Laser-activated shape memory polymer microactuator for thrombus removal following ischemic stroke: preliminary in vitro analysis

Due to the narrow (3-h) treatment window for effective use of the thrombolytic drug recombinant tissue-type plasminogen activator (rt-PA), there is a need to develop alternative treatments for ischemic stroke. We are developing an intravascular device for mechanical thrombus removal using shape memory polymer (SMP). We propose to deliver the SMP microactuator in its secondary straight rod form (length=4 cm, diameter=350 /spl mu/m) through a catheter distal to the vascular occlusion. The microactuator, which is mounted on the end of an optical fiber, is then transformed into its primary corkscrew shape by laser heating (diode laser, /spl lambda/=800 nm) above its soft-phase glass transition temperature (T/sub gs/=55/spl deg/C). Once deployed, the microactuator is retracted, and the captured thrombus is removed to restore blood flow. The SMP is doped with indocyanine green (ICG) dye to increase absorption of the laser light. Successful deployment of the microactuator depends on the optical properties of the ICG-doped SMP, as well as the optical coupling efficiency of the interface between the optical fiber and the SMP. Spectrophotometry, thermal imaging, and computer simulation aided the initial design effort and continue to be useful tools for optimization of the dye concentration and laser power. Thermomechanical testing was performed to characterize the elastic modulus of the SMP. We have demonstrated laser activation of the SMP microactuator in air at room temperature, suggesting this concept is a promising therapeutic alternative to rt-PA.     

Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine

Indole-containing compounds demonstrate an array of biological activities relevant to numerous human diseases. The biological activities of diverse indole-based agents are driven by molecular interactions between indole agent and critical therapeutic target. The chemical inventory of medicinally useful or promising indole compounds spans the entire structural spectrum, from simple synthetic indoles to highly complex indole alkaloids. In an analogous fashion, the chemistry behind the indole heterocycle is unique and provides rich opportunities for extensive synthetic chemistry, enabling the construction and development of novel indole compounds to explore chemical space. This review will present heterocyclic chemistry of the indole nucleus, indole compounds of clinical use, complex indole alkaloids and indole-inspired discovery efforts by multiple research groups interested in using novel indole-containing small molecules to drive discoveries in human biology and medicine.     

Design, fabrication, and testing of a bistable electromagneticallyactuated microvalve

A bistable electromagnetically actuated microvalve was designed, processed, and tested. The valve was designed to control a water flow of 0.05-0.5 μs from a reservoir at a pressure of 1-2000 Pa. The two valve components were fabricated in silicon, the upper piece comprises an electroplated gold coil, and the lower piece is an Ni/Fe alloy beam. The bistable capability was achieved by balancing the elastic forces on the beam with the magnetic forces due to a 46-μm-thick rolled magnetic foil. The design includes the flow through the orifice, squeeze film damping due to beam motion, beam elasticity, and electromagnetics. The microvalve was tested for power consumption, flow rate, time response, Ni/Fe alloy composition, and magnetic foil properties. The valve operates at 1-2 V in both air and water     

A microfabricated electrochemical actuator for large displacements

A large-displacement electrochemical actuator was designed, fabricated, and tested. The large displacement is obtained by using a corrugated membrane made by physical vapor deposition of Parylene sandwiched with an intermediate layer of sputtered platinum. The layered structure is approximately 8-μm thick, with 26 grooves approximately 120-μm deep, and with a radial period of 350 μm. The electrochemical cell consists of platinum electrodes with a 1 M H₂ SO₄ solution. Hydrogen and oxygen gas is generated to displace the membrane. Although the actuator can operate at a voltage as low as 1.23 V, the experimentally determined efficiency of converting electrical energy to mechanical work is only 0.37%. The governing equations for the conservation of mass, momentum (equilibrium), energy, and the entropy generation rate were formulated assuming that the gas bubbles either nucleate without growth or grow without nucleation. For the nucleation case, simulations were performed for constant pressure isothermal actuation, and the average experimental efficiency was bounded by simulations with gas bubble radii between 1×10^-6 m and 1×10^-6 m. The predicted ratio of the power dissipated to the electrical power supplied is 1.37 for isothermal actuation