New device selects healthy sperm

A new sperm-sorting device built at Stanford filters the unfit from the fit and could help improve infertility treatments.

This illustration depicts how the SPARTAN device sorts unshapely and damaged sperm (in pink) from healthier sperm (blue). The unshapely sperm are diverted by the pillars in the device and don't emerge from the filtering system. [The pink and blue colors are used for illustration purposes only and don't denote the presence of an X or Y chromosome.]
Thiruppathiraja Chinnasamy

A device the size of your business card can separate the strong, healthy sperm cells from the duds, and it does so in about 10 minutes, according to a new study led by researchers at the Stanford University School of Medicine and the Worcester Polytechnic Institute.

The sperm-sorting tool is called the Simple Periodic Array for Trapping and Isolation, or SPARTAN. It filters semen through rows and rows of pillars fitted for healthy sperm.

SPARTAN is not the only device of its kind, but its creators assert that it yields high-quality sperm more efficiently and effectively than others and hence could improve infertility treatments.

A paper detailing the work was published online Dec. 27 in Advanced Science. The study’s senior authors are Utkan Demirci, PhD, professor of radiology at Stanford, and Erkan Tüzel, PhD, associate professor of physics, of biomedical engineering and of computer science at Worcester Polytechnic Institute. The lead authors are Stanford postdoctoral scholar Thiruppathiraja Chinnasamy, PhD, and graduate student James Kingsley at WPI.

“SPARTAN picks out the healthiest sperm, but it also allows us to ask deeper questions in the clinic in terms of how much sperm selection really matters for infertility treatments,” Demirci said. Currently, many infertility treatments, like IVF, place emphasis on finding a healthy egg; the quality of the sperm cell is often secondary. But sperm carry critical heritable genetic elements, just like the egg does, and Demirci said sperm selection does play a big role in the quality of the embryo, so it warrants more careful selection. “Maybe SPARTAN can help change the paradigm in the field,” he said.

Simulate before you sort

Before SPARTAN’s final form came to be, Demirci and Tüzel collaborated closely on computer models of the device. The researchers took many of their initial design cues from the female reproductive tract — the original filtering system — modeling some aspects of the tool, such as pH level, after the scrupulous screening system biology had already built. The main difference was the physical interior of the device, which comprises thousands of tiny, vertical pillars, painstakingly aligned and optimally spaced to best trap unshapely sperm. Those that were misshapen — a bent tail; too big of a head — or had low motility would either tucker out, or deflect in the wrong direction and never make it to the finish line.

Utkan Demirci

“We’re basically using microscale pillars as three-dimensional geometrical figures to capture poorly shaped cells while letting the morphologically normal through,” Demirci said.

Compared to other standard clinical sperm-sorting methods — such as the swim-up method, in which semen is placed in a solution, and sperm unable to swim up into it are discarded — SPARTAN yields about twice as many morphologically sound sperm. Swim-up averages 24 percent, while SPARTAN averages 52 percent, the study said.

Over a period of about five years, Tüzel and Demirci tried out a variety of pillar alignments in their models. The arrangements tested patterns of different distances, both vertically and horizontally, and various sizes of pillars, until finally they landed on the most successful array, which they call “periodic structures,” as the pillars stand in series, or periods.

Tüzel and Kingsley, the graduate student who did the computational design and optimization work, said they used fluid physics to model human sperm to show how they move in a complex environment and within the pillar array. “If you randomly selected pillar spacing, it would have taken years to come up with the right design. We used fluid mechanics, optimization and novel computational algorithms to figure out the right spacing with the pillars to get the fastest sperm captured in the least amount of time,” said Tüzel. “If we’d been doing it randomly? Well, no researcher would have done that. It would be a wild goose chase.”

Once the simulation showed the majority of strong, well-shaped swimmers reaching the end of the device, Demirci began to build it in his lab. To his delight, the device performed just as the simulation had predicted. Moreover, the researchers found that cells of the right shape and size could swim in a straight line the fastest and separate themselves from the rest of the pack. Upon further analyses, the strong swimmers also had lower rates of DNA damage.

Just keep swimming

SPARTAN separates the semen passively, meaning the cells swim through the device’s maze on their own. The pillars sit in a fluid that naturally attracts sperm. The whole process takes about 10 minutes. It makes for a pretty easy user manual, Demirci said.

“It’s basically a two-step process: pipette raw semen into one end of the box, then collect the filtered, healthy sperm cells at the other end,” he said.

I believe in the long run, we’re going to see these types of devices replace the current centrifuge-based methods used in embryology labs.

The ease of use is important for standardizing practices in the clinic; fewer steps mean fewer errors. But aside from the speedy sorting, Demirci said the passive nature of the device is crucial. Currently, many sperm-collection techniques use centrifuges, machines that spin samples of fluids and separate the components by density, to collect the sperm cells. The rapid, high-force motion is damaging to the cells, and actually induces destructive molecules called reactive oxygen species that harm the cells’ DNA. Swim-up tactics yield a collection of sperm cells in which 13 percent show DNA fragmentation, a type of DNA damage; SPARTAN brings that number down to about 5 percent, the study said.

Demirci and Tüzel have a patent pending on the technology.

“SPARTAN offers a lot more advantages in terms of speed of sorting and fitness of the cells,” Demirci said. “And I believe in the long run, we’re going to see these types of devices replace the current centrifuge-based methods used in embryology labs.”

The study’s other Stanford co-authors are basic life science research associate Fatih Inci, PhD; and Barry Behr, PhD, professor of obstetrics and gynecology.

Demirci and Behr are members of Stanford Bio-X. Demirci is a member of the Stanford Cardiovascular Institute, the Stanford Cancer Institute and the Stanford Neurosciences Institute. Behr is a member of the Stanford Child Health Research Institute.

A researcher at the University of California-San Francisco also contributed to the work.

This study was funded by the National Science Foundation.

Stanford’s Department of Radiology also supported the work.

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