Paper-Based Platform with an In Situ Molecularly Imprinted Polymer for β-Amyloid

Abstract

Alzheimer's disease (AD) is one of the most common forms of dementia affecting millions of people worldwide. Currently, an easy and effective form of diagnosis is missing, which significantly hinders a possible improvement of the patient's quality of life. In this context, biosensors emerge as a future solution, opening the doors for preventive medicine and allowing the premature diagnosis of numerous pathologies. This work presents a pioneering biosensor that combines a bottom-up design approach using paper as a platform for the electrochemical recognition of peptide amyloid β-42 (Aβ-42), a biomarker for AD present in blood, associated with visible differences in the brain tissue and responsible for the formation of senile plaques. The sensor layer relies on a molecularly imprinted polymer as a biorecognition element, created on the carbon ink electrode's surface by electropolymerizing a mixture of the target analyte (Aβ-42) and a monomer (O-phenylenediamine) at neutral pH 7.2. Next, the template molecule was removed from the polymeric network by enzymatic and acidic treatments. The vacant sites so obtained preserved the shape of the imprinted protein and were able to rebind the target analyte. Morphological and chemical analyses were performed in order to control the surface modification of the materials. The analytical performance of the biosensor was evaluated by an electroanalytical technique, namely, square wave voltammetry. For this purpose, the analytical response of the biosensor was tested with standard solutions ranging from 0.1 ng/mL to 1 μg/mL of Aβ-42. The linear response of the biosensor went down to 0.1 ng/mL. Overall, the developed biosensor offered numerous benefits, such as simplicity, low cost, reproducibility, fast response, and repeatability less than 10%. All together, these features may have a strong impact in the early detection of AD.

Paper-Based Molecular-Imprinting Technology and Its Application

“…Chen et al [ 75 ] also developed a paper-based electrical sensor with molecularly imprinted glucose-recognition sites for the determination of various glucose concentrations in bovine blood solutions. Pereira et al [ 76 ] developed an MIP paper-based platform to detect β-amyloid, a biomarker of Alzheimer’s disease present in blood. These new MIP-PAD sensors have great potential for point-of-care detection applications.…”

Recent molecularly imprinted polymers applications in bioanalysis

“…In short, many kinds of MIP-based biosensor analysis developments have been reported for special targets such as paracetamol (acetaminophen) in plasma (Alanazi et al 2021 ), glycoprotein in human serum sample (You et al 2017 ), uric acid in serum and urine (Göçenoğlu Sarıkaya et al 2017 ), heart-fatty acid binding protein in human serum, human plasma, and bovine serum (Sanati et al 2021 ), β ‑amyloid in serum (Pereira et al 2020 ) and α synuclein in human brain organoids (Lee et al 2020 ) with high accuracy and recovery which may lead to clinical usage as fast and reproducible approaches. The use of MIPs in biological sensing has also been the subject of recent several review studies (Batista et al 2021 ; Kadhem et al 2021 ; Ramanavicius et al 2022 ) (Fig.…”

Novel Trends in Electrochemical Biosensors for Early Diagnosis of Alzheimer’s Disease

“…MIP has also been used in the work of Ozcan and coauthors (2020) and Pereira and coauthors (2020), both aimed to detect A β 42 [ 52 , 53 ]. The classic electrochemical biosensor construction, a glassy carbon electrode with delaminated titanium carbide MXene and multiwalled carbon nanotubes composite covered by MIP, was prepared in the work of Ozcan and coauthors [ 52 ].…”

“…The classic electrochemical biosensor construction, a glassy carbon electrode with delaminated titanium carbide MXene and multiwalled carbon nanotubes composite covered by MIP, was prepared in the work of Ozcan and coauthors [ 52 ]. On the other hand, in the work of Pereira and coauthors, an innovative paper-based platform for carrying MIP was prepared [ 53 ]. Although Ozcan and coauthors have achieved a much lower limit of detection as well as better sensitivity, the construction of Pereira and coauthor is unique in its simplicity and low cost.…”