Ultrasensitive, Multiplex Raman Frequency Shift Immunoassay of Liver Cancer Biomarkers in Physiological Media

Abstract

Highly sensitive multiplex biomarker detection is critical for the early diagnosis of liver cancer. Here, a surface-enhanced Raman scattering (SERS) frequency-shift immunoassay is developed for detection of liver cancer biomarkers α-fetoprotein and Glypican-3 down to subpicomolar concentrations in saline solution. A high temperature modification of the Tollen's method affords silver nanoparticle films with excellent SERS response upon which ordered domains of Raman reporters are chemisorbed by microcontact printing. Shifts in the reporters SERS spectrum in response to a bound antibody's biomarker recognition constitutes the frequency shift assay, exhibiting here exceptional sensitivity and specificity and shown to function in fetal calf serum and in the serum of a patient with hepatocellular carcinoma.

Metal enhanced fluorescence biosensing: from ultra-violet towards second near-infrared window

“…For example, a multiplex SERS frequency shift immunoassay for liver and pancreatic cancer biomarkers has already been developed with high sensitivity. 106 Nanoparticle films with an excellent SERS response have been fabricated capable of multiplexed detection of liver cancer biomarkers by recording two frequency shifts upon an assay. 106 In a similar manner, a separate study demonstrated that immobilization of functionalized gold nanoshells on a gold-coated silicon substrate led to a significant improvement in the SERS signal for pancreatic cancer biomarker detection.…”

“…106 Nanoparticle films with an excellent SERS response have been fabricated capable of multiplexed detection of liver cancer biomarkers by recording two frequency shifts upon an assay. 106 In a similar manner, a separate study demonstrated that immobilization of functionalized gold nanoshells on a gold-coated silicon substrate led to a significant improvement in the SERS signal for pancreatic cancer biomarker detection. 107 This work was used to detect three cancer biomarkers at concentrations as low as 2 ng ml −1 .…”

Recent applications of paper‐based point‐of‐care devices for biomarker detection

“…Detection of tumor markers plays a significant role for early diagnosis, screening, and treatment of cancers. Techniques for tumor marker detection include CL , MS , electrophoresis , and immunoassays . Among them, immunoassays (e.g.…”

Multiplexing Determination of Cancer-Associated Biomarkers by Surface-Enhanced Raman Scattering Using Ordered Gold Nanohoneycomb Arrays

“…Recently, surface-enhanced Raman scattering (SERS) based methods for multiple tumor biomarkers detection have got a lot of attentions because of its narrow 'fingerprint' Raman spectrum from analyte molecule, which enables the SERS to be utilized to recognize and quantify various targets from mixture [31]. With the development of various nanomaterials, SERS was utilized for detecting multiple cancer biomarkers successfully [32][33][34][35][36]. For example, in order to detect AFP and Glypican-3, Tang et al has used silver nanoparticle film as SERS substrate to design SERS frequency-shift immunoassay [32].…”

“…With the development of various nanomaterials, SERS was utilized for detecting multiple cancer biomarkers successfully [32][33][34][35][36]. For example, in order to detect AFP and Glypican-3, Tang et al has used silver nanoparticle film as SERS substrate to design SERS frequency-shift immunoassay [32]. By taking advantages of gold nanoflowers and SERS-active magnetic nanoparticles, a sandwich immunoassay was designed by Song et al to detect CEA and NSE, which showed high specificity and sensitivity [33].…”