How Can Millennial Scientific Meet Your Custom Chromatography Media Needs?

NanoPak-C All Carbon microbeads, which range in size from 5 to 40 µm, are made from natural micro graphite and form the basis of our chromatography products. However, we can also create custom media. For instance, we are developing larger microbeads (over 100 µm), as well as microbeads made of different materials, such as silica, and affinity monolith microbeads for our clients. Our efficient process takes less than a month, starting from initial research and development trials, producing hundreds of milligrams of candidate microbeads, and scaling up to tens of grams of test samples for customers. This blog explains how our technology enables us to collaborate with customers to create customized microbeads that meet their specific separation needs. We also share some case studies.

Technology to create customized microbeads.

Figure 1 illustrates the starting materials, crosslinkers, and optional additives that can be used with our microfluidic microdroplet technology. These options allow us to customize the final microbead product in terms of:

Figure 1. A depiction of the starting materials, crosslinkers, and other additive inputs serves as a toolbox to help create end products with specific physical and chemical properties.

Figure 2. Ilustration of our customizable microbead platform. The input sources are combined through a microdroplet assembly to create mechanically stable spheres.

• Composition

• Structure

• Function

We choose the starting materials based on two main factors:

• Their ability to get trapped in the microdroplet

• Their ability to link with the crosslinkers to form the microbeads (see Figure 2).

Our published articles in ACS Omega and Scientific American explain how our microfluidic microdroplet technology enables the discovery and creation of custom materials.

Here’s a summary of our process for developing custom separation media:

• Mix the starting materials, crosslinkers, and additional additives in varying amounts to create different slurries or inks.

• Introduce the slurries into our microdroplet setup, which handles volumes ranging from microliters to picoliters. The materials inside the microdroplets react as they flow, creating a library of microbead materials.

• Test each microbead material to ensure its composition meets the customer’s separation needs.

• Make adjustments by modifying the slurry composition and process parameters to identify the optimal candidates.

• Identify the right candidates, and scale up using the same setup.

How is our approach different than custom media solutions provides by other vendors?

Other vendors mainly focus on custom media for affinity chromatography. They can usually tailor the properties (pore size, diameter) of one type of microbead (e.g., agarose microbeads, divinyl benzene microbeads). Additionally, they have proficiency in optimizing the functionalization of the affinity ligands (e.g., protein A, protein G) onto these ligands.

Our approach enables custom media development with diverse compositions for various types of chromatography, including normal, reverse-phase, ion-exchange, and affinity chromatography.

Three Case Studies Showing the Flexibility of Our Approach.

Case Study 1: Making Silica Hybrid Microbeads.

The Challenge: A customer in Europe sought silica hybrid microbeads with a diameter exceeding 100 µm and a porosity greater than 500 Å.

Our Approach: We started with silica gel that had a pore size above 500 Å. We mixed this material with a

Figure 3. Digital image of 100 µm average diameter silica hybrid microbeads.

diene or diacrylate monomer as crosslinkers. We also explored the use of an alkyl trimethoxysilane to adhere to the traditional silica sol-gel manufacturing process within our microdroplets. We adjusted the microdroplet parameters to reach a diameter of 100 µm. In three weeks, we prepared several hundred candidate samples (Figure 3) and shipped tens of grams of final microbeads to the customer. Once tested and approved, we can quickly scale up production to tens of kilograms.

Case Study 2: Large Carbon Microbeads for Ghostbuster Columns.

The Challenge: A customer in India needed large carbon microbeads (500-900 µm) to remove low-polarity impurities from ghostbuster columns. These impurities cause ghost peaks in high-performance liquid chromatography (HPLC) during analysis.

Our Approach: We adjusted the binder compositions of the graphitic carbon slurry to change the

Figure 4. Digital photograph of 600 µm diameter carbon microbeads.

microbead properties, enhancing their ability to trap non-polar small molecules. We created two batches: one with an average diameter of 600 µm and the other with an average of 900 µm (Figure 4). We provided tens of grams of each batch to the customer, who packed them into columns and tested them at third-party facilities. This process took four weeks. We will scale up production to kilogram quantities for the customer.

Case Study 3: Creating Monolith Microbeads Embedded with Protein G-Conjugated Agarose.

The Challenge: A professor at a university required assistance in preparing a 96-well Protein G-based plate to isolate IgG from plasma samples. The professor used Protein G resins in a dispersive solid-phase extraction format.

Our Solution: We recommended employing our porous microbead-based fritless monolith manufacturing technique to integrate the protein G resins, resulting in a consistent resin bed. This configuration enhances the extraction process by merging the porous microbead monolith material and media into a uniform bed, thereby eliminating the need for frits. This approach also enables the processing of samples with increased viscosity, prevents blockages, and facilitates high-throughput sample processing.

For more information on how our NanoPak-C All Carbon media or custom media services can address your pharmaceutical purification challenges or to request samples, please email us at inquiry@millennialscientific.com, call us at 855 388 2800, or fill in our online form.