Development of a Multimodal System Combining Optical Diffraction Tomography and Raman Spectroscopy

Professor Jun Ki Kim of Asan Medical Center : “Cell-level precision analysis expected to enable early diagnosis and personalized monitoring”

▲ (From left) Professor Jun Ki Kim of the Department of Convergence Medicine at Asan Medical Center and University of Ulsan College of Medicine, with researchers Minju Cho and Junseop Hwang

Eosinophilic Granulomatosis with Polyangiitis (EGPA), a rare disease, is often misdiagnosed or diagnosed late because its early symptoms resemble those of asthma or nasal allergies. Recently, a Korean research team successfully distinguished EGPA by capturing subtle changes in eosinophils using advanced light based imaging technology.

A research team led by Professor Jun Ki Kim from the Department of Convergence Medicine at Asan Medical Center and University of Ulsan College of Medicine developed a “multimodal system combining optical diffraction tomography and Raman spectroscopy,” enabling the simultaneous analysis of the physical structure and chemical composition of single cells. Using this system, the team identified pathophysiological characteristics of eosinophils in EGPA patients with a diagnostic accuracy of 96%.

The study was published in the latest issue of Materials Today Advances, a leading journal in the fields of chemistry and biomedical science, with a five year impact factor of 10.0.

EGPA is a condition characterized by systemic vasculitis accompanied by elevated eosinophil counts in peripheral blood. If not managed in a timely manner, it can affect multiple organs, including the lungs, nerves, and skin. Due to its highly variable clinical manifestations, it is difficult to precisely classify disease status using conventional clinical indicators alone, and invasive tissue biopsies are sometimes required, placing a significant burden on patients.

Because EGPA is difficult to distinguish from asthma in its early stages, there has been a growing need for advanced diagnostic technologies that can objectively differentiate the disease and quantitatively track its progression and treatment response.

The research team isolated eosinophils from patients with EGPA who visited the Division of Allergy at Asan Medical Center and applied their newly developed multimodal system to analyze these cells.

First, optical diffraction tomography (ODT) was used to reconstruct the three dimensional refractive index distribution within cells without fluorescent labeling, enabling quantitative analysis of physical parameters such as cellular density and condensation state.

Next, the same cells were sequentially analyzed using Raman spectroscopy to obtain molecular chemical information. In this process, the researchers applied an algorithm targeting high refractive index regions of eosinophil granules to extract key molecular features. This approach minimized background noise while enhancing disease specific signals. Granules are intracellular organelles that contain a variety of chemical substances and proteins. Because their cores are densely packed and strongly interact with light, they serve as effective high refractive index targets.

By integrating these physical and chemical indicators into a classification model, the researchers were able to distinguish eosinophils from EGPA patients from those of control groups with up to 96% accuracy.

Professor Jun Ki Kim from the Department of Convergence Medicine at Asan Medical Center and University of Ulsan College of Medicine stated, “Conventional cell analysis requires preprocessing such as fluorescent labeling or staining, making it difficult to simultaneously correlate structural and molecular information at the single cell level. This study demonstrates that precise profiling is possible by simultaneously acquiring three dimensional physical parameters and Raman based molecular information from a single eosinophil in a label free, non-destructive manner.”

He added, “This technology can be expanded beyond EGPA to serve as a cell level diagnostic and monitoring platform for various eosinophil related diseases. It is expected to provide an important reference for early identification of asthma patients at risk of EGPA and for objectively tracking treatment response.”

This study was supported by the National Research Foundation of Korea, funded by the Ministry of Science and ICT.