Super Bound States in the Continuum on a Photonic Flatband: Concept, Experimental Realization, and Optical Trapping Demonstration.

In this Letter, we theoretically propose and experimentally demonstrate the formation of a super bound state in a continuum (BIC) on a photonic crystal flat band. This unique state simultaneously exhibits an enhanced quality factor and near-zero group velocity across an extended region of the Brillouin zone. It is achieved at the topological transition when a symmetry-protected BIC pinned at k=0 merges with two Friedrich-Wintgen quasi-BICs, which arise from the destructive interference between lossy photonic modes of opposite symmetries. As a proof of concept, we employ the ultraflat super BIC to demonstrate three-dimensional optical trapping of individual particles. Our findings present a novel approach to engineering both the real and imaginary components of photonic states on a subwavelength scale for innovative optoelectronic devices.

Standardized high-dimensional spectral cytometry protocol and panels for whole blood immune phenotyping in clinical and translational studies.

Flow cytometry is the method of choice for immunophenotyping in the context of clinical, translational, and systems immunology studies. Among the latter, the Milieu Intérieur (MI) project aims at defining the boundaries of a healthy immune response to identify determinants of immune response variation. MI used immunophenotyping of a 1000 healthy donor cohort by flow cytometry as a principal outcome for immune variance at steady state. New generation spectral cytometers now enable high-dimensional immune cell characterization from small sample volumes. Therefore, for the MI 10-year follow up study, we have developed two high-dimensional spectral flow cytometry panels for deep characterization of innate and adaptive whole blood immune cells (35 and 34 fluorescent markers, respectively). We have standardized the protocol for sample handling, staining, acquisition, and data analysis. This approach enables the reproducible quantification of over 182 immune cell phenotypes at a single site. We have applied the protocol to discern minor differences between healthy and patient samples and validated its value for application in immunomonitoring studies. Our protocol is currently used for characterization of the impact of age and environmental factors on peripheral blood immune phenotypes of >400 donors from the initial MI cohort.

Unveiling Candida albicans intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response.

Candida albicans is a commensal yeast present in the gut of most healthy individuals but with highly variable concentrations. However, little is known about the host factors that influence colonization densities. We investigated how microbiota, host lifestyle factors, and genetics could shape C. albicans intestinal carriage in 695 healthy individuals from the Milieu Intérieur cohort. C. albicans intestinal carriage was detected in 82.9% of the subjects using quantitative PCR. Using linear mixed models and multiway-ANOVA, we explored C. albicans intestinal levels with regard to gut microbiota composition and lifestyle factors including diet. By analyzing shotgun metagenomics data and C. albicans qPCR data, we showed that Intestinimonas butyriciproducens was the only gut microbiota species whose relative abundance was negatively correlated with C. albicans concentration. Diet is also linked to C. albicans growth, with eating between meals and a low-sodium diet being associated with higher C. albicans levels. Furthermore, by Genome-Wide Association Study, we identified 26 single nucleotide polymorphisms suggestively associated with C. albicans colonization. In addition, we found that the intestinal levels of C. albicans might influence the host immune response, specifically in response to fungal challenge. We analyzed the transcriptional levels of 546 immune genes and the concentration of 13 cytokines after whole blood stimulation with C. albicans cells and showed positive associations between the extent of C. albicans intestinal levels and NLRP3 expression, as well as secreted IL-2 and CXCL5 concentrations. Taken together, these findings open the way for potential new interventional strategies to curb C. albicans intestinal overgrowth.

Design, Analysis, and Optimization of a Plasmonic Slot Waveguide for Mid-Infrared Gas Sensing.

In this work, we investigated the optimization of a plasmonic slot waveguide (PSWG) in the mid-IR region particularly for a representative wavelength of 4.26 µm, which is the absorption line of CO2 and thus particularly relevant for applications. We analysed the mode features associated with metal-dielectric-metal (MDM), dielectric-metal-dielectric (DMD), and truncated metal film (TMF) structures with respect to the considered PSWG. Subsequently, the mode features of the PSWG were considered based on what we outlined for MDM, DMD, and TMF structures. Furthermore, as confinement factor and propagation length are two crucial parameters for absorption sensing applications, we optimized the PSWG based on a figure of merit (FOM) defined as the product of the aforementioned quantities. To characterize the propagation length, the imaginary part of the effective mode index of a guided mode was considered, leading to a dimensionless FOM. Finally, we investigated the PSWG also for other wavelengths and identified particularly attractive wavelengths and geometries maximizing the FOM.

Design of a Slab Tamm Plasmon Resonator Coupled to a Multistrip Array Waveguide for the Mid Infrared.

In this work, we present and analyze a design of an absorber-waveguide system combining a highly sensitive waveguide array concept with a resonant selective absorber. The waveguide part is composed of an array of coupled strip waveguides and is therefore called a coupled strip array (CSA). The CSA is then coupled to the end of a slab Tamm plasmon (STP-) resonator, which is composed of a quasicrystal-like reflector formed by the patterning of a silicon slab and an interfacing tungsten slab. The concept describes an emitter-waveguide or waveguide-detector system featuring selective plasmon-enhanced resonant absorption or emission. These are crucial properties for corresponding optical on-chip integrated devices in context with evanescent field absorption sensing in fluids or gases, for example. Thus, the concept comprises a valuable and more cost-effective alternative to quantum cascade lasers. We designed the lateral dimensions of the STP resonator via a simple quasi-crystal approach and achieved strong narrowband resonances (emittance and Q-factors up to 85% and 88, respectively) for different silicon thicknesses and substrate materials (air and silicon oxide). Moreover, we analyze and discuss the sensitivity of the complete emitter-waveguide system in dependence on the slab thickness. This reveals the crucial correlation between the expected sensitivity assigned to the absorber-waveguide system and field confinement within the silicon.

Ultra-Narrow SPP Generation from Ag Grating.

In this study, we investigate the potential of one-dimensional plasmonic grating structures to serve as a platform for, e.g., sensitive refractive index sensing. This is achieved by comparing numerical simulations to experimental results with respect to the excitation of surface plasmon polaritons (SPPs) in the mid-infrared region. The samples, silver-coated poly-silicon gratings, cover different grating depths in the range of 50 nm-375 nm. This variation of the depth, at a fixed grating geometry, allows the active tuning of the bandwidth of the SPP resonance according to the requirements of particular applications. The experimental setup employs a tunable quantum cascade laser (QCL) and allows the retrieval of angle-resolved experimental wavelength spectra to characterize the wavelength and angle dependence of the SPP resonance of the specular reflectance. The experimental results are in good agreement with the simulations. As a tendency, shallower gratings reveal narrower SPP resonances in reflection. In particular, we report on 2.9 nm full width at half maximum (FWHM) at a wavelength of 4.12 µm and a signal attenuation of 21%. According to a numerical investigation with respect to a change of the refractive index of the dielectric above the grating structure, a spectral shift of 4122nmRIU can be expected, which translates to a figure of merit (FOM) of about 1421 RIU-1. The fabrication of the suggested structures is performed on eight-inch silicon substrates, entirely accomplished within an industrial fabrication environment using standard microfabrication processes. This in turn represents a decisive step towards plasmonic sensor technologies suitable for semiconductor mass-production.

Connection of BANK1, Tolerance, Regulatory B cells, and Apoptosis: Perspectives of a Reductionist Investigation.

BANK1 transcript is upregulated in whole blood after kidney transplantation in tolerant patients. In comparison to patients with rejection, tolerant patients display higher level of regulatory B cells (Bregs) expressing granzyme B (GZMB+) that have the capability to prevent effector T cells proliferation. However, BANK1 was found to be decreased in these GZMB+ Bregs. In this article, we investigated seven different transcriptomic studies and mined the literature in order to make link between BANK1, tolerance and Bregs. As for GZMB+ Bregs, we found that BANK1 was decreased in other subtypes of Bregs, including IL10+ and CD24hiCD38hi transitional regulatory B cells, along with BANK1 was down-regulated in activated/differentiated B cells, as in CD40-activated B cells, in leukemia and plasma cells. Following a reductionist approach, biological concepts were extracted from BANK1 literature and allowed us to infer association between BANK1 and immune signaling pathways, as STAT1, FcγRIIB, TNFAIP3, TRAF6, and TLR7. Based on B cell signaling literature and expression data, we proposed a role of BANK1 in B cells of tolerant patients that involved BCR, IP3R, and PLCG2, and a link with the apoptosis pathways. We confronted these data with our experiments on apoptosis in total B cells and Bregs, and this suggests different involvement for BANK1 in these two cells. Finally, we put in perspective our own data with other published data to hypothesize two different roles for BANK1 in B cells and in Bregs.

Figures of merit for mid-IR evanescent-wave absorption sensors and their simulation by FEM methods.

Proper optimization of a photonic structure for sensing applications is of extreme importance for integrated sensor design. Here we discuss on the definition of suitable parameters to determine the impact of photonic structure designs for evanescent-wave absorption sensors on the achievable resolution and sensitivity. In particular, we analyze the most widespread quantities used to classify photonic structures in the context of sensing, namely the evanescent-field ratio (or evanescent power factor) and the confinement factor Γ. We show that, somewhat counterintuitively, the confinement factor is the only parameter that can reliably describe the absorption of the evanescent-field in the surrounding medium, and, by quantifying the discrepancy between the two parameters for a set of realistic photonic structures, we demonstrate that using the evanescent-field ratio can lead to a wrong classification of the performance of different structures for absorption sensing. We finally discuss the most convenient simulation strategies to retrieve the confinement factor by FEM simulations.

Designing Mid-Infrared Gold-Based Plasmonic Slot Waveguides for CO2-Sensing Applications.

Plasmonic slot waveguides have attracted much attention due to the possibility of high light confinement, although they suffer from relatively high propagation loss originating from the presence of a metal. Although the tightly confined light in a small gap leads to a high confinement factor, which is crucial for sensing applications, the use of plasmonic guiding at the same time results in a low propagation length. Therefore, the consideration of a trade-off between the confinement factor and the propagation length is essential to optimize the waveguide geometries. Using silicon nitride as a platform as one of the most common material systems, we have investigated free-standing and asymmetric gold-based plasmonic slot waveguides designed for sensing applications. A new figure of merit (FOM) is introduced to optimize the waveguide geometries for a wavelength of 4.26 µm corresponding to the absorption peak of CO2, aiming at the enhancement of the confinement factor and propagation length simultaneously. For the free-standing structure, the achieved FOM is 274.6 corresponding to approximately 42% and 868 µm for confinement factor and propagation length, respectively. The FOM for the asymmetric structure shows a value of 70.1 which corresponds to 36% and 264 µm for confinement factor and propagation length, respectively.

Clinical and immunological follow-up of very long-term kidney transplant recipients treated with calcineurin inhibitors indicates dual phenotypes.

Operationally tolerant kidney transplant recipients harbor an immunological signature, associated with low rejection risk, and focused on B lymphocytes. Here, we investigated whether patients with long-term transplantation and still on immunosuppressive therapy would present such a signature of low immunological rejection risk, compared to more recently transplanted patients. Of 114 kidney transplant recipients enrolled, 38 with more than 25 years of graft survival and stable graft function under calcineurin inhibitors, were matched with two different groups of transplanted patients (10-15 and 5-7 years after transplantation). Three phenotypes associated with low immunological rejection risk (Tfh, B and regulatory T cells), initially found in operationally tolerant kidney transplant recipients, and the composite score of tolerance (combination of six transcriptomic markers, age at transplantation and age at sampling) were analyzed. We found that very long-term patients were characterized by a significantly lower percentage of total B cells, a significantly higher proportion of CD24HiCD38Lo memory B cells, significantly fewer CD24LoCD38Lo naive B cells, and a significantly lower proportion of PD1HiCCR7Lo Tfh lymphocytes than more recently transplanted patients. This phenotype is associated with a positive composite score of tolerance in patients transplanted for more than 25 years. Thus, our study suggests a dual phenotype in very long-term kidney transplanted patients with an immunological profile associated with low rejection risk.

Toward a better definition of hematopoietic progenitors suitable for B cell differentiation.

The success of inducing human pluripotent stem cells (hIPSC) offers new opportunities for cell-based therapy. Since B cells exert roles as effector and as regulator of immune responses in different clinical settings, we were interested in generating B cells from hIPSC. We differentiated human embryonic stem cells (hESC) and hIPSC into B cells onto OP9 and MS-5 stromal cells successively. We overcame issues in generating CD34+CD43+ hematopoietic progenitors with appropriate cytokine conditions and emphasized the difficulties to generate proper hematopoietic progenitors. We highlight CD31intCD45int phenotype as a possible marker of hematopoietic progenitors suitable for B cell differentiation. Defining precisely proper lymphoid progenitors will improve the study of their lineage commitment and the signals needed during the in vitro process.

Transcriptional meta-analysis of regulatory B cells.

Regulatory B cells (Bregs) have the ability to regulate inflammation in various pathological situations, making them key players in immune regulation. Several mechanisms have been described and we recently identified a GZMB expressing Breg population in kidney transplanted patients who tolerate a kidney graft. To further investigate their biology and mechanisms, we conducted a transcriptomic analysis by RNAseq of these cells and we performed the first weighted meta-analysis of publicly available transcriptomic data from published Breg studies both in humans and mice. We identified two distinct and unique transcriptional signatures of 126 and 93 genes, respectively, associated with these Bregs. While we highlighted genes coding for proteins with potent involvement in regulatory functions, proliferation, and coding for transcription factors, the comparison between humans and mice did not allow identifying a common pattern. Thus, our results suggest distinct species-restricted Breg transcriptional signatures in humans and mice.

Increased degradation of ATP is driven by memory regulatory T cells in kidney transplantation tolerance.

Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process. The conserved proportion of memory Tregs leads to the establishment of a pro-tolerogenic balance in operationally tolerant patients. Memory Tregs in tolerant patients display normal capacity to degrade extracellular ATP/ADP. In contrast, memory Tregs from patients with stable graft function do not have this ability. Finally, in vitro, immunosuppressive drugs may favor the lower proportion of memory Tregs in stable patients, but they have no effect on CD39-dependent ATP degradation and do not explain memory Treg lack of extracellular ATP/ADP degradation ability. Thus, intrinsic active regulatory mechanisms may act long after immunosuppressive drug arrest in operationally tolerant patients and may contribute to kidney allograft tolerance via the maintenance of CD39 Treg function.