Dr. Gerrit Van den Engh
Cytopeia Inc.

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History has shown that inventions often emerge at the interface between two seemingly-disparate disciplines. Dr. Gerrit Van den Engh of Cytopeia Inc. is an example of a scientist who has successfully filled a specialized niche at such an interface. In developing the first practical high-speed sorter for flow cytometry, Dr. Van den Engh has brought the power of physics to bear on important biological questions.

Dr. Van den Engh, who is a native of Amsterdam, initially began to study biology at the University of Leiden. He added physics to his curriculum his second year, and went on to earn a “doctoraal” degree, which is a seven year degree that encompasses the US equivalent of a bachelor’s degree plus a few years of graduate-level study. He then moved to the Erasmus University of Rotterdam, where he became a staff scientist in the Department of Radiobiology. He later returned to the University of Leiden, where he earned a Ph.D. in Biophysics.

Following his graduate studies, he continued his work on isolation methods for hematopoietic stem cells, the type of stem cells that form blood cells. His experiments necessitated the use of a device called a “flow cytometer” to differentiate between different types of cells. Flow cytometry is a technique in which microscopic particles are suspended in a stream of fluid, and are measured or quantitated by a laser beam based on chemical or physical characteristics of the particle, such as fluorescence or light scattering. While a number of different types of particles may be analyzed by flow cytometer, a common application is to use the machine to analyze the characteristics of individual cells. Flow cytometers are capable of measuring features of cells that have been labeled with compounds that make them fluoresce. Flow cytometry enables researchers to observe characteristics of a large number of cells, one cell at a time.

Flow cytometry instruments often include a device called a “cell sorter”. A cell sorter monitors scatter and fluorescence signals to classify individual cells as they fall through the path of a laser. The information is recorded, and used to sort the cells into different tubes using electrostatic charges. Cell sorters are especially useful because they enable researchers to sort living cells that may be used or propagated in further experiments.

Dr. Van den Engh used a commercial cell sorter in his studies, but found that the instrument was too slow to be of practical use. This led him to take a sabbatical at the Los Alamos National Laboratory, where he could learn more about technology used in cell sorting and find ways to speed up the process. Los Alamos National Laboratory has a long history of involvement in cell sorting technology, as the first prototype cell sorter was built there in 1965.

After moving to New Mexico in 1983, he found that Los Alamos didn’t offer much in terms of after-work entertainment. To keep occupied in the evenings, he acquired a copy of “The Art of Electronics” by Horowitz and Hill, and began reading about electronic circuits. His night time reading led him to develop the electronics for a faster and more accurate cell sorter. He considers “The Art of Electronics” his “bible” and continues to keep a copy of it in his office.

Later that year, he transferred to the Lawrence Livermore National Laboratory, where the Human Genome Project was just getting underway. While a visiting scientist at Lawrence Livermore, he built a flow cytometer that incorporated the speedy cell sorting electronics that he devised at Los Alamos.

During his time at Lawrence Livermore, it became apparent that the technical improvements in flow cytometry that were being developed for stem cell research could be used to classify and sort chromosomes, the thread-like packages of DNA and protein that contain the genetic material responsible for heredity. Chromosome sorting is an essential step for analyzing the massive amounts of genetic material required to elucidate genome sequences, and has been used extensively in the Human Genome Project. Following classification and sorting by a cell sorter, the chromosomes can then be further analyzed to determine what genes are present, as well as the individual nucleotide sequences of the genes. Dr. Van den Engh, along with his wife, Dr. Barbara Trask received a patent for the use of flow cytometry to sort chromosomes in 1988.

In 1992, Dr. Van den Engh and Dr. Trask were contacted by Leroy Hood and invited to join the Department of Molecular Biotechnology at the University of Washington. As a founding member of the department, Dr. Van den Engh was involved in a number of different patents related to improvements of the cell sorting technology. Several years later, when Leroy Hood left the University of Washington and founded the Institute for Systems Biology (ISB), Dr. Van den Engh and Dr. Trask followed. With the goal of developing the next generation of fast, compact, and less-expensive cell sorters, Dr. Van den Engh founded Cytopeia, one of the first commercial enterprises to emerge from the ISB.

The inFlux cell sorter

At Cytopeia, Dr. Van den Engh and his colleagues have designed and constructed a small, modular, robust, easy-to-use cell sorter, called inFlux. In contrast to the large bench-top instruments that have been the standard in laboratories for a number of years, the inFlux cell sorter produced by Cytopeia is small enough to be wheeled around on a cart. Further, the small size of the instrument does not lead to a compromise in performance or speed, and is capable of sorting up to 50,000 cells per second.

As the questions asked by biologists become increasingly complex, so does the need for instrumentation necessary to address the questions. While instrumentation has traditionally fallen under the umbrella of physics, Dr. Van den Engh views his strength as his ability to create instruments that are based in physics but are user-friendly to biologists. Currently, Dr. Van den Engh’s laboratory at Cytopeia is working to devise new methods for analyzing single cells and single DNA molecules, and is in the process of developing an automated process for large-scale DNA sequencing and the isolation of microorganisms from environmental samples.

In addition, due to its size and portability, the inFlux sorter will be used on the Thomas G. Thompson, the research ship of the School of Oceanography of the University of Washington, where it will be utilized to help discover new organisms in the ocean. Further, inFlux instruments have also recently been installed at the Bermuda and Hawaii research stations where scientists study the relationship between marine microbes and global warming.

Davis Wright Tremaine congratulates Dr. Van den Engh on his many successes and is pleased to feature him in our Inventor Spotlight.

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