Influence Mechanisms of Liquid Milk Matrix on Aptamer-based Detection and Corresponding Elimination Methods

Aptamers are promising recognition elements for food detection. These short, single-stranded DNA or RNA molecules are small, easy to synthesize and highly specific. However, complex sample matrices can severely interfere with aptamer–target binding, reducing sensitivity and specificity, and limiting their practical applications. Liquid milk is a complex food matrix that is rich in proteins, fats, and bioactive substances, so studying its interference mechanisms and elimination approaches is highly valuable. This review summarises the four main mechanisms of milk matrix interference: non-specific adsorption, optical background interference, mass transfer hindrance and chemical interference. We then classify anti-interference strategies by target type (micro-organisms, biomacromolecules, and small molecules/ions), covering physical separation, anti-fouling of interfaces, signal amplification, integrated platforms, and aptamer optimisation. We also outline current challenges and future directions. This work provides theoretical references and methodological guidance for the development of robust aptasensors in complex real samples and reveals design principles for mitigating the effects of the matrix across sample pretreatment, interface engineering and signal readout.