Time-of-Flight Based Nanochannel Sensing Platforms for Real Time Bioanalysis

Louisiana State University, Baton Rouge LA

Investigators

Abstract

1067583 Park The ability to acquire quantitative information on molecular inputs in near real time offers many exciting new opportunities in diverse applications such as basic biology, medicine, forensics, and homeland security. Nanochannel-based technologies have demonstrated potential as a technology in the analysis of biopolymers, but their use is still in its infancy and replete with research challenges. The goal of this proposed work is to develop an innovative nanofluidic biosensor utilizing time-of-flight (ToF)-based transduction of single molecules in a 2D nanochannel for accelerating the acquisition rate of chemical/biochemical information to near real time irrespective of the targets being analyzed. In order to fulfill the promise of this exciting field, multidisciplinary research efforts, aimed at both the engineering and scientific challenges, are imperative. The main scientific innovation is the employment of a new sensing mechanism, namely ToF transduction to identify different molecules (we will use peptides as example targets in this application) the size of which is comparable to the dimensions of the nanochannels. During translocation of a peptide through the nanochannel, its mobility is determined by the ionic state of the molecule as well as the interactions between the molecule and walls of the nanochannel. The ToF for the translocation will provide a signature uniquely specific to the molecule being monitored. The engineering innovation includes low-cost fabrication of multi-scale fluidic platforms consisting of micro- to macroscale fluidic networks and sub-50 nm nanochannels in polymer substrates via direct molding. Use of polymer substrates is predicated by their ability to be produced using replication technologies as well as the availability of polymers with a broad range of surface chemistries, which enables optimization of biomolecule/nanochannel wall interactions to facilitate ToF identification. Using the developed technologies emanating from this application, further innovative discovery efforts will be generated for a broader user community due to the systems? low-cost and simple operation with the ultimate goal being application of these novel biosensors for the real time identification of single monomers to elucidate the primary structure of biopolymers, such as nucleic acids and proteins. Intellectual Merit: The proposed research will integrate critical studies in fabrication, assembly, biophysical characterization and simulations, to formulate a detailed understanding of the translocation behavior of peptides through nanochannels. Through fundamental studies of the physics of the confined translocation of single peptides, controlling parameters that maximize the discrimination between individual peptides will be identified. Low cost fabrication, enabled by the use of polymers, will be achieved by the use of parallel processes such as nanoimprint lithography in the fabrication of an array of nanochannel sensing platforms over a large area. Completion of the proposed work will demonstrate the feasibility of this ToF-based sensing mechanism and lay the groundwork for the development of low cost fabrication strategies for the nanochannel sensing platforms for broader applications. Broader Impacts: Education and outreach activities will exploit the revolutionary and multidisciplinary nature of the emerging field of nanochannel-based biosensors to engage K-12, teachers and undergraduate students in science,technology, engineering, and mathematics. To this end, the following activities will be pursued: (1) develop experimental nanotechnology teaching modules; (2) give seminars for secondary education students; (3) initiate undergraduate and graduate students in research; and (4) recruit undergraduate and graduate students from underrepresented groups. These activities will take advantage of the education and outreach infrastructure already in place at LSU and its Center for BioModular Multi-Scale Systems. This infrastructure includes several nationally recognized programs devoted to under-represented students.