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The Need for Change: Seeking Better Methods for Detecting Residual Dynabeads

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Halo Labs
ISCT Industry Member

In cell therapy manufacturing, sometimes the smallest things can pose the biggest challenges. Case in point: residual Dynabeads®. These magnetic particles, used for cell selection and activation, can inadvertently remain in a finished drug product, jeopardizing patient safety.¹

The FDA has recommended limits to mitigate this risk: no more than 100 residual beads per 3,000,000 cells. However, achieving this standard is far from straightforward due to the limitations of current detection methods. ¹

Take hemocytometry, for instance. This widely-used technique, which relies on light microscopy and manual counting, falls short in a number of ways. It’s not only slow and subjective but also struggles to accurately distinguish cells from Dynabeads. This difficulty arises from the similarities in size and appearance between these two components within a sample, often leading to significant undercounting of beads or misidentification of beads vs. cells. Such inaccuracies can compromise the safety and efficacy of a final drug product. ¹

Other conventional cell and subvisible particle analysis tools—like flow cytometers—don't fare much better either. They typically undercount beads and have trouble distinguishing residual Dynabeads from cells and other subvisible particles, and do not provide “live images” of particles.¹

This problem highlights the urgent need for more reliable, automated, and specific methods for detecting and quantifying residual Dynabeads in cell therapies.

Aura CL and Aura+: Pioneering Solutions to Detect and Quantify Residual Dynabeads

To address these challenges, Halo Labs has developed the first and only automated solutions to detect and count these hard to detect contaminants:

Aura®+: Fully configured to support applications across protein, antibody, cell, and gene therapy workflows, Aura+ brings particle characterization to earlier stages of therapeutic development, so you can make better decisions sooner.

Aura CL®: Powered by innovative technology, Aura CL is the ultimate tool to identify, count, and characterize subvisible particle contaminants introduced in cell therapy manufacturing.

Combining Backgrounded Membrane Microscopy with Side Illumination Membrane Imaging: Quantifying Cells versus Beads

Aura's advanced toolset empowers users to make informed decisions within a crowded cell space. This is a significant improvement as other methods can be inefficient and error-prone.

Two automated technologies work in tandem to accurately identify and quantify cells versus beads—Backgrounded Membrane Imaging (BMI) and Side Illumination Membrane Imaging (SIMI). Together, they provide a comprehensive snapshot of highly concentrated cells with single-digit counts of Dynabeads. They combine high-throughput imaging with automated data analysis to provide a rapid, objective, and reproducible means of quantifying residual Dynabeads in cell therapies.

Figure 1. With BMI and SIMI working together, you get a fuller picture of highly concentrated cells with single digit counts of Dynabeads.

SIMI takes automation one step further with its unique “x-ray” vision—allowing it to identify even a single Dynabead among hundreds of thousands of cells. As a cutting-edge technology, SIMI detects light scattering, specifically high refractive index particles, including those protruding out of the membrane surface. It measures a particle's average intensity based on the amount of light scattered or absorbed from side illumination.

Particles that scatter light typically indicate inorganic matter protruding from the membrane, such as glass or plastic. In contrast, particles that absorb light are indicative of metallic particles like residual Dynabeads, and absorbing oils, all of which also protrude from the membrane.

Figure 2. Biological aggregates are mechanically compliant and lay flat on the surface of the membrane (left), whereas extrinsic contaminants protrude, providing greater SIMI signature (right).

Aura CL and Aura+ are more than just tools, they are game-changers within cell therapy manufacturing, especially for those who require immediate quality assessment based on decentralized or point-of-care manufacturing models. Tackling the challenges associated with residual Dynabead detection, these ground-breaking technologies provide greater accuracy and higher throughput in counting compared to the cumbersome and error prone currently used methods.

With the ability to resolve false positive counts through high magnification measurements, single Dynabead identity can be confirmed by size. This feature is just one of the ways Aura CL and Aura+ ensure precision in detection. They also stand apart as the only automated solution capable of measuring single Dynabeads in concentrated cell therapy solutions while offering built-in orthogonal confirmation through various objectives and light sources.

Don’t just take our word for it. Download our technical note for a study showcasing how residual Dynabeads were detected in a concentrated cell therapy product using Aura CL and Aura+ systems. https://www.halolabs.com/resource/residual-dynabead-detection/[DN1]