工科系奈微米生醫流體實驗室

Multifunctional Gold/Fluorescent Nano-Mushrooms for Raman Sensing, Cancer Marker Targeting, and Drug Delivery (J. Mat. Chem. 2012, J. Phy. Chem. C 2011, Anal. Chem. 2009)

This work reports a top-down manufactured monodisperse mushroom-like fluorescent nanoparticle with multifunctions for being SERS-active Raman sensor, cancer marker, and drug delivery carrier. A one-step oxygen p lasma treatment tailored commercial fluorescent polystyrene beads (PSBs) with a corrugated hemisphere and simultaneously vary the entire surface with carboxylic groups. Followed by a gold coating on the corrugated hemisphere, our Au-coated fluorescent nano-mushrooms (AuFNMs) were formed to possess dual-module surfaces of upper plasmonic gold semishell and bottom fluorescent carboxylation polystyrene. Basic surface modificati on assembly of anti-CD44 monoclonal antibody and sulfo-NHS-SS-biotin disulfide linker could bind onto the lower carboxyl and higher gold surfaces through peptide and Au-S bonds, respectively. Then, the AuFNMs can target cell-surface glycoprotein of CD44 on cancer cells and release their loads inside cell membrane via the cleavable disulfide bonds reacted with cytoplasm for ~30min. A 12-fold recognition on cancer cells (HeLa and MCF-7) can be reached compared to a normal cell (chondrocyte). Besides, the surface-modified AuFNMs suspension was verified with >99% purified and uniformed nanoparticles in a concentration of ~10¹⁰ numbers/mL in 2 mL DI water. For the applications of 3D confocal particle tracking and Raman mapping, the AuFNMs demonstrate excellent long-lasting single-particle fluorescence and superior biomolecule sensing ability.

Mesoporous Silica Nanoparticle (Nano Today 2011, J. Mat. Chem. 2010, 2009)

In this serials work, a Mesoporous Silica Nanoparticle with Tri-Functionalization was employed for Comprehensive Cancer Theranostics- including Imaging, Targeting and Therapy. In 10^-3, the three dimensional (3D) interface energy transfers in hexagonal mesoporous silica nanoparticles (MSNs) can significantly enhance the photodynamic effect. By providing a well-defined mesoporous nanostructure, we established an efficient and controllable energy transfer mechanism via the facile modification of a two-photon antenna molecule and photosensitizer on different topological domains in the MSN. The cytotoxicity induced by the singlet oxygen, generated following relay of energy transfer, was demonstrated in both in vitro and in vivo breast cancer models. Therefore, our results contribute new insight to the highly efficient energy transfer within a single nanoparticle for two-photon activated PDT, worthwhile for studying its potential for development in clinical translation.

A perfusion-based micro opto-fluidic system (PMOFS) for continuouslyin-situ immune sensing (Lab Chip 2009, Nanotech. 2008)

This research proposes a novel perfusion-based micro opto-fluidic system (PMOFS) as a reusable immunosensor for in-situ and continuous protein detection. The PMOFS includes a fiber optic interferometry (FOI) sensor housed in a micro-opto-fluidic chip covered with a microdialysis membrane. It features a surface regeneration mechanism for continuous detection. Gold nanoparticles (GNPs) labeled anti-rabbit IgG were used to enhance the immune conjugation signal by the elongated optical path from GNPs conjugation. Surface regeneration of the sensor was achieved through local pH level m anipulation by means of a photoactive molecule, o-Nitrobenzaldehyde (o-NBA), which triggered the elution of immune complexes. Experimental results showed that the pH level of the o-NBA solution can be reduced from 7 to 3.5 within 20 seconds under UV irradiation, sufficient for an effective elution process. The o-NBA molecules, contained within poly(ethylene glycol) diacrylate (PEG) complexes, were trapped within the sensing compartment by the microdialysis membrane and would not leak into the outside environment. The pH variation was also limited in the neighborhood of the sensor surface, resulting in a self-contained sensing system. In-situ immune detection and surface regeneration of the sensing probe has been successfully carried out for two identical cycles by the same sensing probe, and the cycle time can be less than 8 minutes, which is so far the fastest method for continuous monitoring on protein/peptide molecules. In addition, the interference fringe shift of the sensor is linearly related to the concentration of anti-cytochrome C antibody solution and the detection limit approaches 10 ng/ml.