An implantable microdevice to perform high-throughput in vivo drug sensitivity testing in tumors

Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure, through minimally invasive biopsy of a small region of a single tumor. This assay takes into consideration physiologic effects that contribute to drug response by allowing drugs to interact with the living tumor in its native microenvironment. Because these effects are crucial to predicting drug response, we envision that these devices will help identify optimal drug therapy before systemic treatment is initiated and could improve drug response prediction beyond the biomarkers and in vitro and ex vivo studies used today. These devices may also be used in clinical drug development to safely gather efficacy data on new compounds before pharmacological optimization.National Cancer Institute (U.S.) (Innovative Molecular Analysis Technologies Program R21-CA177391)Kibur Medical, Inc

Methane to methanol in supercritical water

We examined the feasibility of producing methanol from the partial oxidation of methane in near-critical and supercritical water. Oxygen was always the limiting reactant. The parameter space investigated experimentally included temperatures between 349 and 481 [deg]C, batch holding times between 1 and 9 min, water densities between 0.15 and 0.35 g mL-1, initial methane to water molar ratios between 0.05 and 0.27, and initial methane to oxygen molar ratios between 10 and 26. Experiments within this parameter space led to methane conversions up to 6%, and oxygen conversions up to 100%. Methanol, carbon monoxide, and carbon dioxide were the major products. The methanol selectivities ranged from 0.04 to 0.75, with the highest selectivities occurring at the lower conversions. The highest methanol yield was 0.7%. Reactions performed in glass-lined reactors proceeded to higher conversions than did reactions in stainless-steel reactors under otherwise identical conditions. A detailed chemical kinetics model showed that the methanol selectivity increased with temperature and with the methane to oxygen molar ratio, but decreased with increasing oxygen conversion. The methanol yield showed the same trends with temperature and the methane to oxygen ratio, but the yield increased with oxygen conversion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31518/1/0000440.pd