A sandwich-type aptasensor for point-of-care measurements of low-density lipoprotein in plasma based on aptamer-modified MOF and magnetic silica composite probes

Abstract

Robust, rapid, and specific assays for point-of-care testing of plasma low-density lipoprotein (LDL) are needed for the early diagnosis of cardiovascular diseases (CVD). While immuno-sensors have been widely used for this purpose, they suffer from high costs and difficult sample preparation. Here, we designed a magnetically controllable sandwich-type aptasensor to detect LDL based on disposable screen-printed electrodes (SPE). First, Fe3O4@SiO2 was employed to rapidly capture and separate LDL in plasma. An aptamer (Apt) and ferrocene (Fc) co-immobilized UiO-66 metal–organic framework was used as a signal tag (MOF-Fc@Apt) and was conjugated with the LDL on Fe3O4@SiO2. The sandwich complex can be magnetically adsorbed on SPE for signal generation. At optimum conditions, the material could detect LDL in plasma with a linear range of 1.0 ng·mL−1–100 μg·mL−1 and low detection (LOD) limit of 0.3 ng·mL−1 (S/N = 3). The system exhibited many distinctive advantages: First, Fe3O4@SiO2 replaced expensive immunosorbent to capture and isolate LDL from complex plasma samples with acceptable selectivity. The MOF-based signal tags could encapsulate a large amount of Fc and Apt to increase the detection selectivity and sensitivity. Second, the LDL sandwich complex conjugated with the composite probes could be easily adsorbed on the SPE for signal development by the magnet and washed away after removing the magnet. Thus, the measurement platform is reusable. Third, the entire detection process was as quick as 20 min, and the sample volume was only 0.1 mL. These features made the assay a good candidate for point-of-care testing of LDL for early diagnosis of CVD.