rate up to 90%, but below 36% in the case of advanced GC patients. [1a] An effective approach of early GC detection requires the combination of initial pre-selection of high-risk individuals and follow-up endoscopy examination, while its largescale application is facing challenges like low cost-efficiency (e.g., inefficient preselection by non-specific risk factors), poor patient compliance, and shortage of experienced endoscopists, etc. [2b] Therefore, it is pressing to develop a rapid and noninvasive method to discover biomarkers and diagnose early GC with an improved prognosis.Liquid biopsy allows the detection of oncotarget biomarkers through non-invasive techniques from biofluids (e.g., blood), holding promise for early screening of GC in clinics. [4] Various genetic (e.g., circulating tumor DNA (ctDNA)) [5] and protein (e.g., carcino embryonic antigen (CEA)) biomarkers in human blood have been discovered for GC diagnosis, but the applicable performance is limited by suboptimal accuracy (e.g., sensitivity of 13% for CEA), [6] high cost (€140 per test), [7] and lack of validation in early GC patients. [1b,8] Besides genes and proteins, metabolites serve as direct signatures of biochemical activity and are associated with gastric carcinogenesis. [9] Mass spectrometry (MS), particularly laser desorption/ionization (LDI) MS, is a powerful analytical tool capable of the simultaneous detection and spatial mapping of various metabolites. [10] However, it is offset in metabolic profiling with Gastric cancer (GC) is a multifactorial process, accompanied by alterations in metabolic pathways. Non-invasive metabolic profiling facilitates GC diagnosis at early stage leading to an improved prognostic outcome. Herein, mesoporous PdPtAu alloys are designed to characterize the metabolic profiles in human blood. The elemental composition is optimized with heterogeneous surface plasmonic resonance, offering preferred charge transfer for photoinduced desorption/ionization and enhanced photothermal conversion for thermally driven desorption. The surface structure of PdPtAu is further tuned with controlled mesopores, accommodating metabolites only, rather than large interfering compounds. Consequently, the optimized PdPtAu alloy yields direct metabolic fingerprints by laser desorption/ionization mass spectrometry in seconds, consuming 500 nL of native plasma. A distinct metabolic phenotype is revealed for early GC by sparse learning, resulting in precise GC diagnosis with an area under the curve of 0.942. It is envisioned that the plasmonic alloy will open up a new era of minimally invasive blood analysis to improve the surveillance of cancer patients in the clinical setting.

Diagnostics is the key in screening and treatment of cancer. As an emerging tool in precision medicine, metabolic analysis detects end products of pathways, and thus is more distal than proteomic/genetic analysis. However, metabolic analysis is far from ideal in clinical diagnosis due to the sample complexity and metabolite abundance in patient specimens. A further challenge is real‐time and accurate tracking of treatment effect, e.g., radiotherapy. Here, Pd–Au synthetic alloys are reported for mass‐spectrometry‐based metabolic fingerprinting and analysis, toward medulloblastoma diagnosis and radiotherapy evaluation. A core–shell structure is designed using magnetic core particles to support Pd–Au alloys on the surface. Optimized synthetic alloys enhance the laser desorption/ionization efficacy and achieve direct detection of 100 nL of biofluids in seconds. Medulloblastoma patients are differentiated from healthy controls with average diagnostic sensitivity of 94.0%, specificity of 85.7%, and accuracy of 89.9%, by machine learning of metabolic fingerprinting. Furthermore, the radiotherapy process of patients is monitored and a preliminary panel of serum metabolite biomarkers is identified with gradual changes. This work will lead to the application‐driven development of novel materials with tailored structural design and establishment of new protocols for precision medicine in near future.