When scientists study cells, they need to know how much oxygen each cell consumes to determine its metabolism. However, existing technology limits this study to groups of cells, not individual cells. Lihong Wang, PhD, plans to change that.
Wang, the Gene K. Beare Distinguished Professor of Biomedical Engineering at Washington University in St. Louis, has received a three-year, $300,000 grant from the National Science Foundation (NSF) to study oxygen consumption rates of individual cells using photoacoustic microscopy, a novel imaging technology he developed that uses light and sound to measure change.
"When you image a group of cells, you assume all cells are identical, but they are not -- cells are heterogeneous and consume oxygen differently," says Wang, who also is affiliated with the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. "We will measure oxygen consumption on a per-cell basis, but measure many cells at the same time, giving us high specificity and a high-speed, high-yield throughput. As a result, we will be able to rapidly map distributions of cellular metabolism."
Wang and his collaborators will use hemoglobin, a protein in red blood cells that carries oxygen, as a biocompatible sensor to determine oxygen consumption. Hemoglobin changes color when oxygenated or deoxygenated. The color change is too slight to see using conventional microscopy, confocal microscopy or two-photon microscopy, but photoacoustic microscopy is exquisitely sensitive to color change, Wang says.
"Once cells are loaded into a matrix of wells, all we have to do is to use light-induced ultrasound to sense the color of hemoglobin next to each well," Wang says. "The rate of change in color of hemoglobin is used to compute the consumption rate of oxygen by each cell."
The proposed technology can lead to further understanding of a wide range of biological systems, from single cells to ecosystems, Wang says. Potential applications include gauging cellular health and metabolic state for stress response and in toxicity studies. Environmentally, oxygen-linked respiration is the main sink of organic matter in nature, and it can be considered as a fundamental component of global element cycling. Differences in oxygen uptake within complex natural communities can lend insights into the use of energy sources in the environment, as well as into primary production.
Wang is collaborating with Jun Zou, PhD, associate professor of electrical & computer engineering at Texas A&M University.
A leading researcher on new methods of cancer imaging, Wang has received more than 30 research grants as the principal investigator with a cumulative budget of more than $38 million. His research on non-ionizing biophotonic imaging has been supported by the NIH, National Science Foundation (NSF), the U.S. Department of Defense, The Whitaker Foundation and the National Institute of Standards and Technology.
Wang and his lab were the founders of a new type of medical imaging that gives physicians a new look at the body's internal organs, publishing the first paper on the technique in 2003. Called functional photoacoustic tomography, the technique relies on light and sound to create detailed, color pictures of tumors deep inside the body and may eventually help doctors diagnose cancer earlier than is now possible and to more precisely monitor the effects of cancer treatment -- all without the radiation involved in X-rays and CT scans or the expense of MRIs.
In September 2012 he received one of 10 NIH Director's Pioneer Awards from among 600 applicants. The award supports individual scientists of exceptional creativity who propose pioneering -- and possibly transforming -- approaches to major challenges in biomedical and behavioral research. He also has received the NIH FIRST, the NSF's CAREER Award, the Optical Society's C. E. K. Mees Medal and IEEE's Technical Achievement Award for seminal contributions to photoacoustic tomography and Monte Carlo modeling of photon transport in biological tissues and for leadership in the international biophotonics community.
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