Cennamo Nunzio, Bossi Alessandra Maria, Arcadio Francesco, Maniglio Devid, Zeni Luigi
Department of Engineering, University of Campania Luigi Vanvitelli, Aversa, Italy.
Department of Biotechnology, University of Verona, Verona, Italy.
Front Bioeng Biotechnol. 2021 Dec 21;9:801489. doi: 10.3389/fbioe.2021.801489. eCollection 2021.
Soft, deformable, molecularly imprinted nanoparticles (nanoMIPs) were combined to nano-plasmonic sensor chips realized on poly (methyl methacrylate) (PMMA) substrates to develop highly sensitive bio/chemical sensors. NanoMIPs (d < 50 nm), which are tailor-made nanoreceptors prepared by a template assisted synthesis, were made selective to bind Bovine Serum Albumin (BSA), and were herein used to functionalize gold optical nanostructures placed on a PMMA substrate, this latter acting as a slab waveguide. We compared nanoMIP-functionalized non-optimized gold nanogratings based on periodic nano-stripes to optimized nanogratings with a deposited ultra-thin MIP layer (<100 nm). The sensors performances were tested by the detection of BSA using the same setup, in which both chips were considered as slab waveguides, with the periodic nano-stripes allocated in a longitudinal orientation with respect to the direction of the input light. Result demonstrated the nanoMIP-non optimized nanogratings showed superior performance with respect to the ultra-thin MIP-optimized nanogratings. The peculiar deformable character of the nano-MIPs enabled to significantly enhance the limit of detection (LOD) of the plasmonic bio/sensor, allowing the detection of the low femtomolar concentration of analyte (LOD ∼ 3 fM), thus outpassing of four orders of magnitude the sensitivies achieved so far on optimized nano-patterned plasmonic platforms functionalized with ultra-thin MIP layers. Thus, deformable nanoMIPs onto non-optimized plasmonic probes permit to attain ultralow detections, down to the quasi-single molecule. As a general consideration, the combination of more plasmonic transducers to different kinds of MIP receptors is discussed as a mean to attain the detection range for the selected application field.
将柔软、可变形的分子印迹纳米颗粒（nanoMIPs）与在聚甲基丙烯酸甲酯（PMMA）基板上实现的纳米等离子体传感器芯片相结合，以开发高灵敏度的生物/化学传感器。NanoMIPs（直径<50nm）是通过模板辅助合成制备的定制纳米受体，对牛血清白蛋白（BSA）具有选择性结合能力，在此用于对置于PMMA基板上的金光学纳米结构进行功能化，后者充当平板波导。我们将基于周期性纳米条纹的未优化的nanoMIP功能化金纳米光栅与具有沉积超薄MIP层（<100nm）的优化纳米光栅进行了比较。使用相同的装置通过检测BSA来测试传感器性能，其中两个芯片都被视为平板波导，周期性纳米条纹相对于输入光的方向纵向排列。结果表明，nanoMIP-未优化的纳米光栅相对于超薄MIP-优化的纳米光栅表现出卓越的性能。nano-MIPs独特的可变形特性能够显著提高等离子体生物/传感器的检测限（LOD），使得能够检测到低飞摩尔浓度的分析物（LOD ∼ 3fM），从而比目前在具有超薄MIP层功能化的优化纳米图案等离子体平台上所达到的灵敏度高出四个数量级。因此，在未优化的等离子体探针上使用可变形nanoMIPs能够实现超低检测，直至准单分子水平。一般而言，讨论了将更多等离子体换能器与不同种类的MIP受体相结合，作为实现所选应用领域检测范围的一种手段。
