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Development of a multiplex nanofluidic assay for selective detection and monitoring of Alzheimer's disease biomarkers

Final Report Summary - NANOASSAY (Development of a multiplex nanofluidic assay for selective detection and monitoring of Alzheimer's disease biomarkers)

The objective of the NANOASSAY project was to develop a nanofluidic device that was capable of selectively detecting biomarkers relevant to Alzheimer’s disease (AD). This was the first major step needed in an effort to create a more sensitive and reproducible diagnostic tool that could be used to detect the presence of the disease prior to the appearance of symptoms.

In this project, a robust nanofluidic device was successfully manufactured from silicon using standard microfabrication procedures. The design consists of two large microchannels that are connected by a small nanochannel. Controlled flow through all the channels was then established with the implementation of a pressure controlled flow system. By manipulating the pressure on each of the inlets the direction of the flow across the nanochannel could be directed. Utilizing this system, the surfaces of the channel walls were modified to create a discrete region in the nanochannel where the analyte of interest could be selectively captured. We focused on the detection of biomarkers for AD that are readily found in cerebrospinal fluid (CSF), in particular amyloid-beta. To achieve this, both silane and aldehyde chemistries were used to prepare the surface for biomolecule attachment. The microchannels were first passivated with blocking agents to ensure that sample integrity was maintained for detection and the nanochannel could be discretely functionalized with antibodies specific to the analyte of interest. The main innovation of this work is that total binding of the analyte occurs within the nanochannel, as all of the sample of interest within the nanochannel is exposed to the channel surface. We successfully demonstrated this and continued to work on quantifying the amount of analyte within the sample, as the levels of each biomarker of interest can be indicative of disease state. Throughout the project the milestones outlined for the time completed were reached and the work was also extended to include a computer based data analysis method to ensure sample analysis is performed in a consistent and unbiased manner. Challenges do remain for the work, in particular, development of an accurate method for measuring the volume that flows through the nanochannel in real-time, which is necessary for biomarker quantification.

We believe that further development of this system could lead to earlier and more accurate diagnoses of AD and other similar diseases, enabling more effective disease monitoring as well as assist in the search for better therapeutic interventions. Achievement of this would result would have a significant impact on society as it would potentially improve the life expectancy and contribution of AD suffers and early intervention would result in a significant reduction in the economic burden this disease currently causes.