ARLINGTON, Va., Sept. 29, 2003 -- Biomedical engineers have developed a prototype lab-on-a-chip for harvesting healthy sperm cells to increase male fertility.

The microscale integrated sperm sorter (MISS) separates strong swimmers---sperm cells that are most likely to fertilize an egg--- from aimlessly drifting spermatozoa that are essentially incapable of fertilization.

"The system allows separation and detection of motile sperm from small samples that are difficult to handle using conventional sperm sorting techniques," said Whitaker investigator Shuichi Takayama, Ph.D., of the University of Michigan.

Takayama's device, slightly larger than a penny, is an inexpensive, easy-to-use sorter that men could ultimately use at home to measure fetility or test the outcome of a vasectomy or vasectomy reversal.

"Since sperm motility is a sensitive indicator of toxicity, the MISS may
also be useful as a toxicology test," said study co-author Gary D.
Smith, Ph.D., associate professor of Obstetrics and Gynecology at the
University of Michigan Medical School. The research was described in Analytical Chemistry in April and in the July/August issue of Reproductive BioMedicine Online.

The rectangular device was built using conventional techniques similar to those used in making computer chips. It has two input chambers at one end and two collection chambers at the other. A channel extends from each input chamber, merging into a single pipe for some distance, then separating before entering the two collection chambers.

The MISS requires no power source. Fluids are set into motion by the forces of surface tension and gravity, which combine to produce a steady flow. The device also takes advantage of laminar flow, in which two liquid streams can be made to run side-by-side without mixing. This is what happens in the middle of the MISS when the two fluid channels merge.

To operate the device, a semen sample is placed in one input chamber. A second chamber is filled with salt water. The two fluids move toward the opposite end of the device, combining in the middle into a single laminar flow.

While the two streams are side-by-side, swimming sperm will cross the laminar boundary and enter the salt water. Nonswimmers go with the flow and stay in the original stream. When the two streams separate into the collection chambers, one chamber will have swimmers, the other will not.

The purity of sorted sperm samples that arrive in the collection chamber is nearly 100 percent.

This approach to sperm sorting has additional advantages compared to conventional sorting techniques. It avoids processes, such as centrifugation, that can damage sperm. It can be combined with a color-coded readout for a self-contained , easy-to-use home test. The MISS, which sorts by motility, coincidentally selects sperm cells that lack physical abnormalities, such as a misshapen head or crimped tail.

In theory, a single sperm cell is all that is needed to fertilize an egg. But it can be impractical to isolate and harvest the most viable sperm cells using conventional laboratory techniques.

"Doctors frequently resort to hand sorting through dead sperm and debris to find a 'good' sperm, a procedure that can take hours in some cases," the researchers wrote.

About one in 10 couples have fertility problems and 40 percent of these cases have absent or abnormal sperm. Conventional fertility treatments are effective in many cases, but are less effective when sperm counts are very low.

The MISS is an offshoot of a larger research project funded by a 2001 Whitaker Foundation Biomedical Engineering Research Grant. Takayama's laboratory is investigating a number of cell-sorting approaches, including methods that isolate cells based on their size and their molecular signalling. The group is also investigating ways to sort cells using artificial blood vessel linings (endothelia). Clinical diagnosis of disease relies heavily on the ability to analyze the cellular composition of blood. In the long run, Takayama's research aims to improve disease diagnosis and treatment.

In addition to Dr. Smith, Takayama's collaborators on the MISS project include Brenda Cho, Timothy Shuster, Xiaoyue Zhu, and David Chang, all of the University of Michigan.

Contact:
Frank Blanchard, The Whitaker Foundation
Shuichi Takayama, University of Michigan