Micro- and Nanosystems for Biotechnology

Emphasizing their emerging capabilities, this volume provides a strong foundation for an understanding of how micro- and nanotechnologies used in biomedical research have evolved from concepts to working platforms. Volume editor Christopher Love has assembled here a highly interdisciplinary group of authors with backgrounds ranging from chemical engineering right up to materials science to reflect how the intersection of ideas from biology with engineering disciplines has spurred on innovations. In fact, a number of the basic technologies described are reaching the market to advance the discovery and development of biopharmaceuticals. The first part of the book focuses on microsystems for single-cell analysis, examining tools and techniques used to isolate cells from a range of biological samples, while the second part is dedicated to tiny technologies for modulating biological systems at the scale of individual cells, tissues or whole organisms. New tools are described which have a great potential for (pre)clinical development of interventions in a range of illnesses, such as cancer and neurological diseases. Besides describing the promising applications, the authors also highlight the ongoing challenges and opportunities in the field.

Auteur
J. Christopher Love is associate professor in chemical engineering at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology(MIT, USA). He is also an associate member at the Eli and Edythe L. Broad Institute, and at the Ragon Institute of MGH, MIT, and Harvard (USA). Dr. Love received his Ph.D. in 2004 at Harvard University (USA). He extended his research into immunology at Harvard Medical School from 2004-2007. His research centers on using simple microsystems to monitor cells from clinical samples in human disease, and on developing new approaches to manufacture biologic drugs efficiently and affordably. Dr. Love was named a Dana Scholar for Human Immunology and a Keck Distinguished Young Scholar in Medical Research in 2009. He is also a Camille Dreyfus Teacher-Scholar.

Sang Yup Lee is Distinguished Professor at the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST). He is currently the Director of the Center for Systems and Synthetic Biotechnology, Director of the BioProcess Engineering Research Center, and Director of the Bioinformatics Research Center. He has published more than 500 journal papers, 64 books and book chapters, and more than 580 patents (either registered or applied). He received numerous awards, including the National Order of Merit, the Merck Metabolic Engineering Award, the ACS Marvin Johnson Award, Charles Thom Award, Amgen Biochemical Engineering Award, Elmer Gaden Award, POSCO TJ Park Prize, and HoAm Prize. He currently is Fellow of American Association for the Advancement of Science, the American Academy of Microbiology, American Institute of Chemical Engineers, Society for Industrial Microbiology and Biotechnology, American Institute of Medical and Biological Engineering, the World Academy of Science, the Korean Academy of Science and Technology, and the National Academy of Engineering of Korea. He is also Foreign Member of National Academy of Engineering USA. He is currently honorary professor of the University of Queensland (Australia), honorary professor of the Chinese Academy of Sciences, honorary professor of Wuhan University (China), honorary professor of Hubei University of Technology (China), honorary professor of Beijing University of Chemical Technology (China), and advisory professor of the Shanghai Jiaotong University (China). Lee is the Editor-in-Chief of the Biotechnology Journal and Associate Editor and board member of numerous other journals. Lee is currently serving as a member of Presidential Advisory Committee on Science and Technology (Korea).

Jens Nielsen is Professor and Director to Chalmers University of Technology (Sweden) since 2008. He obtained an MSc degree in Chemical Engineering and a PhD degree (1989) in Biochemical Engineering from the Technical University of Denmark (DTU) and after that established his independent research group and was appointed full Professor there in 1998. He was Fulbright visiting professor at MIT in 1995-1996. At DTU, he founded and directed the Center for Microbial Biotechnology. Jens Nielsen has published more than 350 research papers, co-authored more than 40 books and he is inventor of more than 50 patents. He has founded several companies that have raised more than 20 million in venture capital. He has received numerous Danish and international awards and is member of the Academy of Technical Sciences (Denmark), the National Academy of Engineering (USA), the Royal Danish Academy of Science and Letters, the American Institute for Medical and Biological Engineering and the Royal Swedish Academy of Engineering Sciences.

Professor Gregory Stephanopoulos is the W. H. Dow Professor of Chemical Engineering at the Massachusetts Institute of Technology (MIT, USA) and Director of the MIT Metabolic Engineering Laboratory. He is also Instructor of Bioengineering at Harvard Medical School (since 1997). He received his BS degree from the National Technical University of Athens and his PhD from the University of Minnesota (USA). He has co-authored approximately 400 research papers and 50 patents, along with the first textbook on Metabolic Engineering. He has been recognized by numerous awards from the American Institute of Chemical Engineers (AIChE) (Wilhelm, Walker and Founders awards), American Chemical Society (ACS), Society of industrial Microbiology (SIM), BIO (Washington Carver Award), the John Fritz Medal of the American Association of Engineering Societies, and others. In 2003 he was elected member of the National Academy of Engineering (USA) and in 2014 President of AIChE.

Contenu

List of Contributors XI

About the Series Editors XVII

Preface XIX

Part I Microsystems for Single-Cell Analysis 1

1 Types of Clinical Samples and Cellular Enrichment Strategies 3
KohMeng Aw Yong, Zeta Tak For Yu, Krystal Huijiao Guan, and Jianping Fu

1.1 Introduction 3

1.2 Types of Clinical Samples 4

1.2.1 Solid Clinical Samples 4

1.2.1.1 Cellular Subtypes Found in Solid Clinical Samples 5

1.2.2 Liquid Clinical Samples and Cellular Subtypes 8

1.2.2.1 Blood 8

1.2.2.2 Bone Marrow 9

1.2.2.3 Placental or Umbilical Cord Blood 10

1.2.2.4 Urine 10

1.2.2.5 Cerebrospinal Fluid (CSF) 10

1.2.2.6 Saliva 11

1.3 Sample Processing and Conventional Methods of Cell Enrichment 11

1.3.1 Processing Solid Clinical Samples 11

1.3.1.1 Processing Liquid Samples 12

1.3.2 Cell Enrichment 12

1.3.2.1 Laser Capture Microdissection (LCM) 12

1.3.2.2 Density Gradient Centrifugation 13

1.3.2.3 Fluorescence-Activated Cell Sorting (FACS) 13

1.3.2.4 Magnetic Activated Cell Sorting (MACS) 15

1.3.2.5 CellSearchTM 15

1.4 Microscale/Nanoscale Devices for Cellular Enrichment 16

1.4.1 Filtration Approaches 16

1.4.2 Hydrodynamic Mechanisms 17

1.4.3 Surface Treatments 19

1.4.4 Magnetophoresis 19

1.4.5 Electrophoresis 20

1.4.6 Acoustophoresis 21

1.4.7 Optical Tweezers/Traps 22

1.5 Conclusion 23

References 23

2 Genome-Wide Analysis of Single Cells and the Role of Microfluidics 29
Sayantan Bose and Peter A. Sims

2.1 Motivation for Single-Cell Analysis of Genomes and Transcriptomes 29

2.2 Single-Cell Genomics 30

2.2.1 Major Technical Challenges 30

2.2.2 Approaches to Single-Cell Genomics 31

2.2.3 The Application and Impact of Microfluidics in Single-Cell Genomics 34

2.3 Single-Cell Transcriptomics 36

2.3.1 Major Technical Challenges 36

2.3.2 Approaches to Single-Cell Transcriptomics 39

2.3.3 Application and Impact of Microfluidics in Single-Cell Transcriptomics 42

2.4 The Future of Genome-Wide Singl…