Parametric Study of Nanopore Versus Analyte Dimensions for Viral Detection Optimization

Developing our ability to quickly and accurately assess the presence of potentially harmful biomaterials is an essential endeavor for several reasons, including public health and national security. In particular, current approaches for detecting viruses are quite sensitive, but often require labeling for virus identification and may take hours for detection and up to several days for confirmation.The resistive pulse technique was introduced in 1970 as a candidate for rapid, label-free viral sensing in which viruses suspended in an electrolyte were driven through a single pore hundreds of nanometers in diameter embedded in a micron-thick polymer membrane. By characterizing the magnitude and duration of ionic current blockages, the virion's size and geometry could be extracted. However, due to the dimensions of the system relative to the size of viruses (∼25nm to 600nm), these early devices could not achieve the sensitivity required. Recently, researchers have taken advantage of developments in nanofabrication techniques to create smaller pores and thinner membranes to address device sensitivity.Building on these recent reports, we systematically investigate the role of membrane thickness and pore diameter relative to the size of the analyte using a focused ion beam to prepare nanopores in silicon nitride membranes. Employing synthetic nanospheres as models for viral particles, we explore a representative range of particle sizes to optimize device performance. In doing so, we aim to not only present a more complete assessment of the limitations of this approach (including the need for tailored pores or multiplexed platforms to detect a broad range of viruses) but also illustrate pathways to address these through straightforward modifications to the fundamental sensor design.This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-502091