype) which produced a hardcopy print out of a size distribution using calculation programs held on punch-tapes.

The Malvern ST1800 is always remembered for the chair – this one goes without saying. Of course the chair was an essential accessory, as the calculations took so long! haha

In the late 1970’s, when laser diffraction systems were first introduced, they all used the Fraunhofer approximation which assumes: Particles are much larger than the wavelength of light employed (ISO13320 defines this as being greater than 40λ i.e. 25μm when a He-Ne laser is used); All sizes of particles scatter with equal efficiencies; Particles are opaque and transmit no light. 

These assumptions were not accurate or representative of the sample which gave rise to large errors especially for material with very small particles. As computing power increased, it then became possible to apply Mie theory. This allows for more accurate results for a wider range of sample types over a larger size range. Mie theory models are based on scattering from particles and account for refraction of light as opposed Fraunhofer which is based on scattering from slits and discs and only considers diffraction from surfaces.

1980-1984

Malvern 2200 was built for spray measurements and was very successful. It also used the principle of Fraunhofer to determine particle and droplet size analysis from the diffraction pattern from particles illuminated by a laser beam. This was the first system built to a complete Malvern design, and the first to be exported. Alongside it, the Malvern 3300 was launched, providing basic liquid dispersion and dry powder analysis. 

1984-1996

The Malvern 2600 is Malvern’s best known early system. Available for wet or dry samples or spray analysis, it included a range of dispersion accessories. Big advances in software design led to features such as an ‘Easy’ mode where users could make a complete measurement using 5 function keys. Alongside this was a ‘Master’ mode, which allowed people to develop their own measurement macros. You can guess what this master mode became!

1988-1992

The Mastersizer 1000 was the first instrument to wear the Mastersizer label and the first to employ Mie Theory for analysing the data from sub-micron samples. This system was produced with built-in, automated dispersion units for sample delivery and was combined with advanced software which started the move to QC applications.

1994-2005

The Mastersizer S was the first wide-angle measuring system produced by Malvern. A single lens covered the entire range from 0.05 – 900 microns. However, the system required a long bench and a 1000mm lens to measure up to 3500 microns. This system set down the basics for Malvern’s most successful system – the Mastersizer 2000.

1998-2014 

Mastersizer 2000 launched a quarter of a century ago.

The legacy Mastersizer 2000 system used the powerful capabilities of Mie theory through the inclusion of a database of refractive indices to provide particle size measurement for many different materials, both wet and dry. It offered a broad measurement range, 0.02μm to 2000μm, and exemplary accuracy of +/- 1%. Full automation and software-driven Standard Operating Procedures eliminate user variability and streamline analysis, making measurement a simple and routine task. A wide range of ‘plug and play’ dispersion cassettes ease the switchover from one sample type to another and optimise flexibility.

Approaching a quarter of a century after its launch, the groundbreaking Mastersizer 2000 reached the end of its formal support life in April 2022. Although the manufacture of the Mastersizer 2000 system ceased in 2015, Malvern Panalytical gave a commitment to fully support the Mastersizer 2000 for the following 7 years during which many of the electronic and hardware components used within the system were no longer available to maintain the Mastersizer 2000. Thousands of users have already made the successful transition from the Mastersizer 2000 to the Mastersizer 3000.

Mastersizer 3000 extends the boundaries (2012+)

Mastersizer 2000 was a very tough act to follow! Renown for being the most widely used laser diffraction particle sizing system globally, the Mastersizer 3000 was launched in 2011 as the replacement. Building on the strengths of its predecessor, the new system has advanced significantly over the last decade both in terms of the core optical hardware used to deliver high performance and the intuitive software that makes that performance accessible to the user. As a mature technology, this modern laser diffraction system offers an extended size range over a smaller footprint, and more versatile wet and dry powder sampling options. Extended size range capabilities open up the possibility for new, previously unfeasible applications, from characterising small particles with distributions extending from 10nm, to beads and granules up to several millimetres (3.5mm) in size. More powerful light sources and advances in miniaturisation of detectors, coupled with high-precision folded optics, allow higher performance to be obtained within a smaller instrument footprint. The powerful blue light source used for fine particle measurements is kept on the same axis and uses the same detectors as the red laser source for the coarse particle measurements. As shown in the diagram below, this set-up not only increases sensitivity to fine particles but makes combining light scattering data from both sources more straightforward.

Substantial developments have also occurred in the hardware used to prepare the sample for measurement. In wet measurement, for example, new accessories that more efficiently apply ultrasound and agitation can cut dispersion times by as much as 50%. For dry powder samples, extensive development of dry dispersion units has enhanced the performance leading to shorter measurement times and lower environmental impact to the widest range of materials.

Laser diffraction particle size analysers like the Mastersizer operate on fundamental scattering principles; therefore, no calibration is necessary. Instead, Quality Audit Standards which are essentially high quality and carefully prepared glass beads, have been produced to provide users with a single-shot, polydisperse transfer standard that enables them to verify the performance of their systems on a regular basis, as part of regulatory requirements, compliant with ISO13320.

Loved by our customers and proud to own a Mastersizer 

The Mastersizer 3000 has recently been awarded a coveted ‘Gold Seal of Quality’ via SelectScience. A direct result of user feedback, SelectScience’s Seals of Quality are awarded to the top 0.1% of products that consistently receive the highest customer review ratings on their website. The Mastersizer has more than 100 reviews from scientists at an average rating of more than 4.5 out of 5, and is a technology continuing to do so much to help so many.

So what does all this mean for you?

Ultimately, Mastersizer 3000 has made lives easier, saved people time and money, helped smooth processes and improve end products, and in many cases eased headaches and bottlenecks.

We can go further together to make the invisible, visible

At ATA Scientific, we don’t just sell our instruments – through collaboration with a broad range of industries and academic institutions, we play a key role in optimising product development and manufacturing processes. We support our customers by providing optimal material characterisation techniques used in a wide range of industries together with key insights into the application, measurements and analysis to fully understand material behaviour. 

Contact us for more information today!