Multidimensional Mapping Method Using an Arrayed Sensing System for Cross-Reactivity Screening

When measuring chemical information in biological fluids, challenges of cross-reactivity arise, especially in sensing applications where no biological recognition elements exist. An understanding of the cross-reactions involved in these complex matrices is necessary to guide the design of appropriate sensing systems. This work presents a methodology for investigating cross-reactions in complex fluids. First, a systematic screening of matrix components is demonstrated in buffer-based solutions. Second, to account for the effect of the simultaneous presence of these species in complex samples, the responses of buffer-based simulated mixtures of these species were characterized using an arrayed sensing system. We demonstrate that the sensor array, consisting of electrochemical sensors with varying input parameters, generated differential responses that provide synergistic information of sample. By mapping the sensing array response onto multidimensional heat maps, characteristic signatures were compared across sensors in the array and across different matrices. Lastly, the arrayed sensing system was applied to complex biological samples to discern and match characteristic signatures between the simulated mixtures and the complex sample responses. As an example, this methodology was applied to screen interfering species relevant to the application of schizophrenia management. Specifically, blood serum measurement of antipsychotic clozapine and antioxidant species can provide useful information regarding therapeutic efficacy and psychiatric symptoms. This work proposes an investigational tool that can guide multi-analyte sensor design, chemometric modeling and biomarker discovery.

在对生物体液（biological fluids）中的化学信息进行检测时，常会遭遇交叉反应（cross-reactivity）带来的挑战，尤其是在缺乏生物识别元件（biological recognition elements）的传感应用场景中。深入理解这类复杂基质中发生的交叉反应，对于指导设计适配的传感系统至关重要。本研究提出了一套用于探究复杂流体中交叉反应的研究方法。首先，本研究在缓冲液体系（buffer-based solutions）中完成了对基质组分的系统性筛选。其次，为了模拟这些组分在复杂样品中共存时产生的影响，本研究利用阵列式传感系统（arrayed sensing system），对缓冲液配制的上述组分模拟混合体系的响应信号进行了表征。研究表明，由输入参数各异的电化学传感器（electrochemical sensors）组成的传感阵列，能够产生差异化响应信号，从而提供样品的协同化学信息。通过将传感阵列的响应信号映射至多维热图（multidimensional heat maps）中，本研究可比对阵列内不同传感器以及不同基质间的特征信号指纹。最后，本研究将该阵列传感系统应用于复杂生物样品，以识别并匹配模拟混合体系与复杂样品响应之间的特征信号指纹。以精神分裂症（schizophrenia）诊疗应用场景为例，本研究使用该方法筛选了相关干扰组分。具体而言，对血清（blood serum）中的抗精神病药物氯氮平（clozapine）以及抗氧化组分进行检测，能够为治疗效果评估与精神症状监测提供有效参考信息。本研究提出了一套可用于指导多分析物传感系统设计、化学计量学建模（chemometric modeling）以及生物标志物发现（biomarker discovery）的研究工具。