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

这个小型企业创新研究(SBIR)第一阶段项目的目标是开发一种生物传感器阵列，用于医疗点(POCT)检测有毒酒精。传感器阵列最终将成为一种完全一次性的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甲醇和乙二醇组分的检测。酶生物传感器之所以被使用，是因为它们对目标具有特异性--然而，催化酒精的酶显示出与一系列酒精的交叉反应，这阻碍了它们的使用。这项研究提出了一种酶生物传感器的范式转变，并利用这种非特异性反应，通过使用一系列微型制造的传感器和线性计算来计算有毒酒精的浓度，即使在干扰物存在的情况下也可以获得临床相关信息。目前，中毒性酒精暴露死亡人数占最致命毒素组的第六位。在美国，每年也有大约7万例非致命的中毒酒精病例。目前的检测技术仅限于气相色谱，虽然非常准确，但并不容易获得，而且不能在临床相关的时间范围内产生结果。没有检测有毒酒精的POCT系统，急诊医生被迫依靠非特定的身体症状进行诊断。为了谨慎起见，订购了可能有害的(乙醇疗法)或昂贵的(福米培唑)治疗，从而导致医疗成本增加。对中毒酒精进行可靠和准确的POCT诊断将显著提高护理质量，并最大限度地减少不必要的治疗。

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.