Development and characterization of Au-YSZ surface plasmon resonance based sensing materials: high temperature detection of CO.

Au-YSZ nanocomposite films exhibited a surface plasmon resonance absorption band around 600 nm that underwent a reversible blue shift and narrowed upon exposure to CO in air at 500 degrees C. A linear dependence of the sensing signal was observed for CO concentrations ranging between 0.1 and 1 vol % in an air carrier gas. This behavior of the SPR band, upon exposure to CO, was not observed when using nitrogen as the carrier gas, indicating an oxygen-dependent reaction mechanism. Additionally, the SPR band showed no measurable signal change upon exposure to CO at temperatures below approximately 400 degrees C. The oxygen and temperature-dependent characteristics, coupled with the oxygen ion formation and conduction properties of the YSZ matrix, are indicative of charge-transfer reactions occurring at the three-phase boundary region between oxygen, Au, and YSZ, which result in charge transfer into the Au nanoparticles. These reactions are associated with the oxidation of CO and a corresponding reduction of the YSZ matrix. The chemical-reaction-induced charge injection into the Au nanoparticles results in the observed blue shift and narrowing of the SPR band.

Investigation of nerve injury through microfluidic devices.

Traumatic injuries, both in the central nervous system (CNS) and peripheral nervous system (PNS), can potentially lead to irreversible damage resulting in permanent loss of function. Investigating the complex dynamics involved in these processes may elucidate the biological mechanisms of both nerve degeneration and regeneration, and may potentially lead to the development of new therapies for recovery. A scientific overview on the biological foundations of nerve injury is presented. Differences between nerve regeneration in the central and PNS are discussed. Advances in microtechnology over the past several years have led to the development of invaluable tools that now facilitate investigation of neurobiology at the cellular scale. Microfluidic devices are explored as a means to study nerve injury at the necessary simplification of the cellular level, including those devices aimed at both chemical and physical injury, as well as those that recreate the post-injury environment.

A two-compartment organotypic model of mammalian peripheral nerve repair.

BACKGROUND: Schwann cells in the distal stump of transected nerve upregulate growth factors that support regeneration on a modality-specific basis. It is unclear, however, which of these preferentially support motor axon regeneration. Identification of these factors will require a model that can isolate growth factor effects to growing axons while reproducing the complex three-dimensional structure of peripheral nerve. NEW METHOD: A two-compartment PDMS base is topped by a collagen-coated membrane that supports a spinal cord cross-section above one compartment. Fluorescent motoneurons in this section reinnervate a segment of peripheral nerve that directs axons through a water-tight barrier to the second compartment, where nerve repair is performed. RESULTS: Motoneurons remain healthy for several weeks. The axons they project through the water-tight barrier survive transection and cross a nerve repair in substantial numbers to reinnervate an additional nerve segment. Fluidic isolation of the two compartments was confirmed with a dye leakage test, and the physiologic integrity of the system was tested by retrograde labeling of only those motor neurons to which tracer was exposed and by limitation of toxin effects to a single compartment. COMPARISON WITH EXISTING METHODS: Nerve repair cannot be modeled in monolayer cell culture. Our previous organotypic model accurately modeled nerve repair, but did not allow individual control of motoneuron and growth cone environments. CONCLUSIONS: This model isolates treatment effects to growing axons while reproducing the complex three-dimensional structure of peripheral nerve. Additionally, it facilitates surgical manipulation of tissues and high-resolution imaging.

Valve-based microfluidic compression platform: single axon injury and regrowth.

We describe a novel valve-based microfluidic axon injury micro-compression (AIM) platform that enables focal and graded compression of micron-scale segments of single central nervous system (CNS) axons. The device utilizes independently controlled "push-down" injury pads that descend upon pressure application and contact underlying axonal processes. Regulated compressed gas is input into the AIM system and pressure levels are modulated to specify the level of injury. Finite element modeling (FEM) is used to quantitatively characterize device performance and parameterize the extent of axonal injury by estimating the forces applied between the injury pad and glass substrate. In doing so, injuries are normalized across experiments to overcome small variations in device geometry. The AIM platform permits, for the first time, observation of axon deformation prior to, during, and immediately after focal mechanical injury. Single axons acutely compressed (~5 s) under varying compressive loads (0-250 kPa) were observed through phase time-lapse microscopy for up to 12 h post injury. Under mild injury conditions (< 55 kPa) ~73% of axons continued to grow, while at moderate (55-95 kPa) levels of injury, the number of growing axons dramatically reduced to 8%. At severe levels of injury (> 95 kPa), virtually all axons were instantaneously transected and nearly half (~46%) of these axons were able to regrow within the imaging period in the absence of exogenous stimulating factors.

Compartmentalized microfluidic culture platform to study mechanism of paclitaxel-induced axonal degeneration.

Chemotherapy induced peripheral neuropathy is a common and dose-limiting side effect of anticancer drugs. Studies aimed at understanding the underlying mechanism of neurotoxicity of chemotherapeutic drugs have been hampered by lack of suitable culture systems that can differentiate between neuronal cell body, axon or associated glial cells. Here, we have developed an in vitro compartmentalized microfluidic culture system to examine the site of toxicity of chemotherapeutic drugs. To test the culture platform, we used paclitaxel, a widely used anticancer drug for breast cancer, because it causes sensory polyneuropathy in a large proportion of patients and there is no effective treatment. In previous in vitro studies, paclitaxel induced distal axonal degeneration but it was unclear if this was due to direct toxicity on the axon or a consequence of toxicity on the neuronal cell body. Using microfluidic channels that allow compartmentalized culturing of neurons and axons, we demonstrate that the axons are much more susceptible to toxic effects of paclitaxel. When paclitaxel was applied to the axonal side, there was clear degeneration of axons; but when paclitaxel was applied to the soma side, there was no change in axon length. Furthermore, we show that recombinant human erythropoietin, which had been shown to be neuroprotective against paclitaxel neurotoxicity, provides neuroprotection whether it is applied to the cell body or the axons directly. This observation has implications for development of neuroprotective drugs for chemotherapy induced peripheral neuropathies as dorsal root ganglia do not possess blood-nerve-barrier, eliminating one of the cardinal requirements of drug development for the nervous system. This compartmentalized microfluidic culture system can be used for studies aimed at understanding axon degeneration, neuroprotection and development of the nervous system.