Chemists Work to Speed Up Diagnosis of Deadly Disease

By Nadia M. Whitehead

UTEP News Service

Meningitis acts fast and can become fatal in as little as 24 hours, but diagnosis of the deadly disease is slow – sometimes taking two or three days.

Xiujun Li
Professor of Chemistry Xiujun (James) Li, Ph.D.

“For other diseases like malaria, you have time to take the patient to a clinic or hospital to see what’s wrong, but since meningitis is so fast, we really need a quicker method of diagnosis,” said Xiujun (James) Li, Ph.D., assistant professor of chemistry at The University of Texas at El Paso.

Li recently was awarded a $419,000 grant from the National Institute of General Medical Sciences to study and develop a more rapid, low-cost and highly sensitive diagnosis of meningitis.

Similar to pregnancy test strips, his plan is to create a small, paper-based lab-on-a-chip – a device that integrates multiple laboratory functions onto a tiny microchip – as the new diagnosis method.

Meningitis is a severe bacterial and viral infection causing inflammation of the membranes that cover the brain and spinal cord.

Current diagnosis methods for the disease are either too slow, expensive, or require invasive procedures that may not be possible in low-resource settings. They include gram staining, cell culture and real-time PCR, a relatively new technology that costs upwards of $40,000.

“Cell culture usually takes more than two days,” said Maowei Dou, a doctoral chemistry student at UTEP who is working on the project. For the procedure, cells are obtained from patients via a blood test or lumbar puncture, a painful process of puncturing the spine and collecting cerebrospinal fluid (CSF). Also known as a spinal tap, the analysis of CSF is the most “definitive diagnosis of meningitis,” according to the Mayo Clinic.

Patients’ cells collected from the procedures are then cultured, or grown, to see what bacteria is present.

According to Li, gram staining – which involves staining the cells to distinguish two types of bacteria – is a little faster, but not as reliable due to low sensitivity.

“This sort of technology can work for us here in the United States, but in low-resource settings, like Africa, it’s not possible,” said Li, who conducted postdoctoral work on microfluidics at Harvard University and the University of California, Berkeley. “Those locations may not have the money for equipment and labs, or trained personnel to carry out the procedures. They may not even have electricity. So the question is, how can we solve this issue?”

Point-of-care testing with Li’s extremely simple, low-cost device will potentially help.

“We are developing a non-invasive, instrument-free diagnostic method with high sensitivity capable of detecting even a few bacteria in detection zones,” he said.

Still in the first phases of the study, the chip the team has designed is a hybrid device made out of chromatography paper and a cost-effective plastic.

Using laser-cutting technology, Li created multiple channels, or capture zones, on the device for simultaneous detection of the three main bacteria that cause meningitis.

“Once we finish, we hope our device can be used for multiplexed detection of the disease,” Dou said. “That way you can detect exactly which bacteria has caused meningitis from the patient’s [blood] sample.”

Identification of the exact bacteria causing the disease is vital because treatment and antibiotics differ for each type.

In his studies, Dou recently found that the device was extremely successful in diagnosing meningitis caused by the bacteria Neisseria meningitisdis.

The results were available in less than one hour.

Xiujun (James) Li
Doctoral chemistry student Maowei Dou, left, and Assistant Professor of Chemistry Xiujun (James) Li, Ph.D., are working to create a quicker way to diagnose meningitis. Photo by J.R. Hernandez / UTEP News Service

Right now, Dou is working to see if it can successfully diagnose the other two bacteria.

While the team is developing the hybrid device, a new research fellow will be hired to develop a fully paper-based test – although manufacturing the hybrid device is not much more expensive.

Both researchers, who are particularly interested in helping break the Meningitis Belt in Africa, believe that either chip will be applicable for third-world countries. They foresee untrained personnel carrying around the portable device and easily diagnosing patients.

Originally from China, Dou came to UTEP specifically to work with Li on his project.

“I think it’s very cool that you can tell whether someone tests positive or negative with this sort of platform,” Dou said. “It makes me feel like I am a medical doctor. The neatest part of the device is that it’s very practical and can be used in low-resource settings where it is needed most.”

The chip still will benefit countries like the United States, where just this past November more than 400 people were affected by a meningitis outbreak and 31 died.

Other UTEP collaborators involved in the study include Siddhartha Das, Ph.D., professor of biological sciences; Delfina Dominguez, Ph.D, professor of clinical laboratory sciences; and undergraduate researcher Alejandra Valadez.

Meningitis experts David Stephens, Ph.D., of Emory University and Gregory Moe, Ph.D., from the Children’s Hospital Oakland Research Institute (CHORI) also are collaborating on the project.

In the future, clinical trials of the developed devices for meningitis diagnosis may be completed at CHORI.