Their project is one of 76 grants announced by the Gates Foundation in the third funding round of Grand Challenges Explorations.
To receive funding Wright and Haselton showed in a two-page application how their idea falls outside current scientific paradigms and might lead to significant advances in global health. The initiative is highly competitive, receiving more than 3,000 proposals in this round.
Wright and Haselton’s innovative idea is to develop a simple, low-cost diagnostic test for malaria infection suitable for locations that lack electricity, refrigeration and highly trained technicians. The idea is based on the phenomenon that causes coffee-ring stains on the kitchen counter: When a liquid like coffee that contains a suspension of fine particles evaporates from a flat surface, the particles tend to accumulate along the outer edge. The proposed malaria test consists of two liquids and specially treated glass slides. Liquid A is mixed with the blood sample. A drop of the mixture is placed on the glass slide and left to dry. Once it has dried, the slide is washed with liquid B. If the washing reveals a purple ring, the person is infected. If it washes clean, then the person is not.
One of the keys to this test is the knowledge that the malaria parasite, P. falciparum, produces a unique protein called HRP II and excretes it into the blood stream. HRP II is known for its ability to bind to multiple metal atoms. The scientists have taken advantage of this by creating a capture agent that contains nickel atoms with a spacing that bonds particularly tightly with the parasite protein. First, they attach this capture agent to the surface of gold nanoparticles and dissolve it in a liquid solvent to make liquid A. Next, they coat the surface of the glass slides with the capture agent.
When liquid A is mixed with infected blood, the gold nanoparticles and the malaria proteins stick together for form large aggregations. The size of the nanoparticles has been chosen so that they change color from light pink to purple when they aggregate in this fashion. When a drop of the liquid is placed on a glass slide and begins to dry, the clusters move to the outer edge of the drop where they come into contact with the surface. When they do, the capture agent on the glass surface binds to the malaria proteins, anchoring the clusters in place to produce a visible ring.
“A recent World Health Organization survey of existing malaria diagnostic kits found that they are all based on antibodies, which require refrigeration, have a very limited shelf live and consequently are not very reliable,” Wright said. “By using inorganic chemistry, instead of biology, to probe for HRP II, our approach should have a very long shelf life even in the remotest areas. The simplicity of the color change means that the test kit won’t require a lot of training to administer.” The major question the scientists have to answer is how sensitive the test can be made: If it is sensitive enough then it could be done with saliva instead of blood, making it even easier to administer.
“The winners of these grants show the bold thinking we need to tackle some of the world’s greatest health challenges,” said Dr. Tachi Yamada, president of the Gates Foundation’s Global Health Program. “I’m excited about their ideas and look forward to seeing some of these exploratory projects turn into life-saving breakthroughs.”
