MOLECULARLY IMPRINTED POLYMER-BASED BIOSENSORS FOR THE DETECTION OF ALZHEIMER'S DISEASE BIOMARKERS

Greta Pilvenytė1, Raimonda Bogužaitė1, Vilma Ratautaitė1, 2, Arūnas Ramanavičius1, 2

1 Laboratory of Nanotechnology, State Research Institute Center for Physical Sciences and Technology, Sauletekio av. 3, Vilnius LT-10257, Lithuania.

2 Department of Physical Chemistry, Institute of Chemistry, Faculty of Chemistry and Geosciences, Vilnius University, Naugarduko str. 24, Vilnius LT-03225 Lithuania

[email protected]

According to the World Health Organization, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and other neurological disorders will become the second leading cause of death by 2040 [1]. Early detection and treatment may improve symptoms, relieve pain, and increase mobility, and quality of life. Proteins such as amyloid-β peptides, and phosphorylated-Tau are biomarkers of Alzheimer's disease can be used for the detection of this disease at an early stage of pathogenesis.

The accurate diagnosis of Alzheimer's disease is complicated and routinely performed by invasive, time-consuming, and expensive analysis like cerebrospinal fluid analysis or neuroimaging techniques. However, obvious limitations, such as the need for trained personnel, expensive instruments, complicated procedures, and long detection times, prevent the widespread use of these methods.

Therefore, new detection techniques such as MIP-based electrochemical sensors are being developed, providing a wide range of possibilities for the development of biosensors. MIP-based electrochemical biosensors are devices built with a transducer and recognition element with an imprinted polymer to determine the presence of an analyte. The main advantages of MIP-based electrochemical sensors are low-cost, easy preparation, advanced storage stability, and quick read-out time [2]. The ability to imprint template molecules at room temperature without denaturation or conformational changes is a major feature of MIP-based sensors [3]. Electrochemical biosensors also offer the advantage of detecting various biomarkers in complex biological fluids such as blood, saliva, and urine [2, 4-8].

To improve the selectivity and sensitivity of biosensors, various semiconductor structures such as copper oxide [6], multi-walled carbon nanotubes, delaminated titanium carbide MXenes [7] are being developed, but conducting polymers are most commonly used [3-4, 7]. Among the many conducting polymers, such as polyaniline, polythiophene, and poly(3,4- ethylenedioxythiophene), polypyrrole is one of the most suitable for molecular imprinting [2, 3].

This presentation reviews recent advances in the design of MIP-based biosensors for the detection of Alzheimer's disease biomarkers such as amyloid-β peptides [4, 7] and phosphorylated-Tau protein [8].


[1] K. Gammon, Neurodegenerative disease: Brain windfall, Nature 515(7526) (2014) 299-300. https://doi.org/10.1038/nj7526-299a.

[2] S. Ramanavicius, A. Jagminas, A. Ramanavicius. Advances in Molecularly Imprinted Polymers Based Affinity Sensors (Review). Polymers 13, 974 (2021). https://doi.org/10.3390/polym13060974.

[3] D. Plausinaitis, L. Sinkevicius, U. Samukaite-bubniene, V. Ratautaite, Evaluation of electrochemical quartz crystal microbalance based sensor modified by uric acid-imprinted polypyrrole, Talanta. 220 (2020) 121414. https://doi.org/10.1016/j.talanta.2020.121414.

[4] S. Ramanavicius, U. Samukaite-Bubniene, V. Ratautaite, M. Bechelany, A. Ramanavicius. Electrochemical molecularly imprinted polymer based sensors for pharmaceutical and biomedical applications (review). J. Pharm. Biomed. Anal., 215, 114739 (2022). https://doi.org/10.1016/j.jpba.2022.114739.

[5] S. Zukauskas, A. Rucinskiene, V. Ratautaite, A. Ramanaviciene, G. Pilvenyte, M. Bechelany, A. Ramanavicius. Electrochemical Biosensor for the Determination of Specific Antibodies against SARS-CoV-2 Spike Protein. Int. J. Mol. Sci. 2023, 24, 718. https://doi.org/10.3390/ijms24010718.

[6] F.T.C. Moreira, B.A.G. Rodriguez, R.A.F. Dutra, M.G.F. Sales, Redox probe-free readings of a β-amyloid-42 plastic antibody sensory material assembled on copper@carbon nanotubes, Sens. Actuat. B-Chem., 264 (2018) 1-9. https://doi.org/10.1016/j.snb.2018.02.166.

[7] N. Özcan, H. Medetalibeyoglu, O. Akyıldırım, N. Atar, M.L. Yola, Electrochemical detection of amyloid-β protein by delaminated titanium carbide MXene/multi-walled carbon nanotubes composite with molecularly imprinted polymer, Materials Today Communications, 23 (2020) 101097. https://doi.org/10.1016/j.mtcomm.2020.101097.

[8] A. Ben Hassine, N. Raouafi, F.T.C. Moreira, Novel Electrochemical Molecularly Imprinted Polymer-Based Biosensor for Tau Protein Detection, Chemosensors, 9 (2021) 238. https://doi.org/10.3390/chemosensors9090238.