A new imaging technology gives scientists the ability to simultaneously measure as many as 100 or more distinct features in or on a single cell. In a disease such as cancer, that capability would provide a much better picture of what's going on in individual tumor cells.
A Stanford University School of Medicine team led by Cathy Shachaf, PhD, an instructor in microbiology and immunology, has for the first time used specially designed dye-containing nanoparticles to simultaneously image two features within single cells.
Although current single-cell flow cytometry technologies can do up to 17 simultaneous visualizations, this new method has the potential to do far more. The new technology works by enhancing the detection of ultra-specific but very weak patterns, known as Raman signals, which molecules emit in response to light.
In a study published April 15 in the online journal PLoS-ONE, the Stanford team showed they were able to simultaneously monitor changes in two intracellular proteins that play crucial roles in the development of cancer.
Successful development of the new technique may improve scientists' ability not only to diagnose cancer--for example, by determining how aggressive tumors' constituent cells are--but to eventually separate living, biopsied cancer cells from one another based on characteristics indicating their stage of progression, and their degree of resistance to chemotherapeutic drugs. That would expedite the testing of treatments targeting a tumor's most recalcitrant cells, Shachaf said.
Cancer starts out in a single cell, she explained, and its development is often heralded by changes in the activation levels of certain proteins. In the world of cell biology, one common way for proteins to get activated is through a process called phosphorylation that slightly changes a protein's shape, in effect turning it on.
Two intracellular proteins, Stat1 and Stat6, play crucial roles in the development of cancer. The Stanford team was able to simultaneously monitor changes in phosphorylation levels of both proteins in lab-cultured myeloid leukemia cells. The changes in Stat1 and Stat6 closely tracked those demonstrated with existing visualization methods, establishing proof of principle for the new approach, Shachaf said.
While the new technology so far has been used only to view cells on slides, it could eventually be used in a manner similar to flow cytometry, the current state-of-the-art technology, which lets scientists visualize single cells in motion.