Microfluidic Plasmonic Bio-Sensing of Exosomes by Using a Gold Nano-Island Platform

A bio-sensing method, based on the plasmonic property of gold nano-islands, has been developed for detection of exosomes in a clinical setting. The position of the gold plasmon band in the UV-Visible spectrum depends on the size and shape of gold nanoparticles as well as on the surrounding environment. By adsorbing various chemical entities, or binding them, the gold plasmon band will shift toward longer wavelengths and the shift is proportional to the concentration. Exosomes transport cargoes of molecules and genetic materials to proximal and distal cells. Presently, the standard method for their isolation and quantification from body fluids is by ultracentrifugation, not a practical method to be implemented in a clinical setting. Thus, a versatile and cutting-edge platform is required to selectively detect and isolate exosomes for further analysis at clinical level. The new sensing protocol, instead of antibodies, makes use of a specially synthesized polypeptide (Vn96), to capture and quantify the exosomes from different media, by binding the heat shock proteins from exosomes. The protocol has been established and optimized by using a glass substrate, in order to facilitate the next stage, namely the transfer of the protocol to a microfluidic environment. After each step of the protocol, the UV-Vis spectrum was recorded and the position of gold Localized Surface Plasmon Resonance (LSPR) band was measured. The sensing process was modelled, taking into account the characteristics of the nano-island structure, prepared by thermal convection and annealing. The optimal molar ratios of the most important chemical entities, involved in the detection of exosomes were calculated as well. Indeed, it was found that the results of the sensing process depend on the two major steps: the molar ratios of streptavidin to biotin-PEG-Vn96 and, the final step, the capture of exosomes by the biotin-PEG-Vn96 complex. The microfluidic device designed for sensing of exosomes consists of a glass substrate, sealed by a PDMS layer that contains the channel and a collecting chamber. In the device, the solutions of linker, cross-linker, etc., are pumped over the gold nano-islands and an Ocean Optics spectrometer is used to measure the position of the Au plasmon band at each step of the sensing. The experiments have shown that the shift of the Au LSPR band is proportional to the concentration of exosomes and, thereby, exosomes can be accurately quantified. An important advantage of the method is the ability to discriminate between exosomes having different origins.

Enhancement of Raman Scattering using Photonic Nanojet and Whispering Gallery Mode of a Dielectric Microstructure

We report the enhancement of Raman scattering signal by one order of magnitude using photonic nanojet (PNJ) of a lollipop shaped dielectric microstructure (LSDM) fabricated by a pulsed CO₂ laser. Here, the PNJ is generated by illuminating sphere portion of the LSDM with non-resonant laser. Unlike the surface enhanced Raman scattering (SERS) technique, this technique is simple, and the obtained results are highly reproducible. In addition, an efficient technique is proposed to enhance the SERS signal with the help of high quality factor optical resonance (whispering gallery mode) of a LSDM. From the theoretical simulations, it has been found that at least an order of magnitude enhancement in the SERS signal could be achieved easily using the proposed technique. We strongly believe that this report will enable the research community for improving the Raman scattering signals.

Relaxation Dynamics of Quantum Emitters Resonantly Coupled to a Localized Surface Plasmon

We investigate relaxation dynamics of a quantum dipole emitter (QDE), e.g., a molecule or quantum dot, located near a metal nanoparticle (MNP) exhibiting a dipolar localized surface plasmon (LSP) resonance at the frequency of the QDE radiative transition. It is shown that under the condition of the QDE-MNP characteristic relaxation time being much shorter than that of the QDE in free-space but much longer than the LSP lifetime. It is also shown that energy dissipation in the QDE-MNP system is relatively weak with the probability of the photon emission being about 0.75, a number which, rather surprisingly, does not explicitly depend on the metal absorption characteristics. The degree of entanglement measured by the concurrency takes the maximum value, while the distances between the QDEs and metal ball approximately are equal.

Profile Controlled Gold Nanostructures Fabricated by Nanosphere Lithography for Localized Surface Plasmon Resonance

Localized surface plasmon resonance (LSPR) is the coherent oscillation of conductive electrons confined in noble metallic nanoparticles excited by electromagnetic radiation, and nanosphere lithography (NSL) is one of the cost-effective methods to fabricate metal nanostructures for LSPR. NSL can be categorized into two major groups: dispersed NSL and closely pack NSL. In recent years, gold nanocrescents and gold nanoholes with vertical sidewalls fabricated by dispersed NSL, and silver nanotriangles and gold nanocaps on silica nanospheres fabricated by closely pack NSL, have been reported for LSPR biosensing. This paper introduces several novel gold nanostructures fabricated by NSL in LSPR applications, including 3D nanostructures obtained by evaporating gold obliquely on dispersed nanospheres, nanoholes with slant sidewalls, and patchy nanoparticles on closely packed nanospheres, all of which render satisfactory sensitivity for LSPR sensing. Since the LSPR spectrum is very sensitive to the shape of the metal nanostructures, formulas are derived and software is developed for calculating the profiles of the obtainable metal nanostructures by NSL, for different nanosphere masks with different fabrication conditions. The simulated profiles coincide well with the profiles of the fabricated gold nanostructures observed under scanning electron microscope (SEM) and atomic force microscope (AFM), which proves that the software is a useful tool for the process design of different LSPR nanostructures.