Method development of comprehensive two-dimensional liquid chromatography: A new metric for preliminary column selection.

To elevate the separation performance, two-dimensional liquid chromatography (2D-LC) uses two chromatographic columns with different stationary phases to diversify solute interactions with the resin, hence providing a second "dimension" to solute-specific separation. Developing methods for 2D-LC starts therefore with preliminary column selection. Selecting columns that yield (metaphorically) orthogonal dimensions is of utmost importance, but remains challenging.

In-silico method development and optimization of on-line comprehensive two-dimensional liquid chromatography via a shortcut model.

Comprehensive two-dimensional liquid chromatography (LCxLC) represents a valuable alternative to conventional single column, or one-dimensional, liquid chromatography (1D-LC) for resolving multiple components in a complex mixture in a short time. However, developing LCxLC methods with trial-and-error experiments is challenging and time-consuming, which is why the technique is not dominant despite its significant potential. This work presents a novel shortcut model to in-silico predicting retention time and peak width within an RPLCxRPLC separation system (i.

Identifying a core protein signature of small extracellular vesicles derived from B-cell precursor acute lymphoblastic leukaemia.

Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies.

Predicting sample injection profiles in liquid chromatography: A modelling approach based on residence time distributions.

The pharmaceutical and bio-pharmaceutical industries rely on simulations of liquid chromatographic processes for method development and to reduce experimental cost. The use of incorrect injection profiles as inlet boundary condition for these simulations may, however, lead to inaccurate results. This study presents a novel modelling approach for accurate prediction of injection profiles for liquid chromatographic columns.

On the apparent dispersion coefficient of the equilibrium dispersion model: An asymptotic analysis.

To model chromatography, researchers have developed several approaches. These cover a broad range of applications and, depending on the assumptions adopted, have different levels of accuracy. In general, the most suitable modelling approach is the simplest that can describe a process with the desired accuracy.

Iatrogenic Neonatal Esophageal Perforation: A European Multicentre Review on Management and Outcomes.

Background: The aim of this multicenter retrospective study and literature review was to review management and outcomes of neonatal esophageal perforation (NEP).

Methods: Protocol data were collected from four European Centers on gestational age, factors surrounding feeding tube insertion, management and outcomes.

Results: The 5-year study period (2014-2018) identified eight neonates with median gestational age of 26 + 4 weeks (23 + 4-39) and median birth weight 636 g (511-3500).

Rising to Ostrom's challenge: an invitation to walk on the bright side of public governance and public service.

In this programmatic essay, we argue that public governance scholarship would benefit from developing a self-conscious and cohesive strand of "positive" scholarship, akin to social science subfields like positive psychology, positive organizational studies, and positive evaluation. We call for a program of research devoted to uncovering the factors and mechanisms that enable high performing public policies and public service delivery mechanisms; procedurally and distributively fair processes of tackling societal conflicts; and robust and resilient ways of coping with threats and risks. The core question driving positive public administration scholarship should be: Why is it that particular public policies, programs, organizations, networks, or partnerships manage do much better than others to produce widely valued societal outcomes, and how might knowledge of this be used to advance institutional learning from positives?

Hydrodynamic Characterization of Phase Separation in Devices with Microfabricated Capillaries.

Capillary microseparators have been gaining interest in downstream unit operations, especially for pharmaceutical, space, and nuclear applications, offering efficient separation of two-phase flows. In this work, a detailed analysis of the dynamics of gas?liquid separation at the single meniscus level helped to formulate a model to map the operability region of microseparation devices. A water?nitrogen segmented flow was separated in a microfabricated silicon-glass device, with a main channel (width, W = 600 ?m; height, H = 120 ?m) leading into an array of 276 capillaries (100 ?m long; width = 5 ?m facing the main channel and 25 ?m facing the liquid outlet), on both sides of the channel.

Fouling of an anion exchange chromatography operation in a monoclonal antibody process: Visualization and kinetic studies.

Fouling of chromatographic resins over their operational lifetimes can be a significant problem for commercial bioseparations. In this article, scanning electron microscopy (SEM), batch uptake experiments, confocal laser scanning microscopy (CLSM) and small-scale column studies were applied to characterize a case study where fouling had been observed during process development. The fouling was found to occur on an anion exchange (AEX) polishing step following a protein A affinity capture step in a process for the purification of a monoclonal antibody.

Design of high productivity antibody capture by protein A chromatography using an integrated experimental and modeling approach.

An integrated experimental and modeling approach for the design of high productivity protein A chromatography is presented to maximize productivity in bioproduct manufacture. The approach consists of four steps: (1) small-scale experimentation, (2) model parameter estimation, (3) productivity optimization and (4) model validation with process verification. The integrated use of process experimentation and modeling enables fewer experiments to be performed, and thus minimizes the time and materials required in order to gain process understanding, which is of key importance during process development.

Optimal economic design and operation of single- and multi-column chromatographic processes.

Single-column chromatography is widely used in the biopharmaceutical industries, although multi-column alternatives in the form of simulated moving bed (SMB) processes are now emerging. It may be difficult, however, to determine which column alternative will be best suited for a given application, and this work sets out to address this issue. A systematic approach is presented that is based on a full economic appraisal of each process alternative based on an optimization of the net annual profit.