Nanophotonics for bacterial detection and antimicrobial susceptibility testing

Photonic biosensors are a major topic of research that continues to make exciting advances. Technology has now improved sufficiently for photonics to enter the realm of microbiology and to allow for the detection of individual bacteria. Here, we discuss the different nanophotonic modalities used in this context and highlight the opportunities they offer for studying bacteria. We critically review examples from the recent literature, starting with an overview of photonic devices for the detection of bacteria, followed by a specific analysis of photonic antimicrobial susceptibility tests. We show that the intrinsic advantage of matching the optical probed volume to that of a single, or a few, bacterial cell, affords improved sensitivity while providing additional insight into single-cell properties. We illustrate our argument by comparing traditional culture-based methods, which we term macroscopic, to microscopic free-space optics and nanoscopic guided-wave optics techniques. Particular attention is devoted to this last class by discussing structures such as photonic crystal cavities, plasmonic nanostructures and interferometric configurations. These structures and associated measurement modalities are assessed in terms of limit of detection, response time and ease of implementation. Existing challenges and issues yet to be addressed will be examined and critically discussed

Dielectric metasurface for high-precision detection of large unilamellar vesicles.

Extracellular vesicles (EVs) are very promising biomarkers for the diagnosis of various diseases, including cardiovascular, infectious and neurodegenerative disorders. Of particular relevance is their importance in cancer liquid biopsy, where they play a key role in the early detection and monitoring of the tumour. A number of technologies have recently been developed to improve the performance of current EV detection methods, but a technique that can provide high resolution, high accuracy and a multiplexing capability for the detection of several biomarkers in parallel remains a challenge in this field. Here, we demonstrate the detection of large unilamellar vesicles, which are excellent models of EVs, down to a concentration <103 EV ml−1 (<10 pM) using a dielectric resonant metasurface. This result represents an improvement in performance and functionality compared to competing plasmonic and electrochemical modalities and is due to the strong resonance amplitude and high Q-factor of our metasurface. We also verify the selectivity of the approach by detecting vesicles that have been surface-functionalised with a CD9 protein. The ease of integration of our method into a point-of-care instrument offers a path towards personalised cancer medicine

Ultra-high Q/V hybrid cavity for strong light-matter interaction

The ability to confine light at the nanoscale continues to excite the research community, with the ratio between quality factor Q and volume V, i.e., the Q/V ratio, being the key figure of merit. In order to achieve strong light-matter interaction, however, it is important to confine a lot of energy in the resonant cavity mode. Here, we demonstrate a novel cavity design that combines a photonic crystal nanobeam cavity with a plasmonic bowtie antenna. The nanobeam cavity is optimised for a good match with the antenna and provides a Q of 1700 and a transmission of 90%. Combined with the bowtie, the hybrid photonic-plasmonic cavity achieves a Q of 800 and a transmission of 20%, both of which remarkable achievements for a hybrid cavity. The ultra-high Q/V of the hybrid cavity is of order of 106 (λ/n)−3, which is comparable to the state-of-the-art of photonic resonant cavities. Based on the high Q/V and the high transmission, we demonstrate the strong efficiency of the hybrid cavity as a nanotweezer for optical trapping. We show that a stable trapping condition can be achieved for a single 200 nm Au bead for a duration of several minutes (ttrap > 5 min) and with very low optical power (Pin = 190 μW)

Exploring the Limit of Multiplexed Near-Field Optical Trapping

Optical trapping has revolutionized our understanding of biology by manipulating cells and single molecules using optical forces. Moving to the near-field creates intense field gradients to trap very smaller particles, such as DNA fragments, viruses, and vesicles. The next frontier for such optical nanotweezers in biomedical applications is to trap multiple particles and to study their heterogeneity. To this end, we have studied dielectric metasurfaces that allow the parallel trapping of multiple particles. We have explored the requirements for such metasurfaces and introduce a structure that allows the trapping of a large number of nanoscale particles (>1000) with a very low total power P < 26 mW. We experimentally demonstrate the near-field enhancement provided by the metasurface and simulate its trapping performance. We have optimized the metasurface for the trapping of 100 nm diameter particles, which will open up opportunities for new biological studies on viruses and extracellular vesicles, such as studying heterogeneity, or to massively parallelize analyses for drug discovery

Extended Kalman Filtering Projection Method to Reduce the 3σ Noise Value of Optical Biosensors

Optical biosensors have experienced a rapid growth over the past decade because of their high sensitivity and the fact that they are label-free. Many optical biosensors rely on tracking the change in a resonance signal or an interference pattern caused by the change in refractive index that occurs upon binding to a target biomarker. The most commonly used method for tracking such a signal is based on fitting the data with an appropriate mathematical function, such as a harmonic function or a Fano, Gaussian, or Lorentz function. However, these functions have limited fitting efficiency because of the deformation of data from noise. Here, we introduce an extended Kalman filter projection (EKFP) method to address the problem of resonance tracking and demonstrate that it improves the tolerance to noise, reduces the 3σ noise value, and lowers the limit of detection (LOD). We utilize the method to process the data of experiments for detecting the binding of C-reactive protein in a urine matrix with a chirped guided mode resonance sensor and are able to improve the LOD from 10 to 1 pg/mL. Our method reduces the 3σ noise value of this measurement compared to a simple Fano fit from 1.303 to 0.015 pixels. These results demonstrate the significant advantage of the EKFP method to resolving noisy data of optical biosensors

On Metalenses with Arbitrarily Wide Field of View

Metalenses are nanostructured surfaces that mimic the functionality of optical elements. Many exciting demonstrations have already been made, for example, focusing into diffraction-limited spots or achromatic operation over a wide wavelength range. The key functionality that is yet missing, however, and that is most important for applications such as smartphones or virtual reality, is the ability to perform the imaging function with a single element over a wide field of view. Here, by relaxing the constraint on diffraction-limited resolution, we demonstrate the ability of single-layer metalenses to perform wide field of view (WFOV) imaging while maintaining high resolution suitable for most applications. We also discuss the WFOV physical properties and, in particular, we show that such a WFOV metalens mimics a spherical lens in the limit of infinite radius and infinite refractive index. Finally, we use Fourier analysis to explain the dependence of the FOV on the numerical aperture

Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM–AIRO–AISP–ANISC–AURO–Fondazione AIOM–SIAPEC/IAP–SIBioC–SICO–SIF–SIGE–SIGU–SIU–SIURO–UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations