An integrated source of broadband quadrature squeezed light

An integrated silicon nitride resonator is proposed as an ultra-compact source of bright single-mode quadrature squeezed light at 850 nm. Optical properties of the device are investigated and tailored through numerical simulations, with particular attention paid to loss associated with interfacing the device. An asymmetric double layer stack waveguide geometry with inverse vertical tapers is proposed for efficient and robust fibre-chip coupling, yielding a simulated total loss of -0.75 dB/facet. We assess the feasibility of the device through a full quantum noise analysis and derive the output squeezing spectrum for intra-cavity pump self-phase modulation. Subject to standard material loss and detection efficiencies, we find that the device holds promises for generating substantial quantum noise squeezing over a bandwidth exceeding 1 GHz. In the low-propagation loss regime, approximately -7 dB squeezing is predicted for a pump power of only 50 mW.Comment: 23 pages, 12 figure

Measurement-induced macroscopic superposition states in cavity optomechanics

We present a novel proposal for generating quantum superpositions of macroscopically distinct states of a bulk mechanical oscillator, compatible with existing optomechanical devices operating in the readily achievable bad-cavity limit. The scheme is based on a pulsed cavity optomechanical quantum non-demolition (QND) interaction, driven by displaced non-Gaussian states, and measurement-induced feedback, avoiding the need for strong single-photon optomechanical coupling. Furthermore, we show that single-quadrature cooling of the mechanical oscillator is sufficient for efficient state preparation, and we outline a three-pulse protocol comprising a sequence of QND interactions for squeezing-enhanced cooling, state preparation, and tomography.Comment: 7 pages, 5 figure

A novel assay for monitoring internalization of nanocarrier coupled antibodies

BACKGROUND: Discovery of tumor-selective antibodies or antibody fragments is a promising approach for delivering therapeutic agents to antigen over-expressing cancers. Therefore it is important to develop methods for the identification of target- and function specific antibodies for effective drug delivery. Here we describe a highly selective and sensitive method for characterizing the internalizing potential of multivalently displayed antibodies or ligands conjugated to liposomes into tumor cells. The assay requires minute amounts of histidine-tagged ligand and relies on the non-covalent coupling of these antibodies to fluorescent liposomes containing a metal ion-chelating lipid. Following incubation of cells with antibody-conjugated liposomes, surface bound liposomes are gently removed and the remaining internalized liposomes are quantitated based on fluorescence in a high throughput manner. We have termed this methodology "Chelated Ligand Internalization Assay", or CLIA. RESULTS: The specificity of the assay was demonstrated with different antibodies to the ErbB-2 and EGF receptors. Antibody-uptake correlated with receptor expression levels in tumor cell lines with a range of receptor expression. Furthermore, Ni-NTA liposomes containing doxorubicin were used to screen for the ability of antibodies to confer target-specific cytotoxicity. Using an anti-ErbB2 single chain Fv (scFv) (F5) antibody, cytotoxicity could be conferred to ErbB2-overexpressing cells; however, a poly(ethylene glycol)-linked lipid (DSPE-PEG-NTA-Ni) was necessary to allow for efficient loading of the drug and to reduce nonspecific drug leakage during the course of the assay. CONCLUSION: The CLIA method we describe here represents a rapid, sensitive and robust assay for the identification and characterization of tumor-specific antibodies capable of high drug-delivery efficiency when conjugated to liposomal nanocarriers

Differential Measurement of Trident Production in Strong Electromagnetic Fields

In this paper, we present experimental results and numerical simulations of trident production, $e^-\rightarrow e^-e^+e^-$, in a strong electromagnetic field. The experiment was conducted at CERN for the purpose of probing the strong-field parameter $\chi$ up to 2.4, using a 200 GeV electron beam penetrating a 400 $\mu$m thick germanium crystal oriented along the $\langle 110\rangle$ axis. For the current experimental parameters we found that the trident process is primarily a two-step process, and show remarkable agreement between theoretical predictions and experimental data. This paper is an extension of the previously published paper (Phys. Rev. Lett. 130, 071601 (2023)) and features new analysis differential in the energy of the produced positron and electron in the trident process. Even for the more demanding differential analysis, we find good agreement between theoretical predictions and experimental data, while a slight discrepancy is found in the high energy tail of the trident spectrum. This discrepancy could be an indication of the direct process, but further investigation is needed due to the large uncertainties in this part of the spectrum. Finally we present a suggestion for a future experiment, aiming to probe the direct process using thin crystals

Therapeutic efficacy of anti-ErbB2 immunoliposomes targeted by a phage antibody selected for cellular endocytosis

AbstractMany targeted cancer therapies require endocytosis of the targeting molecule and delivery of the therapeutic agent to the interior of the tumor cell. To generate single chain Fv (scFv) antibodies capable of triggering receptor-mediated endocytosis, we previously developed a method to directly select phage antibodies for internalization by recovering infectious phage from the cytoplasm of the target cell. Using this methodology, we reported the selection of a panel of scFv that were internalized into breast cancer cells from a nonimmune phage library. For this work, an immunotherapeutic was generated from one of these scFv (F5), which bound to ErbB2 (HER2/neu). The F5 scFv was reengineered with a C-terminal cysteine, expressed at high levels in Escherichia coli, and coupled to sterically stabilized liposomes. F5 anti-ErbB2 immunoliposomes were immunoreactive as determined by surface plasmon resonance (SPR) and were avidly internalized by ErbB2-expressing tumor cell lines in proportion to the levels of ErbB2 expression. F5-scFv targeted liposomes containing doxorubicin had antitumor activity and produced significant reduction in tumor size in xenografted mice compared to nontargeted liposomes containing doxorubicin. This strategy should be applicable to generate immunotherapeutics for other malignancies by selecting phage antibodies for internalization into other tumor types and using the scFv to target liposomes or other nanoparticles