Endomicroscopy for in situ optical biopsy and therapy

(a-b) OCT images of human eye in vivo;(c) Autoconfocal microscopy imaged fixed rat retina tissue; (d) All near-infrared two photonmicroscopy imaged a mouse kidney

We develop novel optical imaging technologies aimed at in situ optical biopsy and therapeutic applications.  Optical biopsy refers to methods that utilize the properties of light to obtain a diagnosis of disease during endoscopy. We explore endoscopy-compatible optical imaging methods and instrumentation based on our core technologies that include ultrahigh-speed optical coherence tomography (OCT) and confocal microscopy. OCT provides high-resolution cross-sectional images of biological tissues, and has been successfully applied to various clinical studies such as retina disease diagnosis. Confocal microscopy allows for high-resolution, high-contrast, three-dimensional images of scattering tissues by rejecting out-of-focus background. We also investigate other functional imaging modalities such as fluorescence and nonlinear microscopy to enable comprehensive assessment of biological specimens. Our target clinical applications include gastroenterology and cardiology, and we are currently working on a new endomicroscopytechnology in collaboration with Cardiology Division at Yonsei University College of Medicine.


Advanced live cell imaging technologies

SD-OCPM and 2PM imaged stained muntjac sking fibroblasts. (a) 2PFM; (b) SD-OCPM intensity; (c) SD-OCPM phase; (d) SD-OCPM phase gradient

We aim to extend the boundaries of quantitative, label-free cell imaging techniques to  enable high-throughput, quantitative cell monitoring. With the growing demand for large amount of various cell types for cell therapy and drug discovery, development of high-throughput cell monitoring tools is highly imminent. We take multi-modal approaches for investigation of cellular signatures and mechanics, and combine mathematical/numerical tools with the developed optical technologies, which altogether can serve as a quantitative metric for cell-based research.One of our core technologies is referred to as spectral-domain optical coherence phase microscopy (SD-OCPM). SD-OCPM is based on the principle of spectral-domain OCT, and enables quantitative phase imaging of live cells with nanometer-level path length sensitivity. We developed a multi-modal microscope that combines SD-OCPM and two-photon fluorescence microscopy (2PFM) to visualize subcellular structures of cellular specimens.


High-throughput molecular diagnostics


A number of molecular diagnostic platforms have been developed to measure abundance of molecules with high-sensitivity, and gain valuable insights into biology at the systems level. Many of these techniques, however, require time-consuming specimen purification and amplification strategies, and may lack the ability for multiplexed measurements desirable in identifying complex diseases, or may not be amenable for easy point-of-care translation. We pursue direct, low-cost, high-throughput molecular assays suitable for point-of-care detection of biomarkers, proteins, and DNA mutation.

Light-based manipulation and control of biological systems

Traditionally, light has been used to detect structures and dynamics of biological systems (e.g., cells and tissue), but the concept of using light as a means to control biological systems is relatively unexplored. We are interested in developing novel applications, where light plays an active role in controlling and triggering specific biological processes. Our strategies include the use of interaction between nanostructures and light to perturb biological systems, with particular applications of high-throughput drug delivery to stem and neuronal cells, and light-mediated control of neuronal signal pathways in combination with other agents and modalities.