Department of NanoEngineering, University of California at San Diego, La Jolla, 92093-0448, USA.
Anal Chim Acta. 2011 Oct 3;703(1):94-100. doi: 10.1016/j.aca.2011.07.023. Epub 2011 Jul 23.
We report on the development of a rapid enzyme logic gate-based electrochemical assay for the assessment of traumatic brain injury (TBI). The concept harnesses a biocatalytic cascade that emulates the functionality of a Boolean NAND gate in order to process relevant physiological parameters in the biochemical domain. The enzymatic backbone ensures that a high-fidelity diagnosis of traumatic brain injury can be tendered in a rapid fashion when the concentrations of key serum-based biomarkers reach pathological levels. The excitatory neurotransmitter glutamate and the enzyme lactate dehydrogenase were used here as clinically-relevant input TBI biomarkers, in connection to the low-potential detection of the NADH product in the presence of methylene green at a glassy carbon electrode. A systematic optimization of the gate and the entire protocol has resulted in the effective discrimination between the physiological and pathological logic levels. Owing to its robust design, the enzyme-based logic gate mitigates potential interferences from both physiological and electroactive sources and is able to perform direct measurements in human serum samples. Granted further detailed clinical validation, this proof-of-concept study demonstrates the potential of the electrochemical assay to aid in the rapid and decentralized diagnosis of TBI.
我们报告了一种基于快速酶逻辑门的电化学分析方法的开发，用于评估创伤性脑损伤 (TBI)。该概念利用了生物催化级联，模拟了布尔与非门的功能，以便在生化领域处理相关的生理参数。酶骨架确保了当关键血清生物标志物的浓度达到病理水平时，可以快速提供高保真度的创伤性脑损伤诊断。这里使用兴奋性神经递质谷氨酸和酶乳酸脱氢酶作为临床相关的输入 TBI 生物标志物，与在玻碳电极上存在亚甲绿时低电势检测 NADH 产物相关联。对门和整个协议的系统优化导致了有效区分生理和病理逻辑水平。由于其稳健的设计，基于酶的逻辑门可以减轻来自生理和电化学源的潜在干扰，并能够对人血清样本进行直接测量。经过进一步详细的临床验证，这项概念验证研究表明，电化学分析在创伤性脑损伤的快速和分散诊断中具有辅助作用。
