Multi-compartmentalized, inorganic-organic hybrid nanostructures have been studied in biomedical applications due to their compositional and structural differences in each compartment. The combination of these hybrid nanostructures with metallic nanoparticle clusters would be attractive due to their interparticle plasmonic coupling for photonics-based biosensing. We herein report a new class of compartmentalized bimetal cluster-poly(aniline) hybrid nanostructures (CBCPHNs) for surface-enhanced Raman scattering (SERS)-based, multiplexed detection of autoantibodies in early diagnosis of rheumatoid arthritis (RA). The bimetallic nanoparticle clusters (BNCs) were prepared in a core-shell form by Raman dye-induced aggregation of gold nanoparticles (GNPs) for the core and reduction of silver ions onto GNP nanoclusters for the shell. Subsequently, CBCPHNs were formed by one-directional growth of poly(aniline) via surface-templated polymerization of aniline monomers as well as additional Ag deposition onto BNCs in the presence of a surfactant. The CBCPHNs showed significant electromagnetic field enhancement at both GNP aggregates and Au core-Ag shell gaps of the BNCs, whereas the poly(aniline) counter-compartment served as a biomolecular conjugation site. In addition, we developed a sandwich-type immunoassay platform using these hybrid nanostructures as SERS nanoprobes and magnetic beads (MBs) for early diagnosis of RA in multiplexing. Autoantibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factor immunoglobulin M (RF IgM) were simultaneously detected, and quantified measuring SERS signals of sandwich-type immunocomplexes. Multiplexing of anti-CCP and RF IgM was achieved in low concentration ranges, and their limits of detection were 0.68 IU/mL and 0.93 IU/mL, respectively. These hybrid nanostructures with collective functionalities represent potential nanomaterials for multiplexed detection of autoantibodies.

由于其在每个隔室中的组成和结构差异，已经在生物医学应用中研究了多隔室的无机-有机杂化纳米结构。这些杂化纳米结构与金属纳米颗粒簇的组合将是有吸引力的，这是由于它们用于基于光子学的生物传感的颗粒间等离子体耦合。我们在此报告了一类新的类化双金属簇-聚（苯胺）杂化纳米结构（CBCPHNs），用于基于表面增强拉曼散射（SERS）的自身抗体在风湿性关节炎（RA）的早期诊断中的多重检测。通过拉曼染料诱导的金纳米颗粒（GNP）的聚集和银离子在GNP纳米簇上的还原，以核-壳形式制备了双金属纳米颗粒簇（BNC）。后来，CBCPHN是通过苯胺单体的表面模板聚合以及在表面活性剂存在下将更多的Ag沉积到BNC上而通过聚苯胺的单向生长形成的。CBCPHNs在BNP的GNP聚集体和Au核-Ag壳间隙处均显示出明显的电磁场增强，而聚苯胺反室充当生物分子结合位点。此外，我们开发了使用这些杂化纳米结构作为SERS纳米探针和磁珠（MBs）的三明治型免疫测定平台，用于RA的早期诊断。同时检测针对环状瓜氨酸肽（anti-CCP）和类风湿因子免疫球蛋白M（RF IgM）的自身抗体，并定量测量夹心型免疫复合物的SERS信号。在低浓度范围内实现了抗CCP和RF IgM的多路复用，其检出限分别为0.68 IU / mL和0.93 IU / mL。这些具有集体功能的杂化纳米结构代表了用于自身抗体多重检测的潜在纳米材料。