ABSTRACT

The application of micromachining technologies for biomedical research has fostered the development of microscale technologies for advanced in vitro cell analysis such as microfluidic cellular microarrays, micro-cell culture systems, and specialized microanalytical platforms. The greatest benefit of these miniaturized cell chip systems is the ability to provide quantitative data in real time to shed light on rapidly changing, dynamic biological systems. Additionally, lab-on-a-chip systems for biomedical applications have shown to exhibit high reliability, reproducibility, and robustness, while affording the opportunity to conduct measurements under physiologically-relevant conditions, which is considered one the key criteria for next-generation cell-based assays. This chapter presents a short overview on fabrication methods of microfluidic

6.1 Introduction .................................................................................................. 103 6.2 Materials, Components, and Sensing Strategies ........................................... 104

6.2.1 Materials and Fabrication Methods of Cell Chips ............................ 104 6.2.2 Liquid Handling and Actuation Strategies for Cell Chips ................ 105 6.2.3 Integrated Sensor Systems ................................................................ 106

6.3 Microfluidic 2D and 3D Life-Cell Microarrays .......................................... 107 6.3.1 Microfluidic Single-Cell Microarrays .............................................. 112 6.3.2 Microfluidic Multicell Microarrays .................................................. 113 6.3.3 Microfluidic 3D Cell Microarrays ................................................... 114

6.3.3.1 Hydrogel-Based Microfluidic Systems .............................. 115 6.3.3.2 Hydrogel-Free 3D Cell-Based Microfluidic Systems......... 116

6.4 Application of Lab-on-a-Chip Technology-Selected Topics ..................... 117 6.4.1 Quality Control for Cell-Based Therapy Applications ..................... 117

6.4.1.1 On-Chip Flow Cytometry, Single Cell Manipulation, and Isolation ....................................................................... 118

6.4.1.2 Immunoassay-on-Chip for Quality Control Applications .... 118 6.4.2 Lab-on-a-Chip for Stem Cell Biology Applications ......................... 119

6.4.2.1 On-Chip Cultivation of Stem Cells .................................... 119 6.4.2.2 3D Stem Cell Cultivation and Application ........................ 121

6.5 Future Perspectives and Current Challenges ................................................ 122 References .............................................................................................................. 122

devices, fluid actuators, and biosensors for cell-based applications, describes microfluidic single-cell, multicell and three-dimensional (3D) cell culture arrays, and reflects on recent lab-on-a-chip advances and their applications for quality-control and stem cell biology.