Fig. 1. Design and synthesis of the pH ratiometrically responsive SERRS probe. (A) Illustration presenting the acidic margin-guided brain tumor surgery by intra-operatively determining tissue pH values/malignancies in tumor cutting edges. (B) Chemical structure of the pH-responsive reporter molecule IR7p and the control reporter IR7 without pH sensitivity. (C) Synthesis of pH responsive SERRS probe AuS-IR7p and the control probe AuS-IR7. (i) Sodium citrate; (ii) ascorbic acid, AgNO₃; (iii) IR7p; (iv) HS-PEG^5K-NHS, cysteine-modified angiopep2 peptide; (v) IR7; (vi) HS-PEG^5K-OMe.