Nucleic Acid-Functionalized Gold Nanowires Co-Fabricated With Millimeter-Scale Contact Pads by Oxygen Plasma-Assisted E-Beam Lithography for Microchannel Integrated Biosensing Applications

The nucleic acid-based biosensor technologies are useful to precisely detect genetic footprints at low concentrations with high specificity and selectivity. They commonly rely on incorporating nucleic acid probes onto optical, electrochemical, or electrical transducers. Among various sensing modalities, approaches based on direct electrical measurements offer advantages in label-free detection, portability for point-of-care analysis, and direct integration with electronic readout circuits facilitating data processing, transfer, and remote interpretation. In this work, we demonstrate a novel fabrication approach, which couples conventional optical lithography and oxygen plasma-based etching with high-resolution electron-beam lithography to rapidly pattern poly(methyl methacrylate) (PMMA) e-beam resist at varying feature sizes (i.e., both large and small device areas), which would otherwise require extremely long exposure durations up to days with stand-alone e-beam lithography. This allows the fabrication of realistic biosensor chips in arrayed format, co-integrating millimeter (mm)-scale electrical peripherals and nanoscale (nm) sensing elements utilizing a simple and high-throughput process. The feasibility of the approach is demonstrated by successful immobilization of thiol-functionalized peptide nucleic acid (PNA) probes on similar to 60-nm-wide gold nanowires (AuNWs) integrated with a polydimethylsiloxane (PDMS) microchannel. The fabrication of biochips, integration with microfluidics, and self-assembly of PNA probes are characterized by optical microscope imaging, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS).