Optical biosensor based on SERS with signal calibration function for quantitative detection of carcinoembryonic antigen

Abstract

Monitoring the levels of cancer biomarkers is essential for cancer diagnosis and evaluation. In this study, a novel sandwich type sensing platform based on surface-enhanced Raman scattering (SERS) technology was developed for the detection of carcinoembryonic antigen (CEA), with a limit of detection (LOD) of 0.258 ng/mL. In order to achieve sensitive detection of CEA in complex samples, gold nanoparticle monolayer modified with CEA antibodies and with aptamer-functionalized probes was fabricated to target CEA. Two gold layers were integrated into the SERS platform, which greatly enhanced the signal of the probe by generating tremendous "hot spots". Meanwhile, the intensity ratio of Raman probes and the second-order peak of the silicon wafer was used to achieve dynamic calibration of the Raman probe signal. Excitingly, this sensing platform was capable of distinguishing cancer patients from healthy individuals via CEA concentrations in blood samples with the accuracy of 100%. This sandwich structure SERS sensing platform presented promising potential to be an alternative tool for clinical biomarker detection in the field of cancer diagnosis.

Fig. 1.

Assembly schematic of SERS sensing platform based on sandwich structure: fabrication process of aptamer-functionalized SERS probes and immune-modified nanoparticle monolayers and specific capture of target CEA.

Fig. 2.

Size distribution (a), UV-vis spectra (b) and zeta potentials (c) obtained for Au NPs (I), Au@4MBA&Apt@BSA NPs (II) and Au@4MBA&Apt@BSA@CEA NPs (III). (d) SERS spectra of SERS sensor platform assembly process. (e)TEM image of Au NPs. (f) SEM image of self-assembled two-dimensional substrate, insert: SERS mapping for two-dimensional substrate.

Fig. 3.

(a) Raman spectra with different concentrations of CEA from 1 ng/mL−10µg/mL obtained on CEA SERS sensing planform. (b) The enlarged portion at the dotted line in (a). (c) CEA detection logarithmic concentration curves generated by ratio of the peaks at 940 cm⁻¹and 1583 cm⁻¹ (I₁₅₈₃/I₉₄₀). (d)Average Raman spectra of different concentrations of CEA without intensity correction. (e)CEA detection logarithmic concentration curves generated by plotting the average intensity at 1583 cm⁻¹. (f)Selectivity of the detection of CEA (1 ng/mL), with the blank control and the interfering substances of BSA and AFP presented at the same concentration.

Fig. 4.

(a) Comparison of the mean SERS spectra for the normal serum versus that of the breast cancer with 940 cm⁻¹ intensity correction. (b) SERS intensity ratio (I_1583cm⁻¹/I_940cm⁻¹) in 20 serum samples obtained on CEA SERS sensing planform. (c) Distribution of spectral peak intensities at I_1583cm⁻¹/I_940cm⁻¹ in healthy humans(n = 10) and breast cancer patients (n = 10). (d) Distribution of spectral peak intensities at 1583cm⁻¹ in healthy humans(n = 10) and breast cancer patients (n = 10). *P value < 0.05. **P value < 0.01. ***P value < 0.001.