Sara A. Brenner

Nanomedicine: promises and challenges for the future of public health

As the scope of nanotechnology applications in medicine evolves, it is important to simultaneously recognize and advance contributions germane to public health. A wide range of innovations in nanomedicine stand to impact nearly every medical specialty and unveil novel ways to improve the quality and extend the duration of life – these gains can be measured at both individual and population levels. For example, heart disease and cancer combined make up approximately half of all deaths in the United States per year, and already, advances in nanomedicine demonstrate great potential to reduce rates of morbidity and mortality due to these diseases. Meanwhile, public health applications of nanomedicine such as rapid and portable diagnostics and more effective vaccinations have the potential to revolutionize global health. Research driven by innovators across disciplines such as engineering, biology, medicine, and public health should collaborate in order to achieve maximal potential impact in health for individuals and populations. In turn, knowledge gaps regarding the potential health and safety implications of exposure to engineered nanomaterials must be continuously addressed and actively researched. Dynamic, proactive, and socially responsible research will drive nanomedicine as it plays an increasingly integral and transformative role in medicine and public health in the 21st century.

Hyperspectral microscopy as an analytical tool for nanomaterials

Hyperspectral microscopy is an advanced visualization technique that combines hyperspectral imaging with state-of-the-art optics and computer software to enable the rapid identification of materials at the micro- and nanoscales. Achieving this level of resolution has traditionally required time-consuming and costly electron microscopy techniques. While hyperspectral microscopy has already been applied to the analysis of bulk materials and biologicals, it shows extraordinary promise as an analytical tool to locate individual nanoparticles and aggregates in complex samples through rapid optical and spectroscopic identification. This technique can be used to not only screen for the presence of nanomaterials, but also to locate, identify, and characterize them. It could also be used to identify a subset of samples that would then move on for further analysis via other advanced metrology. This review will describe the science and origins of hyperspectral microscopy, examine current and emerging applications in life science, and examine potential applications of this technology that could improve research efficiency or lead to novel discoveries.

Occupational Exposure to Airborne Nanomaterials: An Assessment of Worker Exposure to Aerosolized Metal Oxide Nanoparticles in Semiconductor Wastewater Treatment

This study characterized potential inhalation exposures of workers to nanometal oxides associated with industrial wastewater treatment processes in a semiconductor research and development facility. Exposure assessment methodology was designed to capture aerosolized engineered nanomaterials associated with the chemical mechanical planarization wafer polishing process that were accessible for worker contact via inhalation in the on-site wastewater treatment facility. The research team conducted air sampling using a combination of filter-based capture methods for particle identification and characterization and real-time direct-reading instruments for semi-quantitation of particle number concentration. Filter-based samples were analyzed using electron microscopy and energy-dispersive x-ray spectroscopy while real-time particle counting data underwent statistical analysis. Sampling conducted over 14 months included 5 discrete sampling series events for 7 job tasks in coordination with on-site employees. The number of filter-based samples captured for analysis by electron microscopy was: 5 from personal breathing zone, 4 from task areas, and 3 from the background. Direct-reading instruments collected data for 5 sample collection periods in the task area and the background, and 2 extended background collection periods. Engineered nanomaterials of interest (Si, Al, Ce) were identified by electron microscopy in filter-based samples from all areas of collection, existing as agglomerates (>500 nm) and nanoparticles (100 nm–500 nm). Particle counts showed an increase in number concentration during and after selected tasks above background. While additional data is needed to support further statistical analysis and determine trends, this initial investigation suggests that nanoparticles used or generated by chemical mechanical planarization become aerosolized and may be accessible for inhalation exposures by workers in wastewater treatment facilities. Additional research is needed to further quantify the level of exposure and determine the potential human health impacts.

Health and safety implications of occupational exposure to engineered nanomaterials

The rapid growth and commercialization of nanotechnology are currently outpacing health and safety recommendations for engineered nanomaterials. As the production and use of nanomaterials increase, so does the possibility that there will be exposure of workers and the public to these materials. This review provides a summary of current research and regulatory efforts related to occupational exposure and medical surveillance for the nanotechnology workforce, focusing on the most prevalent industrial nanomaterials currently moving through the research, development, and manufacturing pipelines. Their applications and usage precedes a discussion of occupational health and safety efforts, including exposure assessment, occupational health surveillance, and regulatory considerations for these nanomaterials.

Perspectives on the design of safer nanomaterials and manufacturing processes

Abstract A concerted effort is being made to insert Prevention through Design principles into discussions of sustainability, occupational safety and health, and green chemistry related to nanotechnology. Prevention through Design is a set of principles, which includes solutions to design out potential hazards in nanomanufacturing including the design of nanomaterials, and strategies to eliminate exposures and minimize risks that may be related to the manufacturing processes and equipment at various stages of the lifecycle of an engineered nanomaterial.

SEM analysis of particle size during conventional treatment of CMP process wastewater

Engineered nanomaterials (ENMs) are currently employed by many industries and have different physical and chemical properties from their bulk counterparts that may confer different toxicity. Nanoparticles used or generated in semiconductor manufacturing have the potential to enter the municipal waste stream via wastewater and their ultimate fate in the ecosystem is currently unknown. This study investigates the fate of ENMs used in chemical mechanical planarization (CMP), a polishing process repeatedly utilized in semiconductor manufacturing. Wastewater sampling was conducted throughout the wastewater treatment (WWT) process at the fabrication plants on-site wastewater treatment facility. The goal of this study was to assess whether the WWT processes resulted in size-dependent filtration of particles in the nanoscale regime by analyzing samples using scanning electron microscopy (SEM). Statistical analysis demonstrated no significant differences in particle size between sampling points, indicating low or no selectivity of WWT methods for nanoparticles based on size. All nanoparticles appeared to be of similar morphology (near-spherical), with a high variability in particle size. EDX verified nanoparticles composition of silicon- and/or aluminum-oxide. Nanoparticle sizing data compared between sampling points, including the final sampling point before discharge from the facility, suggested that nanoparticles could be released to the municipal waste stream from industrial sources.

Cutaneous exposure scenarios for engineered nanoparticles used in semiconductor fabrication: a preliminary investigation of workplace surface contamination

Abstract Background: Numerous studies are ongoing in the fields of nanotoxicology and exposure science; however, gaps remain in identifying and evaluating potential exposures from skin contact with engineered nanoparticles in occupational settings. Objectives: The aim of this study was to identify potential cutaneous exposure scenarios at a workplace using engineered nanoparticles (alumina, ceria, amorphous silica) and evaluate the presence of these materials on workplace surfaces. Methods: Process review, workplace observations, and preliminary surface sampling were conducted using microvacuum and wipe sample collection methods and transmission electron microscopy with elemental analysis. Results: Exposure scenarios were identified with potential for incidental contact. Nanoparticles of silica or silica and/or alumina agglomerates (or aggregates) were identified in surface samples from work areas where engineered nanoparticles were used or handled. Conclusions: Additional data are needed to evaluate occupational exposures from skin contact with engineered nanoparticles; precautionary measures should be used to minimize potential cutaneous exposures in the workplace.

Hyperspectral imaging of nanoparticles in biological samples: Simultaneous visualization and elemental identification

While engineered nanomaterials (ENMs) are increasingly incorporated into industrial processes and consumer products, the potential biological effects and health outcomes of exposure remain unknown. Novel advanced direct visualization techniques that require less time, cost, and resource investment than electron microscopy (EM) are needed for identifying and locating ENMs in biological samples. Hyperspectral imaging (HSI) combines spectrophotometry and imaging, using advanced optics and algorithms to capture a spectrum from 400 to 1000 nm at each pixel in an enhanced dark‐field microscopic (EDFM) image. HSI‐EDFM can be used to confirm the identity of the materials of interest in a sample and generate an image “mapping” their presence and location in a sample. Hyperspectral mapping is particularly important for biological samples, where ENM morphology is visually indistinct from surrounding tissue structures. While use of HSI (without mapping) is increasing, no studies to date have compared results from hyperspectral mapping with conventional methods. Thus, the objective of this study was to utilize EDFM‐HSI to locate, identify, and map metal oxide ENMs in ex vivo histological porcine skin tissues, a toxicological model of cutaneous exposure, and compare findings with those of Raman spectroscopy (RS), energy‐dispersive X‐ray spectroscopy (EDS), and scanning electron microscopy (SEM). Results demonstrate that EDFM‐HSI mapping is capable of locating and identifying ENMs in tissue, as confirmed by conventional methods. This study serves as initial confirmation of EDFM‐HSI mapping as a novel and higher throughput technique for ENM identification in biological samples, and serves as the basis for further protocol development utilizing EDFM‐HSI for semiquantitation of ENMs. Microsc. Res. Tech. 79:349–358, 2016.

Identification of Metal Oxide Nanoparticles in Histological Samples by Enhanced Darkfield Microscopy and Hyperspectral Mapping

Nanomaterials are increasingly prevalent throughout industry, manufacturing, and biomedical research. The need for tools and techniques that aid in the identification, localization, and characterization of nanoscale materials in biological samples is on the rise. Currently available methods, such as electron microscopy, tend to be resource-intensive, making their use prohibitive for much of the research community. Enhanced darkfield microscopy complemented with a hyperspectral imaging system may provide a solution to this bottleneck by enabling rapid and less expensive characterization of nanoparticles in histological samples. This method allows for high-contrast nanoscale imaging as well as nanomaterial identification. For this technique, histological tissue samples are prepared as they would be for light-based microscopy. First, positive control samples are analyzed to generate the reference spectra that will enable the detection of a material of interest in the sample. Negative controls without the material of interest are also analyzed in order to improve specificity (reduce false positives). Samples can then be imaged and analyzed using methods and software for hyperspectral microscopy or matched against these reference spectra in order to provide maps of the location of materials of interest in a sample. The technique is particularly well-suited for materials with highly unique reflectance spectra, such as noble metals, but is also applicable to other materials, such as semi-metallic oxides. This technique provides information that is difficult to acquire from histological samples without the use of electron microscopy techniques, which may provide higher sensitivity and resolution, but are vastly more resource-intensive and time-consuming than light microscopy.

NIOSH field studies team assessment: Worker exposure to aerosolized metal oxide nanoparticles in a semiconductor fabrication facility

ABSTRACT The ubiquitous use of engineered nanomaterials—particulate materials measuring approximately 1–100 nanometers (nm) on their smallest axis, intentionally engineered to express novel properties—in semiconductor fabrication poses unique issues for protecting worker health and safety. Use of new substances or substances in a new form may present hazards that have yet to be characterized for their acute or chronic health effects. Uncharacterized or emerging occupational health hazards may exist when there is insufficient validated hazard data available to make a decision on potential hazard and risk to exposed workers under condition of use. To advance the knowledge of potential worker exposure to engineered nanomaterials, the National Institute for Occupational Safety and Health Nanotechnology Field Studies Team conducted an on-site field evaluation in collaboration with on-site researchers at a semiconductor research and development facility on April 18–21, 2011. The Nanomaterial Exposure Assessment Technique (2.0) was used to perform a complete exposure assessment. A combination of filter-based sampling and direct-reading instruments was used to identify, characterize, and quantify the potential for worker inhalation exposure to airborne alumina and amorphous silica nanoparticles associated with th e chemical mechanical planarization wafer polishing process. Engineering controls and work practices were evaluated to characterize tasks that might contribute to potential exposures and to assess existing engineering controls. Metal oxide structures were identified in all sampling areas, as individual nanoparticles and agglomerates ranging in size from 60 nm to >1,000 nm, with varying structure morphology, from long and narrow to compact. Filter-based samples indicated very little aerosolized material in task areas or worker breathing zone. Direct-reading instrument data indicated increased particle counts relative to background in the wastewater treatment area; however, particle counts were very low overall, indicating a well-controlled working environment. Recommendations for employees handling or potentially exposed to engineered nanomaterials include hazard communication, standard operating procedures, conservative ventilation systems, and prevention through design in locations where engineered nanomaterials are used or stored, and routine air sampling for occupational exposure assessment and analysis.