Glasswing-Butterfly-Inspired Multifunctional Scleral Lens and Smartphone Raman Spectrometer for Point-of-Care Tear Biomarker Analysis.

Augmenting contact lenses with sensing capabilities requires incorporating multiple functionalities within a diminutive device. Inspired by multifunctional biophotonic nanostructures of glasswing butterflies, a nanostructured scleral lens with enhanced optical, bactericidal, and sensing capabilities is reported. When used in conjunction with a smartphone-integrated Raman spectrometer, the feasibility of point-of-care applications is demonstrated. The bioinspired nanostructures made on parylene films are mounted on the anterior and posterior side of a scleral lens to create a nanostructured lens. Compared to unstructured parylene, nanostructured parylene minimizes glare by 4.3-fold at large viewing angles up to 80o . When mounted on a scleral lens, the nanostructures block 2.8-fold more ultraviolet (UVA) light while offering 1.1-fold improved transmission in the visible regime. Furthermore, the nanostructures exhibit potent bactericidal activity against Escherichia coli, killing 89% of tested bacteria within 4 h. The same nanostructures, when gold-coated, are used to perform rapid label-free multiplex detection of lysozyme and lactoferrin, the protein biomarkers of the chronic dry eye disease, in whole human tears using drop-coating deposition Raman spectroscopy. The detection of both proteins in whole human tear samples from different subjects using the nanostructured lens produced excellent correlation with commercial enzyme-based assays while simultaneously displaying a 1.5-fold lower standard deviation.

Phase-Separated Nanophotonic Structures by Inkjet Printing.

The spontaneous phase separation of two or more polymers is a thermodynamic process that can take place in both biological and synthetic materials and which results in the structuring of the matter from the micro- to the nanoscale. For photonic applications, it allows forming quasi-periodic or disordered assemblies of light scatterers at high throughput and low cost. The wet process methods currently used to fabricate phase-separated nanostructures (PSNs) limit the design possibilities, which in turn hinders the deployment of PSNs in commercialized products. To tackle this shortcoming, we introduce a versatile and industrially scalable deposition method based on the inkjet printing of a polymer blend, leading to PSNs with a feature size that is tuned from a few micrometers down to sub-100 nm. Consequently, PSNs can be rapidly processed into the desired macroscopic design. We demonstrate that these printed PSNs can improve light management in manifold photonic applications, exemplified here by exploiting them as a light extraction layer and a metasurface for light-emitting devices and point-of-care biosensors, respectively.

Overcoming evanescent field decay using 3D-tapered nanocavities for on-chip targeted molecular analysis.

Enhancement of optical emission on plasmonic nanostructures is intrinsically limited by the distance between the emitter and nanostructure surface, owing to a tightly-confined and exponentially-decaying electromagnetic field. This fundamental limitation prevents efficient application of plasmonic fluorescence enhancement for diversely-sized molecular assemblies. We demonstrate a three-dimensionally-tapered gap plasmon nanocavity that overcomes this fundamental limitation through near-homogeneous yet powerful volumetric confinement of electromagnetic field inside an open-access nanotip. The 3D-tapered device provides fluorescence enhancement factors close to 2200 uniformly for various molecular assemblies ranging from few angstroms to 20 nanometers in size. Furthermore, our nanostructure allows detection of low concentration (10 pM) biomarkers as well as specific capture of single antibody molecules at the nanocavity tip for high resolution molecular binding analysis. Overcoming molecule position-derived large variations in plasmonic enhancement can propel widespread application of this technique for sensitive detection and analysis of complex molecular assemblies at or near single molecule resolution.

Bioinspired Disordered Flexible Metasurfaces for Human Tear Analysis Using Broadband Surface-Enhanced Raman Scattering.

Flexible surface-enhanced Raman scattering (SERS) has received attention as a means to move SERS-based broadband biosensing from bench to bedside. However, traditional flexible periodic nano-arrangements with sharp plasmonic resonances or their random counterparts with spatially varying uncontrollable enhancements are not reliable for practical broadband biosensing. Here, we report bioinspired quasi-(dis)ordered nanostructures presenting a broadband yet tunable application-specific SERS enhancement profile. Using simple, scalable biomimetic fabrication, we create a flexible metasurface (flex-MS) of quasi-(dis)ordered metal-insulator-metal (MIM) nanostructures with spectrally variable, yet spatially controlled electromagnetic hotspots. The MIM is designed to simultaneously localize the electromagnetic signal and block background Raman signals from the underlying polymeric substrate-an inherent problem of flexible SERS. We elucidate the effect of quasi-(dis)ordering on broadband tunable SERS enhancement and employ the flex-MS in a practical broadband SERS demonstration to detect human tear uric acid within its physiological concentration range (25-150 µM). The performance of the flex-MS toward noninvasively detecting whole human tear uric acid levels ex vivo is in good agreement with a commercial enzyme-based assay.

Fabry-Pérot optical sensor and portable detector for monitoring high-resolution ocular hemodynamics.

Our understanding of ocular hemodynamics and its role in ophthalmic disease progression remains unclear due to the shortcomings of precise and on-demand biomedical sensing technologies. Here, we report high-resolution in vivo assessment of ocular hemodynamics using a Fabry-Pérot cavity-based micro-optical sensor and a portable optical detector. The designed optical system is capable of measuring both static intraocular pressure and dynamic ocular pulsation profiles in parallel. Through a dynamic intensity variation analysis method which improves sensing resolution by 3-4 folds, our system is able to extract systolic/diastolic phases from a single ocular pulsation profile. Using a portable detector, we performed in vivo studies on rabbits and verified that ophthalmic parameters obtained from our optical system closely match with traditional techniques such as tonometry, electrocardiography, and photo-plethysmography.

Aluminum Metasurface with Hybrid Multipolar Plasmons for 1000-Fold Broadband Visible Fluorescence Enhancement and Multiplexed Biosensing.

Aluminum (Al)-based nanoantennae traditionally suffer from weak plasmonic performance in the visible range, necessitating the application of more expensive noble metal substrates for rapidly expanding biosensing opportunities. We introduce a metasurface comprising Al nanoantennae of nanodisks-in-cavities that generate hybrid multipolar lossless plasmonic modes to strongly enhance local electromagnetic fields and increase the coupled emitter's local density of states throughout the visible regime. This results in highly efficient electromagnetic field confinement in visible wavelengths by these nanoantennae, favoring real-world plasmonic applications of Al over other noble metals. Additionally, we demonstrate spontaneous localization and concentration of target molecules at metasurface hotspots, leading to further improved on-chip detection sensitivity and a broadband fluorescence-enhancement factor above 1000 for visible wavelengths with respect to glass chips commonly used in bioassays. Using the metasurface and a multiplexing technique involving three visible wavelengths, we successfully detected three biomarkers, insulin, vascular endothelial growth factor, and thrombin relevant to diabetes, ocular and cardiovascular diseases, respectively, in a single 10 µL droplet containing only 1 fmol of each biomarker.

Enhanced broadband fluorescence detection of nucleic acids using multipolar gap-plasmons on biomimetic Au metasurfaces.

Recent studies on metal-insulator-metal-based plasmonic antennas have shown that emitters could couple with higher-order gap-plasmon modes in sub-10-nm gaps to overcome quenching. However, these gaps are often physically inaccessible for functionalization and are not scalably manufacturable. Here, using a simple biomimetic batch-fabrication, a plasmonic metasurface is created consisting of closely-coupled nanodisks and nanoholes in a metal-insulator-metal arrangement. The quadrupolar mode of this system exhibits strong broadband resonance in the visible-near-infrared regime with minimal absorptive losses and effectively supresses quenching, making it highly suitable for broadband plasmon-enhanced fluorescence. Functionalizing the accessible insulator nanogap, analytes are selectively immobilized onto the plasmonic hotspot enabling highly-localized detection. Sensing the streptavidin-biotin complex, a 91-, 288-, 403- and 501-fold fluorescence enhancement is observed for Alexa Fluor 555, 647, 750 and 790, respectively. Finally, the detection of single-stranded DNA (gag, CD4 and CCR5) analogues of genes studied in the pathogenesis of HIV-1 between 10 pM-10 µM concentrations and then CD4 mRNA in the lysate of transiently-transfected cells with a 5.4-fold increase in fluorescence intensity relative to an untransfected control is demonstrated. This outcome promises the use of biomimetic Au metasurfaces as platforms for robust detection of low-abundance nucleic acids.

Glucose Sensing Using Surface-Enhanced Raman-Mode Constraining.

Diabetes mellitus is a chronic disease, and its management focuses on monitoring and lowering a patient's glucose level to prevent further complications. By tracking the glucose-induced shift in the surface-enhanced Raman-scattering (SERS) emission of mercaptophenylboronic acid (MPBA), we have demonstrated fast and continuous glucose sensing in the physiologically relevant range from 0.1 to 30 mM and verified the underlying mechanism using numerical simulations. Bonding of glucose to MPBA suppresses the "breathing" mode of MPBA at 1071 cm-1 and energizes the constrained-bending mode at 1084 cm-1, causing the dominant peak to shift from 1071 to 1084 cm-1. MPBA-glucose bonding is also reversible, allowing continuous tracking of ambient glucose concentrations, and the MPBA-coated substrates showed very stable performance over a 30 day period, making the approach promising for long-term continuous glucose monitoring. Using Raman-mode-constrained, miniaturized SERS implants, we also successfully demonstrated intraocular glucose measurements in six ex vivo rabbit eyes within ±0.5 mM of readings obtained using a commercial glucose sensor.

High-performance flexible metal-on-silicon thermocouple.

We have demonstrated metal-on-silicon thermocouples with a noticeably high Seebeck coefficient and an excellent temperature-sensing resolution. Fabrication of the thermocouples involved only simple photolithography and metal-liftoff procedures on a silicon substrate. The experimentally measured Seebeck coefficient of our thermocouple was 9.17 × 10-4 V/°K, which is 30 times larger than those reported for standard metal thin-film thermocouples and comparable to the values of alloy-based thin-film thermocouples that require sophisticated and costly fabrication processes. The temperature-voltage measurements between 20 to 80 °C were highly linear with a linearity coefficient of 1, and the experimentally demonstrated temperature-sensing resolution was 0.01 °K which could be further improved up to a theoretical limit of 0.00055 °K. Finally, we applied this approach to demonstrate a flexible metal-on-silicon thermocouple with enhanced thermal sensitivity. The outstanding performance of our thermocouple combined with an extremely thin profile, bending flexibility, and simple, highly-compatible fabrication will proliferate its use in diverse applications such as micro-/nanoscale biometrics, energy management, and nanoscale thermography.

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices.

Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si3N4 substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation.

Biocompatible Multifunctional Black-Silicon for Implantable Intraocular Sensor.

Multifunctional black-silicon (b-Si) integrated on the surface of an implantable intraocular pressure sensor significantly improves sensor performance and reliability in six-month in vivo studies. The antireflective properties of b-Si triples the signal-to-noise ratio and increases the optical readout distance to a clinically viable 12 cm. Tissue growth and inflammation response on the sensor is suppressed demonstrating desirable anti-biofouling properties.

An Ion Gel as a Low-Cost, Spin-Coatable, High-Capacitance Dielectric for Electrowetting-on-Dielectric (EWOD).

For many practical electrowetting-on-dielectric (EWOD) applications, the use of high-capacitance dielectric materials is critically demanded to induce a large surface tension modulation. Thin-film dielectric layers such as Parylene C, silicon dioxide (SiO2), and aluminum oxide (Al2O3) have been commonly used for EWOD. However, these dielectric materials are fabricated by conventional integrated circuit (IC) processes which are typically time-consuming and require complex and expensive laboratory setups such as high-vacuum facilities. In this article, a novel ion gel material was demonstrated as a spin-coatable and high-capacitance dielectric for low-cost EWOD applications. The ion gel offers a 2 or 3 order higher capacitance (c ≈ 10 µF/cm(2)) than conventional dielectrics commonly used for EWOD while being fabricated through a simple low-cost spin-coating process. We discuss the fundamentals of an ion gel dielectric, its fabrication process of spin coating, and the interaction with a hydrophobic layer for practical EWOD applications. The ion gel films, which consist of a copolymer, poly(vinylidene fluoride-co-hexafluoropropylene) [P(VDF-HFP)], and an ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [EMIM][TFSI], were successfully deposited on ITO substrates by using a simple spin-coating process. The experimental demonstrations validated the theoretical modeling of the ion gel layer as a high-capacitance dielectric. The EWOD performance of the ion gel samples was compared to that of other conventional dielectric materials to show the performance improvement.