Potential, challenges and limitations. Automation through the increased adoption and development of HTS approaches can further streamline testing procedures, while eliminating the possibility of operator bias. HTS can also encourage research groups to establish databases on relevant toxicological determinants of MNMs, which will facilitate grouping and read across approaches for both innovation and regulation. The availability of a large database of reliable information about MNM toxicity generated through in vitro HTS methods will also arguably facilitate the prioritization of those materials that require in vivo testing and thus reduce the number of animals used in testing. Another benefit worth noting is that the faster scanning possible using an automated platform can increase the statistical power of results, through maximising the number of cells scored, while still saving time compared with visual scoring (Xxxxxxxxxx et al 2011). The reduction in cost and time for testing is however perhaps where HTS methods hold the greatest potential. It has recently been estimated that the time taken to complete evaluation of existing MNMs would be more than 30 years and the costs for testing them on an individual basis would be tremendous (Xxxx, 2009). The aforementioned HTS approaches for hazard assessment of MNMs clearly allows for a reduction in the time required for toxicity testing while increasing data outcomes. However, the cost-effectiveness of these approaches also needs to be considered. Cost-effectiveness analyses involve complex economic indicators and have been used to measure the relative value of a new or modified technology in terms of the cost per benefit gained. This type of analysis takes into account short-term costs, e.g. the cost per new endpoint identified or per time saved, and long-term costs, e.g. the cost per hazardous MNM identified versus the gains in terms of human disease prevention and environment protection. Thus, while short-term costs comprise mainly the direct costs associated with laboratory expenditure, the long-term costs are related to the societal costs and are much more complex to measure. Focusing merely on direct costs, HTS/HCA technologies are expected to reduce the costs of MNM development, as has happened in drug discovery (Xxxxxxxxx 2012), due to the greater number of NPs/NMs and experimental conditions simultaneously assayed, and the lower amounts of test samples and consumables required, provided that the adequate equipment or accessories are availabl...
Potential, challenges and limitations. OCs arguably have several benefits compared to the current approach of in vitro testing. An overview of these perceived benefits of OCs over static models is compiled in Table 2. Table 2: Overview of advantages of OC devices compared to traditional in vitro assays. Shear stress Shear stress is the stress on a surface (of e.g. a cell) caused by the physical force of the movement of liquid along this surface. It is established that cell behaviour is different in the presence of fluidic shear stress. Defined concentrations gradients Through the fluid flow of the culture medium, complex concentration grades are achievable. Repeated flow stream lamination can for example promote cell chemotaxis, i.e. the migration of cells (e.g. macrophages) in response to a stimulus. Homogenous chemical distribution in medium Only a small portion of the administered dose reaches the cell membrane. Colloidal behaviour, particle sedimentation and diffusion have to be taken into consideration when correcting for the initial dose at the start of the experiment. With microfluidics a homogenous suspension of chemicals in culture medium can be applied to the cell membrane under continuous perfusion, thereby creating a more physiological relevant situation. Micropatterning possible Micropatterning allows for improved control over homo- and heterotypic cell-cell interactions and easier 3D culturing. These micropatterns can be used to control the geometry of adhesion and therefore the orientation of the cell division axis and is needed for the maintenance of stem cells or the exact placement of cell on a sensor. Sensor integration With the integration of biosensors in the device itself, a more reliable and quantitative monitoring of cell behaviour can be obtained (e.g. electrical activity, cytotoxicity measurements, optical sensors, cell based bio-sensors, microscale patch clamp devices). Mechanical strains (Cyclic) mechanical strain can accentuate toxic and inflammatory effects and enhance the transport of particles over organ barriers High throughput screening Small size will eventually allow multiple tests in one plate and allow for robotic plating and reading. In addition, due to a highly controlled environment, it is possible to reduce the otherwise labour- intensive micromanipulations that can be required in experimental assays. Expanded cell viability High optimal control over environmental conditions for cell-based assays, including waste removal by medium flow, increases the ce...
Potential, challenges and limitations. The SbD concept clearly aims to reduce uncertainties associated with MNMs while they are still in development and therefore before they reach any market application. This has the potential to ensure that the risks of products launched in the market are known and managed, that the predicted benefits outweigh any residual risks, and that industrial actors reach a situation of regulatory preparedness as their products develop. It could also enhance the public trust that innovators care about human health and environmental safety in addition to their profit margins and potentially increase acceptability for (consumer) products containing MNMs where this may prove problematic. Through its implementation, it also holds the potential to create a closer collaboration not only between product developers and safety scientists but also between scientists, innovators and regulators in which all work together to further common aims of technology development that is safe for human health and the environment. However, there are some potential challenges for such an approach that should be recognised. Firstly, it is important to acknowledge that SbD was first utilised in an engineering industry in which there were known risks and uncertainties. For MNMs, however, we are still in the process of developing standards for safety testing and therefore we do not have a reliable body of knowledge on the risks that can simply be incorporated into design processes. This makes the applicability of this concept in practice very challenging for MNMs and the value and accuracy of any screening approaches, control banding, or grouping according to risk potentials still needs confirmation in practice. Furthermore, a close collaboration between industry and scientists may actually create challenges around the independence and autonomy of nanosafety scientists. This may not only be a challenge for the scientists themselves but also for public trust in the research and any products it may have supported. This has certainly been the case for biotechnology in which safety research that has been funded, supported or done in collaboration with industry has been regarded as problematic and not necessarily trustworthy. Concerns can, for example, exist around what a close collaboration between innovators and scientists would entail for publishing results with negative findings, and tensions can be foreseen on potential conflicting interests in (not) publishing research findings, depending on how ...
Potential, challenges and limitations. The concept of RRI offers significant potential for reorienting innovation processes and practices so as to enhance the social acceptability and environmental sustainability of new products. It also offers significant potential for working as a supplement or extension for the framework of SbD that is increasingly being adopted within the NANoREG project. This is due to the way in which it a) brings in questions focused on the purposes of innovation, b) it extends collaborative engagement to include citizens, civil society and those with social science expertise, c) it incorporates broader questions and issues at stake such as those of ethics and sustainability, d) and it recognises the need to move forward in the face of pervasive uncertainty without a belief that risks can necessarily be thoroughly assessed and designed out. However, despite its potential to improve innovation governance, the concept also faces a number of challenges and limitations. Much like SbD, the first of these refers to the question of how we define RRI and how we see it as distributed. Just as for safety, the meaning and interpretation of responsibility and/or product desirability can differ across individuals and stakeholder groups. There can also be a significant divergence between what people may recognise and say they are responsible for and how they enact their responsibilities in practice. There will also never be a single correct answer for these issues and they will always need to be deliberatively discussed and negotiated in practice. Moreover, with the focus of RRI on addressing social and environmental challenges and needs, questions may arise about how these needs are defined and prioritized, as well as what would constitute a desirable product or outcome. Furthermore, depending on how it is approached and defined, notions of RRI can be seen to challenge currently entrenched ideas of scientific and economic freedom, such as the autonomy of researchers and innovators to define what is interesting to work on and develop into products for the market. Indeed, RRI implies quite a different relationship between science and society than has dominated in recent years, namely one in which social actors and issues are given more influence and power over the shaping of science and innovation. This means that the concept can face significant resistance from actors benefiting from or comfortable with the current model. The interpretive flexibility of RRI also has implications for t...
