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Magnetic bead separation

Mistake #4 in CLIA IVD-kit manufacturing: Neglecting process scalability

When developing a CLIA IVD-kit, the initial focus is on the biomarker and how to coat the magnetic beads. Magnetic Bead Separation conditions usually get swept to one side.

FREE Download: Five critical mistakes in CLIA IVD-kits manufacturing

During these early stages, separation processes are usually developed on a small scale using existing laboratory magnetic racks. Once the kit has been developed, the batch volume is increased and a different magnetic separator is used. If the working conditions are not well defined, the magnetic force over the beads is completely different with the new system, which is when losses and irreversible aggregation problems occur. A costly re-engineering process is then needed to resolve these issues and to keep losses and clump formation to levels low enough to provide a cost-effective and efficient production process.

But, what problems are encountered when scaling up inhomogeneous magnetic separation racks?

Figure 11. Schematic representation of magnetic force on a small scale (left) and a large scale (right) inhomogeneous magnetic separation racks

Remember to download our free guide Five critical mistakes in CLIA IVD-kits manufacturing to learn about all these mistakes:

On a small scale, it is easy to have a high magnetic field gradient. Even if all the beads are not magnetically saturated the separation time is short because the distances travelled are also short. But inhomogeneous conditions on a larger scale involves greater losses (lower force at larger distances) and exponentially longer separation times. Over short distances, forces can be higher, increasing the risk of irreversible aggregation. The latter issue is aggravated by longer separation times.

In contrast, homogenous Magnetic Bead Separation conditions are easy to scale up. When using homogenous gradient the force can be kept constant even at large volumes. As a result, a Magnetic Bead Separation process without magnetic beads losses, and without irreversible aggregation of the beads can be reproduced at different volumes. To do this, beads need to be magnetically saturated for optimal performance (constant force). In advanced Magnetic Bead systems like SEPMAG® systems, the device always maintains the same suboptimal volume at instant t=0 (about 7% of the volume), guaranteeing that the whole batch volume is subject to constant force whatever the scale.

Figure 12 Error4

Figure 12 Advanced Magnetic Bead Separation systems at different scales.

The key to avoiding Mistake #4 (Neglecting process scalability) is to correctly validate the magnetic separation conditions early on in the development process, preferably when working on a small scale.

Working with homogenous Magnetic Bead Separation from the initial small volume, will give you a well-defined process condition, which makes scaling-up straightforward. It also drastically reduces the length of time and the resources needed to move from R&D to production, and to scale up larger volumes when the demand for kits so requires.

Figure 13 Error4

Figure 13 Use of small tubes in homogenous Magnetic Bead Separation systems. The magnetic force over all beads is the same when a large bottle is placed in the system.

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Lluis M. Martínez | SEPMAG Chief Scientific Officer

Founder of SEPMAG, Lluis holds a PhD in Magnetic Materials by the UAB. He has conducted research at German and Spanish academic institutions. Having worked in companies in Ireland, USA and Spain, he has more than 20 years of experience applying magnetic materials and sensors to industrial products and processes. He has filed several international patents on the field and co-authored more than 20 scientific papers, most of them on the subject of magnetic particle movement.

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