Photonic MEMS for NIR in-situ

We report on a novel sensing technique combining photonics and microelectromechanical systems (MEMS) for the detection and monitoring of gas emissions for critical environmental, medical, and industrial applications. We discuss how MEMS-tunable vertical-cavity surface-emitting lasers (VCSELs) can be exploited for in-situ detection and NIR spectroscopy of several gases, such as O{sub 2}, N{sub 2}O, CO{sub x}, CH{sub 4}, HF, HCl, etc., with estimated sensitivities between 0.1 and 20 ppm on footprints {approx}10{sup -3} mm{sup 3}. The VCSELs can be electrostatically tuned with a continuous wavelength shift up to 20 nm, allowing for unambiguous NIR signature determination. Selective concentration analysis in heterogeneous gas compositions is enabled, thus paving the way to an integrated optical platform for multiplexed gas identification by bandgap and device engineering. We will discuss here, in particular, our efforts on the development of a 760 nm AlGaAs based tunable VCSEL for O{sub 2} detection

FUNCTIONALIZED LATERAL SURFACE COATED LASERS FOR CHEM-BIO DETECTION

We present a class of compact, monolithic, photonic sensors consisting of multiple section edge emitting lasers with functionalized lateral surface coatings for low level detection of chemical or biological agents. Specifically, we discuss 8 {micro}m x 250 {micro}m Pd-coated H{sub 2} sensors and configurations to reduce the minimum detection limit from 138ppm for passive sensors to 1ppm for active sensors. Compared with conventional optical H{sub 2} sensors that use fiber gratings, surface plasmon resonances, or surface reflectance, our sensors offer the advantages of smaller size, wider dynamic range, monolithic integration of laser source and detector, and 2-D scalability to arrays of sensors that are functionalized to detect different agents

Electrical and Optical Gain Lever Effects in InGaAs Double Quantum Well Diode Lasers

In multisection laser diodes, the amplitude or frequency modulation (AM or FM) efficiency can be improved using the gain lever effect. To study gain lever, InGaAs double quantum well (DQW) edge emitting lasers have been fabricated with integrated passive waveguides and dual sections providing a range of split ratios from 1:1 to 9:1. Both the electrical and the optical gain lever have been examined. An electrical gain lever with greater than 7 dB enhancement of AM efficiency was achieved within the range of appropriate DC biasing currents, but this gain dropped rapidly outside this range. We observed a 4 dB gain in the optical AM efficiency under non-ideal biasing conditions. This value agreed with the measured gain for the electrical AM efficiency under similar conditions. We also examined the gain lever effect under large signal modulation for digital logic switching applications. To get a useful gain lever for optical gain quenched logic, a long control section is needed to preserve the gain lever strength and a long interaction length between the input optical signal and the lasing field of the diode must be provided. The gain lever parameter space has been fully characterized and validated against numerical simulations of a semi-3D hybrid beam propagation method (BPM) model for the coupled electron-photon rate equation. We find that the optical gain lever can be treated using the electrical injection model, once the absorption in the sample is known

Tumor-responsive, multifunctional CAR-NK cells cooperate with impaired autophagy to infiltrate and target glioblastoma

Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking have rendered glioblastoma (GBM) highly resistant to therapy. As a result, GBM immunotherapies have failed to demonstrate sustained clinical improvements in patient overall survival (OS). To overcome these obstacles, here we describe a novel, sophisticated combinatorial platform for GBM: the first multifunctional immunotherapy based on genetically-engineered, human NK cells bearing multiple anti-tumor functions, including local tumor responsiveness, that addresses key drivers of GBM resistance to therapy: antigen escape, poor immune cell homing, and immunometabolic reprogramming of immune responses. We engineered dual-specific CAR-NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumor-specific, locally-released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site specific activity in the tissue and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells, but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising new NK cell-based combinatorial strategy that can target multiple clinically-recognized mechanisms of GBM progression simultaneously