Researchers from the State Universities of Campinas (Unicamp) and Federal Universities of São Carlos (UFSCar) developed an electrochemical sensor that detects Parkinson's disease at different stages. Manufactured using a common 3D printer, the device can anticipate diagnosis, allowing early treatment, and also works as a model for identifying other diseases, according to an article published in the journal Sensors and Actuators B: Chemical.
“The sensor quickly indicates the concentration of the PARK7/DJ-1 protein in human blood plasma and synthetic cerebrospinal fluid. The molecule is related to Parkinson's disease at levels below 40 micrograms per liter [40 μg/L]”, explains Cristiane Kalinke, post-doctoral fellow at the Institute of Chemistry at Unicamp (IQ-Unicamp), visiting researcher at Manchester Metropolitan University (United Kingdom) and first author of the article. “With the advantage of being able to be printed in different formats and sizes, including in miniature, creating truly portable devices, which require a very small amount of sample.”
To build the sensor, the researchers used a commercial filament basically composed of polylactic acid (a biodegradable polymer known by its acronym in English PLA) associated with a conductive material (graphene) and other additives. Three electrodes were printed in plastic with 3D technology and underwent a chemical treatment that made them even more conductive and stimulated the formation of functional groups (carboxylic) on their surfaces, which bind with antibodies. The activation process involved removing the insulating polymeric surface of the electrodes by immersing them in sodium hydroxide (NaOH) and applying an electrical potential (positive and negative). Then, the specific reaction between the antibodies and the PARK7/DJ-1 protein is promoted to provide the diagnosis.
The next steps of the work, which were supported by FAPESP (projects 13/22127-2, 17/21097-3, 19/00473-2 and 21/07989-4), were to immobilize specific antibodies to PARK7/DJ-1 on the surface of the electrodes and apply the sensor to detect the protein at three concentration levels: 30 μg/L, 40 μg/L and 100 μg/L. The average concentration in patients diagnosed with Parkinson's at different stages is approximately 30 ± 9 μg/L, according to literature data.
“Rarely a patient goes to a medical appointment looking for a routine exam to detect Parkinson’s at an early stage – when it is suspected, physical and behavioral symptoms have probably already manifested and the disease is already well established”, says Juliano Alves Bonacin, professor from the Department of Inorganic Chemistry at the Unicamp Chemistry Institute (IQ-Unicamp) and supervisor of the study. “Our idea was to build a very simple and very cheap device that would allow monitoring over time and alert doctors and patients in the event of changes in PARK7/DJ-1 levels, which is especially useful if analyzed together. with other biomarkers.”
Concept proof
An important legacy of the study is that it functions as a proof of concept by demonstrating the versatility of this type of printing as a platform for the immobilization of biomolecules.
“We were able to print all the components of an electrochemical cell on a 3D printer, using just a polymer as a conductive material,” says Kalinke. “In this specific work, the materials were commercial, that is, they were purchased ready-made, but, little by little, we are developing new filaments for 3D printing in our laboratory as well.”
According to the authors, the platform opens doors for the diagnosis of other diseases – in the case of the PARK7/DJ-1 protein specifically, in addition to neurological problems, it is linked to type 2 diabetes, infertility and some types of cancer. But the objective is to expand its use to other biomarkers and, in fact, Kalinke is already working on manufacturing a sensor for diagnosing yellow fever.
“Imagine that an outbreak of a certain disease occurs in a specific region”, explains Bonacin. “With a few 3D printers and some electrodes, it would be possible to produce a sensor like ours on site.”
The study also included the collaboration of Craig E. Banks, professor at the Faculty of Science and Engineering at Manchester Metropolitan University, professor Bruno Campos Janegitz and researcher Paulo Roberto de Oliveira, both from UFSCar - Campus Araras.
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