Exploring the fundamental limit of antimicrobial susceptibility by near-single-cell electrical impedance spectroscopy.

Many novel susceptibility tests are being developed to tackle the worldwide problem of antimicrobial resistance (AMR). The key driver behind these developments, that is the need to reduce the response time, requires an understanding of which bacterial characteristic needs to be monitored to provide a rapid and ideally universal signature of susceptibility. Many characteristics have already been studied, most notably bacterial growth, metabolism and motility. Here, we consider electrical impedance to directly access bacterial metabolism, which can be considered a fundamental indicator of bacterial viability. By studying the electrical response of individual bacteria to an antibiotic challenge, we detect antimicrobial action close to its biological limit. Specifically, we find that it takes 30-60 min to register significant changes in impedance for clinical concentrations of antibiotics, in line with other rapid indicators. Our findings suggest that 60 min is the fundamental lower limit of response time for a realistic susceptibility test at clinically relevant antibiotic concentrations.

Dielectric nanohole array metasurface for high-resolution near-field sensing and imaging.

Dielectric metasurfaces support resonances that are widely explored both for far-field wavefront shaping and for near-field sensing and imaging. Their design explores the interplay between localised and extended resonances, with a typical trade-off between Q-factor and light localisation; high Q-factors are desirable for refractive index sensing while localisation is desirable for imaging resolution. Here, we show that a dielectric metasurface consisting of a nanohole array in amorphous silicon provides a favourable trade-off between these requirements. We have designed and realised the metasurface to support two optical modes both with sharp Fano resonances that exhibit relatively high Q-factors and strong spatial confinement, thereby concurrently optimizing the device for both imaging and biochemical sensing. For the sensing application, we demonstrate a limit of detection (LOD) as low as 1 pg/ml for Immunoglobulin G (IgG); for resonant imaging, we demonstrate a spatial resolution below 1 µm and clearly resolve individual E. coli bacteria. The combined low LOD and high spatial resolution opens new opportunities for extending cellular studies into the realm of microbiology, e.g. for studying antimicrobial susceptibility.

Multiparameter antibiotic resistance detection based on hydrodynamic trapping of individual E. coli.

There is an urgent need to develop novel methods for assessing the response of bacteria to antibiotics in a timely manner. Antibiotics are traditionally assessed via their effect on bacteria in a culture medium, which takes 24-48 h and exploits only a single parameter, i.e. growth. Here, we present a multiparameter approach at the single-cell level that takes approximately an hour from spiking the culture to correctly classify susceptible and resistant strains. By hydrodynamically trapping hundreds of bacteria, we simultaneously monitor the evolution of motility and morphology of individual bacteria upon drug administration. We show how this combined detection method provides insights into the activity of antimicrobials at the onset of their action which single parameter and traditional tests cannot offer. Our observations complement the current growth-based methods and highlight the need for future antimicrobial susceptibility tests to take multiple parameters into account.

Backscattering design for a focusing grating coupler with fully etched slots for transverse magnetic modes.

Grating couplers are a fundamental building block of integrated optics as they allow light to be coupled from free-space to on-chip components and vice versa. A challenging task in designing any grating coupler is represented by the need for reducing back reflections at the waveguide-grating interface, which introduce additional losses and undesirable interference fringes. Here, we present a design approach for focusing TM grating couplers that minimizes these unwanted reflections by introducing a modified slot that fulfills an anti-reflection condition. We show that this antireflection condition can be met only for the Bloch mode of the grating that concentrates in the dielectric. As a consequence the light is scattered from the grating coupler with a negative angle, referred to as "backscattering design". Our analytic model shows that the anti-reflection condition is transferrable to grating couplers on different waveguide platforms and that it applies for both TE and TM polarizations. Our experimentally realized focusing grating coupler for TM-modes on the silicon photonics platform has a coupling loss of (3.95 ± 0.15) dB at a wavelength of 1.55 µm. It has feature sizes above 200 nm and fully etched slots. The reflectivity between the grating coupler and the connected waveguide is suppressed to below 0.16%.

Coupling between multimode fibers and slab waveguides.

In guided-wave optics, using gratings to couple between single mode waveguides and single mode fibers and vice versa is well-established. In contrast, the coupling between multimode waveguides is more complex and a much less understood topic, even though multimode coupling is essential for the excitation of guided modes from spatially incoherent sources or for the extraction of spatially incoherent radiation from a guided-wave platform. Here, we present the design for a grating that couples multiple modes of a 2D slab waveguide into a multimode fiber and vice versa and discuss the corresponding challenges. We highlight the importance of matching mode numbers and scattering angles and show that the coupling efficiency can readily drop to low values. We present a rudimentary design that illustrates the key issues by demonstrating the coupling from a multimode fiber into a waveguide slab and back into another fiber, which achieves a total efficiency of -34 dB. By modeling the same geometry, we achieve good agreement, which allows us to explain the physics of the coupler and to suggest improvements. Future options are discussed to improve the coupling elements with a better directivity in order to achieve a maximal coupling efficiency. Our findings can be exploited for improving the multimode light injection into and out of integrated guided-wave optical systems.