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: 10004726
• 负责人: Hans Boehringer
• 金额: $ 121.44万
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004726
• 关键词: Address; Affinity; Algorithms; Animal Model; Animals; Antidotes; Area; Bar Codes; Binding; Biological Assay; Blood; Blood specimen; Buffers; Burn Centers; Chemical Warfare; Chemicals; Chemistry; Clinical; Clinical Research; Computer software; Cyanides; Cytolysis; Detection; Development; Devices; Diagnostic; Diagnostic tests; Early Diagnosis; Erythrocytes; Family suidae; Feedback; Fingers; Fire - disasters; Gases; Generations; Government; Hand; Health Professional; Human; Image Analysis; Individual; Ingestion; Inhalation; Licensure; Life; Manuals; Measures; Methods; Microfluidics; Molds; Optics; Oryctolagus cuniculus; Patients; Performance; Phase; Plasma; Poison; Poisoning; Price; Production; Reader; Reagent; Reproducibility; Research; Risk; Sampling; Schedule; Sensitivity and Specificity; Skin; Small Business Innovation Research Grant; Sodium Chloride; Strategic Planning; System; Systems Integration; Test Result; Testing; Therapeutic Agents; Time; Toxic effect; Treatment Efficacy; United States National Institutes of Health; Vitamin B 12; Whole Blood; Work; analog; base; chemical release; chemical threat; clinical diagnostics; clinically relevant; cobinamide; commercialization; cost; design; emergency service responder; first responder; improved; instrument; manufacturing process; medical countermeasure; miniaturize; optical imaging; optical sensor; performance tests; point of care; portability; programs; prototype; rapid detection; rapid diagnosis; sample collection; sensor; smoke inhalation; software development; tool; ultraviolet; usability; validation studies; weapons; weapons of mass destruction

PROJECT SUMMARY The objective of this proposal is to complete the development and verify the performance of a field-deployable, fully integrated sensor for the rapid and early diagnosis of cyanide poisoning in whole blood. Cyanide is an extremely potent and rapid acting poison. It can be inhaled or absorbed across the skin as cyanide gas or ingested as cyanide salt, and has multiple mechanisms of toxicity. Smoke inhalation containing cyanide is one of the main causes of cyanide related casualties in residential fires. Antidotes to cyanide poisoning are currently available, although at a high price. While new and more effective therapeutic agents are in development, there is no rapid diagnostic test to support emergency personnel and first responders who have a need to measure cyanide levels in whole blood quickly in order to safely and effectively treat exposed individuals. Our test is intended to fill that niche. We propose to complete the development of our prototype sensor into a fully functional and integrated test device and to verify its performance. We have established and proven the chemistry and functionality of the chemical sensor and we have integrated the sensor into a microfluidic cartridge that collects a measured amount of blood from a finger-stick, contains all the reagents and buffers, and houses the cyanide sensor. In our prototype microfluidic cartridge a fixed amount of a whole blood sample is collected, the red blood cells are lysed, then passed through the sensor, followed by a manually actuated wash step. In this phase we will first complete the integration of the cyanide sensor and lysis/wash buffer reagents into the microfluidic cartridge after making improvements to and optimizing the cartridge to resolve remaining performance challenges. Testing to qualify and verify the disposable will be done initially with our prototype benchtop reader. In parallel, our main efforts will focus on the hand-held reader development. After a concept stage, alpha versions of the field-deployable instrument will be developed and tested with the cartridge to confirm functionality and to identify areas for improvement. In addition, alpha readers will be evaluated in a usability study with intended users, firefighters and EMT’s, to evaluate their performance and obtain feedback to improve the design and functionality of the system. Hardware and software development of our reader are then scheduled to progress to a pre-production stage and undergo extensive complete system testing prior to the end of this project. The preproduction system performance, disposable and instrument, will be thoroughly evaluated with samples from cyanide exposed rabbits and pigs, as animal models, and spiked human blood. Verification studies for this Phase will include the confirmation of sensitivity/specificity (≥95%), limit of detection (≤20 µM), dynamic range (20-150 µM), accuracy/reproducibility (≤20% variability), assay time (≤5 minutes), and other studies that are typically required for FDA approval. Clinical studies with production equivalent tests will be initiated upon completion of this Phase.

项目摘要 该提案的目的是完成开发并验证可掩盖的绩效， 完全集成的传感器，以快速和早期诊断全血的氰化物中毒。 氰化物是一种极具潜力和迅速作用的毒药。它可以作为氰化物掺入或吸收整个皮肤 气体或摄入为氰化物盐，具有多种毒性机制。吸入含有氰化物的烟雾 是居民大火中与氰化物相关的伤亡的主要原因之一。氰化物中毒的解毒剂是 目前可用，尽管价格高。虽然新的，更有效的治疗剂 开发，没有快速的诊断测试来支持急诊人员和有急救人员 需要快速测量全血的氰化物水平，以安全有效地治疗暴露的人。 我们的测试旨在填补这个利基市场。 我们建议将原型传感器的开发完成到功能齐全且集成的测试装置中 并验证其性能。我们已经建立并证明了化学物质的化学和功能 传感器和我们将传感器集成到一个微流体弹药筒中，该墨盒收集了测得的血液 在手指粘的情况下，包含所有试剂和缓冲液，并容纳氰化物传感器。在我们的原型中 微流体墨盒收集了固定量的全血样品，红细胞裂解，然后 通过传感器，然后是手动激活的洗涤步骤。在此阶段，我们将首先完成 氰化物传感器和裂解/洗涤缓冲液试剂的整合到微流体弹药筒中 改进并优化墨盒以解决剩余的性能挑战。测试有资格 并验证一次性台式读取器最初将完成一次性。同时，我们的主要努力 将专注于手持读者的开发。经过一个概念阶段，alpha版本的现场剥离版本可 仪器将与墨盒一起开发和测试，以确认功能并确定 改进。此外，将在一项可用性研究中与预期用户，消防员一起评估Alpha读者 和EMT，评估他们的性能并获得反馈以提高设计和功能 系统。然后，安排我们的读者的硬件和软件开发，以进行预生产 在该项目结束之前，阶段并进行了广泛的完整系统测试。预生产系统 性能，一次性和仪器将通过暴露的样品进行彻底评估 兔子和猪作为动物模型，并刺激了人类血液。此阶段的验证研究将包括 确认灵敏度/特异性（≥95％），检测极限（≤20µm），动态范围（20-150 µM）， 准确性/可重复性（≤20％的可变性），测定时间（≤5分钟）和其他通常需要的研究 用于FDA批准。该阶段完成后，将启动具有生产同等测试的临床研究。