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: 8713200
• 负责人: Hans Boehringer
• 金额: $ 78.42万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8713200
• 关键词: Adult; Affinity; Animal Model; Animals; Antidotes; Bacteria; Binding; Biological; Biological Assay; Blood; Blood specimen; Body Fluids; Buffers; Carbon; Carbon Monoxide; Cause of Death; Cessation of life; Characteristics; Chemicals; Chemistry; Clinical Research; Collaborations; Color; Commit; Communities; Country; Cyanides; Cytolysis; Data; Data Analyses; Detection; Development; Devices; Diagnosis; Diagnostic; Early Diagnosis; Electroplating; Emergency Situation; Erythrocytes; Event; Family suidae; Fire - disasters; Food; Gases; Health Professional; Human; Human Resources; Hydrogen Cyanide; Individual; Industrial Accidents; Industry; Laboratories; Lead; Link; Manihot; Manufacturer Name; Measures; Membrane; Metals; Methods; Modification; Nitrogen; Noise; Oryctolagus cuniculus; Patients; Performance; Phase; Plant Roots; Play; Poison; Poisoning; Polylysine; Polymers; Process; Production; Proteins; Pseudomonas aeruginosa; Pump; Reader; Reagent; Reproducibility; Risk; Role; Sampling; Sensitivity and Specificity; Signal Transduction; Site; Small Business Innovation Research Grant; Solid; Source; Staging; Survivors; Systems Integration; Testing; Time; United States; United States National Institutes of Health; Vitamin B 12; Whole Blood; Work; analog; base; chemical release; cobinamide; commercialization; emergency service responder; improved; instrument; performance tests; point of care; programs; prototype; public health relevance; rapid detection; rapid diagnosis; sample collection; smoke inhalation; software development; success; tool; ultraviolet; validation studies; verification and validation; weapons of mass destruction

DESCRIPTION): The objective of this proposal is to complete the development of a field-deployable, fully integrated device for the rapid and early diagnosis of cyanide poisoning in whole blood. The specific spectral shift of the vitamin B12 precursor cobinamide after binding cyanide will be used to measure the amount of cyanide in the sample. 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. However, emergency personnel and first responders have a need to measure the levels of cyanide in whole blood quickly on site in order to treat exposed individuals with an antidote and our test is intended to fill that niche. During feasibility, we demonstrated that we can detect low levels of cyanide in whole blood from rabbits with our concept device. We integrated the cobinamide chemistry into this prototype device by immobilizing modified cobinamide, cobinamide-polymer, on a membrane. To achieve that we had to develop a chemical modification through which the cobinamide retains its characteristic spectral shift when binding cyanide after it has been linked to a polymer. In our prototype device, whole blood was lysed, and then passed through the immobilized cobinamide-polymer, followed by a wash step. The spectral shift of cobinamide upon binding cyanide was measured with a handheld spectrophotometer. We now propose to complete the development of this prototype device into a fully functional and integrated test device. First, we will finalize all the assay components and optimize the chemistry for the test in order to maximize the analytical sensitivity. In parallel we will be developing a sample collection module that will enable us to reproducibly collect a measured amount of whole blood, lyse the red cells and deliver the sample to the test device. Once the device and the sample module have reached the prototype stage, we are initiating the development of a portable instrument which can interpret the test and provide the user with a concentration of cyanide in the sample. The prototype devices will be calibrated and then evaluated with samples from cyanide exposed rabbits and pigs, animal models that have documented success and have been accepted by the scientific and regulatory community. Production devices, sample collection modules and instruments will finally be extensively tested and validated. Validation studies for this Phase wil include the confirmation of sensitivity, specificity, accuracy, precision, and reproducibility and other studies that are typically required for FDA clearance. Clinical studies, including pivotal animal studies are outside the scope of this project and will be initiated upon completion of this Phase.

描述）：本提案的目的是完成一种可现场部署的、完全集成的设备的开发，用于快速和早期诊断全血中的氰化物中毒。结合氰化物后维生素B12前体可宾酰胺的特定光谱位移将用于测量样品中氰化物的量。氰化物是一种非常有效和快速作用的毒药，对人类来说只有50毫克致命。目前还没有用于检测全血中氰化物的便携式快速测试。然而，急救人员和急救人员需要在现场快速测量全血中的氰化物水平，以便用解毒剂治疗暴露个体，我们的测试旨在填补这一空白。在可行性研究期间，我们证明了我们可以用我们的概念设备检测家兔全血中的低水平氰化物。我们通过将改性的可宾酰胺，可宾酰胺-聚合物固定在膜上，将可宾酰胺化学整合到该原型装置中。为了实现这一点，我们必须开发一种化学修饰，通过这种化学修饰，可宾酰胺在与聚合物连接后结合氰化物时保持其特征光谱位移。在我们的原型装置中，全血被裂解，然后通过固定的可宾酰胺-聚合物，随后进行洗涤步骤。用手持式分光光度计测量结合氰化物后的可宾酰胺的光谱位移。我们现在建议完成这个原型设备的开发，成为一个功能齐全的集成测试设备。首先，我们将最终确定所有检测组件，并优化测试的化学成分， 以最大限度地提高分析灵敏度。与此同时，我们将开发一个样本收集 该模块将使我们能够可重复地收集测量量的全血，裂解红细胞并将样本输送到测试设备。一旦设备和样品模块达到原型阶段，我们将开始开发一种便携式仪器，该仪器可以解释测试并向用户提供样品中氰化物的浓度。将对原型装置进行校准，然后使用来自氰化物暴露的兔子和猪的样本进行评估，这些动物模型已记录成功并已被科学和监管界接受。生产设备、样品采集模块和仪器最终将得到广泛的测试和验证。本阶段的验证研究将包括灵敏度、特异性、准确度、精密度和重现性的确认，以及FDA批准通常要求的其他研究。临床研究（包括关键动物研究）不在本项目范围内，将在本阶段完成后启动。