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New microfluidic devices found to be effective method of in-vitro fertilization in mice

October 13, 2005

NN ARBOR, Mich. - Technology that more closely mirrors the natural fertilization process is showing promise as a new method of in-vitro fertilization, researchers at the University of Michigan Health System have found.

The researchers found that microfluidics - an emerging area of physics and biotechnology that deals with the microscopic flow of fluids - can be used successfully for IVF in mice. They also found that lower total numbers and concentrations of sperm were required when using microfluidic channels instead of culture dishes.

"This is an extension of the work we've done in recent years to use microfluidics to separate viable sperm from dead and immature sperm in order to maximize the potential chances of fertilizing an egg," says Gary D. Smith, Ph.D., associate professor of obstetrics and gynecology, urology, and physiology at the U-M Medical School.

"Now that we are using microfluidics for fertilization, what you are starting to see is the whole IVF process happening on a chip," says Smith, senior author of a study in Human Reproduction and director of the Assisted Reproductive Technologies Laboratory and of the Gamete Cryopreservation Laboratory at the Comprehensive Cancer Center.

IVF is a process in which eggs are removed from a woman's body and fertilized with sperm outside the body. Fertilized eggs are then placed in the woman's uterus, where they can develop as in a normal pregnancy.

The study, published online in the journal Human Reproduction, suggests that among other uses, microfluidic channels could be used in some - but not all - instances when a common form of insemination, known as ICSI, otherwise would be employed. ICSI, which stands for intracytoplasmic sperm injection, involves a single sperm being injected directly into an egg, or oocyte.

Smith says ICSI still will be used in many situations, particularly when other types of fertilization have failed in the past, or when the man has an extremely low sperm count or motility. Smith does not think the use of microfluidics will replace ICSI, but he says it could offer another option to many couples whose situations do not require ICSI, a process that can cost an extra $1,500 to $2,500 in addition to standard IVF costs.

"While ICSI bypasses all natural selection, the use of microfluidic channels more closely resembles in vivo insemination. The microfluidic environment also may possess conditions more suitable for efficient sperm-oocyte interaction than the culture dish," he says.

During the early stages of the study, researchers found that, contrary to their initial hypothesis, a much lower fertilization rate was achieved with the microfluidic device (12 percent) than in culture dishes (43 percent). They then hypothesized that as sperm concentration is decreased, fertilization rates would improve in microchannels. At these lower concentrations, the combined fertilization rate was significantly higher in microchannels (27 percent) than in culture dishes (10 percent).

The authors note that the research has only been conducted on mice, and that more testing and possibly the development of auxiliary technology will be needed before IVF by microfluidics is a viable option for humans.

Still, the research is very promising, says lead author Ronald S. Suh, M.D., now with Urology of Indiana LLC in Indianapolis who was a resident in the U-M Department of Urology when he wrote the paper.

"There has been a large amount of research on almost every aspect of IVF. The exciting thing we're seeing here is going the potential of integration of all of these things. In the future, you will be able to take patients with low sperm counts, use microfluidics to select the best sperm, and achieve fertilization in one step," he says. "That integration is really what is going to make microfluidics change IVF."

In addition to Smith and Suh, other authors of the paper are Dana A. Ohl, M.D., professor of urology at the U-M Medical School; Shuichi Takayama, Ph.D., assistant professor of biomedical engineering and of macromolecular science and engineering at the U-M College of Engineering; Xiaoyue Zhu, research fellow in biomedical engineering; and Nandita Phadke, research assistant in biomedical engineering.

Portions of the research were supported by grants from the National Institutes of Health and the College of Engineering Technology Development Fund.

U-M has applied for patents on the microfluidic technology involved in this study. Smith and Takayama have formed a company called Incept BioSystems and stand to profit from commercialization of the products.

University of Michigan Health System