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1IntroductionIn recent years,e lectrochemical biosensors play an important role as detection devices in clinical diagnostic methods.E lectrochemical biosensors have several advantages consisting of simplicity of fabrication, shortr esponse time,l ow cost, high sensitivity,a nd miniaturizability. Based on these fascinating advantages, electrochemical biosensors are going to be in the leading place of the future detection platform at different medical centers [ 1]. In this way,the introduction of new detection labels to replace the ones employed so far is considered as one of the main concerns in this field.Because of the uniqueo ptical, electronic, and mechanical properties,n anomaterials as potent entries in the field of biosensors have attracted considerable attentions in the last two decades [2].V ariousnanostructured materials including noble metal, metal oxide,s emiconductor,a nd hybrid nanoparticles,a sw ell as carbon-based,b iomolecular, and polymeric nanostructures are frequently reported in literature [ 3].T he use of biomacromolecules is av ery appealing strategyf or the synthesis of nanomaterials.A numbero fp roteins with various structuresh ave been used as templates for the synthesis of nanostructures. Amongd ifferent protein structures,n ano-sized cage-like proteins have an internal space that can be employed for encapsulating metal ions asw ell as the other guest molecules.T here are many reports in literature on applying metal-encapsulatedc age-like proteins asa ne lectrochemical probef or bio-analytical detections [4].A mongt he variousn anostructures, metal nanoclusters (NCs) enjoy au nique position because of their distinct properties and potential applications.U nlike encapsulation of metal nanoparticles inside protein cages, NCsa re fluorescenceactive,t hus,a re commonly used as optical probes for the detection of analytes [5].N Cs are almost monodispersed particles consisting of several to tens of atoms less than 2nmi nd iameter with the molecular-like properties of Abstract:W er eport here an ew electrochemical probe for the development of as ensitive,a nd selective sandwich-type electrochemical immunosensor for the detection of epidermal growth factor receptor (EGFR). The probe is an ewly synthesized bovine seruma lbumin (BSA)-templated Pb nanocluster (Pb NC @BSA). Forf abrication of the immunosensor,w ee mployed streptavidincoated magnetic beads (MB) as ap latform for immobilization of the biotinylatedp rimary antibody (Ab 1 ), and utilizedt he Pb NC @BSAc onjugated to secondary antibody (Ab 2 )a sas ignaling probe. After sandwiching the target protein between Ab 1 and Ab 2 ,w ed issolved Pb NC @BSA into an acid, and recorded squarew ave anodic stripping voltammetric (SWASV) signal of the Pb ions as an ana-lytical signal for quantificationo ft he EGFR.T he immunosensor responded linearly towards EGFR within the range of 0.4 ng/mL to 35 ng/mL, with ad etection limit of 8pg/mL. Thei mmunosensor displayed good sensitivity, selectivity,s tability,a nd reproducibility,a nd proved suitable for d...