Paper-based electrochemiluminescence sensor for highly sensitive detection of amyloid-β oligomerization: Toward potential diagnosis of Alzheimer's disease

Abstract

Development of a rapid and sensitive method for Aβ(1-42) aggregation detection is of great importance to overcome the limitations of conventional techniques. In this study, we developed a label-free paper-based electrochemiluminescence sensor for amyloid-β aggregation detection toward potential diagnosis of Alzheimer's disease (AD). The paper-based chip used in the system serves as a low-cost and disposable detection method. In this detection platform, the bonding of [Ru(phen)2dppz]2+ to Aβ(1-42) aggregates results in enhanced electrochemiluminescence due to the change in the polarity of the microenvironment when [Ru(phen)2dppz]2+ intercalated into the β-sheets during oligomerization. The oligomerization process of Aβ(1-42) can be monitored in real time by the novel method, and as low as 100 pM equivalent monomer concentration of Aβ(1-42) could be detected simultaneously. In addition, the cerebrospinal fluid of transgenic AD model mice was tested by this method, which is highly consistent with genetic identification. In addition, we demonstrated that this detection platform could be a potential new method for the screening of Aβ(1-42) aggregation inhibitors, highlighting the practical application capacity of this platform. The platform is label free, low cost and sensitive. Therefore, the proposed platform holds great promise for the diagnosis of AD.

Research progress on the applications of paper chips

“…7.2 One-step method 7.2.1 Screen printing technology. Screen printing technology [54][55][56][57][58][59] is a widely used printing technology in printing plants. This method was later applied to the production of microuidic paper chip technology.…”

“…9.3.3 Electrochemical luminescence detection (ECL). Electrochemiluminescence 57,58,62,64,131,132 is a new analytical technique combining the chemiluminescence detection method with electrochemical means. Electrochemiluminescence (ECL) mainly produces some electro-active substances on the electrode surface by the electrochemical method, and the luminescence phenomenon is accompanied by the formation of excited states between these substances or between these Fig.…”

“…Liu's group 58 developed an Aβ(1–42) aggregation detection method based on an unlabeled paper electrochemical luminescence sensor for the detection of amyloid protein aggregation and the potential diagnosis of Alzheimer's disease. This method is a low-cost, label-free, low-cost, sensitive one-time detection method and overcomes the limitations of traditional technologies, as shown in Fig.…”

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

“…132 Other sensing techniques were also successfully employed in developing electrochemical biosensor of AD with animal-sample tests, which include microelectrode array (MEA), 140 ratiometric photoacoustic nanoprobe, 141 and electrochemiluminescence. 142 As widely understood, tau protein is also an excellent candidate for human sample-based biosensor for AD. An electrochemical biosensor was recently developed to detect tau-381 based on aptamer-antibody sandwich assay in human serum from patients with AD.…”

“… 132 Other sensing techniques were also successfully employed in developing electrochemical biosensor of AD with animal-sample tests, which include microelectrode array (MEA), 140 ratiometric photoacoustic nanoprobe, 141 and electrochemiluminescence. 142 …”