SBIR Phase I: Rapid Toxic Alcohols Detection Using On-Chip Biosensor Array for Emergency Care

这个小企业创新研究（SBIR）第一阶段项目的目标是开发一种生物传感器阵列，用于即时检测有毒酒精。传感器阵列最终将成为一个完全一次性塑料生物芯片的一部分，这将是有史以来第一个用于诊断有毒酒精摄入的POCT系统。这项工作将演示在乙醇存在下检测甲醇和乙二醇。酶生物传感器的使用是因为它们对目标的特异性，然而，催化醇的酶对一系列醇表现出交叉反应性，这阻碍了它们的使用。本研究提出了酶促生物传感器的范式转变，并利用这种非特异性反应，通过使用一系列微制造传感器和线性计算来计算有毒醇的浓度，即使在干扰物存在的情况下，也能获得临床相关信息。目前，接触有毒酒精导致的死亡在最致命的毒素类别中排名第六。在美国，每年也有大约7万例非致命的有毒酒精病例。目前的检测技术仅限于气相色谱法，虽然很难获得非常准确的结果，并且无法在临床相关的时间框架内生成结果。没有检测有毒酒精的POCT系统，急诊医生被迫依靠非特异性身体症状进行诊断。为了谨慎起见，可能有害的（乙醇治疗）或昂贵的（氟米培唑）治疗会导致医疗费用增加。对有毒酒精进行可靠和准确的POCT诊断将显著提高护理质量并尽量减少不必要的治疗。

This Small Business Innovation Research (SBIR) Phase I Project is targeted towards the development of a biosensor array for point-of-care (POCT) detection of toxic alcohols. The sensor arrays would eventually be a part of a fully-disposable, plastic biochip which would be the first ever POCT system for diagnostics of toxic alcohol ingestion. This work will demonstrate the detection of methanol and Ethylene Glycol in the presence of Ethanol. Enzyme biosensors are used because of their specificity to a target - however, enzymes that catalyze alcohols show cross-reactivity to a range of alcohols which has precluded their use to-date. This research proposes a paradigm shift for enzymatic biosensors and to exploit this non-specific response and obtain clinically relevant information by using an array of microfabricated sensors and linear computations to calculate concentrations of toxic alcohols even in the presence of interferants. Toxic alcohol exposure deaths currently account for the 6th most fatal toxin group. There are also ~70,000 non-fatal toxic alcohol cases annually in the US. Current detection technology is limited to Gas Chromatography, which while very accurate is not easily available and results cannot be generated in a clinically relevant time-frame. There is no POCT system for detection of toxic alcohols and emergency physicians are forced to rely on non-specific physical symptoms for diagnosis. To err on the side of caution, potentially harmful (ethanol therapy) or expensive (Fomipezole) treatments are ordered leading to increased healthcare costs. A reliable and accurate POCT diagnostics of toxic alcohol would significantly improve the quality of care and minimize unnecessary treatments.