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NanoDrop 20 Years On

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2021 marks the 20th anniversary of the development of NanoDrop, a line of spectrophotometers that enable molecular biologists to analyze the concentration and purity of their samples rapidly and accurately. In the 20 years since its development, NanoDrop has undergone various iterations, with the most recent instrument – NanoDrop Eight – launched earlier this year.

To celebrate this milestone, Technology Networks spoke with Patrick Brown, product marketing specialist for the Thermo Scientific NanoDrop microvolume UV-Vis spectrophotometers. In this interview, Patrick discusses how the development of NanoDrop helped to significantly increase the speed and accuracy of scientific research. He also tells us more about the evolution of the technology over the past 20 years, highlights some of the most important improvements during this time and explores what the future may hold for NanoDrop.  

Anna MacDonald (AM): Can you describe how scientific research prior to the NanoDrop was adversely impacted by diluted samples and potential contaminants?

Patrick Brown (PB):
Before the launch of NanoDrop in 2001, research was both more time-consuming, and more error-prone due to diluted samples and potential contaminants.

Prior to the introduction of NanoDrop, whether a researcher was quantitating DNA, RNA or protein, highly concentrated samples needed to be diluted to produce accurate measurements. Diluting samples involves multiple manual steps like adding a buffer solution, adding water, and measuring the sample solution, all of which take time and can lead to measurement errors and replicability challenges.

Potential contaminants can also have a negative impact on results. Previously, by looking at two different purity ratios of a sample, one could compare those against set guidelines to infer the purity of their nucleic acid sample. With the advent of advanced mathematical algorithms, such as those launched on the 2015 NanoDrop One, not only could researchers determine what contaminant might be present in a sample, but also identify a more accurate concentration of the nucleic acid purity in their sample.

Ultimately, the process of diluting samples and the possibility of needing to deal with contaminants within a sample made for slow research and inaccurate results. The introduction of the NanoDrop and its evolution over time gave researchers more control over their workflows and enabled them to accomplish tasks faster and more accurately. Today, the NanoDrop Eight offers even higher throughput as it measures high concentrations of samples up to 200 absorbance units without dilution, saving users time and vastly reducing chances for error.

AM: How did scientists in academia originally use NanoDrop to quantitate nucleic acid, namely double-stranded DNA?

The same principles used in 2001 to quantitate nucleic acid are used today as well: once a customer pipettes 1-2 microliters of their sample onto the metal pedestal within an instrument, they lower another instrument pedestal, which touches the sample and creates a surface-tension bridge. By shining light through the sample and comparing it with a “blank,” an absorbance measurement can be calculated.

Even though the workflow hasn’t changed since the launch of the first NanoDrop 20 years ago, speed and ease have improved dramatically. Whether working in a small or high-throughput lab, an academic or industrial setting, researchers can now efficiently and accurately process and analyze up to eight protein and nucleic acid samples
at a time utilizing Thermo Fisher’s Acclaro software.

AM: How have the challenges that
molecular biologists face changed since the launch of NanoDrop One?

Since the introduction of NanoDrop 20 years ago, molecular biologists have faced a few new regulatory challenges. Specifically, some customers require that their research adhere to regulations like the MIQE Guidelines or 21 CFR Part 11.

Over time, the minimum information for the publication of quantitative real-time PCR experiments, known as the MIQE Guidelines, have changed the way researchers need to collect and present data. These guidelines place more stringent criteria around the information researchers should provide when publishing qPCR data to prove their research is accurate and reproduceable. Our NanoDrop instruments ensure that sample quality and measurements meet the stringent concentration and purity of the MIQE-requested Guidelines. Specifically, the introduction of the Acclaro Sample Intelligence Technology software (present in the NanoDrop One and NanoDrop Eight) uses powerful algorithms to find and correct sample contamination.

Additionally, many molecular biologists involved with pharmaceutical research are required to adhere to U.S. FDA Title 21 CFR Part 11, which governs the security of electronic records and signatures to ensure they are trustworthy substitutes for paper records and handwritten signatures. The NanoDrop Eight instrument, when used with Thermo Scientific SciVault software, allows researchers to fully comply with this regulation.

AM: NanoDrop has evolved significantly since its inception 20 years ago. Can you highlight some of the most important improvements in the technology’s history and how they were achieved?

Achieving higher sample quality and improving sample purity are two of the most important improvements throughout NanoDrop’s evolution. Our latest instrument, the NanoDrop Eight, measures nucleic acid samples and can deconstruct a sample’s absorbance spectrum into constituent parts.

Our R&D teams used chemometrics to increase the research possibilities on our NanoDrop instruments. To enable cutting-edge UV-Vis features, they created a library of many different types of spectra encompassing pure samples as well as mixtures of nucleic acid-containing contaminants. That way, when an end user obtains an absorbance measurement for their sample, it’s compared with our entire spectra library. Using chemometrics, the software predicts both the concentration of the sample if it is contaminated, as well as an identification of the contaminant.

AM: What does the future hold for NanoDrop?

Our goal is to make customers’ lives easier, accelerate research, and enable users to publish scientific papers.

This serves as the impetus to continually improve the NanoDrop to meet current and future needs. We continually evolve our NanoDrop instruments to extract and present as much information as possible from a UV-Vis measurement. More efficient sample preparation and workflows, and more thorough analysis helps users make educated decisions about their samples for downstream experiments.

We are continually innovating to better address the needs of our customers, whether adding new software like
Acclaro Sample Intelligence Technology to facilitate decisions related to a sample, or adding new features like those within NanoDrop One or NanoDrop Eight to increase efficiencies surrounding auto-measure and auto-blank. Ultimately, our goal is to decrease sample preparation time, increase research efficiencies and give our customers the most accurate and useful information about their samples.

Patrick Brown was speaking to Anna MacDonald, Science Writer for Technology Networks.