## 2. Aptamers as Biorecognition Element  
Aptamers are short single-stranded DNA or RNA fragments selected by a combinatorial process (Systematic Evolution of Ligands by EXponential Enrichment, SELEX), which was first reported in 1990 [5,6]. Starting from DNA or RNA libraries, this process allowed the identification of unique oligonucleotide molecules able to bind to the target molecule with very high affinity and specificity. Historically, RNA-based libraries were used for the first SELEX selections due to the higher specificity and binding affinity [7]. However, experimental evidence showed that single-stranded DNAs have a comparable propensity to form tertiary structures similar to RNA chains [8]. There is a growing increase in the literature on the use of DNA-based aptamers for biosensing, and this is due first to an easier selection and amplification process as there is no reverse transcription step (necessary when working with RNA molecules), second to the simpler and cheaper synthesis of DNA-attachments, and third to the longer half-life [8,9]. With the advancement and the consolidation of the SELEX process, several aptamers were selected for a wide range of analytes, ranging from very small molecules (pesticides, toxins) up to entire microorganisms. The primary property of aptamers is their mechanism of target binding through a conformational change allowing their application in different sensing methods. Their binding properties make them rivals of the antibodies, the natural MRE; aptamers exhibit an affinity constant in the low nanomolar range, and their high specificity minimizes the probability of false-positive results [10]. Their selection and production do not involve animals, thus ensuring guaranteed sourcing and high batch-to-batch reproducibility. Furthermore, they can be easily modified in a defined manner for their immobilization, for instance, onto a solid support, allowing the choice of the adequate chemistry depending on the substrate [11]. Moreover, they are resistant to heat denaturation and can be used in non-physiological pH solutions. The main differences between aptamers and antibodies are summarized in Table 1.  
[PERSON] et al. compared the performances of aptamers and random- or Fc-oriented immobilized antibodies on the same optical platform (porous-silicon biosensors) in the detection of his-tagged protein in terms of binding rate, dynamic detection range, the limit of detection and selectivity [12]. If aptamer-based and antibody-oriented \begin{table}
\begin{tabular}{c c c} \hline \hline  & **Aptamers** & **Antibodies** \\ \hline Molecular basis & Nucleic acids & Proteins \\ Molecular modifications & Many examples (significant benefits for clinical applications) & Rare case (reduced affinity to antigens) \\ Size & Small–10/15 kDa & Big–150 kDa \\  & Stable even in high temperature and non-physiological pH environment & Susceptible to denaturation in high temperature and non-physiological pH environment \\ Stability & Susceptible to nucleases and rapid clearance rate in vivo & Less susceptible to nucleases and low clearance rate in vivo \\ Targets & Wide range, from ions to whole living cells & Only immunogenic molecules \\ Immobilization & By physical adsorption or chemical bonds & By random or oriented or chemical bonds \\ Immunotoxicity & Non-toxic & May cause a serious response in some patients \\ Specificity & High & High \\ Biochemical reactions & Not limited to physiological conditions & Limited to physiological conditions \\ Cost & Less expensive (solid-phase synthesis) & More expensive (aiminals extraction) \\ Production & Chemical modifications or SELEX & Animals \\ Reproducibility & High batch to batch reproducibility & Low batch to batch reproducibility \\ Ethical concerns & None & Production and development depend on living \\ \hline \hline \end{tabular}
\end{table} 
Table 1. Aptamers versus antibodies. biosensors reached similar results, the first ones would outperform in terms of reusability and storability.