Aptamers are short oligonucleotides with single-stranded regions or peptides that recently started to transform the field of diagnostics. Their unique ability to bind to specific target molecules with high affinity and specificity is at least comparable to many traditional biorecognition elements. Aptamers are synthetically produced, with a compact size that facilitates deeper tissue penetration and improved cellular targeting. Furthermore, they can be easily modified with various labels or functional groups, tailoring them for diverse applications. Even more uniquely, aptamers can be regenerated after use, making aptasensors a cost-effective and sustainable alternative compared to disposable biosensors. This review delves into the inherent properties of aptamers that make them advantageous in established diagnostic methods. Furthermore, we will examine some of the limitations of aptamers, such as the need to engage in bioinformatics procedures in order to understand the relationship between the structure of the aptamer and its binding abilities. The objective is to develop a targeted design for specific targets. We analyse the process of aptamer selection and design by exploring the current landscape of aptamer utilisation across various industries. Here, we illuminate the potential advantages and applications of aptamers in a range of diagnostic techniques, with a specific focus on quartz crystal microbalance (QCM) aptasensors and their integration into the well-established ELISA method. This review serves as a comprehensive resource, summarising the latest knowledge and applications of aptamers, particularly highlighting their potential to revolutionise diagnostic approaches.

The rapid and accurate detection of SARS-CoV-2, particularly its spike receptor-binding domain (S-RBD), was crucial for managing the COVID-19 pandemic. This study presents the development and optimization of two types of aptasensors: quartz crystal microbalance (QCM) and electrochemical sensors, both employing thiol-modified DNA aptamers for S-RBD detection. The QCM aptasensor demonstrated exceptional sensitivity, achieved by optimizing aptamer concentration, buffer composition, and pre-treatment conditions, with a limit of detection (LOD) of 0.07 pg/mL and a linear range from 1 pg/mL to 0.1 µg/mL, and a significant frequency change was observed upon target binding. The electrochemical aptasensor, designed for rapid and efficient preparation, utilized a one-step modification process that reduced the preparation time to 2 h while maintaining high sensitivity and specificity. Electrochemical impedance spectroscopy (EIS) enabled the detection of S-RBD concentrations as low as 132 ng/mL. Both sensors exhibited high specificity, with negligible non-specific interactions observed in the presence of competing proteins. Additionally, the QCM aptasensor’s functionality and stability were verified in biological fluids, indicating its potential for real-world applications. This study highlights the comparative advantages of QCM and electrochemical aptasensors in terms of preparation time, sensitivity, and specificity, offering valuable insights for the development of rapid, sensitive, and specific diagnostic tools for the detection of SARS-CoV-2 and other viruses.