Scent, sweat from human skin attract disease-spreading mosquitoes

Mosquitoes that spread Zika, dengue and yellow fever are guided toward their victims by a scent from human skin. The exact composition of that scent has not been identified until now.

A UC Riverside-led team discovered that the combination of carbon dioxide plus two chemicals, 2-ketoglutaric and lactic acids, elicits a scent that causes a mosquito to locate and land on its victim. This chemical cocktail also encourages probing, the use of piercing mouthparts to find blood.

This chemical mixture appears to specifically attract female Aedes aegypti mosquitoes, vectors of Zika as well as chikungunya, dengue, and yellow fever viruses. This mosquito originated in Africa, but has spread to tropical and subtropical regions worldwide, including the U.S.

Mosquitoes use a variety of cues to locate their victims, including carbon dioxide, sight, temperature, and humidity. However, Cardé’s recent research shows skin odors are even more important for pinpointing a biting site.

Mosquito

Aedes aegyptii mosquito biting a person./CREDIT CDC

“We demonstrated that mosquitoes land on visually indistinct targets imbued with these two odors, and these targets aren’t associated with heat or moisture,” Cardé said. “That leaves skin odor as the key guiding factor.”

Given the significance of odor in helping mosquitoes successfully feed on humans, Cardé wanted to discover the exact chemicals that make our scent so potent for the insects. Part of the equation, lactic acid, was identified as one chemical element in the odor cocktail as long ago as 1968.

Since then, several studies have identified that carbon dioxide combined with ammonia, and other chemicals produced by humans also attract these mosquitoes. However, Cardé, who has studied mosquitoes for 26 years, felt these other chemicals were not strong attractants.

Methods that chemists typically use to identify these chemicals would not have worked for 2-ketoglutaric acid, Cardé said. Gas chromatography, which separates chemicals by their molecular weight and polarity, would have missed this acid.

“I think that these chemicals may not have been found before because of the complexity of the human odor profile and the minute amounts of these compounds present in sweat,” said chemist Jan Bello, formerly of UCR and now with insect pest control company Provivi.

Searching for mosquito attractors, Cardé turned to Bello, who extracted compounds from the sweat in his own feet. He filled his socks with glass beads and walked around with the beads in his socks for four hours per odor collection.

Malaria

Credit: MINDY TAKAMIYA/KYOTO UNIVERSITY ICEMS

“Wearing the beads felt almost like a massage, like squeezing stress balls full of sand, but with your feet,” said Bello. ‘The most frustrating part of doing it for a long time is that they would get stuck in between your toes, so it would be uncomfortable after a while.”

The inconvenience was worth the investment. Bello isolated chemicals from the sweat deposited on the sock beads and observed the mosquitoes’ response to those chemicals. In this way, the most active combination emerged.

Future studies are planned to determine whether the same compound is effective for any other mosquitoes, and why there is such variation in how individuals are apt to be bitten. “Some are more attractive than others to these mosquitoes, but no one’s yet established why this is so,” Cardé said.

Though this discovery may not lead to insights for the development of new repellants, the research team is hopeful their discovery can be used to attract, trap, and potentially kill disease-spreading mosquitoes.

Non-invasive ‘FAST device’ measures the changing size of tumors below the skin

Engineers at the Georgia Institute of Technology and Stanford University have created a small, autonomous device with a stretchable/flexible sensor that can be adhered to the skin to measure the changing size of tumors below. The non-invasive, battery-operated device is sensitive to one-hundredth of a millimeter (10 micrometers) and can beam results to a smartphone app wirelessly in real-time with the press of a button.

In practical terms, the researchers say, their device—dubbed FAST for “Flexible Autonomous Sensor measuring Tumors”—represents a wholly new, fast, inexpensive, hands-free, and accurate way to test the efficacy of cancer drugs. On a grander scale, it could lead to promising new directions in cancer treatment.

Each year researchers test thousands of potential cancer drugs on mice with subcutaneous tumors. Few make it to human patients, and the process for finding new therapies is slow because technologies for measuring tumor regression from drug treatment take weeks to read out a response. The inherent biological variation of tumors, the shortcomings of existing measuring approaches, and the relatively small sample sizes make drug screenings difficult and labor-intensive.

“FAST” sensor/Photo:Stanford University

“In some cases, the tumors under observation must be measured by hand with calipers,” says Alex Abramson, first author of the study and a recent post-doc in the lab of Zhenan Bao at the Stanford School of Engineering and now an assistant professor at Georgia Tech. The use of metal pincer-like calipers to measure soft tissues is not ideal, and radiological approaches cannot deliver the sort of continuous data needed for real-time assessment. FAST can detect changes in tumor volume on the minute-timescale, while caliper and bioluminescence measurements often require weeks-long observation periods to read out changes in tumor size.

FAST’s sensor is composed of a flexible and stretchable skin-like polymer that includes an embedded layer of gold circuitry. This sensor is connected to a small electronic backpack designed by former post-docs and co-authors Yasser Khan and Naoji Matsuhisa. The device measures the strain on the membrane—how much it stretches or shrinks—and transmits that data to a smartphone. Using the FAST backpack, potential therapies that are linked to tumor size regression can quickly and confidently be excluded as ineffective or fast-tracked for further study.

The researchers say that the new device offers few significant advances.

  1. It provides continuous monitoring, as the sensor is physically connected to the mouse/human patients and remains in place over the entire experimental period.
  2. FAST can detect changes in tumor volume on the minute-timescale, while caliper and bioluminescence measurements often require weeks-long observation periods to read out changes in tumor size.
  3. FAST is both autonomous and non-invasive. It is connected to the skin, not unlike a band-aid, battery operated and connected wirelessly. The mouse/human patients are free to move unencumbered by the device or wires, and scientists do not need to actively handle the mice following sensor placement.
  4. FAST packs are also reusable, cost just $60 or so to assemble and can be attached to the mouse/human patients in minutes.
  5. FAST could significantly expedite, automate and lower the cost of the process of screening cancer therapies.

FAST’s sensor is composed of a flexible and stretchable skin-like polymer that includes an embedded layer of gold circuitry.\/Photo:Alex Abramson, Bao Group, Stanford University

The breakthrough is in FAST’s flexible electronic material. Coated on top of the skin-like polymer is a layer of gold, which, when stretched, develops small cracks that change the electrical conductivity of the material. Stretch the material and number of cracks increases, causing the electronic resistance in the sensor to increase as well. When the material contracts, the cracks come back into contact and conductivity improves.

Both Abramson and co-author Naoji Matsuhisa, an associate professor at the University of Tokyo, characterized how these crack propagation and exponential changes in conductivity can be mathematically equated with changes in dimension and volume.

One hurdle the researchers had to overcome was the concern that the sensor itself might compromise measurements by applying undue pressure to the tumor, effectively squeezing it. To circumvent that risk, they carefully matched the mechanical properties of the flexible material to skin itself to make the sensor as pliant and as supple as real skin.

“It is a deceptively simple design,” Abramson says, “But these inherent advantages should be very interesting to the pharmaceutical and oncological communities. FAST could significantly expedite, automate and lower the cost of the process of screening cancer therapies.”