One-dimensional photonic crystal (1D PhC) biosensors are emerging as powerful tools in the fight against diseases like colorectal cancer, a disease affecting millions globally. These innovative sensors exploit a unique property—their ability to detect bio molecular interactions by measuring changes in light. In this paper, we present a novel 1D PhC biosensor design with ultra-high sensitivity for detecting colorectal disorders. The sensor operates by monitoring the defect mode of the photonic crystal through a detailed analysis of light transmittance profiles obtained from excised colorectal tissue samples. The proposed design, consisting of a defect layer sandwiched between two identical periodic layers: [ \(\mathrm {air} \mid (\text{Si} \mid \text{SiO}_{2})^N \mid \mathrm {Defect}\,\mathrm {layer} \mid (\text{Si} \mid \text{SiO}_{2})^N \mid\) air], is optimized to a ternary structure, where a thin polystyrene (PS) film is inserted between silicon (Si) and silicon dioxide (SiO2) layers. This innovation significantly enhances the sensitivity compared to traditional binary structures. We employ the transfer matrix method to investigate the transmission spectra. Our results demonstrate that the ternary 1D biosensor exhibits an exceptional sensitivity of 1821 nm/RIU and a quality factor of 2000, far exceeding those of the binary sensor. This remarkable improvement can be attributed to the introduction of the polystyrene layer, which creates a gradual decrease in the refractive index profile. Consequently, a larger portion of light interacts with the analyte, leading to a stronger light–matter interaction. This translates to a highly sensitive detection method, where the resonant mode will be more sensitive and a significant shift in the near-infrared region is observed due to changes in the refractive index of colorectal tissue. The proposed biosensor offers several advantages—it facilitates label-free detection with real-time analysis, boasts a compact and cost-effective design, and is straightforward to fabricate due to its nanoscale size. Furthermore, its high sensitivity makes it a promising platform for various biomedical sensing applications beyond colorectal cancer detection, such as the detection of other biomarkers, monitoring drug delivery, or studying cellular interactions.