Development of a Field-Deployable Device to Rapidly Measure Blood Cyanide Levels

开发可现场部署的设备来快速测量血氰化物水平

• 批准号: 8199403
• 负责人: Hans Boehringer
• 金额: $ 28.71万
• 依托单位: DIAGNOSTIC CONSULTING NETWORK, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199403
• 关键词: Adult; Advocate; Affinity; Area; Bacteria; Binding; Biological; Biological Assay; Blood; Blood specimen; Body Fluids; Breathing; Buffers; Carbon; Carbon Monoxide; Cause of Death; Cessation of life; Chemistry; Cigarette Smoker; Clinic; Communities; Country; Cyanides; Cytolysis; Detection; Development; Device Designs; Devices; Diagnosis; Early Diagnosis; Economics; Electroplating; Emergency Situation; Event; Film; Fingers; Fire - disasters; Food; Gases; Goals; Health Personnel; Human; Human Resources; Hydrogen Cyanide; Imagery; Industrial Accidents; Industry; Laboratories; Liquid substance; Manihot; Measures; Medical; Metals; Methods; Monitor; Nitrogen; Patients; Phase; Plant Roots; Plasma; Play; Poison; Poisoning; Polymers; Procedures; Process; Pseudomonas aeruginosa; Reader; Reagent; Reproducibility; Risk; Role; Saliva; Sampling; Screening procedure; Sensitivity and Specificity; Septicemia; Small Business Innovation Research Grant; Source; Survivors; System; Technology; Testing; Thiocyanates; Time; United States; Validation; Vitamin B 12; Whole Blood; Work; analog; base; chemical release; cobinamide; design; emergency service responder; improved; in vivo; innovation; instrument; novel; prototype; rapid detection; rapid diagnosis; response; sample collection; sensor; smoke inhalation; smoking cessation; ultraviolet; weapons of mass destruction

DESCRIPTION (provided by applicant): The objective of this proposal is to assess the feasibility of a fully integrated device for the rapid and early diagnosis of cyanide poisoning in whole blood using the spectral shift of the vitamin B12 precursor cobinamide upon binding with cyanide as an indicator. Cyanide is an extremely potent and rapid acting poison with as little as 50 mg fatal to humans. Currently there are no portable rapid tests for the detection of cyanide in whole blood available. The primary goal of this proposal is to demonstrate feasibility of the cobinamide-cyanide chemistry in a rapid test using a whole blood sample from a finger-stick. The total assay time from the sample collection to a valid result will be less than 5 minutes. The innovation in this proposal is to incorporate the cobinamide chemistry with blood separation technology, fluid path designs, and a detection area, all integrated in a compact, disposable device which can be interpreted with a handheld visualization system. Feasibility work of this novel rapid assay for detecting blood cyanide through cobinamide will initially focus on several technical approaches for the device design. Parallel paths to pursue a wet chemistry design, a design where the reagents are dried in the device, and a combination thereof will be considered, compared and evaluated. In all of the proposed methods the whole blood sample will be added to the device, followed by an integrated whole blood processing step to yield a plasma sample. Either prior to or immediately after the whole blood separation and lysis, the sample will be mixed with the on-board reagent, dried or wet, and possibly buffers. The processed sample-reagent mixture then moves through the device through various fluid paths to a detection area. To allow for sufficient mixing time between the sample and the reagents, different fluid paths, mixing chambers, polymeric time-gates, and dissolvable films will be evaluated with the goal of maximizing the interaction time. The spectral shift of cobinamide upon binding of cyanide to cobinamide will be measured in the detection area using a handheld or small, portable reader instrument. Upon successful completion of this Phase 1 project we intend to further develop our concept/prototype assay, complete the device design and integrate the finished test with a reader instrument through a Phase 2 proposal. Specific aims for a Phase 2 of this project include the validation of the cobinamide-based device for measuring cyanide in blood. Results will be compared to two established methods for measuring cyanide in biological samples. The sensitivity, specificity, accuracy, precision, and reproducibility of the devices will be determined. Additional studies will be designed to obtain regulatory approval and subsequently we will commercialize the test. If successful, this test will provide the medical community and first responders with a fast, reliable and economic alternative to determine cyanide poisoning. PUBLIC HEALTH RELEVANCE: Cyanide poisoning has been recognized as a threat from smoke inhalation and potentially through weapons of mass destruction, but there are currently no methods available to rapidly detect cyanide in blood from at-risk patients. The objective of the proposed work is to assess the feasibility of a fully integrated method for the rapid and early detection and diagnosis of cyanide poisoning in whole blood using the spectral shift of the vitamin B12 precursor cobinamide upon binding with cyanide as an indicator. Successful accomplishment of the goals of this project will be the basis for the development of a test to detect and measure cyanide blood poisoning which will allow healthcare providers to treat patients quickly and effectively.

描述（由申请人提供）：本提案的目的是评估一种完全集成的装置的可行性，该装置利用维生素 B12 前体钴酰胺与氰化物结合后的光谱位移来快速、早期诊断全血中的氰化物中毒。指标。氰化物是一种极强且作用迅速的毒物，只要 50 毫克即可对人类致命。目前还没有可用于检测全血中氰化物的便携式快速检测仪。该提案的主要目标是证明钴酰胺氰化物化学在使用指尖采全血样本进行快速测试中的可行性。从样本采集到获得有效结果的总检测时间将不到 5 分钟。该提案的创新之处在于将钴酰胺化学与血液分离技术、流体路径设计和检测区域结合起来，所有这些都集成在一个紧凑的一次性设备中，该设备可以用手持可视化系统进行解释。这种通过钴酰胺检测血氰化物的新型快速检测方法的可行性工作最初将集中于设备设计的几种技术方法。将考虑、比较和评估追求湿化学设计、试剂在装置中干燥的设计及其组合的并行路径。在所有提出的方法中，全血样本将被添加到设备中，然后进行集成的全血处理步骤以产生血浆​​样本。在全血分离和裂解之前或之后，样品将与机载试剂（干的或湿的）以及可能的缓冲液混合。然后，经过处理的样品-试剂混合物穿过设备，通过各种流体路径到达检测区域。为了使样品和试剂之间有足够的混合时间，将对不同的流体路径、混合室、聚合物时间门和可溶解薄膜进行评估，以最大化相互作用时间。氰化物与钴酰胺结合后，钴酰胺的光谱位移将使用手持式或小型便携式读数仪在检测区域进行测量。成功完成第一阶段项目后，我们打算进一步开发我们的概念/原型测定，完成设备设计，并通过第二阶段提案将完成的测试与读取器仪器集成。该项目第二阶段的具体目标包括验证用于测量血液中氰化物的基于钴酰胺的装置。结果将与测量生物样品中氰化物的两种既定方法进行比较。将确定设备的灵敏度、特异性、准确性、精密度和再现性。我们将设计更多研究以获得监管部门的批准，随后我们将将该测试商业化。如果成功，该测试将为医学界和急救人员提供快速、可靠且经济的替代方案来确定氰化物中毒。 公众健康相关性：氰化物中毒已被认为是吸入烟雾以及可能通过大规模杀伤性武器造成的威胁，但目前尚无方法可以快速检测高危患者血液中的氰化物。拟议工作的目的是评估一种完全集成的方法的可行性，该方法使用维生素 B12 前体钴酰胺与氰化物结合后的光谱位移作为指示剂，用于快速、早期检测和诊断全血中的氰化物中毒。该项目目标的成功实现将为开发检测和测量氰化物血液中毒的测试奠定基础，从而使医疗保健提供者能够快速有效地治疗患者。