Novel Operation Strategy to Obtain a Fast Gas Sensor for Continuous ppb-Level NO2 Detection at Room Temperature Using ZnO-A Concept Study with Experimental Proof.

A novel sensor operation concept for detecting ppb-level NO2 concentrations at room temperature is introduced. Today's research efforts are directed to make the sensors as fast as possible (low response and recovery times). Nevertheless, hourly mean values can hardly be precisely calculated, as the sensors are still too slow and show baseline drifts. Therefore, the integration error becomes too large. The suggested concept follows exactly the opposite path. The sensors should be made as slow as possible and operated as resistive gas dosimeters. The adsorption/desorption equilibrium should be completely shifted to the adsorption side during a sorption phase. The gas-sensitive material adsorbs each NO2 molecule (dose) impinging and the sensor signal increases linearly with the NO2 dose. The actual concentration value results from the time derivative, which makes the response very fast. When the NO2 adsorption capacity of the sensor material is exhausted, it is regenerated with ultraviolet (UV) light and the baseline is reached again. Since the baseline is newly redefined after each regeneration step, no baseline drift occurs. Because each NO2 molecule that reaches the sensor material contributes to the sensor signal, a high sensitivity results. The sensor behavior of ZnO known so far indicates that ZnO may be suitable to be applied as a room-temperature chemiresistive NO2 dosimeter. Because UV enhances desorption of sorbed gas species from the ZnO surface, regeneration by UV light should be feasible. An experimental proof demonstrating that the sensor concept works at room temperature for ppb-level NO2 concentrations and low doses is given.

T-cell functionality testing is highly relevant to developing novel immuno-tracers monitoring T cells in the context of immunotherapies and revealed CD7 as an attractive target.

Cancer immunotherapy has proven high efficacy in treating diverse cancer entities by immune checkpoint modulation and adoptive T-cell transfer. However, patterns of treatment response differ substantially from conventional therapies, and reliable surrogate markers are missing for early detection of responders versus non-responders. Current imaging techniques using 18F-fluorodeoxyglucose-positron-emmission-tomograpy (18F-FDG-PET) cannot discriminate, at early treatment times, between tumor progression and inflammation. Therefore, direct imaging of T cells at the tumor site represents a highly attractive tool to evaluate effective tumor rejection or evasion. Moreover, such markers may be suitable for theranostic imaging. Methods: We mainly investigated the potential of two novel pan T-cell markers, CD2 and CD7, for T-cell tracking by immuno-PET imaging. Respective antibody- and F(ab´)2 fragment-based tracers were produced and characterized, focusing on functional in vitro and in vivo T-cell analyses to exclude any impact of T-cell targeting on cell survival and antitumor efficacy. Results: T cells incubated with anti-CD2 and anti-CD7 F(ab´)2 showed no major modulation of functionality in vitro, and PET imaging provided a distinct and strong signal at the tumor site using the respective zirconium-89-labeled radiotracers. However, while T-cell tracking by anti-CD7 F(ab´)2 had no long-term impact on T-cell functionality in vivo, anti-CD2 F(ab´)2 caused severe T-cell depletion and failure of tumor rejection. Conclusion: This study stresses the importance of extended functional T-cell assays for T-cell tracer development in cancer immunotherapy imaging and proposes CD7 as a highly suitable target for T-cell immuno-PET imaging.

Immuno-PET Imaging of Engineered Human T Cells in Tumors.

Sensitive in vivo imaging technologies applicable to the clinical setting are still lacking for adoptive T-cell-based immunotherapies, an important gap to fill if mechanisms of tumor rejection or escape are to be understood. Here, we propose a highly sensitive imaging technology to track human TCR-transgenic T cells in vivo by directly targeting the murinized constant TCR beta domain (TCRmu) with a zirconium-89 ((89)Zr)-labeled anti-TCRmu-F(ab')2 fragment. Binding of the labeled or unlabeled F(ab')2 fragment did not impair functionality of transgenic T cells in vitro and in vivo Using a murine xenograft model of human myeloid sarcoma, we monitored by Immuno-PET imaging human central memory T cells (TCM), which were transgenic for a myeloid peroxidase (MPO)-specific TCR. Diverse T-cell distribution patterns were detected by PET/CT imaging, depending on the tumor size and rejection phase. Results were confirmed by IHC and semiquantitative evaluation of T-cell infiltration within the tumor corresponding to the PET/CT images. Overall, these findings offer a preclinical proof of concept for an imaging approach that is readily tractable for clinical translation. Cancer Res; 76(14); 4113-23. ©2016 AACR.

Synthesis, spectroscopic, and analyte-responsive behavior of a polymerizable naphthalimide-based carboxylate probe and molecularly imprinted polymers prepared thereof.

A naphthalimide-based fluorescent indicator monomer 1 for the integration into chromo- and fluorogenic molecularly imprinted polymers (MIPs) was synthesized and characterized. The monomer was equipped with a urea binding site to respond to carboxylate-containing guests with absorption and fluorescence changes, namely a bathochromic shift in absorption and fluorescence quenching. Detailed spectroscopic analyses of the title compound and various models revealed the signaling mechanism. Titration studies employing benzoate and Z-L-phenylalanine (Z-L-Phe) suggest that indicator monomers such as the title compound undergo a mixture of deprotonation and complex formation in the presence of benzoate but yield hydrogen-bonded complexes, which are desirable for the molecular imprinting process, with weakly basic guests like Z-l-Phe. Compound 1 could be successfully employed in the synthesis of monolithic and thin-film MIPs against Z-L-Phe, Z-L-glutamic acid, and penicillin G. Chromatographic assessment of the selectivity features of the monoliths revealed enantioselective discrimination and clear imprinting effects. Immobilized on glass coverslips, the thin-film MIPs of 1 displayed a clear signaling behavior with a pronounced enantioselective fluorescence quenching dependence and a promising discrimination against cross-analytes.