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Watching aluminum melt in picoseconds
RESEARCH NEWS
Needles on the microscale cause less pain BIOMATERIALS
Photograph shows an array of polymer microneedles that are 1000 µm high. (Courtesy of Mark R. Prausnitz, Georgia Institute of Technology.)
Researchers from the Georgia Institute of Technology have developed micrometer-scale needles to deliver drugs, proteins, and particles into the body with a minimum of pain [D. V. McAllister et al., Proc. Natl. Acad. Sci. USA (2003), 100 (24), 13755]. For over a century, hypodermic needles have been used to deliver drugs but their large size (compared to the drugs being delivered) is often unnecessary, causes pain, and has limited targeting ability. “We’ve opened up the potential use of microneedles for delivering a broad range of therapeutics,” says principal investigator Mark R. Prausnitz. “Fabricating both hollow and solid microneedles in a variety of shapes, sizes, and materials allows us to deliver large molecules with significant therapeutic interest such as insulin, proteins produced by the biotech industry, and nanoparticles that could encapsulate a drug or
demonstrate the ability to deliver a virus for vaccinations.” The researchers fabricated 1-1000 µm microneedles from metals, Si, glass, and biodegradable polymers using techniques originally developed for the microelectronics industry. Solid Si microneedles were etched from substrates using lithography and reactive ion etching (RIE). By using inductively coupled plasma RIE prior to the lithographic patterning and RIE steps, hollow microneedles can be formed. Si microneedle masters enable molds to be created from which metal microneedles can be fabricated by electrodeposition. Solid needles are simply formed by continuing plating until the molds are full. Polymer microneedles can be similarly fabricated by melting the material into polydimethylsiloxane micromolds, applying a vacuum, and peeling off the mold. Conventional drawn-glass micropipette techniques are used to create glass microneedles. Fabrication of metal and polymer microneedles could be readily carried out in a conventional manufacturing environment and these materials have established safety records in medical devices. Biodegradable polymers could be used, so that if microneedles break off in the skin, they simply disintegrate over time. The microneedles are large enough to allow delivery of small drugs, macromolecules, nanoparticles, and fluids, but sufficiently small to avoid causing pain because there are no nerves in 10-15 µm stratum corneum outer layer of skin. They enable highly targeted delivery, even on an intracellular level, and skin permeability to agents such as insulin is also increased. “We’ve shown that microneedles can serve as a hybrid drug delivery system, combining the advantages of conventional needles – which deliver drugs easily – with transdermal patches that are more patient-friendly,” says Prausnitz. “I expect that within the next five years a microneedle device will become available for clinical use.”
Watching aluminum melt in picoseconds METALS AND ALLOYS An atomic-level view of melting Al reveals that the solid shakes itself apart in under 3.5 ps. Researchers at the University of Toronto, Canada observed the solid-liquid transition in real time using diffraction patterns obtained with femtosecond electron pulses [Siwick et al., Science (2003) 302, 1382]. The experimental system built by Bradley J. Siwick and colleagues uses a laser-driven, 30 keV electron source. The photoactivated electron gun can provide sub-500 fs pulses with
6
January 2004
sufficient electron density to allow structure determinations. A laser pulse was used to drive the phase transition, superheating 20 nm thick films of Al above its melting point temperature. Electron diffraction patterns were obtained at delay intervals of 500 ps. The sequence of diffraction patterns reveals the atomic configuration of the material as it melts. The patterns change in 3.5 ps from a sequence of rings characteristic of the face-centered cubic structure of
polycrystalline Al to a single broad ring indicative of the liquid state. The data is characteristic of a transition propagated by oscillations of Al atoms from their equilibrium positions induced by the rapid heating from the laser pulse. The team also calculated the timedependent atomic pair correlation function from the diffraction patterns. The results confirm the loss of longdistance crystalline order, leaving only short-range correlations in the liquid state.
The researchers believe femtosecond electron diffraction offers a general technique that could provide atomic detail in other ultrafast transitions. They suggest condensed-phase processes, surface chemistry, and time-resolved protein crystallography are all candidates for investigation. “Chemists think of reactions in terms of atoms moving around as bonds are broken and formed,” says Jason R. Dwyer. “It is one of the dreams of chemistry to be able to actually watch that as it happens.”
Needles on the microscale cause less pain BIOMATERIALS
Photograph shows an array of polymer microneedles that are 1000 µm high. (Courtesy of Mark R. Prausnitz, Georgia Institute of Technology.)
Researchers from the Georgia Institute of Technology have developed micrometer-scale needles to deliver drugs, proteins, and particles into the body with a minimum of pain [D. V. McAllister et al., Proc. Natl. Acad. Sci. USA (2003), 100 (24), 13755]. For over a century, hypodermic needles have been used to deliver drugs but their large size (compared to the drugs being delivered) is often unnecessary, causes pain, and has limited targeting ability. “We’ve opened up the potential use of microneedles for delivering a broad range of therapeutics,” says principal investigator Mark R. Prausnitz. “Fabricating both hollow and solid microneedles in a variety of shapes, sizes, and materials allows us to deliver large molecules with significant therapeutic interest such as insulin, proteins produced by the biotech industry, and nanoparticles that could encapsulate a drug or
demonstrate the ability to deliver a virus for vaccinations.” The researchers fabricated 1-1000 µm microneedles from metals, Si, glass, and biodegradable polymers using techniques originally developed for the microelectronics industry. Solid Si microneedles were etched from substrates using lithography and reactive ion etching (RIE). By using inductively coupled plasma RIE prior to the lithographic patterning and RIE steps, hollow microneedles can be formed. Si microneedle masters enable molds to be created from which metal microneedles can be fabricated by electrodeposition. Solid needles are simply formed by continuing plating until the molds are full. Polymer microneedles can be similarly fabricated by melting the material into polydimethylsiloxane micromolds, applying a vacuum, and peeling off the mold. Conventional drawn-glass micropipette techniques are used to create glass microneedles. Fabrication of metal and polymer microneedles could be readily carried out in a conventional manufacturing environment and these materials have established safety records in medical devices. Biodegradable polymers could be used, so that if microneedles break off in the skin, they simply disintegrate over time. The microneedles are large enough to allow delivery of small drugs, macromolecules, nanoparticles, and fluids, but sufficiently small to avoid causing pain because there are no nerves in 10-15 µm stratum corneum outer layer of skin. They enable highly targeted delivery, even on an intracellular level, and skin permeability to agents such as insulin is also increased. “We’ve shown that microneedles can serve as a hybrid drug delivery system, combining the advantages of conventional needles – which deliver drugs easily – with transdermal patches that are more patient-friendly,” says Prausnitz. “I expect that within the next five years a microneedle device will become available for clinical use.”
Watching aluminum melt in picoseconds METALS AND ALLOYS An atomic-level view of melting Al reveals that the solid shakes itself apart in under 3.5 ps. Researchers at the University of Toronto, Canada observed the solid-liquid transition in real time using diffraction patterns obtained with femtosecond electron pulses [Siwick et al., Science (2003) 302, 1382]. The experimental system built by Bradley J. Siwick and colleagues uses a laser-driven, 30 keV electron source. The photoactivated electron gun can provide sub-500 fs pulses with
6
January 2004
sufficient electron density to allow structure determinations. A laser pulse was used to drive the phase transition, superheating 20 nm thick films of Al above its melting point temperature. Electron diffraction patterns were obtained at delay intervals of 500 ps. The sequence of diffraction patterns reveals the atomic configuration of the material as it melts. The patterns change in 3.5 ps from a sequence of rings characteristic of the face-centered cubic structure of
polycrystalline Al to a single broad ring indicative of the liquid state. The data is characteristic of a transition propagated by oscillations of Al atoms from their equilibrium positions induced by the rapid heating from the laser pulse. The team also calculated the timedependent atomic pair correlation function from the diffraction patterns. The results confirm the loss of longdistance crystalline order, leaving only short-range correlations in the liquid state.
The researchers believe femtosecond electron diffraction offers a general technique that could provide atomic detail in other ultrafast transitions. They suggest condensed-phase processes, surface chemistry, and time-resolved protein crystallography are all candidates for investigation. “Chemists think of reactions in terms of atoms moving around as bonds are broken and formed,” says Jason R. Dwyer. “It is one of the dreams of chemistry to be able to actually watch that as it happens.”