Octet® VHH Biosensors
Bring clarity to every step of your nanobody® pipeline with Octet® VHH Biosensors providing fast, reliable binding kinetics and quantitation in one streamlined workflow across drug discovery, development, and QC. Purpose-built for VHHs, Octet® VHH Biosensors deliver real-time kinetic and quantitation analysis in both crude and purified samples. Achieve high-throughput screening with a wide dynamic range, strong specificity, and cost-effective reuse for repeatable results.
Overview
Octet® VHH Biosensors supply:
- Kinetic and quantitation analysis of VHHs, label-free and in real time
- Compatibility with crude and purified samples for seamless, end-to-end workflows
- Wide quantitation dynamic range of 0.04 – 100 μg/mL with typical precision of CV <10%
- High specificity for VHHs with strong ligand loading and sensitivity
- Efficient regeneration for re-use up to 10 times to maximize cost-effectiveness
- Proven utility across lead identification and optimization, cell line development, process development, and quality control
In biotechnology and medicine the terms nanobody® and VHH are often used interchangeably for single domain antibodies. These small format versions of traditional antibodies have become important tools across diagnostics and cell and gene therapies.
It all started in 1989 when Professor Raymond Hamers and his team at Vrije Universiteit Brussel discovered an unusual antibody in camels infected with Trypanosoma evansi (1). These antibodies lacked light chains and consisted only of heavy chain fragments, later named heavy chain only antibodies (HcAbs). The team then optimized the creation of single domain antibodies and patented their method. In 1994 they introduced VHH to describe the isolated variable domain of a heavy chain only antibody. Single domain antibody fragments from camelid heavy chain only antibodies were first described in 1993. Ablynx® introduced the term nanobody® in 2003, and after key patents expired in 2013 interest and commercialization expanded in research, diagnostics, and therapy (2).
VHH fragments are typically selected from large cDNA libraries using phage or yeast display, which supports efficient production and engineering. Compared with conventional antibodies they offer high affinity and specificity, structural robustness, and deep tissue penetration. They measure about 2.5 nm by 4 nm and weigh around 15 kDa, about one tenth the size of a traditional monoclonal antibody (mAb). Nanobody® is a registered trademark of Ablynx®, and its use spread widely beyond the company. The first approved nanobody® based drug, Caplacizumab from Ablynx® for a blood disorder, was approved in 2018 by the European Union and 2019 by the United States FDA, respectively (3|4). Today nanobodies® (Nbs) are often used as a general term for these compact and versatile fragments. At Sartorius we use VHH instead of nanobody® to respect the trademarked origin.
IgG antibodies are Y shaped and require both the heavy chain variable domain and the light chain variable domain to bind antigens, with six complementarity determining regions involved. In HCAbs only three complementarity determining regions located in the VHH region provide equivalent antigen binding. VHH is the smallest and most compact functional unit of heavy chain only antibodies®, and its simpler smaller structure provides specific advantages unique to this modality.
1. Hamers-Casterman, C.; Atarhouch, T.; Muyldermans, S.; Robinson, G.; Hamers, C.; Songa, E.B.; Bendahman, N.; Hamers, R. Naturally occurring antibodies devoid of light chains. Nature 1993, 363, 446–448. https://doi.org/10.1038/363446a0
2. Jin BK, Odongo S, Radwanska M, Magez S. NANOBODIES®: A Review of Diagnostic and Therapeutic Applications. Int J Mol Sci. 2023;24(6):5994. https://doi.org/10.3390/ijms24065994
3. Duggan, S. Caplacizumab: First Global Approval. Drugs 2018, 78, 1639–1642. https://doi.org/10.1007/s40265-018-0989-0
4. Blair, H.A., Lyseng-Williamson, K.A. Caplacizumab in acquired thrombotic thrombocytopenic purpura: a profile of its use. Drugs Ther Perspect 35, 263–270 (2019). https://doi.org/10.1007/s40267-019-00632-w
Key features
The Octet® VHH Biosensors enable easy, high-throughput and label-free kinetic and quantitation analysis of VHH or VHH, which refers to the isolated variable domain of a heavy chain-only antibody, in both crude and purified cell culture samples during the development and manufacture of VHH therapeutics.
These biosensors offer high binding capacity, sensitivity, and a wide dynamic range. They can be regenerated up to 10 times for kinetic and quantitation assays while maintaining consistent and precise measurements. This makes them a cost-effective option for a wide range of high-throughput applications, including lead identification and optimization, cell line development, process development, and QC in both crude and purified protein samples.
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Frequently Asked Questions
A VHH antibody—also called a nanobody® or single-domain antibody—is the isolated variable domain of a camelid heavy-chain–only antibody. It comprises just the heavy-chain variable region (no light chain), is ~15 kDa, and retains full antigen-binding capacity.
Thanks to their small size, stability, high affinity and specificity, and ease of engineering and production, VHHs are widely used in research, diagnostics, and therapeutics. They can serve as both primary and secondary antibody reagents and are cited in thousands of publications.
Conventional antibodies are typically envisioned as Y-shaped molecules composed of multiple components. Effective antigen binding requires both the heavy-chain (VH) and light-chain (VL) variable domains, with a total of six complementarity-determining regions (CDRs) — three from each chain — forming the binding interface.
By contrast, heavy-chain antibodies (HCAbs) achieve comparable antigen recognition using only three CDRs, all located within the VHH domain, the smallest and most compact functional unit of HCAbs. This streamlined, smaller architecture imparts distinct advantages unique to the VHH modality.
VHH antibodies offer notable advantages over conventional IgG antibodies. Their small size (~12–15 kDa vs ~150 kDa) enables superior tissue and tumor penetration and access to recessed or catalytic epitopes, aided by their often-extended CDR3 loops. They are highly soluble and exceptionally stable across broad pH and temperature ranges, frequently refolding after denaturation and maintaining binding in reducing intracellular environments, which supports aerosolized or lyophilized formulations.
Production is simpler and more cost-effective because they are single polypeptide chains that express at high yields in bacteria or yeast without requiring glycosylation. The modular architecture of VHH makes it easy to build multivalent or multispecific formats, fuse them to enzymes, toxins, imaging agents, or Fc/albumin binders, and deploy them as intrabodies, CAR targeting domains, or structural chaperones for difficult targets like GPCRs.
VHHs excel when you need small, stable, easy-to-engineer binders with superior tissue access, intracellular use, or rapid imaging/diagnostics; conventional antibodies remain advantageous for long systemic exposure and Fc-driven therapeutic effects.
NANOBODY® , NANOBODIES®, and Ablynx® are registered trademarks of Ablynx N.V.
