Compact capillary high performance liquid chromatography system for pharmaceutical on-line reaction monitoring.

Due to their size, conventional high performance liquid chromatographs (HPLCs) are difficult to place close to a reaction vessel within a pharmaceutical manufacturing or development site. Typically, long transfer lines are required to move sample from the reactor to the HPLC for analysis and high solvent usage is required. However, herein a compact and modular separation system has been developed to enable co-location of an HPLC with a small-scale reactor for reaction monitoring in the synthesis of active pharmaceutical ingredients.

Small footprint liquid chromatography-mass spectrometry for pharmaceutical reaction monitoring and automated process analysis.

Liquid chromatography (LC) has broad applicability in the pharmaceutical industry, from the early stages of drug discovery to reaction monitoring and process control. However, small footprint, truly portable LC systems have not yet been demonstrated and fully evaluated practically for on-line, in-line or at-line pharmaceutical analysis. Herein, a portable, briefcase-sized capillary LC fitted with a miniature multi-deep UV-LED detector has been developed and interfaced with a portable mass spectrometer for on-site pharmaceutical analysis.

Small-Footprint, Field-Deployable LC/MS System for On-Site Analysis of Per- and Polyfluoroalkyl Substances in Soil.

Per- and polyfluoroalkyl substances (PFASs) are emerging environmental pollutants of global concern. For rapid field site evaluation, there are very few sensitive, field-deployable analytical techniques. In this work, a portable lightweight capillary liquid chromatography (capLC) system was coupled with a small footprint portable mass spectrometer and configured for field-based applications.

Advances in Automated Piston Liquid-Liquid Microextraction Technique.

A new automated micro liquid-liquid extraction technique was successfully developed. This novel syringe-based technique capitalizes on the advantages of vigorous fluid agitation and the shearing effect of two fluids with different properties to achieve high extraction efficiency. The technique is at least 20 times faster than mechanical shaking or sonication in achieving a similar recovery even with a hydrophilic probe molecule such as 1,4-dioxane in an aqueous medium.

Hyphenated sample preparation-electrospray and nano-electrospray ionization mass spectrometry for biofluid analysis.

Stand-alone electrospray ionization mass spectrometry (ESI-MS) has been advancing through enhancements in throughput, selectivity and sensitivity of mass spectrometers. Unlike traditional MS techniques which usually require extensive offline sample preparation and chromatographic separation, many sample preparation techniques are now directly coupled with stand-alone MS to enable outstanding throughput for bioanalysis. In this review, we summarize the different sample clean-up and/or analyte enrichment strategies that can be directly coupled with ESI-MS and nano-ESI-MS for the analysis of biological fluids.

Automated liquid-liquid extraction of organic compounds from aqueous samples using a multifunction autosampler syringe.

Liquid-liquid extraction is one of the most widely used and simplest sample preparation techniques. However, consumption of large volumes of organic solvent and manual handling are two major drawbacks of this technique. A multifunction autosampler syringe is introduced which permits automated liquid-liquid extraction in an enclosed operating environment, with low consumption of organic solvents.

A Comparison of Commercially Available Screen-Printed Electrodes for Electrogenerated Chemiluminescence Applications.

We examined a series of commercially available screen-printed electrodes (SPEs) for their suitability for electrochemical and electrogenerated chemiluminescence (ECL) detection systems. Using cyclic voltammetry with both a homogeneous solution-based and a heterogeneous bead-based ECL assay format, the most intense ECL signals were observed from unmodified carbon-based SPEs. Three commercially available varieties were tested, with Zensor outperforming DropSens and Kanichi in terms of sensitivity.

Recent advances in stir-bar sorptive extraction: Coatings, technical improvements, and applications.

Stir-bar sorptive extraction (SBSE) is a popular solvent-less sample preparation method, which is widely applied for the sampling and preconcentration of a wide range of non-polar solutes. A typical stir-bar for SBSE is composed of a polydimethylsiloxane (PDMS) film, coated onto a glass jacket with an incorporated magnet core. Sampling is carried out by direct immersion or by exposing the stir-bar to the headspace of the sample.

Miniature Multiwavelength Deep UV-LED-Based Absorption Detection System for Capillary LC.

A new miniature deep UV absorbance detector has been developed using low-cost and high-performance LEDs, which can be operated in both scanning (230 to 300 nm) and individual wavelength (240, 255, and 275 nm) detection modes. The detector is mostly composed of off-the-shelf components, such as LEDs, trifurcated fiber optic assembly, a capillary Z-type flow cell, and photodiodes. It has been characterized for use with a standard capillary LC system and was benchmarked against a standard variable wavelength capillary LC detector.

Ultraviolet absorbance detector based on a high output power 235 nm surface mounted device-type light-emitting diode.

A new miniaturised capillary flow-through deep-UV absorbance detector has been developed using a microscale surface mounted device- type light-emitting diode (LED) (Crystal IS OPTAN 3535-series), emitting at 235 nm and with a half-height band width of 12 nm, and a high-sensitivity Z-shaped flow-cell. Compared with a previously reported TO-39 ball lens LEDs emitting at 235 nm, the new generation LED produced a 20-fold higher optical output and delivered up to 35 times increase in external quantum efficiency (EQE). The Z-cell was based on a reflective rectangular optical path with cross-sectional dimensions of 100 × 100 µm and a physical optical pathlength of 1.

In-Syringe Electrokinetic Protein Removal from Biological Samples prior to Electrospray Ionization Mass Spectrometry.

Here, an electrokinetic extraction (EkE) syringe is presented allowing for on-line electrokinetic removal of serum proteins before ESI-MS. The proposed concept is demonstrated by the determination of pharmaceuticals from human serum within minutes, with sample preparation limited to a 5× dilution of the sample in the background electrolyte (BGE) and application of voltage, both of which can be performed in-syringe. Signal enhancements of 3.

Fully automated, low-cost ion chromatography system for in-situ analysis of nitrite and nitrate in natural waters.

A cost-effective, automated and portable IC has been developed for in-situ analysis of nitrite and nitrate in natural waters. The system employed 3D printed pumps for eluent delivery and a deep-UV LED based optical detector. Isocratic separation and selective detection of nitrite and nitrate was achieved in under 3 min.

Miniature and fully portable gradient capillary liquid chromatograph.

A robust, portable and miniature battery powered gradient capillary liquid chromatograph (total weight ∼2.7 kg, without battery ∼2.0 kg), with integrated microfluidic injection, column heating and high sensitivity low-UV absorbance detection is presented.

Integrated 3D printed heaters for microfluidic applications: Ammonium analysis within environmental water.

A multi-material 3D printed microfluidic reactor with integrated heating is presented, which was applied within a manifold for the colorimetric determination of ammonium in natural waters. Graphene doped polymer was used to provide localised heating when connected to a power source, achieving temperatures of up to 120 °C at 12 V, 0.7 A.

Development of polydimethylsiloxane-microdiamond composite materials for application as sorptive devices.

The development and application of non-porous and porous sorptive rods, comprised of polydimethylsiloxane-microdiamond (PDMS-MD) composites, is reported. The PDMS-MD composites were made porous using inorganic salt (NaCl and NaHCO) particles as dissolvable templates. Materials with pore size of ~40 µm down to ~5 µm were produced.

In-Syringe Electrokinetic Ampholytes Focusing Coupled with Electrospray Ionization Mass Spectrometry.

A 25 μL analytical glass syringe has been used for isoelectric focusing (IEF) utilizing the stainless-steel needle and plunger as electrodes. The generation of protons and hydroxyl ions at the electrodes facilitated a neutralization reaction boundary (NRB) mechanism to focus different amphoteric compounds, such as hemoglobin, bovine serum albumin, R-phycoerythrin, and histidine, within minutes. After optimization of different experimental parameters affecting the IEF process and the coupling of the IEF syringe with electrospray ionization mass spectrometry (ESI-MS), a BGE composed of NHAc, 1.

Recent advances in open tubular capillary liquid chromatography.

This review covers advances and applications of open tubular capillary liquid chromatography (OT-LC) over the period 2007-2018. Under the right conditions OT-LC columns have the potential to offer superior column efficiency, higher overall peak capacity, and higher column permeability compared to packed capillary and monolithic columns. However, such advantages are highly dependent upon column format and dimensions, and to date in liquid chromatography the advantages of open tubular format columns have been most widely discussed and applied in the field of proteomics.

Selective capillary electrophoresis separation of mono and divalent cations within a high-surface area-to-volume ratio multi-lumen capillary.

In this study, the separation of inorganic mono and divalent cations using multi-lumen silica capillaries (MLCs) of 126 channels, each with either 4 or 8 μm inner diameter, was investigated using capillary electrophoresis and on-capillary capacitively coupled contactless conductivity detection (CE-CD). MLCs provided sufficiently high surface area-to-volume ratios to generate significant wall ion-exchange interactions for the divalent cations, which significantly affected resultant selectivity, whereas monovalent cations were predominantly separated by simple electrophoresis. The resultant hybrid selectivity was seen for both 4 and 8 μm channel multi-lumen capillaries, without any preconditioning or capillary wall modification.

Preconcentration by solvent removal: techniques and applications.

Preconcentration is the aspect of analytical method development covering the need to improve detection sensitivity. This review collects the advances in a diversity of approaches to achieve preconcentration by solvent removal. Evaporation in microfluidic and paper-based devices is reported in a variety of forms and later compared to membrane-assisted evaporation.

On-line solvent exchange system: Automation from extraction to analysis.

Removal of organic solvent from sample extracts is required before analysis by reversed phase HPLC to preserve chromatographic performance and allow for bigger injection volumes, boosting sensitivity. Herein, an automated on-line extraction evaporation procedure is integrated with HPLC analysis. The evaporation occurs inside a 200 μm microfluidic channel confined by a vapor permeable membrane.

Low-Cost Passive Sampling Device with Integrated Porous Membrane Produced Using Multimaterial 3D Printing.

Multimaterial 3D printing facilitates the rapid production of complex devices with integrated materials of varying properties and functionality. Herein, multimaterial fused deposition modeling (MM-FDM) 3D printing was applied to the fabrication of low-cost passive sampler devices with integrated porous membranes. Using MM-FDM 3D printing, the device body was produced using black polylactic acid, with Poro-Lay Lay-Felt filament used for the printing of the integrated porous membranes (rubber-elastomeric polymer, porous after removal of a water-soluble poly(vinyl alcohol) component).

Miniaturized micromachined gas chromatography with universal and selective detectors for targeted volatile compounds analysis.

An effective analytical strategy for targeted analysis of volatile organic compounds which combines two orthogonal separation mechanisms and multiple tunable detection in a compact transportable analytical system is introduced. This strategy uses a commercially available micromachined gas chromatograph comprising a micromachined on-board thermal conductivity detector. The chromatograph capability is enhanced by incorporating a modified diode array detector and a radio frequency modulated ion mobility spectrometry microfabricated electromechanical system.

Comparison of cation-exchange capillary columns used for ion chromatographic separation of biogenic amines.

The selectivity for 15 biogenic amines and amino acids shown by three capillary cation-exchange columns, IonPac CS19, CS12A and CS17 (250 × 0.4 mm ID, all from Thermo Fisher Scientific), exhibiting medium, medium low and ultra-low hydrophobicity, and either carboxylic or mixed carboxylic/phosphonic acid functional groups, was investigated. A mixed mode retention mechanism was revealed with ion-exchange, hydrophobic and hydrogen bonding interactions contributing to retention of polar organic molecules on these phases.

High sensitivity deep-UV LED-based z-cell photometric detector for capillary liquid chromatography.

A new high sensitivity deep-UV LED photometric detector with a z-type flow cell (45 nL or 180 nL) for miniaturised and portable capillary liquid chromatography (LC) was designed and fabricated to overcome sensitivity limitations due to short pathlength in on-capillary detectors. The new detector has a 10 mm geometric pathlength and uses high intensity light-emitting diodes (LED) as light sources in the deep-UV range (254 nm and 280 nm). No optical reference was necessary due to the low drift in the signal.