Fluidic operation of a polymer-based nanosensor chip for analysing single molecules

Swarnagowri Vaidyanathan, Bioengineering Program, The University of Kansas, Lawrence, KS 66045, USA.
Sachindra Gamage, Department of Chemistry, The University of Kansas, Lawrence, KS 66045, USA.
Kavya Dathathreya, Department of Chemistry, The University of Kansas, Lawrence, KS 66045, USA.
Renee Kryk, Department of Mechanical Engineering, The University of Kansas, Lawrence, KS 66045, USA.
Anishkumar Manoharan, Department of Chemistry, The University of Kansas, Lawrence, KS 66045, USA.
Zheng Zhao, Bioengineering Program, The University of Kansas, Lawrence, KS 66045, USA.
Lulu Zhang, Department of Chemistry, The University of Kansas, Lawrence, KS 66045, USA.
Junseo Choi, Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66047, USA.
Daniel Park, Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66047, USA.
Sunggook Park, Center of BioModular Multiscale Systems for Precision Medicine, Lawrence, KS 66047, USA.
Steven A. Soper, Bioengineering Program, The University of Kansas, Lawrence, KS 66045, USA.

Abstract

Most medical diagnostic tests are expensive, involve slow turnaround times from centralized laboratories and require highly specialized equipment with seasoned technicians to carry out the assay. To facilitate realization of precision medicine at the point of care, we have developed a mixed-scale nanosensor chip featuring high surface area pillar arrays where solid-phase reactions can be performed to detect and identify nucleic acid targets found in diseased patients. Products formed can be identified and detected using a polymer nanofluidic channel. To guide delivery of this platform, we discuss the operation of various components of the device and simulations (COMSOL) used to guide the design by investigating parameters such as pillar array loading, and hydrodynamic and electrokinetic flows. The fabrication of the nanosensor is discussed, which was performed using a silicon (Si) master patterned with a combination of focused ion beam milling and photolithography with deep reactive ion etching. The mixed-scale patterns were transferred into a thermoplastic via thermal nanoimprint lithography, which facilitated fabrication of the nanosensor chip making it appropriate for diagnostics. The results from COMSOL were experimentally verified for hydrodynamic flow using Rhodamine B as a fluorescent tracer and electrokinetic flow using single fluorescently labelled oligonucleotides (single-stranded DNAs, ssDNAs).