The Institute of Scientific and Industrial Research , Osaka University , 8-1 Mihogaoka , Ibaraki, Osaka 567-0047 , Japan.
Department of Chemical Science and Engineering, School of Materials and Chemical Technology , Tokyo Institute of Technology , 2-12-1, O-okayama , Meguro-ku, Tokyo 152-8552 , Japan.
J Am Chem Soc. 2018 Dec 5;140(48):16834-16841. doi: 10.1021/jacs.8b10854. Epub 2018 Nov 26.
Immunosensing is a bioanalytical technique capable of selective detections of pathogens by utilizing highly specific and strong intermolecular interactions between recognition probes and antigens. Here, we exploited the molecular mechanism in artificial nanopores for selective single-virus identifications. We designed hemagglutinin antibody mimicking oligopeptides with a weak affinity to influenza A virus. By functionalizing the pore wall surface with the synthetic peptides, we rendered specificity to virion-nanopore interactions. The ligand binding thereof was found to perturb translocation dynamics of specific viruses in the nanochannel, which facilitated digital typing of influenza by the resistive pulse bluntness. As amino acid sequence degrees of freedom can potentially offer variety of recognition ability to the molecular probes, this peptide nanopore approach can be used as a versatile immunosensor with single-particle sensitivity that promises wide applications in bioanalysis including bacterial and viral screening to infectious disease diagnosis.
免疫传感是一种生物分析技术，能够通过利用识别探针和抗原之间高度特异性和强的分子间相互作用来选择性地检测病原体。在这里，我们利用人工纳米孔中的分子机制进行选择性的单病毒识别。我们设计了具有弱亲和力的血凝素抗体模拟寡肽来模拟流感病毒 A。通过在孔壁表面功能化合成肽，我们使病毒-纳米孔相互作用具有特异性。研究发现，配体结合会干扰特定病毒在纳米通道中的迁移动力学，从而通过电阻脉冲钝度促进流感的数字分型。由于氨基酸序列自由度可以为分子探针提供多种识别能力，这种肽纳米孔方法可以用作具有单粒子灵敏度的多功能免疫传感器，有望在生物分析中广泛应用，包括细菌和病毒筛选到传染病诊断。
