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，为患者提供实时、即时的高铁血红蛋白含量测量。高铁血红蛋白的高含量会导致组织缺氧甚至死亡。高铁血红蛋白血症通常由环境或与工作相关的化学品暴露引起，以及由药物制剂如局部麻醉剂、对乙酰氨基酚和含有亚硝酸盐和/或硝酸盐的药物引起。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。呼吸衰竭患者吸入一氧化氮治疗已被证明可导致高铁血红蛋白水平升高，因为吸入的一氧化氮可与血红蛋白结合形成亚硝基血红蛋白，亚硝基血红蛋白可迅速氧化为高铁血红蛋白。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的分数。无创、可靠的高铁血红蛋白传感器将对治疗决策时间产生重大影响。第一阶段项目的具体目标是：(1)开发一种无创高铁血红蛋白传感器，该传感器采用最新、最先进、廉价、可靠和持久的光源和探测器；(2)设计和开发传感器操作和数据分析算法，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，并检查传感器的性能。(4)对关键的工程、临床和监管问题进行初步调查，这将有助于II期的成功。一个对无创高铁血红蛋白传感器有潜在巨大需求的领域是新生儿重症监护病房。吸入式一氧化氮治疗有效地减少了体外膜氧合治疗的需要。由于长时间吸入一氧化氮会导致高铁血红蛋白水平升高，因此实时、无创的高铁血红蛋白传感器将成为一种宝贵的工具，特别是对于血容量有限和/或难以建立静脉通道的新生儿。该传感器还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，能否准确测定高铁血红蛋白的浓度是至关重要的。无创、可靠的高铁血红蛋白传感器将对治疗决策时间产生重大影响。

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.