Real-time Highly Sensitive Measurement of Myocardial Infarction Biomarkers Using Silicon-based Ellipsometric Biosensors

실리콘 기반 타원편광계식 바이오센서를 이용한 심근경색 생체표지자의 실시간 초고감도 진단 농도 측정

Abstract

We report highly sensitive detection of myocardial infarction biomarkers, such as myoglobin and cTnI, within several hundred seconds using a rotating-analyzer ellipsometer and a biosensor with biochips fabricated on a $SiO_2$-coated tilted silicon substrate. We choose the running buffer to be pure phosphate-buffered saline (PBS) or 10% mixed human serum. When we choose the running buffer to be pure PBS, we obtain diagnostic densities of pure myocardial infarction biomarkers of up to 1 ng/ml and 5 pg/ml respectively. Meanwhile, when we use PBS with 10% human serum, the measured densities of myoglobin and cTnI were up to 1 ng/mL and 1 pg/mL respectively. The measured diagnostic densities are less than 1/15 and 1/80 (in cases of myoglobin and cTnI respectively) of those referenced by the World Health Organization.

$2^{\circ}$ 기울어진 산화막 코팅 실리콘 기판의 바이오칩과 프리즘으로 제작한 바이오센서와 검광자 회전 타원편광계를 이용하여 심근경색 생체표지자인 미오글로빈과 cTnI의 진단 농도를 수백 초 내에 실시간 초고감도로 측정하는데 성공하였다. 러닝 버퍼로는 순수한 phosphate buffered saline (PBS) 또는 PBS에 10% 인간 혈청을 섞은 러닝 버퍼를 사용하였다. PBS 조건에서는 미오글로빈과 cTnI가 각각 1 ng/mL와 5 pg/mL로 측정되었으며, PBS에 인간 혈청을 10% 섞은 조건에서는 미오글로빈과 cTnI는 각각 1 ng/mL과 1 pg/mL로 측정되었다. 이러한 심근경색 생체표지자의 진단 농도는 현재 제시된 세계보건기구의 심근경색 진단 기준 농도보다 미오글로빈은 1/15배 낮고, cTnI는 1/80배 낮다.

Fig. 1. Schematic diagram of the rotating analyzer ellipsometer.

Fig. 2. Photo of the experimental setup of rotating analyzer ellipsometer with a silicon based ellipsometric biosensor.

Fig. 3. Schematic diagram of the ellipsometric biosensor on the sample stage shown in Fig. 2.

Fig. 4. Production process of the dextran SAM biochip using a silcon plate.

Fig. 5. Measurement precision of biochip thickness variation during 300 s when the running buffer and the correcting biochip are PBS andan external biochip, respectively.

Fig. 6. Graph of the real-time super-sensitive diagnostic density of myoglobin by using the rotating analyzer ellipsometer and a biosensor with biochips fabricated by a SiO₂ coated tilted silicon substrate, when the running buffers are (a) pure PBS and (b) PBS with 10% human serum.

Fig. 7. Graph of the real-time super-sensitive diagnostic density of cTnI by using the rotating analyzer ellipsometer and a biosensor with biochips fabricated by a SiO₂ coated tilted silicon substrate, when the running buffers are (a) pure PBS and (b) PBS with 10% human serum.

Table 1. Comparison of data of Ψ obtained by the theoretical calculation, the commercial instrument (M-2000), and the silicon based ellipsometric biosensor (SISE), when the air plays a role of a running buffer

Table 2. Comparison of data of Ψ of a SiO₂ standard specimen obtained by using the commercial instrument (M-2000) and the silicon based ellipsometric biosensor (SISE), when PBS plays a role of a running buffer