Higher Antarctic ice sheet accumulation and surface melt rates revealed at 2 km resolution.

Antarctic ice sheet (AIS) mass loss is predominantly driven by increased solid ice discharge, but its variability is governed by surface processes. Snowfall fluctuations control the surface mass balance (SMB) of the grounded AIS, while meltwater ponding can trigger ice shelf collapse potentially accelerating discharge. Surface processes are essential to quantify AIS mass change, but remain poorly represented in climate models typically running at 25-100 km resolution. Here we present SMB and surface melt products statistically downscaled to 2 km resolution for the contemporary climate (1979-2021) and low, moderate and high-end warming scenarios until 2100. We show that statistical downscaling modestly enhances contemporary SMB (3%), which is sufficient to reconcile modelled and satellite mass change. Furthermore, melt strongly increases (46%), notably near the grounding line, in better agreement with in-situ and satellite records. The melt increase persists by 2100 in all warming scenarios, revealing higher surface melt rates than previously estimated.

Measuring glacier mass changes from space-a review.

Glaciers distinct from the Greenland and Antarctic ice sheets are currently losing mass rapidly with direct and severe impacts on the habitability of some regions on Earth as glacier meltwater contributes to sea-level rise and alters regional water resources in arid regions. In this review, we present the different techniques developed during the last two decades to measure glacier mass change from space: digital elevation model (DEM) differencing from stereo-imagery and synthetic aperture radar interferometry, laser and radar altimetry and space gravimetry. We illustrate their respective strengths and weaknesses to survey the mass change of a large Arctic ice body, the Vatnajökull Ice Cap (Iceland) and for the steep glaciers of the Everest area (Himalaya). For entire regions, mass change estimates sometimes disagree when a similar technique is applied by different research groups. At global scale, these discrepancies result in mass change estimates varying by 20%-30%. Our review confirms the need for more thorough inter-comparison studies to understand the origin of these differences and to better constrain regional to global glacier mass changes and, ultimately, past and future glacier contribution to sea-level rise.

Blood microsampling technologies: Innovations and applications in 2022.

With the development of highly sensitive bioanalytical techniques, the volume of samples necessary for accurate analysis has reduced. Microsampling, the process of obtaining small amounts of blood, has thus gained popularity as it offers minimal-invasiveness, reduced logistical costs and biohazard risks while simultaneously showing increased sample stability and a potential for the decentralization of the approach and at-home self-sampling. Although the benefits of microsampling have been recognised, its adoption in clinical practice has been slow. Several microsampling technologies and devices are currently available and employed in research studies for various biomedical applications. This review provides an overview of the state-of-the-art in microsampling technology with a focus on the latest developments and advancements in the field of microsampling. Research published in the year 2022, including studies (i) developing strategies for the quantitation of analytes in microsamples and (ii) bridging and comparing the interchangeability between matrices and choice of technology for a given application, is reviewed to assess the advantages, challenges and limitations of the current state of microsampling. Successful implementation of microsampling in routine clinical care requires continued efforts for standardization and harmonization. Microsampling has been shown to facilitate data-rich studies and a patient-centric approach to healthcare and is foreseen to play a central role in the future digital revolution of healthcare through continuous monitoring to improve the quality of life.

An automated online three-phase electro-extraction setup with machine-vision process monitoring hyphenated to LC-MS analysis.

Sample preparation is a labor-intensive and time-consuming procedure, especially for the bioanalysis of small-volume samples with low-abundant analytes. To minimize losses and dilution, sample preparation should ideally be hyphenated to downstream on-line analysis such as liquid chromatography-mass spectrometry (LC-MS). In this study, an automated three-phase electro-extraction (EE) method coupled to machine vision was developed, integrated with a robotic autosampler hyphenated to LC-MS. Eight model compounds, i.e. amitriptyline, clemastine, clomipramine, haloperidol, loperamide, propranolol, oxeladin, and verapamil were utilized for the optimization and evaluation of the automated EE setup. The stability of automated EE was evaluated by monitoring the acceptor droplet size by machine vision and recording the current during EE. A Design of Experiment approach (Box-Behnken design) was utilized to optimize the critical parameters of the EE method, i.e., the ratio of formic acid in the sample to acceptor phase, extraction voltage, and extraction time. The developed quadratic models showed good fitness (p < 0.001, R2 > 0.95). Automated EE could be achieved in less than 2 min with enrichment factors (EF) up to 387 and extraction recoveries (ER) up to 97% for academic samples. Finally, the optimized EE method was successfully applied to both spiked human urine and plasma samples with low-concentration (50 ng mL-1) analytes and a low starting sample volume of 20 µL of plasma and urine in 10-fold diluted samples. The developed automated EE setup is easy to operate, provides a fast extraction method for analytes from volume-limited biological samples, and is hyphenated with on-line LC-MS analysis. Therefore, this method can provide fast and automated sample preparation to solve bottlenecks in high-throughput bioanalysis workflows.

Automated Segmented-Flow Analysis - NMR with a Novel Fluoropolymer Flow Cell for High-Throughput Screening.

High-throughput analysis in fields such as industrial biotechnology, combinatorial chemistry, and life sciences is becoming increasingly important. Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique providing exhaustive molecular information on complex samples. Flow NMR in particular is a cost- and time-efficient method for large screenings. In this study, we have developed a novel 3.0 mm inner diameter polychlorotrifluoroethylene (PCTFE) flow cell for a segmented-flow analysis (SFA) - NMR automated platform. The platform uses FC-72 fluorinated oil and fluoropolymer components to achieve a fully fluorinated flow path. Samples were repeatably transferred from 96-deepwell plates to the flow cell by displacing a fixed volume of oil, with a transfer time of 42 s. 1H spectra were acquired fully automated with 500 and 600 MHz NMR spectrometers. The spectral performance of the novel PCTFE cell was equal to that of commercial glass cells. Peak area repeatability was excellent with a relative standard deviation of 0.1-0.5% for standard samples, and carryover was below 0.2% without intermediate washing. The sample temperature was conditioned by using a thermostated transfer line in order to reduce the equilibration time in the probe and increase the throughput. Finally, analysis of urine samples demonstrated the applicability of this platform for screening complex matrices.

Development of a fast, online three-phase electroextraction hyphenated to fast liquid chromatography-mass spectrometry for analysis of trace-level acid pharmaceuticals in plasma.

Sample preparation is a challenge for high-throughput analysis, especially for volume-limited samples with low-abundant analytes. Ideally, sample preparation enriches the analytes of interest while removing the interferents to reduce the matrix effect and improve both sensitivity and quantification. In this study, a three-phase electroextraction (EE) method hyphenated to fast online liquid chromatography-mass spectrometry (LC-MS) was developed. Four model acidic drugs of relevance for drug monitoring in plasma, i.e. naproxen, fenoprofen, flurbiprofen, and ibuprofen, were utilized for the optimization and evaluation of the method. A Design of Experiment approach (Box-Behnken design) was used to optimize the critical parameters of the method, i.e., the type of organic solvent, pH of the sample and acceptor phase, and the extraction voltage and time. Good fitness (P < 0.02, R2 > 0.95) was observed for the developed quadratic model. Extraction could be achieved in less than 2 min (115 s) with enrichment factors (EF) up to 190 and extraction recoveries (ER) up to 38% for academic samples. Additionally, the optimized three-phase EE method was successfully applied to spiked plasma samples with low-abundant (50 ng mL-1) analytes and a low sample volume of 15 µL plasma in 10-fold diluted samples. Finally, two crucial contributors to the matrix effect of three-phase EE application on plasma samples were determined. Specifically, the ion-suppression effect in the MS source was reduced by the fast LC separation, and the matrix effect during extraction was negligible for the diluted protein-precipitated plasma samples. The developed three-phase EE method is easy to operate and provides fast and online extraction of trace-level acidic analytes from volume-limited biological samples. Therefore, this method can provide a potential solution for sample-preparation bottlenecks in high-throughput bioanalysis workflows.

A high-throughput, ultrafast, and online three-phase electro-extraction method for analysis of trace level pharmaceuticals.

Sample preparation is often reported as the main bottleneck of analytical processes. To meet the requirements of both high-throughput and high sensitivity, improved sample-preparation methods capable of fast analyte preconcentration are urgently needed. To this end, a new three-phase electroextraction (EE) method is presented that allows for ultrafast electroextraction hyphenated to flow-injection analysis mass spectrometry (FIA-MS). Four model compounds, i.e., propranolol, amitriptyline, bupivacaine, and oxeladin, were used to optimize and evaluate the method. Within only 30 s extraction time, enrichment factors (EF) of 105-569 and extraction recoveries (ER) of 10.2%-55.7% were achieved for these analytes, with limits of detection (LODs) ranging from 0.36 to 3.21 ng mL-1, good linear response function (R2 > 0.99), low relative standard deviation (0.6%-17.8%) and acceptable accuracy (73-112%). Finally, the optimized three-phase EE method was successfully applied to human urine and plasma samples. Our three-phase electroextraction method is simple to construct and offers ultrafast, online extraction of trace amounts of analytes from biological samples, and therefore has great potential for high-throughput analysis.

Damage accelerates ice shelf instability and mass loss in Amundsen Sea Embayment.

Pine Island Glacier and Thwaites Glacier in the Amundsen Sea Embayment are among the fastest changing outlet glaciers in West Antarctica with large consequences for global sea level. Yet, assessing how much and how fast both glaciers will weaken if these changes continue remains a major uncertainty as many of the processes that control their ice shelf weakening and grounding line retreat are not well understood. Here, we combine multisource satellite imagery with modeling to uncover the rapid development of damage areas in the shear zones of Pine Island and Thwaites ice shelves. These damage areas consist of highly crevassed areas and open fractures and are first signs that the shear zones of both ice shelves have structurally weakened over the past decade. Idealized model results reveal moreover that the damage initiates a feedback process where initial ice shelf weakening triggers the development of damage in their shear zones, which results in further speedup, shearing, and weakening, hence promoting additional damage development. This damage feedback potentially preconditions these ice shelves for disintegration and enhances grounding line retreat. The results of this study suggest that damage feedback processes are key to future ice shelf stability, grounding line retreat, and sea level contributions from Antarctica. Moreover, they underline the need for incorporating these feedback processes, which are currently not accounted for in most ice sheet models, to improve sea level rise projections.

Observing and Modeling Ice Sheet Surface Mass Balance.

Surface mass balance (SMB) provides mass input to the surface of the Antarctic and Greenland Ice Sheets and therefore comprises an important control on ice sheet mass balance and resulting contribution to global sea level change. As ice sheet SMB varies highly across multiple scales of space (meters to hundreds of kilometers) and time (hourly to decadal), it is notoriously challenging to observe and represent in models. In addition, SMB consists of multiple components, all of which depend on complex interactions between the atmosphere and the snow/ice surface, large-scale atmospheric circulation and ocean conditions, and ice sheet topography. In this review, we present the state-of-the-art knowledge and recent advances in ice sheet SMB observations and models, highlight current shortcomings, and propose future directions. Novel observational methods allow mapping SMB across larger areas, longer time periods, and/or at very high (subdaily) temporal frequency. As a recent observational breakthrough, cosmic ray counters provide direct estimates of SMB, circumventing the need for accurate snow density observations upon which many other techniques rely. Regional atmospheric climate models have drastically improved their simulation of ice sheet SMB in the last decade, thanks to the inclusion or improved representation of essential processes (e.g., clouds, blowing snow, and snow albedo), and by enhancing horizontal resolution (5-30 km). Future modeling efforts are required in improving Earth system models to match regional atmospheric climate model performance in simulating ice sheet SMB, and in reinforcing the efforts in developing statistical and dynamic downscaling to represent smaller-scale SMB processes.

Experimental and numerical study of band-broadening effects associated with analyte transfer in microfluidic devices for spatial two-dimensional liquid chromatography created by additive manufacturing.

Conventional one-dimensional column-based liquid chromatographic (LC) systems do not offer sufficient separation power for the analysis of complex mixtures. Column-based comprehensive two-dimensional liquid chromatography offers a higher separation power, yet suffers from instrumental complexity and long analysis times. Spatial two-dimensional liquid chromatography can be considered as an alternative to column-based approaches. The peak capacity of the system is ideally the product of the peak capacities of the two dimensions, yet the analysis time remains relatively short due to parallel second-dimension separations. Aspects affecting the separation efficiency of this type of systems include flow distribution to homogeneously distribute the mobile phase for the second-dimension (2D) separation, flow confinement during the first-dimension (1D) separation, and band-broadening effects during analyte transfer from the 1D separation channel to the 2D separation area. In this study, the synergy between computational fluid dynamics (CFD) simulations and rapid prototyping was exploited to address band broadening during the 2D development and analyte transfer from 1D to 2D. Microfluidic devices for spatial two-dimensional liquid chromatography were designed, simulated, 3D-printed and tested. The effects of presence and thickness of spacers in the 2D separation area were addressed and leaving these out proved to be the most efficient solution regarding band broadening reduction. The presence of a stationary-phase material in the 1D channel had a great effect on the analyte transfer from the 1D to the 2D and the resulting band broadening. Finally, pressure limit of the fabricated devices and printability are discussed.

On-line microfluidic immobilized-enzyme reactors: A new tool for characterizing synthetic polymers.

Biodegradable polymeric materials may eventually replace biostable materials for medical applications, including therapeutic devices, scaffolds for tissue engineering, and drug-delivery vehicles. To further develop such materials, a more fundamental understanding is necessary to correlate parameters including chemical-composition distribution within a macromolecular structure with the final properties of the material, including particle-size. A wide variety of analytical techniques have been applied for the characterization of polymer materials, including hyphenated techniques such as comprehensive two-dimensional liquid chromatography (LC × LC). In this context, we have investigated enzymatic degradation of polyester-based nanoparticles, both in-solution and by the use of an immobilized-enzyme reactor (IMER). We have demonstrated for the first time the implementation of such an IMER in a size-exclusion chromatography system for on-line degradation and subsequent analysis of the polymer degradation products. The effect of residence times ranging from 12 s to 4 min on polymer degradation was assessed. IMER-assisted degradation is much faster compared to in-solution degradation, which requires several hours to days, and opens the possibility to use such reactors in LC × LC modulation interfaces.

Seasonal to decadal variability in ice discharge from the Greenland Ice Sheet.

Rapid changes in thickness and velocity have been observed at many marine-terminating glaciers in Greenland, impacting the volume of ice they export, or discharge, from the ice sheet. While annual estimates of ice-sheet wide discharge have been previously derived, higher-resolution records are required to fully constrain the temporal response of these glaciers to various climatic and mechanical drivers that vary in sub-annual scales. Here we sample outlet glaciers wider than 1 km (N = 230) to derive the first continuous, ice-sheet wide record of total ice sheet discharge for the 2000-2016 period, resolving a seasonal variability of 6 %. The amplitude of seasonality varies spatially across the ice sheet from 5 % in the southeastern region to 9 % in the northwest region. We analyze seasonal to annual variability in the discharge time series with respect to both modelled meltwater runoff, obtained from RACMO2.3p2, and glacier front position changes over the same period. We find that year-to-year changes in total ice sheet discharge are related to annual front changes (r 2 = 0.59, p = 10-4) and that the annual magnitude of discharge is closely related to cumulative front position changes (r 2 = 0.79), which show a net retreat of > 400 km, or an average retreat of > 2 km at each surveyed glacier. Neither maximum seasonal runoff or annual runoff totals are correlated to annual discharge, which suggests that larger annual quantities of runoff do not relate to increased annual discharge. Discharge and runoff, however, follow similar patterns of seasonal variability with near-coincident periods of acceleration and seasonal maxima. These results suggest that changes in glacier front position drive secular trends in discharge, whereas the impact of runoff is likely limited to the summer months when observed seasonal variations are substantially controlled by the timing of meltwater input.

Nanoparticle Analysis by Online Comprehensive Two-Dimensional Liquid Chromatography combining Hydrodynamic Chromatography and Size-Exclusion Chromatography with Intermediate Sample Transformation.

Polymeric nanoparticles have become indispensable in modern society with a wide array of applications ranging from waterborne coatings to drug-carrier-delivery systems. While a large range of techniques exist to determine a multitude of properties of these particles, relating physicochemical properties of the particle to the chemical structure of the intrinsic polymers is still challenging. A novel, highly orthogonal separation system based on comprehensive two-dimensional liquid chromatography (LC × LC) has been developed. The system combines hydrodynamic chromatography (HDC) in the first-dimension to separate the particles based on their size, with ultrahigh-performance size-exclusion chromatography (SEC) in the second dimension to separate the constituting polymer molecules according to their hydrodynamic radius for each of 80 to 100 separated fractions. A chip-based mixer is incorporated to transform the sample by dissolving the separated nanoparticles from the first-dimension online in tetrahydrofuran. The polymer bands are then focused using stationary-phase-assisted modulation to enhance sensitivity, and the water from the first-dimension eluent is largely eliminated to allow interaction-free SEC. Using the developed system, the combined two-dimensional distribution of the particle-size and the molecular-size of a mixture of various polystyrene (PS) and polyacrylate (PACR) nanoparticles has been obtained within 60 min.

Prototyping of thermoplastic microfluidic chips and their application in high-performance liquid chromatography separations of small molecules.

The present paper discusses practical aspects of prototyping of microfluidic chips using cyclic olefin copolymer as substrate and the application in high-performance liquid chromatography. The developed chips feature a 60mm long straight separation channel with circular cross section (500µm i.d.) that was created using a micromilling robot. To irreversibly seal the top and bottom chip substrates, a solvent-vapor-assisted bonding approach was optimized, allowing to approximate the ideal circular channel geometry. Four different approaches to establish the micro-to-macro interface were pursued. The average burst pressure of the microfluidic chips in combination with an encasing holder was established at 38MPa and the maximum burst pressure was 47MPa, which is believed to be the highest ever report for these polymer-based microfluidic chips. Porous polymer monolithic frits were synthesized in-situ via UV-initiated polymerization and their locations were spatially controlled by the application of a photomask. Next, high-pressure slurry packing was performed to introduce 3µm silica reversed-phase particles as the stationary phase in the separation channel. Finally, the application of the chip technology is demonstrated for the separation of alkyl phenones in gradient mode yielding baseline peak widths of 6s by applying a steep gradient of 1.8min at a flow rate of 10µL/min.

A cyclic-olefin-copolymer microfluidic immobilized-enzyme reactor for rapid digestion of proteins from dried blood spots.

A critical step in the bottom-up characterization of proteomes is the conversion of proteins to peptides, by means of endoprotease digestion. Nowadays this method typically uses overnight digestion and as such represents a considerable bottleneck for high-throughput analysis. This report describes protein digestion using an immobilized-enzyme reactor (IMER), which enables accelerated digestion times that are completed within seconds to minutes. For rapid digestion to occur, a cyclic-olefin-copolymer microfluidic reactor was constructed containing trypsin immobilized on a polymer monolithic material through a 2-vinyl-4,4-dimethylazlactone linker. The IMER was applied for the rapid offline digestion of both singular protein standards and a complex protein mixture prior to liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) analysis. The effects of protein concentration and residence time in the IMER were assessed for protein standards of varying molecular weight between 11 and 240kDa. Compared to traditional in-solution digestion, IMER-facilitated protein digestion at room temperature for 5min yielded similar results in terms of sequence coverage and number of identified peptides. Good repeatability was demonstrated with a relative standard deviation of 6% for protein-sequence coverage. The potential of the IMER was also demonstrated for a complex protein mixture in the analysis of dried blood spots. Compared to a traditional workflow a similar number of proteins could be identified, while reducing the total analysis time from 22.5h to 4h and importantly omitting the sample-pre-treatment steps (denaturation, reduction, and alkylation). The identified proteins from two workflows showed similar distributions in terms of molecular weight and hydrophobic character.

Geodetic measurements reveal similarities between post-Last Glacial Maximum and present-day mass loss from the Greenland ice sheet.

Accurate quantification of the millennial-scale mass balance of the Greenland ice sheet (GrIS) and its contribution to global sea-level rise remain challenging because of sparse in situ observations in key regions. Glacial isostatic adjustment (GIA) is the ongoing response of the solid Earth to ice and ocean load changes occurring since the Last Glacial Maximum (LGM; ~21 thousand years ago) and may be used to constrain the GrIS deglaciation history. We use data from the Greenland Global Positioning System network to directly measure GIA and estimate basin-wide mass changes since the LGM. Unpredicted, large GIA uplift rates of +12 mm/year are found in southeast Greenland. These rates are due to low upper mantle viscosity in the region, from when Greenland passed over the Iceland hot spot about 40 million years ago. This region of concentrated soft rheology has a profound influence on reconstructing the deglaciation history of Greenland. We reevaluate the evolution of the GrIS since LGM and obtain a loss of 1.5-m sea-level equivalent from the northwest and southeast. These same sectors are dominating modern mass loss. We suggest that the present destabilization of these marine-based sectors may increase sea level for centuries to come. Our new deglaciation history and GIA uplift estimates suggest that studies that use the Gravity Recovery and Climate Experiment satellite mission to infer present-day changes in the GrIS may have erroneously corrected for GIA and underestimated the mass loss by about 20 gigatons/year.

Spatial and temporal Antarctic Ice Sheet mass trends, glacio-isostatic adjustment, and surface processes from a joint inversion of satellite altimeter, gravity, and GPS data.

We present spatiotemporal mass balance trends for the Antarctic Ice Sheet from a statistical inversion of satellite altimetry, gravimetry, and elastic-corrected GPS data for the period 2003-2013. Our method simultaneously determines annual trends in ice dynamics, surface mass balance anomalies, and a time-invariant solution for glacio-isostatic adjustment while remaining largely independent of forward models. We establish that over the period 2003-2013, Antarctica has been losing mass at a rate of -84 ± 22 Gt yr-1, with a sustained negative mean trend of dynamic imbalance of -111 ± 13 Gt yr-1. West Antarctica is the largest contributor with -112 ± 10 Gt yr-1, mainly triggered by high thinning rates of glaciers draining into the Amundsen Sea Embayment. The Antarctic Peninsula has experienced a dramatic increase in mass loss in the last decade, with a mean rate of -28 ± 7 Gt yr-1 and significantly higher values for the most recent years following the destabilization of the Southern Antarctic Peninsula around 2010. The total mass loss is partly compensated by a significant mass gain of 56 ± 18 Gt yr-1 in East Antarctica due to a positive trend of surface mass balance anomalies.

Towards ultra-high peak capacities and peak-production rates using spatial three-dimensional liquid chromatography.

In order to successfully tackle the truly complex separation problems arising from areas such as proteomics research, the development of ultra-efficient and fast separation technology is required. In spatial three-dimensional chromatography, components are separated in the space domain with each peak being characterized by its coordinates in a three-dimensional separation body. Spatial three-dimensional (3D-)LC has the potential to offer unprecedented resolving power when orthogonal retention mechanisms are applied, since the total peak capacity is the product of the three individual peak capacities. Due to parallel developments during the second- and third-dimension separations, the analysis time is greatly reduced compared to a coupled-column multi-dimensional LC approach. This communication discusses the different design aspects to create a microfluidic chip for spatial 3D-LC. The use of physical barriers to confine the flow between the individual developments, and flow control by the use of (2)D and (3)D flow distributors is discussed. Furthermore, the in situ synthesis of monolithic stationary phases is demonstrated. Finally, the potential performance of a spatial 3D-LC systems is compared with the performance obtained with state-of-the-art 1D-LC and (coupled-column) 2D-LC approaches via a Pareto-optimization approach. The proposed microfluidic device for 3D-LC featuring 16 (2)D channels and 256 (3)D channels can potentially yield a peak capacity of 8000 in a total analysis time of 10 minutes.

Design of a microfluidic device for comprehensive spatial two-dimensional liquid chromatography.

This study discusses the design aspects for the construction of a microfluidic device for comprehensive spatial two-dimensional liquid chromatography. In spatial two-dimensional liquid chromatography each peak is characterized by its coordinates in the plane. After completing the first-dimension separation all fractions are analyzed in parallel second-dimension separations. Hence, spatial two-dimensional liquid chromatography potentially provides much higher peak-production rates than a coupled column multi-dimensional liquid chromatography approach in which the second-dimension analyses are performed sequentially. A chip for spatial two-dimensional liquid chromatography has been manufactured from cyclic olefin copolymer and features a first-dimension separation channel and 21 parallel second-dimension separation channels oriented perpendicularly to the former. Compartmentalization of first- and second-dimension developments by physical barriers allowed for a preferential flow path with a minimal dispersion into the second-dimension separation channels. To generate a homogenous flow across all the parallel second-dimension channels, a radially interconnected flow distributor containing two zones of diamond-shaped pillars was integrated on-chip. A methacrylate ester based monolithic stationary phase with optimized macroporous structure was created in situ in the confines of the microfluidic chip. In addition, the use of a photomask was explored to localize monolith formation in the parallel second-dimension channels. Finally, to connect the spatial chip to the liquid chromatography instrument, connector ports were integrated allowing the use of Viper fittings. As an alternative, a chip holder with adjustable clasp locks was designed that allows the clamping force to be adjusted.

Using contemporary liquid chromatography theory and technology to improve capillary gradient ion-exchange separations.

The gradient-performance limits of capillary ion chromatography have been assessed at maximum system pressure (34.5 MPa) using capillary columns packed with 4.1 µm macroporous anion-exchange particles coated with 65 nm positively-charged nanobeads. In analogy to the van-Deemter curve, the gradient performance was assessed applying different flow rates, while decreasing the gradient time inversely proportional to the increase in flow rate in order to maintain the same retention properties. The gradient kinetic-performance limits were determined at maximum system pressure, applying tG/t0=5, 10, and 20. In addition, the effect of retention on peak width was assessed in gradient mode for mono-, di-, and trivalent inorganic anions. The peak width of late-eluting ions can be significantly reduced by using concave gradient, resulting in better detection sensitivity. A signal enhancement factor of 8 was measured for a late-eluting ion when applying a concave instead of a linear gradient. For the analysis of a complex anion mixture, a coupled column with a total length of 1.05 m was operated at the kinetic-performance limit applying a linear 250 min gradient (tG/t0=10). The peak capacity varied between 200 and 380 depending on analyte retention, and hence on charge and size of the ion.