Product development is a time-consuming, expensive process for CLIA-IVD kit manufacturers. There are several steps involved:
- Selecting the biomarker
- Choosing the right coupling
- Selecting the right magnetic bead
You are well versed with the first two points but what is “the right bead”? Assuming you have the right biomarker and a perfect coupling, the ideal magnetic bead should have the following properties:
- High recovery/fast separation, compatible with the timing of the analyzer step. It needs to be fast enough during large-scale production processes without high bead and coupled biomarker losses.
- No aggregation problems. Beads should be easy to re-suspend. It makes no sense to separate quickly if several additional sonication steps are required, which are difficult processes to control/implement in large volumes.
- Low kit-to-kit variability. Batch aliquots (typically less than a milliliter) of production batches (liters scale) must be consistent. If not, variability causes problems when interpreting the results in the analyzer.
This chapter explains the first of the five most common mistakes when manufacturing CLIA IVD-kits. We will be posting a chapter of this series every week, so make sure you don't miss any of them. You can also download our free guide Five critical mistakes in CLIA IVD-kits manufacturing to learn about all these mistakes:
What happens when these requirements are not met?
The most common response to defective magnetic separation is that the magnetic beads is to blame. Users then contact the magnetic bead supplier (or alternative supplier) for protracted discussions about the product, revision of the coating protocols… a lengthy process that consumes significant resources and generally delays the product development and/or launch.
If a biomarker couples well with the magnetic bead, changing the magnetic beads is extremely expensive, delays the project and in most cases does not solve the problem.
How does the device affect biomagnetic separation? Let us illustrate it with an example. The figure show how the same suspension of magnetic beads behaves in two different biomagnetic separation systems.
The magnetic rack on the left (blue), separates slowly. This means waiting for a long time to complete the separation or accepting high losses of beads and biomarkers. However, if we wait for a long time in order to avoid losses, some beads are affected by irreversible aggregation problems as the force over the earlier separated beads (the closest to the bottom part) are subjected to an extremely high local force for protracted periods.
If the effect of the separation rack is ignored and the only results considered are those of magnetic bead performance, we will reach the wrong conclusion that alternative beads are required.
However, the behavior of exactly the same suspension in an Advanced Biomagnetic Separation System (right, orange) paints a very different picture of the situation. The beads separate quickly, all moving at approximately the same speed. Irreversible aggregation problems disappear, because local retention force and exposure times are much shorter.
As stated in the previous chapter, you need to look at the biomagnetic separation process as a whole, remembering that the force depends on both the magnetic beads and the separation device. This will mean you avoid making Mistake #1 (Blaming the magnetic beads).
What is our recommendation for CLIA-IVD kits manufacturers?
We suggest that rather than using different magnetic beads, you will find it cheaper and quicker to check whether the problem lies with the magnetic separation rack.
If your suspension works well with a different Biomagnetic Separation Systems, you will see that the problem is not the magnetic beads and that there is no need to rebuild the coating protocol.
- Five critical mistakes when using Biomagnetic Separation in CLIA IVD-kits manufacturing
- How can we specify a Biomagnetic Separation Process?