Acute　myocardial　infarction　(AMI)　is　one　of　the　leading　causes　of　human　mortality　worldwide.　In　the　early　stages　of　AMI,　the　patient’s　electrocardiogram　(ECG)　may　not　change,　so　the　fast,　sensitive,　and　accurate　detection　of　the　specific　biomarker　of　cardiac　troponin　I　(cTnI)　is　of　great　importance　in　the　early　diagnosis　of　AMI.　In　this　work,　for　the　first　time,　electrostatic　nanoaggregates　of　negatively　charged　Au　nanoparticles　and　positively　charged　trisbipyridine　ruthenium(II)　ions　(i.e.,　(−)AuNPs|[Ru(bpy)3]2+　ENAs)　as　novel　and　signal-amplifying　surface-enhanced　Raman　scattering　(SERS)　tags　were　synthesized　in　an　easy　and　rapid　(3]2+　ENAs　exhibited　strong　SERS　activity　due　to　the　multiple　Raman-active　units　(three　bpy　ligands)　carried　by　each　[Ru(bpy)3]2+　complex　ion　and　abundant　hotspots　in　each　SERS　tag.　The　developed　(−)AuNPs|[Ru(bpy)3]2+　ENAs-based　SERS-ICTS　has　been　validated　to　be　applicable　in　detection　of　cTnI　in　human　serum　with　excellent　sensing　performances,　such　as　fast　testing　(5　min)　and　a　low　detection　limit　(60　pg/mL).　It　is　envisioned　that　the　developed　(−)AuNPs|[Ru(bpy)3]2+　ENAs-based　SERS-ICTS　sensor　may　have　promising　applications　in　point　of　care　testing　of　various　biomarkers　in　clinic.　Additionally,　this　work　may　inspire　the　finding　and　the　application　of　new　types　of　Raman　reporter　molecules　based　on　high　valent　metal-multi　ligand　coordination　compounds　like　[Ru(bpy)3]2+　©　2024　American　Chemical　Society.