1. Nanomechanical sensor for rapid and ultrasensitive detection of tumor markers in serum using nanobody
- Author
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Kainan Mei, Wenjie Wu, Shangquan Wu, Tianhao Yan, Jianye Wang, Depeng Rao, Qingchuan Zhang, Ye Chen, and Yu Wang
- Subjects
Early cancer ,nanobody-based biosensor ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,adsorption-induced inactivation ,Thiol group ,stress enhancement ,General Materials Science ,Electrical and Electronic Engineering ,Binding site ,Receptor ,Tumor marker ,Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Orders of magnitude (mass) ,0104 chemical sciences ,tumor markers ,Covalent bond ,Biophysics ,early cancer detection ,0210 nano-technology ,Research Article ,Macromolecule - Abstract
Early cancer diagnosis requires ultrasensitive detection of tumor markers in blood. To this end, we develop a novel microcantilever immunosensor using nanobodies (Nbs) as receptors. As the smallest antibody (Ab) entity comprising an intact antigen-binding site, Nbs achieve dense receptor layers and short distances between antigen-binding regions and sensor surfaces, which significantly elevate the generation and transmission of surface stress. Owing to the inherent thiol group at the C-terminus, Nbs are covalently immobilized on microcantilever surfaces in directed orientation via one-step reaction, which further enhances the stress generation. For microcantilever-based nanomechanical sensor, these advantages dramatically increase the sensor sensitivity. Thus, Nb-functionalized microcantilevers can detect picomolar concentrations of tumor markers with three orders of magnitude higher sensitivity, when compared with conventional Ab-functionalized microcantilevers. This proof-of-concept study demonstrates an ultrasensitive, label-free, rapid, and low-cost method for tumor marker detection. Moreover, interestingly, we find Nb inactivation on sensor interfaces when using macromolecule blocking reagents. The adsorption-induced inactivation is presumably caused by the change of interfacial properties, due to binding site occlusion upon complex coimmobilization formations. Our findings are generalized to any coimmobilization methodology for Nbs and, thus, for the construction of high-performance immuno-surfaces. Electronic Supplementary Material Supplementary material (experimental section, HER2 detection using anti-HER2-mAb-functionalized microcantilevers) is available in the online version of this article at 10.1007/s12274-021-3588-4.
- Published
- 2021