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Posted on Tue, May 19, 2015

Scale-up Challenges in Biomagnetic Separation Processes

The last two decades have seen an explosive growth in the use of magnetic beads in Life Science, with sustained double figure sales increase all across the industry. The main driver of this success has been the use of magnetic beads as a solid phase on Chemiluminescence Immunoassays (CLIA) kits. Thanks to its easy automation, this technique has become the preferred choice for high throughput In Vitro Diagnostic.

The commercial success of CLIA analyzers has forced the IVD-kit manufacturers (and magnetic beads manufacturers) to ramp production for coping with the demand. The early strategy was to increase the number of lots by keeping them at the same volume and maintaining the same operational procedures. The problem with this approach, however, is that it needs a proportional increase of highly skilled workers. In addition to that, strict quality controls would be needed to ensure that each single lot falls within the acceptable range of functionality and yields. Producing 100 lots of 100 ml for getting a total of 10 L of magnetic bead suspension needs to prove that each single 100 ml lot is equivalent for guarantee that each single IVD-kit falls inside the accepted tolerances. The high costs of this approach force manufacturers to explore simpler and cost-effective ways to cope with the increasing demand.

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The alternative approach is to keep the number of batches almost constant but increase the volume per batch. Increasing the lot volume allows companies to maintain labor and QC costs. If correctly implemented, the repercussion of labor and QC on the individual kits will decrease proportionally to the batch volume. However, in order to succeed, you will need in-lot consistency that makes every single aliquot (usually below 1 ml) compliant with the required tolerances. Scaling-up Biomagnetic Separation processes is not just simply using a bigger magnet. It is far more complicated. In this asrticle and the following ones we will provide you the best tips to make this process a less complicated one. 

 

Have a right start to Scale-up

Developing magnetic beads based products is a long process. For a diagnostic kit, a protein purification product or a new application, it's necessary to select the right biomarker, the coating surface and the magnetic bead. These three aspects are usually checked with great detail while looking for the right characteristics and protocols. Unfortunately, many times, little attention is paid to the biomagnetic separation process itself. In most cases, all the development is performed using the available small volume magnetic separator or, sometimes, just a small magnet.

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If the development is smooth, the magnetic separators seem to be an unimportant issue. The problems usually appear when the volume of the experiments needs to be scaled up from the usual few milliliters to the tenths of liters. The results seem to be inconsistent when the scale changes, losses increase, attempts of using ‘bigger magnets’ lead to irreversible aggregation problems, and re-suspension becomes a nightmare. These problems are also present at the initial scale, but they tend to be attributed to the lack of performance of the biomarker or the magnetic bead.

The truth is that, in many cases, the problem is on the magnetic separator itself. Developers have paid great attention to specify the characteristics of the antibody/protein, bead size and magnetic content, surface properties, temperature and composition of the incubation buffer. But not to the biomagnetic separation process itself. In most of the cases, the only specified parameter for the process is the separation time for the specific device used.

The right start is to understand the biomagnetic separation process itself (as we did with all the other materials and methods used during the development), then fix the parameters governing it. This way, we will be able to specify the separation conditions, evaluate different values of the magnetic force and objectively validate biomagnetic separation process.

Remember to download The 7 Keys for Successfully Scaling-up Biomagnetic Separation Processes in order to learn much more about this useful technique:

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