A microsensor array for biochemical sensing

A microsensor array to measure chemical properties of biological liquids is presented. A hybrid integration technique is used to mount four sensor chips on a micro flow channel: a pressure, temperature, pH, combined pO2 and pCO2 sensor chip. This results in a microsensor array which is developed to meet the technical requirements for space applications. The integration method allows to integrate other types of sensor chips. This multi-purpose and multi-user approach makes the microsensor array suitable for various biochemical applications

Exploration of the selectivity and retention behavior of alternative polyacrylamides in temperature responsive liquid chromatography

Temperature responsive liquid chromatography (TRLC) allows for separation of organic solutes in purely aqueous mobile phases whereby retention is controlled through temperature. The vast majority of the work has thus far been performed on poly[N-isopropylacrylamide] (PNIPAAm)-based columns, while the performance of other temperature responsive polymers has rarely been compared under identical conditions. Therefore, in this work, two novel TRLC phases based on poly[N-n-propylacrylamide] (PNNPAAm) and poly[N,N-diethylacrylamide] (PDEAAm) are reported and compared to the state of the art PNIPAAm based column. Optimal comparison is thereby obtained by the use of controlled radical polymerizations, identical molecular weights, and by maximizing carbon loads on the silica supporting material. Analysis of identical test mixtures of homologue series and pharmaceutical samples revealed that PNNPAAm performs in a similar way as PNIPAAm while offering enhanced retention and a shift of the useable temperature range toward lower temperatures. PDEAAm offers a range of novel possibilities as it depicts a different selectivity, allowing for enhanced resolution in TRLC in, for example, coupled column systems. Reduced plate heights of 3 could be obtained on the homemade columns, offering the promise for reasonable column efficiencies in TRLC despite the use of bulky polymers as stationary phases in HPLC

Enhancing the possibilities of comprehensive two-dimensional liquid chromatography through hyphenation of purely aqueous temperature-responsive and reversed-phase liquid chromatography

Comprehensive two-dimensional liquid chromatography (LC X LC) allows for substantial gains in theoretical peak capacity in the field of liquid chromatography. However, in practice, theoretical performance is rarely achieved due to a combination of undersampling, orthogonality, and refocusing issues prevalent in many LC X LC applications. This is intricately linked to the column dimensions, flow rates, and mobile-phase compositions used, where, in many cases, incompatible or strong solvents are introduced in the second-dimension (D-2) column, leading to peak broadening and the need for more complex interfacing approaches. In this contribution, the combination of temperature-responsive (TR) and reversed-phase (RP) LC is demonstrated, which, due to the purely aqueous mobile phase used in TRLC, allows for complete and more generic refocusing of organic solutes prior to the second-dimension RP separation using a conventional 10-port valve interface. Thus far, this was only possible when combining other purely aqueous modes such as ion exchange or gel filtration chromatography with RPLC, techniques which are limited to the analysis of charged or high MW solutes, respectively. This novel TRLC x RPLC combination relaxes undersampling constraints and complete refocusing and therefore offers novel possibilities in the field of LC x LC including temperature modulation. The concept is illustrated through the TRLC x RPLC analysis of mixtures of neutral organic solutes

A new discriminative criterion for the development of Franz diffusion tests for transdermal pharmaceuticals

PURPOSE. In vitro skin/membrane permeation profiling of topical pharmaceuticals is an important overall quality attribute in the evaluation of product consistency and it is also used for IVIVR (in vitro - in vivo relationship) purposes in product development and change control. Franz diffusion cell (FDC) experiments are emerging as a generally accepted methodology in this field, where the choice of operational conditions requires a data-supported justification towards the discriminating power of the test. A response function is therefore proposed to objectively quantify the discriminating power. METHODS. We evaluated the usefulness of the proposed response function by studying one of the operational conditions, i.e. the influence of receptor medium composition, on the FDC in vitro penetration behaviour of the model compound testosterone formulated in four different topical preparations, using both artificial membranes and dermatomed human skin. A second application is a FDC test system for spilanthol. RESULTS. From the obtained cumulative amount of the active (testosterone or spilanthol) in the receptor fluid versus time curves, the permeability coefficient Kp of the active from each formulation was calculated. The evaluation of the discriminating power of the different media was performed using our new objective response function based upon an equal spread criterion of normalised Kp values. CONCLUSION. The proposed new criterion was found to be useful for the rational design of an in vitro diffusion test for transdermal pharmaceuticals. We demonstrated significant differences in discriminating power between the different media used: (a) for testosterone-containing formulations, it was shown that HPBCD-containing media are more discriminative compared to ethanol- or BSA-containing media; (b) for spilanthol-containing formulations, PBS containing formulations also gave better discriminating results than ethanol-based receptor media

Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis

BACKGROUND & AIMS: Maintenance treatment with vedolizumab, a monoclonal antibody that inhibits the gut-selective α4β7 integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of vedolizumab for maintenance treatment. Subcutaneous vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis. METHODS: We performed a phase 3, double-blind, double-dummy trial at 141 sites in 29 countries from December 18, 2015 through August 21, 2018. Patients with moderately to severely active ulcerative colitis received open-label treatment with intravenous vedolizumab 300 mg at weeks 0 and 2. At week 6, patients with clinical response were randomly assigned maintenance treatment with subcutaneous vedolizumab 108 mg every 2 weeks, intravenous vedolizumab 300 mg every 8 weeks, or placebo. The primary end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1. RESULTS: Among the randomized 216 patients, clinical remission at week 52 was achieved by 46.2%, 42.6%, and 14.3% of patients in the subcutaneous vedolizumab, intravenous vedolizumab, and placebo groups, respectively (subcutaneous vedolizumab vs placebo: Δ32.3%; 95% confidence interval, 19.7%-45.0%; P < .001). The subcutaneous vedolizumab group also had greater endoscopic improvement and durable clinical response at week 52 compared with placebo (both P < .001). The incidence of injection-site reactions was more frequent in patients given subcutaneous vedolizumab (10.4%) than intravenous vedolizumab (1.9%) or placebo (0%); these were not treatment limiting, most were mild, and none resulted in discontinuation. Subcutaneous and intravenous vedolizumab safety profiles were otherwise similar. CONCLUSIONS: Subcutaneous vedolizumab is effective as maintenance therapy in patients with moderately to severely active ulcerative colitis who had a clinical response to intravenous vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14. ispartof: GASTROENTEROLOGY vol:158 issue:3 pages:562-+ ispartof: location:United States status: publishe