Electrokinetic Micro- and Nanofluidic Technologies for Quantitative Detection of Viral Nucleic Acids

Sumita Pennathur, Ph.D.
Associate Professor of Mechanical Engineering
University of California, Santa Barbara

Rapidly evolving acute respiratory infectious diseases (for example, Influenza, Severe Acute Respiratory  Syndrome  (SARS),  Middle  East  Respiratory  Syndrome  (MERS),  and  West  Nile Flavivirus (WNF)) now have significantly deleterious impacts on human health and economic productivity worldwide. Due to their highly contagious nature, and rapid negative impact on human health and economies, these diseases require developing a simple, high throughput, and immediate  (within  30  minutes)  screening  methodology  that  can  affordably  and  accurately determine  virus  diagnosis,  so  that treatments  can  be  administered  in  a  timely  fashion. Furthermore, the expense of anti-virals now prohibits broad distribution even in developed countries. The diagnostic approaches that we are developing in the Pennathur lab enables rapid regionally based deployment of medications to stymie the spread of viruses. These approaches include  (1)  the  development  of  a  nanofluidic  conductivity  sensor  for  general  nucleic  acid detection, (2) fluorescent silver nanocluster DNA probes (AgNC-DNA) combined with microfluidic capillary electrophoresis (mCE), to detect and identify DNA sequences from HepA, HepB and HepC viruses, and (3) microfluidic tangential flow filtration (μTFF) of blood and serum for efficient on-chip sample preparation.

Specifically, we have developed a novel nanofluidic-based platform for the efficient detection of nucleic acids. The transduction method is label-free, inducing the formation DNA complexes that result in changes in flow velocity and current in a nanofluidic channel. This innovation takes into account the changes in surface and bulk conductivity in a nanochannel due to the concentration of ions in the bulk. Furthermore, we have developed a method for modifying a low cost, molecular beacon-like AgNC-DNA probe so that multiple DNA sequences can be detected and identified simultaneously and rapidly using microfluidic capillary electrophoresis. As a demonstration, we used this technique to design probes for nucleic acid targets of Hepatitis A, B and C virus. Finally, to truly make this work translational, we have developed a microfluidic based method for biological sample filtration. Such a method allows for facile integration with the above diagnostic sensors, and uses tangential flow filtration methods to effectively isolate targets of interest.

Dr. Pennathur received her B.S. and M.S. in Aerospace and Aeronautical Engineering from M.I.T. (2000 and 2001 respectively), and Ph.D. in Mechanical Engineering from Stanford University (2006). Prior to joining UCSB in 2007, she performed postdoctoral studies at both Sandia National Laboratories and University of Twente and held multiple positions at various companies and schools such as Sandia National Laboratories, Stanford University, National Institute of Standards and Technology, Tigris Corporation, Lockheed Martin, and MIT.