Cavity-Enhanced Photoacoustic Detection Using Acoustic and Fiber-Optic Resonators

A wineglass has been used as an acoustic resonator to enhance the photoacoustic signal generated by laser excitation of absorbing dyes in solution. The amplitude of the acoustic signal was recorded using a fiber-optic transducer based on a Fabry-Pérot cavity attached to the rim of the wineglass. The optical and acoustic properties of the setup were characterized, and it was used to quantify the concentration of phosphomolybdenum blue and methyl red solutions. Detection limits of 1.2 ppm and 8 muM were obtained, respectively.

The PD-1/PD-L1 Axis: An Immune-Mediated Mechanism of Chemoresistance in Cancer

The ability of tumour cells to avoid immune destruction (immune escape) and their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer. The interaction between specific molecules on the surface of tumour cells with their corresponding receptors on immune effector cells can result in inhibition of these effector cells, consequently allowing tumour cells to evade the host’s anti-tumour immune response. The interaction of the Programmed Death Ligand 1 (PD-L1) on the surface of tumour cells with the Programmed Death-1 (PD-1) receptor on cytotoxic T lymphocytes leads to inactivation of these immune effectors, and is a specific example of an immune escape mechanism tumour cells use to avoid immune destruction. Clinically, antibodies capable of blocking the PD-1/PD-L1 interaction have demonstrated significant therapeutic benefit, and are currently being used to help bolster patients’ immune response against malignant cells in a variety of cancer types. Here we show that the PD-1/PD-L1 interaction also leads to tumour cell resistance to conventional chemotherapeutic agents. Incubation of PD-L1-expressing human and mouse tumour cells with PD-1-expressing Jurkat T cells or purified recombinant PD-1 resulted in tumour cell resistance to doxorubicin and docetaxel. Interference with the PD-1/PD-L1 interaction using blocking anti-PD-1 or anti-PD-L1 antibody or shRNA-mediated gene silencing resulted in attenuation of PD-1/PD-L1-mediated drug resistance. Moreover, inhibition of the PD-1/PD-L1 signalling axis using anti-PD-1 antibody enhanced the effect of doxorubicin chemotherapy to inhibit 4T1 tumour cell metastasis in an in vivo mouse model of mammary carcinoma. These findings indicate that blockade of the PD-1/PD-L1 axis may be a useful approach to immunosensitize and chemosensitize tumours in cancer patients and provide a rationale for the use of anti-PD-1/PD-L1 antibodies as adjuvants to chemotherapy.

Absolute Absorption Cross-Section Measurement of a Submonolayer film on a silica microresonator

Conventional absorption spectroscopy is not nearly sensitive enough for quantitative overtone measurements on submonolayer coatings. While cavity-enhanced absorption detection methods using microresonators have the potential to provide quantitative absorption cross sections of even weakly absorbing submonolayer films, this potential has not yet been fully realized. To determine the absorption cross section of a submonolayer film of ethylene diamine (EDA) on a silica microsphere resonator, we use phase-shift cavity ringdown spectroscopy simultaneously on near-IR radiation that is Rayleigh backscattered from the microsphere and transmitted through the coupling fiber taper. We then independently determine both the coupling coefficient and the optical loss within the resonator. Together with a coincident measurement of the wavelength frequency shift, an absolute overtone absorption cross section of adsorbed EDA, at submonolayer coverage, was obtained and was compared to the bulk value. The smallest quantifiable absorption cross section is σmin 2.7 × 10−12 cm2. This absorption cross section is comparable to the extinction coefficients of, e.g., single gold nanoparticles or aerosol particles. We therefore propose that the present method is also a viable route to absolute extinction measurements of single particles.