Myat Noe Hsu

Immunoassays are an important tool in various bioanalytical settings, such as clinical diagnostics, biopharmaceutical analysis, environmental monitoring, and food testing. An enzyme‐linked immunosorbent assay (ELISA) is usually used to amplify immunoassay signals; however, it requires labor‐intensive and time‐consuming procedures, which hinders its application to rapid cytokine detection. In this study, a nano‐in‐micro composite system, where immunosensing polystyrene beads (≈320 nm) are incorporated within a stimuli‐responsive microgel matrix (≈40 µm) via microfluidics, is investigated. The intrinsic volume phase‐transition change properties of the smart microgels allows an enzyme‐free enhanced immunoassay, enabling instant enhancement in signal‐to‐noise ratios of ≈5‐fold. This nano‐in‐micro hydrogel composite offers a simple yet highly effective method for sensitive and multiplexed cytokine analysis without complex enzyme‐based signal amplification steps, greatly benefitting advanced immune medicine.

Secreted proteins determine a range of cellular functionalities correlated with human health and disease progression. Because of cell heterogeneity, it is essential to measure low abundant protein secretions from individual cells to determine single‐cell activities. In this study, an integrated platform consisting of smart hydrogel immunosensors for the sensitive detection of single‐cell secretions is developed. A single cell and smart hydrogel microparticles are encapsulated within a droplet. After incubation, target secreted proteins from the cell are captured in the smart hydrogel particle for immunoassay. The temperature‐induced volume phase transition of the hydrogel biosensor allows the concentration of analytes within the gel matrix to increase, enabling high‐sensitivity measurements. Distinct heterogeneity for live cell secretions is determined from 6000 cells within 1 h. This method is tested for low abundant essential secretions, such as interleukin‐6, interleukin‐8, and monocyte chemoattractant protein‐1 secretions of both suspended cells (HL60) and adherent cells (MCF7 and MDA‐MB‐231). This platform is highly flexible and can be used to simultaneously measure a wide range of clinically relevant cellular secretions; it thus represents a novel tool for precise biological assays.

Excessive scar formation can form disabling contractures that result in a debilitating psychological outcome. Sustainable hydrophobic corticosteroid release in vivo is essential to regulate the wound healing process. Functional hydrogel particles are widely applied for sustainable release. However, due to the limited aqueous solubility of hydrophobic compounds, most of the corticosteroid is released from the hydrogels within seconds, causing undesirable scar formation and recurrence. In this study, a novel polymerization-induced phase separation is investigated to form well-defined polyethylene glycol diacrylate (PEGDA) core/alginate shell structured hydrogel particles using microfluidics without toxic organic solvents. Based on their wettability preference, hydrophobic corticosteroid-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles are compartmentalized in the PEGDA core during polymerization to control the corticosteroid release. The distribution of the PLGA nanoparticles is precisely regulated by the phase separation boundary and characterized using a fluorescent dye. The thickness of the shell and partition coefficients are determined using the UV intensity and irradiation period. Upon encapsulation of the PLGA nanoparticles within the poly(PEGDA) core, a long-term corticosteroid treatment is developed and effective scar therapeutic outcomes are evaluated using both in vitro and in vivo models.

The poor solubility of many newly discovered drugs has resulted in numerous challenges for the time-controlled release of therapeutics. In this study, an advanced drug delivery platform to encapsulate and deliver hydrophobic drugs, consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels, was developed. PLGA nanoparticles were used as the hydrophobic drug carrier, while the PEG matrix functioned to slow down the drug release. Encapsulation of the hydrophobic agents was characterized by fluorescence detection of the hydrophobic dye Nile Red within the microgels. In addition, the microcomposites prepared via the droplet-based microfluidic technology showed size tunability and a monodisperse size distribution, along with improved release kinetics of the loaded cargo compared with bare PLGA nanoparticles. This composite system has potential as a universal delivery platform for a variety of hydrophobic molecules.