A research team led by Professor Inki Kim of the Department of Biophysics at Sungkyunkwan University(SKKU)— with co-first authors Han-Jun Cho and Youngjun Kim (PhD candidates) — working alongside a team led by Professor Jong-Chan Park (co-first author Nahyun Yoon, master's candidate), has developed an "organoid-on-a-chip" technology that verifies the efficacy of Parkinson's disease treatments in real time. The technology combines a stem cell–derived "mini-brain" with a nanoplasmonic sensor engineered to maximize light–matter interaction.

An organoid is a "three-dimensional mini-organ" grown from human stem cells to closely resemble an actual organ. The research team created an organoid modeled on the brainstem, the core region connecting the brain and spinal cord that regulates functions such as breathing and movement. Parkinson's disease is a representative neurodegenerative disorder in which damage to dopamine-secreting cells — which transmit motor signals in the brain — causes tremors and muscle rigidity.

Conventional drug research has required destroying cells or using special staining methods to observe drug response, making it difficult to continuously track when a drug begins to take effect and how long that effect lasts in living tissue. The research team overcame this limitation by harnessing the "light resonance" phenomenon that occurs when light strikes gold nanostructures far smaller than the width of a human hair. By attaching an artificial DNA material (an aptamer) that responds only to dopamine onto a sensor surface combining gold nanoholes with a vertical optical cavity, the team achieved ultra-precise detection (~8.3 picomolar) of secreted dopamine levels without damaging the mini-brain tissue.

Using a microfluidic chip environment that precisely delivers culture medium and drugs through microscale channels, the team measured the response of Parkinson's brainstem organoids in real time over 12 hours. The results captured, in fine detail, the full process by which dopamine secretion — which had declined in the disease model — recovered after administration of the Parkinson's treatment L-DOPA. Notably, the team also confirmed that increasing drug concentration does not always improve therapeutic outcomes, successfully identifying the optimal dosage that is both safest and most effective for patients.

This achievement demonstrates that the timing of a drug's onset, peak effect, and duration of action can be precisely measured hour-by-hour in a model that mimics human brain tissue. The technology is expected to significantly narrow the gap between animal testing and human clinical trials, shortening drug development timelines and

"This research is significant in that it opens a path to continuously monitoring the drug response of living human tissue over time using an ultra-precision optical sensor," said Professor Inki Kim. "We plan to further develop this into a core platform for patient-specific drug development and disease treatment."

The findings were published in ACS Nano, a leading international journal in the field of nanoscience.