A reusable laser wrapped graphene-Ag array based SERS sensor for trace detection of genomic DNA methylation

• Published in: Biosensors & bioelectronics Vol. 92; pp. 755 - 762
• Main Authors: Ouyang, Lei, Hu, Yaowu, Zhu, Lihua, Cheng, Gary J., Irudayaraj, Joseph
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.06.2017
• Subjects: 5-Methylcytosine - analogs & derivatives; 5-Methylcytosine - analysis; Antibodies, Immobilized - chemistry; Biosensing Techniques - instrumentation; Biosensing Techniques - methods; Cell Line, Tumor; Cytosine - analogs & derivatives; Cytosine - analysis; DNA - chemistry; DNA Methylation; Equipment Design; Gold - chemistry; Graphene-Ag array; Graphite - chemistry; Humans; Laser wrapping; Metal Nanoparticles - chemistry; Metal Nanoparticles - ultrastructure; Reproducibility of Results; SERS; Silver - chemistry; Spectrum Analysis, Raman - instrumentation; Spectrum Analysis, Raman - methods; DNA methylation; SERS; Graphene-Ag array; Laser wrapping
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2016.09.072

Methylation is an important epigenetic DNA modification that governs gene expression. The genomic level of methylated DNA and its derivatives may serve as important indicators for the initiation and progression of cancers among other diseases. In this effort we propose a new laser wrapped graphene-Ag array as a highly sensitive Surface-enhanced Raman spectroscopy (SERS) sensor for the detection of methylated DNA (5-methylcytosine, 5mC) and its oxidation derivatives namely 5-hydroxymethylcytosine (5-hmC) and 5-carboxylcytosine (5-caC). Excellent sensitivity and reproducibility were achieved with the laser wrapped graphene-Ag array as a substrate, with the graphene layer acting as an enhancer of the SERS signal due to the effective coupling of the electromagnetic field. In summary, fast (less than 60min) and sensitive (at a limit of detection 0.2pgμL−1, ie. 1.8pmolL−1) detection of methylated DNA and its derivatives was realized with the ability to distinguish methylation levels from a mixture at 0.1%. The sensitive and accurate detection in DNA extracted from cells was also accomplished. Furthermore our graphene wrapped approach circumvents the direct interaction between Ag array and the analytes, thus improving the reusability of the SERS substrate even after five cycles of use. •A laser wrapped graphene-Ag array is fabricated for SERS the detection of methylated DNA.•Excellent sensitivity and fine reproducibility was achieved with the graphene layer.•Fast (less than 1 hour) and sensitive (~1.8pmolL−1) detection was realized.•Excellent selectivity and accuracy was achieved with the affinity-based enrichment strategy with both standard and real cell samples.•The graphene wrapped approach improved the reusability of the SERS substrate even after five cycles of use.