# Potentiometric Biosensor Based on Artificial Antibodies for an Alzheimer Biomarker Detection
## 1 Introduction  
Several peptides/proteins are being considered as potential biomarkers for predicting the early stages of Alzheimer's disease (AD). Numerous clinical studies show that the concentrations of these biomarkers in biological fluids correlate with the progression of early-stage disease [1]. The mechanism driving the progression of AD is related to the formation of senile plaques and neurofibrillary tangles, which are responsible for the death of neurons and lead to memory loss and symptomatic behavioural changes [2, 3, 4, 5]. Current hypotheses also include circulating A\(\beta\)-42 oligomers as potentially neurotoxic (not just the plaques) [6, 7, 8, 9, 10, 11, 12]. The detection of A\(\beta\)-42 is based on immunochemical reactions, e.g., conventional ELISAs [13], which are highly sensitive and selective, but time-consuming, unstable, and expensive. Several biosensors have been described in the literature for the detection of A\(\beta\)-42 by electrochemical [14, 15], surface plasmon resonance (SPR) [16, 17, 18, 19, 20, 21] and field-effect transistor(FET) [22; 23; 24; 25] detection. Electrochemical biosensors have been extensively studied due to their promising properties in terms of scalability and price. This transduction technique has a higher sensitivity and reproducibility compared to other transduction instruments and allows for point-of-care (PoC) analysis [15; 26; 27; 28; 29; 30; 31], but requires a sensitive and selective antigen recognition material. Antibodies are commonly used as capture and recognition elements [27; 32; 33; 34; 35]. However, this biological element of recognition has some limitations in terms of its stability, price, and reusability. For this reason, we have developed in this work a plastic antibody for the selective recognition of A\(\beta\)-42. Some plastic antibodies for the selective recognition of A\(\beta\)-42 have been described in the literature with electrochemical transduction using impedance or square wave voltammetry techniques [14; 15; 36; 37; 38; 39]. To the best of our knowledge, this is the first plastic antibody-based sensor with potentiometric transduction for the detection of AD biomarkers in PoC described in the literature. Potentiometric sensors have several advantages in terms of simple procedures and highly specific/sensitive properties. Ion-selective electrodes (ISEs) with polymeric-selective membranes and solid-state contact have been used extensively and offer several advantages in terms of their precision, response time, cost of analysis, selectivity and sensitivity over a wide concentration range [40; 41; 42; 43]. The development of sensing materials based on molecular imprinting polymer technology (MIP) with the size and charge of a specific ion can lead to precise selective interactions [44; 45]. Various immobilization strategies for the integration of MIPs and biosensors have been described in the literature. These include: (i) in situ polymerization (bulk) [46], (ii) epitope method [47] or (iii) surface imprinting with chemical or UV initiation [48; 49]. In surface imprinting, the molecules are attached to the surfaces in a layer-by-layer approach. In this strategy, the number of binding sites or cavities tends to increase, which is crucial for reaching the desired detection limit [50; 51]. Some nanomaterials, such as carbon allotropes and metallic or magnetic nanoparticles, are used to improve binding sites due to their high surface-to-area ratio [52; 53; 54]. Carbon nanotubes (CNTs) are widely used in biosensing as conducting transducers or as carriers for the immobilization of target molecules. CNTs exhibit good properties in terms of their conductivity and high surface-to-area ratio and are an ideal nanomaterial for protein/peptide immobilization [55; 56; 57; 58; 59; 60; 61]. Overall, this work describes the synthesis of a plastic antibody for an AD biomarker detection with potentiometric transduction in PoC. The peptide is bound to the surface of SWCNTs that were previously carboxylated.