Record Count: 64
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DESCRIPTION (provided by applicant):
In responding to HazMat emergencies, practice not only makes perfect, it also saves lives. Under the Phase I SBIR grant, Amethyst Research developed a software simulation tool called HazCommand. Our Phase II goal is to create a model platform for credentialing operational competency of initial company officers responding to HazMat incidents. The credential will reflect the responder's ability to demonstrate operational competency that meets local operating procedures and NIMS/ICS and NFPA standards. By creating such a HazMat Incident Command System credentialing component for the Philadelphia Fire Department, we will have produced a concrete roadmap for other organizations to create their own standards-based credentialing program. Amethyst Research will accomplish this goal by 1) creating a comprehensive set of HazMat incident scenarios, 2) developing reliable evaluation metrics and competency- assessment credentialing processes, 3) developing support for metrics capture and reporting, and 4) evaluating the credentialing processes on representative sample. This project aims to mature a software simulation tool called HazCommand for training emergency responders in command and control, strategy, tactics, and communication, into a full-fledged learning platform. This project should impact public health by improving response by firefighters to HazMat incidents.
DESCRIPTION (provided by applicant): Cytochrome P450 (CYP) enzymes catalyze the majority of known drug metabolism and the bulk of these reactions occur in the liver. As a consequence, many clinically relevant drug-drug interactions are associated with inhibition and/or induction of a specific CYP enzyme. Modifications of CYP activities can have profound effects on therapeutic efficacy and can lead to life-threatening toxicity. In order to provide an early warning system for potential serious side effects, detection of specific CYPs responsible for drug metabolism and drug-drug interactions is a goal of all pre-clinical studies. An ideal CYP assay should be rapid, robust, reliable, reproducible, and amenable to automation in multiwell plate formats. This research will develop a microplate format high throughput whole zebrafish CYP functional assay for assessing drug metabolism and drug safety. Based on genetic and physiological similarity to humans, zebrafish show promise as an efficient, predictive animal model for assessing drug metabolism and drug safety. PUBLIC HEALTH RELEVANCE: Project Narrative The zebrafish assay will facilitate detection of specific cytochromes responsible for drug metabolism and drug-drug interactions, and provide an early warning system for potential serious side effects,
DESCRIPTION (provided by applicant): The goal of this Phase II program is develop, test and produce a prototype field analytical instrument for electrochemical monitoring of arsenic in drinking water. This program seeks to provide a new avenue to laboratory-quality arsenic detection and quantification in a field-portable device at reasonable cost. The long term vision for this technology is that it will become a key environmental science tool to support the development of strategies to prevent arsenic-related disease in individuals and population and to help people liver longer, healthier lives, a key aspect of the mission of NIEHS. We envision this technology also having a role in the international arsenic contamination picture, particularly in countries such as Bangladesh, where over 70% of drinking water wells contain toxic concentrations of arsenic. Specific Aims of the Phase II program will include design and construction of a prototype field-portable analytical system for detection of arsenic in drinking water at concentrations between sub-ppb and many ppm. The performance of the instrument will be characterized in the lab for the effects of real sample issues, including several classes of interferences and environmental variables. Once fully characterized, the prototype will be tested in the field with selected stakeholders in the drinking water distribution system arena. The new prototype technology will be benchmarked against standard analytical laboratory methods and other available field tests, such as colorimetric kits. During Phase I, favorable comparison to standard analytical laboratory analysis has already been obtained on drinking water samples from New Mexico and remediation treatment process water from Nevada. These results provide high confidence that the proposed analytical methodology will be an effective tool to prevent arsenic related disease from drinking water exposure. In the United States and globally, contamination of drinking water by naturally occurring arsenic puts populations at risk of a variety of arsenic-related diseases. The proposed Phase II program will provide a cost- effective and highly accurate way to monitor arsenic in drinking water at the site of the water source. The long- term vision for this technology is that it will become a useful tool for helping to arsenic-related disease among exposed populations.
DESCRIPTION (provided by applicant): The use of chlorine for the disinfection of domestic water supplies produces a range of halogenated organic compounds as a result of chemical reactions between the chlorine and naturally occurring organic material (NOM). These disinfection byproducts (DBFs) occur at parts per billion level and the consumption of chlorinated water containing these compounds has been linked to an increased incidence of a number of cancers and other ailments. As a consequence, it is highly desirable to reduce the levels of these DBFs in drinking water in order to limit their impact on human health. Current methods for DBP removal tend to focus on the reduction of NOM prior to the chlorination process. However, available technologies are only moderately effective or are cost prohibitive for large-scale applications (e.g. reverse osmosis). Triton proposes to use selective adsorbents to remove the DBFs after the chlorination step. During the Phase I project, it was demonstrated that certain hydrophobic nanoporous sorbents have great advantages over existing materials for a cost effective and efficient removal of DBFs. This Phase II proposal addresses the experimentation for both POU and POE devices necessary to qualify the adsorbent material, relative to standards set forth by both the EPA and the National Sanitation Foundation (NSF). Importantly, this proposed effort also addresses the commercialization of these materials in POU and POE devices with existing companies in the drinking water treatment industry.
The proposed Triton's approach of adsorbing DBFs with a special adsorbing bed of material in both POU and POE devices has the following advantages:
Municipal treatment facilities can continue to use time-tested halogens as the primary and/or secondary means of disinfection, saving billions of dollars in infrastructure required to convert to new water treatment methods such as UV and Ozone. The retrofitable nature of the adsorbent media into POE and POE devices permits suppliers of water treatment devices to expand their market offering without the need to build new devices. Consumers can readily have access to the new technology through the existing marketplace infrastructure and devices.
Crisp Terms/Key Words: cost effectiveness, nanotechnology, evaluation /testing, technology /technique development, water treatment, water pollution, adsorption, waste treatment, hydropathy
DESCRIPTION (provided by applicant)
A field-portable instrument that can determine the blood level of specific toxic metals is vital in establishing the link between toxic exposure and genetic expression in that it aides in identification of genes whose expression is modified by exposure. Such data is critical for both laboratory and epidemiological studies. Standard assay methods require samples be sent to off-site laboratories, increasing costs and errors, and imposing a delay in identifying exposure sources. The overall goal of the proposed work will be to develop a small, easy-to-use, handheld instrument used with disposable silicon microchips to provide rapid, in field simultaneous detection of lead, cadmium, copper and zinc in blood. The microsampling and assay chip, which integrates a microneedle comparable in size to a human hair for painless blood drawing with a microcuvette containing an electrochemical detection structure, can be cost-effectively fabricated using MEMS (microelectromechanical systems) technology. The assay will employ electrochemical-stripping analysis; a proven technique for accurate and precise detection of trace amounts of toxic heavy metals. The assay permits detection of the analytes without requiring sample de-oxygenation, and uses an internal standard to avoid the need for external calibration. It is thus ideal for field use and can be used by untrained personnel. In addition, self-metering of sample volume will provide for accurate determination of levels of the four metals in blood. Phase I will demonstrate feasibility by: developing the assay and validating it with in vitro testing, designing the microchip and fabricating key components, and developing measurement and control instrumentation. In Phase II, a complete prototype system will be fabricated and evaluated via in vitro and animal testing.
DESCRIPTION (provided by applicant): Radiation Monitoring Devices, Inc. (RMD) proposes to develop a field-portable instrument for the detection and identification of pathogenic viruses that are collected by an aerosol concentrator. It will incorporate modular, microfluidic platforms designed to capture and concentrate the sample for a rapid, two-stage analysis. The first employs pathogen capture on antibody-decorated, paramagnetic nanospheres and will provide rapid, preliminary warning based on the hydrodynamic properties of the nanoparticles when the targeted viruses are bound. This stage will monitor the relaxation of the magneto-optical birefringence of the nanoparticles and will trigger an alarm when the birefringence relaxation rate drops off dramatically. The methodology allows for continuous surveillance over virtually unlimited periods. The second stage will provide either confirmation or correction to the preliminary identification. It is based on the ability to interrogate the captured nucleic acid with a series of unique probes that change their fluorescence properties when they hybridize with specific nucleotide sequences of suspected viral genes. We will compare the speed and sensitivity of detecting these genes by fluorescence generated from molecular beacons, and by the temporal correlation of fluorescence issued from tagged probes. The detection method exhibiting the best performance will be incorporated into the sensor. In each case, Nucleic Acid Sequence Based Amplification (NASBA), an isothermal nucleotide amplification scheme, will be employed to raise the number of target template copies to detectable levels. The biosensor will integrate the two stages of sample transfer, amplification, and analysis in a microfluidic architecture that enables high throughput processing and parallel detection of multiple probes. Employing both proportional mode avalanche photodiode (APD) detectors and Geiger-mode muAPDs that are responsive to extremely low light levels, sensitivity to low virus titers will be possible.
This proposal solicits funding for developing an instrument to detect and identify pathogenic viruses in a rapid, automated two-step analysis that can be used by emergency workers who are responding to a suspected release of airborne (waterborne) agents. The first step screens the sample to determine if there are any virus particles that possess a targeted group of exposed coat proteins. If the answer is affirmative, the virus is isolated and its nucleic acid is analyzed to determine if it carries pathogen genes.
DESCRIPTION (provided by applicant A miniature, battery-powered monitor will be developed for measurement of hourly concentrations of chemical constituents of PM2.5 aerosols that are important to human exposure. The method utilizes a laminar-flow, water condensation method to provide a concentrated, "ready-to-analyze" deposit of ambient particles. Many deposits will be contained on a single collection wafer designed for automatic analysis by common liquid chromatographic methods. The objective is wide-scale, inexpensive time-resolved monitoring of individual constituents of ambient particulate matter for personal exposures assessment. PUBLIC HEALTH RELEVANCE: Proposed is the development of a compact, battery powered monitor to provide time-resolved measurements of personal exposures to many of the toxic chemical components of PM2.5. Short- term exposures to high levels may be important for understand the respiratory and cardiovascular health effects of exposure. This research improves the time-resolution and the range of chemical components that can be measured in personal monitoring studies.
DESCRIPTION (provided by applicant): No ozone monitors exist today that are small enough, sensitive enough, and selective enough for widespread use in detecting and tracking low part-per-billion (ppb) levels of ozone that can be used for detailed research of the health effects of human exposure to low-ppb concentrations ozone, particularly for sensitive individuals such as asthmatics, children, and the elderly. Improved ozone sensors are needed in order to make reliable in-field exposure measurements for individuals with asthma and other respiratory diseases. Improved understanding of the impacts of environmental toxins, such as ozone, on public health can eventually result in increased protections for at-risk individuals. Synkera Technologies is proposing the development and validation of a new, credit-card sized device that will be able to detect low levels of ozone (<12 ppb) in real-time with the required spatial resolution in order to aid research on respiratory diseases. This sensor will build upon recent advances in electrochemical sensing technology to create a next generation product that is significantly smaller, faster, more sensitive, stable and lower cost than any electrochemical sensor available today. The novel sensor will be a solid-state electrochemical device, based on existing nanotechnology expertise available at Synkera, with a form factor that will allow for integration into small monitors Phase I will demonstrate the feasibility of the approach by fabricating and extensively testing prototype sensors. Proof-of-concept will be established if we are able to demonstrate the feasibility of detection of low ppb ozone levels (~10 ppb) with sufficient selectivity and stability. In Phase II the ozone sensors will be optimized, electronics to operate the sensors will be developed, prototype monitors will be produced, and field trials will be performed. PUBLIC HEALTH RELEVANCE: The development of a wearable, easy to use, point-of-contact ozone monitor will allow for widespread population studies to further explore the affects of environmental exposure on respiratory incidents and respiratory disease. Such a device will support programs like the NIH- wide Genes and Environment Initiative (GEI), which seeks to identify major genetic susceptibility factors for diseases of public health significance and develop technology for measurement of potential causative environmental exposures. This type of research and development will provide significant information regarding health disparities that may lead to differential health outcomes.
DESCRIPTION (provided by applicant): This Phase II SBIR proposal describes the development of a prototype device for monitoring the presence of a number of hazardous chemicals in the air. This device is fundamentally different than typical spectroscopic instruments in that it uses enzyme-based plastics as sensing elements. Phase I showed that enzymatic plastics can be employed to continuously monitor the environment when properly adapted to a simple device. Agentase will adapt its proven enzyme-based chemistries for nerve, blood, and blister agent detection into forms that are compatible with continuous monitoring in the proposed Phase II effort. After optimizing individual sensors for sensitivity to agents and response time, a battery of experiments will be conducted to ensure that sensors have sufficient shelf life, operational lifetimes, and resistance to environmental interference. Custom built hardware will also be constructed to house the sensors and ensure their proper implementation. The work plan concludes with a series of operational assessments that serve as a true test of product feasibility prior to use in studies with warfare grade chemical agents. Successful completion of the effort will provide an inexpensive tool for monitoring air quality for the presence of hazardous chemicals. Once hardened and validated, such a device can be used to warn against an event of chemical terrorism. Early detection of released chemicals is the key to minimizing the impact of a chemical event on site and ensuring the best possible medical and emergency responses.
DESCRIPTION (provided by applicant)
Caldera Pharmaceutical's will use their unique, R&D100-award-winning Reagentless Pharmacoproteomic Measurement (RPM) high-throughput technology to identify biomarkers of response to environmental stressors (BRES). Caldera developed RPM in collaboration with Los Alamos National Laboratory. RPM allows the identification and measurement of BRES consisting of protein-metal adducts and metabolites. We propose to develop BRES to define patterns of response to benefit the Gene Environment Initiative, focusing on xenobiotic biotransformation in human disease like Autism. Our BRES will lead to reliable measurements of exposures, which can be correlated with variable susceptibility to metal toxicity in the human population. This provides valuable information involving metabolic pathways for the Gene Environment Initiative (GEI). We will measure exposure to metal stressors in biospecimens by developing BRES that can identify exposure to particular chemical forms of toxic metals. Protein:metal adducts formed in individual patients may be correlated to genetic differences regulating metallothionein or other metallome proteins thought to be related to autism. RPM can monitor simultaneous exposure to toxins, such as arsenic, cadmium, lead, and mercury (thimerasol), as well as exposure to essential metals (zinc, iron, selenium, etc.). Individuals with autism may have varying genes that biotransform and detoxify metals differently, leading to varying accumulation and disease susceptibility.
Crisp Terms/Key Words: biomarker, immunologic assay /test, metabolism, biotransformation, ligand, heavy metal, environmental stressor, method development, gene environment interaction, clinical research, protein protein interaction, high throughput technology, environmental exposure, proteomics
DESCRIPTION (provided by applicant): The mission of the National Institutes of Health (NIH) is "science in pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability." Pursuant to that mission, the National Institute of Environmental Health Sciences (NIEHS) released the RFP topic stating their objective and mission that "human health and human disease result from three interactive elements: environmental exposure, genetic susceptibility, and age. The mission of NIEHS is to reduce the burden of human disease and dysfunction from environmental causes by understanding each of these components and how they interrelate." The proposed project from X-ray Optical Systems (XOS) will make a significant contribution for both the NIH and NIEHS Missions, as well as meet the needs of the NIEHS research objective. This project involves development and application of a low-power, compact, reliable, easy-to-operate instrument for measurement of trace elements in any liquid, gel, or solid that can be homogenized for individual environmental exposure assessment. The analyzer can be used in the home, place of employment, and recreational settings for patients undergoing study and treatment for major diseases or for individual and occupational health risk assessment. Abnormal levels of bio-essential metals (iron, copper, and zinc) as well as toxic trace elements (mercury, lead, cadmium, and arsenic) are known to be associated with many health disorders such as cancer, cognitive impairment, and neurological symptoms. The presence of metals is well-known in most neurodegenerative pathologies, such as excess serum copper or brain iron accumulation, which are associated with Wilson's, Alzheimer's, and Parkinson's disease. In spite of their recognized importance, personal exposure to these metals is not routinely measured or monitored in body fluids and tissues or in materials in personal environments. This is due in large part to the difficulty and expense of trace metal measurements in the field or clinic. The proposed analyzer is based on new, powerful, proprietary, monochromatic doubly curved crystal (DCC) and polychromatic polycapillary x-ray optics technology that greatly increases the efficiency and sensitivity for elemental analysis. This new analyzer has the potential to offer an inexpensive, portable, robust, safe, easy-to-operate elemental analyzer for measurements taken on-site, with little or no sample preparation. Furthermore, this will reduce costs for large scale studies such as the Genes, Environment and Health Initiative (GEI), and the National Children's Study (NCS). The proposed analyzer will facilitate much needed links between genetics & exposure research leading to improvements in quality of life while reducing healthcare costs related to a variety of chronic conditions.
Public Health Relevance: The proposed new, trace-element, portable, personal environmental exposure analyzer will enable researchers to examine individual exposure to toxic and bioessential trace elements in the home or place of employment without having to collect, store, track, ship, dispose, or transfer samples through central laboratories. The fluids and materials analyzer can be used to detect and quantify, in minutes, trace elements in any liquid, gel or solid that can be homogenized by using an inexpensive, compact, safe, reliable, simple-to-use instrument for on-site measurements. This instrument will have a broad, positive impact on public health by accelerating research capabilities, enabling new studies to more rapidly gather information, (i.e. to link the genetic and environmental correlations), reducing study costs by testing onsite without delays, improving research data available for studies of specific patient populations (such as Alzheimer's or Asthma), and facilitating individual exposure measurements for family or occupational health assessment.
DESCRIPTION (provided by applicant): In Phase I, we have developed a novel approach to the analysis of toxicogenomics data based on functional categorization and signature networks. The method enables identification of pathways and biological networks most different between gene expression response to drug action, and it can be applied for categorization of molecular profiles by toxicity categories. We have also functional profiling on a large dataset of hepatotoxic compounds from CEBS database. In Phase II, we propose to formalize the new approach in algorithms and build a semi-automated module for generation of signature networks specific for a toxicity type. We will also build a reference database of quantitative functional descriptors for toxic categories which can be used for categorizing of molecular profiles for novel compounds. We will develop a workflow for functional analysis of toxicogenomics datasets and a reporting protocol which sponsor companies can use for voluntary submission of toxicogenomics data to FDA and the reviewers for evaluation of the submitted data. Finally, we propose to build a novel integrated platform for functional data mining of toxicogenomics data and reporting, MetaTox. MetaTox will include the manually curated database of human biology created at GeneGo, a general datamining toolkit (networks, pathways, cellular processes, disease and toxicity categories), pre-processed toxicogenomics data from public domain, and the tools created in the scope of this project (signature networks module and the database of functional descriptors for toxicity categories). In Phase II, we propose to complete the set of tools and workflows for functional analysis of toxicogenomics data. This will include a novel module for generation and comparison of signature networks for different toxic categories, matrix of quantitative functional categories and a new toxicogenomics platform MetaTox
DESCRIPTION (provided by applicant)
Phoenix Biosystem intends to leverage the in-house expertise in sensors, microfluidics, and microelectronics to design, develop and validate novel, battery powered portable measurement technologies which, by the end of the Phase II funding period, will result in field-deployable tools that would provide accurate internal assessment of internal dose and/or activity of priority environmental exposures in real time. The sensors would have the ability to measure multiple agents within a single class of exposure i.e. pesticides. The Phase I prototype will detect personal exposure to OP conjugates in whole blood samples. Since the resultant OP conjugate typically correlates directly with the OP structure, an antibody-based nanoarray analysis would be superior to the current, end point-based colorimetric method.
DESCRIPTION (provided by applicant): This three-phase Small Business Innovation Research project addresses one the most significant problems in public health protection: monitoring of indoor air quality and controlling the ventilation systems in residential, office and industrial buildings. The development of a novel advanced microsensor for detecting gaseous formaldehyde in air is proposed. The sensing method utilizes the conductivity change induced, upon exposure to formaldehyde, in a layer of tin oxide. Cross-sensitivity to other volatile organic chemicals is eliminated by patterning of the tin oxide surface by an inert protecting layer with sub-nanometer pores, each shaped to selectively host a single formaldehyde molecule. Incorporation of this novel sensing material into a high-area nanostructured sensor platform will enable production of highly sensitive, selective, low-power, and low-cost formaldehyde microsensors. The Phase I project will demonstrate the feasibility of the proposed approach through fabrication of sensors and their comprehensive testing in conditions simulating contaminated indoor air. To ensure successful Phase II product development and Phase III commercialization, partnership has been secured with one of the leading developers of components and systems for energy applications. By combining coordination chemistry with nanotechnology and microfabrication, the proposed approach is likely to enable a novel family of low-cost highly sensitive and selective sensor systems for precise quantitative monitoring of human exposures to toxicants. Thus, the proposed research is highly relevant to the mission of the National Institute Of Environmental Health Sciences.
Public Health Relevance: The project addresses one the most significant problems in public health protection: monitoring of indoor air quality and controlling the ventilation systems in residential, office, and industrial buildings. The development of novel advanced sensors for detecting formaldehyde - one of the most ubiquitous and dangerous for human health air contaminants - is proposed. The proposed technology will enable a novel family of high-performance and low-cost sensor systems for generating precise and quantitative measures of human exposure to harmful chemicals at the point of contact.
DESCRIPTION (provided by applicant): Quantitative monitoring of personal exposure to environmental toxins is currently limited by expense, inconvenience and lack of appropriate technology, yet such monitoring is needed for investigation of health effects caused by low dose, chronic exposure to compounds such as pesticides or industrial toxins. We have previously demonstrated that low concentrations of a semi-volatile organophosphate pesticide can be detected from a vapor phase by utilizing chemically functionalized, nanostructured surfaces and liquid crystals (Platypus( technology). What is needed, however, is a monitor that simultaneously measures exposure to multiple compounds. In this proposal, we will demonstrate the feasibility of developing Platypus( technology for the quantitative and simultaneous detection of two different classes of semi-volatile pesticides (carbamates and organophosphates) and for the discrimination of specific compounds within each class of pesticide. The technology developed in this project can be adapted for detection of other industrial or environmental contaminants that are semi-volatile, and thus it has the potential to serve as the basis for a broadly useful, convenient and inexpensive class of passive monitors for multi-compound personal exposure assessment and environmental monitoring. In this proposal, we are developing a small, inexpensive wearable device which will provide a measurement of an individual's exposure to multiple chemicals present in his or her environment over a period of a day to a few weeks. This data is essential for associating exposure to specific compounds with adverse affects on public health.
DESCRIPTION (provided by applicant)
It is proposed to develop (during phase I and II) a person portable, highly sensitive and selective, broad band, real time data acquisition, GPS enabled and remotely accessible by wireless or by internet a "Personal Exposure Monitor" for the detection of trace amounts of harmful chemical species present in the exhaled breath of a human being. This instrument will employ a novel atmospheric pressure "supersonic pulsed ion beam source, (SPIBS)" recently developed by the principal investigator of this proposal and a miniature focusing time-of-flight mass spectrometer (FTOF-MS), also developed by the principal investigator for NASA in the past (published in the NASA Tech Brief Journal, 2004). Utilizing this combination, mass spectra of exhaled breath, covering the entire mass range of chemicals of present interest, will be obtained by employing the charged particle counting technique that is capable of a large dynamic range permitting sensitive detection of trace species in an air sample where other chemical species may be present in high concentrations. The novelty lies in the fact that the exhaled breath will be introduced into the vacuum system, housing the miniature FTOF-MS and the charged particle detector, in the form of short pulses (~ 100 ms duration) of supersonic beams for mass analysis. This will reduce the load on the vacuum pumps that are normally used in routinely employed mass spectrometers where the sample of air to be mass analyzed is introduced continuously. This continuous introduction of air sample into the vacuum chamber of a mass spectrometer requires large and heavy vacuum pumps employing differential pumping methods. This makes them heavy, bulky and excessively power consuming. On the other hand, pulsed introduction reduces the gas load and permits the use of recently available light weight miniature vacuum pumps requiring low power for their operation. The principal investigator of this proposal has recently developed a vacuum system in which the room air can be introduced in the form of short pulses lasting approximately 100 ms without increasing the vacuum chamber's pressure beyond about 10-6 Torr. A TOF can be operated in this pressure range and several thousands TOF mass spectra can be obtained in this short interval of time. The "personal Exposure Monitor" proposed here for the analysis of exhaled breath will be person portable and can be accommodated in a back pack. It will have the following novel features: 1) Light weight (estimated to be less than 3.6 kg which includes a miniature Alcatel turbo pump, a diaphragm pump and an electronics box), 2) will operate with power provided by a 24 volts power pack consisting of miniature Li batteries put together in the form of a belt (weight of this belt is estimated to be less than 4 Kg), 3) it will be low power consuming ( less than 250 watts), 4) pulsed introduction of the exhaled breath for sensitive detection (ppb range) of chemicals of present interest, 5) real time and fast data acquisition, 6) wireless data transmission, and 7) capable of multiple analyte measurement or the measurement of ozone alone. Such an instrument is not commercially available at the present time to make any comparison. The R & D during the Phase I will utilize our breadboard instrument to prove the concept of pulsed introduction of contaminated air procured from gas companies, measure its sensitivity, and mass selectivity. During Phase II a person portable instrument will be fabricated by utilizing the results of Phase I and limited field tested.
DESCRIPTION (provided by applicant)
An inexpensive disposable sensing element that is worn as a vapor exposure monitor or used for urinalysis is proposed for real-time monitoring of pesticide exposure. This sensor, coupled to a battery operated reader, is a direct need for the NIH Exposure Biology Program and has the potential for detect other exposures as well. The sensor is based on Surface-Enhanced Raman Spectroscopy (SERS), which allows precise detection of chemicals that adsorb strongly to roughened SERS sensors, like pesticides, into the high ppt range. The SERS sensors, vapor deposited gold films with subsequent electrochemical roughening, are inexpensive to make, operate in vapor phase under a wide humidity range and in solution. As the sensors are tuned to the analytes of interest, interferences from more concentrated chemicals is limited. In this program, the SERS sensors would be worn as badges to monitor and quantify daily pesticide exposure to a worker by irreversibly binding any pesticide that comes in contact with the SERS sensor. The sensors would also measure pesticide metabolites in urine, providing the NIH with more data on the daily exposure/daily ingestion of pesticides. The SERS sensors will be read using a battery operated Raman instrument with keyed sampling chamber that ensures the SERS sensing elements are automatically aligned into the system. The compact system would be fully automated and incorporate a spectral library with chemometric analysis. Identification and quantification of any detected pesticides would be reported to the field technician. A single reader can be used for evaluation of hundreds of participants.
The core concepts of this technology have been developed and demonstrated. Literature results show SERS detection of organochlorine pesticides and EIC Laboratories has detected organophosphate pesticides in vapor and aqueous phases. Field detection of trace levels of explosives has been demonstrated by EIC Laboratories. The two year Phase I program is designed to expand the pesticides studied, demonstrate detection to CDC listed limits, show an adequate usable field lifetime for the SERS sensing elements, design a fieldable reader, perform a detailed interferences analysis and demonstrate that variances in the urine matrix will not affect the SERS measurement precision. Commercial: EIC Laboratories will commercialize the technology by manufacturing the SERS sensors and battery operated Raman readers. The components will be sold commercially through In Photonics, an affiliated company under common ownership.
DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project will develop an innovative biochip for rapid screening of pesticide residues in water and food samples. The proposed biochip will be built on BioDetection Instruments' exclusively-licensed patented technology and previous work on biosensors that are based on microfluidics, interdigitated microelectrodes (IMEs), and the electrochemical measurement of an indicator of microorganisms' physiological activity. An inexpensive and robust biomaterial that can sense the relevant bioactivity/toxicity of a class of widely-used pesticides will be immobilized onto the surface of an IME. A cover will be attached to the modified IME with a microfluidic channel exposed to the IME. Physiological activity of the immobilized organism will be monitored in the absence and presence of atrazine, a model pesticide, by electrochemical measurement of the indicator, and the IME signal intensity is expected to be related to the pesticide concentration. One of the primary Phase I goals is to prove the concept by demonstrating the detection of atrazine in less than 10 min with a detection limit of = 1 ppb (= 5 nM). The biochip will have the combined advantages of the biomaterial, microfluidics, and IME measurement such as low cost, high sensitivity, rapid speed, etc.. Contamination of water and food by pesticides and the potential hazard to human health remain major concerns of our society. Current pesticide detection methods such as HPLC, GC, and rapid test kits require sophisticated instruments, skilled personnel, extensive sample pretreatment, expensive bioreagents and/or intensive manual operations, and thus are unsuitable for on-site or routine screenings. Part of the challenge that faces the regulatory agencies and industries is to find better technologies for the rapid detection of low-level pesticide residues.
Public Health Relevance: The proposed biochip technology will be a rapid and inexpensive method to screen drinking water, beverages, and food products on-site or on-line for the presence of pesticide residues. Using a network of screening tests followed by confirmatory analysis will assure both producers and consumers that these products are free of dangerous levels of pesticide residues and will enhance the protection and safety of the nation's water and food supply.
DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project will develop a reagentless biosensor for online monitoring of microbial contaminants in drinking water. The biosensor is based on incorporating several newly emerging technologies into BioDetection Instruments' proprietary sensing platform. A novel monolithic column will be developed that encapsulates a unique sensing material that can specifically and directly detect an indicator bacterium with no need for the addition of any reagents. The monolithic column will be characterized by a hierarchical pore structure, high surface area, small diffusion path length, and low hydraulic resistance, which are favorable for streamlining the detection efficacy. Online monitoring of microbial contamination will be realized simply by pumping or injecting the water sample through the monolithic biosensing column along with on-column optical detection. In Phase II, the research will be extended to develop a multichannel biosensor system for online monitoring of multiple waterborne pathogens. The CDC reports that each year, 4 billion episodes of diarrhea result in an estimated 2 million deaths, and waterborne bacterial infections may account for as many as half of these episodes and deaths. The prevention of disease outbreaks relies on timely and efficient detection of disease-causing microorganisms. However, the detection of bacterial contaminants in drinking water still relies on cell growth-based methods, which are extremely time-consuming, typically requiring at least 24 hours and complicated multi-steps to confirm the analysis. Even current rapid methods such as ELISA and PCR still require enrichment of samples for 8-24 hours and take several hours to get only qualitative (positive/negative) results. Part of the challenge that faces both regulatory agencies and water plants, charged with protecting public health, is to find better, cost- effective, faster technologies for rapid detection of waterborne pathogens. PUBLIC HEALTH RELEVANCE: The proposed product will provide a reagentless assay for online monitoring of microbial contaminants in drinking water. Drinking water treatment facilities, bottled water and beverage manufacturers, as well as private well owners will benefit from the development of the proposed system. Using the proposed product, they will be able to monitor their water sources for microbial contaminations and promptly take corrective measures.
DESCRIPTION (provided by applicant):
MetaMedia Training International, Inc. and HazMatIQ LLC have formed a company to develop a library of Hazardous Materials courseware and related resources, integrated into a Learning Management System (LMS). The first product in the library to be developed under this SBIR grant request, HazMatIQ Four Step System, will take advantage of advanced training technologies and blended learning. Based upon HazMatIQ's highly successful classroom training delivery system, this project aims to transfer the training to an online version to facilitate a larger audience, reduce training costs, and allow 24/7 accessibility. HazmatIQ will provide responders with comprehensive training of the characteristics of hazardous chemicals, simplifying the overly complex approach currently being provided in classrooms and textbooks. In addition to the actual content related to chemical compounds, an interactive design that simulates the fidelity of a real-world emergency response involving multiple hazardous chemicals will be designed. This virtual experience will bring actual case studies to life using interactive video, 3-D animations, and graphics. The ability to deliver quality Hazardous Materials/ WMD training online has become relevant due to the increased level of technical expertise expected from Emergency Responders and the current inability of Responders to receive this training. Online training alleviates many problems faced by public safety professionals training, allowing students to train on their schedule while on duty and with the ability to start and stop in the event of an emergency incident. Traditional training on duty requires personnel to be taken out of service, leading to service gaps. Off duty training is costly since responders are traditionally paid overtime. Training is generally reduced or eliminated once funding has been exhausted. MetaMedia will use the internet to deliver high quality, job related pertinent hazardous materials and safety training to a large audience at a low cost. Accessing training at the user's convenience leads to increased training, which will convey to a safer and more effective response to a hazardous event. An LMS will track student participation and evaluation results generating a report based on specific department needs. This report can then be used by training officers to document their members' participation.
DESCRIPTION (provided by applicant): Microarrays are a powerful way to measure the impact of contaminants in the environment, and sheepshead minnows (Cyprinodon variegatus) are the most commonly used species in salt water environmental testing. In this proposal, we explain how we will develop and validate a large microarray (5,000+ genes) in sheepshead minnows. We will conduct a number of short and long term exposures on sheepshead minnows using several anthropogenic compounds (pyrene, copper, cadmium, and bisphenol A), then use the microarrays to measure the gene expression signatures for these compounds. This data, along with a variety of physiological endpoints, will be the basis for a relational database. We will analyze the data and decipher the patterns resulting from the various exposures to identify the unique fingerprints for each compound. Microarrays in sheepshead minnows will round out EcoArray's offering of microarrays for environmentally significant aquatic species. Measurement and analysis of environmental contaminants is very important to the EPA in its Superfund monitoring activities, and the sheepshead minnow is an important species that is routinely used for the monitoring of coastal superfund sites. In addition, diagnosis of ecotoxological effects at the gene level in sentinel species like sheepshead minnow offer the promise of future ability to tie ecotoxicology to human health, a goal of the National Center for Toxicogenomics. Experiments by our research group and others have shown that microarrays can be used to detect changes in gene expression caused by exposure to contaminants, and it is clear that contaminants have unique genetic signatures. Because many contaminants act at the gene level to induce or repress gene expression through both receptor-mediated and non-receptor mediated pathways, microarrays can help to elucidate signaling pathways that are affected. In general, microarrays offer a direct, effective way to provide detailed data about the biological effects of the environment on animals. In addition, analysis using microarrays is generally considerably less expensive than current testing methods. With the successful completion of this grant, we will incorporate the sheepshead minnow microarray and its database into our existing product line and sell it to the EPA, USGS, researchers in academia, as well as industrial concerns interested in compound screening and environmental monitoring/remediation.
This project will result in a fully developed microarray for ecotoxicology testing in salt water. This microarray, together with the database this project will begin, can provide detailed, gene-level data on the biological impact of a chemical or an environment. In so doing, it can lead to assessment not only of water quality, but also of the implications of chemicals and environments for human health.
DESCRIPTION (provided by applicant)
The proposed project will develop and demonstrate a personal exposure monitor which combines a novel aerosol concentrator, a micro-particle collector, and a microfluidic sample processing and detection platform customized to perform a broad range of assays, coupled to automated data recording and/or transmitting equipment and a position-monitoring device (such as a GPS unit) to provide time- and space-resolved measurements of a wide range of environmental agents. This exposure monitor will significantly improve the ability to localize exposure events in space and time and will provide a critical tool for use in resolving uncertainties about the relationships between exposure and human health impacts.
In the proposed project we will customize our aerodynamic lens aerosol concentrator technology for use in a portable air sampler, we will integrate the aerosol concentrator with a capillary aerosol particle collector, and we will interface this particle collection system to a microfluidics card where biological or chemical assays will be carried out and the results detected. Enertechnix, Inc. will be responsible for adapting its existing aerosol concentration and collection technology and Micronics, Inc. will adapt its commercial microfluidics card technology for use in a portable exposure monitor. The University of Washington will develop specific assays that can be adapted for implementation in the microfluidics environment for detection of target biological and chemical agents.
Aerosol handling components will be developed by Enertechnix using engineering and CFD modeling capabilities previously developed for other Government-funded projects. These components will be tested using an existing, fully instrumented aerosol chamber and a variety of standard diagnostic methods for particle and bacterial detection such as epi-fluorescence microscopy, bulk fluorescence, culture, real-time PCR, etc. Microfluidic circuitry will be designed and prototyped by Micronics using methods and tools previously developed for production of similar microfluidic cards employing nucleic acid and immunological assays and electrochemical and other detection methods. Specific assays will be developed by the University of Washington using its extensive expertise and laboratory facilities in the areas of microbiology, chemistry, environmental science (atmospheric pollutant detection and characterization), etc.
DESCRIPTION (provided by applicant): The goal of this SBIR project is the development of an improved inorganic ion exchanger with an extremely high selectivity for Sr2+. This ion exchanger will improve the extraction of 90Sr from groundwater at the sites around the US and the world that have become contaminated through mishap or poor handling of nuclear materials, some of which are in contact with aquifers and bodies of water used as drinking water supplies. 90Sr is a ?-emitting isotope with an extremely low maximum safe exposure limit. (The drinking water limit is 8 pCi/L.) Development of this material will make a significant contribution to safer drinking water. In Phase I of this project we demonstrated that the substitution of SnlV and SilV for part of the SbV in the pyrochlore-structured antimonic acid (Sb2O5 4 H2O) increased both the compound's affinity for Sr+2 and its selectivity for strontium over calcium by a factor of nearly four. (A strong preference for Sr+2 is important, because the strontium is always found with a large excess of calcium.) The resulting material has a capacity for 90Sr over 200 times that of the clinoptilotile currently used to collect strontium in pump-and-treat systems. In Phase II we will refine the composition of the exchanger and scale-up the synthesis. The material will be evaluated in complete detail for use as a column material for extracting 90Sr from ground water out of the ground or as the active component in a permeable reactive barrier to block the motion of 90Sr in ground water in the ground. In plain language: Adding tin or silicon to antimonic acid greatly improves its ability to remove strontium from aqueous solutions in the presence of the very similar calcium. This makes it an excellent choice for removing radioactive strontium-90 from ground water either at the surface, or while still in the ground.
Crisp Terms/Key Words: chemical synthesis, strontium, tin, antimony, ion exchange chromatography, radionuclide, radioactive waste, silicon, environmental toxicology, ground water, water pollution, water sampling /testing, water treatment, technology /technique development, calcium ion
DESCRIPTION (provided by applicant)
Airborne particulate matter (PM) derived from a variety of natural sources (volcanic activity, forest fires) is omnipresent. However, human activity since the industrial revolution and the advent of the internal combustion engine has substantially increased the concentration of PM, particularly in urban areas. Human derived PM tends to be of smaller size, facilitating entry into the body through the respiratory and digestive tracts, as well as through the skin. It also tends to have adsorbed chemical species with greater toxicity than its natural counterparts. The explosive growth of nanotechnology in research and consumer products (sunscreens, cosmetics, paint) is also creating an array of ultrafine materials with largely unknown health effects. Despite numerous studies implicating PM in various disorders including acute respiratory infections, lung cancer, and chronic respiratory and cardiovascular diseases, the specific biological mechanisms involved are not fully understood. Pathologics seeks to leverage its proprietary Arrayed Imaging Reflectometery (AIR) biosensing platform to build a device capable of capturing the detailed physiological response to PM exposure by profiling key marker proteins in conveniently available biosamples such as a finger pick of blood, urine, mucous, saliva, etc. Currently, such testing takes hours and is often done with individual tests. AIR is capable of sensitive and simultaneous protein detection with a device that is currently the size of a laptop computer. The low complexity of the testing platform will also enable the development of handheld units that would be particularly useful for profiling exposure response in the field. In addition to saving time and offering greater convenience these multiplex sensors will allow far more molecular data to be collected than is currently feasible.
Crisp Terms/Key Words: environmental exposure, protein protein interaction, portable biomedical equipment, technology /technique development, immunologic assay /test, reflection spectrometry, monitoring device, biomarker, air pollution
DESCRIPTION (provided by applicant): This project proposes to build and test a 20 L capacity Remediator for medical wastes. Infectious Medical Wastes (IMW), mainly from hospitals, represents a major component of hazardous wastes generated in the U.S.. In fact, more than 4.5 million tons are generated per year. Hospital waste remediation was a $1.5 billion industry in 2003. Incineration remains the predominant disposal method, with continued problems of environmental pollution, severe local opposition, transportation, high costs and the threat of recent (1997) laws shutting down incinerators. This firm recently demonstrated a novel technique for remediation of IMW that involves submersing the IMW in proprietary liquids that are specifically activated by microwaves to generate antimicrobial and antiviral activity in a manner as or more effective than an autoclave. This technique uses unique, microwave-active liquids, proprietary microwave enhancers and simple, ambient-pressure techniques. It yields an extremely inexpensive, rapid, environmentally benign, local, point-of-service methodology for remediation of IMW, usable much as a local-area photocopier or shredder. The Phase 1 work further developed this, demonstrating application to a wide variety of mixed IMW, including metallic parts, bandages, gloves, cotton, etc. and actual hospital wastes. Typically, 400 g of wastes in 650 mL of microwave liquid could be remediated in 7 minutes using a 1.1 KW oven, with final weight/-volume reductions to < 15% of original. Detailed analyses of thermal degradation products of the microwave liquid and wastes showed none. A mechanical prototype of a Remediator was built and a fully-microwave-functional prototype was designed and evaluated. AOAC Sporicidal Tests and microwave-vs.-heat-only tests were also done in the prior work. In the proposed Phase 2 work, a fully functional Remediator will be built, tested and refined, to arrive at a design suitable for handing over to a large contract manufacturer. AOAC Sporicidal and quantitative tests and tests with actual hospital wastes will be used to verify performance, along with comparisons with extant benchmark methods. The work is a collaborative effort with a highly specialized microwave design company, one of the world's premier university microwave chemistry groups, the Regional Bio-Defense Lab, and a large hospital. Estimated remediation costs are $900/ton for this firm's technology, vs. $2900/ton for incineration, and more for microwave-steam methods. This firm's technology's estimated capital cost is less than $8 K for a 30 kg/hr throughput, as compared to $18 K for on-site autoclaving and $80 K for microwave-steam. PUBLIC HEALTH RELEVANCE: The technology could, potentially, entirely replace incineration of medical wastes (already beset with public health problems) as well as expensive methods such as in-situ autoclaving and microwave-steaming, yielding an inexpensive, environmentally benign, and local, point-of-service method for medical waste remediation, to great public benefit [1-26]. Independent studies [2-4] show it could initially (within 5 years) capture about 10% to 30% of the more than $2 billion (in 2008) medical waste remediation market, possibly more subsequently. This firm's technology's estimated running costs are 1/3 to 1/6 that of other methods, its capital costs are 1/3 to 1/10 of other methods, and, in contrast to other methods which (with the exception of incineration) leave a large amount of residual waste, it leaves less than 15% of the original volume of waste.
DESCRIPTION (provided by applicant): According to the Cincinnati Children's Hospital Medical Center report, carbon monoxide is the leading cause of accidental death by poisoning. More recent estimates reveal 3,500-4,000 people die each year due to accidental CO exposure; and an additional 10,000 seek medical attention. Carbon monoxide exposure is especially dangerous for unborn babies, infants, and children because they have smaller bodies and faster metabolisms -- they absorb carbon monoxide quicker and at lower levels. Toxic levels of carbon monoxide can be up to ten times higher in the fetus than the mother. Possible mitigation requires a reliable, early warning CO detector. High sensitivity and complete reversibility are two desirable characteristics that are lacking severely in CO detectors currently available in the market. During Phase I, InnoSense LLC has demonstrated a thin film-based CO sensor sensitive to 5 ppm CO responding within five seconds. The sensor has also shown reversibility within five seconds. The Phase II project would: (a) Fine-tune the CO indicator for shortening the response/recovery times by 50% or more, (b) Conduct extensive performance studies to evaluate for how long and how effectively this sensor would perform reliably in the presence of contaminants likely to be found in a typical household. PUBLIC HEALTH RELEVANCE: Sensitive to Low PPM and Reversible Sensor for CO Phase II Project Narrative A key goal of the Phase II project is to fine-tune the CO indicator formulation. The Phase II work builds on the thin film formulation developed during Phase I utilizing ormosil matrix. This formulation strategy along with the fiber bundle approach complements the Principal Investigator's earlier patents covering basic ingredients of the CO indicator. Together, the sensing platform is expected to offer devices that would have multi-analyte detection capability. InnoSense LLC has systematically assembled and developed chemical sensor capabilities, materials science expertise, and home-built optoelectronic test and measurement devices. The company has also assembled a competent scientific team having seventy person-years of experience developing commercially viable sensor products. Given these resources and its commitment to the area of medically relevant sensors, InnoSense LLC is uniquely positioned to make effective use of the Phase II funding to study development of this life-saving device especially for a vulnerable portion of our populace - the elderly, infants and pregnant women carrying the unborn.
DESCRIPTION (provided by applicant): The availability of safe drinking water is a substantial health concern. The introduction of water chlorination as a standard water treatment has resulted in a significant decrease in the number of waterborne diseases. However disinfection byproducts (DBPs) are formed by the reactions between chlorine and the natural organic matter (NOM) dissolved in water. Long-term exposure to DBPs may increase the risk of cancer and other adverse health effect. As a consequence, the U.S. Environmental Protection Agency (EPA) has implemented stringent limits for DBPs in drinking water. Although the use of alternative disinfectants have been proposed, they also produce their own toxic byproducts. And water plant approaches to reduce the amount of NOM in the source water prior to chlorination step are not technically sound due to the requirement of a new water treatment plant that is costly to construct and operate. Thus, new methods for elimination of DBPs in drinking water at the point-of-use (POU) are strongly needed.
The objective of the Phase II proposal is to design, fabricate and test a new, small-scale photocatalytic oxidation system for POU water treatment. The aim is to provide a unique, low-cost consumer device designed to effectively eliminate DBPs and microorganisms at the location where water is consumed. The proposed system provides attractive benefits over other POU technologies because it adds nothing harmful to the water, does not require routine service, does not provide a harbor for microorganism growth, and water contaminants including DBPs and microorganisms are destroyed, not just transferred from water to solid phase, and therefore, it does not create a waste disposal problem.
During the Phase I project, Lynntech developed and successfully tested bench scale photocatalytic systems capable of fast degradation of a variety of microorganisms and DBPs to well bellow EPA recommended levels. It overcame limitations of other photocatalytic system including deactivation by inorganic ions. The heart of Lynntech's water treatment is the use of effective photocatalyst nanoparticles immobilized on an active matrix. The photocatalyst material is integrated into an ingenious reactor design that minimizes mass transfer and allows for fast treatment times. During the Phase II, an optimized automated GEN I POU photocatalytic water treatment will be developed. We will test it for its reliability, repeatability, ease of use, manufacturability and ease of assembly while minimizing its cost. Its operation will be on-line, and user interaction will be limited to the replacement of the UV lamps after about 5,000 hours of use. GEN I POU system will be extensively tested with DBPs and microorganisms commonly found in tap water.
The proposed system has a high potential for user acceptance and has immediate commercial applications in many areas where high quality water is needed. Key segments where the proposed technology can have an immediate impact include hospital, schools, pharmacies, cafeteria, commercial and residential buildings, etc.
The availability of safe drinking water is a substantial health concern. The introduction of water chlorination as a standard water treatment has resulted in a significant decrease in the number of waterborne diseases, but disinfection byproducts (DBPs) are formed by the reactions between chlorine and the natural organic matter (NOM) dissolved in water, and long-term exposure to DBPs may increase the risk of cancer and other adverse health effect. The aim of this Phase II proposal is to provide a unique, low-cost, small-scale photocatalytic oxidation system for point-of-use water treatment device designed to effectively eliminate DBPs and microorganisms at the location where water is consumed.
Crisp Terms/Key Words: nanotechnology, nonbiomedical equipment, technology /technique development, water treatment, water sampling /testing, microorganism toxicology, photochemistry, oxidation, catalyst
DESCRIPTION (provided by applicant): The average person in the U.S. contains detectable levels of more than 100 industrial compounds, pollutants, and chemicals, but predicting the relative risk of this exposure, especially over time, is challenging (US CDC, 2003). Successful development and commercialization of next-generation, low-cost, high-performance technology for predicting compound toxicity would help assess safe levels of environmental exposure-thereby reducing national healthcare costs and producing safer working/living environments. This exposure to environmental toxins plays an important role in aging and oxidation processes, which are key risk factors of macular degeneration, a process that eventually leads to blindness. Importantly, however, there are currently no accepted or practical tests for measuring the retinal toxicity of compounds directly. In vivo assessments of retinal toxicity, when performed, require large numbers of animals, are time-consuming and expensive, and do not provide data on toxicity progression. The ability to prepare stable primary mixed retinal cultures in vitro would allow screening and prioritization of further toxicity testing in a rapid and cost-effective manner. Ideally, such a system should allow differentiation of light-dependent toxicity [phototoxicity] and general toxic effects, and would mimic in vivo toxicity. Therefore, the overall goal of this multi-phase SBIR project is to develop, validate, and commercialize Ocuscreen(tm), Acucela's proprietary retinal culture screening system, as a next-generation in vitro system for ranking the relative (photo)toxicity of environmental toxins, and to have this assay incorporated as a part of the regulatory framework for the commercialization of chemicals. The Specific Aims for Phase I of this project are to identify a group of known retinal toxicants, to prove the feasibility of ranking their (photo)toxic potential, and finally to show these rankings correlate with in vivo literature data. Demonstrating that we can predict (photo)toxicity (or lack thereof) in a small class of representative compounds will establish the predictive potential of our new system within the limited scope of the Phase I proof-of-concept project, and will set the stage for a larger Phase II demonstration effort. Phase I will also provide sufficient data for Ocuscreen to be nominated as an alternative test method to the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and will allow us to determine how well Ocuscreen meets ICCVAM performance standards. Phase II work will involve establishing a large photoreceptor toxicity database of chemicals-built both from existing knowledge and results from our assay system-to improve the predictive accuracy of compound safety. Phase III of the project will be focused on establishing a commercial screening service for photoreceptor toxicity. Even without formal regulatory adoption, the ability to accurately predict toxic potential will provide a compelling service to chemical companies and will represent an important step in protecting human health. The average person in the U.S. contains detectable levels of more than 100 industrial compounds, pollutants, and chemicals, but predicting the risk of this exposure, especially to eye toxicity, is challenging. Current prediction methods require large numbers of animals, are time-consuming and expensive, and do not provide data on toxicity progression. The overall goal of this project is to develop, validate, and commercialize Acucela's proprietary retinal culture screening system as a next-generation, practical in vitro system for evaluating the health effects of environmental toxicants.
DESCRIPTION (provided by applicant): Environmental toxicants are increasingly linked to adverse birth outcomes such as low birth weight, preterm birth, birth defects and developmental delays. Inner-city populations are at higher risk for adverse birth outcomes and also are more likely to be exposed to environmental toxicants. Obstetric providers are seeking clarification about the true risks of many environmental exposures and what message they should deliver to their patients. Patients in this population are confused by the conflicting messages they receive from providers and peers about behaviors and exposures that could put their fetus at risk. The Institute of Medicine and the National Environmental Education and Training Foundation recommend the integration of environmental health concepts into all levels of medical and nursing education. In the proposed SBIR Phase II project called Managing Environmental Risks in Pregnancy, Vida Health Communications, Inc. will complete the development and evaluation of the web-based provider training and patient education multi-media prototyped in Phase I. The final products of this research will be (1) a cross disciplinary web-based training offering continuing education for obstetric providers serving urban populations, (2) an educational DVD in English and Spanish and group discussion guide for showing to patients in clinic and office waiting areas or in facilitated group discussions, (3) a library of colorful support materials in English and Spanish at appropriate levels of literacy for providers to print and distribute to patients made available both as electronic documents (pdf) and in preprinted form. The interventions will be evaluated using focus groups representative of the target audiences. Evaluators will use well-documented qualitative techniques to analyze focus group data. This project will advance the environmental health training of obstetric providers serving urban populations that may be at risk for exposure to substances that can harm their developing fetus. It will also provide much needed education, at appropriate literacy levels, for at-risk women about ways that they can moderate fetal exposure to environmental risks in pregnancy. Narrative: We are beginning to recognize the scope of environmental toxicants that urban-living pregnant women may be exposed to. Given the rapid development of a fetus, especially in the early months of pregnancy, avoidance of exposure is at present the most effective way to mitigate potential harm. This research will contribute to knowledge of how prenatal care providers can interest, inform and motivate pregnant women who likely bear the greatest risk of exposure, so they can protect the fetus and improve the chance of giving birth to a healthy, normal infant.
DESCRIPTION (provided by applicant)
Numerous pollutant compounds are continuously released into the environment during their production, use and disposal. The resulting mixtures contaminate the environment and can be a potential threat to human beings. Heavy metals are significant environmental pollutants because they tend to persist in the environment, tend to bioaccumulate and can result in adverse health effects when ingested or inhaled. These metal species can be measured in human tissue or fluids such as blood or urine, usually in central laboratories using complex methods such as high-performance liquid chromatography inductively coupled plasma mass spectroscopy. However, in view of the high labor and analytical costs and long time delays associated with centralized laboratory analyses, there is an immediate need for a portable and inexpensive system for on-site monitoring of exposure to heavy metals in living systems, especially humans, as a result of exposure through drinking water, environmental, and industrial sources. Field deployable monitoring systems for in-situ, on-site, personal human exposure assessment will allow realtime monitoring of exposure to trace toxic metals, and facilitate the use of bio-monitoring data by allowing the instrument to be taken to the sample rather than the traditional way of bringing the sample to the laboratory.
The overall objective of this project is to develop a portable, self-contained, easy-to-use monitor for simultaneous on-site measurement of arsenic, cadmium, mercury and lead metals from one urine sample, in near real time, to assess personal exposure. The proposed sensor will combine the high sensitivity of a specialized electrochemical measurement technique with a unique microarray electrode material and configuration. During Phase I, we will investigate sensor design configurations, electrode material composition, and the preliminary operating conditions which will demonstrate the feasibility of the unique microchip sensor prototype for detection of arsenic and cadmium species. At the conclusion of the Phase I/II program, a compact, packaged prototype sensor instrument will have been developed, tested and utilized in pilot epidemiological field trials.
DESCRIPTION (provided by applicant): The soil nematode, Caenorhabditis elegans (C. elegans), is a promising model organism to assess the effects of potential developmental and neurological toxicants on multi-cellular organisms. However, to determine the possibility of using C. elegans as a practical and efficient model in toxicology studies, medium throughput technologies must be created to monitor phenotypic characteristics including growth, size, reproduction, feeding, and movement. Methods in current practice are not conducive to medium-throughput studies because they are often manual and laborious to perform. There is a noticeable lack of computerized automated quantitative C. elegans analysis tools that perform well in the presence of differing experimental conditions. We propose to develop a commercial product that will be composed of a computerized microscope system that allows investigators to perform advanced automated, quantitative analyses of the locomotion and other complex behaviors of freely moving C. elegans nematodes. We believe that introduction of a robust commercial software solution will significantly contribute to further replacement and reduction of conventional toxicology tests by alternative in vivo toxicology assays using C. elegans. Public Health Relevance: The proposed project will enable research using the model organism, Caenorhabditis elegans (C. elegans), to occur at a faster pace than is currently feasible by allowing complex and laborious tasks currently performed manually to be done automatically. This will allow researchers to increase the throughput of studies involving quantitative behavioral analysis. The overall effect of this project will significantly improve the productivity and effectiveness of research in such diverse fields as toxicology, environmental monitoring, ecology and neuroscience research.
DESCRIPTION (provided by applicant): US Department of Transportation and international regulations require testing of all chemicals for skin corrosivity, which is defined as destruction of human skin at the site of contact. For safe handling and transportation purposes, each corrosive is assigned a "packing group" designation, which depends on how quickly skin damage occurs. Previously accepted test methods have utilized rabbits to determine packing groups. However, corrosive chemicals are very harsh and can cause considerable discomfort and/or severe pain to the animals. A number of in vitro tests have been developed but none of them adequately meet all of the US regulatory and market needs. The goal of this project will be to utilize a human skin-like in vitro model, EpiDermTM, to develop and validate an in vitro assay to determine skin corrosivity packing groups. Phase I research will determine the assay parameters necessary to differentiate between the 4 corrosivity packing groups. A preliminary prediction model (PM) will be developed using 12 reference chemicals and PM will be tested with an additional 28 test materials. After fine tuning the PM, interlaboratory reproducibility and interlaboratory transferability of the assay will be assessed. Successful completion of the Phase I goals will constitute the pre-validation process for proceeding to formal assay validation studies in Phase II. PUBLIC HEALTH RELEVANCE: Skin corrosivity testing is necessary to insure the safe handling and transport of chemicals. Animal-based test methods suffer from animal welfare concerns and current in vitro methods do not meet all US regulatory requirements. This project will develop an in vitro assay to determine skin corrosivity packing groups and fulfill all testing and regulatory needs.
DESCRIPTION (provided by applicant): Solidus Biosciences, Inc. is developing a proprietary Metabolizing Enzyme Toxicology Assay Chip (MetaChip), along with a xenobiotic metabolism and toxicity screening device that uses these chips (the MetaReader), for high- throughput analysis of drug metabolism and toxicity. The MetaChip integrates the high-throughput metabolite- generating capability of P450 catalysis with human cell-based screening on a single microscale platform. As a result, P450-generated drug-candidate metabolites can be generated and screened against human cell lines even if the metabolites are unstable. The MetaChip platform along with the MetaReader provides Solidus Biosciences with an enabling technology that will have myriad applications in both early stage and preclinical toxicology testing. Solidus is therefore developing the first technology and associated products that can rapidly replicate human metabolism and perform in vitro toxicity testing in a single, automated, high-throughput manner. Consequently, Solidus' products have significant commercial potential and the promise to greatly benefit human health. The proposed Phase II program will focus on the full optimization of the MetaChip and on the design, preparation, and operation of the MetaReader, both of which can be readily combined with other in vitro toxicology and metabolite profiling approaches that deal with ADME (adsorption, distribution, metabolism, and excretion) of xenobiotics. The specific aims and milestones for the Phase II STTR are to: 1. Optimize P450 loading, activity, and stability within sol-gel matrices and generate sol-gels with physicochemical properties that accurately and reproducibly mimic the human liver; 2. Perform rapid P450 inhibition assays on the MetaChip using well-known inhibitors of the different human P450 isoforms; 3. Complete development of the collagen gel and other 3D cell culture techniques for growth inhibition assays on the MetaChip; 4. Expand the repertoire of metabolic enzymes to include phase II drug metabolism enzymes. This also includes addition of glutathione for conjugation to metabolites generated in the MetaChip; 5. Co-develop (with an industrial collaborator) the MetaReader to streamline the application of sample, the enzymatic reaction and assay steps, and image analysis in a simple operating scheme; 6. Use the fully operational MetaChip platform to correlate in vitro toxicity results to in vivo toxicity results. This aim involves components of the ICCVAM validation process. The end result of the Phase II study will be a fully operational and integrated device, the MetaReader, that will become an important tool in early-stage testing of drug and drug-candidate toxicity, and in the development of in vitro models that mimic human metabolism.
Crisp Terms/Key Words: high throughput technology, microarray technology, genetic screening, combinatorial chemistry, cell line, technology /technique development, cytotoxicity, cytochrome P450, growth inhibitor, enzyme inhibitor, drug screening /evaluation, drug metabolism, biotechnology
DESCRIPTION (provided by applicant):
Skilled Service Personnel (SSP) support emergency response organizations during an emergency incident, and include laborers, operating engineers, carpenters, ironworkers, sanitation workers and utility workers. SSP called to an emergency incident rarely have recent detailed training on the chemical, biological, radiological, nuclear and/or explosives (CBRNE) agents they may encounter or the personal protection equipment (PPE) relevant to the incident. This increases personal risk to the SSP and mission risk at the incident site. Training for SSP has been identified as a critical need by the National Institute for Environmental Health Sciences, Worker Education and Training Program. The proposed SBIR Phase II project addresses this SSP training shortfall by developing a wireless lesson delivery system called the Just-In-Time Training for Emergency Incidents System (JITTEIS). SSP dispatched to an emergency incident receive brief site-specific multimedia lessons on their cell phones derived from the Occupational Safety and Health Administration (OSHA) #7600 Disaster Site Worker Course. The lessons describe the CBRNE threats and safety protocols (including PPE) identified by the Safety Officer (SO) at the incident site. Users are permitted to upload new content for immediate broadcast, such as pictures or video clips of newly discovered hazards. JITTEIS builds upon the Phase I effort, which achieved (1) interoperability among diverse mobile devices, wireless service providers, calling plans, and incident management systems, (2) instructional designs and production procedures for lessons rendered on mobile devices user modeling and system ergonomics, (3) pushed versus pulled content delivery, and (4) training adaptation to rapidly changing threats. The proposed effort will complete the development of a fully operational JITTEIS, develop a set of available training lessons based on needs, and deploy and evaluate the system in two settings that together encompass many of the requirements of CBRNE incidents: a large New Jersey construction sites involving hazardous waste material and a distributed work force, and the command center and distributed vehicle fleet of New Jersey's largest paramedic organization. It is anticipated that JITTEIS will become a valuable commercial service to emergency response organizations and other organizations with widely dispersed, mobile workforces who need safety and health just-in-time training and information.
DESCRIPTION (provided by applicant):
Skilled Support Personnel (SSP) are essential to site recovery, yet they are often under-trained in hazmat response and may lack knowledge of how to cope with specific incidents. Poor training and rusty skills lead to injury to themselves and others, as well as making the overall situation worse. Beyond full instructional courses, a continuum of training and real-time performance support is needed to enable these crews to work effectively. Mini-course modules for enroute and onsite training, on-the-job performance aids and simple checklists, and access to live expert mentors who support decision making or deliver mini lesson Just-in-Place(r) should all have a place in this training and performance support package. Just-in-Place(r) is our proprietary approach to delivering content and services, tied to context relevant factors such as: time, location, skills, tasks and who or what is nearby. The project team will meet this need by building the Viyant Hazmat Skilled Support Personnel Just in Place Performance Support System (Viyant Hazmat) in collaboration with established hazmat training organizations and service providers. Viyant Hazmat will enable mobile Just-in-Place training materials, performance aids, and checklists to be accessed at the job site and permit real-time collaboration with hazmat and medical experts at remote locations. Not only will SSPs be able to talk directly with experts, the experts' situational understanding will be increased by using web collaboration tools allowing the onsite SSP to send live images and video to remotely located experts. Viyant Hazmat comprises an integrated suite of computer hardware, ranging from wearable computers to cell phones, wireless communications, mixed reality software tools, content authoring tools, administration tools and support services that are optimized for improving safety and effective decision making. The specific target audience for this Phase I effort is demolition crews at Superfund, brownfields and disaster sites. Other hazmat audiences will be addressed during commercialization. Viyant Hazmat will be built on the Company's Viyant(tm) Standard Edition platform, which is currently being used to facilitate equipment repair, maintenance and installation training and operations for technicians at a distance. Our research will include: 1) prototyping the Viyant Hazmat software system; 2) conducting system usability and ergonomics testing with demolition workers with and without personal protective equipment; 3) developing sample mini training modules, performance aids and checklists based on existing training materials from partner service providers; 4) testing learning effectiveness of incident-specific training materials; and 5) field testing the system.
DESCRIPTION (provided by applicant): Cost-effective catalytic DNA biosensors for heavy metal ions such as lead(II), uranium(VI), mercury(II), and cadmium(II) will be developed. They will be tested for on-site, real-time detection and quantification with minimal rates of false positive or false negative results. Exposure to these metal ions can cause severe adverse health effects, such as damages to brain, kidneys, and cancers, to human beings, especially children. Current technologies for metal detection employ either expensive or sophisticated instruments or simple sensors, many of which have high rates of false positive or false negative results. Therefore there is an urgent need of reliable portable heavy metal sensors for government inspectors, environmental monitors, household users, clinicians in rural or remote areas, and first-responders in the war against terrorism, where on-site, real-time, and cost-effective detection and quantification are critical and the market for heavy metal detection is estimated to be >$650 million. The project is based on several innovations in the PI's group at the University of Illinois that takes advantage of state-of-the-art tools in catalytic DNA biology, catalytic molecular beacons biotechnology and nanoparticle nanotechnology. Catalytic DNA molecules specific for heavy metal ions will be obtained through in vitro selection, and converted to fluorescent (for quantitative measurement) and colorimetric (for qualitative and semi-quantitative measurement) sensors by combining the DNA with fluorophore/quencher pairs and gold nanoparticles, respectively. The feasibility of transforming the innovations into commercial success at the DzymeTech has been established in the NIH STTR Phase I project (1R41ES014125-01), in which catalytic DNA sensors for lead(II) and uranium(VI) have been obtained that have high sensitivity (e.g., ~ 11 ppt) and selectivity (e.g., > 1 million fold). This Phase II application addresses critical issues of transferring the sensor design into prototypes of sensor kits for markets. The customer requirements will be determined and prototype components and protocols will be developed. They include: "Obtain all four fluorescent and colorimetric sensors for Pb(II), U(VI), Cd(II), and Hg(II). Characterize the sensors by determining the detection limit and selectivity of each sensor. "Design and characterize prototype sensor kits for each metal ion. Including sensor components, storage condition and test protocol optimization, high/low temperature stability tests and reproducibility tests with sensors from multiple-batches. "Test field samples to study interference and matrix effects. Real field samples, including soil and water samples will be collected and tested. Sensor performance with real samples will be used to evaluate the commercialization values of the sensor kits.
PUBLIC HEALTH RELEVANCE: Highly sensitive and selective catalytic DNA sensors for lead(II), uranium(VI), cadmium(II), and mercury(II) will be developed for cost-effective on-site and real-time detection and quantification. Heavy metal ions are widely present in the environment, causing significant health problems such as damages to brain, kidney, and neural system to human beings, especially children. Convenient portable sensors developed in this project will enable government inspectors, environmental monitors, household users, clinicians and first-responders make informed decision about remediation and monitoring strategy and thus improve human health and quality of life.
DESCRIPTION (provided by applicant): Among the various functional imaging techniques, SPECT maintains an important role in the study of disease models in small animals as well as in patient care. Many SPECT-labeled imaging probes that have highly specific distributions with very little background are being used to measure a wide range of biological parameters of importance in small animals including substrate metabolism, blood flow, hypoxia, protein synthesis and receptor characteristics. The utility of this important modality has been significantly enhanced in recent years by the development of methods to image transgene expression in vivo. Furthermore, SPECT is capable of dual-isotope imaging for correlating two biological processes with a single imaging study. Recent demand for small animal SPECT has also been driven by the pharmaceutical industry where in vivo quantification of biological processes to measure an agent's mechanism of action and its concentration at the site of action is necessary. Each of these applications requires excellent spatial resolution, not only because of the small scale of the details to be imaged but also for the demanding detection and estimation tasks. Unfortunately, existing SPECT instrumentation does not provide the required performance, so the development of a high-resolution detector is essential for the improvement of future SPECT systems. To address these issues, we propose to develop a novel detector based on a unique design of a scintillator coupled to a very high spatial resolution readout. Specifically, the scintillator design and fabrication will minimize the loss of resolution arising from parallax errors due to depth-of-interaction effects within the scintillator, while maintaining very high efficiency for the detection of incident radiation. This combination of scintillator and readout, when coupled to a custom designed collimator, will form a SPECT detector module that can achieve extremely fine spatial resolution and high sensitivity in a cost-effective manner. The effort subsequent to the successful development of the detector module will focus on the development of a complete small-animal SPECT system as a prototype product.
DESCRIPTION (provided by applicant): Recent scientific investigations have shown that many chemicals used in plastics, pharmaceuticals, pesticides, cosmetics, food additives, etc., are endocrine disruptors (EDs). EDs interfere in various ways with hormones such as estrogens to have significant adverse effects on many behavioral and physiological processes. ED effects (e.g. estrogenic or anti-estrogenic) sometimes occur at very low (picomolar to nanomolar) concentrations, especially on fetal or developing mammals (including humans). The prevalence and actions of EDs in our environment warrant the development of valid assay methods. Consequently, various governmental bodies (e.g., EPA, FDA, and ICCVAM) and proactive corporations have explicitly expressed a desire to have in vitro robotic assays for EDs, such as anti-estrogenic activity (anti-EA). However, no robotic anti-EA assay is commercially available. To begin to meet these governmental, scientific and commercial needs, CertiChem (CCi) has completed a Phase I SBIR grant showing that it is feasible to develop an anti- EA robotic assay that would be valid (i.e., reliable, accurate, versatile, rapid, and cost effective) using MCF-7 cells. In this Phase II application, CCi now proposes to develop this robotic assay for anti-EA for commercialization by repeatedly assaying a set of 78 reference test chemicals to confirm the reliability and accuracy of CCi's proposed anti- EA assay. CCi also proposes to demonstrate the versatility of this assay by examining the anti-EA in a set of antioxidants used in foodstuffs and plastics. Finally, CCi proposes to perform HPLC separation assays on some reference test chemicals to confirm that their anti-EA is not due to contamination and to enhance the versatility of this assay for commercial use. Development of a robotic screening assay for anti-EA is commercially, scientifically, and socially important because of the large number of chemicals (>10,000) - much less chemical mixtures - that should now be screened for anti-EA by profit, non-profit, or governmental entities. Development of a robotic assay for anti-EA is desired as part of the mission of NIEHS, EPA and ICCVAM. Recent scientific investigations have shown that many (perhaps over 10,000) chemicals used in common products such as plastics, pesticides, cosmetics, and food additives have estrogenic/anti-estrogenic activities that severely interfere with normal estrogen actions to produce adverse effects on many behavioral, reproductive, and physiological processes in humans. In this Phase II proposal, CertiChem (CCi) proposes to develop a very sensitive and accurate assay to measure anti-estrogenic activity in a set of reference test chemicals and in common consumer products. CCi proposes to use these data and CCi's data on estrogenic activity on many chemicals to identify which chemicals have anti-estrogenic activity and to work with various firms to design consumer products that are free of chemicals that release anti-estrogenic or estrogenic activities.
DESCRIPTION (provided by applicant):
The objective of this proposal is to develop a curricula of role specific online e-Learning courses that meet the needs of a diverse workforce of Hazardous Material workers in the transport modalities of: highway, marine, air, rail, and International. This specifically relates to the goals of the Worker Education Training Program and Health Worker 2010. Hypothesis: Online e-Learning can improve mandated workforce Hazardous Material training by increasing individualization, using the web to simplify dissemination, and shortening time-to-competence, while saving costs. Phase I developed and implemented a highly interactive, e-Leaming course, HazMat Truck, and supporting systems. Experts and workers have favorably evaluated the streamlined approach, time-savings, and opportunity to practice designed into the course. Phase II proposes to broaden that study in number and occupation and to develop a curricula of courses with interactivity that addresses the needs of workers in all transport modes. Once finalized, courses will be translated to Spanish and test-marketed. Phase III will sell or license the courses to companies required to provide training combined with the unique delivery system that specifies exactly the right course to take, maintains training records, and sends refresher reminders. Technological innovation will provide: (1) a curriculum of up-to-date, interactive courses that meets diverse needs, (2) a protocol that matches competency needs to course content, (3) analysis of the efficacy of e- Learning for this population, (4) a customization database that can add state, local, and institution specific requirements to the generic courses. The potential commercial outcome will benefit workers and companies. Millions of people in the US, federally mandated to receive workplace Hazardous Material training, often they do not receive it due to time, travel, or language. These courses will solve that. Companies responsible for delivering yearly training could save $1.4 billion per year in the US and ensure valid, up-to-date training, available anytime, anywhere.
DESCRIPTION (provided by applicant): In this Phase II project, BlueInGreen, LLC will build a hypersaturated dissolved ozone (HYDOZTM) unit to deploy in a large pilot-scale study at Springdale Wastewater Treatment Facility (SWWTF) in Springdale, Arkansas. Furthermore, BlueInGreen will collaborate with the University of Arkansas to measure the ability of HYDOZ ozonation to remove refractory microbes and stable chemical contaminants from wastewater effluent in both lab-scale and pilot- scale studies. Phase I results demonstrated the increased efficiency and effectiveness of HYDOZ ozone treatment at bench scale compared to conventional ozonation systems. Phase II research will focus on stable contaminants and refractory microbes that are not removed from wastewater using standard chlorine-based disinfection. We will show that the use of the HYDOZ to treat wastewater at centralized wastewater treatment facilities is a viable method economically and technologically to prevent the release of pharmaceutical residuals and resistant microbes to the environment. This project directly addresses the mission of the National Institute of Environmental Health Sciences to reduce the burden of human disease and dysfunction from the environment and will demonstrate both the efficacy and efficiency of HYDOZ ozonation of wastewater effluent. The specific Phase II objectives are: " Objective 1: Compare cost and efficacy of the HYDOZ to standard disinfection/decontamination technology (BlueInGreen). Milestone 1: The capitol and operating cost of HYDOZ systems is superior to chlorine-based disinfection systems, and based on standard effluent quality parameters, the HYDOZ systems are superior to chlorine-based disinfection systems for treatment of wastewater effluent. " Objective 2: Study HYDOZ destruction of a range of chemical contaminants in wastewater effluent (BlueInGreen). Milestone 2: The HYDOZ ozonation systems will cause a minimum 90% reduction in concentration of at least six chemical contaminants from wastewater effluent. " Objective 3: Study HYDOZ destruction of plasmids and refractory microbes in wastewater effluent (University of Arkansas). Milestone 3: The HYDOZ ozonation systems will cause a minimum 90% reduction in concentration of plasmids and refractory microbes from wastewater effluent.
PUBLIC HEALTH RELEVANCE: The goal of this project is to use the hypersaturated dissolved ozone (HYDOZTM) system to remove stable chemical/pharmaceutical residuals and refractory microbes from wastewater. Successful reduction of the occurrence of these contaminants in the aqueous environment will reduce long-term impacts on ecosystems and humans, and reduce the spread of antibiotic resistant microbes. The widespread use of this device will significantly contribute to the reduction of antibiotic resistant pathogens in the human ecosystem and help maintain the efficacy of medically important antibiotics.
DESCRIPTION (provided by applicant): Genomic methods simultaneously report both specific and holistic assessments of biological systems an ideal property when assessing the potential impact of chemicals on ecosystems and the environment. To date, however, genomics infrastructures have not been developed for one of the most commonly used and accepted environmental toxicity monitoring organisms Ceriodaphnia dubia. In this Phase II proposal, we expand on our Phase I work by sequencing a large number of C. dubia cDNAs using high-throughput sequencing. After sequence assembly and annotation, we will print a 4x70,000-element oligonucleotide microarray representing at least 10,000 distinct genes. This array will be used to perform toxicity tests on four reference toxins with different chemical properties. Each of the chemicals tested will be assayed at three different concentrations. We will define expression signatures for each of the toxins and attempt to correlate expression results with known toxicity mechanisms. In addition, we will perform one 7-day exposure at a low concentration of a toxin known to have chronic effects and note how the expression profile changes over time. Finally, we will assemble a highly annotated Ceriodaphnia database that has been integrated into a bioinformatics infrastructure that will allow easy interpretation and sharing of hybridization data.This project aims to develop DNA microarrays for the identification and understanding of environmental toxicity in the one of the key organisms used for testing environmental toxicity the water flea Ceriodaphnia dubia. DNA microarrays are a uniquely powerful method of identifying and characterizing environmental toxicity due to their ability to combine many specific tests to achieve a global understanding of toxic effects.
High throughput DNA sequencing and NimbleGen based array synthesis will be used to produce fully annotated and commercial ready microarrays for use both in academic and commercial settings. In addition to commercially available Ceriodaphnia microarrays, Eon Corporation will facilitate use of these arrays through contracted performance of microarray based tests, and distribution of an expression analysis database that incorporates identification, function, and expression information for each element/gene.
Technologies for environmental toxicity testing have fallen 15 years behind those now commonly used in pharmaceutical toxicity testing. Without new technologies for identifying and characterizing environmental toxins, the increasing variety and quantity of chemicals released into the environment will mount untold environmental and human health tolls.
DESCRIPTION (provided by applicant): In this proposal we respond to the call by the National Institute of Environmental Health Sciences (NIEHS) in the PHS 2007-2 Omnibus Solicitation for "new products/devices, tools, assays to improve our ability to precisely measure environmental exposures to individuals with high temporal and spatial resolution." According to the solicitation, the device should be of appropriate scale to be field deployable and/or wearable. Ozone, formed in photochemical air pollution, has well documented adverse effects on human health, including reduction of lung function and aggravation of preexisting respiratory disease such as asthma. Emergency department visits, daily hospital admissions and mortality increase during episodes of high ozone concentration. A Personal Ozone Monitor (POM) is required for environmental health studies of the physiological effects of ozone and for validating computer models of human exposure such as the Air Pollution Exposure (APEX) model used by the Environmental Protection Agency to assist in establishing national air quality standards. We propose to develop a small (4 x 3 x 1 inch), light weight (d 1 lb), low power (d 3 watts), low cost (d $800 in parts) battery-operated POM based on the well established method of UV absorbance. The instrument will result from further miniaturization of a backpack-sized instrument already commercialized by 2B Technologies and successfully tested as a personal exposure monitor. The pocket-sized POM will have a precision and accuracy of better than 2 ppb and make new measurements every 10 s. The instrument will have an internal data logger and USB computer interface for downloading data into a personal computer. During Phase I, we will evaluate and select miniaturized components, design and construct a prototype POM, test the prototype for effects of orientation, vibration and rapid temperature and humidity change, and, finally, characterize the instrument with respect to the analytical figures of merit of linearity, precision and accuracy. PUBLIC HEALTH RELEVANCE: A pocket-sized, battery powered Personal Ozone Monitor (POM) will be developed and tested. The POM, which will be based on the well established method of UV absorbance, will facilitate physiological studies of the adverse effects of ozone, formed in air pollution, on human health.
DESCRIPTION (provided by applicant): Arsenic is one of the most serious environmental contaminants in the United States. The traditional method for arsenic remediation involves excavating the contaminated soil and disposing it in hazardous waste landfills. This method is highly labor intensive and costly, especially for large sites. An alternative remediation technique is phytoremediation, the use of plants to remove toxins from contaminated soils or water and concentrate the toxins in the biomass compared to the environment. Edenspace is an industry leader in the use of plants to remediate arsenic from contaminated soil or water and has worked on numerous sites across the country. Arsenic phytoremediation currently uses an arsenic-accumulating fern plant. While this perennial tropical plant is effective is accumulating and removing arsenic from the soil, its use is limited by the need to transplant young plants rather than growing plants from seed, and by its low tolerance for sustained temperatures below -5¿C. Development of alternative crops that are more widely adapted with similar abilities to accumulate arsenic will provide enhanced capabilities to address the problem of environmental arsenic. For this STTR project Edenspace and its research partner, the University of Massachusetts (UMass) propose to develop enhanced plants for arsenic phytoremediation. A number of plant and microbial genes have been isolated and characterized that confer fourfold increases in arsenic tolerance and uptake in the model plant Arabidopsis thaliana. Because this plant has low commercial potential for remediation due to its small size, the team will bioengineer a highbiomass, non-food variety of a row crop, Brassica napus, with the transgenes. In Phase I, Edenspace will confirm that the transgenic B. napus shows the same arsenic tolerance and uptake phenotype observed in transgenic Arabidopsis, which will lead in Phase II to a small scale field demonstration. PUBLIC HEALTH RELEVANCE: Arsenic is a highly toxic substance found either naturally in the environment or concentrated by human activity at contaminated sites, and provides significant health concerns to humans and wildlife. This project intends to develop an effective and economical technology capable of removing arsenic from the environment using plants and lowering the public's risk of exposure to arsenic.
DESCRIPTION (provided by applicant): Several US agencies and regulators require low-cost chemical sensors for detecting and monitoring environmental clean-up, remediation, and decommissioning processes where groundwater may be contaminated. The sensors must be capable of detecting contaminants in the sub-surface groundwater and must be compatible with use in a range of environments. Most significantly, these customers require a low-cost alternative to its current expensive and labor intensive methods, namely using mobile laboratories. The project will result in the innovative use of low-cost sensor systems that will be capable of detecting and monitoring for dense non-aqueous phase liquids in the subsurface and groundwater, unattended, and in real- time from within a push-probe, using a chemicapacitor array and miniature preconcentrator. Seacoast's Phase I research will focus on developing the sensor array, demonstrating sensitivity to chlorinated hydrocarbons at relevant concentrations, and field tests in actual contaminated sites. The ultimate goal is to provide the DOD, DOE, NIEHS and other agencies with a method to map and track subsurface contamination plumes in real-time without requiring an operator. The systems will have MEMS microcapacitor sensor arrays that can monitor for leaks of toxic chemicals, contaminants from wastes, and changes in groundwater streams. A preconcentrator collects the contaminants and releases them to a microsensor array. The sensor arrays are filled with several chemoselective polymers whose dielectric permittivity changes when exposed to different vapors, creating a fingerprint response for each chemical. An array of differently responding sensors and pattern recognition can thereby compensate for changes in humidity, temperature, and composition. These low-power systems can be left unattended and transmit data wirelessly or through USB to a central location. The most important application to public health and safety is unattended monitoring of drinking water, water treatment processes, and water sources. The potential commercial markets include building chemical process monitoring and control, toxic vapor leak detection, industrial process control, and industrial health and safety. Transitioning the developed prototype to other markets where worker and public health, environmental health and regulatory compliance will be investigated to reduce the financial risks and broaden the acceptance of the technology. PUBLIC HEALTH RELEVANCE: This proposal will describe a potential method to specifically address the need for detecting groundwater contaminants and long-term monitoring of contaminated sites, by providing an unattended sensor system that tracks contamination in real-time and transmits contaminant concentrations. Such a system would be used in tandem with other methods, to provide comprehensive contamination management at DOE, DOD, and Superfund sites where ground and water clean-up projects are already underway. The proposed work will focus on detection of chlorinated hydrocarbons, which are described as among the most common pollutants in groundwater and soils at DOE sites.
DESCRIPTION (provided by applicant): The goal of this Phase II Small Business Innovative Research (SBIR) application is to create a series of educational materials for the National Institute of Environmental Health Sciences (NIEHS) entitled Powers of Inquiry: Using Image Analysis to Explore Environmental Health Science. The ten lessons to be published by the project will employ four advanced technology tools-NASA Image2000 (NI2K), ArcExplorer Java Edition for Education (AJEE), Imaged, and Weblmage-to lead middle and high school students through inquiry- based explorations often case studies related to the mission of NIEHS. In Powers of Inquiry, students will use NI2K, AJEE, ImageJ, and Weblmage to display and enhance digital images from research being conducted by NIEHS-supported and other scientists. With these tools and the support provided by the Powers of Inquiry materials, students will strengthen their science and technology skills, become better consumers of scientific data, and develop an appreciation for the role that NIEHS plays in protecting the health of the nation. A "powers of ten" format will organize the lessons in Powers of Inquiry. Each lesson in the series will zoom in on environmental health issues, starting at the planetary level and moving through lessons about the stratosphere, coastal regions, communities, neighborhoods, homes, human organs, microscopic organisms, and human tissue cells to arrive at a lesson on the benefits and risks of molecule- sized nanotechnologies. The educational goal of the Powers of Inquiry materials will be to introduce environmental health science to middle and high school students with an engaging visual medium that involves them in inquiry-based activities supporting accomplishment of state and national standards for science, mathematics, technology, and reading education. The materials will be developed by Science Approach, a for-profit organization founded by staff from the Center for Image Processing in Education (CIPE). CIPE, a well-respected nonprofit provider of instructional materials and professional development services to teachers, has a successful track record of developing and commercializing instructional materials similar to Powers of Inquiry.
Crisp Terms/Key Words: educational resource design /development, clinical research, interactive multimedia, digital imaging, human subject, health science research, field study, environmental health, secondary school, elementary school, computer program /software
DESCRIPTION (provided by applicant)
Polycyclic aromatic hydrocarbons (PAHs) constitute a complex group formed from incomplete combustion of organic carbon and are found in significant amounts in automobile exhaust, cigarette smoke, various foods, and industrial waste by-products. They represent serious, ubiquitously environmental contaminants. PAHs contamination of individuals occurs by inhalation, ingestion, or contact. Some PAHs are carcinogenic, teratogenic, and mutagenic. Biomonitoring is essential to make precise, quantitative measurements of personal exposure to environmental chemical/biological agents because it can provide an assessment of the integrated uptake through all exposure routes. Conventional biomonitoring methods are often complex, time-consuming, labor intensive, and expensive.
Immunoassay is probably the most commonly used technology for the detection and quantification of biomolecules in the diagnosis and management of disease. Current trends in the development of immunoassay methodologies are miniaturization, multiple detection, and automation. On the other hand, nanotechnology has recently boomed because of the availability of new investigative tools. This technology makes it possible to characterize chemical and mechanical properties at a single molecular level, discover novel phenomena and processes, and provide science with a wide range of tools, materials, devices, and systems with unique characteristics.
The aim of this project is to develop a novel multiple biological sensor combining immunoassay (antibodybased detection) and emerging nanotechnology (a nanoscale biosensor) to assess real time and continuous readout of internal exposure to priority environmental chemical agents, specifically to PAHs. In this innovative approach, the presence of targeted biomolecules in serum is monitored by specific antigen-antibody interaction at the nanoscale. Specific antigen-antibody interactions make this approach highly precise to identify specific antigens, such as biomarkers for PAH exposure, enabling accurate assessment of the exposure. Other advantages of this approach over conventional immunoassay techniques are (i) no other signal-generating moieties (labeling agents) are needed to measure the antigen-antibody interaction, (ii) multiplex assessment of informative and predictive serum biomarkers is possible, and (iii) wide range of applications. During the Phase I project, the proof-of-concept will be established, including the detection of antibody/antigen interactions in serum and in the presence of other biomarkers of other environmental exposure set.
The proposed system has a high potential for user acceptance and has immediate commercial applications in many areas. Key segments in the medical diagnostic markets where the proposed technology can have an immediate impact include hospitals, clinics, clinical laboratories, medical insurance companies, and point-of-care uses.
DESCRIPTION (provided by applicant): Occupational exposures are estimated to account for 9-15% of adult asthma cases. Among the most common causes of occupational asthma are isocyanates, reactive chemicals necessary to make polyurethane products (construction, automotive, military, medical, foam, coatings, adhesives). Millions of people are currently employed in industries that utilize isocyanates, and the work-force at risk for exposure continues to grow along with consumer demand for polyurethane. Recognition and diagnosis of isocyanate asthma can be challenging for both patients and physicians. Symptoms can be insidious and difficult to associate with the workplace, especially delayed responses, which are often mistakenly attributed to environmental triggers. In workers that develop immunologic hypersensitivity to isocyanate, long-lasting decrements in lung function may occur, and persist years after exposure ceases. Exposure is the only known risk factor for isocyanate asthma, and is the major target for disease prevention. Contemporary industrial hygiene technologies (respirators, "spray booths") reduce, but cannot eliminate workplace exposure. New cases of isocyanate asthma continue to occur in an estimated 5 - 10 % of those occupationally exposed, and represent a substantial public health problem. Despite the well-known allergenicity of isocyanates, occupational exposure assessment and disease screening is limited. Diagnostic assays that reliably differentiate sensitivity to isocyanate vs other asthma triggers are greatly needed for clinical practice as well as workplace screening. Biomarkers of isocyanate exposure are also needed to help guide and monitor industrial hygiene efforts. We hypothesize that isocyanate serology assays can be developed as a strategy for disease surveillance and industrial hygiene (exposure) monitoring to help protect individuals who are occupationally exposed to isocyanate. The serodiagnostics that would be developed in this project are new in two major ways. (1) They would be based upon novel "isocyanate antigens", produced using a mixed phase (vapor/aerosol/liquid) exposure system developed by our laboratory, which mimics the air/liquid interface of the bronchial fluid that lines human airways. (2) They would utilize biomarkers of allergy (IgE) to detect hypersensitive individuals, AND make use of immunologic markers of isocyanate exposure (IgG), to help target and monitor industrial hygiene efforts. The final product of this project would be a sensitive and specific ELISA kit, incorporating these unique qualities, which would have widespread value for clinicians, research scientists, industrial management and health care providers. Published findings from our laboratory predict the ELISA kit will be far superior to the only 1 other similar product currently available commercially (by a single supplier that dominates the market), and will dispel false conclusions that may have been drawn from previous studies using isocyanate antigens of questionable biologic relevance. PUBLIC HEALTH RELEVANCE: This grant application focuses on developing a better understanding the allergenicity of isocyanates, a major cause of occupational asthma world-wide. The expected product of the study will be a serodiagnostic assay, based upon novel isocyanate-protein complexes, that can be used to protect workers health by (1) identifying hypersensitive workers, (2) identifying exposure hot spots in the workplace (3) monitoring internal exposure and (4) monitoring the effectiveness of industrial hygiene efforts.
DESCRIPTION (provided by applicant):
4.4.6 Project Summary Abstract During Phase I, MetaMedia Training teamed with the Rail Workers Hazardous Materials Training Program to produce the prototype DVD training tool entitled }Lessons Learned from Graniteville.} The specific aim of the Phase II project is to complete the design and develop a full interactive virtual experience that will reduce the risk faced by Rail Workers, First Responders, and the community when dealing with incidents involving hazardous materials transported by rail. If First Responders and Rail Workers follow a systematic approach to handling emergency incidents, public safety and workers' safety and health will be better protected and disasters may be mitigated more rapidly. This research is relevant to public health due to the increasing level of hazardous materials being transported via rail, and the current lack of adequate training materials for emergency personnel responding to such incidents. Approximately 800,000 shipments of hazardous substances travel daily throughout the United States, frequently through densely populated areas where the consequences of an acute release could result in environmental damage, severe injury, or death. In 2006 there were three recorded instances of chlorine tank car derailments in the United States. The DVD brings to life as a facilitated training exercise the catastrophic Norfolk Southern railroad derailment that occurred in Graniteville, SC in 2005. The collision released over 11,000 gallons of chlorine gas, causing nine deaths, injuring hundreds, and displacing hundreds more civilians. We have incorporated compelling and realistic interactive video simulations of hazardous materials incidents, instructive three dimensional computer animations, and engaging team exercises to produce an effective training tool that successfully transfers knowledge as noted in the subsequent evaluation. MetaMedia's application of DVD technology will take advantage of the unique features of DVD, such as high-quality motion video, interactive branching, and low-cost delivery systems to bring real-world simulations into the classroom. The deliverables for Phase II will be a completed DVD program providing up to 4 hours of content, including recommendations resulting from the evaluation, additional components of the interactive experience, and instructor and student guides. 4.4.7 Project Narrative This research is relevant to public health due to the increasing level of hazardous materials being transported via rail, and the current lack of adequate training materials for emergency personnel responding to such incidents. Approximately 800,000 shipments of hazardous substances travel daily throughout the United States, frequently through densely populated areas where the consequences of an acute release could result in environmental damage, severe injury, or death. Exposure to chlorine gas shipments alone, traveling to drinking water and waste water treatment plants, exposes more than 25 million Americans who live near these facilities and one million more living in cities and towns along the rail delivery routes.1 DHS and security experts continue to warn of the risk for industrial chemicals used by terrorists as weapons of mass destruction. Terrorists have attacked and blown up several trucks carrying chlorine in Iraq. There are over 63,999 chemicals used outside the laboratory environment as reported by the Chemical Abstracts Service). DOT regulates over 3,800 hazardous materials in transportation, as listed in 49 CFR. EPA lists 15 chemicals that account for two-thirds of all chemical releases. Over 70% of all hazardous materials in the United States are shipped in railroad tank cars. 1 Toxic Trains and the Terrorist Threat, Paul Orun, National Labor College, Rail Workers Hazardous Materials Training, April 2007.
DESCRIPTION (provided by applicant): Zeomatrix, a small business, is proposing to research and develop a remediation technology for chlorinated volatile organic carbons (CVOCs). CVOCs are ubiquitous groundwater pollutants. Left on their own they persist in nature for over 100 years. Most are toxic to humans, and some (including trichloroethylene) have been linked to cancer. A recently completed 17 year study by the United States Geological Survey found that chlorinated VOCs are present in nearly every aquifer in the United States. It is estimated that full scale remediation of these compounds in groundwater will cost in excess of $200 billion. The product being developed is a visible light photocatalyst which will promote the rapid reduction of CVOC compounds to less toxic materials. Current commercial photocatalysts are employed as oxidative catalysts, and thus they are less efficient at remediation in the presence of dissolved organic matter, a common component of groundwater. Zeomatrix utilizes high throughput screening methods to rapidly and cost effectively develop new photocatalysts. The Phase I research will be performed using custom-designed parallel photocatalyst screening instrumentation in order to evaluate a large number of candidate materials and identify the optimal reductive photocatalyst. The research will be focused on the following specific aims: one, to synthesize an array of catalyst support geometries based on design of experiments (DoE) protocol and using an automated deposition system custom-engineered by Zeomatrix to deposit various metal/metal oxide combinations and then screen for reductive photocatalytic activity under visible light; and, two, to screen the reductive photocatalysts selected from the initial screening experiments for activity versus chosen test compounds (trichloroethylene, trichloroethane), under a range of experimental conditions (pH, ionic strength, dissolve organic content). Selection of the optimal photocatalyst will be based on rapid degradation kinetics (turn over frequency), and efficacy under adverse conditions (high ionic strength, pH extremes, and high dissolved organic content). The results of the Phase I research will be used to determine the feasibility of applying the selected photocatalyst for the remediation of CVOCs. Phase II studies would be performed to further optimize the photocatalyst, and to perform a large scale pilot study on actual polluted groundwater. The combination of rapid kinetics with the use of low cost visible light would make this an attractive remediation option to address the extensive problem of CVOC contamination.
The goal of this research is the development of a novel remediation technology for the break down of chlorinated volatile organic carbons in water. Chlorinated volatile organic carbons are found in nearly every aquifer in the US. Left on their own they persist in nature for over 100 years. Most are toxic to humans, and they accumulate in fatty tissue making them a danger to human health even at low levels. Some have been linked to cancer and over twenty are currently regulated in public water supplies by the United States Environmental Protection Agency.
DESCRIPTION (provided by applicant): We have developed and prevalidated an in vitro screening test for phototoxicity, the Enhanced Phototoxicity Assay in Reconstituted Skin (EPARS), to replace the current standard animal phototoxicity tests. The phototoxic potential of chemicals, cosmetics, dietary supplements and Pharmaceuticals are a major and growing concern in the consumer products industry, but society and the government have demanded decreased use of experimental animals. EPARS is more objective, faster, and less expensive than animal tests. To-date, no alternative phototoxicity test has been validated in the U.S. (via ICCVAM), although the 3T3 Neutral Red Uptake (3T3NRU) assay has been accepted in the E.U. after validation by ECVAM. EPARS is significantly superior to the 3T3NRU viability test because it overcomes several of the 3T3NRU test's limitations. Specifically: (1) EPARS is based upon a differentiated tissue model that closely parallels human skin morphology, instead of a fibroblast monolayer; (2) the tissues are composed of primary human keratinocytes in a 3D culture system, a more relevant model than a mouse tumor cell line; and (3) test substances can be applied directly, avoiding the often problematic solubilization of formulations into culture media. If developed to its full potential, EPARS would be the most accurate assay available to identify potential phototoxic agents in humans. We propose to confirm the reproducibility, sensitivity, specificity and predictability of EPARS by testing an expanded list of known phototoxins and validate the most predictive and accurate tissue viability endpoints identified in Phase I. We will also use human gene microarrays to measure changes in gene expression patterns and identify genes that can be used as predictors for induction of phototoxicity. This Phase II work will supplement and strengthen the foundation of EPARS in preparation for submission to U.S. regulatory agencies as an alternative to animal phototoxicity testing.
DESCRIPTION (provided by applicant)
Pesticides pose a significant health hazard to the general public and especially individuals working or living around farmland. Pesticides can enter the drinking water supply via run-off into lakes and streams. People can be exposed to pesticides by inhalation, swallowing or by skin or eye contact resulting in poisoning symptoms including: excessive sweating, chills or thirst, chest pains, difficulty breathing, and muscle cramps. To help prevent exposure to these toxic compounds, Lynntech proposes to develop a wearable/portable sensor that can detect, identify and determine the concentration of these compounds within a variety of matrices, i.e. air, water and/or soil in a rugged and reliable device. Using cutting-edge nanotechnology, Lynntech will fabricate miniaturized sensors coupled with innovative enzyme matrices that have the potential to identify P-O, P-S, and P-F type pesticides individually, providing an improved sensing platform for critiquing their source. The proposed sensor technology will be extremely lightweight and long-lasting due to its lowpower requirement, small size, and enhanced enzyme stabilization. The proposed pesticide sensor will have commercial applications in both remote and/or point-of-use monitoring all water supplies, protecting farmers/crop-sprayers or military soldiers in the battlefield against chemical warfare agents which are often in the form detectable by the proposed sensor.
Lynntech's Phase I research will consist of several proof-of-concept experiments which will involve the demonstration and characterization/optimization of the signal response's sensitivity, selectivity and propensity to give false-positive responses. Phase II research will continue with the advancement of the sensing platform with the design, assembly and testing of the first-generation wearable sensor with automated sampling, processing and data display. The research team consisting of a group of research engineers and scientists with backgrounds in sensor design and fabrication, enzyme characterization, software/hardware programming and electrochemistry, making this research project truly multidisciplinary, thereby providing the necessary expertise to make this project a success.
DESCRIPTION (provided by applicant): This Small Business Technology Transfer Phase I project will develop a prototype online perchlorate monitor for a resin bed perchlorate remediation reactor. The device will be have less than 4 ppb limit- of-detection, provide results in less than 3 min., and require only periodic microchip replacement as routine maintenance. Currently, perchlorate can only be detected below 10 ppb using laboratory based equipment requiring trained technicians and, most importantly, at least several hours of time, and therefore, impractical for online monitoring. The Henry Group at Colorado State University has recently demonstrated sub ppb perchlorate detection using a patent-pending lab-on-a-chip technology with results that include real water sample testing. This technology opens the door for online monitoring of perchlorate remediation operations, which will significantly reduce the costs. Entire resin beds costing $100k in materials and additional costs in disposal would no longer be needed. This Phase I proposal will: 1. Develop pumps, valves, instrumentation, etc. to assemble a field deployable device, 2. Optimize our microchip functions by incorporating a sample membrane barrier and assessing nonhazardous alternative internal standards, and 3. Method validation and field testing. PUBLIC HEALTH RELEVANCE: Human exposure to perchlorate is of concern because of the potential for impaired thyroid function, leading to a number of developmental delays and other medical problems. Its prevalence in the environment only gained interest in the late 1990's, once a method was developed for its detection at the 4 ppb level. In 2005 after being added to the Environmental Protection Agency's (EPA) Unregulated Contaminant Monitoring Rule (UCMR1) list, a sampling of 2800 large water systems and 800 smaller systems, representing less than 10% of all US water systems, revealed contamination in 153 sites over 25 states. As of 2005, 120 remediation projects were underway, including 15 superfund sites, costing hundred's of millions of dollars to fund, mostly coming from government coffers. Our online monitoring device will significantly reduce costs for remediation. In addition to lowering costs to existing remediation, it will also allow smaller communities address cleanup that would otherwise not have enough resources.
DESCRIPTION (provided by applicant)
Conventional environmental exposure monitoring requires bulky instrumentation without providing a personalized history of environmental exposure. Valencell's long-term goal is to provide a noninvasive, low-profile, real-time, affordable personal environmental exposure monitor platform that is virtually unnoticed by the user for maximum performance and convenience. This platform will provide a quantitative, reliable, in-field measurement of personal-level, point-of-contact exposure to a variety of airborne chemical toxins of particular interest to health conscious end-users, sports enthusiasts, the immunocompromised, and medical professionals. Integrated Bluetooth communication protocols will be employed towards sending real-time information wirelessly to a cell phone or PDA. In turn, this information can then be sent wirelessly to online databases for storing and processing information relating personal health with personal environmental factors and user demographics.
The specific goal of this Phase I feasibility study is the development of a novel sensor element providing the flexibility of monitoring volatile organic compounds (VOCs), ozone, carbon monoxide, polycyclic aromatic hydrocarbons (PAHs), and other reactive airborne species in the same compact device. Filament-heated tin oxide VOC sensors, the workhorse of solid-state VOC sensing, are sufficiently compact but require significant operating power and lack vapor specificity. Valencell's innovative approach is the development of a novel wide band gap (WBG) VOC sensor offering enhanced vapor specificity and dramatically reduced power consumption over standard metal oxide sensors. This innovation enables the development of a novel, low-power (<10 mW), real-time (<100 ms sampling), compact (< 10 cm3), wearable VOC monitor capable of long-term battery-powered operation, high specificity, and broad sensitivity (0.1 to 1000 ppm).
In this program, Valencell will fabricate sensor electrodes from novel WBG metal-oxide films deposited by North Carolina State University (NCSU). The functionality of these sensor electrodes will then be validated by evaluating the sensitivity and specificity of each electrode in a bell jar VOC test bed. The sensor electrodes will then be integrated into a self-contained VOC sensor prototype such that the predicted performance specifications can be statistically validated in the VOC test bed.
Crisp Terms/Key Words: air pollution, monitoring device, organic chemical, electrode, case history, information system, metal oxide, technology /technique development, clinical research, portable biomedical equipment, environmental exposure
DESCRIPTION (provided by applicant):
Under current regulatory policies, chemicals that are believed to comprise both a significant exposure and health risk in the human population are selected to undergo testing for toxicity and carcinogenic potency. The traditional method for evaluating carcinogenic activity and chronic toxicity of a specific chemical has been the two-year bioassay. Due to relatively large amounts of resources involved, each bioassay costs between 2 million and 4 million dollars and takes several years to complete. According to the National Toxicology Program (NTP), the number of chemicals currently tested stands at 505 in long-term studies and 66 in short-term tests, and only a single sub-chronic study. By comparing the number of completed bioassays with the 70,000 to 85,000 chemicals in commerce today it is impossible to apply the current testing system to all chemicals of concern. Alternative approaches must be developed in the interest of protecting human health and in saving economic resources. To develop an efficient and accurate assessment of the carcinogenic potential of an unknown chemical we propose to: (1) identify a set of genes that is predictive of chemically induced hepatocarcinogenesis in a standard rodent 2-year bioassay using a tissue-engineered rodent liver model; and (2) apply the diagnostic gene expression profile derived from the rodent studies to the equivalent tissue-engineered human liver model to evaluate cross-species scaling of the chemically-induced carcinogenic endpoint. To accomplish this, in vivo exposures and exposures of engineered three-dimensional liver co-cultures will be performed with a training set of compounds that include non-hepatocarcinogens and hepatocarcinogens of the following classes: genotoxic, non-genotoxic, sex-dependent and species-dependent. Microarray analysis will be performed on mRNA derived from the exposed animal and liver cultures and the results used to identify gene sets that are statistically predictive of hepatocarcinogenicity in the two-year animal bioassay. A commercial product derived from this research will enable prioritization of hepatocarcinogenic potential of untested chemicals and allow a significant savings of time, money and animals for both governmental agencies as well as private industry related to chemical manufacturing, food additives and pharmaceuticals.
DESCRIPTION (provided by applicant): The heavy metals cadmium and lead are both serious environmental contaminants that are listed among the top ten hazards by the Agency for Toxic Substances and Disease Registry (U.S. Department of Health and Human Services) based on their toxicity and prevalence in the environment. For example, lead contamination is widespread due to the ubiquitious use of lead based paints until 1978. Even recently, the USEPA estimated that 12 million homes have lead in their yards at levels exceeding the new 400 ppm standard for play areas, while 4.7 million homes exceed the new 1,200 ppm standard for the rest of the yard. Traditional means of remediation, excavation and removal of the contaminated soils, is not feasible for such a large area, but phytoremediation, or the use of plants to take up contaminants, can provide an alternative, cost-effective, method.
While plants have been identified that can tolerate high levels of toxic metals in their environment, many of these plants are unsuitable for phytoremediation based on the low amounts of biomass they produce or their limited growing range. To improve the potential for phytoremediation of metals such as lead and cadmium, the laboratory of Dr. Julian Schroeder at the University of California, San Diego, has identified two candidate genes that have been demonstrated to increase metal tolerance and accumulation in plants. The first gene, 3-ECS encodes the key enzyme in the synthesis of glutathione, an essential component in metal tolerance and the oxidative stress response. The second gene, YCF1, encodes an ABC transporter that transports glutathione metal complexes into the vacuole, sequestering the metals there and reducing cellular toxicity of the metals. These two genes will be stacked together in a single plant to test the hypothesis that they will act synergistically together and provide significantly increased tolerance. The potential of the transgenic plant for phytoremediation will be demonstrated with soil collected from contaminated sites, followed in Phase II with a field trial at one of these sites. Toxic metals such as cadmium and lead are consistently classified as among the top environmental hazards by the Environmental Protection Agency and U.S. Department of Health and Human Services, but traditional remediation methods are too expensive to address the widespread contamination. This SBIR project will develop enhanced plants that can accumulate greater levels of cadmium and lead than naturally occurring plants, allowing for removal of the metals from contaminated soil or water. These plants could lead to novel remediation technologies with reduced environmental impact than traditional solutions.
DESCRIPTION (provided by applicant)
The goal of this project is to develop a GPS-enabled multi-analyte sensor that can detect and measure exposure to trace gases present in air, specifically ozone, carbon monoxide and carbon dioxide gases. This sensor is based on the innovative exploitation of the anchoring of liquid crystals to a surface functionalized with metal ions. In preliminary studies we have demonstrated the ability to identify combinations of metals that selectively bind ozone and to design multi-arrays of metals that create fingerprints specific for functional groups. We also demonstrated the use of this new technology to rapidly (~ 10 seconds) measure exposure to ppb concentrations of an organophosphate compound. The sensing surfaces we created could be tuned to be reversible, were unaffected by humidity, and responded in a dose-dependent manner. These data strongly support the feasibility of PlatypusTM technology as the basis of a compact, multi-analyte, field deployable personal device for detection of exposure to trace gases. In this proposal we will develop a sensor subsystem and integrate it with GPS-enabled components that track and store information such as degree of exposure, time and duration of exposure and exact location of exposure events. Our intended product will allow simple uploading of the data to a computer and will be tested under field conditions. Such a product is needed to facilitate the understanding of human susceptibility to environmental exposures.
DESCRIPTION (provided by applicant): We believe that unique volatile signatures are associated with fungal outbreaks associated with production of aflatoxin. The long-term goal of the project is to demonstrate the feasibility of our innovative nano-crystalline tin oxide sensor detecting these unique Microbial Volatile Organic Compounds (MVOCs) at very low levels and differentiating between low levels of these unique organic vapors and other Volatile Organic Compounds and MVOC's. The resulting detector would be set inside a grain storage container to protect food safety. The first aim in this research is to identify a catalyst and operating condition, which allow these unique volatiles to be selectively detected in crop enclosures containing both the unique volatiles and potential identified interferants. Combinatorial chemistry methodology will be used to establish the conditions for unique volatile selectivity. Secondly, our aim is to provide baseline information, under biologically relevant conditions to substantiate the use of particular volatiles as markers of aflatoxin contamination. This will be accomplished by carrying out research on host plant-fungus interactions involved in the aflatoxin contamination process and doing volatile analysis on different fungal strains. The conductance response of the sensor is proportional to the concentration of these gases; that is, the higher the concentration of the gas, the greater the response. At the conclusion of this project, we expect to have demonstrated proof of principle for a sensor capable of selectively determining concentrations of unique mold related volatiles as low as 1 ppb in the presence of other typical crop related volatiles. Aflatoxins are toxic metabolites produced by certain molds in/on foods and feeds. The substance is so toxic that it is one of 19 contaminants-along with mercury and DDT-for which the U.S. Food and Drug Administration imposes strict tolerance levels in food, with only trace amounts allowed. Aflatoxins have been associated with various diseases, such as aflatoxicosis, in livestock, domestic animals and humans throughout the world. Aflatoxins have received greater attention than any other mycotoxins because of their demonstrated potent carcinogenic effect in susceptible laboratory animals and their acute toxicological effects in humans. The greatest threat of health hazards to humans come from long term exposures of tainted food products, either from spoilage or from consuming milk or meat from animals that have been fed contaminated feed. The USDA noted that countries that lack the means to regulate and monitor the presence of aflatoxin leave their inhabitants open to unknown poisonings that can continue over long periods of time. Throughout the world, approximately 4.5 billion persons are chronically exposed to largely uncontrolled amounts of the toxin where the toxic affect of aflatoxin on immunity and nutrition combine to negatively affect health factors.
Mycotoxins are carcinogenic compounds that are products of the mold Aspergillus. They affect up to 30% of the worlds food supply and the resulting conclusion is that approximately 4.5 billion persons worldwide are chronically exposed to largely uncontrolled amounts of the toxin. No animal species including humans are immune to aflatoxin poisoning with the greatest threat of health hazards to humans coming from long-term exposure of tainted food products, either from spoilage or from consuming milk or meat from animals that have been fed contaminated feed.
DESCRIPTION (provided by applicant): Environmental or intentional exposure to a broad variety of chemical agents can alter normal endocrine function. The effects of these "endocrine disruptors" (ED) can have serious health implications including deleterious effects to reproductive capacity, fetal development, the immune system, and carcinogenesis. Current animal tests are expensive, use a large number of animals, and are not necessarily applicable to humans. Thus, a validated, human in vitro method to identify ED is an area of great importance. This research project will develop such a test method. Phase I research will prevalidate MatTek's organotypic vaginal- ectocervical (VEC-FT) tissue model for use in identifying endocrine disruptors (ED). A battery of 25 model compounds with known ED activity will be used. Changes to key hormonal receptors, enzyme activity, tissue structure, proliferation, and gene expression will be monitored. These data will be used to develop a prediction model that will be a sensitive and specific predictor of ED potential. During Phase II, the test method will undergo formal validation in a multi-center, GLP study. The prevalidated in vitro test to be developed for assessing the endocrine disrupting potential of chemicals/ formulations will have enormous environmental and public health significance. Evaluation of endocrine disruptors is important to minimize hazards to humans and wildlife exposed to chemicals that interfere with normal hormonal regulation. The proposed human organotypic tissue based assay will provide a sensitive and specific assay method to screen a large number of endocrine disrupting chemicals at a reduced cost.
DESCRIPTION (provided by applicant): The long-term goal of the collaboration between the USC and Southern Sun BioSystems is to create a plant breeding and remediation technology-development center which would supply hardware, protocols for breeding-selection and mass production of elite plants for nurseries and remediation businesses, with licensing and tracking mechanisms for protecting intellectual property. This project is built on the successful demonstration of the feasibility of our novel technology for in vitro breeding of a large biomass plant for field-scale phytoremediation. The technology transfer capitalizes on Southern Sun's innovative mass propagation technologies and on somaclonal breeding by amplification of the genetic variation-generating step, that is the number of cell divisions in the totipotent cell cultures subjected to selection. A commercialization plan for elite plant sales and breeding technology is supported by letters of commitment from a variety of remediation and biomass utilizing businesses. Phase II objectives: (1) the frequency and extent of somaclonal variation in second round of culture and (2) preselection using the same pollutant (testing physiological constraints on dehalogenation); (3) add valuable new traits (morphological variations, higher cellulose to lignin ratio) to elite lines from Phase I and (4) to a salt tolerant line; (5) improve mass propagation, transportation, acclimatization by prevention of hyperhydricity; (6) certify elite lines by determining first order detoxification rate constant in hydroponic system, (7) by testing stability of the new traits, and by crop trials to demonstrate remediation of trichlorophenol (and biomass production) of TCP at Southern Sun (8a), and to demonstrate biomass production and remediation of a select pollutant in city sewage sludge at BioTech, Inc., Cayce SC (8b), and potentially in hog lagoons in Clinton, NC. Phase II will produce: elite lines with certified superior haloorganic detoxification ability with added traits to promote end uses, sufficient in vitro stock for mass propagation/field applications, an improved strategic efficiency, cost per unit output, of elite plants for phytoremediation, and pre-booked sales.
DESCRIPTION (provided by applicant): Mutation to DNA is a primary mechanism by which cancers arise. These events have also been implicated in diseases such as atherosclerosis, and processes such as aging. Therefore, there is an important need for sensitive analytical methods which facilitate the study of mutagenesis, as well as the identification of chemical or physical agents that can mutate DNA. Methods for measuring in vivo mutation currently exist, each with their own advantages and limitations. While some are based on colony formation and require tissue culture work, others rely on expensive, proprietary trangenic rodents. The in vivo mutation assay that is proposed herein is based on the Pig-a locus. The Pig-a gene product is essential for the biosynthesis of glycosyl-phosphatidylinositol (GPI) anchors. Mutations giving rise to nonfunctional GPI anchors prevent certain proteins from being expressed on the cell surface, and this represents a phenotype which can be measured by flow cytometry. Importantly, harvested cells are not cultured before analysis, thus the need for costly- and labor-intensive tissue culture work is eliminated. Furthermore, since Pig-a is an endogenous gene located on the X-chromosome, it is likely that this mutation scoring system will be applicable to any mammalian species of toxicologic interest, including humans. As was the case for Phase I, the proposed Phase II experiments will focus on two readily obtained cell populations for the determination of GPI-anchor deficiency: peripheral blood erythrocytes (total) and an immature fraction of erythrocytes (reticulocytes). Whereas Phase I feasibility studies were conducted strictly with mice, these experiments will consider exposures of both mice and rats to each of six prototypical mutagens. The treatment schedule and the blood harvest times will be varied in order to determine the most appropriate experimental designs. Other experiments will involve isolation and DNA sequencing of GPI-anchor deficient erythroid progenitors from mutagen-treated mice. The presumptive Pig-a mutant colonies will be sequenced to provide mutation spectra data that helps validate the system as an effective mutagenesis assay. Upon successful completion of these proposed experiments, society will benefit as pharmaceutical and chemical companies eliminate genotoxicants from their new product development processes more efficiently. Furthermore, if the system proves compatible with human blood specimens, myriad other research activities will benefit as data generated in laboratory animal models are easily extended to include real-world human exposure scenarios, including: 1) clinical trials, 2) post-market survallience of drugs, 3) environmental exposures, and 4) occupational exposures. PUBLIC HEALTH RELEVANCE: It is well known that DNA damage is a precursor to the development of cancer and other significant diseases. It is, therefore, in the interest of public health to reduce the occurrence of mutagenic chemicals in the environment, in our drugs, and from our workplaces. This research project will refine and validate a powerful new method for detecting mutagenic agents, thereby enhancing the nation's ability to effectively reduce exposure to these toxic compounds.
DESCRIPTION (provided by applicant)
This SBIR project is in response to the call for the development of field-deployable or wearable personal sensors for monitoring point-of-contact exposures to airborne chemicals through biosample testing. The broad objective of this proposal is to develop an extremely sensitive and selective biosensor device capable of detecting and discriminating proteins in human serum samples taken from patients suspected of being exposed to potentially harmful levels of organophosphate-based pesticides. This represents a novel approach in biomarker analysis because each organophosphate (OP) pesticide results in a distinct protein "fingerprint" structure that can be identified, distinguished from other agents and their conjugates, and quantified. Using ATERIS Technologies novel sensor thin polymer film technology, reporter domains will be customized with specific protein-recognition molecules that detect the OP poisoned proteins. This will make it possible to develop an inexpensive, yet highly rapid, sensitive, and accurate device to analyze exposure to OP pesticides, assess the type and extent of OP agent exposure and then this information will guide the therapeutic intervention necessary. The major milestones in this Phase I SBIR project are first to isolate biorecognition proteins capable of discriminating between native and OP-poisoned human proteins, then show proof-of-principal for the sensitivity and reliability of the film sensor element. In the Phase II of this program, the detection films will be incorporated into a reader device and the reproducibility and accuracy of detection of OP-modified proteins in actual serum samples will be determined. The data generated will guide the design of the commercial biosensor device. The end user of such a device will be the field personnel likely to be exposed to OP pesticides and clinical laboratories likely to encounter patients that are suspected to have been exposed to OP chemical agents.
DESCRIPTION (provided by applicant): This SBIR application is submitted in response to the objectives of the NIEHS Predictive Test Systems for Safety Evaluation Program by developing, standardizing, and validating sensitive and specific new and novel tests or batteries of tests . Primary human CD34+ bone marrow stem cells will be used as a novel biological system to identify predictive biomarkers of altered immune system differentiation, cellular toxicity, and genotoxicity. Human CD34+ bone marrow stem cells are pluripotent cells that possess the potential of self-renewal, proliferation, and differentiation toward different lineages of blood cells. Human CD34+ cells can be directed to differentiate in vitro and expand along specific cell lineages of immune cells. This lineage-specific differentiation of CD34+ cells is a complex biological process that includes the combinatorial and coordinated expression of genetic pathways that drive cellular proliferation and the acquisition of specialized cell functions. A screening assay based on human primary cells would be useful to assess the predictive power, or in vitro in vivo correlation, of high-throughput screens based on tumor cell lines. As cell lines derived from tumors often lack many critical genes that regulate cellular responses to stressors, the results of environmental agents tested in tumor cell line-based assays may have limited relevance to human health and disease, and there is a need for a human primary cell- based screening assay. This Phase I SBIR has three specific aims: Miniaturize human TK6 cell assay as a prototype assay to establish FCM-based measures of cytotoxicity, apoptosis, cell cycle arrest, oxidative DNA damage and DNA double strand breaks, adapt biological endpoints established in human TK6 cells with human CD34+ stem cells, establish cellular and molecular biomarkers of human CD34+ stem cell differentiation along specific lineages, assess impact of toxicants on CD 34+ health status and differentiation. Since bone marrow stem cells play a pivotal role in the function of the hematopoietic and immune systems and are the putative target cell population of concern for a host human cancers and diseases, the results obtained from these systems are biologically relevant to human disease and can be extrapolated to humans. The human CD34+ stem cell multiplex assay proposed here is ideally suited as platform to assess toxicity for environmental agents and pre-clinical drug candidates, as well a follow-up test system for high-throughput testing initiatives. PUBLIC HEALTH RELEVANCE: Stem cells have the unique ability among all of the cells of the human body of self- renewal, that is, they can remain in a primitive unspecialized state. Under the right conditions, they can give rise to specialized cells of the body (differentiation) like the heart, liver, or pancreas. CD34+ stem cells are the stem cell of bone marrow that differentiates into all of the cells in the blood (white and red blood cells). Therefore, these cells present a unique model system to understand and assess the effects of environmental agents and new drug candidates to predict or anticipate toxicity in humans.