Assessing the influence of small structural modifications in simple DNA-based nanostructures on their role as drug nanocarriers.

DNA nanotechnology leverages Watson-Crick-Franklin base-pairing interactions to build complex DNA-based nanostructures (DNS). Due to DNA specific self-assembly properties, DNS can be designed with a total control of their architecture, which has been demonstrated to have an impact on the overall DNS features. Indeed, structural properties such as the shape, size and flexibility of DNS can influence their biostability as well as their ability to internalise into cells. We present here two series of simple DNS with small and precise variations related to their length or flexibility and study the influence that these structural changes have on their overall properties as drug nanocarriers. Results indicate that shorter and more flexible DNS present higher stability towards nuclease degradation. These structural changes also have a certain effect on their cell internalisation ability and drug release rate. Consequently, drug-loaded DNS cytotoxicity varies according to the design, with lower cell viability values obtained in the DNS exhibiting faster drug release and larger cell interaction rates. In summary, small changes in the structure of simple DNS can have an influence on their overall capabilities as drug nanocarriers. The effects reported here could guide the design of simple DNS for future therapeutic uses.

Heparin-Coated Dendronized Hyperbranched Polymers for Antimalarial Targeted Delivery.

The rampant evolution of resistance in Plasmodium to all existing antimalarial drugs calls for the development of improved therapeutic compounds and of adequate targeted delivery strategies for them. Loading antimalarials in nanocarriers specifically targeted to the parasite will contribute to the administration of lower overall doses, with reduced side effects for the patient, and of higher local amounts to parasitized cells for an increased lethality toward the pathogen. Here, we report the development of dendronized hyperbranched polymers (DHPs), with capacity for antimalarial loading, that are coated with heparin for their specific targeting to red blood cells parasitized by Plasmodium falciparum. The resulting DHP-heparin complexes exhibit the intrinsic antimalarial activity of heparin, with an IC50 of ca. 400 nM, added to its specific targeting to P. falciparum-infected (vs noninfected) erythrocytes. DHP-heparin nanocarriers represent a potentially interesting contribution to the limited family of structures described so far for the loading and targeted delivery of current and future antimalarial compounds.

Circular Optical Phased Array with Large Steering Range and High Resolution.

Light detection and ranging systems based on optical phased arrays and integrated silicon photonics have sparked a surge of applications over the recent years. This includes applications in sensing, free-space communications, or autonomous vehicles, to name a few. Herein, we report a design of two-dimensional optical phased arrays, which are arranged in a grid of concentric rings. We numerically investigate two designs composed of 110 and 820 elements, respectively. Both single-wavelength (1550 nm) and broadband multi-wavelength (1535 nm to 1565 nm) operations are studied. The proposed phased arrays enable free-space beam steering, offering improved performance with narrow beam divergences of only 0.5° and 0.22° for the 110-element and 820-element arrays, respectively, with a main-to-sidelobe suppression ratio higher than 10 dB. The circular array topology also allows large element spacing far beyond the sub-wavelength-scaled limits that are present in one-dimensional linear or two-dimensional rectangular arrays. Under a single-wavelength operation, a solid-angle steering between 0.21π sr and 0.51π sr is obtained for 110- and 820-element arrays, respectively, while the beam steering spans the range of 0.24π sr and 0.57π sr for a multi-wavelength operation. This work opens new opportunities for future optical phased arrays in on-chip photonic applications, in which fast, high-resolution, and broadband beam steering is necessary.

Dendron-functionalised hyperbranched bis-MPA polyesters as efficient non-viral vectors for gene therapy in different cell lines.

Gene therapy has become a relevant tool in the biomedical field to treat or even prevent some diseases. The effective delivery of genetic material into the cell remains a crucial step to succeed in this purpose. In the search for efficient non-viral vectors, a series of amino-terminated dendronized hyperbranched polymers (DHPs) of different generations based either on bis-MPA or bis-GMPA have been designed. All of them have demonstrated an accurate ability to complex two types of genetic materials, a plasmid DNA and a siGFP, yielding dendriplexes. Moreover, some of them have proved to be able to deliver the genetic material inside the cells, resulting in the effective accomplishment of the desired genetic modification and improving the activity of some commercial transfection reagents. Different cell lines, including cancer and mesenchymal stem cells, have been studied here to evaluate the ability of DHPs as vectors for transfection. Treatments based on mesenchymal stem cells are gaining importance due to their pluripotency. Thus, it is of special relevance to introduce a genetic modification into a mesenchymal cell line as it allows it to act over a wide spectrum of tissues after inducing cellular differentiation.

Broadband 2 × 2 multimode interference coupler for mid-infrared wavelengths.

Beam splitters are core components of photonic integrated circuits and are often implemented with multimode interference couplers. While these devices offer high performance, their operational bandwidth is still restrictive for sensing applications in the mid-infrared wavelength range. Here we experimentally demonstrate a subwavelength-structured 2×2 multimode interference coupler with high performance in the 3.1-3.7µm range, doubling the bandwidth of a conventional device.

Millimeter-long metamaterial surface-emitting antenna in the silicon photonics platform.

Integrated optical antennas are key components for on-chip light detection and ranging technology (LIDAR). In order to achieve a highly collimated far field with reduced beam divergence, antenna lengths on the order of several millimeters are required. In the high-index contrast silicon photonics platform, achieving such long antennas typically demands weakly modulated gratings with lithographic minimum feature sizes below 10 nm. Here, we experimentally demonstrate a new, to the best of our knowledge, strategy to make long antennas in silicon waveguides using a metamaterial subwavelength grating (SWG) waveguide core loaded with a lateral periodic array of radiative elements. The mode field confinement is controlled by the SWG duty cycle, and the delocalized propagating mode overlaps with the periodic perturbations. With this arrangement, weak antenna radiation strength can be achieved while maintaining a minimum feature size as large as 80 nm. Using this strategy, we experimentally demonstrate a 2-millimeter-long, single-etched subwavelength-engineered optical antenna on a conventional 220 nm SOI platform, presenting a measured far-field beam divergence of 0.1° and a wavelength scanning sensitivity of 0.13°/nm.

Suspended germanium waveguides with subwavelength-grating metamaterial cladding for the mid-infrared band.

In recent years, sensing and communication applications have fueled important developments of group-IV photonics in the mid-infrared band. In the long-wave range, most platforms are based on germanium, which is transparent up to ∼15-µm wavelength. However, those platforms are limited by the intrinsic losses of complementary materials or require complex fabrication processes. To overcome these limitations, we propose suspended germanium waveguides with a subwavelength metamaterial lateral cladding that simultaneously provides optical confinement and allows structural suspension. These all-germanium waveguides can be fabricated in one dry and one wet etch step. A propagation loss of 5.3 dB/cm is measured at a wavelength of 7.7 µm. These results open the door for the development of integrated devices that can be fabricated in a simple manner and can potentially cover the mid-infrared band up to ∼15 µm.

DNA-Based Nanocarriers to Enhance the Optoacoustic Contrast of Tumors In Vivo.

Optoacoustic tomography (OT) enables non-invasive deep tissue imaging of optical contrast at high spatio-temporal resolution. The applications of OT in cancer imaging often rely on the use of molecular imaging contrast agents based on near-infrared (NIR) dyes to enhance contrast at the tumor site. While these agents afford excellent biocompatibility and minimal toxicity, they present limited optoacoustic signal generation capability and rapid renal clearance, which can impede their tumor imaging efficacy. In this work, a synthetic strategy to overcome these limitations utilizing biodegradable DNA-based nanocarrier (DNA-NC) platforms is introduced. DNA-NCs enable the incorporation of NIR dyes (in this case, IRDye 800CW) at precise positions to enable fluorescence quenching and maximize optoacoustic signal generation. Furthermore, these DNA-NCs show a prolonged blood circulation compared to the native fluorophores, facilitating tumor accumulation by the enhanced permeability and retention (EPR) effect. In vivo imaging of tumor xenografts in mice following intravenous administration of DNA-NCs reveals enhanced OT signals at 24 h when compared to free fluorophores, indicating promise for this method to enhance the optoacoustic signal generation capability and tumor uptake of clinically relevant NIR dyes.

Coherent silicon photonic interferometric biosensor with an inexpensive laser source for sensitive label-free immunoassays.

Over the past two decades, integrated photonic sensors have been of major interest to the optical biosensor community due to their capability to detect low concentrations of molecules with label-free operation. Among these, interferometric sensors can be read-out with simple, fixed-wavelength laser sources and offer excellent detection limits but can suffer from sensitivity fading when not tuned to their quadrature point. Recently, coherently detected sensors were demonstrated as an attractive alternative to overcome this limitation. Here we show, for the first time, to the best of our knowledge, that this coherent scheme provides sub-nanogram per milliliter limits of detection in C-reactive protein immunoassays and that quasi-balanced optical arm lengths enable operation with inexpensive Fabry-Perot-type lasers sources at telecom wavelengths.

Perfectly vertical surface grating couplers using subwavelength engineering for increased feature sizes.

We present perfectly vertical grating couplers for the 220 nm silicon-on-insulator platform incorporating subwavelength metamaterials to increase the minimum feature sizes and achieve broadband low back-reflection. Our study reveals that devices with high coupling efficiencies are distributed over a wide region of the design space with varied back-reflections, while still maintaining minimum feature sizes larger than 100 nm and even 130 nm. Using 3D-finite-difference time-domain simulations, we demonstrate devices with broadband low back-reflection of less than -20dB over more than 100 nm bandwidth centered around the C-band. Coupling efficiencies of 72% and 67% are achieved for minimum feature sizes of 106 nm and 130 nm, respectively. These gratings are also more fabrication tolerant compared to similar designs not using metamaterials.

Mapping the global design space of nanophotonic components using machine learning pattern recognition.

Nanophotonics finds ever broadening applications requiring complex components with many parameters to be simultaneously designed. Recent methodologies employing optimization algorithms commonly focus on a single performance objective, provide isolated designs, and do not describe how the design parameters influence the device behaviour. Here we propose and demonstrate a machine-learning-based approach to map and characterize the multi-parameter design space of nanophotonic components. Pattern recognition is used to reveal the relationship between an initial sparse set of optimized designs through a significant reduction in the number of characterizing parameters. This defines a design sub-space of lower dimensionality that can be mapped faster by orders of magnitude than the original design space. The behavior for multiple performance criteria is visualized, revealing the interplay of the design parameters, highlighting performance and structural limitations, and inspiring new design ideas. This global perspective on high-dimensional design problems represents a major shift in modern nanophotonic design and provides a powerful tool to explore complexity in next-generation devices.

Optimizing the Limit of Detection of Waveguide-Based Interferometric Biosensor Devices.

Waveguide-based photonic sensors provide a unique combination of high sensitivity, compact size and label-free, multiplexed operation. Interferometric configurations furthermore enable a simple, fixed-wavelength read-out making them particularly suitable for low-cost diagnostic and monitoring devices. Their limit of detection, i.e., the lowest analyte concentration that can be reliably observed, mainly depends on the sensors response to small refractive index changes, and the noise in the read-out system. While enhancements in the sensors response have been extensively studied, noise optimization has received much less attention. Here we show that order-of-magnitude enhancements in the limit of detection can be achieved through systematic noise reduction, and demonstrate a limit of detection of ∼ 10 - 8 RIU with a silicon nitride sensor operating at telecom wavelengths.

Broadband fiber-chip zero-order surface grating coupler with 0.4 dB efficiency.

Surface grating couplers enable efficient coupling of light between optical fibers and nanophotonic waveguides. However, in conventional grating couplers, the radiation angle is intrinsically wavelength dependent, thereby limiting their operation bandwidth. In this Letter, we present a zero-order surface grating coupler in silicon-on-insulator which overcomes this limitation by operating in the subwavelength regime. By engineering the effective refractive index of the grating region, both high coupling efficiency and broadband operation bandwidth are achieved. The grating is assisted by a silicon prism on top of the waveguide, which favors upward radiation and minimizes power losses to substrate. Using a linear apodization, our design achieves a coupling efficiency of 91% (-0.41 dB) and a 1-dB bandwidth of 126 nm.