Ensuring reliable assays: Why the ideal microplate is an invisible one

Microplate

In a DDW Sitting Down With podcast with Diana Spencer, Charles Powell, CEO of Aurora Microplates, discusses how microplate technology has evolved to keep up with changing trends in drug discovery and why this ubiquitous, almost invisible, tool can have a huge impact on the reliability of scientific investigations.

DS: Aurora Microplates was launched in the mid 1990s. Can you tell us how the company started and how it has changed over the years?

CP: Aurora Biosciences was founded around the discoveries of Dr Roger Tsien, who was a professor at the University of California in San Diego. Early operations focused on the discovery of green fluorescent protein (GFP), which played a very big role in early drug discovery research operations using cellular assays. A lot of biosciences was funded and built around the construction of highly automated very high throughput, coined Ultra High Throughput Screening. Leveraging this, the very first microplate that Aurora Biosciences made was a 3456 well microplate.

Aurora Biosciences was then acquired by Vertex Pharmaceuticals, but this led to a touch of a conflict because the products were being used by potentially competitive pharmaceutical companies. So Aurora Discovery was formed, which operated until 2009 when we merged the business with Nexus Biosystems. Then Nexus was acquired by Brooks Automation and we were able to acquire the Aurora business in October 2015. Since that time, we’ve operated as Aurora Microplates, until almost two years ago, when Zeon Chemical and Aurora merged and so today Aurora is run as a division of Zeon.

DS: So you’ve seen quite a lot of change. What would you say the company has learned during this time?

CP: The operational dogma that we have stuck with is to focus on quality, to continuously look for ways to improve cleanliness, flatness and clarity and to listen very closely to customers’ needs. Sometimes they’re not able to very well articulate what their needs might be, but they can share what frustrates them with the tools they’re using and we have always paid great attention to how our microplates are being used. Most importantly, we learned that a microplate should be an invisible carrier of an assay. Meaning it shouldn’t contribute to results in that assay, positive or negative, it should be invisible, it should just simply hold the reaction. We find that scientists in early-stage drug discovery are very creative, very innovative and extremely helpful. They’ve been our guiding light over these many years.

DS: Having started with a broader range of products, why did Aurora decide to specialise in microplates specifically?

CP: The microplate is perhaps the most ubiquitously used work article in modern laboratory science, you’d be hard pressed to walk into any laboratory in the world and not find some version of a microwell plate being used to conduct a multivariant assay or test. And we liked that. We liked that a lot. It means that we can have a positive effect on a wide range of discovery science by providing a high performance and high-quality part.

DS: As we know, precision is integral to drug discovery. How do you feel the materials used in a microplate can affect what happens in the lab?

CP: The raw material makes a huge contribution to the ultimate performance of a microplate. Going back to the days of Aurora Biosciences, the company’s mantra was to be able to stage a reaction in as little as one microlitre. With that small amount of volume and the associated small amount of reactive material being used, if you lose any signal because components of the assay can stick to the walls of the wells of a microplate, your signal to noise ratios compress rapidly and you don’t have a window with which to conduct that test.

In the beginning, the predominant material used to make microplates was polystyrene – it’s very affordable and generally easily accessed and supplied. But it comes with surface charge that will absorb proteins, DNA, and other things, unless you do something to treat that surface. Aurora tried to make plates out of polystyrene and could not make them get a signal to noise ratio that was appropriate to conduct viable assays.

We needed a replacement polymer. Cyclic olefin polymer was an experimental resin made by Zeon chemical in Japan, and today Zeon is still the only manufacturer of cyclic olefin polymer in the world. Upon examination of the physical, chemical, optical and biocompatibility properties of this material, it became obvious to the science group at Aurora that this would be ideal.

DS: Can you tell me how a chemical reaction could be altered by using a poor quality microplate?

CP: Numerous things can affect the final results. Some materials have metals that get trapped into plastic that can leach in the presence of commonly used solvents in the drug discovery world. Other aspects of the plate that can contribute to problematic data would be surface energy. If there’s charge on the surface that can attract biomolecules, proteins, enzymes, etc., to the walls of the wells, you lose your signal and simply don’t have an assay that can be reliable. Other components that can affect the results are things like plate flatness, or lack of flatness, especially for imaging and high content fluorescent imaging work, where super consistent flat plates are vital to get very good clarity in image data. Things like acoustic dispensing and using pin tools to transfer liquids from one plate to another all rely heavily on very consistent plates.

DS: What kind of temperatures do microplates need to withstand throughout the drug discovery process?

CP: Microplates are built to be optimised for various applications. There are plates that are built specifically to be storage plates, that can exist comfortably at minus 80 without any compromise to their mechanical memory, and plates that need to go up to over 100 degrees to be used in thermal cycling applications for polymerase chain reaction applications and other genetic analysis kinds of applications. Our plates have been used by our customers from minus 80, all the way up to over 120 degrees without losing their mechanical memory. In other words, they don’t change shape or become completely distorted when exposed to high and low temperatures and then brought back to room temperature.

DS: Can you tell me why the manufacturing technique is so important when it comes to microplates? How do you ensure that you get a consistent product every time?

CP: In our case, we operate inside of a class 10,000 cleanroom, using HEPA filters and enclosures to ensure that dust and electricity, static electricity specifically, don’t become a part of the final product, and we keep the cleanroom clean, we don’t have cardboard or paper which are little dust factories. Everything is packaged in antistatic bags to dissipate any static that might become relevant. We pay great attention to our mould design, which has a lot to do with consistency in performance. We adhere to some very critical and highly rigorous cleanliness and calibration standards. We operate in an ISO 13485 quality environment, so we’re mandated to have corrective and preventative actions in place, should a problem be reported.

DS: Aurora was acquired by the Zeon Corporation in 2022, what impact has that acquisition had on the company’s products?

CP: It’s been fantastic. I’m proud to say that if I could have picked the ideal outcome for the long-term future of the company, it would been to merge with the company that supplies all of our raw materials. As a result, Aurora microplates is the only microplate company in the world that has direct ownership of the supply of all of its raw material, we are not dependent on anyone else. That was very meaningful during Covid-19, because we never encountered a shortage of raw material and our customers were not compromised in their ability to conduct their work during that period of time.

Zeon is very eager to continue to expand the product offerings that we can bring to our customers, whether it’s in decorating plates with new and different kinds of treatments or coatings, or other aspects in new and evolving assay techniques and technologies, or the introduction of all-new footprint plates, for example, 96 well plates for imaging, or new versions of 384 or 1536 well plates. We’ll continue to work on that today and in the future.

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