Using patches of synthetic skin to test blood-sucking behavior of mosquitoes

If watching animals feast on human blood for 30-plus hours isn't your idea of fun, don't worry. The robot can do it.

Rice University bioengineers have teamed up with tropical medicine experts from Tulane University to take some of the pain out of studying the feeding behavior of mosquitoes. The insects' bites can spread diseases like malaria, dengue and yellow fever, but setting up experiments to examine their behavior can take a big bite out of lab budgets.

"Many mosquito experiments still rely on human volunteers and animal subjects," said Kevin Janson, a Rice bioengineering graduate student and lead co-author of a study about the research published this week in Frontiers in Bioengineering and Biotechnology. Live subject testing can be expensive, and Janson said the "data can take many hours to process."

So he and his co-authors found a way to automate the collection and processing of that data using inexpensive cameras and machine-learning software. To eliminate the need for live volunteers, their system uses patches of synthetic skin made with a 3D printer. Each patch of gelatin-like hydrogel comes complete with tiny passageways that can be filled with flowing blood.

To create the stand-ins for skin, Rice's team, which included Janson and his Ph.D. adviser Omid Veiseh, used bioprinting techniques that were pioneered in the lab of former Rice professor Jordan Miller.

For feeding tests, as many as six of the hydrogels can be placed in a transparent plastic box about the size of a volleyball. The chambers are surrounded with cameras that point at each blood-infused hydrogel patch. Mosquitos are placed in the chamber, and the cameras record how often the insects land at each location, how long they stay, whether or not they bite, how long they feed and the like.

The system was tested at the laboratory of Dawn Wesson, a mosquito expert and associate professor of tropical medicine at Tulane's School of Public Health and Tropical Medicine. Wesson's research group has facilities for breeding and testing large populations of mosquitoes of varying species.

In the proof-of-concept experiments featured in the study, Wesson, Janson and co-authors used the system to examine the effectiveness of existing mosquito repellents made with either DEET or a plant-based repellent derived from the oil of lemon eucalyptus plants. Tests showed mosquitoes readily fed on hydrogels without any repellent and stayed away from hydrogel patches coated with either repellent. While DEET was slightly more effective, both tests showed each repellent deterred mosquitoes from feeding.

Veiseh, the study's corresponding author and an assistant professor of bioengineering in Rice's George R. Brown School of Engineering, said the results suggest the behavioral test system can be scaled up to test or discover new repellents and to study mosquito behavior more broadly. He said the system also could open the door for testing in labs that couldn't previously afford it.

It provides a consistent and controlled method of observation. The hope is researchers will be able to use that to identify ways to prevent the spread of disease in the future."

Omid Veiseh, study's corresponding author and assistant professor of bioengineering in Rice's George R. Brown School of Engineering

Wesson said her lab is already using the system to study viral transmission of dengue, and she plans to use it in future studies involving malaria parasites.

"We are using the system to examine virus transmission during blood feeding," Wesson said. "We are interested both in how viruses get taken up by uninfected mosquitoes and how viruses get deposited, along with saliva, by infected mosquitoes.

"If we had a better understanding of the fine mechanics and proteins and other molecules that are involved, we might be able to develop some means of interfering in those processes," she said.

This research was supported by the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.