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Researchers Explore Use of Laser-Made Graphene, DNA Aptamers for Point-of-Care Biosensor Testing

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NEW YORK ─ An international research group, developing technology that could simplify the fabrication of a point-of-care biosensor platform, is aiming to enable production in low-resource settings where more tests are urgently needed.  

The device uses an inexpensive laser to fabricate detection electrodes made from an emerging nanomaterial, graphene, which is derived from an inexpensive plastic. DNA aptamers are then used on assays as substitutes for antibodies to target proteins of interest. While the DNA aptamers are custom developed by a supplier using the researchers' specifications, electrodes made from graphene are so easy to fabricate, it could be done at home, said Antje Baeumner, one of the test's developers and head of the Institute of Analytical Chemistry and Biosensors at the University of Regensburg in Germany.

Baeumner is a corresponding author of a recent study published in Biosensors and Bioelectronics that describes the biosensor and its manufacturing process. Working with Min-Ho Lee and Junghong Min, who are biosensor researchers at Chung-Ang University in South Korea, Baeumner built a proof-of-concept test that has a limit of detection that they said is suitable for diagnostic testing.

The researchers reported detecting low nanomolar levels in blood for thrombin, a substance that plays a role in wound healing and can be used to diagnose and monitor blood disorders. Additionally, in unpublished work, they have also shown that the technology can detect levels of glucose, lactate, potassium, and general conductivity in sweat. That, according to Baeumner, shows the potential for broader diagnostic applications for its graphene and aptamer biosensor.

The clinical utility and performance of the platform would need to be validated in extensive clinical testing and receive regulatory approvals prior to its commercialization. However, the developers believe it could eventually find a home in low-resource and other point-of-care diagnostic settings, so the platform would have to be affordable and easy to fabricate where testing is done.

Baeumner noted that the technology may already have many of the characteristics that can lead to tests that are inexpensive and easy to make. Reel-to-reel fabrication, an emerging process for creating electronic devices on a roll of flexible plastic, can easily be implemented using the technology, Baeumner said, adding that such technology "is perfectly suited for the production of point-of-care sensors being produced locally and not requiring special centralized facilities."

Polyimide, the plastic material used to fabricate graphene, is broadly available and cheap, Baeumner noted. In its study, after using software to sketch out the design and shape of interest, the group leveraged a carbon dioxide laser to fabricate interdigitated graphene electrodes that resemble interlocking fingers and enable the detection of changes in capacitance.

Further, the plastic in which the biosensor is embedded is flexible, meaning it could one day be wrapped around a wrist, similar to a wearable device, and used as an in vitro diagnostic assay to detect biological properties in sweat, Baeumner said.

A change in capacitance, an electrical property that reflects the storage of electrical charge, is part of a strategy to enable detection via a single-step reaction. The laser-made graphene and DNA aptamers, taken together, enable "label-free biosensors," which eliminate the need for multiple recognition elements and washing steps familiar in traditional lateral flow tests to get accurate diagnostic signals, Baeumner said.

Synthesized in a laboratory, the DNA aptamers can be designed to detect different proteins, are reproducible, and can be reordered if needed from a supplier, she said.

The platform seems "straightforward and easy to fabricate, so from a manufacturing perspective, this could be cost effective," Harvard University Wyss Institute biosensor developer Pawan Jolly said in an interview. However, the developers would need a few more years to "derisk the platform before it can be translated as a potential product," he added.

Aptamers can be easy to source and they show promise as alternatives to antibodies – they have superior stability and sensitivity, which is important for biosensor development. However, these alternatives to antibodies have been around for many years and still need to "prove their success on a commercial level," said Jolly, who is not affiliated with the work of Baeumner and her colleagues.

Nonetheless, the new biosensor platform looks promising, he said, and by switching to different aptamers, the researchers can develop additional diagnostic applications. Future initiatives could include the development and screening of aptamers for additional indications, and making the platform "mass manufacturable with good reproducibility," Jolly noted.

Giuseppe Spoto, a professor of chemical sciences at the University of Catania in Italy, who is developing a photonic biosensor detection platform, noted that there has been extensive research into biosensing applications that could take advantage of "the superior properties of graphene." Baeumner and her colleagues have recognized the importance of designing new devices that can be fabricated at a large scale and low cost, Spoto said, adding, "That is a strong point favoring the future development of the new aptamer-based capacitive biosensor" for diagnostic applications.

The researchers have successfully shown that the "material's superior capacitive response" enables the "detection of a clinically relevant marker with performance compatible with a point-of-care device," said Spoto who is not affiliated with the team developing the graphene biosensor.

Baeumner added that she and her colleagues are exploring other diagnostic applications for laser-induced graphene that including the potential to integrate the material with isothermal amplification for detection. Further, the group is exploring options for commercialization including the potential to launch a startup or collaborate with a diagnostic company interested in broadening its portfolio and using the biosensor technology to develop new products.