Surface‐enhanced Raman imaging of intact cancer cell membrane on a rough aluminum substrate

Abstract The plasma membrane of cancer cells displays differences in lipid and protein composition which distinguish them from healthy cells. Certain molecules have such prominent vibrational characteristics that they can be considered cancer biomarkers. Although Raman spectroscopy is a label‐free non‐invasive method of chemical analysis, it, however, has been limited by weak signals from the membrane compared to the bulk interior of cells. Surface‐enhanced Raman scattering (SERS) on plasmonic gold and silver substrates has previously been used to overcome this limitation. However, the high cost, poor repeatability, and toxicity of these noble metals hinder their practical applications. These challenges may be solved by using different materials and nanostructures. Here, we performed SERS imaging of ovarian cancer cells on rough aluminum substrates and extracted the Raman signals of intact cell membranes by comparing these with the corresponding measurements on Si substrates. We used atomic force microscopy (AFM) for Raman signal calibration. The comparison of cancer and normal cell membranes revealed the different lipid/protein peak ratios in cytoplasm and nucleus‐proximal areas. These Raman signatures of the ovarian cancer can be used as new biomarkers. This method may be extended to other types of cancer biosensing based on aluminum plasmonics.