The probe-like nanostructure features a hairpin-looped DNA sequence (~30–45 bases in length), which is attached to a silver nanoparticle with an average diameter of 30 nm. One end of the hairpin probe is labeled with a dye molecule that can be detected using Raman spectroscopy. At the other end, the probe is conjugated to the silver nanoparticle.

The loop sequence of the hairpin probe is designed to recognize a specific gene of interest. In the absence of the target DNA, due to the stem-loop configuration ("closed" state), the Raman label is in close proximity to the metal nanoparticle. Laser excitation of the MS probe produces a strongly amplified electromagnetic field on the metal nanoparticle surface (surface plasmon) and induces an intense Raman signal from the label, often referred to as a surface-enhanced Raman scattering (SERS) signal.

On the other hand, in the presence of the specific target DNA, hybridization between the target and hairpin probe occurs, disrupts the stem-loop configuration and spatially separates the Raman label from the silver nanoparticle ("open" state). Because the intensity of the SERS signal depends strongly on the distance between the Raman label and the metal nanoparticle, the open-state configuration results in a strongly reduced (quenched) SERS signal intensity.

The plasmonic nanoprobes play the role of "molecular sentinels" patrolling the sample solution by switching their warning light on and off when significant event occurs. The multiplex capability of the molecular sentinel nanoprobes was demonstrated by mixing differently labeled nanoprobes targeting two breast cancer biomarkers, erbB-2 and ki-67 genes. It is noteworthy that the SERS measurements can be performed immediately following the hybridization reactions in a homogeneous assay (in other words, without washing steps), which greatly simplifies the assay procedures for multiplex gene detection.

The results of the study of graduate student Hsin-Neng Wang and professor Tuan Vo-Dinh at Duke University demonstrate that the MS nanoprobe technique can provide a useful diagnostic tool for multiplexed DNA detection of multiple medical biomarkers in a single homogeneous solution.