The early screening and diagnosis of various infectious diseases is critical to public health and homeland security. The application of plasmonic nanoantennas on early-stage disease detection has attracted considerable attentions due to its ultra-high sensitivity, design flexibility and low cost. Recently the incorporation of sensitive plasmonic nanoantennas into fluidic channels (plasmofluidics) have proven advantageous in fast, label-free, and multiplexed detection of biological entities. However, challenges exist to achieve high-sensitivity plasmofluidic sensing of biological nanoparticles such as viral particles and exosomes. The refractometric resonance shifts are generally small, typically <5 nm. This is due to a small refractive index contrast of the biological nanoparticles with the buffer background and also lack of high-sensitivity antenna designs to probe the large particles (40-150 nm).
Here we present a novel and generic plasmofluidic sensor design to achieve high-sensitivity detection of various antigens (e.g., influenza, Zika viruses and exosomes). Our sensor consists of strongly coupled antennas, i.e. nanobar dimers (bright mode) and U shaped bar (coupling to dimer, dark mode), that creates a sharp Fano resonance with a very narrow FWHM (e.g. 70 nm at resonance wavelength 990 nm). Our gold sensor array is surface functionalized with streptavidin, which further binds to biotinylated antibodies that selectively capture the antigen to be detected. The combination of Fano resonance design and the antibodies allow high-sensitivity and high-specificity detection, and the incorporation of different antibodies in multiple fluidic channels allow multiplexed detection of different antigens on one single fluidic chip.
Our sensor design has a number of advantages. First, it enables high-sensitivity dual mode sensing by simultaneously detecting the resonance shift and the spectral intensity modulation. Second, the plasmonic hotspots can be designed at different dimensions, as large as >100 nm, with a uniform electric field intensity enhancement to probe the biological nanoparticles. Third, nanobar dimers and U shaped bar synergistically behave as effective traps in fluidic channels to capture the antigen virus into hot spots.
Our full-wave simulation shows that the captured virus particles (assumed ~80 nm in diameter) can lead to 3-6 nm shift and 4.2-5.5% reflection intensity modulation at the same time – 5 to 10 times better than demonstrated plasmonic sensors. The resonance shift and intensity modulation can be further amplified by 2-3 times by binding the captured antigen with a second antibody conjugated with gold nanoparticles. Our simulation indicates that our proposed structure can be a promising high-sensitivity optical detector of a variety of antigens, with an estimated limit of detection about two orders of magnitude better than ELISA.
The sensor fabrication and antigen detection are ongoing and will be presented at the conference.