Custom Affinity Resins and Ligands | Thermo Fisher Scientific

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Addressing affinity capture challenges in downstream processes

Affinity capture steps are often expected to resolve complexity early in downstream processing (DSP), yet limitations in selectivity, closely related product variants, or sensitivity to elution conditions can constrain performance. In complex feedstreams, standard affinity resins may struggle to discriminate between target and impurities or require elution conditions that compromise yield or product quality.

CaptureSelect technology enables custom affinity resin and ligand development when fully evaluated affinity chromatography resins show that key attributes—such as selectivity or elution behavior—are limiting capture-step performance. Affinity resins and ligands are then designed to meet molecule-specific requirements, aligning capture performance with downstream process objectives.

A structured, platformed approach to custom affinity development

CaptureSelect custom affinity resin and ligand development has demonstarted success in over 60 programs since 2003 over multiple decades and is executed through a defined, milestone-based program designed to translate molecular requirements into process-aligned affinity capture solutions. CaptureSelect ligand libraries are evaluated using staged screening and decision points that are anchored to process-relevant data, including selectivity, elution behavior, and robustness. This structured progression enables informed technical decisions while maintaining alignment with downstream workflow requirements as process understanding matures.

Library construction
Target definition
Ligand screening
Prototype development
Lead selection

Library construction

Build a CaptureSelect ligand library around your target protein to create a focused starting set for affinity screening. Library construction can be executed for a single target when one molecule drives the program or scaled to support up to 10 targets in parallel when multiple candidates or formats need to be evaluated.

Target definition/performance criteria

Define the target context up front to anchor ligand discovery to downstream performance needs. Target proteins, representative feedstreams, and operating constraints are characterized early, such as elution pH limits or feedstream variability, to establish clear screening criteria before library interrogation begins. Programs draw from more than 100 immune libraries or apply a custom immune library based on the target, with multi-layer phage display panning used to enrich reactive clones. This upfront definition aligns selectivity, elution behavior, and stability expectations with how the affinity capture step must function within the broader purification workflow.

Ligand screening/selectivity assessment

Screen large CaptureSelect ligand libraries using a tailored, high-throughput screening (HTS) workflow to identify CaptureSelect custom chromatography ligands that meet defined process performance criteria. More than 400 ligand leads are evaluated in parallel for specificity, binding kinetics (KD), mild elution behavior, and stability, enabling rapid differentiation between viable and non-viable options. CaptureSelect affinity ligands employ the CDR1-3 paratope of a natural immune globulin, thus offering excellent target specificity and selectivity, such as selectively binding to conformational epitopes. This data-driven screening approach helps minimize development risks early by focusing follow-on work on ligands likely to meet downstream capture requirements, informed by experience across more than 60 CaptureSelect custom affinity resin and ligand programs.

Prototype development/evaluation

Advance selected ligands into prototype affinity resins using scalable yeast-based ligand production capable of multi-kilogram output. These ligand prototypes are immobilized on standard agarose backbones. Prototypes are evaluated early using representative feedstreams and intended process conditions, with technical support to assess capacity, selectivity, elution behavior, and stability before narrowing candidates for lead assessment.

Lead selection

Narrow development to two lead ligand–resin prototypes immobilized on agarose and/or POROS resins and evaluate them under conditions that reflect intended process operation. In-house testing uses process-relevant materials to assess elution profiles, achievable one-step purity, ligand stability, and performance across operating ranges relevant to scale-up. Lead prototypes can be shared with customers as Research Use Only resins at liter scale, supported by technical guidance to confirm fit within the capture step before advancement toward cGMP suitability.

Evaluate affinity resins and ligands for process fit

Confirm process fit by testing how candidate CaptureSelect affinity resins and ligands perform under representative capture conditions. Evaluation focuses on whether predefined performance criteria are met, including selectivity in relevant feedstreams, robustness across operating and cleaning conditions, and consistency of capacity and elution behavior across column formats and residence times. Results are used to determine whether the affinity capture step meets technical requirements for progression without introducing unacceptable performance limitations.

Start from existing candidates

Accelerate development by initiating programs from existing CaptureSelect ligand candidates already identified within the internal development pipeline. These candidates can serve as technically informed starting points when prior selectivity, binding capacity, or application relevance aligns with the target molecule. Beginning from validated pipeline assets can shorten early screening phases while preserving the same structured path toward a fit-for-purpose affinity resin.

Table 1. CaptureSelect affinity target pipeline*

	Product stage	Protein	Antibody	Virus/Delivery
Products	Bioprocess Products	HSA, FX, tPA, AAT-XL, FSH, hCG, TSH, hGH, C-tagXL, POROS C1-inhXL, POROS ClusterinClear	FcXP, POROS FcXP, KappaXP, LambdaXP, CH1-XL, IgE	POROS AAV8, AAV9, AAVX
Products	RUO Products	POROS FibXL, ATIII, Prothrombin, GM-CSF, Factor II(a), Factor H	POROS IgM-XL, IgA-XL	POROS Adv5, POROS BacuClear Lenti VSVG, Exosomes (CD81)
Ligand R&D	Stage WP4: Lead selection	HSA-XL, EPO / Darbepoetin, Protein C	IgY-Fc
	Stage WP3: Prototype testing	Factor V, Factor XI, Factor XIII IL15, CRM197 CHO-HCPs: Legumain, PLBL2	Mouse and Rat IgG-Fc	GP64, dsRNA Exosomes (CD9) SARS-CoV2
	Stage WP2: Ligand screening	Factor VIII, Factor XII, Tenecteplase, Hyaluronidase, Haptoglobin, IFNα/β, IL2, IL2R CHO-Lipases: LPL, LAL, LPLA2	Dog and Cat IgG-Fc	Exosomes (CD63) Plasmid DNA, HSV
	Stage WP1: Libraries	Human plasma, Cytokine receptors. CHO-HCPs	Various Ab isotypes and species	Non-Immune libraries: enveloped and non-enveloped viruses (Oncolytic: HSV / VSV / Vaccinia)

*This list may not include new targets or advancements. Contact us for an updated list.

Designed to integrate into downstream purification workflows

Design CaptureSelect custom affinity resins and ligands, considering how capture-step attributes influence downstream process design. Selectivity, elution conditions, and operating ranges are considered in the context of downstream polishing strategies, including ion exchange (IEX), hydrophobic interaction (HIC), or mixed-mode chromatography (MMC). This approach helps avoid shifting complexity to later unit operations and supports smoother integration of the affinity step within the overall downstream purification workflow.

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Discover custom chromatography resin development

Explore additional chromatography resin development services designed to address purification challenges beyond affinity capture alone. Custom chromatography resin development applies the same structured, data-driven approach to define resin and ligand attributes, such as selectivity, capacity, and operating behavior, based on how the molecule performs across the full downstream workflow

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Collaborate with our specialists

Engage in a technical, scientist-to-scientist discussion focused on your molecule, feedstream, and downstream objectives. Collaboration centers on understanding process context, data gaps, and development constraints to determine whether CaptureSelect custom affinity resin and ligand development is appropriate.

Bongers L, Franken LE, Hoch D et al. (2026) Selectivity for full AAV capsids in affinity capture with camelid ligands. J Chromatogr A. 1767:466644. doi:10.1016/j.chroma.2025.466644.

Pabst, TM et al. (2016) Camelid VHH affinity ligands enable separation of closely related biopharmaceuticals. Biotechnol. J. doi: 10.1002/biot.201600357

Beyer T, Lohse S, Berger S et al. (2009) Serum-free production and purification of chimeric IgA antibodies. J Immunol Methods. 346(1-2):26-37.

Kuroiwa Y, Kasinathan P, Sathiyaseelan T et al. (2009) Antigen-specific human polyclonal antibodies from hyperimmunized cattle. Nat Biotechnol. 27(2):173-81

McCue JT, Selvitelli K, Walker J. (2009) Application of a novel affinity adsorbent for the capture and purification of recombinant factor VIII compound. J Chromatogr A. 1216(45):7824-30.

Enabling custom solutions for downstream processing

Solving purification bottlenecks in biotherapeutics with custom resin solutions

Custom chromatography solutions for complex biotherapeutics

Frequently asked questions

A CaptureSelect custom affinity resin approach is typically considered when commercially available affinity resins no longer meet process requirements despite optimization efforts. This often occurs when limitations in selectivity, co-purification of closely related variants, constrained elution conditions, or insufficient purity or yield persist. In these cases, developing a resin and ligand tailored to the specific molecule and feedstream can better align affinity capture performance with downstream process objectives.

Success is defined by whether the affinity resin and ligand meet the predefined performance criteria required for the intended capture step. Evaluation is based on data generated during screening and prototype development, focusing on selectivity, binding behavior, elution profiles, and ligand stability. Lead candidates are then assessed under representative process conditions to confirm consistent performance, scalability considerations, and suitability for integration into the downstream purification workflow.

CaptureSelect custom affinity resin and ligand development can be integrated at multiple stages, including early process development. Programs may begin when molecule characterization or process definition is still evolving, using available target and feedstream information to guide initial screening. A good understanding of critical process and product-related impurities is essential to define screening parameters. As development progresses, resin and ligand performance data help refine assumptions, supporting alignment with later-stage scale-up and manufacturing requirements.

Thermo Fisher Scientific supports scalability and cGMP readiness by advancing selected affinity leads through controlled ligand production, qualified resin manufacturing, and documented verification activities. This includes establishing master and working cell banks, producing qualified resin batches for process evaluation, developing ligand-leakage assays, and offering supporting documentation aligned with regulatory expectations as programs progress toward manufacturing use.

CaptureSelect custom affinity resin and ligand development integrates with existing downstream processes by designing the capture step to function within the constraints of the existing purification workflow. Ligand selectivity, elution conditions, and operating ranges are evaluated with downstream polishing steps in mind to avoid creating bottlenecks. This allows the affinity step to complement established unit operations instead of requiring broad process redesign or reverification.

Chromatography resources

Access additional chromatography resources for deeper technical support. These materials focus on purification fundamentals, resin behavior, and workflow considerations that can support decision-making during process development and optimization.

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