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 ).