摘要
表面等离子体共振（SPR）技术，以非标记、实时、高灵敏的特点广泛应用于生物分析领域。近年来，SPR与多种分析手段联用的技术不断涌现，体现出SPR技术强大的生命力。本文以SPR-电化学联用技术为切入点，重点基于SPR信号与电化学信号之间的定量关系，分别针对法拉第及非法拉第过程，探讨电位信号调控SPR响应规律，以及在生物分析领域的优势及潜在应用。
基于SPR-电化学联用技术中SPR响应与法拉第过程电化学电流的关系，特别针对电势扫描技术中不可逆与准可逆电极过程，进行了理论数值计算以及实验验证，对原有理论及可逆过程的分析进行了有益的补充。SPR响应与参与法拉第过程的氧化-还原物质转变过程相关，直接反映了物质浓度随电势扫描速度和电极过程的可逆程度的关系。
针对电化学中非法拉第过程，将SPR与交流阻抗技术结合。研究了不同频率交流电位信号调控下的SPR信号响应规律，并根据等效电路模型进行了理论验证及影响因素讨论。结果表明，通过SPR信号的交流部分可以获取界面的阻抗信息，即以光学信号得到电化学阻抗信息；而SPR信号的直流部分为常规SPR信号。对于生物分子相互作用体系，对比了表面等离子体电化学阻抗信号与常规SPR信号的不同特点。表面等离子体电化学阻抗能够避免溶液体相折射率变化与非特异性吸附的干扰，只对生物分子特异性结合产生响应。
此项技术在阻抗成像领域有特别的优势，由SPR图像可直接计算得到界面阻抗图像，其时间、空间分辨率都得到极大的提高。基于此，利用表面等离子体阻抗显微成像技术研究了活细胞内源性G蛋白偶联受体激活过程，同时得到细胞光学和电化学阻抗的成像图像，具有毫秒级、亚细胞尺度的分辨率。实验结果表明，HeLa细胞组胺受体激活后，会引发下游各级细胞通路响应，导致细胞成像信号一系列特征性的改变。实验中还特别发现了不同细胞之间第二信使分子响应时间的异质性和亚细胞尺度上细胞粘附性改变的空间分布特性。阻抗成像也能够给出组胺受体激活后细胞内钙离子流动的动态过程信息。实验结果为理解组胺引发机体发炎过程提供了单细胞层次上的信息，为相关疾病治疗和药物研发提供了有益的参考。
Surface plasmon resonance (SPR) biosensor is a label-free, real-time, highlysensitive technique, which was widely used in the bioanalysis. The combination of SPRwith complementary analytical techniques has become increasingly popular recently.Here, we focus on the plasmonic based electrochemical technique. Based on thequantitative relationship between SPR and electrochemical signals, we studied thepotential modulated SPR response during faradaic and nonfaradaic process, anddiscussed the advantages of plasmonic based electrochemical technique in thebioanalysis as well as its potential applications.
Firstly, we studied SPR responses during the faradaic process, especially for theirreversible and quasi-reversible electrode processes of potential sweep methods. Wediscussed numerical solutions and used model systems to prove the theories. The resultsdemonstrated that SPR response is closely related to the concentration changes ofred-ox substance at different potential scan rates and reversibility of the reactions.
For the relationship between SPR response and non-faradaic current, we studiedplasmonic based electrochemical impedance spectroscopy. SPR signals were acmodulated by applying ac potential to the SPR chip surface. The ac component of SPRsignals gives the electrochemical impedance, and the dc component is the conventionalSPR. Over a range of frequency, the plasmonic based impedance was in quantitativeagreement with the conventional electrochemical impedance. The results demonstratethe possibility that optical means can measure the impedance signals. We compared theperformances of plasmonic based impedance and conventional SPR signals of thebiomolecular interaction. We found that plasmonic based impedance is sensitive tospecific molecular binding on the chip surface and less sensitive to bulk refractive indexchanges or nonspecific binding.
Plasmonic based impedance has more advantages when it works in imaging mode.We can directly obtain the impedance information of the interface from SPR imageswith high temporal and spatial resolutions, comparing to other traditionalelectrochemical imaging techniques. We used plasmonic based impedance microscopyto study the endogenous G protein-coupled receptor (GPCR) stimulations of live cellswith subcellular and millisecond spatial-temporal resolutions. We used histamine to trigger GPCR activations of HeLa cells. The obtained images revealed theheterogeneous cell initial responses to histamine stimulation, and visualized thedistribution and strength of cell adhesion modulation by histamine triggered GPCRactivations. The impedance images also indicated the calcium flux after GPCRactivations. The imaging and mapping results offered visualized information ofpermeability modulation during allergic inflammatory process of intact epithelia cells.The findings will also promote the development of novel inflammation therapeutics andantihistamine drugs in the future.
引文
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