Three-dimensional (3D) cell culture platforms have recently received a great deal of attention, as these systems are able to recapitulate the in vivo microenvironment of tissues or tumors. Herein, we describe adjustable and versatile elastomeric well structures for spheroid formation and their use for in situ analyses as a tunable 3D cell culture platform. Elastomeric spherical wells are fabricated using a one-step interfacial reaction between aqueous droplets on immiscible liquid polydimethylsiloxane (PDMS) without any template or expensive equipment. Because of their differing surface tensions, spherical wells are spontaneously formed on liquid PDMS with various sizes and curvatures that are easily controlled. Using arrays of these optimized wells, single tumor spheroids within each well were successfully formed at high efficiency (up to 97%) by coculturing tumor cells and fibroblasts to reflect the complex microenvironment of cancer tissue. Moreover, the tumor spheroids formed within the interfacial wells were directly applied for observing drug responses and monitoring reactive oxygen species (ROS) to investigate tumor cell responses to drugs or their 3D microenvironment. We believe that our proposed platform provides a significant contribution to the multimodal analyses of anticancer therapeutics and the tumor microenvironment.

Plasmonic nanocavities have been used as a novel platform for studying strong light−matter coupling, opening access to quantum chemistry, material science, and enhanced sensing. However, the biomolecular study of cavity quantum electrodynamics (QED) is lacking. Here, we report the quantum electrodynamic behavior of chlorophyll-a in a plasmonic nanocavity. We construct an extreme plasmonic nanocavity using Au nanocages with various linker molecules and Au mirrors to obtain a strong coupling regime. Plasmon resonance energy transfer (PRET)-based hyperspectral imaging is applied to study the electrodynamic behaviors of chlorophyll-a in the nanocavity. Furthermore, we observe the energy level splitting of chlorophyll-a, similar to the cavity QED effects due to the light− matter interactions in the cavity. Our study will provide insight for further studies in quantum biological electron or energy transfer, electrodynamics, the electron transport chain of mitochondria, and energy harvesting, sensing, and conversion in both biological and biophysical systems.

Histones are closely related to the state of chromatin, and epigenetic modification of their tail results in regulation in cells. Therefore, developing various analytical tools to map the changes in position and distribution of histone modifications is helpful in studying underlying mechanisms. Herein, we propose a high-spatial and colourimetric imaging method using plasmonic nanoparticles as probes to visualize heterochromatin histone markers in a single nucleus. We visualized the reorganization between repressive histone markers, H3K9me3 and H3K27me3, caused by oncogene-induced senescence based on the scattering colours and spectral shift of plasmonic nanoprobes to longer wavelengths using their distance-dependent coupling effect. The measured scattering profiles were correlated with the computation results simulating the scattering spectra according to the arrangements and distances among the plasmonic nanoprobes. The plasmonic nanoprobe-based high-spatial hyperspectral imaging provides an advanced way to study the dynamics of histone modifications for predicting the progression of diseases or senescence.