A dual-modality immunosensor for simple and reliable detection of nitrated alpha-synuclein in serum based on silver-coated MOF

Nitrated a-syn (nitro-a-syn) is a biomarker for Parkinson's desease (PD), and its sensitive detection in serum is of great importance for early PD diagnosis. Silver-coated copper MOF (Cu-MOF@Ag) with outstanding oxidase activity and electrochemical response property was designed and synthesized. Cu-MOF@Ag exhibited excellent oxidase activity with a low K-m value (0.568 mM), avoiding the addition of strong oxidant to catalyze chromogenic substrate, which enhanced the colorimetric stability. Silver nanoparticles as an electrochemical signal reporter can be easily decorated on the surface of Cu-MOF with bifunctional groups (-SH and -NH2) material, which can increase the electrochemical signal output. The a-syn antibody modified Cu-MOF@Ag and nitro-a-syn modified magnetic nanoparticle were used as immunoprobes to specifically capture nitro-a-syn. A dual-modal immunosensor was fabricated for the simple and reliable detection of nitro-a-syn based on Cu-MOF@Ag. Combing colorimetric and electrochemical detection, nitro-a-syn can be determined quantitatively within a wide linear range (10-350 ng/mL) with low detection limit (0.5 ng/mL). The ability of the sensor with magnetic separation and dual signal analysis allowed to successfully detect nitro-a-syn and distinguish PD patients from healthy people (P < 0.005). Thanks to its excellent selectivity, stability, and the precision of 2.69%, the dual-modal sensor has potential clinical application for nitro-a-syn detection and paves a new way for PD diagnosis at its early stage.

Automated summary

A silver-coated copper MOF (Cu-MOF@Ag) was designed and synthesized for the sensitive detection of nitro-a-syn, a biomarker for Parkinson's disease (PD). The Cu-MOF@Ag exhibited excellent oxidase activity and electrochemical response property, and combined colorimetric and electrochemical detection for the quantification of nitro-a-syn. The dual-modal immunosensor showed great potential for nitro-a-syn detection and early diagnosis of PD.