A research team led by Professor Jinsung Park of the Department of Biomechatronic Engineering at Sungkyunkwan University(SKKU), in collaboration with a team led by Professor Gwanghui Ryu of the Department of Otorhinolaryngology - Head and Neck Surgery at Samsung Medical Center, has developed a highly sensitive electrochemical biosensor capable of rapidly and accurately diagnosing cerebrospinal fluid (CSF) leaks that may occur following head surgery or trauma. The team established an innovative diagnostic platform that uses enzymes to detect extremely subtle differences in sugars attached to protein surfaces and converts these differences into measurable electrical signals.
Cerebrospinal fluid is a clear liquid that surrounds the brain and spinal cord and protects them from physical impact. Following severe head trauma or brain surgery, CSF can leak through defects in the skull and drain from the nose or ears. Because an untreated leak can lead to serious infections such as meningitis, rapid and accurate diagnosis is essential. A key diagnostic biomarker is β₂-transferrin, a protein that is structurally almost identical to ordinary transferrin found in the blood but lacks specific terminal sugars called sialic acids.
Conventional immunoassays recognize the overall structure of a protein, making it difficult to clearly distinguish normal transferrin from forms in which some of these sugars are missing. More sophisticated analytical techniques can take several hours and require complex instrumentation, limiting their immediate use in operating rooms or emergency departments.
To address this challenge, the research team focused not on the protein itself, but on the vacant sites left behind when the sugars are absent. The researchers used a specific enzyme, α-2,3-sialyltransferase, to selectively recognize these exposed sites and attach new sugar molecules to them, while amplifying the resulting reaction as an electrical signal. In normal proteins, the relevant sites are already occupied and therefore do not react with the enzyme. In sialic acid-deficient transferrin associated with CSF, however, the enzyme recognizes the vacant sites and produces a detectable signal.
The team further enhanced the performance of the sensor (ESGNS) by incorporating gold nanostructured electrodes capable of amplifying extremely weak signals. The developed sensor accurately detected the target substance at concentrations as low as 0.135 μg/mL, even in complex biological environments such as blood and bodily fluids.
Tests using actual patient CSF samples showed a strong correlation with conventional precision analytical methods (R² = 0.912), while reducing the analysis time to within 95 minutes. The researchers also successfully integrated the sensor with a compact, palm-sized portable reader, demonstrating its potential for point-of-care diagnosis that could provide results directly at the patient’s bedside.
Professor Jinsung Park said, “The key achievement of this study is the selective identification of subtle differences in sugar structures on protein surfaces through enzymatic reactions and the precise conversion of those differences into electrical signals. Following additional clinical validation, we aim to develop this technology into a rapid diagnostic device for emergency settings and further expand it into a diagnostic platform for a wide range of intractable diseases associated with changes in protein glycosylation.”
This research was supported by the Ministry of Science and ICT, the National Research Foundation of Korea (NRF) through the Mid-Career Researcher Program, Bio & Medical Technology Development Program, and Sejong Science Fellowship, as well as by the Ministry of Health and Welfare.
Chemical Engineering Journal