High selectivity sensing of bovine serum albumin: The combination of glass nanopore and molecularly imprinted technology.

Recently, resistive-pulse based nanopore analysis has made great progress. However, when it is used for the detection of similar substances, such as proteins, DNA, RNA and other biological molecules, the signal is poor. In order to realize the purpose of good testing, the solutions proposed by researchers include surface modification of nanopore or special data processing equipment and software, which are still complicated. In this manuscript, molecularly imprinted technology and nanopore sensing technology are combined together, based on the specific rebinding of molecularly imprinted polymer coated SiO2 nanoparticles to bovine serum albumin, the nanoparticles at different imprinting stages can be distinguished through resistive-pulse signals when they pass through the nanopores, achieving high selective and sensitive detection of bovine serum albumin in complex samples. The linear range of this nanopore-based sensor is from 0.5 nmol/L to 50 nmol/L with a 0.3 nmol/L detection limit. This method also possesses the advantages of strong specificity, good selectivity of molecularly imprinted polymer for target recognition and adsorption, and the controllable diameter and easy preparation of solid nanopores. Compared with the antibody-based or aptamer-based protein detection strategy, method in this manuscript is simple and easy to implement, which not only provides good selectivity and sensitivity for the detection of proteins in complex biomedical samples, but also opens up new application fields for nanopore sensing.