The mass spectrometer, a machine previously used to detect metal contamination in circuits and minerals, can be used to examine the identity and behaviors of individual cells, Stanford researchers demonstrate in this week’s Science magazine.
The ability of the new procedure to identify more characteristics of each cell at once comes as a major breakthrough to immunologists, stem cell researchers and cancer scientists alike.
“Suddenly we go from seeing 10-15 parameters up to 30-100,” said Garry Nolan, professor of microbiology and immunology, whose lab did the research on this project.
He described this development as “a quantum leap” that allows scientists to “look more deeply into normal and abnormal immune cell development and cancers.”
According to Erin Simonds, a doctoral researcher in Nolan’s lab working on leukemia research, the lab has used this technology to examine differences between cancer cells and normal cells to better understand the disease process. Scientists can also use the mass spectrometer to better identify individual cancers and might one day be able to personalize cancer drug therapies.
“It gives cancer researchers a much broader perspective…it allows you to look at the entire cancer in one shot and look at the way that cancer is quite heterogeneous,” he said. “Once you find the parameters that help define a person’s cancer or get a fingerprint of that person’s cancer, then you can tailor therapy to treat that person’s cancer more effectively.”
Sean Bendall, a postdoctoral scholar and fellow first author of the study, explained that the machine would help speed up the scientific process and hopefully lead to therapies. He saw it being used to screen the effectiveness of drugs on multiple types of cells to help determine side effects. It could also be utilized to differentiate stem cell lines and help further that field of research.
“Being able to ask more questions all at once leads to more answers, and it just makes things move faster,” he said.
Researchers at the University of Toronto developed the mass spectrometer itself and had the idea of applying it to single cell analysis. They enlisted Nolan as an expert in single cell biology to apply previous biological analysis tools to the machine in an effort to facilitate the machine’s transition to the biology lab.
Nolan and the Toronto researchers based the technique on the traditional Fluorescence Activated Cytometry System (FACS) developed by Leonard Herzenberg at Stanford in the 1970s. Nolan pursued his doctoral work in the Herzenberg lab in the 1980s. The FACS can test up to 10 or 12 cell parameters at once by attaching antibodies to the cell labeled with organic fluorescent molecules. It then reads the cells by capturing the emitted light frequencies from the fluorescents as the cells pass through an activating laser.
The mass spectrometer labels molecules in the cell with rare earth elements from the bottom of the periodic table, which are attached to antibodies instead of organic fluorescents. The signals from these elements are more easily differentiated than wavelengths of different colors.
“When you look at a rainbow, the colors aren’t totally separate. One color blends into the next…and so with anything that uses light-based detection, there are only so many colors or dyes you can use before everything blends together and you can’t measure things anymore,” Bendall said.
Mass spectrometry allows for higher resolution measurement because different elements have distinct masses and, unlike light, these signals do not blend.
The single cells labeled with different metals are then heated to vaporization and the machine reads the ions of any elements bound by antibodies to the cell. The resulting readings allow scientists to determine which of the multiple parameters a given cell exhibits, giving a clear picture of that cell’s identity.
The machine is commercially available and is being adopted by labs around the world.