Winkler Thomas E, Stevenson Florence O, Kim Eunkyoung, Kang Mijeong, Payne Gregory F, Kelly Deanna L, Ghodssi Reza
MEMS Sensors and Actuators Laboratory (MSAL), Institute for Systems Research, Department of Electrical and Computer Engineering, University of Maryland, College Park, MD 20742, USA.
Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
IEEE Sens Lett. 2018 Mar;2(1). doi: 10.1109/LSENS.2017.2782883. Epub 2017 Dec 13.
We present a perspective on microsystems integration aspects for concurrent cellular and molecular sensing in a lab-on-a-chip device. While of interest for a range of applications, very few - narrowly focused - examples of such devices can be found in the literature. Here, we approach the challenge from a systems level, considering sensor integration both in parallel and in series. Our study is specifically geared toward schizophrenia treatment, where concurrent blood monitoring of the antipsychotic clozapine and white blood cells could lead to improved treatment outcomes. We evaluate the critical system components for either design, namely plasma skimming (parallel) and in-blood clozapine detection (series). We find that plasma skimming is infeasible, but for the first time demonstrate direct detection of clozapine in whole blood. With a corresponding series-integrated microsystem, we finally demonstrate downstream white blood cell analysis on the same samples using impedance cytometry. We thus present the first lab-on-a-chip device capable of label- and reagent-free concurrent sensing of cellular and molecular markers.
我们展示了一种关于微系统集成方面的观点，用于在芯片实验室设备中同时进行细胞和分子传感。尽管这类设备在一系列应用中具有吸引力，但在文献中只能找到极少数（且重点狭窄）的此类设备示例。在这里，我们从系统层面应对这一挑战，考虑传感器的并行和串联集成。我们的研究特别针对精神分裂症治疗，其中同时对抗精神病药物氯氮平和白细胞进行血液监测可能会改善治疗效果。我们评估了这两种设计的关键系统组件，即血浆撇取（并行）和血液中氯氮平检测（串联）。我们发现血浆撇取不可行，但首次证明了在全血中直接检测氯氮平。通过相应的串联集成微系统，我们最终使用阻抗细胞术对相同样本进行了下游白细胞分析。因此，我们展示了首个能够对细胞和分子标记物进行无标记、无试剂同时传感的芯片实验室设备。
