질병진단이 가능한 고감도 실시간 타원편광측정기술 개발에 관한 연구

Abstract

Ellipsometry is the high precision optical measurement technique that measures polarization state of light upon reflection (or transmission) from the sample (thin film thickness) surface. Spectroscopic ellipsometry can be used to measure film thickness with high precision due to its high surface sensitivity , makes it a very versatile technology used in many different applications. For example, critical dimension metrology in the semiconductor industry and biosensing. Surface plasmon resonance (SPR) based biosensors are a leader in the disease diagnosis, uses refractive index (RI) change for sensing parameter. However, RI strongly depends on the environmental factors such as temperature and pressure, put limits their use in detection of low concentration analyte. In this study, the ellipsometric biosensor was investigated to overcome this limitation of present sensing technology.

Solution Immersed Silicon (SIS) ellipsometric biosensor is designed for disease diagnosis application with a new cost-effective approach. SIS sensor uses thickness change as the sensing parameter instead of RI, unlike SPR sensors. SIS sensors work at the non-reflecting condition (NRC) for p-polarized wave, refers to as the pseudo-Brewster angle, where ellipsometric parameters (Ψ, Δ) show very high sensitivity. At NRC, Ψ varies with thickness change due to the interaction of analyte protein with the sensor surface, which is translated to the SIS signal after proper calibration, depends on the wavelength of probing laser. The 532 nm laser gives dΨ = 0.2265 for 1 nm thickness change. The Ψ shows linear dependance on thickness, which is essential for the ideal sensor. SIS sensor chip is just Si wafer coated with a dielectric polymer, which can be functionalized for the specific biomarker, easy to make and cheap. Additionally, it does not need reference channel. In SIS sensor structure, liquid flows between the sensor chip and prism, means sensor chip is always in a liquid pool under prism, hence the name. Back-reflection from the prism surface adds noise, eliminated by tilting prism by 2 degrees. Two fold noise reduction was obtained. With the ideal condition, 0.003 picometer precision was achieved.

Acute myocardial infraction (AMI) and Hepatitis B Virus (HBV) have a high mortality rate, early diagnosis followed by immediate medicare could save thousands of lives. Biomarkers of AMI (Myoglobin, creatine kinase-MB (CK-MB) and HBV (HBsAg) appear in the blood stream very early but in low concentration which is below the capacity of present sensing technology. The capability of SIS sensors was tested by measuring these biomarkers in PBS and human serum medium. The limit of detection was 1 and 10 picomole for PBS and human serum samples.

In conclusion, SIS sensors have label-free, high-precision, high sensitive and real-time measurement capability and with cost-effective. These attributes make this technology suitable for point-of-care applications.