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Stanford Researchers Harness Nanoparticles to Track Cancer-Cell Changes.

STANFORD, Calif. -- The more dots there are, the more accurate a picture you get when you connect them. A new imaging technology could give 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 What's Going On is a record by American soul singer Marvin Gaye. Released on May 21, 1971 (see 1971 in music), What's Going On reflected the beginning of a new trend in soul music.  in individual tumor cells.

A Stanford University School of Medicine Stanford University School of Medicine is affiliated with Stanford University and is located at Stanford University Medical Center in Stanford, California, adjacent to Palo Alto and Menlo Park.  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 flow cytometry (flōˑ sī·tˑ·m  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, that molecules emit in response to light.

In a study to be published April 15 in the online journal PLoS-ONE, the Stanford team was 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 cancers--for example, by determining how aggressive tumors' constituent cells are--but to eventually separate living, biopsied cancer cells cells once believed to be peculiar to cancers, but now know to be epithelial cells differing in no respect from those found elsewhere in the body, and distinguished only by peculiarity of location and grouping.

See also: Cancer
 from one another based on characteristics indicating their stage of progression or their degree of resistance to chemotherapeutic drugs. That would expedite the testing of treatments targeting a tumor's most recalcitrant recalcitrant adjective Poorly responsive to therapy  cells, said Shachaf, a cancer researcher who works in a laboratory run by the study's senior author, Garry Nolan, PhD, associate professor of microbiology and immunology and a member of Stanford's Cancer Center.

Cancer starts out in a single cell, and its development is often heralded by changes in the activation levels of certain proteins. In the world of cell biology Cell biology

The study of the activities, functions, properties, and structures of cells. Cells were discovered in the middle of the seventeenth century after the microscope was invented.
, one common way for proteins to get activated is through a process called phosphorylation phosphorylation, chemical process in which a phosphate group is added to an organic molecule. In living cells phosphorylation is associated with respiration, which takes place in the cell's mitochondria, and photosynthesis, which takes place in the chloroplasts.  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 myeloid leukemia
n.
See myelogenous leukemia.
 cells. The changes in Stat1 and Stat6 closely tracked those demonstrated with existing visualization methods, establishing proof of principle for the new approach.

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. In flow cytometry, cells are bombarded with laser light as they pass through a scanning chamber. The cells can then be analyzed and, based on their characteristics, sorted and routed to different destinations within the cytometer.

Still, flow cytometry has its limits. It involves tethering fluorescent dye Noun 1. fluorescent dye - a yellow dye that is visible even when highly diluted; used as an absorption indicator when silver nitrate solution is added to sodium chloride in order to precipitate silver chloride (turns pink when no chloride ions are left in solution and  molecules to antibodies, with different colors tied to antibodies that target different molecules. The dye molecules respond to laser light by fluorescing--echoing light at exactly the same wavelength, or color, with which they were stimulated. The fluorescence's strength indicates the abundance of the cell-surface features to which those dyes are now attached. But at some point, the light signals given off by multiple dyes begin to interfere with one another. It is unlikely that the number of distinct features flow cytometry can measure simultaneously will exceed 20 or so.

The new high-tech dye-containing particles used by the Stanford team go a step further. They give off not just single-wavelength fluorescent echoes but also more-complex fingerprints comprising wavelengths slightly different from the single-color beams that lasers emit. These patterns, or Raman signals, occur when energy levels of electrons are just barely modified by weak interactions among the constituent atoms in the molecule being inspected.

Raman signals are emitted all the time by various molecules, but they're ordinarily too weak to detect. To beef up their strength, the Stanford team employed specialized nanoparticles produced by Intel Corp., each with its own distinctive signature. Intel has designed more than 100 different so-called COINs, or composite organic-inorganic nanoparticles: These are essentially sandwiches of dye molecules and atoms of metals such as silver, gold or copper whose reflective properties amplify a dye molecule's Raman signals while filtering out its inherent fluorescent response. The signals are collected and quantified by a customized, automated microscope.

Shachaf anticipates being able to demonstrate simultaneous visualization of nine or 10 COIN-tagged cellular features in the near future and hopes to bring that number to 20 or 30, a new high, before long. "The technology's capacity may ultimately far exceed that number," she added. Some day it could be used for more than 100 features. Meanwhile, another group outside Stanford, now collaborating with the Nolan group, has developed a prototype device that can detect Raman signals in a continuous flow of single cells, analogous to flow cytometry but with higher resolving power resolving power: see telescope.
Resolving power (optics)

A quantitative measure of the ability of an optical instrument to produce separable images.
, Shachaf said.

The study was funded by the National Cancer Institute's Center for Cancer Nanotechnology Excellence Focused on Therapy Response and by the Flight Attendant Medical Research Institute. Other Stanford contributors were researchers Sailaja Elchuri, PhD, and Dennis Mitchell Dennis Allen Mitchell (born February 20, 1966) is a former American athlete, winner of gold medal in 4x100 m relay at the 1992 Summer Olympics.

Born in Havelock, North Carolina, Mitchell placed fourth in 100 m at the 1988 Summer Olympics and missed a probable gold medal in
 of the Nolan lab; engineering and materials science materials science

Study of the properties of solid materials and how those properties are determined by the material's composition and structure, both macroscopic and microscopic.
 graduate student Ai Leen Koh; and Robert Sinclair Robert Sinclair († 1398) was a late 14th century bishop of Orkney and bishop of Dunkeld. Before becoming a bishop, he was dean of the bishopric of Moray and had obtained a Bachelor's degree in Law. , PhD, professor of materials science and engineering Materials science and engineering

A multidisciplinary field concerned with the generation and application of knowledge relating to the composition, structure, and processing of materials to their properties and uses.
.

The Stanford University School of Medicine consistently ranks among the nation's top 10 medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital Stanford Hospital is located at 300 Pasteur Drive, Stanford, California, 94305.[1] It is world-renowned for its work in cardiovascular medicine and surgery, organ transplantation, neurology, neurosurgery, and cancer diagnosis and treatment.  & Clinics and Lucile Packard Children's Hospital Lucile Packard Children's Hospital (LPCH) is a hospital located on the Stanford University campus in Palo Alto, California. It is staffed by over 650 physicians and 4,750 staff and volunteers. . For information about all three, please visit http://stanfordmedicine.org/about/news.html.
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Date:Apr 15, 2009
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