Development of Janus Particles Enabled Rotational Diffusometry for Ultrasensitive Biosensing
Han-Sheng Chuang, Senior Member, ASME & AIChE
Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
oswaldchuang@mail.ncku.edu.tw
Abstract
Brownian motion is a self-driving natural phenomenon in which tiny particles show rapid and random movement in liquids. Brownian motion features high robustness, high sensitivity, high reliability, and ease of use. Recently, this technique has also been extended to biomedical applications, such as an investigation of microorganisms and rapid diagnosis of diseases with specific biomarkers. Unlike the conventional translational Brownian motion, rotational Brownian motion appears to show high sensitivity in the change of particle diameter according to the Debye-Stokes-Einstein relation. By taking advantage of this powerful relation, we aimed to quantify the rotational diffusivity by developing functionalized Janus particles. With Janus particles, ultrasensitive detection with a biomarker, tumor necrosis factor alpha (TNF-α), was then conducted for demonstration in this research. Janus particles were fabricated by coating half side of 1-μm fluorescent polystyrene (PS) particles with a 50-nm gold film and purified with filter papers. The signal of rotational Brownian motion was expressed on the Janus particles in terms of blinking fluorescence. The particles were conjugated with capture anti TNF-α IgG to enable sandwiched immunocomplexes comprising capture antibody-antigen-probe antibody in the presence of TNF-α. The probe antibody was later conjugated with 200-nm PS particles to enhance the diameter change. Correlation time was derived from the blinking frequency by the cross-correlation algorithm. Significant blinking frequencies were observed between immunocomplexed and plain Janus particles. A calibration curve exhibited that the correlation time declined with the increased concentrations of TNF-α. The optimal limit of detection of TNF-α measured by the rotational diffusometry achieved as low as 1 pg/mL. Enhancement was also observed on the comparison of Janus particles with and without the 200-nm PS particles. The rotational diffusometry provides an insightful ultrasensitive biosensing capability for early-stage diseases with trace analytes.
Short Bio
Han-Sheng Chuang is currently a full professor in the Department of Biomedical Engineering at National Cheng Kung University, Taiwan. Dr. Chuang received his bachelor and master degrees from the Department of Mechanical Engineering at NCKU in 1998 and 2000, respectively. He worked with Professor Steve T. Wereley for advanced microfluidics and received his Ph.D. from the School of Mechanical Engineering at Purdue University in 2010. After graduation, he received an appointment as a postdoctoral researcher at University of Pennsylvania and worked with Professor Haim H. Bau. Since starting the current position in 2011, he has received the 2014 and 2019 Young Researcher Career Grants from the Ministry of Science and Technology, the 2015 Young Scholar Award from the TCUS, and the 2016 Excellent Teaching Award as well as the 2020 Excellent Research Award from NCKU. In addition, he is currently president of the Association of Chemical Sensors in Taiwan. Dr. Chuang’s research interests are mainly focused on bio-micro/nano-fluidics, Bio-MEMS/NEMS, optical diagnostics, and C. elegans.