Up to 300†K lasing with GeSn-On-Insulator microdisk resonators.

GeSn alloys are the most promising direct band gap semiconductors to demonstrate full CMOS-compatible laser integration with a manufacturing from Group-IV materials. Here, we show that room temperature lasing, up to 300 K, can be obtained with GeSn. This is achieved in microdisk resonators fabricated on a GeSn-On-Insulator platform by combining strain engineering with a thick layer of high Sn content GeSn.

DAC-less PAM-4 generation in the O-band using a silicon Mach-Zehnder modulator.

We demonstrate 20-Gb/s 4-level pulse amplitude modulation (PAM-4) signal generation using a silicon Mach-Zehnder modulator (MZM) in the O-band. The modulator is driven by two independent binary streams, and the PAM-4 signal is thus generated directly on the chip, avoiding the use of power-hungry digital-to-analog converters (DACs). With optimized amplitude levels of the binary signals applied to the two arms of the MZM, a pre-forward error correction (FEC) bit-error rate (BER) as low as 7.6 × 10-7 is obtained. In comparison with a commercially available LiNbO3 modulator, the penalty is only 2 dB at the KP4 FEC threshold of 2.2 × 10-4.

Thermally stable hybrid cavity laser based on silicon nitride gratings.

In this paper, we show the experimental results of a thermally stable Si3N4 external cavity (SiN EC) laser with high power output and the lowest SiN EC laser threshold to our knowledge. The device consists of a 250 µm sized reflective semiconductor optical amplifier butt-coupled to a passive chip based on a series of Si3N4 Bragg gratings acting as narrow reflectors. A threshold of 12 mA has been achieved, with a typical side-mode suppression ratio of 45 dB and measured power output higher than 3 mW. Furthermore, we achieved a mode-hop free-lasing regime in the range of 15-62 mA and wavelength thermal stability up to 80°C. This solves the challenges related to cavity resonances' thermal shift and shows the possibility for this device to be integrated in dense wavelength-division multiplexing (WDM) and heat-intensive optical interconnects technologies.

Simplified modeling and optimization of silicon modulators based on free-carrier plasma dispersion effect.

In this paper, a simplified model of silicon phase modulators is presented that enables favorable accuracy together with a substantial reduction in computational effort and without the requirement of semiconductor TCAD device simulation software. This permits fast optimization of the different parameters of a modulator. The model was successfully implemented in Phoenix Optodesigner optical software allowing the optimization of silicon phase shifters for different applications. Moreover, this model presents a great potential for the simulation of modulators based on PN interdigitated junctions, which normally require complex and time consuming 3D simulations. Simulation time was reduced by a factor of 6 for the lateral PN junction based modulator, and two orders of magnitude reduction was obtained for interdigitated PN junctions based modulators.

Programmable insect cell carriers for systemic delivery of integrated cancer biotherapy.

Due to cancer's genetic complexity, significant advances in the treatment of metastatic disease will require sophisticated, multi-pronged therapeutic approaches. Here we demonstrate the utility of a Drosophila melanogaster cell platform for the production and in vivo delivery of multi-gene biotherapeutic systems. We show that cultured Drosophila S2 cell carriers can stably propagate oncolytic viral therapeutics that are highly cytotoxic for mammalian cancer cells without adverse effects on insect cell viability or gene expression. Drosophila cell carriers administered systemically to immunocompetent animals trafficked to tumors to deliver multiple biotherapeutics with little apparent off-target tissue homing or toxicity, resulting in a therapeutic effect. Cells of this Dipteran invertebrate provide a genetically tractable platform supporting the integration of complex, multi-gene biotherapies while avoiding many of the barriers to systemic administration of mammalian cell carriers. These transporters have immense therapeutic potential as they can be modified to express large banks of biotherapeutics with complementary activities that enhance anti-tumor activity.

Tensile-strained germanium microdisk electroluminescence.

We report room temperature electroluminescence of tensile-strained germanium microdisks. The strain is transferred into the microdisks using silicon nitride stressors. Carrier injection is achieved with Schottky contacts on n-type doped germanium. We show that a biaxial tensile-strain up to 0.72% can be transferred by optimizing the carrier injection profile. The transferred strain is measured by the electroluminescence spectral red-shift and compared to finite element modeling. We discuss the impact of this strain level to achieve population inversion in germanium.

Clonal variation in interferon response determines the outcome of oncolytic virotherapy in mouse CT26 colon carcinoma model.

In our earlier studies, Semliki Forest virus vector VA7 completely eliminated type I interferon (IFN-I)-unresponsive human U87-luc glioma xenografts, whereas interferon-responsive mouse gliomas proved refractory. Here, we describe in two clones of CT26 murine colon carcinoma, opposed patterns of IFN-I responsiveness and sensitivity to VA7. Both CT26WT and CT26LacZ clones secreted biologically active interferon in vitro upon virus infection but only CT26WT cells were protected. Focal infection of CT26WT cultures was self-limiting but could be rescued using IFN-I pathway inhibitor Ruxolitinib or antibody against IFNß. Whole transcriptome sequencing (RNA-Seq) and protein expression analysis revealed that CT26WT cells constitutively expressed 56 different genes associated with pattern recognition and IFN-I signaling pathways, spanning two reported anti-RNA virus gene signatures and 22 genes with reported anti-alphaviral activity. Whereas CT26WT tumors were strictly virus-resistant in vivo, infection of CT26LacZ tumors resulted in complete tumor eradication in both immunocompetent and severe combined immune deficient mice. In double-flank transplantation experiments, CT26WT tumors grew despite successful eradication of CT26LacZ tumors from the contralateral flank. Tumor growth progressed uninhibited also when CT26LacZ inoculums contained only a small fraction of CT26WT cells, demonstrating dominance of IFN responsiveness when heterogeneous tumors are targeted with interferon-sensitive oncolytic viruses.

Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by direct cytolysis and induction of antitumor immunity.

Rhabdoviruses (RVs) are currently being pursued as anticancer therapeutics for various tumor types, notably leukemia. However, modest virion production and limited spread between noncontiguous circulating leukemic cells requires high-dose administration of RVs, which exceeds the maximum tolerable dose of the live virus. Furthermore, in severely immunosuppressed leukemic patients, the potential for uncontrolled live virus spread may compromise the safety of a live virus approach. We hypothesized that the barriers to oncolytic virotherapy in liquid tumors may be overcome by administration of high-dose non-replicating RVs. We have developed a method to produce unique high-titer bioactive yet non-replicating rhabdovirus-derived particles (NRRPs). This novel biopharmaceutical is multimodal possessing direct cytolytic and immunomodulatory activity against acute leukemia. We demonstrate that NRRP resistance in normal cells is mediated by intact antiviral defences including interferon (IFN). This data was substantiated using murine models of blast crisis. The translational promise of NRRPs was demonstrated in clinical samples obtained from patients with high-burden multidrug-resistant acute myeloid leukemia. This is the first successful attempt to eradicate disseminated cancer using a non-replicating virus-derived agent, representing a paradigm shift in our understanding of oncolytic virus-based therapies and their application toward the treatment of acute leukemia.