Chad Lieber

Lighting the Way

August / September 2005 By: Robyn Eifertsen Volume 3 Number 4

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A curious skin outbreak has struck the starship Enterprise. To ascertain the source of the problem the ship's doctor sweeps a flashlight-like sensor across a crew member's arm. Without even having to touch the patient, he discovers a microscopic pathology.

This could be a scene from an episode of Star Trek, right? Stuff of science fiction? Well, perhaps not for too much longer.Researchers like Chad Lieber of the Center for Biophotonics Science and Technology in Davis, Calif., are studying how pathologists can use light within tissue to diagnose disease without having to perform a biopsy.

"It sounds kind of Star Trekkish when you get down to the details, but it's being developed in laboratories all over the world," says Lieber, referring to how new technologies are advancing the study of light interactions with living cells and tissue.

Lieber, a postdoctoral researcher at the University of California at Davis Medical Center, helps staff the optical tissue characterization lab at the CBST. The center is the only one in the nation funded by the National Science Foundation that's dedicated to biophotonics—€”the study of light and radiant energy in biology and medicine.

The optical tissue research, led by Lawrence Livermore National Lab physicist and researcher Stavros Demos, includes cataloging the different light reactions that occur within specific cancerous and non-cancerous cells. In doing so, the researchers hope to develop a library of information as well as tools that will one day reduce or eliminate the need to conduct time-intensive and often painful diagnostic biopsies.

Their optical research is also leading them in the direction of finding new ways to diagnose Alzheimer's disease and ways to test the viability of donated organs.

The undertaking is one of nearly 30 research projects currently being conducted at 10 institutions. The center's 100 collaborators include researchers, physicians and engineers from UC Davis, Lawrence Livermore, UC Berkeley, UC San Francisco, Alabama A&M University, Stanford University, University of Texas at San Antonio, Hampton University and Fisk University.

The center is funded with $52 million over the next 10 years including a $40 million grant from the NSF as well as state grants and private funding.

Applications of biophotonics vary from using light to image or selectively treat tumors, to sequencing DNA and identifying single biomolecules within cells. The center supports the development of a broad range of biophotonic technologies that include a bench top x-ray laser for cellular imaging, phototonic tools to dissect the molecular mechanisms of cardiovascular disease, laser tweezer-assisted cellular spectroscopy to detect early signs of leukemia, and light-based high-throughput techniques to detect infectious disease.

Officials say the center's objective is to collaborate with industry to accelerate biophotonics technology development and deliver this new technology into the hands of health-care providers. It is considered to be the West Coast's hub for biophotonics research that business partners can use to make new, leading-edge medical devices.

Since opening in 2002, the center has exceeded its quota of applying for at least 8 patents a year, according to the center's director, Dennis Matthews. He says that the center has more than 20 commercial partners and has helped create three new startups, including Berkeley-based Sierra Interventions, which has developed a new catheter device based on photo-activated shaped memory polymers.

Within the center, molecular and cellular biologists are using biophotonics to understand basic biology, says Frank Y.S. Chuang, the center's associate director for science education integration, who coordinates the center's research projects.

"There are still a lot of questions we haven't figured out about cell and molecular biology so we've got a lot of areas of study within biophotonics," Chuang says. "The expertise we are building up is being able to examine and visualize living tissue."

For example, Chuang says center scientists are using biophotonics to study how signals get inside and outside of the cell to better understand the mechanisms that lead to atherosclerosis and cardiovascular disease.

"Our scientists are trying to develop a vascular mimetic, a living working blood vessel they can study under the microscope," he says. Some of the most exciting applications of biophotonics are its application to DNA and infectious disease detection.

He says biophotonics can take DNA research to the next level. "To see the DNA and to see how our body goes about repairing it. If we were able to understand that maybe we would be able to help DNA research along," Chuang says. He adds that researchers are studying ways of using biophotonics to detect infectious diseases.

"We are always worried about infectious diseases, but because of 9/11 and the use of biological weapons we are all more interested now, from a national security point of view, to knowing how to quickly detect them," he says.
Researchers are studying how the use of attaching fluorescents to antibodies naturally attracted to germs could help identify infectious diseases.

Overall, the center's research projects are broken down into three areas:bioimaging, molecular and cellular biophotonics and medical biophotonics such as Demos's optical diagnosis study.

Within the center's bioimaging realm is an ultra-high resolution light microscopy project led by UC San Francisco assistant physiology professor Mats Gustafsson. Gustafsson's new team is studying ways to improve light microscopy resolution. He hopes that by developing new forms of light microscopy scientists can see smaller features than the laws of optics normally allow.

"One trick, which is called —€˜structured illumination microscopy' involves projecting patterns of light onto the object and processing the resulting images with a computer," Gustafsson says. "This trick has allowed us to double the resolution, and certain nonlinear versions of the same trick can reach much further than that."

According to Gustafsson light microscopy has become a very powerful tool in biology. "Our hope is that the improved resolution offered by the structured illumination techniques will allow researchers to apply these strengths to a new class of questions at a previously unreachable size and scale," he says. In the short term, his project will be a research tool that will aid the progress of biological research in general.

The UC Davis site is one of six universities originally chosen in 2002 by NSF to establish a science and technology center. Other centers explore topics from space weather to water purification systems.The Davis center recently opened a new building that the center's co-director, Dr. James E. Boggan, believes will increase synergy and productivity.

Such improvements are something, researcher Leiber says is probably increasingly important to investors and entrepreneurs. "In the case of biophotonics, the field is still so young that there is very little industry yet," he says. "The industry is just starting to get hold of it; 10 years ago if you saw any of this it was from small startup companies. Now you have Siemens, GE and Johnson & Johnson interested. These heavy hitters are picking up on it."

The center also has an educational component. Chuang hopes that the allure of being able to see living cells more closely with the human eye will attract more students of science into the field of biophotonics.

For Lieber, he hopes that biophotonics will someday reach the general public as has one of the science's pioneering applications—€”pulse oxymeters. The fingertip devices are used to measure hemoglobin and pulse rate. Lieber, who has extensively studied skin cancers, hopes that one day the public may be able to check for signs of melanoma, for example, as easily as it is to check your heart rate at the grocery store.

"Hopefully one day people will be able to put this funny-looking lesion under the light and it will be able to tell you if you have cancer or some disease," Lieber says. "I don't know if any of that would ever occur outside the lab in our lifetime but this (biophotonics research) is the foundation."

Robyn Eifertsen is a freelance writer in the Sacramento area.