Biological sensing with metamaterials
Ordered lattices of nanostructures with unique electromagnetic properties not found in nature offer novel sensing possibilities for diagnosis, treatment, and management of disease.
Unlocking the potential of emerging technofields such as robotics, synthetic biology, the internet of things, and neurotechnology relies on integrated sensing systems. In such systems, sensory feedback can offer a multidimensional platform for closed-loop control and autonomous activity. Advanced sensing capabilities are provided by wearable health monitors, imaging contrast agents, spectroscopic labels and rulers, and biomarker detection. These are accelerating the availability of personalized biomedicine in critical areas such as real-time diagnostics, telemedicine, and drug delivery.
Opportunities that could be supported by kaleidoscopic sensory feedback, however, are limited by the size, sensitivity, specificity, dynamic range, and transducibility of current sensing regimes, whether electronic, optical, or physicochemical.1 Existing electronic sensors are approaching limitations resulting from Moore's law scalability, required power, limited transfer response, and intrinsic losses. Diffraction, opacity, and lack of selectivity constrain available optical sensors. Physicochemical sensors are restricted by portability, analyte kinetics, and regeneration. However, recent advances in nanotechnology and optics are converging to address these barriers by supporting the development of novel sensor materials.
Metamaterials—rationally designed materials with attributes not found in natural materials—offer novel sensing platforms with unique advantages, particularly for diagnosis, treatment, and management of disease. Metamaterials consist of nanostructures called meta-atoms arranged periodically in a dielectric matrix.2 Particular physical and chemical properties of the meta-atoms and their geometric arrangement allow local light structuring at subwavelength scales.3 Isolated nanostructures analogous to meta-atoms have emerged as contrast agents, spectroscopic labels, sensors, drug delivery vehicles, and thermal ablation agents.4 Colleagues and I have shown that, by redesigning these nanostructures and assembly into ordered lattices, we can improve sensitivity (see Figure 1), selectivity, and resolution across broader spectral regions, such as the near-IR water window, and so increase their utility for biological systems.5
Until now, the inherent complexity of physical models has made it necessary to rely on numerical analysis when designing meta-atom and metamaterial systems to optimize performance for a selected application.6 However, integrating metamaterials into biological devices and systems calls for tractable expressions from which we can distinguish principles for design and operation.7
Approximate solutions for inducing intense, local electromagnetic fields in metamaterials can provide near-field electromagnetic field maps as well as far-field spectral responses based on phenomenological descriptions of meta-atoms and the surrounding dielectric.8 We have found that approximate solutions provide a useful guide for designing real structures, for which pragmatic considerations may limit physical dimensions and operational implementation.9 By comparing features of modeled and measured systems, we have been able to validate numerical analyses and refine both numerical descriptions and fabricated materials.
In our nano-bio-photonics lab, we have co-ordinated numerical analysis, fabrication, and characterization of meta-atoms and metamaterials. As a result, we have identified four factors to consider when designing and preparing metamaterials for bio/optical sensors. First, resonance energies of meta-atoms are responsive to changes in their surface-area-to-mass ratio as well as to their arrangement in a periodic lattice.10 Ordering into a diffractive lattice, for example, increases the resonance energy and sensitivity of plasmon resonant nanoparticles. Second, resonant coupling between plasmon and photonic modes is uniquely dependent on polarizability and diffraction for periodic ensembles of meta-atoms.11 The relative influence of factors that affect this dependence can be visualized with a combination of complex trigonometric and dipole sum approximations. Third, internal reflectance within metamaterials enhances dissipation.12 Snell's law can describe this internal reflection of transverse optical rays that result from diffuse reflection, Rayleigh scattering, or diffraction. Finally, the balance between electrochemical and surface forces controls bottom-up lithography and metallization of metamaterials.13 As an example, geometric articulation of hydrophilic patches on an otherwise hydrophobic surface can support galvanic self-assembly of nanospheres into ordered lattices in aqueous solution at ambient conditions. This approach replaces capital- and labor-intensive top-down patterning and deposition using extreme energetic and environmental conditions.
In summary, we have distinguished between the interactive effects of meta-atom geometry, opto-electronic coupling, optothermal dissipation, and mechanofluidic forces in metamaterials, developing improved approaches for subwavelength structuring of light. We are in the process of implementing these advances to accelerate the design, fabrication, characterization, and implementation of metamaterials for diagnosis, treatment, and management of disease. Possibilities include low-loss design and economic, scalable manufacture of optoelectronic sensors, or miniaturization of wireless, embeddable high-resolution optodes (optical sensing devices). Such devices could enable bidirectional wireless communication and control of specific indications in vivo as well as remote whole-body monitoring of a patient's condition, expanding opportunities for proactive health management and telemedicine, respectively.
D. Keith Roper is the Charles W. Oxford Professor of Emerging Technologies at the University of Arkansas and a fellow of the American Institute for Medical and Biological Engineering. His research examines electrodynamics and thermodynamics in nano- and metamaterials and bio/chemical systems for biomedicine, sustainable energy, and optoelectronics.