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Mass detection finds new resonance
mt0704pg7-23.qxd
09/03/2004
09:48
Page 20
RESEARCH NEWS
Mass detection finds new resonance NANOTECHNOLOGY
Scanning electron micrograph of vaccinia virus particles on the 4 µm x 1.8 µm cantilever beam fabricated by Bashir and coworkers. (Copyright © 2004 American Institute of Physics.)
Researchers have recently fabricated nanoscale cantilevers that can detect masses in the femtogram and attogram range. The small size of the cantilevers means their resonant frequency changes significantly in response to small masses. Such nanoelectromechanical systems (NEMS) could find application in clinical diagnosis and combating bioterrorism. Harold G. Craighead and colleagues at Cornell University, Tel Aviv University, Israel, and the Institute of Bioengineering and Nanotechnology, Singapore fabricated Si cantilevers 165 nm thick, 500 nm wide, and 4 µm long with a 1 µm x 1 µm paddle at the end [Ilic et al., J. Appl. Phys. (2004) 95, DOI: 10.1063/1.1650542]. Under vacuum, it is possible to detect the mass of Au dots
and adsorbed thiolate layers with a sensitivity of 0.39 ag. A Purdue University team led by Rashid Bashir has used a similar Si cantilever to detect individual vaccinia viruses with average masses of 9.5 fg [Gupta et al., Appl. Phys. Lett. (2004) 84 (10), DOI: 10.1063/1.1667011]. “We have been able to marry the cantilever work with an actual biological test case,” says Bashir. “Our cantilevers are also used in air and are more amenable to integration into hand-held devices for actual use.” Bashir hopes to attach antibodies to the NEMS devices to detect specific viruses, something that Craighead’s group is also working on. “We have done similar, unpublished experiments that can detect the mass of antibody-bound viruses,” he says. Michael L. Roukes of the California Institute of Technology is working on similar NEMS mass sensors and filed a patent in 2001 that included data showing attogram sensitivity. “In the intervening years we have pushed our sensitivity to the zeptogram scale,” claims Roukes. His group has developed a system that can detect in situ adsorption of molecular species. “It allows us to ‘fire’ a very small number of molecules at the sensors and weigh them in real time,” says Roukes. “This is really what is necessary to turn NEMS mass sensing into true mass spectrometry.”
April 2004
A new study indicates how polymer structures could be engineered for controlled drug delivery in response to environmental signals. Chun Wang and coworkers from Massachusetts Institute of Technology and AP Pharma, Inc. have designed and produced polymer microspheres capable of delivering DNA vaccines to cells [Wang et al., Nat. Mater. (2004) 3 (3) 190]. DNA vaccines could offer a number of advantages over conventional ones, which use weakened or inactivated pathogens. Instead, DNA encoding a protein antigen is introduced directly into cells. The cells produce the antigen, eliciting an immune response. However, naked DNA is readily degraded in the body, so an efficient delivery system is necessary. The approach developed by Wang
observed using a fluorescence microscope. The researchers demonstrate the use of the composite nanoparticles for cell separation and detection. An antibody for cyclin E, a protein that is only expressed on the surface of breast cancer cells, is covalently attached to the nanoparticles. The antibody-labeled particles are incubated with a suspension of cancer cells. The cells are then separated from the solution and observed under a microscope. The team is currently assessing the separation capabilities of the particles. Preliminary measurements suggest that one cancer cell can be separated from 10 000 red blood cells. Jonathan Wood
Jonathan Wood
Jonathan Wood
NANOTECHNOLOGY
20
BIOMATERIALS
et al. involves encapsulating DNA in spherical poly(ortho ester) or POE particles, ~5 µm in diameter. Particles of this size are thought to be preferentially taken up by cells that play a role in initiating an immune response. POE was chosen as it degrades at weakly acidic pH to form nontoxic products without compromising the bioactivity of the DNA vaccine. Such pH values are found in the cell compartments in which the microspheres are taken up. The researchers show the efficacy of this delivery system in mice. “We have shown in our preliminary study that this approach is able to generate potent immune responses against a model antigen in animals and to suppress the growth of tumor,” says Wang. “These new biomaterials have significant potential in making DNA vaccination a clinical reality for combating viral infections (such as HIV) and cancer.”
Separate and detect Zeev Rosenzweig and colleagues at the University of New Orleans, Tulane University, and the Xavier University of Louisiana have synthesized nanoparticles that are both magnetic and luminescent [Wang et al., Nano Lett. (2004) DOI: 10.1021/nl035010n]. The particles could be used in a variety of biological technique involving magnetic separation followed by fluorescent detection. The particles consist of a shell of luminescent CdSe/ZnS quantum dots attached to a γ-Fe2O3 superparamagnetic core particle. The average diameter of the composite particles is 20 nm with a size variation of ±15%. The combined properties of the particles allow them to be separated from solution using a permanent magnet and easily
Responsive drug delivery
09/03/2004
09:48
Page 20
RESEARCH NEWS
Mass detection finds new resonance NANOTECHNOLOGY
Scanning electron micrograph of vaccinia virus particles on the 4 µm x 1.8 µm cantilever beam fabricated by Bashir and coworkers. (Copyright © 2004 American Institute of Physics.)
Researchers have recently fabricated nanoscale cantilevers that can detect masses in the femtogram and attogram range. The small size of the cantilevers means their resonant frequency changes significantly in response to small masses. Such nanoelectromechanical systems (NEMS) could find application in clinical diagnosis and combating bioterrorism. Harold G. Craighead and colleagues at Cornell University, Tel Aviv University, Israel, and the Institute of Bioengineering and Nanotechnology, Singapore fabricated Si cantilevers 165 nm thick, 500 nm wide, and 4 µm long with a 1 µm x 1 µm paddle at the end [Ilic et al., J. Appl. Phys. (2004) 95, DOI: 10.1063/1.1650542]. Under vacuum, it is possible to detect the mass of Au dots
and adsorbed thiolate layers with a sensitivity of 0.39 ag. A Purdue University team led by Rashid Bashir has used a similar Si cantilever to detect individual vaccinia viruses with average masses of 9.5 fg [Gupta et al., Appl. Phys. Lett. (2004) 84 (10), DOI: 10.1063/1.1667011]. “We have been able to marry the cantilever work with an actual biological test case,” says Bashir. “Our cantilevers are also used in air and are more amenable to integration into hand-held devices for actual use.” Bashir hopes to attach antibodies to the NEMS devices to detect specific viruses, something that Craighead’s group is also working on. “We have done similar, unpublished experiments that can detect the mass of antibody-bound viruses,” he says. Michael L. Roukes of the California Institute of Technology is working on similar NEMS mass sensors and filed a patent in 2001 that included data showing attogram sensitivity. “In the intervening years we have pushed our sensitivity to the zeptogram scale,” claims Roukes. His group has developed a system that can detect in situ adsorption of molecular species. “It allows us to ‘fire’ a very small number of molecules at the sensors and weigh them in real time,” says Roukes. “This is really what is necessary to turn NEMS mass sensing into true mass spectrometry.”
April 2004
A new study indicates how polymer structures could be engineered for controlled drug delivery in response to environmental signals. Chun Wang and coworkers from Massachusetts Institute of Technology and AP Pharma, Inc. have designed and produced polymer microspheres capable of delivering DNA vaccines to cells [Wang et al., Nat. Mater. (2004) 3 (3) 190]. DNA vaccines could offer a number of advantages over conventional ones, which use weakened or inactivated pathogens. Instead, DNA encoding a protein antigen is introduced directly into cells. The cells produce the antigen, eliciting an immune response. However, naked DNA is readily degraded in the body, so an efficient delivery system is necessary. The approach developed by Wang
observed using a fluorescence microscope. The researchers demonstrate the use of the composite nanoparticles for cell separation and detection. An antibody for cyclin E, a protein that is only expressed on the surface of breast cancer cells, is covalently attached to the nanoparticles. The antibody-labeled particles are incubated with a suspension of cancer cells. The cells are then separated from the solution and observed under a microscope. The team is currently assessing the separation capabilities of the particles. Preliminary measurements suggest that one cancer cell can be separated from 10 000 red blood cells. Jonathan Wood
Jonathan Wood
Jonathan Wood
NANOTECHNOLOGY
20
BIOMATERIALS
et al. involves encapsulating DNA in spherical poly(ortho ester) or POE particles, ~5 µm in diameter. Particles of this size are thought to be preferentially taken up by cells that play a role in initiating an immune response. POE was chosen as it degrades at weakly acidic pH to form nontoxic products without compromising the bioactivity of the DNA vaccine. Such pH values are found in the cell compartments in which the microspheres are taken up. The researchers show the efficacy of this delivery system in mice. “We have shown in our preliminary study that this approach is able to generate potent immune responses against a model antigen in animals and to suppress the growth of tumor,” says Wang. “These new biomaterials have significant potential in making DNA vaccination a clinical reality for combating viral infections (such as HIV) and cancer.”
Separate and detect Zeev Rosenzweig and colleagues at the University of New Orleans, Tulane University, and the Xavier University of Louisiana have synthesized nanoparticles that are both magnetic and luminescent [Wang et al., Nano Lett. (2004) DOI: 10.1021/nl035010n]. The particles could be used in a variety of biological technique involving magnetic separation followed by fluorescent detection. The particles consist of a shell of luminescent CdSe/ZnS quantum dots attached to a γ-Fe2O3 superparamagnetic core particle. The average diameter of the composite particles is 20 nm with a size variation of ±15%. The combined properties of the particles allow them to be separated from solution using a permanent magnet and easily
Responsive drug delivery