A microfluidic device inspired by leaky tumor vessels for hematogenous metastasis mechanism research.

Endothelial intercellular pores of tumor vessels generally lead to enhanced interstitial flow and may facilitate the migration of tumor cells. The permeability of tumor vessels causes a concentration gradient of growth factors (CGGF) from blood vessels to tumor tissues, which is opposite to the direction of interstitial flow. In this work, exogenous chemotaxis under the CGGF is demonstrated as a mechanism of hematogenous metastasis. A bionic microfluidic device inspired by endothelial intercellular pores of tumor vessels has been designed to study the mechanism. A porous membrane vertically integrated into the device using a novel compound mold is utilized to mimic the leaky vascular wall. The formation mechanism of the CGGF caused by endothelial intercellular pores is numerically analyzed and experimentally verified. The migration behavior of U-2OS cells is studied in the microfluidic device. The device is divided into three regions of interest (ROI): primary site, migration zone, and tumor vessel. The number of cells in the migration zone increases significantly under the CGGF, but decreases under no CGGF, indicating tumor cells may be guided to the vascellum by exogenous chemotaxis. Transendothelial migration is subsequently monitored, demonstrating the successful replication of the key steps in vitro in the metastatic cascade by the bionic microfluidic device.

Franck-Condon Blockade and Aggregation-Modulated Conductance in Molecular Devices Using Aggregation-Induced Emission-Active Molecules.

We report an effective modulation of the quantum transport in molecular junctions consisting of aggregation-induced-emission(AIE)-active molecules. Theoretical simulations based on combined density functional theory and rate-equation method calculations show that the low-bias conductance of the junction with a single tetraphenylethylene (TPE) molecule can be completely suppressed by strong electron-vibration couplings, that is, the Franck-Condon blockade effect. It is mainly associated with the low-energy vibration modes, which is also the origin of the fluorescence quenching of the AIE molecule in solution. We further found that the conductance of the junction can be lifted by restraining the internal motion of the TPE molecule by either methyl substitution on the phenyl group or by aggregation, a mechanism similar to the AIE process. The present work demonstrates the correlation between optical processes of molecules and quantum transport in their junction, and thus opens up a new avenue for the application of AIE-type molecules in molecular electronics and functional devices.

Numerical investigations on the electromagnetic enhancement effect to tip-enhanced Raman scattering and fluorescence processes.

In the present work, we theoretically study the electromagnetic (EM) enhancement of the Raman and fluorescence signals for a molecule placed in a nanocavity formed by a metallic tip and substrate that mimics a tip-enhanced Raman scattering (TERS) setup using three-dimensional finite element method calculations. The influence of tip size and tip-molecule distance on the EM enhancements of the incident field as well as the radiative and non-radiative decay rates of the molecule are systematically investigated. Simulation results show that the maximum EM enhancement to the incident light as provided by the localized surface plasmon resonance in the nanocavity can reach ∼285 for the configuration considered in the present work. Meanwhile, it was found that, at the classical limit, decreasing the apex radius or the tip-molecule distance can both reduce the spatial distribution (as characterized by the full width at half maximum) of the Raman enhancement in a linear fashion. Moreover, simulation results show that the nonlocal dielectric response of the tip and the substrate plays a key role to the fluorescence quantum yield of the molecule. However, it was found that the strong EM excitation enhancement is the dominating factor for the tip enhanced fluorescence (TEF) effect and stronger fluorescence enhancement has been found when increasing the apex radius or reducing the tip-molecule distance with an incident wavelength of 532 nm. The best TERS and TEF enhancements were found to be ∼[Formula: see text] and ∼[Formula: see text], respectively, with the tip-molecule distance around 1 nm.

Density-matrix evaluation of the enhancement to resonant Raman scattering and fluorescence of molecules confined in metallic nanoparticle dimers.

In the present work we study the surface-enhanced resonant Raman scattering (SERRS) and fluorescence (SEF) spectra of a general model molecule confined in metallic dimers consisting of Ag, Au and hybrid AuAg nanoparticles (NPs). The electromagnetic (EM) enhancement factors were simulated by the generalized Mie scatting method and the scattering cross section of the molecules were obtained by density-matrix calculations. The influence of the size of the NPs and the separation between the dimer on the Raman scattering and fluorescence were systematically studied and analyzed in detail. It was found that the SERRS mainly related to EM enhancement and the SEF depended on the competition between EM enhancement and quantum yield, both of which could be controlled by tuning the radius and separation of the metallic dimers. The optimal radius of the NPs for SERRS were found to be around 30 nm for AgNPs, 40 nm for AuNPs and 50 nm for hybrid AuAgNPs. The strongest Raman enhancement as predicted by the theoretical simulations were 6.2 × 1010, 1.5 × 107 and 5.2 × 108 for the three types of structures, respectively. These results could offer valuable information for the design of metallic substrates for surface enhanced Raman and fluorescence measurements.