Noninvasive Methemoglobin Monitoring Technology

描述（由申请人提供）：本研究旨在满足对无创、可靠和具有成本效益的高铁血红蛋白传感器的关键需求。长期目标是开发一种商业级传感器，提供患者高铁血红蛋白分数的实时即时测量。高铁血红蛋白的高分数导致组织缺氧，甚至死亡。甲氧血红蛋白血症通常是由环境或工作相关的化学品暴露引起的，以及由药物如局部麻醉剂、对乙酰氨基酚和含有亚硝酸盐和/或硝酸盐的药物引起的。儿童，尤其是4个月以下的儿童，特别容易患高铁血红蛋白血症。用吸入的一氧化氮治疗呼吸衰竭患者已显示导致高铁血红蛋白水平增加，因为吸入的一氧化氮可与血红蛋白联合收割机结合形成亚硝酰血红蛋白，其迅速氧化成高铁血红蛋白.在高铁血红蛋白血症的治疗中，有必要能够准确地测量高铁血红蛋白分数。一个非侵入性和可靠的高铁血红蛋白传感器将有很大的影响治疗决策时间。该第一阶段项目的具体目标是（1）开发一种非侵入性高铁血红蛋白传感器，其结合了最新的、最先进的、廉价的、可靠的和持久的光源和检测器，（2）设计和开发用于传感器操作和数据分析的算法，利用基于第一原理的现象学模型，（3）进行动物研究，以证明传感器的可行性和实用性，并检查传感器性能，以及（4）对关键工程、临床和监管问题进行初步调查，这些问题将有助于II期的成功。对非侵入性高铁血红蛋白传感器有潜在巨大需求的一个领域是新生儿重症监护室。吸入一氧化氮治疗有效地减少了对体外膜肺氧合治疗的需要。由于长时间暴露于吸入的一氧化氮会导致高铁血红蛋白水平升高的高风险，因此实时、非侵入性高铁血红蛋白传感器将成为一种非常宝贵的工具，特别是对于血容量有限和/或难以建立IV通路的新生儿。该传感器还可应用于输血医学和防御化学战剂和氰化物中毒。血液中高浓度的高铁血红蛋白会导致组织缺氧甚至死亡。在高铁血红蛋白血症的治疗中，能够准确测量高铁血红蛋白浓度至关重要。一个非侵入性和可靠的高铁血红蛋白传感器将有很大的影响治疗决策时间。

DESCRIPTION (provided by applicant): This research is designed to meet a critical need for a noninvasive, reliable, and cost-effective methemoglobin sensor. The long-term objective is to develop a commercial-grade sensor that provides realtime, point-of-care measurement of methemoglobin fraction in patients. High fractions of methemoglobin lead to tissue hypoxia and even death. Methemo-globinemia is commonly caused by environmental or work-related chemical exposures, and from pharmaceutical agents such as local anesthetics, acetaminophen, and drugs containing nitrites and/or nitrates. Children, especially those younger than four months of age, are particularly susceptible to methemoglobinemia. Treatment with inhaled nitric oxide for patients with respiratory failure has been shown to lead to increased methemoglobin levels, since the inhaled nitric oxide can combine with hemoglobin to form nitrosyl- hemoglobin, which is rapidly oxidized to methemoglobin. In the treatment of methemoglobinemia, it is necessary to be able to measure the methemoglobin fraction accurately. A noninvasive and reliable methemoglobin sensor will have great impact on therapeutic decision time. The specific aims of this Phase I project are (1) to develop a noninvasive methemoglobin sensor that incorporates the most current, state-of-the-art, inexpensive, reliable, and long-lasting light sources and detectors, (2) to design and develop algorithms for sensor operation and data analysis, utilizing phenomenological models that are based on first principles, (3) to conduct an animal study to demonstrate the feasibility and utility of the sensor and to examine the sensor performance, and (4) to perform a preliminary investigation of critical engineering, clinical, and regulatory issues that will contribute to the success of a Phase II. One area that has a potentially huge demand for noninvasive methemoglobin sensors is the Neonatal Intensive Care Units. The inhaled nitric oxide therapy effectively decreases the need for extracorporeal membrane oxygenation treatment. Since prolonged exposure to inhaled nitric oxide poses high risks for elevated methemoglobin levels, a realtime, noninvasive methemoglobin sensor will become an invaluable tool especially for neonates with limited blood volumes and/or difficult-to- established IV access. The sensor also has applications in transfusion medicine and in the defense against chemical warfare agents and cyanide poisoning. High concentrations of methemoglobin in blood lead to tissue hypoxia and even death. In the treatment of methemoglobinemia, it is critical to be able to measure the methemoglobin concentration accurately. A noninvasive and reliable methemoglobin sensor will have great impact on therapeutic decision time.