Sangmin Lee1 Chan Ho Park1 Shin-Hyun Kim1

1, Korea Advanced Institute of Science and Technology, Daejeon, , Korea (the Republic of)

In-situ monitoring of pH is of great importance in biomedical fields as pH affects activities of enzyme and drug and is a symptom of certain diseases. It is known that the microenvironment of cancer cells is weakly acidic due to the secretion of lactic acid through anaerobic respiration. Therefore, pH can be an effective indicator for cancers. However, it is very difficult to use conventional litmus papers or pH-meters for measurement of local pH in cellular environments. To provide an injectable, implantable, suspendable platform of pH sensors, we suggest a microcapsule-type sensor that is composed of the pH-responsive optical sensor in the core and semipermeable polymer in the shell. As a template to produce microcapsules, monodisperse water-in-oil-in-water (W/O/W) double-emulsion droplets are prepared using a capillary microfluidic device. The innermost water phase contains molybdenum disulfide (MoS2) nanosheets whose surfaces are grafted by pH-responsive polymers with a fluorescent group at the distal end. As the middle oil phase, a photocurable resin of polysiloxanes modified with methacrylate is used. The double-emulsion drops are irradiated by ultraviolet, which leads to the polymerization of the resin, forming a semipermeable solid shell. The pH-responsive polymer that links the MoS2 nanosheets and fluorescent groups are designed to show a drastic conformation change in the range of pH 6.0-7.4. At physiological condition of pH 7.4, the pH-responsive polymer is collapsed so that the fluorescent groups are brought to the optical quencher of MoS2, yielding a weak fluorescence due to the Forster resonance energy transfer (FRET). By contrast, at cancer microenvironment with pH 6.3, the pH-responsive polymer is highly extended, increasing fluorescent intensity. As the pH sensors are encapsulated by a semipermeable shell, they are free from dilution with physiological fluids and adhesion of proteins and lipids, thereby maintaining the sensing performance in a physiological environment. The microcapsule sensors can be injected, implanted, and suspended in any target volumes, which enables the in-situ monitoring of pH in the microenvironment where the microcapsules are located.