Assistant Professor NYU Langone Health, United States
Introduction: Plasmonic and dielectric metasurface-based biosensors integrated with microfluidics represent a key platform technology in the space of disease diagnostics and high-throughput biomarker screening. Recent progress in this direction has demonstrated ultrahigh sensing performance, e.g., a limit of detection (LOD) below 1 nanogram per milliliters, through tailor-designed resonance modes. However, the reliance on high-precision nanofabrication processes limits the broad adoption of meta-sensors. On the one hand, top-down lithographic techniques, such as e-beam lithography (EBL), focused ion-beam milling (FIB), are expensive with a low throughput, precluding cost-effective scale-up and commercialization potential. On the other hand, low-cost bottom-up self-assembly techniques such as nanosphere lithography (NSL) suffer from a low patterning quality lacking long-range order. Therefore, ultrasensitive meta-sensors compatible with scalable fabrication remain challenging. Here, by improving NSL patterning quality, we demonstrate scalable metasurface-based biosensors using plasmonic nanohole arrays (NHA) as an example, which achieve the sensing performance comparable to the state-of-the-art NHA biosensors fabricated by top-down lithography.
Materials and
Methods: Conventional NSL is based on an interfacial process called “Marangoni convection”, where polystyrene (PS) beads are introduced to the glass/air/water interface to self-assemble into hexagonal, close-packed monolayer. We improve the NSL quality by mechanical rubbing of solid PS beads against a soft and flat surface. Monolayer of PS hexagonal bead arrays can thus be formed, transferred to a glass substrate, and etched by oxygen plasma for fine tuning of the feature size in the nanoscale. These ordered nanopatterns of PS beads are then used as masks for metal (Au) deposition. After removing the PS bead monolayer by ultrasonication in toluene, the resulting plasmonic NHA were integrated with microfluidics and biofunctionalized with capturing antibodies for biosensing.
Results, Conclusions, and Discussions: The PS monolayers prepared by the conventional interfacial process were composed of randomly orientated small domains (Fig. 1a SEM image), which could cause potential degradation in sensing performance. In contrast, the mechanical method significantly improved the uniformity with superior long-range order (Fig. 1b optical image), which provided uniform NHA over the centimeter scales (Fig. 1c inset AFM image). After integration with microfluidics, the scalable plasmonic NHAs allow sensitive detection of refractive index (RI) changes, with a bulk RI sensitivity of 521 nm/RIU and a LOD of 0.0004 RIU (Fig. 1d). With such high RI sensitivity and structural uniformity, our scalable NHA devices rival those produced by EBL and FIB. These functionalized sensors are demonstrated to detect biomolecules (IgG as an example) with LOD reaching below 1 ng/mL (Fig. 1e).
Scalable manufacturing and optofluidic integration of metasurface biosensors are crucial to realize their full potential in point-of-care diagnostics and high-throughput screening of drug targets. Importantly, by improving NSL patterning quality and uniformity, our scalable meta-sensors achieved sensing performance comparable to that of EBL fabricated devices, which can be further improved by optimization of the functionalization process. While Au NHA was demonstrated as an example, our method can be applied to other dielectric metasurfaces. The choice of substrates can also be expanded to enable promising applications such as wearable devices and lab-on-fiber technology.
