Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of chemotherapy for cancer, and has limited effective treatment options. Autologous conditioned serum (ACS) is an effective biologic therapy used by intra-articular injection for patients with osteoarthritis. However, ACS has not been systematically tested in the treatment of peripheral neuropathies such as CIPN. It has been generally assumed that the analgesic effect of this biologic therapy results from augmented concentrations of anti-inflammatory cytokines and growth factors. Here we report that a single intrathecal injection of human conditioned serum (hCS) produced long-lasting inhibition of paclitaxel chemotherapy-induced neuropathic pain (mechanical allodynia) in mice, without causing motor impairment. Strikingly, the analgesic effect of hCS in our experiments was maintained even 8 weeks after the treatment, compared with non-conditioned human serum (hNCS). Furthermore, the hCS transfer-induced pain relief in mice was fully recapitulated by rat or mouse CS transfer to mice of both sexes, indicating cross-species and cross-sex effectiveness. Mechanistically, CS treatment blocked the chemotherapy-induced glial reaction in the spinal cord and improved nerve conduction. Compared to NCS, CS contained significantly higher concentrations of anti-inflammatory and pro-resolving mediators, including IL-1Ra, TIMP-1, TGF-ß1, and resolvins D1/D2. Intrathecal injection of anti-TGF-ß1 and anti-Il-1Ra antibody transiently reversed the analgesic action of CS. Nanoparticle tracking analysis revealed that rat conditioned serum contained a significantly greater number of exosomes than NCS. Importantly, the removal of exosomes by high-speed centrifugation largely diminished the CS-produced pain relief, suggesting a critical involvement of small vesicles (exosomes) in the beneficial effects of CS. Together, our findings demonstrate that intrathecal CS produces a remarkable resolution of neuropathic pain mediated through a combination of small vesicles/exosomes and neuroimmune/neuroglial modulation.

Dispersion tuning and route reconfiguration of acoustic waves in valley topological phononic crystals.

The valley degree of freedom in crystals offers great potential for manipulating classical waves, however, few studies have investigated valley states with complex wavenumbers, valley states in graded systems, or dispersion tuning for valley states. Here, we present tunable valley phononic crystals (PCs) composed of hybrid channel-cavity cells with three tunable parameters. Our PCs support valley states and Dirac cones with complex wavenumbers. They can be configured to form chirped valley PCs in which edge modes are slowed to zero group velocity states, where the energy at different frequencies accumulates at different designated locations. They enable multiple functionalities, including tuning of dispersion relations for valley states, robust routing of surface acoustic waves, and spatial modulation of group velocities. This work may spark future investigations of topological states with complex wavenumbers in other classical systems, further study of topological states in graded materials, and the development of acoustic devices.

Acoustofluidic separation of cells and particles.

Acoustofluidics, the integration of acoustics and microfluidics, is a rapidly growing research field that is addressing challenges in biology, medicine, chemistry, engineering, and physics. In particular, acoustofluidic separation of biological targets from complex fluids has proven to be a powerful tool due to the label-free, biocompatible, and contact-free nature of the technology. By carefully designing and tuning the applied acoustic field, cells and other bioparticles can be isolated with high yield, purity, and biocompatibility. Recent advances in acoustofluidics, such as the development of automated, point-of-care devices for isolating sub-micron bioparticles, address many of the limitations of conventional separation tools. More importantly, advances in the research lab are quickly being adopted to solve clinical problems. In this review article, we discuss working principles of acoustofluidic separation, compare different approaches of acoustofluidic separation, and provide a synopsis of how it is being applied in both traditional applications, such as blood component separation, cell washing, and fluorescence activated cell sorting, as well as emerging applications, including circulating tumor cell and exosome isolation.

Theory and experiment on resonant frequencies of liquid-air interfaces trapped in microfluidic devices.

Bubble-based microfluidic devices have been proven to be useful for many biological and chemical studies. These bubble-based microdevices are particularly useful when operated at the trapped bubbles' resonance frequencies. In this work, we present an analytical expression that can be used to predict the resonant frequency of a bubble trapped over an arbitrary shape. Also, the effect of viscosity on the dispersion characteristics of trapped bubbles is determined. A good agreement between experimental data and theoretical results is observed for resonant frequency of bubbles trapped over different-sized rectangular-shaped structures, indicating that our expression can be valuable in determining optimized operational parameters for many bubble-based microfluidic devices. Furthermore, we provide a close estimate for the harmonics and a method to determine the dispersion characteristics of a bubble trapped over circular shapes. Finally, we present a new method to predict fluid properties in microfluidic devices and complement the explanation of acoustic microstreaming.

Tuning surface-enhanced Raman scattering from graphene substrates using the electric field effect and chemical doping.

Graphene recently has been demonstrated to support surface-enhanced Raman scattering. Here, we show that the enhancement of the Raman signal of methylene blue on graphene can be tuned by using either the electric field effect or chemical doping. Both doping experiments show that hole-doped graphene yields a larger enhancement than one which is electron-doped; however, chemical doping leads to a significantly larger modulation of the enhancements. The observed enhancement correlates with the changes in the Fermi level of graphene, indicating that the enhancement is chemical in nature, as electromagnetic enhancement is ruled out by hybrid electrodynamical and quantum mechanical simulations.

A single-layer, planar, optofluidic switch powered by acoustically driven, oscillating microbubbles.

Merging acoustofluidic mixing with optofluidic integration, we have demonstrated a single-layer, planar, optofluidic switch that is driven by acoustically excited oscillating microbubbles. The device was found to have a switching speed of 5 Hz, an insertion loss of 6.02 dB, and an extinction ratio of 28.48 dB. With its simplicity, low fluid consumption, and compatibility with other microfluidic devices, our design could lead to a line of inexpensive, yet effective optical switches for many lab-on-a-chip applications.

Shifts in plasmon resonance due to charging of a nanodisk array in argon plasma.

A method for generating charge-induced plasmonic shifts, using argon plasma to charge nanoparticle arrays, is presented. Particles develop a negative charge, due to enhanced collisions with high-temperature electrons, in low-temperature plasmas. The negative charge generated causes a blue shift in the localized surface plasmon resonance. The dynamics of the shift were recorded and discussed. This effect could be used as a real-time method for studying the dynamics for charging in plasma.

Single-step holographic fabrication of large-area periodically corrugated metal films.

We have developed a simple, high-throughput, and cost-effective method to fabricate one-dimensional and two-dimensional periodically corrugated silver films over centimeter scale areas. This fabrication uses a single-step holographic patterning technique with laser intensities as low as 88.8 mW/cm(2) to deposit silver nanoparticles directly from solution to create gratings with periodicities of 570 nm. A dip in the transmission spectrum for these samples is observed due to certain visible wavelengths coupling to surface plasmon polaritons (SPPs) and the peak wavelength of this dip has a linear relationship with the surrounding material's refractive index (RI) with a sensitivity of 553.4 nm/RIU. The figure of merit (the ratio of refractive index sensitivity to the full width at half maximum (FWHM)) is typically in the range of 12-23. Our technique enables single-step fabrication of uniform, sub-wavelength periodic metal structures over a large area with low cost. Such sub-wavelength periodic metal structures are promising candidates as disposable sensors in applications such as affordable environmental monitoring systems and point-of-care diagnostics.