Improving liquid chromatography efficiency: channels structured with micro-pillars

Band dispersion has been measured in micromachined separation channels structured with orderly disposed cylindrical micropillars. It was found that with an optimal channel design the band broadening could be lower by a factor of 3 than in packed columns with a comparable particle size. The positioning of the row of pillars closest to the side wall was a decisive factor in influencing band broadening

Immobilized-Enzyme Reactors Integrated into Analytical Platforms: Recent Advances and Challenges

Immobilized-enzyme reactors (IMERs) are flow-through devices containing enzymes that are physically confined or localized with retention of their catalytic activities. IMERs can be used repeatedly and continuously and have been applied for (bio)polymer degradation, proteomics, biomarker discovery, inhibitor screening, and detection. Online integration of IMERs with analytical instrumentation, such as high-performance liquid chromatography (HPLC) systems, reduces the time needed for multi-step workflows, reduces the need for sample handling, and enables automation. However, online integration can also be challenging, as reaching its full potential requires complex instrumental setups and experienced users. This review aims to provide an assessment of recent advances and challenges in online IMER-based (analytical) LC platforms, covering publications from 2014-2021. A critical discussion of challenges often encountered in IMER fabrication, sample preparation, integration into the analytical workflow, long-term usage, and of potential ways to overcome these is provided. Finally, the obstacles preventing the proliferation of IMERs as efficient tools for high-throughput pharmacological, industrial, and biological studies are discussed

Confinement of Monolithic Stationary Phases in Targeted Regions of 3D-Printed Titanium Devices Using Thermal Polymerization

Abstract In this study, we have prepared thermally initiated polymeric monolithic stationary phases within discrete regions of 3D-printed titanium devices. The devices were created with controllable hot and cold regions. The monolithic stationary phases were first locally created in capillaries inserted into the channels of the titanium devices. The homogeneity of the monolith structure and the interface length were studied by scanning a capacitively coupled conductivity contactless detector (C4D) along the length of the capillary. Homogeneous monolithic structures could be obtained within a titanium device equipped with a hot and cold jacket connected to two water baths. The confinement method was optimized in capillaries. The sharpest interfaces (between monolith and empty channel) were obtained with the hot region maintained at 70 °C and the cold region at 4 or 10 °C, with the latter temperature yielding better repeatability. The optimized conditions were used to create monoliths bound directly to the walls of the titanium channels. The fabricated monoliths were successfully used to separate a mixture of four intact proteins using reversed-phase liquid chromatography. Further chromatographic characterization showed a permeability (Kf) of ∼4 × 10–15 m2 and a total porosity of 60%. Since their introduction in the chromatographic world, porous polymer monoliths have proven to be powerful separation media. These chromatographic supports have been widely applied for applications, such as microscale liquid chromatography (LC) of peptides and proteins, but have also been used in capillary electrochromatography (CEC),(1) gas chromatography (GC),(2) sample preparation,(3) and catalysis.(4) The ease of preparation of monoliths, diverse chemistry options, and high permeabilities have made them popular materials for analytical devices, such as microfluidic chips for LC. In the past decade, miniaturization has been realized by developing lab-on-a-chip solutions, where several analytical processes can be integrated within a few square centimeters. In such systems, due to the small channels and articulated geometries, the particle-packing procedure has proven to be challenging.(5) In contrast, monolithic beds are usually created in situ by free-radical polymerization of monomers in the presence of porogens and they are well-suited for chip-based separations. The proliferation of microfluidic devices has spurred new interest in polymer monoliths for applications such as enzymatic reactors(6,7) and microfluidic mixers.(8) This development has been boosted by the advent of additive manufacturing (or 3D-printing), which allows for rapid prototyping of complex structures, converting computer-aided-design (CAD) models into physical objects. Unfortunately, the use of 3D-printed analytical devices for chromatographic analysis is limited by the solvent compatibility of some materials (e.g., acrylate-based polymers) and in some cases by their transparency at the desired wavelength (e.g., UV or IR wavelengths). Several successful steps have been taken to locally photopolymerize monolithic stationary phases in discrete regions of microfluidic devices.(9−12) Heat is an alternative way to transfer energy to the monomer precursors for initiating the polymerization. However, accurate control of temperature in small confined spaces is more difficult to achieve, and so far only few steps have been taken in this direction.(13) In this work, two methods are explored to achieve confined thermal polymerization. The first approach involves direct contact (DC) between Peltier elements and the surface of a titanium device. In the second approach, recirculating jackets are used for localized heating and cooling (heating/cooling jackets, HCJ). The latter approach resembles a recirculation-based freeze–thaw valve.(14) In both approaches, defined hot (HR) and cold (CR) regions are created. We aim to fabricate poly(styrene-co-divinylbenzene) (PS-DVB) monolithic stationary phases within a 3D-printed titanium microfluidic device through polymerization at 70 °C, and to separate intact proteins using this device

Experimental investigation of the band broadening originating from the top and bottom wall in micromachined non-porous pillar array columns

We report on the experimental investigation of the effect of the top and bottom wall plates in micromachined nonporous pillar array columns. It has been found that their presence yields an additional c-term type of band broadening that can make up a significant fraction of the total band broadening (at least if considering nonporous pillars and a nonretained tracer). Their presence also induces a clear (downward) shift of the optimal velocity. These observations are, however in excellent quantitative agreement with the theoretical expectations obtained from a computational fluid dynamics study. The presently obtained experimental results, hence, demonstrate that the employed high aspect ratio Bosch etching process can be used to fabricate micromachined pillar arrays that are sufficiently refined to achieve the theoretical performance limit

On the origin of X-shaped radio galaxies

After a brief, critical review of the leading explanations proposed for the small but important subset of radio galaxies showing an X-shaped morphology (XRGs) we propose a generalized model, based on the jet-shell interaction and spin-flip hypotheses. The most popular scenarios for this intriguing phenomenon invoke either hydrodynamical backflows and over-pressured cocoons or rapid jet reorientations, presumably from the spin-flips of central engines following the mergers of pairs of galaxies, each of which contains a supermassive black hole (SMBH). We confront these models with a number of key observations and thus argue that none of the models is capable of explaining the entire range of salient observational properties of XRGs, although some of the arguments raised in the literature against the spin-flip scenario are probably not tenable. We then propose here a new scenario which also involves galactic mergers but would allow the spin of the central engine to maintain its direction. Motivated by the detailed multi-band observations of the nearest radio galaxy, Centaurus A, this new model emphasizes the role of interactions between the jets and the shells of stars and gas that form and rotate around the merged galaxy and can cause temporary deflections of the jets, occasionally giving rise to an X-shaped radio structure. Although each of the models is likely to be relevant to a subset of XRGs, the bulk of the evidence indicates that most of them are best explained by the jet-shell interaction or spin-flip hypotheses.Comment: 19 pages, major revision including two Appendices and a Table, accepted in Research in Astronomy and Astrophysic

Effects of general practitioner training and family support services on the care of home-dwelling dementia patients - Results of a controlled cluster-randomized study

<p>Abstract</p> <p>Background</p> <p>More than 90% of dementia patients are cared for by their general practitioners, who are decisively involved in the diagnosis, therapy and recommendation of support services. <it>Objective: </it>To test whether special training of general practitioners alters the care of dementia patients through their systematic recommendation of caregiver counseling and support groups.</p> <p>Method</p> <p>129 general practitioners enrolled 390 dementia patients and their informal caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A constituted usual care, in Arm B and C support groups and caregiver counseling (in Arm B one year after baseline, in Arm C at baseline) were recommended by the general practitioners. The general practitioners received arm-specific training. Diagnostic and therapeutic behavior of physicians was recorded at baseline. Informal caregivers were questioned in follow-up after 2 years about the utilization of support services.</p> <p>Results</p> <p>The diagnostic behavior of the general practitioners conforms to relevant guidelines. The procedure in newly-diagnosed patients does not differ from previously diagnosed patients with the exception of the rate of referral to a specialist. About one-third of the newly-diagnosed dementia patients are given an anti-dementia drug. The utilization of support groups and counseling increased five- and fourfold, respectively. Utilization of other support services remained low (< 10%), with the exception of home nursing and institutional short-term nursing.</p> <p>Conclusion</p> <p>Trained general practitioners usually act in conformity with guidelines with respect to diagnosing dementia, and partly in conformity with the guidelines with respect to recommended drug therapy. Recommendations of support services for informal caregivers by the general practitioner are successful. They result in a marked increase in the utilization rate for the recommended services compared to offers which are not recommended by the general practitioner.</p> <p>Trial registration</p> <p>ISRCTN68329593</p

Kinemetry of SINS High-Redshift Star-Forming Galaxies: Distinguishing Rotating Disks from Major Mergers

We present a simple set of kinematic criteria that can distinguish between galaxies dominated by ordered rotational motion and those involved in major merger events. Our criteria are based on the dynamics of the warm ionized gas (as traced by H-alpha) within galaxies, making this analysis accessible to high-redshift systems, whose kinematics are primarily traceable through emission features. Using the method of kinemetry (developed by Krajnovic and co-workers), we quantify asymmetries in both the velocity and velocity dispersion maps of the warm gas, and the resulting criteria enable us to empirically differentiate between non-merging and merging systems at high redshift. We apply these criteria to 11 of our best-studied rest-frame UV/optical-selected z~2 galaxies for which we have near infrared integral field spectroscopic data from SINFONI on the VLT. Of these 11 systems, we find that >50% have kinematics consistent with a single rotating disk interpretation, while the remaining systems are more likely undergoing major mergers. This result, combined with the short formation timescales of these systems, provides evidence that rapid, smooth accretion of gas plays a significant role in galaxy formation at high redshift.Comment: Accepted for publication in the Astrophysical Journal. 24 pages, 14 figure

Does a Family Meetings Intervention Prevent Depression and Anxiety in Family Caregivers of Dementia Patients? A Randomized Trial

Family caregivers of dementia patients are at increased risk of developing depression or anxiety. A multi-component program designed to mobilize support of family networks demonstrated effectiveness in decreasing depressive symptoms in caregivers. However, the impact of an intervention consisting solely of family meetings on depression and anxiety has not yet been evaluated. This study examines the preventive effects of family meetings for primary caregivers of community-dwelling dementia patients.A randomized multicenter trial was conducted among 192 primary caregivers of community dwelling dementia patients. Caregivers did not meet the diagnostic criteria for depressive or anxiety disorder at baseline. Participants were randomized to the family meetings intervention (n = 96) or usual care (n = 96) condition. The intervention consisted of two individual sessions and four family meetings which occurred once every 2 to 3 months for a year. Outcome measures after 12 months were the incidence of a clinical depressive or anxiety disorder and change in depressive and anxiety symptoms (primary outcomes), caregiver burden and quality of life (secondary outcomes). Intention-to-treat as well as per protocol analyses were performed.A substantial number of caregivers (72/192) developed a depressive or anxiety disorder within 12 months. The intervention was not superior to usual care either in reducing the risk of disorder onset (adjusted IRR 0.98; 95% CI 0.69 to 1.38) or in reducing depressive (randomization-by-time interaction coefficient = -1.40; 95% CI -3.91 to 1.10) or anxiety symptoms (randomization-by-time interaction coefficient = -0.55; 95% CI -1.59 to 0.49). The intervention did not reduce caregiver burden or their health related quality of life.This study did not demonstrate preventive effects of family meetings on the mental health of family caregivers. Further research should determine whether this intervention might be more beneficial if provided in a more concentrated dose, when applied for therapeutic purposes or targeted towards subgroups of caregivers.Controlled-Trials.com ISRCTN90163486