Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting Functions.

The development of biocompatible and nontoxic surface-enhanced Raman scattering (SERS) nanoparticles is of considerable current interest because of their attractive biomedical applications such as ultrasensitive in vitro diagnostics, in vivo tumor imaging, and spectroscopy-guided cancer surgery. However, current SERS nanoparticles are prepared and stored in aqueous solution, have limited stability and dispersibility, and are not suitable for lyophilization and storage by freeze-drying or other means. Here, we report a simple but robust method to coat colloidal SERS nanoparticles by naturally derived biomimetic red blood cell membranes (RBCM), leading to a dramatic improvement in stability and dispersibility under freeze-thawing, lyophilization, heating, and physiological conditions. The results demonstrate that the lyophilized SERS nanoparticles in the solid form can be readily dissolved and dispersed in physiological buffer solutions. A surprising finding is that the RBCM-coated SERS particles are considerably brighter (by as much as 5-fold) than PEGylated SERS particles under similar experimental conditions. This additional enhancement is believed to arise from the hydrophobic nature of RBCM's hydrocarbon chains, which is known to reduce electronic dampening and boost electromagnetic field enhancement. A further advantage in using biomimetic membrane coatings is that the bilayer membrane structure allows nonvalent insertion of molecular ligands for tumor targeting. In particular, we show that cyclic-RGD, a tumor-targeting peptide, can be efficiently inserted into the membrane coatings of SERS nanoparticles for targeting the ανß3 integrin receptors expressed on cancer cells. Thus, biomimetic RBCMs provide major advantages over traditional polyethylene glycols for preparing SERS nanoparticles with improved dispersibility, higher signal intensity, and more efficient biofunctionalization.

Merging Ion Concentration Polarization between Juxtaposed Ion Exchange Membranes to Block the Propagation of the Polarization Zone.

The ion concentration polarization (ICP) phenomenon is one of the most prevailing methods to preconcentrate low-abundance biological samples. The ICP induces a noninvasive region for charged biomolecules (i.e., the ion depletion zone), and targets can be preconcentrated on this region boundary. Despite the high preconcentration performances with ICP, it is difficult to find the operating conditions of non-propagating ion depletion zones. To overcome this narrow operating window, we recently developed a new platform for spatiotemporally fixed preconcentration. Unlike preceding methods that only use ion depletion, this platform also uses the opposite polarity of the ICP (i.e., ion enrichment) to stop the propagation of the ion depletion zone. By confronting the enrichment zone with the depletion zone, the two zones merge together and stop. In this paper, we describe a detailed experimental protocol to build this spatiotemporally defined ICP platform and characterize the preconcentration dynamics of the new platform by comparing them with those of the conventional device. Qualitative ion concentration profiles and current-time responses successfully capture the different dynamics between the merged ICP and the stand-alone ICP. In contrast to the conventional one that can fix the preconcentration location at only ~5 V, the new platform can produce a target-condensed plug at a specific location in the broad ranges of operating conditions: voltage (0.5-100 V), ionic strength (1-100 mM), and pH (3.7-10.3).