Even less invasive than these optical nanoprobes is a novel ultrasonic holography technique that provides a noninvasive way of looking inside a cell.
Nanomaterial-based drug delivery and nanotoxicology are two of the areas that require sophisticated methods and techniques for characterizing, testing, and imaging nanoparticulate matter inside the body. In particular, the potential risk factors of certain nanomaterials have become a topic of heated discussion.Most, if not all, toxicological studies on nanoparticles rely on current methods,practices, and terminology as gained and applied in the analysis of micro- and ultrafine particles and mineral fibers. The development of novel imaging techniques that can visualize local populations of nanoparticles at nanometer resolution within the structures of cells—without destroying or damaging the cells—is therefore important.
Researchers in the United States have demonstrated that at ultrasonic frequencies, intracellular nanomaterial causes sufficient wave scattering that a probe outside the cell can respond to it.
‘‘The novelty of our findings lies in the fact that it provides an alternative way of studying a cell under ambient conditions, i.e. without placing it in a vacuum,coating it with a metal, bombarding it with electrons, or inserting other molecules, as is the case with other techniques such as electron microscopy or fluorescent tagging,’’ explains Ali Passian, a researcher with the Nanoscale Science and Devices Group at the Oak Ridge National Laboratory (ORNL) in Tennessee, USA.
‘‘The use of nanomaterials is becoming ubiquitous and there is therefore a pressing need to understand how engineered nanomaterials interact with biological species,’’ Passian says. ‘‘Health effects and environmental factors are currently of major importance in our group at ORNL and a lot of our research resources have been focused on tackling the associated problems.’’
He points out that with this novel imaging technique, scientists do not need to cut up the cell or inject artificial light-emitting molecules to find out whether or not a certain type of nanomaterial is present inside it. This avoids altering the intracellular configuration when attempting to pinpoint the nanoparticles.
The relatively new technique known as scanning near field ultrasound holography (SNFUH) is a revolutionary approach which provides noninvasive nanoscale imaging capabilities for deeply buried and embedded structures. It offers the ability to acquire simultaneous topography and holography information with nanoscale image resolution. SNFUH synergistically integrates three disparate approaches: a unique combination of SPM platform (which enjoys excellent lateral and vertical resolution) coupled to microscale ultrasound source and detection (which facilitates ‘looking’ deeper into structures, section by section) and a novel holography approach (to enhance phase resolution and phase coupling in imaging).
Applying these techniques to biological structures, it becomes possible to image soft samples and probe structures that are below their surfaces. For instance, if a cell is oscillated at megahertz frequencies using a piezoelectric crystal, the ultrasonic waves traveling through the oscillating cell structure may weakly drive an AFM cantilever that is in contact with the cell surface, as long
as the elastic properties of the cell can support a propagation mode in the ultrasonic spectrum.
In their work, Passian and his team explored the viability of SNFUH as a technique to probe cellular uptake of nanoparticles. Specifically, they tried to determine the cellular fate of single-walled carbon nanohorns (carbon nanotubes aggregates having conical tips are referred to as carbon nanohorns)using a mouse model to detect and visualize particles within lavage cells and blood.
‘‘We found that the nanoparticles cause sufficient phase change for it to be measured with an external probe,’’ he describes the research findings. ‘‘Bear in mind that the nanoparticles were not artificially placed within the cell but got there as a result of exposing a living mouse to carbon nanohorns and then sacrificing the mouse a few days later and preparing the sample cells.’’ ‘‘The sizes of these particles are statistically consistent with the size distribution (70–110 nm) established from analyzing several AFM images of the nanohorn solution, indicating that individual nanoparticles, rather than larger aggregates, were taken up by the macrophages,’’ explains Passian.
‘‘The contrast measures the phase of the local tip–cell surface coupling and originates from the difference in elasticity and density between the nanohorns and the cell.’’
This work clearly demonstrates that specific problems that require subsurface knowledge can be tackled using this technique. This will mostly benefit research areas such as nanotoxicological investigations, drug delivery, and pharmaceutical work where, so far, most studies can only target the surface of samples and suffer from the lack of probes that can, with nanoscale resolution, provide information on what may be within a sample.
Passian explains the team’s next challenge: ‘‘Our next step is to enable our approach to visualize the interior of a cell in its natural milieu, that is, in a fluid.’’
Featured scientist: Ali Passian
Organization: Nanoscale Science and Devices Group, Oak Ridge
National Laboratory, Oak Ridge, TN, USA
Relevant publication: Laurene Tetard, Ali Passian, Katherine T.
Venmar, Rachel M. Lynch, Brynn H. Voy, Gajendra Shekhawat,
Vinayak P. Dravid, Thomas Thundat: Imaging nanoparticles in cells
by nanomechanical holography. Nat. Nanotechnol., 3, 501–505.
Source
Nano-Society
www.rsc.org/nanoscience
Nanomaterial-based drug delivery and nanotoxicology are two of the areas that require sophisticated methods and techniques for characterizing, testing, and imaging nanoparticulate matter inside the body. In particular, the potential risk factors of certain nanomaterials have become a topic of heated discussion.Most, if not all, toxicological studies on nanoparticles rely on current methods,practices, and terminology as gained and applied in the analysis of micro- and ultrafine particles and mineral fibers. The development of novel imaging techniques that can visualize local populations of nanoparticles at nanometer resolution within the structures of cells—without destroying or damaging the cells—is therefore important.
Researchers in the United States have demonstrated that at ultrasonic frequencies, intracellular nanomaterial causes sufficient wave scattering that a probe outside the cell can respond to it.
‘‘The novelty of our findings lies in the fact that it provides an alternative way of studying a cell under ambient conditions, i.e. without placing it in a vacuum,coating it with a metal, bombarding it with electrons, or inserting other molecules, as is the case with other techniques such as electron microscopy or fluorescent tagging,’’ explains Ali Passian, a researcher with the Nanoscale Science and Devices Group at the Oak Ridge National Laboratory (ORNL) in Tennessee, USA.
‘‘The use of nanomaterials is becoming ubiquitous and there is therefore a pressing need to understand how engineered nanomaterials interact with biological species,’’ Passian says. ‘‘Health effects and environmental factors are currently of major importance in our group at ORNL and a lot of our research resources have been focused on tackling the associated problems.’’
He points out that with this novel imaging technique, scientists do not need to cut up the cell or inject artificial light-emitting molecules to find out whether or not a certain type of nanomaterial is present inside it. This avoids altering the intracellular configuration when attempting to pinpoint the nanoparticles.
The relatively new technique known as scanning near field ultrasound holography (SNFUH) is a revolutionary approach which provides noninvasive nanoscale imaging capabilities for deeply buried and embedded structures. It offers the ability to acquire simultaneous topography and holography information with nanoscale image resolution. SNFUH synergistically integrates three disparate approaches: a unique combination of SPM platform (which enjoys excellent lateral and vertical resolution) coupled to microscale ultrasound source and detection (which facilitates ‘looking’ deeper into structures, section by section) and a novel holography approach (to enhance phase resolution and phase coupling in imaging).
Applying these techniques to biological structures, it becomes possible to image soft samples and probe structures that are below their surfaces. For instance, if a cell is oscillated at megahertz frequencies using a piezoelectric crystal, the ultrasonic waves traveling through the oscillating cell structure may weakly drive an AFM cantilever that is in contact with the cell surface, as long
as the elastic properties of the cell can support a propagation mode in the ultrasonic spectrum.
In their work, Passian and his team explored the viability of SNFUH as a technique to probe cellular uptake of nanoparticles. Specifically, they tried to determine the cellular fate of single-walled carbon nanohorns (carbon nanotubes aggregates having conical tips are referred to as carbon nanohorns)using a mouse model to detect and visualize particles within lavage cells and blood.
‘‘We found that the nanoparticles cause sufficient phase change for it to be measured with an external probe,’’ he describes the research findings. ‘‘Bear in mind that the nanoparticles were not artificially placed within the cell but got there as a result of exposing a living mouse to carbon nanohorns and then sacrificing the mouse a few days later and preparing the sample cells.’’ ‘‘The sizes of these particles are statistically consistent with the size distribution (70–110 nm) established from analyzing several AFM images of the nanohorn solution, indicating that individual nanoparticles, rather than larger aggregates, were taken up by the macrophages,’’ explains Passian.
‘‘The contrast measures the phase of the local tip–cell surface coupling and originates from the difference in elasticity and density between the nanohorns and the cell.’’
This work clearly demonstrates that specific problems that require subsurface knowledge can be tackled using this technique. This will mostly benefit research areas such as nanotoxicological investigations, drug delivery, and pharmaceutical work where, so far, most studies can only target the surface of samples and suffer from the lack of probes that can, with nanoscale resolution, provide information on what may be within a sample.
Passian explains the team’s next challenge: ‘‘Our next step is to enable our approach to visualize the interior of a cell in its natural milieu, that is, in a fluid.’’
Featured scientist: Ali Passian
Organization: Nanoscale Science and Devices Group, Oak Ridge
National Laboratory, Oak Ridge, TN, USA
Relevant publication: Laurene Tetard, Ali Passian, Katherine T.
Venmar, Rachel M. Lynch, Brynn H. Voy, Gajendra Shekhawat,
Vinayak P. Dravid, Thomas Thundat: Imaging nanoparticles in cells
by nanomechanical holography. Nat. Nanotechnol., 3, 501–505.
Source
Nano-Society
www.rsc.org/nanoscience
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