Rapid Turnaround Fabrication of Peptide Nucleic Acid (PNA)-Immobilized Nanowire Biosensors by O2-Plasma Assisted Lithography of e-Beam Resists

Nucleic acid-based biosensors are useful to precisely detect genetic footprints at low concentrations with high specificity and selectivity. 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 electronbeam 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 standalone e-beam lithography. This allows fabrication of realistic biosensor chips in arrayed format, co-integrated with millimeter (mm)-scale electrical peripherals to 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 $\sim 60$ nm-wide gold nanowires (AuNWs) enclosed in an SU-8 fluidic reservoir. Fabrication of biochips and self-assembly of PNA probes are characterized by optical microscope imaging, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR).