**Abstract**

Detection of nanometer-sized biomarkers is a research topic that attracts much attention as an application for early diagnosis of diseases. Biopsy monitoring by analyzing cell secretion in a non-destructive way has many advantages in the field of biomedicine. We introduce the Raman signal enhancement method on a biosensing chip based on surface-enhanced Raman diagnosis. This approach has the advantage because the ZnO nanorods are grown to form nanoscale porosity and are coated with gold to enable size selective biomarker detection. After sputtering gold on the grown ZnO nanostructures, the unique feature of clustering the nanorod's heads first appeared. The grain formation on the head was the main factor for the localized surface plasmon resonance (LSPR) enhancement, and this fact could be verified by finite element analysis. It has been demonstrated in breast cancer cell line that the cell viability is also high in such gold-clad ZnO nanostructure-based surface-enhanced substrates. For bioapplication, interstitial cystitis/bladder pain syndrome (IC/BPS) animal model was prepared by injecting HCl into the bladder of a rat, and urine was collected a week later to conduct Raman spectroscopy experiments.

**Keywords:** surface-enhanced Raman spectroscopy (SERS), ZnO nanorods, gold clustering, finite element method (FEM), cell viability, interstitial cystitis/bladder pain syndrome (IC/BPS)
