Multiplexed SERS Detection of Soluble Cancer Protein Biomarkers with Gold–Silver Alloy Nanoboxes and Nanoyeast Single-Chain Variable Fragments

• Published in: Analytical chemistry (Washington) Vol. 90; no. 17; pp. 10377 - 10384
• Main Authors: Li, Junrong, Wang, Jing, Grewal, Yadveer S, Howard, Christopher B, Raftery, Lyndon J, Mahler, Stephen, Wang, Yuling, Trau, Matt
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 04.09.2018
• Subjects: Alloys - chemistry; Biomarkers; Biomarkers, Tumor - metabolism; Cancer; Cancer screening; Chains; Chemistry; Early Detection of Cancer; Enzyme-Linked Immunosorbent Assay; Fragments; Gold; Gold - chemistry; Gold alloys; Gold base alloys; Growth factors; Humans; Limit of Detection; Medical treatment; Metal Nanoparticles - chemistry; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Monoclonal antibodies; Multiplexing; Nanostructured materials; Neoplasm Proteins - metabolism; Neoplasms - diagnosis; Patients; PD-1 protein; Proteins; Raman spectra; Sensitivity; Silver; Silver - chemistry; Silver base alloys; Single-Chain Antibodies - chemistry; Spectrum Analysis, Raman - methods
• DOI: 10.1021/acs.analchem.8b02216
• ISSN: 0003-2700

Highly sensitive, multiplexed detection of soluble cancer protein biomarkers can facilitate early cancer screening as well as enable real-time monitoring of patients’ sensitivity and resistance to therapy. Current technologies for detection of soluble cancer protein biomarkers, e.g., enzyme-linked immunosorbent assay, however, suffer from limited sensitivity, as well as the requirement of expensive monoclonal antibodies, which undergo the quality variability. Herein, we propose a sensitive, cheap, and robust surface-enhanced Raman scattering technology to detect a panel of soluble cancer protein biomarkers, including soluble programmed death 1 (sPD-1), soluble programmed death-ligand 1 (sPD-L1) and soluble epithermal growth factor receptor (sEGFR), which are related to disease progression and treatment efficacy. In this assay, gold-silver alloy nanoboxes that have strong Raman signal enhancement capability were used as plasmonic nanostructures to facilitate highly sensitive detection. In addition, nanoyeast single-chain variable fragments were utilized as mAb alternatives to allow specific and stable protein capture performance. We successfully detected sPD-1, sPD-L1, and sEGFR with a limit of detection of 6.17 pg/mL, 0.68 pg/mL, and 69.86 pg/mL, respectively. We further tested the detection of these three soluble cancer protein biomarkers in human serum and achieved recovery rates between 82.99% and 101.67%. We believe our novel platform that achieves sensitive, multiplexed, and specific detection of soluble cancer protein biomarkers could greatly benefit cancer treatment and improve patient outcome.