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Sensor-embedded Kidney and Liver Microphysiological Systems for Drug and Disease Analysis

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Abstract
Advanced cell culture technique, organ-on-a-chip (OoC) caters the capacity to mimic human physiology with reverse engineered biological formulation of human organs and multi-organs. The prime perspective of 3D cell culture is engineering human physiology for disease modeling to enhance drug screening analytics. Mimicking human physiology with complex in vitro model brings the prospect to replace the usage of laboratory animals for drug screening. Human metabolism is primarily carried out in liver with its excretion taking place in kidney makes these two organs vital for drug screen studies. Additionally, current OoC based MPS systems are mainly dependent upon conventional end-point bioassays comprising of PCR, western blots, and biochemical assays. It is challenging to perform conventional bioassays to analysis MPS systems owing to their complexity as well as reduced cell number and culture media quantity for sample collection. Such analytical limitation in MPS highlights the potential to integration the real-time or continuous sensors for efficient monitoring of cell conditions and responses. This thesis work encompasses the development of microfluidic liver and kidney MPS systems to emulate the development of disease and drug treatment with the integration of sensors. Liver and Kidney MPS were established with the integration of impedance-based transepithelial electrochemical resistance (TEER) sensor, optical pH sensor, and albumin immunosensor for monitoring of disease model development and drug efficacy measurements which were further validated by conventional bioassays. As albumin exhibits the function, the integrated microfluidic human serum albumin immunosensor facilitated the albumin screening for disease and drug analysis. This thesis contributes for the improvement of continuous monitoring of MPS by expanding the disease modeling capacity of OoC technology for a rapid development of drugs.
Author(s)
Asif, Arun
Issued Date
2022
Awarded Date
2022. 2
Type
Dissertation
URI
https://dcoll.jejunu.ac.kr/common/orgView/000000010595
Alternative Author(s)
아시프, 아룬
Affiliation
제주대학교 대학원
Department
대학원 에너지응용시스템학부 메카트로닉스공학전공
Advisor
Choi, Kyung Hyun
Table Of Contents
1. Objectives of Thesis 1
2. Introduction 2
3. Research Background 5
3.1. Kidney Microphysiological System 5
3.2. Liver Microphysiological System 6
3.3. Microfluidic Sensors 8
3.3.1. Electrochemical Sensor 8
3.3.2. Impedimetric Sensor 9
3.3.4. Electrochemical Immunosensor 10
4. Methodology 12
4.1. OoC-based MPS Design and Development 12
4.2. Sensor Development 13
4.2.1. Transepithelial Electrochemical Resistance Sensor 13
4.2.2. Albumin Immunosensor Development for Liver MPS 14
4.3. OoC Models 17
4.3.1. Kidney MPS Cell Culture 17
4.3.2. Liver MPS Cell culture 17
4.4. Biochemical Assays 18
4.4.1. Viability Assay and ELISA Measurement from Kidney MPS 18
4.4.2. Albumin, Urea, and P450 Assays 19
4.4.3. Immuno-fluorescence Staining 19
4.5. Computational Fluid Simulation 20
4.6. Statistical Analysis 20
5. Results 21
5.1. Kidney MPS with TEER Sensor 21
5.1.1. Proximal Tubule Cells and Fibroblasts Mixed Culture 21
5.1.2. Inflammatory Nephrotoxicity 21
5.1.3. Drug Treatment 22
5.1.4. Viability Analysis 25
5.1.5. KIM-1 and HSP70 ELISA Measurements 26
5.2. Liver MPS with Albumin Immunosensor 27
5.2.1. Electrochemical Analysis of Human Serum Albumin Sensor 27
5.2.2. Liver MPS Design 27
5.2.3. Sensor Testing for 24 Hours 28
5.2.4. Sensor Testing for 6 Days 29
5.2.5. Biochemical Measurements 31
5.2.6. Fluid Dynamics Simulation 32
6. Discussion 34
7. Conclusion and Future Perspectives 36
References 37
Degree
Doctor
Publisher
제주대학교 대학원
Appears in Collections:
Faculty of Applied Energy System > Mechatronics Engineering
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