Single Cell Interrogation using Optofluidic Platforms for Systems Immunology
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Single Cell Interrogation using Optofluidic Platforms for Systems Immunology Serap Aksu ETH Zurich Department of Biosystems Science and Engineering Mattenstrasse 26, 4058 Basel, CH. ABSTRACT The main objective of this report is to demonstrate novel engineering technologies to investigate regulatory mechanisms of systems immunology in a time-dependent and highthroughput manner. Understanding of immune system behavior is crucial for accurate prognosis of infections and identification of diseases at early stage. An ultimate goal of biomedical engineering is to develop predictive models of immune system behavior in tissue, which necessitates a comprehensive map of dynamic (time-dependent) input-output relationships at the individual cell level. Traditionally, biochemical analysis on the cell signaling is obtained from bulky cell ensembles which average over relevant individual cell response. The response consists firstly of signaling protein (cytokine) secretions which are released during a disease state and which are used to activate the immune system to respond to the disease. We investigate the cytokine secretion dynamics of a single immune cell in response to the stimulant using automated and comprehensive optofluidic platforms. These platforms enable survival and manipulation of single cells in compartments having compatible sizes with cells as well as provide precise control over the type, dose and time-course of the stimulant. The cytokine secretion dynamics of single cell are typically explained by measuring the types, rates, frequencies and concentrations of various cytokines. For the quantitative measurements, label free localized surface plasmon resonance (LSPR) based biosensor can be integrated within the microfluidic device. Microfluidic channels can confine secreted cytokines in compartments, minimize dilution effects and increase detection sensitivity for label free plasmonic biosensing. The direct application of LSPR to in-situ live cell function analysis is still in its infancy and use of such in-situ, real time, and label free biodetection will effortlessly provide high-throughput quantitative bioanalysis for understanding immune system behavior. INTRODUCTION The immune system involves extraordinarily complex and dynamic communications network that exists among the many different kinds of immune system cells that patrol the body [1-2]. Comprehensive characterization of immune cells and their functions is critical to precisely monitor immune conditions of the human body upon screening infectious diseases. Immune cells constantly receive signaling inputs such as pathogen-emitted molecules, use gene regulatory pathways to process these signals, and generate outputs by secreting signaling molecules like cytokines (Figure 1) [3]. Characterizing the input-output relationship of a biological system helps in understanding its regulatory mechanisms, and allows us to build models and predict how the system will operate in complex scenarios, such as tissue response to infection [4]. A major obstacle has been sign
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