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）：该提案的目的是完成一种可在全血中快速和早期诊断氰化物中毒的快速和早期诊断。结合氰化物后维生素B12前体cobinamide的特定光谱移位将用于测量样品中氰化物的量。氰化物是一种极有效且迅速的毒药，对人类的致命性只有50毫克致命。当前，没有可用于全血的氰化物检测的便携式快速测试。但是，急救人员和急救人员需要快速测量现场全血的氰化物水平，以便用解毒剂治疗暴露的人，我们的测试旨在填补该利基市场。在可行性期间，我们证明我们可以使用概念装置从兔子中检测到全血的低水平。我们通过将修饰的核氧化酰胺凝血酰胺 - 聚合物固定在膜上，将Cobinamide化学的化学融合到该原型装置中。为此，我们必须开发一种化学修饰，当结合氰化物与聚合物链接后，核酰胺通过该化学修饰保留其特征光谱移位。在我们的原型装置中，全血被裂解，然后穿过固定的凝血酶聚合物，然后进行洗涤步骤。用手持分光光度计测量结合氰化物时核酰胺的光谱移位。现在，我们建议将该原型设备的开发完成到功能齐全和集成的测试设备中。首先，我们将最终确定所有测定组件，并优化化学测试以进行测试 为了最大程度地提高分析灵敏度。同时，我们将开发一个样本收集 将使我们能够可重复地收集测得的全血，将红色细胞裂解并将样品传递到测试装置的模块。一旦设备和样品模块达到原型阶段，我们就开始开发便携式仪器，该工具可以解释测试并为用户提供样品中的氰化物浓度。原型设备将进行校准，然后用来自氰化物暴露的兔子和猪的样品进行评估，这些样品已记录了成功的动物模型，并已被科学和法规群落接受。生产设备，样品收集模块和仪器最终将经过广泛的测试和验证。对此阶段的验证研究包括确认灵敏度，特异性，准确性，精确性和可重复性以及其他通常是FDA清除所需的研究。包括关键动物研究在内的临床研究超出了该项目的范围，将在此阶段完成后开始。