Imagine administering a diagnostic test for Ebola while sweltering in an airtight hooded spacesuit—with thick rubber gloves on your fingers. Then consider waiting for results while someone else operates the technology that signals whether it’s a grave illness or a more ordinary infection that the person is suffering.
Thinking about devices in the hands of the people actually using them is exactly what a team of biomedical scientists and engineers from Harvard Medical School and MIT are doing as they design a diagnostic to detect Ebola virus and other dangerous microbes.
A cheap, reliable test made of paper that can rapidly determine infection is the goal of a team led by Lee Gehrke, HMS professor of microbiology and immunobiology and the Hermann von Helmholtz Professor of Health Sciences and Technology at MIT. They hope to make it as simple to use as a home pregnancy test. How cheap and how fast? Under $10 and under 20 minutes.
“That’s really the mantra of the work we are doing,” Gehrke said in an interview in his MIT office. “We are trying to devise devices that are easy to use in austere environments that have no power, no refrigeration, no specialized chemicals, no specialized instrumentation—and can give a quick triage notice of what disease a patient may have.”
Of all the crying needs seen in such abundance in West Africa during the Ebola epidemic, diagnostic testing is high on the list. Health workers need to know who is harboring infection and who is not—quickly—without relying exclusively on sophisticated equipment whose results require off-site interpretation or troubleshooting. Proper treatment and containment of infectious pathogens hang in the balance.
“Is the person handling the test going to have to have a PhD in microbiology, or will it be somebody who just finished cleaning up after a patient and has never seen a rapid test before? Will they be wearing thick gloves to protect themselves?” asked José Gómez-Márquez, director of MIT’s Little Devices Laboratory. “Making sure these things survive in an environment as hellish as what we see in West Africa can be a big challenge.”
For the past five years, long before Ebola began its sweep through Guinea, Liberia and Sierra Leone, Gómez-Márquez and Gehrke have been working with other scientists and engineers in the Harvard-MIT Program in Health Sciences and Technology to bring diagnostic tools to low- and middle-income countries.
Ebola virus infection may be the most terrifying outbreak right now, but other viruses perennially spread misery among people living in countries where health care systems are less than robust. Their common symptom is fever, so distinguishing among dengue fever, Marburg fever, yellow fever and chikungunya virus infections and their subtypes is important.
The researchers hope their answer is on paper, more specifically, 3 millimeter by 15 millimeter (1/8 inch by 9/16 inch) strips of paper that separate gold nanoparticle sensors carrying antibodies and single strands of DNA or RNA called aptamers. These sensors bind to certain microbial proteins in blood or serum that then flow through paper fluidic pathways to create patterns of lines that identify the pathogen.
Gehrke calls it a simple design based on the well-established technology known as lateral flow chromatography, or paper fluidics. The goal of this project is to show that a complex mixture of proteins or sera applied to the device can deliver a clear signal about which virus or pathogen is present in such a way that is not confused by cross-over from other viruses or serotypes.
While their work had advanced the furthest on a multiplexed dengue fever test, the team accelerated its pace on an Ebola test when the crisis emerged in West Africa. Last fall they sent their Ebola test to the Texas Biomedical Research Institute in San Antonio where former HMS colleagues Jean Patterson and Anthony Griffiths are involved in verifying its accuracy in animals experimentally infected with live virus in the institute’s Biosafety Level 4 Laboratory.
What they learn from dengue testing could help shape the Ebola test.
In dengue infection, discerning which serotypes are in a sample is important because immunity from one does not protect against infection with another. Changes in dengue virus samples can predict epidemics in regions where the cyclical, mosquito-borne disease is a threat.
Laboratory testing in Cambridge has shown that the team’s test can pick up the four dengue serotypes. Field testing will begin in the spring in Bucaramanga, Colombia, to make sure that differences in factors such as diet, for example, between populations in Cambridge and Colombia don’t interfere with the results. A sterile lab is different from a real-life clinic, where patients’ leftover blood samples will be used to test the test.
Colleagues in Colombia will also be observing how people use the paper-test device and how a mobile phone app can be enlisted to record and report their findings through simple MMS or SMS messages. The mobile phone removes the subjectivity from analyzing the test results, and the team is focused on developing a culturally and clinically appropriate phone interface to use with the device.
“The challenge with detecting viral proteins or viral antibodies is that their blood levels change during infection,” Gehrke explained. “The added value is that the changing levels provide information about the stage of the infection, which might be relevant to how the patient is treated.”
While the scientists cannot predict when either the Ebola or the dengue test would be ready for use in the real world, Gehrke and Gómez-Márquez said they will be making changes in an iterative way based on the Colombia testers’ results, speeding the process and broadening the definition of codesigners to include testers and their ideas.
To expand crowdsourcing even further, Gómez-Márquez wants to enlist patients as “citizen sensors.” Ultimately the scientists hope to combine data from these tests, which can be used not just in the clinic but also in the home, to create a real-time map of disease spread in parts of the world where mobile phones may be easier to find than health care. Public health researchers now rely on information that can be weeks old, but immediate, verifiable confirmation of infection could better guide medical response.
“We don’t think about this specifically as an Ebola test,” Gehrke said. “Rather, we are developing a platform that could be used for a number of different kinds of tests. Fortunately this Ebola outbreak is waning, but what’s coming next?”