(Invited) Rational Design of Chemiluminescence Biosensor Guided By Single Particle Chemiluminescence Imaging
Authors: Cui Hua , Kong Wei Jun , Wang Wei 
Published: May 2020

During past one decade, chemiluminescence (CL) biosensors have received more and more attention due to its high sensitivity, wide linear range and simple instrumentation. In recent years, CL functionalized materials as probes and interfaces have attracted much attention in biosensors due to their good CL activity, ease assembly and good biocompatibility, leading to high sensitivity [1-3]. However, the design and optimization of these materials have usually carried out by conventional trial-and-error procedures under conditional experiments. In this work, an optical microscope was constructed to acquire the CL emission from single magnetic-polymer hybrid microbead functionalized with N-(4-aminobutyl)-N-ethyl isoluminol and Co2+. The CL imaging and the CL kinetics of single particle were obtained by the developed CL microscope [4]. It was observed that a minor subpopulation of microbeads exhibited intensive and delayed CL emission, whereas most of microbeads demonstrated transient and weak emission. Structural characterizations revealed that the amorphously multi-core microstructures were responsible for the enhanced encapsulation efficiency and optimized CL reaction kinetics. Guided by this knowledge stemming from single particle CL imaging, the synthesis procedure was rationally optimized to enrich the portion of microbeads with better CL performance. By using the new batch of microbeads, the analytical performance for TNT sensor was greatly improved. The detection limit was increased by 59 times from 87 pg/mL to 1.47 pg/mL, and the linear range was expanded by 2 orders of magnitudes, compared with non-optimized batch of microbeads. The present work have not only demonstrated the CL imaging and CL kinetic curve of single microbead for the first time, it has also showed the capability of single particle studies to interrogate the structure-activity relationship in a bottom-up manner and to help the rational design of ensemble CL biosensors towards improved performance.

Acknowledgements

The support of this research by the National Natural Science Foundation of China (Grant No. 21527807) and the National Key Research and Development Program of China (Grant No. 2016YFA0201300) are gratefully acknowledged.

References

[1] M.X.Liu, H.L.Zhang, J.N.Shu, X.Y.Liu, F.Li, H.Cui, Gold Nanoparticles Bifunctionalized by Chemiluminescence Reagent and Catalyst Metal Complexes: Synthesis and Unique Chemiluminescence Property. Analytical Chemistry. 86 (2014) 2857–2861. doi:10.1021/ac5002433.
[2] Z.L.Han, J.N.Shu, Q.S.Jiang, H.Cui, Coreactant-Free and Label-Free Eletrochemiluminescence Immunosensor for Copeptin Based on Luminescent Immuno-Gold Nanoassemblies. Analytical Chemistry. 90 (2018) 6064–6070. doi:10.1021/acs.analchem.7b05406.
[3] R.Yang, F.Li, W.C.Zhang, W.Shen, D.Yang, Z.P.Bian, H.Cui, Chemiluminescence Immunoassays for Simultaneous Detection of Three Heart Disease Biomarkers Using Magnetic Carbon Composites and Three-Dimensional Microfluidic Paper-Based Device. Analytical Chemistry. 91 (2019) 13006–13013. doi:10.1021/acs.analchem.9b03066.
[4] W.J.Kong, Q.Li, W.Wang, X.N.Zhao, S.L.Jiang, T.H.Zheng, Q.Zhang, W.Shen, H.Cui, Rational Design of Functional Materials Guided by Single Particle Chemiluminescence Imaging. Chemical Science. 10 (2019) 5444–5451. doi:10.1039/C9SC00954J.