Development of a compact label-free small molecule measurement system using a periodically nanostructured sensor substrate

Abstract

In order to stay in good health, people have regular checkups. Part of this process involves examining the body for abnormalities. This requires a variety of large, complicated medical equipment to measure a small amount of biomolecules or chemical substances. The rapid advances in microelectromechanical systems (MEMS) and nanotechnology have made it possible to downsize medical equipment and perform health checkups using simpler detection methods such as label-free measurements. Nanomaterials have been used to achieve these goals; however, these require high-level sensor fabrication techniques and may provide lower sensitivity than conventional methods. In this work, we developed a compact label-free small molecule measurement system using a periodically nanostructured sensor substrate. We fabricated the sensor substrate using simple techniques, namely, thermal nanoimprinting and sputtering. The sensor substrate realizes label-free measurements by utilizing surface plasmon resonance (SPR). A collimator is mounted into an optical fiber to reduce noise in real-time measurements. The flow cell height and velocity were investigated with the aim of shortening the equilibrium binding time. We demonstrate the simple yet effective method by performing label-free measurement of a small molecule, namely, cortisol (M.W. = 362 g mol⁻¹), with a concentration of several tens of nanomoles per liter. We demonstrated that the normalized peak wavelength obtained by our measurement system shows good correlation with the cortisol concentration (0 nM, 24.3 nM and 48.6 nM). Our results had a smaller standard deviation than those of the ELISA test.