Description:
TECHNOLOGY AREA(S): Bio Medical
OBJECTIVE: Develop improved fieldable capabilities for the collection and preservation of blood samples for biomonitoring occupational and/or environmental exposures.
DESCRIPTION: At least since the Viet Nam conflict, it has been recognized that exposures to environmental and industrial chemicals during military operations can result in long term adverse health effects for Service members. Exposures to high levels of natural dust, smoke, and industrial pollution during operations in Iraq and Afghanistan have re-emphasized the need for a comprehensive effort to capture exposure data for individuals. Capturing exposure data and understanding the impact of exposures on the individual is integral to the practice of personalized medicine and essential for improving public health risk assessments by eliminating exposure misclassification. A longitudinal set of blood samples collected on a regular basis and as needed on an incident-driven basis extending over a Service member’s career, could function as a biological medical record, documenting exposures and health effects through the Service life cycle and into the veteran’s post-separation life. The most direct method for assessing exposure and health is by using a biosample to analyze biomarkers of exposure and/or effect. Where the health effect of exposure is delayed and/or where the biological half-life of the exposure marker is short, timely collection is imperative. However, collecting and transporting biosamples under operational conditions can be challenging, and analysis in the field may be impossible. Blood is a rich and well-understood source of xenobiotic and biological molecules that can serve as biomarkers of exposure and effect, and the sensitivity of methods for measuring a broad range of such molecules in blood has dramatically increased. Blood spots collected and dried on filter paper cards have been used for many years in drug development, newborn screening, therapeutic drug monitoring, and research. Analytes ranging from metal ions to complex biomolecules (proteins, RNA, DNA) are stable during storage and have been successfully recovered from dried blood spots (DBS). The cards are durable and have a low logistical footprint. However, sample collection using blood spot cards, particularly under field conditions, requires care to avoid sample contamination and possible infection. The spot must be well dried to stabilize the sample, which can be difficult in wet or humid environments. DBS use requires several components, the card itself, media for cleaning the collection site, a needle or lancet for puncturing the skin, and some means of protecting the card for transport and storage. Proposals will address the following aspects: 1) improved materials or methods or platforms for collecting, preserving, and transporting blood specimens and 2) enhanced recovery of analytes. The specific collection platform, material, or approach should aim to simplify collection, reduce logistical burden, and improve analyte recovery in comparison with existing blood spot cards. Note that this topic, especially the Phase I investigations, does not require the use of patient-identified or disease-specific samples. Research may be performed using existing/exempt/synthetic samples, as appropriate for the proposed research and the performing institution. If an offeror plans for the platform or method to be used medical diagnostics, the offeror shall initiate contact with the FDA representatives and provide a clear plan on how FDA clearance will be obtained.
PHASE I: Provide an initial characterization of key aspects of the platform, method or material. Demonstrate potential for enhanced sample preservation, collection simplification, and recovery of critical analytes from preserved blood samples. Demonstrate quantitative results using conventional laboratory technology. The approach must provide advantages in convenience and logistics over collecting samples on conventional blood spot media. The method must provide more rapid drying than conventional blood cards or not require air-drying for analyte stabilization. The method must show reduced potential for contamination and cross-contamination of blood specimens during and after collection. The method must be amenable to simplified collection procedures in comparison with conventional blood spot media. Proposers are encouraged to demonstrate analyte recovery sufficient for analysis using partial preserved specimen samples. The approach should demonstrate enhanced analyte stability/recovery, and/or more facile processing of the dried or preserved sample. Initial analysis may be performed using existing/exempt/synthetic samples. Spike-in analyses are acceptable for Phase I demonstrations using xenobiotics (e.g., pesticides and dioxins), high quality RNA, and moderate abundance serum proteins. RESEARCH INVOLVING ANIMAL OR HUMAN SUBJECTS: The SBIR Program discourages offerors from proposing to conduct Human or Animal Subject Research during Phase I due to the significant lead time required to prepare the documentation and obtain approval, which will delay the Phase I award. All research involving human subjects (to include use of human biological specimens and human data) and animals, shall comply with the applicable federal and state laws and agency policy/guidelines for human subject and animal protection. Research involving the use of human subjects may not begin until the U.S. Army Medical Research and Materiel Command's Office of Research Protections, Human Research Protections Office (HRPO) approves the protocol. Written approval to begin research or subcontract for the use of human subjects under the applicable protocol proposed for an award will be issued from the U.S. Army Medical Research and Materiel Command, HRPO, under separate letter to the Contractor. Non-compliance with any provision may result in withholding of funds and or the termination of the award.
PHASE II: 1) Demonstrate incorporation of the new approach/material into dried or preserved sample absorptive platforms. Demonstrate significant improvement in platform performance in comparison with conventional blood spot cards, including drying time/stabilization time, ease of use, stability, and resistance to contamination and cross-contamination. Evaluate shelf-life. Six month stability testing of preserved blood specimen samples on the new materials and blank preservation material itself should be initiated within the two-year performance period, and testing plans must be developed. 2) Validate feasibility of the sample recovery method developed in Phase I with a practical protocol. Provide a detailed plan for integrating the proposed method for processing and sample analysis post-collection. Demonstrate quantitative recovery of analytes that are currently challenging to assay due to low concentration in the blood (e.g., aM-pM) or high degradation rates in comparison with conventional blood spot cards. Spike in analysis is acceptable for demonstrating limits of detection. Analyses should employ human blood, but it need not be linked to patient identifiers. Show quantitative analyte recovery using standard detection methods for a range of analytes including but not limited to toxic metals, small molecule metabolites, xenobiotic toxicants, and biological macromolecules. The platform should provide reliable measures of high quality low to moderate abundance serum proteins, and mRNAs. Demonstration xenobiotics should be selected from the CDC National Report on Human Environmental Chemicals or from the Biomonitoring California database (http://www.biomonitoring.ca.gov/). To ensure maximum usefulness of the product, proposers are encouraged to consider but are not restricted to methods and technologies compatible with Clinical Laboratory Improvement Amendment (CLIA)-waived analysis, good laboratory practices (GLP), and good manufacturing practice (GMP) procedures
PHASE III: During military operations, Service members operate under conditions where it may be impossible to foresee the type or extent of inadvertent or deliberate hazardous exposures. At present, it is generally not feasible to collect and archive specimens for exposure biomonitoring on an incident-driven basis during operations. Ready commercial availability of materiel for collecting and preserving blood samples would permit improved long-term health risk assessment based on both incident-driven and scheduled sample collection when linked to the Service member’s electronic health and exposure record. Such biosamples would also enhance epidemiological exposure reconstruction and permit the compensation of Service members and veterans based on validated exposure data rather than on presumption. An additional potential market is first responders (fire fighters, hazmat, police, and emergency medical personnel) who can face similar mission-driven challenges. Firefighters in particular are known to be at risk for pulmonary and systemic disorders resulting from toxic exposures. Moreover, it is now recognized that an individual’s life-time health risks are based, in significant measure, on the aggregate exposures he/she has experienced (the individual “exposome”). Actionable responses to the realized and potential effects of exposure require an inexpensive, stable, simple method for capturing and archiving key exposure and health data throughout life. Hence there is an increasing interest in capturing overall exposure data for both individual medical purposes and for evaluating health risk for the general population, currently for research purposes (e.g., CDC’s NHANES program), but also for medical and public health practice in the future. Improved biomonitoring has the potential to provide increased understanding of the consequences of exposure and the opportunity to prevent or control the adverse health consequences of exposure for both military personnel and civilians.
REFERENCES:
1: Christophe P. Stove, Ann-Sofie M.E. Ingels, Pieter M.M. De Kesel and Willy E. Lambert, Dried blood spots in toxicology: From the cradle to the grave? 2012 Critical Reviews in Toxicology 42:230-243 (available in manuscript from https://www.researchgate.net/publication/221845739_Dried_blood_spots_in_toxicology_From_the_cradle_to_the_grave)
2: The Use of Dried Blood Spot Sampling in the National Social Life, Health, and Aging Project 2009 Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 64B (Suppl 1) i131-i136.
3: Stuart A. Batterman, Sergey Chernyak andFeng-ChiaoSu, Measurement And Comparison Of Organic Compound Concentrations In Plasma, Whole Blood, And Dried Blood Spot Samples 2016 Frontiers in Genetics, 7:64.
4: Kristine K. Dennis, Elizabeth Marder, David M. Balshaw, Yuxia Cui, Michael A. Lynes, Gary J. Patti, Stephen M. Rappaport, Daniel T. Shaughnessy, Martine Vrijheid, and Dana Boyd Barr, Biomonitoring in the Era of the Exposome 2016 Environmental Health Perspectives, epublished ahead of print July 6, 2016.
5: Centers for Disease Control and Prevention, National Report on Human Exposure to Environmental Chemicals, https://www.cdc.gov/exposurereport/index.html
KEYWORDS: Biomonitoring, Exposure, Dried Blood Spots, Biomeasures, Diagnostics, Plasma
