Improving paper-based biosensors for the quantification of Alzheimer's disease blood biomarkers using printing techniques

Abstract

Alzheimer's disease is a devastating condition common among elderly people characterized by a progressive and slow brain decay that may take decades to complete. This disease currently affects over 36 million people and, due to population aging, projections indicate that in 25 years this number will triple - resulting in very high cost to health systems. Although the causes for the development of Alzheimer's disease are not well elucidated, it is estimated that the condition has a long asymptomatic period that may last 5 to 10 years. The diagnosis in the preclinical phase is important so that the disease can be treated in advance, slowing its progress. Furthermore, the identification of an increased number of patients in asymptomatic phases provides a larger amount of data for the study of the disease's development, assisting in the search for treatments or even the cure. Currently Alzheimer's diagnosis is complex and it is accomplished by a set of cognitive testing, neuroimaging techniques and analysis of cerebrospinal fluid (CSF). These require specialized equipment and researchers, and are, therefore, expensive. Recently, several blood biomarkers for Alzheimer's disease were identified, enabling the low cost diagnosis on initial stages of the condition. Some of the main ones are Fetuin B, Clusterin and the Precursor of Pancreatic Hormone. These were significantly related to the diagnosis of disease, decreased brain volume and the rate of decline of cognitive functions and can be used for early diagnosis. In Brazil, a low-cost paper-based lateral flow immunoassay is being developed by the applicant for the detection and quantification of these 3 biomarkers simultaneously, allowing the early diagnosis of Alzheimer's disease. For this end, gold nanoparticles are modified using specific antibodies and are further detected using stripping voltammetry and commercial screen-printed carbon electrodes. In this BEPE project we propose the improvement of these devices by creating a paper-based microfluidic chip equipped with printed electrodes. Besides lowering the price of the devices, the proposed approach will also bring more portability and facilitate the operation of the sensors, allowing a point-of-care diagnosis even in low-income countries. After the return to Brazil, these devices will be used for the investigation of the relationship between the concentrations of the biomarkers with the health status of different groups of patients. With the development of this tool, we hope that a greater number of patients may be diagnosed, allowing early treatment and counseling, as well as permitting further study of the mechanism of disease - assisting in the development of treatments and even in the search for a cure. (AU)