Novel Small Molecule POC Biosensor Technology to Revolutionize Early Disease Detection

Aptamers, biosensors made from nucleic acids that bind to specific proteins or small molecules, are increasingly employed in diagnosing various diseases. Their application in cancer detection is particularly promising due to the high cure rate possible with early cancer detection. However, aptamers face significant challenges, such as susceptibility to degradation or aggregation by nucleases and charged proteins found in biological samples like blood or saliva. This limitation has hampered their direct use in clinical samples without prior removal of these molecules. Now, a research team has addressed this issue by using a protein-based microcapsule.

Researchers from Pohang University of Science and Technology (POSTECH, Gyeongbuk, Korea) have devised an aptamer sensor system capable of rapid detection of target molecules directly from biological samples, thus eliminating the need for pretreatment processes. They have developed spherical microcapsules called proteinosomes, based on the self-assembly of protein-polymer amphiphiles. These microcapsules encase an aptasensor featuring a structure-switching aptamer that reacts with target molecules to emit a fluorescent signal instantly. The exterior of the microcapsule consists of a size-selective, semi-permeable membrane, designed to allow only small target molecules through while blocking larger, damaging proteins.

Image: Conceptual representation of the research (Photo courtesy of POSTECH)

This innovative system maintains the aptasensor's optimal performance in untreated biofluids, thus enabling the efficient and quick detection of targets like estradiol, linked to reproductive organ cancers; dopamine, associated with Parkinson’s and Alzheimer’s diseases; and cocaine, which necessitates rapid detection. The capsules safeguard the aptasensors effectively against harmful proteins. For instance, aptasensors within these microcapsules remained unharmed for 18 hours in high concentration nuclease solutions, much more concentrated than typical serum levels. Moreover, by exploiting each capsule's capability to function as a distinct 'reaction vessel,' the team demonstrated the independent operation of multiple aptasensors in a single mixture. This allows for the simultaneous, real-time sensing of various target molecules and monitoring their concentration changes.

"By integrating sample separation and target detection, we have pioneered a novel small molecule point-of-care biosensor technology that is directly applicable to biological samples such as serum," said Professor Seung Soo Oh who led the research. "This platform has the potential to revolutionize medicine, spanning early disease detection and personalized treatment."

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