Holographic microscope boosting expectations in its applications

3D holography technology was originally proposed more than 40 years ago, but its technical limitations have constrained its potential for a long time. Holographic microscopes started to be applied in various fields as late as 2000, and it is only recently that the relevant research has been conducted in full scale on the back of the advancement of related technologies. In particular, this technology has been widening its range of applications in line with the development of various new optical technologies in recent years. In the past, the direction of light was controlled by directly turning the mirror. However, the researchers developed and applied new technology known as the Digital Micromirror Device (DMD) to freely control various kinds of light without requiring mechanical parts.

This made the commercialization of holographic microscopes possible. In addition to that, the technique to quickly process 3D image reconstruction using a Graphics Processing Unit (GPU) has also contributed greatly to the practical use of this technology. This research demonstrated the functional development of 3D holographic microscopes and the possibility of using them in medical research. With the basic research and development conducted at KI for Health Science and Technology, Prof. Yongkeun Park and his team established Tomocube Inc. in fall 2015. Tomocube launched prototypes within six months of its founding. Similar to the general microscope, the holographic microscope they developed looks into the body, but the 3D holographic microscope differs from conventional ones in that it uses a laser to look inside the cells.

In the conventional technique, a specimen should be rotated or a rotating mirror is needed to control the incident angle. However, these methods cause measurement defects due to rotation, and sometimes fine correction is needed to address the instability in the optical system. To overcome these limitations, Prof. Park and his team developed a 3D holographic microscope technology using DMD, and have succeeded in recently commercializing the technology. Thanks to their efforts, various industries are expecting robust advancement. In particular, the use of a 3D holographic microscope allows for the observation of cell fluorescence and internal cell organelles without staining the cells. Conventional techniques for observing cells in threedimensional images such as confocal microscopy and multi-photon microscopy have limitations in that they have to stain cells to do so. In addition, existing techniques for dyeing cells using fluorescent proteins, organic dyes, and quantum dots are not only time-consuming, but also affect the vital phenomenon of the cells in the process of dyeing. The techniques have other limitations as well: the staining method cannot be used in fields such as stem cells and immune cells that need to be injected into the body again. On the other hand, the 3D holography technique, which can produce the result by specifying the refractive index, the optical property originally possessed by the cell, has the merit of solving conventional problems because the dyeing process is not necessary.

Structural studies with reduced limitations and increased expectations

3-dimensional holographic microscopes can measure the living cells for a long time without dyeing them. Plus, various quantitative information such as the cell’s mass and concentration can be accurately measured. “This technology can be seen as a new paradigm of microscopic techniques for observing cells,” said Prof. Park. He continued, “Tomocube has already started to sell and export the products in the first year, with the investment of SoftBank Ventures Korea and Hanmi Pharmaceuticals. The sales began in overseas markets, including Japan and UK, which are known for having high entry barriers in bio device markets. Our product has already been deployed in a number of advanced research institutes such as MIT, the School of Medicine at the University of Pittsburgh, and the German Cancer Center, and used for various research activities.

Moreover, we are in close cooperation with Seoul National University (SNU) Bundang Hospital, SNU Boramae Medical Center, and Asan Medical Center to find out the potential of our product, not only in studies, but also in the early diagnosis of various diseases. Going forward, we expect that our products will contribute to various fields such as pharmaceutical systems, neurochemistry, immunology, hematology, and cell biology.” He also added, “Our study has fared well thanks to the systematic and structured support of Startup KAIST. I hope that high-tech medical device manufacturers and biotechnology companies in Korea continue to grow in the future with the support of highly advanced medical research technologies.”

Prof. Park, Yongkeun
2016 Annual Report