Sensor-integrated organ-on-a-chip platform for real-time impedance spectroscopy of neural cells
Date
2023-12
Authors
Ouedraogo, Lionel Jean Gabriel
Major Professor
Advisor
Hashemi, Nicole N
Lee, Jonghyun
Montazami, Reza
Agba, Emmanuel I
Committee Member
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Abstract
This study presents a comprehensive overview of the research conducted, including a literature review on graphene-based sensors and two research papers focused on the development and characterization of graphene-based sensors integrated into microfluidic chips for real-time monitoring of cell growth and viability, as well as neurons.
The literature review provides a concise overview of graphene-based sensors and their diverse applications. Various types of graphene sensors and their working principles are discussed, including Field-Effect Transistors (FETs), resistive sensors, optical sensors, electrochemical sensors, Surface-Enhanced Raman Spectroscopy (SERS) sensors, strain sensors, and thermal sensors. Each sensor type is described with relevant examples and potential applications.
Additionally, the review delves into organ-on-a-chip systems, the advantages of organ-on-a-chip systems, the challenges and limitations of traditional in vitro and in vivo models are discussed, leading to the potential of organ-on-a-chip systems in addressing these limitations and the role of graphene in organ-on-a-chip systems as biosensors, showcasing its contributions to enhanced functionality and physiological relevance
The studies present the development and characterization of a graphene-based sensor integrated into a microfluidic chip for real-time monitoring of cell growth and viability. The sensor fabrication involved the metabolization of graphene from graphite using a simple and cost-effective method. The sensor design, created using Solidworks, featured electrodes capable of detecting environmental changes through impedance sensing. A mold was created using a cutter plotter to overcome challenges in achieving the desired sensor shape, and the electrodes were printed on a polyester (PETE) membrane. The conductivity of the electrodes was optimized through annealing, considering the temperature limits of the membrane.
The optimal annealing conditions were 150 °C for 40 minutes, with a resistance of approximately 51 Ohms sqr-1, while maintaining membrane integrity. This prevented changes in the membrane's dimensions, pore size, and surface morphology. Graphene synthesis was performed using graphite and bovine serum albumin (BSA) in deionized water, and the produced graphene was characterized using Raman spectroscopy and SEM imaging. Electrochemical characterization demonstrated the stability, sensitivity, and electrochemical behavior of the graphene-based impedance sensor. The chip was then used for microfluidic cell seeding and culturing with C8-D1A mouse astrocytes, and the biocompatibility of the graphene electrodes was confirmed. A protocol was developed for cell culture in the chip resulting in more than 90% cell coverage. Impedance-based techniques, such as Electric Cell-Substrate Impedance Sensing (ECIS) and impedance flow cytometry, were employed for real-time cell proliferation and viability monitoring.
The present study represents the inaugural utilization of a pristine graphene-based sensor within an organ-on-a-chip platform, demonstrating its pioneering application for real-time monitoring and detection of neural cell growth. Impedance measurements showed an increase in impedance as cells adhered to the electrodes and formed a confluent layer within the first 48 hours, followed by a decrease in impedance as cells detached and died in the last 48 hours of culture. The results indicate that the integrated graphene-based impedance sensor is suitable for real-time monitoring of neural cells and can provide valuable insights into cell proliferation and viability.
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