Development of a biochip that delivers intracellular nanomaterials with high efficiency

Professor Aram J. Chung's research results published as the cover paper in the renowned international journal, ACS Nano.

▲ From left: Geum-Young Kang (first author), Professor Aram J. Chung (corresponding author)

The team led by Prof. Aram J. Chung, a professor of Biomedical Engineering at the College of Health Science, have developed a microfluidic platform that can deliver a variety of nanomaterials (gold nanoparticles, functional nanoparticles, synthetic biomolecules, mRNA, etc.) into millions of cells per minute

The study was selected as the cover paper following its online publication in the international journal, ACS Nano (Impact factor = 13.903) on February 19

※ Paper title: Intracellular Nanomaterial Delivery via Spiral Hydroporation

※ Journal link: https://pubs.acs.org/doi/10.1021/acsnano.9b07930 .

※ Primary authors: Professor Aram J. Chung (corresponding author, Korea University), Geum-Young Kang (first author, Korea University master’s program)

The transfer of certain substances into cells is one of the essential experimental processes in cell-based biotechnology and medical applications. For example, gold nanoparticles are used in biotechnology for drug delivery, imaging, biosensing and diagnostics. As another example, intracellular delivery of nucleic acids (DNA, RNA, mRNA, siRNA) enables expression or inhibition of specific genes which can be used in converting CAR-T cells for cancer immunotherapy. In addition, recently, gene editing material (CRISPR-Cas9) is delivered into cells to treat diseases through various genetic manipulations.

Currently, methods such as virus, electroporation or cationic lipofection are used. However, these methods have limitations in cell stability, cost, efficiency and throughput. In order to solve this problem, Professor Aram's team reported for the first time in the industry how to transform cells using spiral vortex flow in a microtubule to instantly open the cell membrane to effectively deliver the target materials through them as shown in the figure below. This study is significant in that it disproves the previous doctrine, revealing that spiral vortex flow occurs in the cruciform microtubules.

The best features of the technology include high cell throughput (millions of cells per minute), high and stable delivery efficiency regardless of the size and type of target material, inexpensive platform price, and access for non-specialists without special training.

[Figure 1 description] Schematic of research direction of cell engineering or cell-based therapy through intracellular mass transfer

[Figure 2 description] (left) Schematic diagram of simple intracellular mass transfer (middle) A technique for transforming cells using a spiral vortex flow in a microfluidic tube and temporarily opening the cell membrane to effectively transfer target substances. (right) Intracellular particle delivery results of gold nanoparticles

Professor Chung said, “Furthermore, if we are currently studying the application of immune cells and stem cells, which are difficult to deliver intracellularly, we have already achieved great success. This platform is in the process of being commercialized for practical use by biotechnology and cell-based therapeutic researchers."

The research was supported by the Samsung Research Funding & Incubation Center for Future Technology and jointly conducted with Amy Shen of OIST (Okinawa Institute of Science and Technology Graduate University) and In-Hee Choi of the University of Seoul.