Using nanotechnology to expand health care access
Treatment for HIV has come a long way since the illness emerged as a serious global health problem in the 1980s. With constant monitoring and the right cocktail of medication, patients with HIV can now live long, healthy lives.
But many individuals who are diagnosed with HIV don’t have access to the proper diagnostics and treatment.
“In the U.S., someone taking medication would check the viral load every once in a while to make sure nothing is going wrong,” said A.T. Charlie Johnson, a professor of physics in the School of Arts & Sciences at the University of Pennsylvania. “But these techniques are expensive, and they require high-tech hospitals, so in low-resource settings like Africa this monitoring is not frequently done. You might have a person taking medication, but something has happened, and the viral load is going way up and they don't know it until the person has very severe symptoms.”
To tackle this global health challenge, a team at Penn is using commercially available nanotechnology to develop a low-cost, handheld diagnostic device that can monitor HIV. Not only would this device increase access to high-quality treatment of HIV in developing countries and disadvantaged parts of the world, it would also lower the cost of health care in the United States.
The project is led by Johnson; David Issadore, an assistant professor in Penn’s School of Engineering and Applied Science; and Ronald Collman, a professor in Penn’s Perelman School of Medicine and director of the Penn Center for AIDS Research.
In November, the team was awarded a Gates Grand Challenges Exploration Grant from the Bill & Melinda Gates Foundation with an initial award of $100,000 with the opportunity to receive follow-on funding of as much as $1 million if the technology can be proven.
Currently, doctors count the amount of the virus in a patient’s blood using a technique called polymerase chain reaction, or PCR, which looks for the nucleic acid inside the virus and amplifies it. Although Issadore says this technique works beautifully, it’s also expensive and slow.
In order to achieve the same sensitivity in a handheld chip, the group at Penn is working to combine two different technologies.
“The object of this is to improve both sides of the puzzle and then think about bringing the puzzle together,” Johnson said.
The researchers in Issadore’s group take advantage of the fact that blood is not inherently magnetic. They mix in magnetic nanoparticles that can be covered in molecules that will stick to the viral particles, which are relatively rare, and make them magnetic. Once the viral particles are magnetic, the researchers are able to pull them out.
“We have the ability to take a large volume of blood, some totally messy sample that has all kinds of cells and proteins and junk in it and sort out the HIV viruses,” Issadore said. “Because all of the other material in blood is not magnetic, it does not interfere with the chip.”
Because graphene, which is just one atom thick, is perfectly two-dimensional, it can be used as an extremely sensitive way of detecting biological signals. When DNA or RNA molecules bind to the graphene, it produces a big change in the conductivity of the atomically thin material, allowing the researchers to detect molecules.
“Every atom, and that means every electronic state, is exposed directly to the environment,” Johnson said “So, if anything changes in the environment, the electrical properties of the material also change.”
Once the viruses have been pulled out using the magnetic nanoparticles, the graphene sensors that Johnson’s lab is working on are able to open them up and look for pieces of RNA that are specific to HIV.
The group has been focusing on making these graphene devices more manufacturable and trying to bridge these ideas into real applications.
In addition to improving treatment of HIV in low-resource settings by supplying a low-cost, portable diagnostic device, Issadore says that this technology could become important in the next generation of HIV treatment.
“Right now we don't cure HIV; we manage the disease,” Issadore said. "Rather than having patients take drugs for the rest of their lives, the hope is that a cure can be developed for HIV. Currently, no one knows how to do that."
One of the problems is that, when patients are given medication, the amount of viruses in their bloods will continue to drop until it goes below the level of sensitivity of the current tests. When the disease gets to this extremely low level, which is called the latent reservoir, it enters a sort of resting state. Although it’s inactive, it’s still in the patient’s body and eventually comes back and becomes a problem again.
Because of this, the only way to know if the treatment has worked is to take it away and wait to see if the disease comes back.
Issadore says that these ultrasensitive detectors might have the potential to measure HIV at even lower levels, which could support research aimed at developing a cure.
But for now the immediate goal of the project is to improve and merge the two technologies and to eventually move beyond working with artificial samples with a known amount of viruses to working with samples from patients in sub-Saharan African countries such as Botswana to see if the device works.
“We're great at managing HIV, but currently we're not as good at making that care accessible to everyone,” Issadore said. “What Charlie and my lab are developing aims to take the technology currently only accessible to people who live near well-equipped hospitals and bring that level of care to everyone in the world."