A Korea University joint research team has developed a highly sensitive optical biosensor using erythrocyte membrane-blanketed nanoparticles.

The research team was led jointly by Professor Park Jinsung from the Department of Electro-Mechanical Systems Engineering and Professor Yoon Dae Sung from the School of Biomedical Engineering.

The research paper was published in Biosensors and Bioelectronics, one of the world’s most prestigious journals in the field of biosensors.

A Korean research team has developed a sensor that detects fibrinogen* over a wide range with ultra-high sensitivity by maximizing the sensitivity of a “localized surface plasmon resonance (LSPR)* sensor,” using an erythrocyte membrane (EM) blanketing technique.

Professor Park Jinsung from the Department of Electro-Mechanical Systems Engineering and Professor Yoon Dae Sung from the School of Biomedical Engineering at Korea University led the research team jointly.

▲ (from left) PhD student Jo Seongjae from the Department of Electro-Mechanical Systems Engineering, Professor Yoon Dae Sung from the School of Biomedical Engineering and Professor Park Jinsung from the Department of Electro-Mechanical Systems Engineering

A cell membrane is a film that forms a boundary between a cell and its outer environment and that plays a key role in cell metabolism by protecting substances inside the cell while supplying nutrients to and discharging wastes from it. Given that there are various receptors on the surface of a cell membrane, the team fabricated a substrate by placing (like a blanket) erythrocyte membranes on the substrate of gold nanoparticles*.

1) Localized surface plasmon resonance (LSPR)

A nanostructure made of metals powerfully scatters and absorbs light of a certain wavelength since this light can cause the collective oscillation of electrons in the conduction band of the nanostructure, a phenomenon known as localized surface plasmon resonance. This absorption characteristic of the nanostructure reacts sensitively to the complex dielectric constant of the medium surrounding the surface of the metallic nanostructure, which enables sensitive detection of a material.

2) Fibrinogen: It plays a key role in blood coagulation. An excess of it can cause cardiovascular diseases, and a deficiency of it may lead to hemophilia.

3) Gold nanoparticles:

Gold nanoparticles are particles sized in nanometers, i.e., 10-9m. They are too small to observe with general optical microscopes and must be observed using high-resolution microscopes such as an atomic force microscope, transmission electron microscope and scanning electron microscope. Gold nanoparticles are a widely used material for sensors through functionalizing them with various materials.

This sensor using a gold nanoparticle substrate maximizes the LSPR effect by placing (like a blanket) EMs on the substrate, which stably immobilizes nanoparticles and prevents their aggregation.

This results in a thousand times bigger detection range (0.001-5 mg/mL) and a higher sensitivity than conventional sensors. Not only the normal region of the fibrinogen, but also all areas of excess and deficiency were detected accurately, and the possibility of in-plasma measurement was also confirmed. A new detection method with an EM-blanketed optical sensor has been suggested.

This opens up new opportunities for the detection of a variety of biomaterials that react with cell membranes using EM-blanketed sensors. PhD student Seongjae Jo, who conducted the experiment, said, "I want to detect a new biomarker that has never been detected with the EM-blanketed sensor."

This research was supported by the funding of a Korea National Research Foundation basic research project (mid-career research - strategic task), biomedical technology development project, and natural simulation innovation technology development project. In recognition of its importance, the research paper was published online in the April 17, 2019, edition of Biosensors and Bioelectronics (Impact factor: 8.173, top 3% by sector), one of the world’s prestigious journals in the field of biosensors.

* Title of the article: Highly sensitive and wide-range nanoplasmonic detection of fibrinogen using erythrocyte membrane-blanketed nanoparticles

* Journal information: Seongjae Jo, Insu Kim, Wonseok Lee, Minwoo Kim, Joohyung Park, Gyudo Lee, Dae Sung Yoon, & Jinsung Park. Highly sensitive and wide-range nanoplasmonic detection of fibrinogen using erythrocyte membrane-blanketed nanoparticles, Biosensors and Bioelectronics, Available online 17 April 2019, ISSN 0956-5663, https://doi.org/10.1016/j.bios.2019.04.030

▲ A schematic diagram of the LSPR substrate fabrication method using the EM-blanketing technique for fibrinogen detection