Single-Atom Nanozymes Linked Immunosorbent Assay for Sensitive Detection of A β 1-40: A Biomarker of Alzheimer's Disease

Zhaoyuan Lyu; Shichao Ding; Nan Zhang; Yang Zhou; Nan Cheng; Maoyu Wang; Mingjie Xu; Zhenxing Feng; Xiangheng Niu; Yuan Cheng; Chao Zhang; Dan Du; Yuehe Lin

doi:10.34133/2020/4724505

Single-Atom Nanozymes Linked Immunosorbent Assay for Sensitive Detection of A β 1-40: A Biomarker of Alzheimer's Disease

Research (Wash D C). 2020 Oct 19:2020:4724505. doi: 10.34133/2020/4724505. eCollection 2020.

Authors

Zhaoyuan Lyu¹, Shichao Ding¹, Nan Zhang², Yang Zhou¹, Nan Cheng¹, Maoyu Wang³, Mingjie Xu⁴, Zhenxing Feng³, Xiangheng Niu¹, Yuan Cheng², Chao Zhang⁵, Dan Du¹, Yuehe Lin¹

Affiliations

¹ School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA.
² Institute of High Performance Computing, Institute of High Performance Computing, Singapore 138632.
³ School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR 97331, USA.
⁴ Irvine Materials Research Institute (IMRI), University of California, Irvine, CA 92697, USA.
⁵ Department of Electrical and Computer Engineering, National University of Singapore, Engineering Drive 3, Singapore 117583.

Abstract

Single-atom nanozymes (SANs) possess unique features of maximum atomic utilization and present highly assembled enzyme-like structure and remarkable enzyme-like activity. By introducing SANs into immunoassay, limitations of ELISA such as low stability of horseradish peroxidase (HRP) can be well addressed, thereby improving the performance of the immunoassays. In this work, we have developed novel Fe-N-C single-atom nanozymes (Fe-N_x SANs) derived from Fe-doped polypyrrole (PPy) nanotube and substituted the enzymes in ELISA kit for enhancing the detection sensitivity of amyloid beta 1-40. Results indicate that the Fe-N_x SANs contain high density of single-atom active sites and comparable enzyme-like properties as HRP, owing to the maximized utilization of Fe atoms and their abundant active sites, which could mimic natural metalloproteases structures. Further designed SAN-linked immunosorbent assay (SAN-LISA) demonstrates the ultralow limit of detection (LOD) of 0.88 pg/mL, much more sensitive than that of commercial ELISA (9.98 pg/mL). The results confirm that the Fe-N_x SANs can serve as a satisfactory replacement of enzyme labels, which show great potential as an ultrasensitive colorimetric immunoassay.