Fig. 1 Publication trend on antibody mimetics between 1986 and 2022

3.2 Keyword Analysis

Keywords demonstrate major research topics in an area with the analysis of burstiness and cluster. Burstiness analysis retrieves keywords with a frequency surge in a particular time period, reflecting stages of rise, bloom and decline of a research topic. Cluster analysis groups keywords into different categories, in which keywords within the same category have high frequency to be co-occurred in an article compared with others. The quality of clusters is determined by the value of silhouette, meaning that clusters with silhouette closest to 1 have the most similarities and homogeneities within cluster and least overlap with other clusters (Chen, 2004 ).
The occurrence of major keywords throughout the development of antibody mimetics is visualized over the timeline. Although the attention of academic community on fundamental research including monoclonal antibody, ligands, gene expression and phage display remain sustained and relatively stable over decades, it is worth noting that research in this field began to enter the stage of therapeutic and diagnostic applications around 2005 (Chu et al., 2006 ; Xu et al., 2005 ).
Cluster analysis showed 1435 keywords with 6039 links (Fig. 2B), of which 18 keywords appear 100 times or more (aptamer, DNA, nanoparticles, binding, selection, biosensor, gold nanoparticles, in vitroselection, assay, protein, aptasensor, ligands, molecules, recognition, sensor, label free, expression, in vitro ). 1435 keywords were clustered into 11 categories with silhouette vales ranging from 0.641 to 0.982, indicating high cluster credibility and relatively high differentiation of branched research areas within this field. The inherent selectivity of antibody mimetics for their antigen (ligand analyte) confers desirable properties on antibodies to develop technologies that exploit binding events, especially in immunoassays and therapeutics. Clusters #1 “aptasensor”, #2 “food safety”, #7 “fluorescence anisotropy”, Clusters #8 “Alzheimer’s disease”, #9 “circulating tumor cells” are all focusing on immunoassay. It is notable that the application of immunoassay in various fields has been fully developed as evidenced by the large number of publications in each cluster. Specifically, it acts as important biomarkers for diagnosis of cancers, degenerative diseases such as Alzheimer’s’ disease and infectious disease such as malaria. Recently, antibody mimetics has been increasingly engineered for detecting bacterial pathogens present in food, water and the environment. This research boom is driven by the development of biosensor technology (Li et al., 2019 ), in which, antibody mimetics that interact with target analyte are combined with physiochemical transducer that transforms the result of the interaction into an optical, piezo-electrical, or electrochemical signal. For example, antibody-nanoparticle bioconjugates have proven to be an ideal vessel for bioconjugation and biosensor purposes due to their unique surface characteristics, optical properties, stability, and consistency. Apart from the wide application in immunoassay, antibody mimetics also play roles in drug delivery for cancer diseases and neurological disorders. Antibody-conjugated drug-loaded nanoparticles can selectively target cells and release large amounts of drugs to treat diseases like cancers (Arruebo et al., 2009 ). This is because they combine both functions of the nanoparticles such as liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, which control drug release, increase drug solubility, protect drug from degradation, and the antibody mimetics, which can bind to their targets with high affinity and better cell penetration (Busch et al., 2019 ).