Next Generation Point-of-care Biomedical Sensors Technologies for Cancer Diagnosis by Pranjal Chandra Yen Nee Tan & Surinder P. Singh

Author:Pranjal Chandra, Yen Nee Tan & Surinder P. Singh
Language: eng
Format: epub
Publisher: Springer Singapore, Singapore

In addition to MS nanoprobes and MSC technology for SERS-based nucleic acid detection, Vo Dinh and his group have recently reported the development of another plasmonic based nanobiosensing platform known as the “inverse molecular sentinel” (iMS) nanoprobe technology for nucleic acid detection (Wang et al. 2015). The iMS technology is based on a ‘OFF-to-ON’ SERS signal switch mechanism which is just the opposite of the ‘ON-to-OFF’ signal switch mechanism of MS technology. The group developed a iMS nanoprobe consisting of a silver-coated gold nanostar (AuNS@Ag) as a SERS enhancer linked to a DNA probe. Similar to the MS nanoprobe, the DNA probe consisted of a hairpin loop structure whose one end is attached to the plasmonic nanostar through a thiol-metal linkage and the other end is labelled with a Raman reporter. In the absence of the target sequence, a single-stranded ‘placeholder sequence’ binds to the hairpin probe and disrupts the hairpin loop structure, thereby moving the Raman label away from the nanostar surface. As a result, in this ‘open’ configuration there is very low SERS intensity (OFF state). However, when the target sequence is present, it first binds to an overhanging region of the probe-placeholder complex and starts to displace the placeholder sequence through a branch migration process ultimately releasing the placeholder from the probe. This allows the probe sequence to return back to its hairpin loop conformation (‘close’ configuration), thereby bringing the Raman label closer to the surface of the plasmonic nanostar, resulting in a strong SERS signal (ON state) (Fig. 8.11 ). Using this iMS nanobiosensor platform, the group reported multiplexed detection of two important breast cancer biomarkers—miR-21 and miR-34a miRNA—from total small RNA extracted from breast cancer cell lines in a single sensing platform with high sensitivity. Different amounts of total small RNA (250 ng, 500 ng and 1 μg) extracted from MCF-7 breast cancer cell line were probed with a 10 μL nanoprobe mixture containing 5 pM of miR-21 nanoprobes and 10 pM of miR-34a nanoprobes, for simultaneous multiplexed detection of these two biomarkers (Wang et al. 2016).

Fig. 8.11Detection scheme of the SERS iMS nanoprobes. Reproduced with permission from Wang et al. (2016). Copyright 2016 American Chemical Society

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