What is the BEL Monolith ?

The BEL monolith is a polymethacrylate adsorbent for the purification of large biomolecules with hydrodynamic diameters between 100 and 2000 nm (Figure 1). The special design of the BEL Monolith offers rapid convective transfer separation of large biomolecules, in particular plasmid DNA (pDNA).

Figure 1: Structure of a polymethacrylate monolith with large channels for convective mass transport

Why BEL Monolith?

  • More tailored to target larger biomolecule (hydrodynamic100nm- 2000nm)

  • Increased yields of plasmid DNA

  • Streamlined processing of the down-steam pDNA purification process (See Figure 2). Ultimately, this leads cost and time reduction for pDNA purification.

  • High purity of super-coiled DNA (> 90%) with the ability to meet Good Manufacturing Practices (cGMP) standards (see Figure 3).

  • Scaleable and easily incorporated into existing facilities

  • At least 20 times more cost-effective than commercially available adsorbents that were compared (see Table 1).

  • Delivers superior performance across key performance indicators (see Table 2).

  • Reusable and can be autoclaved

  • Faster and cheaper to produce than other adsorbents

  • Large average pore size tailored to pDNA results in lower pressure drop, which allows less energy to pump liquid and shear.

    All this equates to huge savings in terms of time and money
    ***** For the summary of other benefits and features please see our brochure.

(Source: Rapid production of therapeutic plasmid DNA: A fundamental engineering approach to vaccine crisis)

Figure 2: Streamline processing with the BEL monolith.  A schematic diagram depicting that the re-design of the downstream pDNA purification process with the monolith substantially reduces the filtration steps required for pDNA purification.

By incorporating the BEL monolith into the downstream process of pDNA production, the process is streamlined down from 3 to 1 purification step.  Because this downstream purification process accounts from 50-80% of the overall cost of production, the substantial amount of time and money that can be saved using this technology can be easily conceived.

Traditionally, diffusion-limited membrane adsorbents have been used for biomolecule processing, which are slow and have limited capacity for purification of large molecules, such as pDNA, as they are more suitable for smaller protein molecules.  Dr Forde has overcome these limitations by creating the BEL monolith, which relies on the convective flow of solute through the adsorbent, as well as having the capacity to tailor pore diameters to target large biomolecules with hydrodynamic diameters between 100-2000nm. As a consequence, significantly improved binding capacities and yields of pDNA are obtained using the monolithic technology. Importantly, it has been proven that in one chromatography step using the monolith technology (see Figure 2), we are able to produce greater than 90% purity of high quality super coiled pDNA, which optimally meets regulatory standards for use in human clinical trials.

(Source: Michael K. Danquah, Gareth M. Forde, The suitability of DEAE-Cl active groups on customized poly(GMA-co-EDMA) continuous stationary phase for fast enzyme-free isolation of plasmid DNA. Journal of Chromatography B, February 2007).

Figure 3: Anion-Exchange Chromatographic purification of plasmid DNA. Peaks 1,2,3,4 and 5 represent loading, washing, RNA, protein and plasmid DNA, respectively.  Using Gel Electrophoresis techniques, no contaminant bands were visible, supporting removal of all contaminants.

Table 1: Comparison of Costs for Commercial Adsorbents and the BEL Adsorbent.

(Source: Towards the design of a scalable and commercially viable technique for plasmid purification using a methacrylate monolithic stationary phase. Journal of  Chemical Technology and Biotechnology)

Table 2: Comparison of the BEL monolith with commercial absorbents across various key performance indicators. The commercially available adsorbent used for comparison are: DEAE Sephrarose FF TM; Q ceramic HyperD 20 TM; Toyopearl DEAE 650 M TM; Fractogel EMD DEAE (S) TM; Source 30Q TM and BIA-CIM DEAE TM.

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