Rolf Loch
Although there are many techniques for cancer diagnosis and treatment, there is still a need for techniques that are more accurate and/or less invasive to the body. One promising scheme, which is useful for diagnosis as well as therapy, is to attach gold nanoparticles to tumor cells and illuminate them with infrared laser light. This technique is much less invasive than chemotherapy, X-ray therapy or surgery. Magnetic resonance imaging is noninvasive and capable of detecting cancer tumors when they are very small, but the equipment and its operation are very expensive, meaning that it is often used at a later stage, when the cancer is already more advanced. Ultrasound therapy offers a much cheaper alternative, but the high intensity sound waves that are necessary for treatment cause tissue heating and cavitation (creation of small pockets of gas in the bodily fluids or tissues that expand and contract/collapse). The long term influence of these side effects are still not known.
Because of their extremely small size, nanoparticles restrict the motion of electrons in one or more directions. This restriction, called quantum confinement, allows the properties of the particles to be modified by changing their size, in contrast to bulk material whose properties are independent of size. In particular, the properties of the surface become dominant and, in the case of noble metals, resonant electromagnetic radiation will induce large surface electric fields that enhance their radiative properties. This means that the particles absorb much more light than would normally be expected and the light that is not absorbed is scattered much more strongly than expected. This absorption and scattering is typically orders of magnitude stronger than the most strongly absorbing molecules and organic dyes. It has been found that gold nanorods and nanocages exhibit strong infrared (IR) absorption and biological compatibility, making them good candidates for use in biological systems. Huang et al. grew gold nanorods of different sizes and showed that different aspect ratios between the rod diameter and the length resulted in different absorption spectra. This showed that it is possible to produce biologically compatible nanoparticles with different optical properties. For further investigation, they chose nanoparticles with an aspect ratio of 3.9 because the absorption band overlaps the wavelength at 800 nm, which is the wavelength of a commercial Ti:sapphire laser. Furthermore, this wavelength is in a region where the light extinction of the human tissue is a minimum, resulting in a penetration depth up to 10 cm, which means that almost the whole human body is accessible.
Due to their strong scattering, gold nanorods have excellent potential as optical contrast agents for molecular imaging. Furthermore, the strongly absorbed IR radiation can be converted into heat efficiently, making it a promising potential photothermal therapeutic agent. In photothermal therapy, optical radiation is absorbed and transformed into heat. The heat causes the proteins and DNA to denature, irreversibly damaging the cell and, consequently, causing its death. Usually, photothermal therapy is done with visible light, which is absorbed by the agent as well as the tissue. The use of IR radiation is favourable because cell tissue is transparent to IR light, making it possible to diagnose and treat tumor cells deeper in the body. The convenient characteristic bioconjugation (binding to biomolecules) of gold nanostructures improves the target selectivity, so that they can stick to particular proteins, which makes it possible to target cancer cells with the nanoparticles and ensure that unhealthy cells receive most of the energy during therapy. As a result, the photothermal destruction of surrounding healthy tissue is minimized and the damage is much less than that caused during x-ray therapy.
Many cancer cells have copies of a protein, called Epidermal Growth Factor Receptor (EGFR), at their surface, which normal healthy tissue cells either do not have or have much fewer copies than cancer cells. The anti-EGFR antibody will naturally attach itself to this protein, which means that nanorods with anti-EGFR on their surface will end up attached to the surfaces of cancer cells. In the article from Huang et al., a synthetic method has been described to attach the gold nanorods to anti-EGFR antibodies. The process begins by coating the nanorods in a bilayer of cetyltrimethyl-ammonium bromide (CTAB). This is then exposed to polystyrenesulfonate (PSS) before the prepared nanorods are mixed with an antibody solution. The antibodies are probably bound to the PSS-coated nanorods by a mechanism called electrostatic physisorption or physical adsorption. This means that liquid molecules only adhere to the surface of a solid through a weak intermolecular interaction, called the Van der Waals force.
Consecutively, Huang et al. cultured (grow under controlled conditions) nonmalignant and malignant cells and immersed them into the anti-EGFR-conjugated nanorods solution for 30 minutes. They showed, by using surface plasmon resonant absorption spectroscopy (a standard technique to measure adsorption on surfaces of nanoparticles) and light scattering imaging, that the malignant cells are easily distinguished from the noncancerous cells due to the larger amount of EGFR on the malignant cells and consequent high concentration of nanorods.
By irradiating the samples with a continuous wave Ti:sapphire laser at different power densities, and successively staining them with a blue dye that only dead cells accumulate, it was shown that the intensity required to cause the destruction of malignant cells (10 W/cm2) is half the value necessary to cause death of normal healthy cells (20 W/cm2). Thus, the researchers have demonstrated the potential for gold nanorods to improve the efficacy of photothermal therapy. In another study by Chen et al., it was found that gold nanocages further lower the intensity threshold required to destroy cancerous cells to 1.5 W/cm2.
In conclusion, the combination of nanotechnology and lasers, in the form of IR irradiated bioconjugated gold nanoparticles, can potentially be of use to effectively and safely diagnose and treat cancer, even in deeper parts of the human body. Primary fluorescent tests with mice were successfully performed by H. Wang et al. by injecting nanorods and imaging them as they flowed through blood vessels before these nanoparticles were, presumably, filtered out of the blood by the kidneys. Thus, we can expect that this promising, minimally invasive and cheap technique has shown great success in early trials. It has the potential to diagnose and treat any type of cancer, and, if proved safe, will become available for routine use in hospitals in the near future.
Monday, December 17, 2007
Monday, December 3, 2007
An innovative containment system for nuclear reactor accidents
Martijn Hendrikx
In response to safety concerns over nuclear Pressurized Water Reactors (PWR), researchers have been investigating innovative ways to prevent and mitigate accidents. A recent development in this research is the concept of containing the molten reactor material that may form during an accident, which is called corium.
To understand and control the formation of corium, a detailed understanding of the thermodynamics of PWR reactors is required. A PWR reactor produces heat through the fission of nuclear fuel (primarily uranium). The fuel is shaped in rods, which are interspersed with rods made from a material that absorbs neutrons strongly to control the fission process. Heat is removed by water flowing along the rods. To prevent the water from boiling, it is kept under high pressure in the reactor vessel, which is made from steel. These elements constitute the core of the nuclear reactor.
Corium is a very hot mixture of molten nuclear fuel and molten reactor components, and may appear similar to lava. It is highly radioactive, dangerous, and is only formed when the operators lose control of the nuclear reaction and the vessel becomes hot enough to melt various components of the core. In the context of reactor safety, special attention will be devoted to the phenomenon of the 'heat knife.' A heat knife is a localized peak in heat transfer rate within the vessel wall, capable of inducing vessel damage. Its formation is the result of melt stratification due to density differences of oxide and metallic compounds present in the corium melt bath. It is evident that the release of corium, which is especially probable if a heat knife forms, into the environment should be prevented at all cost.
Since the control of an accident depends on the specific thermodynamic properties of the reactor core, the researchers have focused their attention on a particular type of reactor: the Russian VVER reactor, the power of which is indicated by a numerical suffix (in Megawatts).
The safety systems presented here prevent the release of corium into the environment. In order to meet modern requirements, they must be based on natural physical forces. Two approaches, based on the treatment and localization of the corium melt (which is called 'catching'), have been proposed. The first approach aims at retaining the corium inside the vessel (in-vessel catchers), whereas the second is based on ameliorating the situation after a substantial amount of corium has been released from the containing vessel (ex-vessel catchers).
In the unfortunate event of corium formation inside the reactor vessel, one should attempt to prevent it from escaping into the environment. Escape is only possible when the hot corium has melted a substantial layer of the vessel wall material, allowing its penetration. A straightforward way to prevent this is by using the concept of in-vessel catchers introduced in 1994, which relies on externally cooling the vessel to protect its integrity.
The cooling mechanism relies on natural circulation of the large amount of water inside the reactor as well as on the flow of boiling water along its exterior surface (boiling water can act as a coolant here due to temperature differences). The heat transfer rate should be large enough to reduce, or at least stabilize, the temperature of the corium inside the vessel, but, on the other hand, it should not exceed some upper limit from which the intense energy flow damages the vessel wall.
The importance of using the correct heat transfer rate has been demonstrated in experimental and theoretical studies. The heat transfer rate is governed by the mass flow rate and the vapor quality, and hence, an appropriate hydraulic circuit can easily satisfy the heat flow requirements. Moreover, it was shown that the thickness of the vessel wall that is unaffected by the corium also determines whether the cooling is effective in retaining the corium.
In the following text, the feasibility of implementing the water jacket safety concept is discussed for various types of reactors. It is already known that for VVER440 reactors, the physical parameters mentioned (heat transfer rate, unaffected wall thickness) allow the water jacket concept to function. However, due to inferior commercial competitiveness of this reactor type, it is important to look at more powerful reactors (640MW, 1000MW and 1500MW) as well.
Fore the case of the VVER-640 reactor, calculations show that the heat flux (this is the heat flow per unit area) at the inner wall depends on two parameters. First, on the melt bath composition, which is subject to continuous change as the core melts. Second, it depends on the thickness of the molten steel layer of the melt bath. When this layer is 30 mm thick, the flux attains its maximum value. Due to the spread of heat over the thick vessel wall, the exterior surface flux is lower than the interior flux. Calculations show that cooling the exterior surface of the VVER-640 reactor vessel is an effective way to reduce the core-melting rate and to retain the corium melt. This information makes the implementation of water jacket in-vessel catcher an attractive option for the VVER-640 reactor.
For the VVER1000 and VVER-1500 reactors however, the water jacket cooling is insufficient. For these larger reactors, the heat flux levels will exceed the safety limits, inevitably resulting in the melt penetrating the vessel wall. Furthermore, new experimental results show that the corium melt is more complicated than previously thought.
In 2004, the Aleksandrov Research Institute of Technology (NITI) produced new experimental data on the corium melt composition. It turned out that inverse stratification of the melt could occur as a result of interactions between its various components. The swapped configuration of melt bath layers excludes heat knife development and may, thus, seem beneficial at first sight. Unfortunately, it also enables the subsequent formation of a three-layer structure (steel-oxide-steel), which does supports heat-knife formation. This means that two counteracting mechanisms have been identified and it remains uncertain which mechanism will be dominant. Furthermore, experiments at OIVT RAN (A Russian research institute) show that an homogenized melt bath with globules of iron may result from corium-steel interaction. Consequently, the heat flux distribution and heat knife formation probability remain uncertain. This has made it impossible to introduce the concept of in-vessel catchers into reactors with capacities above 440 MW. Instead, mitigation has concentrated on containing the corium once it leaves the vessel.
An ex-vessel catcher essentially consists of a basket containing a large volume of sacrificial material (iron- and aluminum oxides). This basket is located below the reactor vessel and is combined with a heat exchanger. When corium leaks from the vessel, it flows into this basket and interacts with the sacrificial material.
The interaction between corium and sacrificial material has many favorable effects. It reduces the heat flow rate thanks to its endothermic nature, excludes heat knife formation (due to inverse stratification), enables water delivery for cooling, prevents the hazardous release of hydrogen, stops nuclear chain reactions in the melt due to its neutron absorbing properties, and, finally, reduces the release of aerosols and gases. The high efficiency of these mechanisms is persistent, as it cannot be affected by the production of more corium.
Ex-vessel catchers can, thus, be implemented in larger reactors (VVER-640, VVER-1000, VVER-1500). The main drawback remains, however, that the treatment of corium only starts after the penetration of the reactor vessel, which is undesirable. Now, however, researchers have started to look at placing ex-vessel corium catchers inside the vessel.
It has been found that sacrificial material, placed in an isolated compartment at the bottom of the reactor vessel, which is extended in length by several meters, can act as an effective in-vessel catcher. In an accident scenario, the corium will enter this compartment and interact endothermically with the material. Outside the vessel, a water jacket is used to remove excess heat. The corium treatment is similar to that of the ex-vessel approach described above, the difference being that catching of the corium happens inside the vessel rather than below it. This novel approach, which clearly justifies the name 'in-vessel catcher', circumvents the main drawback of the ex-vessel catcher.
Assessments show that when the amount of sacrificial material matches the uranium dioxide mass in the core, melt stratification will occur, preventing heat knife formation. Furthermore, the radiation heat flux emanating from the hot melt bath (at around 2100 K) can be reduced by water flowing across the melt bath surface. Unfortunately, the required vessel-extension is rather expensive. However, costs are comparable to that of the ex-vessel catcher. Hence, from a financial point of view the two alternatives are equivalent.
The concept of in-vessel catchers is a promising technology that may improve the safety of nuclear reactors. It enables corium treatment inside the reactor vessel, keeping the environment safe from radioactive contamination. Further analysis is recommended.
In response to safety concerns over nuclear Pressurized Water Reactors (PWR), researchers have been investigating innovative ways to prevent and mitigate accidents. A recent development in this research is the concept of containing the molten reactor material that may form during an accident, which is called corium.
To understand and control the formation of corium, a detailed understanding of the thermodynamics of PWR reactors is required. A PWR reactor produces heat through the fission of nuclear fuel (primarily uranium). The fuel is shaped in rods, which are interspersed with rods made from a material that absorbs neutrons strongly to control the fission process. Heat is removed by water flowing along the rods. To prevent the water from boiling, it is kept under high pressure in the reactor vessel, which is made from steel. These elements constitute the core of the nuclear reactor.
Corium is a very hot mixture of molten nuclear fuel and molten reactor components, and may appear similar to lava. It is highly radioactive, dangerous, and is only formed when the operators lose control of the nuclear reaction and the vessel becomes hot enough to melt various components of the core. In the context of reactor safety, special attention will be devoted to the phenomenon of the 'heat knife.' A heat knife is a localized peak in heat transfer rate within the vessel wall, capable of inducing vessel damage. Its formation is the result of melt stratification due to density differences of oxide and metallic compounds present in the corium melt bath. It is evident that the release of corium, which is especially probable if a heat knife forms, into the environment should be prevented at all cost.
Since the control of an accident depends on the specific thermodynamic properties of the reactor core, the researchers have focused their attention on a particular type of reactor: the Russian VVER reactor, the power of which is indicated by a numerical suffix (in Megawatts).
The safety systems presented here prevent the release of corium into the environment. In order to meet modern requirements, they must be based on natural physical forces. Two approaches, based on the treatment and localization of the corium melt (which is called 'catching'), have been proposed. The first approach aims at retaining the corium inside the vessel (in-vessel catchers), whereas the second is based on ameliorating the situation after a substantial amount of corium has been released from the containing vessel (ex-vessel catchers).
In the unfortunate event of corium formation inside the reactor vessel, one should attempt to prevent it from escaping into the environment. Escape is only possible when the hot corium has melted a substantial layer of the vessel wall material, allowing its penetration. A straightforward way to prevent this is by using the concept of in-vessel catchers introduced in 1994, which relies on externally cooling the vessel to protect its integrity.
The cooling mechanism relies on natural circulation of the large amount of water inside the reactor as well as on the flow of boiling water along its exterior surface (boiling water can act as a coolant here due to temperature differences). The heat transfer rate should be large enough to reduce, or at least stabilize, the temperature of the corium inside the vessel, but, on the other hand, it should not exceed some upper limit from which the intense energy flow damages the vessel wall.
The importance of using the correct heat transfer rate has been demonstrated in experimental and theoretical studies. The heat transfer rate is governed by the mass flow rate and the vapor quality, and hence, an appropriate hydraulic circuit can easily satisfy the heat flow requirements. Moreover, it was shown that the thickness of the vessel wall that is unaffected by the corium also determines whether the cooling is effective in retaining the corium.
In the following text, the feasibility of implementing the water jacket safety concept is discussed for various types of reactors. It is already known that for VVER440 reactors, the physical parameters mentioned (heat transfer rate, unaffected wall thickness) allow the water jacket concept to function. However, due to inferior commercial competitiveness of this reactor type, it is important to look at more powerful reactors (640MW, 1000MW and 1500MW) as well.
Fore the case of the VVER-640 reactor, calculations show that the heat flux (this is the heat flow per unit area) at the inner wall depends on two parameters. First, on the melt bath composition, which is subject to continuous change as the core melts. Second, it depends on the thickness of the molten steel layer of the melt bath. When this layer is 30 mm thick, the flux attains its maximum value. Due to the spread of heat over the thick vessel wall, the exterior surface flux is lower than the interior flux. Calculations show that cooling the exterior surface of the VVER-640 reactor vessel is an effective way to reduce the core-melting rate and to retain the corium melt. This information makes the implementation of water jacket in-vessel catcher an attractive option for the VVER-640 reactor.
For the VVER1000 and VVER-1500 reactors however, the water jacket cooling is insufficient. For these larger reactors, the heat flux levels will exceed the safety limits, inevitably resulting in the melt penetrating the vessel wall. Furthermore, new experimental results show that the corium melt is more complicated than previously thought.
In 2004, the Aleksandrov Research Institute of Technology (NITI) produced new experimental data on the corium melt composition. It turned out that inverse stratification of the melt could occur as a result of interactions between its various components. The swapped configuration of melt bath layers excludes heat knife development and may, thus, seem beneficial at first sight. Unfortunately, it also enables the subsequent formation of a three-layer structure (steel-oxide-steel), which does supports heat-knife formation. This means that two counteracting mechanisms have been identified and it remains uncertain which mechanism will be dominant. Furthermore, experiments at OIVT RAN (A Russian research institute) show that an homogenized melt bath with globules of iron may result from corium-steel interaction. Consequently, the heat flux distribution and heat knife formation probability remain uncertain. This has made it impossible to introduce the concept of in-vessel catchers into reactors with capacities above 440 MW. Instead, mitigation has concentrated on containing the corium once it leaves the vessel.
An ex-vessel catcher essentially consists of a basket containing a large volume of sacrificial material (iron- and aluminum oxides). This basket is located below the reactor vessel and is combined with a heat exchanger. When corium leaks from the vessel, it flows into this basket and interacts with the sacrificial material.
The interaction between corium and sacrificial material has many favorable effects. It reduces the heat flow rate thanks to its endothermic nature, excludes heat knife formation (due to inverse stratification), enables water delivery for cooling, prevents the hazardous release of hydrogen, stops nuclear chain reactions in the melt due to its neutron absorbing properties, and, finally, reduces the release of aerosols and gases. The high efficiency of these mechanisms is persistent, as it cannot be affected by the production of more corium.
Ex-vessel catchers can, thus, be implemented in larger reactors (VVER-640, VVER-1000, VVER-1500). The main drawback remains, however, that the treatment of corium only starts after the penetration of the reactor vessel, which is undesirable. Now, however, researchers have started to look at placing ex-vessel corium catchers inside the vessel.
It has been found that sacrificial material, placed in an isolated compartment at the bottom of the reactor vessel, which is extended in length by several meters, can act as an effective in-vessel catcher. In an accident scenario, the corium will enter this compartment and interact endothermically with the material. Outside the vessel, a water jacket is used to remove excess heat. The corium treatment is similar to that of the ex-vessel approach described above, the difference being that catching of the corium happens inside the vessel rather than below it. This novel approach, which clearly justifies the name 'in-vessel catcher', circumvents the main drawback of the ex-vessel catcher.
Assessments show that when the amount of sacrificial material matches the uranium dioxide mass in the core, melt stratification will occur, preventing heat knife formation. Furthermore, the radiation heat flux emanating from the hot melt bath (at around 2100 K) can be reduced by water flowing across the melt bath surface. Unfortunately, the required vessel-extension is rather expensive. However, costs are comparable to that of the ex-vessel catcher. Hence, from a financial point of view the two alternatives are equivalent.
The concept of in-vessel catchers is a promising technology that may improve the safety of nuclear reactors. It enables corium treatment inside the reactor vessel, keeping the environment safe from radioactive contamination. Further analysis is recommended.
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