Table Of ContentMicro spheres:
Medical
and Biological
Applications
Editors
Alan Rembaum, Ph.D. Zoltan A. Tokes, Ph.D.
Jet Propulsion Laboratory Associate Professor of Biochemistry
California Institute of Technology School of Medicine and Comprehensive
Hydrocarbon Institute Career Center
Department of Chemistry University of Southern California
University of Southern California Los Angeles, California
Los Angeles, California
First published 1988 by CRC Press
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THE EDITORS
Alan Rembaun, Ph.D., was born in 1916 in Ciechanow, Poland. In 1936, he went to
Paris to study at the University of Sorbonne, and later received his “License es Sciences”
from University of Lyon, France. During the Nazi occupation of France, he had to escape
to Spain. He was arrested there and later escaped to England where he joined the Polish
Liberation Forces. After the war, he came to the U.S. where he received his Ph.D. degree
in Chemistry from the Syracuse University of New York in 1956. He joined the faculty at
Akron University in Ohio and established himself as a recognized polymer chemist by
investigating the polymerization of methyl methacrylate, the chemistry of methyl radicals,
polymerization of methyl styrenes, and the electron transfer of siloxanes. In 1959, he went
to Princeton University, New Jersey, to study the decomposition of ethyllithium in tetrah-
ydrofuran and the cesium initiated diene polymerization and copolymerization. Two years
later, at the Jet Propulsion Laboratories, California Institute of Technology, he developed
a new class of block polymers, studied the kinetics of anionic polymerization of acena
phthylene, and investigated polymeric semiconductors. In collaboration with Drs. Felix
Gutman and Allen Hermann, he devised a miniature battery which is now widely used in
cardiac pacemakers. In 1970, he started to devote most of his investigation to novel poly
electrolytes, microspheres, and to their application to biological problems. He and Dr.
William J. Dreyer of California Institute of Technology were involved in the application of
latex spheres to study cell surfaces and in the development of immunolatex microspheres
for scanning electron microscopy. His early work on the synthesis of magnetic polymeric
microspheres of small and uniform size was not only meritorious in its own right in the
field of polymer synthesis, but also provided opportunities for interactions with the disciplines
of biology and medicine.
Dr. Rembaum has published more than 200 scientific papers. He co-authored or edited
5 books and was issued 56 patents. In 1968 and 1984, he received the NASA Gold Medal
Award for exceptional scientific achievements and in 1986, after 24 years of service at the
Jet Propulsion Laboratories, he received the NASA Career Award which recognized his
outstanding scientific and technical contribution. He passed away in June 1986 and will be
remembered as a stimulating, tireless, and inspiring scientist by his friends and colleagues.
Zoltan A. Tokes, Ph.D., is an Associate Professor in the Department of Biochemistry
at the School of Medicine of the University of Southern California. He was born in 1940
in Budapest, Hungary. His initial encounter with biochemistry was at the Technical School
for Fermentation and Food Preservation. In 1957, he came to the U.S. and worked in the
field of mucopolysaccharide biosynthesis as a Research Assistant with Drs. Walter Marx
and John W. Mehl. He received his B.Sc. degree in Chemistry, from the University of
Southern California in 1964 and continued his graduate education at the California Institute
of Technology, Pasadena. His research was on the cell surface changes with differentiation
in Dr. William J. Dreyer’s laboratory. After receiving his Ph.D. in Biochemistry, he joined
the University of Malaya in Kuala Lumpur in 1970 as a lecturer, and conducted research
on the digestive enzymes of carnivorous plants and on the erythrocyte abnormalities found
among the aborigines. In 1972, he joined the Basel Institute for Immunology in Switzerland
under the directorship of Dr. Neils K. Jeme. There he continued his research on the bio
chemistry of the cell surface and in collaboration with Dr. Hansruedi Kiefer he developed
an assay to quantitate the cell surface associated proteolytic activity. He joined the University
of Southern California’s Comprehensive Cancer Center and the Department of Biochemistry
in 1974. His investigation focuses on the molecular events that take place a the cell surface.
Dr. Tokes published more than 50 scientific papers, contriubted 18 books and recieved
serveral U.S. patents. Dr. Tokes claims that there is no such thing as a boring moment in
his laboratory. His laboratory and co-workers are credited with the successful encapsulation
of anthracyclines in liposomes thereby reducing their undesirable host toxicity. They were
successful in generating human monoclonal antibodies which preferentially bind to breast
cancer cells and developing a membrane directed drug delivery with microspheres. His
laboratory was also involved in the characterization of cells surface associated glycoproteins
and proteinase inhibitors. Since 1975, Dr. Tokes served as the director of the Cell Culture
Core Facility of the USC Comprehensive Cancer Center.
This book is gratefully dedicated by Alan Rembaum to his wife Danuta
CONTRIBUTORS
Wilhelm Ansorge, Ph.D. Emma Fernandez-Repollet
Department of Instrumentation Department of Pharmacology
European Molecular Biology Laboratory University of Puerto Rico School of
Heidelberg, West Germany Medicine
San Juan, Puerto Rico
Jon Olav Bjdrgum, Cand.real.
Research Scientist
R. M. Fitch
Division of Applied Chemistry
Louis Laboratory
SINTEF
S. C. Johnson & Sons, Inc.
Trondheim, Norway
Racine, Wisconsin
Robert A. Bloodgood, Ph.D.
Steinar Funderud, Ph.D.
Associate Professor
Biochemist
Department of Anatomy
Apothekemes Laboratory for Special
University of Virginia School of
Preparaters
Medicine
The Norwegian Radium Hospital
Charlottesville, Virginia
Oslo, Norway
F. Chae
Memorial Sloan-Kettering Cancer Center Jean Gruenberg, Ph.D.
New York, New York Department of Cell Biology
European Molecular Biology Laboratory
M. Chang Heidelberg, West Germany
Jet Propulsion Laboratory
California Institute of Technology
Kathryn E. Howell, Ph.D.
Pasadena, California
Department of Cell Biology
European Molecular Biology Laboratory
N. Collins
Heidelberg, West Germany
Memorial Sloan-Kettering Cancer Center
New York, New York
N. Kernan
Michael Colvin, Ph.D. Memorial Sloan-Kettering Cancer Center
Chemist New York, New York
Department of Applied Sciences
Jet Propulsion Laboratory J. Laver
Pasadena, California Memorial Sloan-Kettering Cancer Center
New York, New York
Havard E. Danielsen, M.Sc.
Norsk Hydro’s Institute for Cancer
K. M. Scholsky
Research
Louis Laboratory
The Norwegian Radium Hospital
S.C. Johnson & Sons, Inc.
Oslo, Norway
Racine, Wisconsin
Turid Ellingsen, Dr.ing.
Department of Applied Chemistry A. Schwartz
SINTEF Flow Cytometry Standards Corporation
Trondheim, Norway Research Triangle Park, North Carolina
Tor Lea Kevin L. Ross, Ph.D.
Department of Immunology and Research Fellow
Rheumatology Department of Medical Oncology
Rikshospitalet University Hospital City of Hope National Medical Center
Oslo, Norway Duarte, California
Kjell Nustad, Ph.D.
Per Stenstad, Dr.ing.
Consultant
Research Scientist
Central Laboratory
Department of Industrial Chemistry
The Norwegian Radium Hospital
University of Trondheim
Oslo, Norway
Trondheim, Norway
R. O’Reilly
Memorial Sloan-Kettering Cancer Center Sven-Erik Strand, Ph.D.
New York, New York Associate Professor
Department of Radiation Physics
Chris D. Platsoucas, Ph.D. Lund University
Department of Immunology Lund, Sweden
M.D. Anderson Hospital
Houston, Texas
Jerome A. Streifel
Molecular Biosystems, Inc.
Albrecht Reith, Ph.D.
San Diego, California
Head of Laboratory of Electron
Microscopy and Morphometry
Department of Pathology
Zoltan A. Tokes, Ph.D.
Norsk Hydro’s Institute for Cancer
Associate Professor of Biochemistry
Research
Comprehensive Cancer Center
The Norwegian Radium Hospital
University of Southern California School
Oslo, Norway
of Medicine
Los Angeles, California
Alan Rembaum, Ph.D.
Jet Propulsion Laboratory
California Institute of Technology John Ugelstad, Ph.D.
Hydrocarbon Institute Professor
Department of Chemistry Department of Industrial Chemistry
University of Southern California University of Trondheim
Los Angeles, California Trondheim, Norway
Frode Vartdal, Ph.D.
Senior Registrar
Institute of Immunology and
Rheumatology
Rikshospitalet University Hospital
Oslo, Norway
TABLE OF CONTENTS
Chapter 1
The Covalent Binding of Enzymes and Immunoglobulins to Hydrophilic Microspheres.. 1
Michael Colvin, Adam Smolka, M. Chang, and Alan Rembaum
Chapter 2
Application of Microspheres to Measure Cell Surface Associated Enzyme Activities ... 15
Zoltan A. Tokes
Chapter 3
Magnetic Free Flow Immuno-Isolation System Designed for Subcellular Fractionation . 33
Kathryn E. Howell, Wilhelm Ansorge, and Jean Gruenberg
Chapter 4
Monodisperse Polymer Particles in Immunoassays and Cell Separation...........................53
Kjeil Nustad, Havard Danielsen, Albrecht Reith, Steinar Funderus, Tor Lea, Frode
Vartal, and John Ugelstad
Chapter 5
Microspheres and Cell Separation ..........................................................................................77
Jerome A. Streifel
Chapter 6
The Use of Magnetic Monosized Polymer Particles for the Removal of T Cells from Human
Bone Marrow Cell Suspensions................................................................................................89
Chris D. Platsoucas, F. H. Chae, N. Collins, N. Kernan, J. Laver, T. Ellingsen, P.
Stenstad, J. Bjorgum, A. Rembaum, R. A. Good, R. O’Reilly, and J. Ugelstad
Chapter 7
Polymer Colloids as Controlled Release Devices..................................................................101
Robert M. Fitch and Kevin M. Scholsky
Chapter 8
Targeting of Drug Action to the Cell Surface by Microspheres.........................................123
Kevin Ross and Zoltan A. Tokes
Chapter 9
Microspheres and Phagocytosis.................................................................................................139
Emma Fernandez-Repollet and Abraham Schwartz
Chapter 10
The Use of Microspheres in the Study of Cell Motility....................................................165
Robert A. Bloodgood
Chapter 11
Applications and Characterization of Radiolabeled or Magnetizable Nano- and Micropar
ticles for RES, Lymph and Blood Flow Studies................................................................193
Sven-Erik Strand, Lena Andersson, and Lennart Bergquist
Index 229
1
Chapter 1
THE COVALENT BINDING OF ENZYMES AND IMMUNOGLOBULINS TO
HYDROPHILIC MICROSPHERES
M. Colvin, A. Smolka, A. Rembaum, and M. Chang
TABLE OF CONTENTS
Abstract...........................................................................................................................................2
I. Introduction.........................................................................................................................2
II. Methods..............................................................................................................................3
III. Results.................................................................................................................................5
IV. Discussion..........................................................................................................................8
Acknowledgments.........................................................................................................................12
References......................................................................................................................................12
