Label-Free Biosensors for Cyokine Detection.

[摘要] Cytokines are protein biomarkers secreted by immune cells that serve as mediators in the immune system. The functional phenotypes of immune cells are important in recognizing immune functions and often determined by the dynamic cytokine secretion behaviors of immune cells. As a result, many researchers have attempted to quantify cytokines to develop a new approach to immune diagnosis and therapy. The lack of rapid, sensitive, multiplexed time-course cytokine monitoring techniques poses significant challenges to these research efforts.To fill this technological gap, this thesis has developed label-free biosensing platforms for rapid and sensitive cytokine detection.In the first part of this thesis, an MoS2-based field-effect transistor (FET) biosensor was developed to detect cytokines. This work advanced critical device physics by leveraging the excellent electronic/structural properties of TMDCs in biosensing applications as well as the research capability in analyzing biomolecular interactions with a fM-level sensitivity. In the second part, we demonstrated a nanoparticle based localized surface plasmon resonance (LSPR) biosensing device integrated with microfluidic technology. The quantitative characterization of cytokine secretion behaviors from T-cells under an immunomodulation was studied at high temporal resolution. The biosensors achieved precise measurements with low sample volume, short assay time, high-sensitivity, and negligible sensor crosstalk. Data obtained from this study provided a comprehensive picture of the time-varying cellular functional response during immunosuppression. In the last part, integrated LSPR biosensor within a microfluidic system was developed for cell-based immune functional analysis. By placing cells near the sensing elements, we achieved in-situ measurement of the cytokine secretion behavior of immune cells. The extended function of this platform may further allow us to measure cytokine secretion rate of cells to extract both the magnitude and time constant of the cellular response to an immunological environmental change. Compared to previous labeling techniques for cytokine detection, the label-free FET and LSPR cytokine detection techniques provide rapid, highly sensitive biosensing platforms, suitable for capturing the dynamic nature of immune response. Furthermore, the multiplexed detection capability integrated in a microfluidic system enables us to understand the cytokine-regulated functional characteristics of immune system. These platforms hold significant promise for point-of-care applications in clinical settings.

[发布机构] University of Michigan

[效力级别] Localized Surface Plasmon Resonance Biosensor

[关键词] Label-free biosensing for cytokine biomarker detection;Localized Surface Plasmon Resonance Biosensor;Field-effect Transistor Biosensor;Mechanical Engineering;Engineering;Mechanical Engineering