Abstract: Antibody affinities play an important role in diagnostic, basic research and medical applications. Conventional antibodies are composed of two heavy and two light chains. Both chains contribute to binding of the antigen by their variable domains. In addition to conventional antibodies, llamas produce functional heavy chain antibodies that lack light chains and interact with antigens solely via the variable domain of the heavy chain, designated VHH. Recombinant VHHs are also called single domain antibodies or Nanobodies because of their size in the nm range. In this study we compared the binding of Nanobodies and Nanobody-Fc fusion proteins to human CD38 using Microscale Thermophoresis (MST). This study highlights the potential of MST-Technology in affinity determination of antibody-antigen interactions.