Biological warfare, mad cow disease on UH student’s hit list

Mrinal Shah develops technology to construct biosensors more quickly

A University of Houston student has made an award-winning breakthrough in biosensors that could help bioterrorism researchers in their ability to quickly and accurately detect toxic biological agents.

Mrinal Shah, a doctoral student in chemical engineering at UH, has developed new methods in the use of biosensors that could provide one of the first steps in developing a protein-based biosensor that would help the government in safeguarding the nation.

Working under the direction of Peter Vekilov, a world-renowned expert in the field of nucleation and a chemical engineering professor at the UH Cullen College of Engineering, Shah employs liquid-liquid phase separation – a technique that is similar to the concept behind how oil and water separate. His research makes use of the proteins needed in biosensors and accurately controls the nucleation of those proteins.

“The development of a successful biosensing chip has potential uses that are manifold and urgently needed with several applications that are immediately significant,” Shah said. “If there is biological warfare somewhere, and you put this chip into that environment, you would know exactly what is in that environment, and safety precautions could be taken. That’s the ultimate achievement that every scientist working in protein chips dreams about.”

Biosensing chips are already in use for studies such as the quality control of water and checking glucose levels. Shah’s involvement in the biosensing application began with his initial interest in protein nucleation that occurs with diseases such as Parkinson’s, sickle cell anemia and Alzheimer’s. While his methods may prove useful in the early detection of these diseases, Shah said he is not searching for any cures. He said that what basically happens is the protein is normal inside the body, but then suddenly something happens for it to just start nucleating. The protein misfolds, denatures and begins to aggregate together forming into the disease.

“We’re not finding cures ourselves, but we are finding the mechanisms that follow the formations of these fibers,” Shah said. “Once we know the mechanism, then we also can know by what methods to reduce the rate of its formation. The physics behind the mechanisms is much more interesting to us.”

Shah says there are a number of other applications for the chip, as well, including combating mad cow disease and anthrax.

While working on the initial part of his project – studying the kinetics and the thermodynamics involved to better understand what mechanisms govern the phase separation of nanoscale droplets of protein solution – Shah came up with the idea that could lead to a new potential way of making biosensors that would be fast and easy. He found that control over nucleation is essential to the creation of biosensors.

“It was a difficult project, because we were hoping that one of two approaches would work, and neither of them did,” Vekilov said. “We tried electrophoresis and dielectrophoresis and neither worked. But Mrinal kept working, kept trying new things and finally developed his own method. What we discovered is that the solution has a time-dependent, non-uniform electric field, and this is what causes the nucleation.”

“The next step will be to tag the protein molecule onto the micro-area electrode,” Shah said. “That will be a challenge, but we already have several promising strategies in mind.”

Since winning second place at last year’s Keck Annual Research Conference, Shah has been able to replicate his results, using a more widely used biosensing protein – horseradish peroxidase. The W.M. Keck Center for Computational and Structural Biology is designed to unite modern biological, physical and computational sciences in addressing problems in biology and biomedicine. Its six member institutions include UH, Rice University, Baylor College of Medicine, The University of Texas Health Science Center at Houston, The University of Texas Medical Branch at Galveston and The University of Texas M.D. Anderson Cancer Center.