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Fluorescent nickel sensor could yield health benefits

BioPhotonics
Mar 2010
Hank Hogan, hank.hogan@photonics.com

BERKELEY, Calif. – Too much nickel could make life not worth a plugged nickel because an excess of the metal can adversely affect the respiratory and immune systems. Just how much is too much is a bit of an unknown, however, and it also is somewhat unclear as to how best to treat a nickel overdose.

Now a group of researchers from the University of California, Berkeley, has demonstrated a turn-on fluorescent sensor for detecting nickel in living cells. It could prove useful in studying the cellular regulation and role of the metal, information that associate chemistry professor Christopher J. Chang said is needed.


A turn-on fluorescent sensor highlights cells that have been exposed to nickel. Reused with permission from the American Chemical Society.

“Without an understanding of what roles nickel plays, we don’t know how to treat diseases of overload due to environmental exposure, nor do we know where and how much nickel is needed for diet and vitamin supplements,” he explained.

Chang and his group created the sensor by starting with a BODIPY, or boron dipyrromethene fluorescent dye. They combined this with a nickel cation receptor, creating the sensor NS1. They also found a receptor highly preferential to nickel over zinc and copper by mixing and matching combinations known to bind to the metals.

As reported by the researchers in a recent issue of the Journal of the American Chemical Society, tests done with a spectrophotometer from Varian Inc. of Walnut Creek showed that the probe’s absorption was centered at 495 nm. The emission maximum was at 507 nm, determined with a spectrofluorometer from Photon Technology International of Lawrenceville, N.J. The relative emission intensity rose with increasing nickel levels, verified with solutions ranging from a low of 0 to a high of 100-µM concentration.

In a demonstration of the sensor, the researchers did fluorescence imaging using a Zeiss laser scanning microscope. They used this for live-cell imaging of intracellular nickel levels to distinguish between cells cultured with and without nickel. They also could see when the cells had the nickel removed with a metal chelator; tests showed that the cells still were viable.

Chang said that, not only did the sensor select for nickel over zinc and copper, it also was capable of working in water and was nontoxic enough to be used in biological samples, all important characteristics. NS1 could be applied to study the toxicology of nickel overexposure and could be used in industries where nickel is used for catalytic purposes.

Plans call for sensors with improved sensitivity, with the ability to track nickel in subcellular compartments and with emission in different colors. The goal is to use these reagents to understand how cells handle nickel when healthy, sick or subjected to an overexposure of the metal.

This is part of a larger study of metals in biological systems that have health implications, Chang said. “We are working mainly on aspects of how metals affect brain function, aging and neurodegeneration.”


GLOSSARY
spectrofluorometer
An automatic scanning instrument that is used to study a substance's fluorescence over a wide range of wavelengths. It consists of a radiation source, a grating that functions as the monochromator in selecting the exciting radiation, a second grating that serves as the emission monochromator, and a photoelectric device that is used to detect the emissions.
spectrophotometer
An instrument for measuring spectral transmittance or reflectance.
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