Flow Cytometry In Drug Discovery And Development

This book covers the unique application of flow cytometry in drug discovery and development. The first section includes two introductory chapters, one on flow cytometry and one on biomarkers, as well as a chapter on recent advances in flow cytometry. The second section focuses on the unique challenges and added benefits associated with the use of flow cytometry in the drug development process. The third section contains a single chapter presenting an in depth discussion of validation considerations and regulatory compliance issues associated with drug development.

Flow cytometry is a sensitive and quantitative platform for the measurement of particle fluorescence. In flow cytometry, the particles in a sample flow in single file through a focused laser beam at rates of hundreds to thousands of particles per second. During the time each particle is in the laser beam, on the order of ten microseconds, one or more fluorescent dyes associated with that particle are excited. The fluorescence emitted from each particle is collected through a microscope objective, spectrally filtered, and detected with photomultiplier tubes. Flow cytometry is uniquely capable of the precise and quantitative molecular analysis of genomic sequence information, interactions between purified biomolecules and cellular function. Combined with automated sample handling for increased sample throughput, these features make flow cytometry a versatile platform with applications at many stages of drug discovery. Traditionally, the particles studied are cells, especially blood cells; flow cytometry is used extensively in immunology. This volume shows how flow cytometry is integrated into modern biotechnology, dealing with issues of throughput, content, sensitivity, and high throughput informatics with applications in genomics, proteomics and protein-protein interactions, drug discovery, vaccine development, plant and reproductive biology, pharmacology and toxicology, cell-cell interactions and protein engineering.

This first edition volume demystifies the complex topic of flow cytometry by providing detailed explanations and nearly 120 figures to help novice flow cytometry users learn and understand the bedrock principles necessary to perform basic flow cytometry experiments correctly. The book divides the topic of flow cytometry into easy to understand sections and covers topics such as the physics behind flow cytometry, flow cytometry lingo, designing flow cytometry experiments and choosing appropriate fluorochromes, compensation, sample preparation and controls and ways to assess cellular function using a variety of flow cytometry assays. Written as a series of chapters whose concepts sequentially build off one another, using the list of materials contained within each section along with the readily reproducible laboratory protocols and tips on troubleshooting that are included, readers should be able to reproduce the data figures presented throughout the book on their way to mastering sound basic flow cytometry techniques. Easy to understand and comprehensive, Flow Cytometry Basics for the Non-Expert will be a valuable resource to novice flow cytometry users as well as experts in other biomedical research fields who need to familiarize themselves with a basic understanding of how to perform flow cytometry and interpret flow cytometry data. This book is written for both scientists and non-scientists in academia, government, biotechnology, and medicine.

Drug discovery and development process aims to make available medications that are safe and effective in improving the length and quality of life and relieving pain and suffering. However, the process is very complex, time consuming, resource intensive, requiring multi-disciplinary expertise and innovative approaches. There is a growing urgency to identify and develop more effective, efficient, and expedient ways to bring safe and effective products to the market. The drug discovery and development process relies on the utilization of relevant and robust tools, methods, models, and validated biomarkers that are predictive of clinical effects in terms of diagnosis, prevention, therapy, and prognosis. There is a growing emphasis on translational research, a bidirectional bench to the bedside approach, in an effort to improve the process efficiency and the need for further innovations. The authors in the book discuss the current and evolving state of drug discovery and development.

This handbook covers established and advanced techniques for biomarker analysis, such as guidelines and strategies for assay validation methods; different mathematical models that are necessary in contemporary drug discovery and development; and evaluation of new cytometry methods. Expertly curated by two practicing professionals in drug development and biotherapeutics, individual chapters are selected for novel and sound research; information is chosen based on its relevance to lab applications and clinical trials, such as the topic of selecting animal models for their relevancy to humans. The book is multifaceted, discussing the ethics and issues with biospecimens and providing an in-depth analysis to the differences between pre-clinical and clinical assay development. The book is an essential read for general readers who need an introduction to the history and background of biomarkers, and it also provides critical analyses of various new validation methods for practitioners and researchers.

There has always been some tension between proponents of hypothesis-driven and discovery-driven research in the broad field of life sciences. Academic research has been primarily focused on hypothesis-driven research. However, the success of the human genome project, a discovery-driven research approach, has opened the door to adding other types of discovery-driven research to a continuum of research approaches. In contrast, drug discovery research in the pharmaceutical industry has embraced discovery-driven research for many years. A good example has been the discovery of active compounds from large chemical libraries, through screening campaigns. The success of the human genome project has also demonstrated the need for both academic researchers and industrial researchers to now understand the functions of genes and gene products. The cell is the basic unit of life and it has been at the cellular level where function can be demonstrated most cost-effectively and rapidly. High content screening (HCS) was developed by Cellomics Inc. in the mid-1990s to address the need for a platform that could be used in the discovery-driven research and development required to understand the functions of genes and gene products at the level of the cell.

This book reviews the challenges and opportunities posed by flow chemistry in drug discovery, and offers a handy reference tool for medicinal chemists interested in the synthesis of biologically active compounds. Prepared by expert contributors, the respective chapters cover not only fundamental methodologies and reactions, such as the application of catalysis, especially biocatalysis and organocatalysis; and non-conventional activation techniques, from photochemistry to electrochemistry; but also the development of new process windows, processes and reactions in drug synthesis. Particular attention is given to automatization and library synthesis, which are of great importance in the pharmaceutical industry. Readers will also find coverage on selected topics of general interest, such as how flow chemistry is contributing to drug discovery R&D in developing countries, and the green character of this enabling technology, for example in the production of raw materials for the pharmaceutical industry from waste. Given its scope, the book appeals to medicinal chemistry researchers working in academia and industry alike, as well as professionals involved in scale-up and drug development.