When incorporated into an ellipsometry‐based dual‐prism solution‐immersed silicon sensor, Tr‐Apt13 enabled ultrasensitive detection of PD‐L1–expressing exosomes with a detection limit of ≈9.8 particles mL−1, exhibiting high linearity and stability. Clinical validation using bronchoalveolar lavage fluid (BALF) from lung cancer patients revealed precise discrimination between responders and non‐responders at exosome concentrations as low as 103 particles mL−1, outperforming serum‐based analysis, conventional ELISA, and tissue immunohistochemistry. The gene discussed is CD274; the disease is lung cancer.