Early Diagnosis Equals Early Treatment

The townships outside of Cape Town, South Africa, are so densely packed that between 400,000 and 500,000 people typically live in an area the size of Evanston (pop. 74,239). Every day hundreds of HIV-positive women go to clinics in the center of these townships to deliver their babies. One in three newborns will be infected, but there is no affordable way to tell which ones. If there were, low-cost drugs are available to immediately treat the baby and eradicate the virus.

“This year, more than 4 million people will die in developing countries of diseases that can be treated if diagnosed in time,” says David Kelso (GMcC72, 74), associate professor of biomedical engineering in the McCormick School of Engineering and Applied Science, who recently received a grant from the Bill & Melinda Gates Foundation to develop and produce affordable diagnostic devices for infectious diseases plaguing developing countries. (Earlier this year the foundation awarded a $3 million grant to Northwestern’s Program of African Studies to study HIV prevention strategies in Africa.)

While some diagnostic tests are available for low-income countries in Africa and Asia, they can be improved to detect diseases such as tuberculosis, malaria and HIV/AIDS earlier in the disease process and more cost effectively. Tests need to be easy to use and provide faster results so patients can be diagnosed and begin treatment in one visit to a clinic.

To tackle these challenges, Kelso is putting together a multidisciplinary team of researchers from engineering and the biological sciences to develop new devices in a biotech startup environment. To minimize the cost and time in bringing products to market, the devices will build on proven technologies and components from both commercial and academic sources.

“The antiviral drug shortage is easing up, and now the focus is on reliable, user-friendly diagnostic and monitoring devices that can be used in settings where there is little formal infrastructure or resources,” says Robert Murphy (GFSM81, 84), John Philip Phair Professor of Infectious Diseases at the Feinberg School of Medicine and an investigator on the project. “Having the drugs alone is not enough to provide appropriate care in these tough settings.”

While Kelso’s team works to improve existing technology for use in the developing world, Chad Mirkin, director of Northwestern’s International Institute for Nanotechnology, is creating completely new medical diagnostics that take advantage of nanotechnology, which involves studying and working with materials and devices on the molecular scale. (The technology Kelso is working with is on the micro level.)

Protein biomarkers are known for hundreds of diseases. The problem is that in clinical specimens the proteins often are present in such miniscule amounts that early diagnosis is impossible using conventional methods. Mirkin’s bio-bar-code amplification (BCA) technology, which is a million times more sensitive than conventional methods, makes detection possible.

The technology could lead to a clinical test capable of diagnosing Alzheimer’s disease in its earliest stages.

William Klein, professor of neurobiology and physiology, and two colleagues discovered what is known as an ADDL, a toxic protein that may be responsible for the early neurological deterioration in Alzheimer’s disease. Klein and Mirkin recently teamed up to evaluate the possibility of using BCA to determine if ADDLs are present in cerebral spinal fluid samples from patients with the disease. (An ADDL is only five nanometers wide.) The technology successfully detected tiny amounts of ADDLs and demonstrated that there seems to be a correlation between the ADDL concentration and the state of the disease. BCA also can detect trace amounts of prostate specific antigen (PSA) and anthrax lethal factor.

The method works like this: The antibody of the protein target is attached to both magnetic microparticles and gold nanoparticles. When in solution, the antibodies “recognize” and bind to the protein target (e.g., an ADDL or PSA), sandwiching the protein between the two particles.

The key is that attached to each tiny gold nanoparticle (just 30 nanometers in diameter) are hundreds to thousands of identical strands of DNA. Mirkin calls this “bar-code DNA” because he has designed it as a label specific to the protein target. First the “particle-protein-particle” sandwich is removed magnetically from solution. Then the bar-code DNA — the amplified signal — is removed and read using standard DNA detection methodologies.

“The polymerase chain reaction, which duplicates DNA so it can be analyzed, revolutionized forensics, medicine and biotechnology,” said Mirkin, George B. Rathmann Professor of Chemistry, “but we haven’t had anything of comparable sensitivity for proteins. Now we do. This technology will change the way we do medical diagnostics and treatment.”

The technology is being commercialized and could be used to target biomarkers known for a variety of diseases, including HIV infection, various cancers and Creutzfeldt-Jakob disease, in addition to Alzheimer’s and prostate cancer. — M.F.