Multifunctional Polymeric Nanoneedles with “Full‐Spectrum Intrinsic Internal Standard” for Precise SERS Biosensing

Polymeric micro and nanoneedles have an exceptionally flexible bio‐SERS structure. However, during detection, Raman signals from the polymer often overlap with those from the target molecules, which is unavoidable and severely compromises the accuracy of the results. To address this issue, this study designed and fabricated a silver (poly(vinyl pyrrolidone)‐coated, PVP)/poly(vinylidene fluoride) (PVDF)/gold nanoneedles structure (Ag/PVDF/Au NNs) and proposed a full‐spectrum intrinsic internal standard (FS‐IS) analytical method. In this method, the entire spectra of PVP and PVDF within the Raman fingerprint region are used as an internal standard, and machine learning algorithms are employed to quantitatively analyze the relevant SERS detection from a statistical perspective. Both the experimental and theoretical results demonstrate that this method is more accurate than traditional analysis methods based on embedded or intrinsic internal standards. Using the FS‐IS analysis method, the Ag/PVDF/Au NNs are successfully applied to various biosensing applications, including cancer cell imaging and in situ monitoring of antibiotics in the urine of surgical patients. This study effectively addresses the issue of low detection accuracy in flexible nanoneedle SERS structures and provides valuable insights for the development of other high‐precision detection technologies based on flexible substrates.