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

（描述）：本提案的目标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氰化物中毒。维生素B12前体组合氰化物后的比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迅速起作用的毒药，对人类致命的剂量只有50毫克。目前还没有便携式快速检测全血氰化物的方法。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者，我们的测试旨在填补这一空白。在可行性阶段，我们证明了我们可以用我们的概念装置检测兔子全血中的低水平氰化物。我们通过将改性的cobinamide， cobinamide-polymer，固定在膜上，将cobinamide的化学性质整合到这个原型装置中。为了实现这一目标，我们必须开发一种化学改性，通过这种化学改性，在与氰化物结合后，结合到聚合物上，cobinamide保持其特有的光谱位移。在我们的原型装置中，全血被溶解，然后通过固定的组合酰胺聚合物，接着是洗涤步骤。用手持式分光光度计测定了复方乙酰胺与氰化物结合时的光谱位移。我们现在建议将这个原型设备发展成一个功能齐全的集成测试设备。首先，我们将确定所有的分析成分，并优化化学测试

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.