Application of Zwitterionic Polymer Hydrogels to Optical Tissue Clearing for 3D Fluorescence Imaging

Zwitterionic polymers have both anion and cation groups in the side chain and have been used in various biomedical applications because of the unique properties. In this study, zwitterionic polymer hydrogels are applied to optical tissue clearing for 3D fluorescence imaging. Polyacrylamide hydrogels have been employed in Clear Lipid‐exchanged Acrylamide‐hybridized Rigid Imaging/Immunostaining/In situ‐hybridization‐compatible Tissue‐hYdrogel method. Zwitterionic polymer hydrogels are produced using zwitterionic monomers, such as 3‐[(3‐acrylamidopropyl)dimethylammonio]propane‐1‐sulfonate (DAPS) and 2‐methacryloyloxyethyl phosphorylcholine (MPC), and crosslinkers. The hydrogels made from poly(DAPS‐ co ‐acrylamide) and MPC homopolymers afford the most transparent tumor tissues. However, the tissues cleared using DAPS copolymers‐containing hydrogels became turbid in a refractive index‐matching solution, which are unable to obtain clear 3D fluorescence images. In contrast, the 3D fluorescence imaging is achieved in the MPC polymer‐treated 2‐mm‐thick brain slices after immunostaining. The 3D fluorescence imaging of lung metastasis that is cleared by the MPC hydrogel to demonstrate the possible application to cancer diagnosis is performed. The results indicate the increased potentials of zwitterionic polymer hydrogels, especially MPC polymer hydrogels, in biomedical applications.