Non-invasive Monitoring of α-Synuclein in Saliva for Parkinson’s Disease Using Organic Electrolyte-Gated FET Aptasensor

Abstract

Parkinson’s disease (PD) currently affects more than 1 million people in the US alone, with nearly 8.5 million suffering from the disease worldwide, as per the World Health Organization. However, there remains no fast, pain-free, and effective method of screening for the disease in the ageing population, which also happens to be the most susceptible to this neurodegenerative disease. αSynuclein (αSyn) is a promising PD biomarker, demonstrating clear delineations between levels of the αSyn monomer and the extent of αSyn aggregation in the saliva of PD patients and healthy controls. In this work, we have demonstrated a laboratory prototype of a soft fluidics integrated organic electrolyte-gated field-effect transistor (OEGFET) aptasensor platform capable of quantifying levels of αSyn aggregation in saliva. The aptasensor relies on a recently reported synthetic aptamer which selectively binds to αSyn monomer as the bio-recognition molecule within the integrated fluidic channel of the biosensor. The produced saliva sensor is label-free, fast, and reusable, demonstrating good selectivity only to the target molecule in its monomer form. The novelty of these devices is the fully isolated organic semiconductor, which extends the shelf life, and the novel fully integrated soft microfluidic channels, which simplify saliva loading and testing. The OEGFET aptasensor has a limit of detection of 10 fg/L for the αSyn monomer in spiked saliva supernatant solutions, with a linear range of 100 fg/L to 10 μg/L. The linear range covers the physiological range of the αSyn monomer in the saliva of PD patients. Our biosensors demonstrate a desirably low limit of detection, an extended linear range, and fully integrated microchannels for saliva sample handling, making them a promising platform for non-invasive point-of-care testing of PD.

A Surface Imprinted Polymer EIS Sensor for Detecting Alpha-Synuclein, a Parkinson’s Disease Biomarker

“…Unfortunately, this test cannot be used as a screening tool for early detection of PD as it is highly invasive, requires specialized laboratory equipment, and can take from 5 to 13 days to perform these tests [10]. There are a few promising examples of biosensing platforms suitable for less invasive, less cumbersome, and hence more accessible αSyn quantification, such as our organic electrolyte-gated FET aptasensor platform and Adam et al's electrochemical biosensor [11,12] to list a few. These emerging biosensors rely on a bioreceptor molecule, either an aptamer or an antibody, adding unique complexities to sensor shelf-life and usability as a continuous monitoring device.…”

Next Generation Non-Invasive Biomarker Testing in Saliva: The Organic Electrolyte Gated Field Effect Transistor Aptasensor System

“…The device architecture is fabricated as a side by side microchannel allowing for a blank reference testing to perform calibrations. This work has been published in ACS Sensors as "Non-invasive Monitoring of Alpha-Synuclein in Saliva for Parkinson's Disease using Organic Electrolyte Gated FET Aptasensor" [442]. TIPS-pentacene (Sigma Aldrich, USA) is solution processed as 1 wt % in chlorobenzene (Sigma Aldrich, USA).…”