Improving SERS bioimaging of subcutaneous phantom in vivo with optical clearing

Surface‐enhanced Raman scattering (SERS) has proven to be a promising technique for different types of imaging including preoperative and intraoperative in vivo tumor visualization. However, the strong scattering of the turbid tissue limits its use in subcutaneous areas. In this article, we used an optical clearing technique to improve the SERS signal from a subcutaneous tumor phantom. The phantom is a 2 mm sphere of calcium alginate with incorporated petal‐like gap‐enhanced Raman tags. The use of optical clearing increases the SERS signal target‐to‐background ratio for 5 times and allow to decrease the total imaging time for at least 10 times. In addition, SERS imaging assisted with optical clearing made it possible to more precisely determine the shape and boundaries of the implanted phantom. The combination of optical clearing and SERS is a promising strategy for the clinical imaging of subcutaneous objects that are usually shielded by dermal tissue. The use of optical clearing for in vivo SERS bioimaging of a subcutaneous phantom resulted in significant increase in the SERS signal and allows to reduce accumulation time.