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Practical benefits of graphene-cellulose composites (GCC) are categorical. Diverse salient features like thermal and electrical conductivity, mechanical strength, and durability make GCC advantageous for widespread applications. Despite extensive studies the basic understanding of various fundamental aspects of this novel complex remains deficient. Based on this fact, a critical overview and bibliometric analysis involving the overall prospects of GCC was made wherein a total of 1245 research articles from the Scopus database published during the year 2002 to 2020 were used. For the bibliometric assessment, various criteria including the publication outputs, co-authorships, affiliated countries, and co-occurrences of the authors' keywords were explored. Environmental amiability, sustainability, economy, and energy efficiency of GCC were emphasized. In addition, the recent trends, upcoming challenges, and applied interests of GCC were highlighted. The findings revealed that the studies on GCC related to the energy storage, adsorption, sensing, and printing are ever-increasing, indicating the global research drifts on GCC. The bibliometric map analysis displayed that among the researchers from 61 countries/territories, China alone contributed about 50 % of the international publications. It is asserted that the current article may offer taxonomy to navigate into the field of GCC wherein stronger collaboration networks can be established worldwide through integrated research activities desirable for sustainable development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sample clean-up and pre-concentration are critical components of pharmaceutical analysis. The dispersive liquid-liquid microextraction (DLLME) technique is widely recognized as the most effective approach for enhancing overall detection sensitivity. While various DLLME modes have been advanced in pharmaceutical analysis, there need to be more discussions on pre-concentration techniques specifically developed for this field. This review presents a comprehensive overview of the different DLLME modes used in pharmaceutical analysis from 2017 to May 2023. The review covers the principles of DLLME, the factors affecting microextraction, the selected applications of different DLLME modes, and their advantages and disadvantages. Additionally, it focuses on multi-extraction strategies employed for pharmaceutical analysis.

Microplastic fibers from textiles have been known to significantly contribute to marine microplastic pollution. However, little is known about the microfiber formation and discharge during textile production. In this study, we have quantified microfiber emissions from one large and representative textile factory during different stages, spanning seven different materials, including cotton, polyester, and blended fabrics, to further guide control strategies. Wet-processing steps released up to 25 times more microfibers than home laundering, with dyeing contributing to 95.0% of the total emissions. Microfiber release could be reduced by using white coloring, a lower dyeing temperature, and a shorter dyeing duration. Thinner, denser yarns increased microfiber pollution, whereas using tightly twisted fibers mitigated release. Globally, wet textile processing potentially produced 6.4 kt of microfibers in 2020, with China, India, and the US as significant contributors. The study underlined the environmental impact of textile production and the need for mitigation strategies, particularly in dyeing processes and fiber choice. In addition, no significant difference was observed between the virgin polyesters and the used ones. Replacing virgin fibers with recycled fibers in polyester fabrics, due to their increasing consumption, might offer another potential solution. The findings highlighted the substantial impact of textile production on microfiber released into the environment, and optimization of material selection, knitting technologies, production processing, and recycled materials could be effective mitigation strategies.

A polymer inclusion membrane (PIM) based sampling probe was developed for electrokinetic extraction of drugs from biological fluids. The probe was fabricated by dip-coating a nonconductive glass capillary tube in a homogeneous PIM solution for three cycles. The PIM solution comprised cellulose triacetate (CTA), 2-nitrophenyl octyl ether (NPOE), and 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [EMIM][NTf 2 ] in a ratio of 5:4:2. The developed probe electrokinetically extracted doxorubicin from human plasma, human serum, and dried blood spot (DBS). The practicability and reliability of the electrokinetic extraction were evaluated by LC-MS/MS to quantify the desorption of extracted doxorubicin. Under the optimized conditions, a quantification limit of 0.2-2 ng/mL was achieved for the three biological samples. The probe was further integrated into a portable battery-powered device for safe low-voltage (36 V) electrokinetic extraction. The developed technique is envisioned to provide a more efficient analytical workflow in the laboratory.

A new dispersive inclusion complex microextraction (DICM) approach coupled with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for the determination of n-nitrosamine impurities in different medicinal products is demonstrated for the first time. The proposed DICM procedures consist of a dispersive liquid phase microextraction steps employing cyclodextrin as an inclusion complex agent to extract n-nitrosamines namely N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodiisopropylamine (NDIPA), N-ethyl-N-nitrosoisopropylamine (NEIPA) and N-nitroso-di-n-butylamine (NDBA) present in the medicinal products. The sample solutions were prepared by mixing 5% (m/v) NaCl solution with 1.5 mM β-cyclodextrin and 20 mM sodium dodecyl sulphate to form a stable inclusion complex and subsequently extracted into dichloromethane as an extraction solvent. The enriched solution was reconstituted into aqueous solution prior to UPLC-MS/MS analysis. The method showed good linearity in the range of 0.036-1 ng/mL with a correlation coefficient of at least 0.995, acceptable reproducibility (RSD 0.5-5.8%, n=5), low limits of detection (0.011-0.018 ng/mL), and satisfactory relative recoveries (96-105%). The results obtained were found to be at least 10-fold more sensitive comparable to those obtained using validated direct sample dissolutions coupled with UPLC-MS/MS approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Drug-drug cocrystalllization is a novel mechanism for effective pharmacological combination therapy. In this work, we have demonstrated the preparation of a drug-drug cocrystal of a hypertension drug (Telmisartan; TEL) with a hyperuricemia drug (Febuxostat; FEB) in 1:1 molar ratio using a solvent evaporation method for the first time. Generally, a multi-component system may yield either a eutectic, salt, and/or a cocrystal. This study adopted a methodical orthogonal framework to analyze the final solid form. A single crystal X-ray structural investigation revealed the formation of a heterosynthon with carboxylic and benzimidazole groups of FEB and TEL, respectively, in the triclinic P-1 space group. ΔpKa of the heterosynthon is ∼1.5, hence, based on the empirical rules, a salt-cocrystal continuum is hypothesized. Further, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and Raman spectroscopy were employed to corroborate the hydrogen bond formation in the heterosynthon (-N---H-O-), which confirmed the propensity for cocrystal formation. An accelerated stability study and an in vitro biorelevant dissolution study of the cocrystal were performed, which demonstrated that it is physiochemically stable, but it resulted in a slower dissolution rate when compared with plain drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Stretchable electronics have advanced rapidly and many applications require high repeatability and robustness under various mechanical deformations. It has been described here that how a highly stretchable and reliable conductor composite made from helical copper wires and a soft elastomer, named eHelix, can provide mechanically robust and strain-insensitive electronic conductivity for wearable devices. The reversibility of the mechanical behavior of the metal-elastomer system has been studied using finite element modeling methods. Optimal design parameters of such helical metal-elastomer structures are found. The scaling of multiple copper wires into such helical shapes to form a Multi-eHelix system is further shown. With the same elastomer volume, Multi-eHelix has more conductive paths and a higher current density than the single-eHelix. Integrations of these eHelix stretchable conductors with fabrics showed wearable displays that can survive machine-washes and hundreds of mechanical loading cycles. The integration of the eHelix developed by us with a wearable optical heart rate sensor enabled a wearable health monitoring system that can display measured heart rates on clothing. Furthermore, Multi-eHelix conductors are used to connect flexible printed circuit boards and piezoresistive sensors on a tactile sensing glove for the emerging sensorized prosthetics., (© 2021 Wiley-VCH GmbH.)

One of the major drawbacks of electrophoresis in both capillary and microchip is the unsatisfactory sensitivity. Online sample preconcentration techniques can be regarded as the most common and powerful approaches commonly applied to enhance overall detection sensitivity. While the advances of various online preconcentration strategies in capillary and microchip employing aqueous background electrolytes are well-reviewed, there has been limited discussion of the feasible preconcentration techniques specifically developed for capillary and microchip using nonaqueous background electrolytes. This review provides the first consolidated overview of various online preconcentration techniques in nonaqueous capillary and microchip electrophoresis, covering the period of the last two decades. It covers developments in the field of sample stacking, isotachophoresis, and micellar-based stacking. Attention is also given to multi-stacking strategies that have been used for nonaqueous electrophoresis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Conventional sampling of biological fluids often involves a bulk quantity of samples that are tedious to collect, deliver and process. Miniaturized sampling approaches have emerged as promising tools for sample collection due to numerous advantages such as minute sample size, patient friendliness and ease of shipment. This article reviews the applications and advances of microsampling techniques in therapeutic drug monitoring (TDM), covering the period January 2015 - August 2020. As whole blood is the gold standard sampling matrix for TDM, this article comprehensively highlights the most historical microsampling technique, the dried blood spot (DBS), and its development. Advanced developments of DBS, ranging from various automation DBS, paper spray mass spectrometry (PS-MS), 3D dried blood spheroids and volumetric absorptive paper disc (VAPD) and mini-disc (VAPDmini) are discussed. The volumetric absorptive microsampling (VAMS) approach, which overcomes the hematocrit effect associated with the DBS sample, has been employed in recent TDM. The sample collection and sample preparation details in DBS and VAMS are outlined and summarized. This review also delineates the involvement of other biological fluids (plasma, urine, breast milk and saliva) and their miniaturized dried matrix forms in TDM. Specific features and challenges of each microsampling technique are identified and comparison studies are reviewed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Human skin is a self-healing mechanosensory system that detects various mechanical contact forces efficiently through three-dimensional innervations. Here, we propose a biomimetic artificially innervated foam by embedding three-dimensional electrodes within a new low-modulus self-healing foam material. The foam material is synthesized from a one-step self-foaming process. By tuning the concentration of conductive metal particles in the foam at near-percolation, we demonstrate that it can operate as a piezo-impedance sensor in both piezoresistive and piezocapacitive sensing modes without the need for an encapsulation layer. The sensor is sensitive to an object's contact force directions as well as to human proximity. Moreover, the foam material self-heals autonomously with immediate function restoration despite mechanical damage. It further recovers from mechanical bifurcations with gentle heating (70 °C). We anticipate that this material will be useful as damage robust human-machine interfaces.

Electronic skins are essential for real-time health monitoring and tactile perception in robots. Although the use of soft elastomers and microstructures have improved the sensitivity and pressure-sensing range of tactile sensors, the intrinsic viscoelasticity of soft polymeric materials remains a long-standing challenge resulting in cyclic hysteresis. This causes sensor data variations between contact events that negatively impact the accuracy and reliability. Here, we introduce the Tactile Resistive Annularly Cracked E-Skin (TRACE) sensor to address the inherent trade-off between sensitivity and hysteresis in tactile sensors when using soft materials. We discovered that piezoresistive sensors made using an array of three-dimensional (3D) metallic annular cracks on polymeric microstructures possess high sensitivities (> 10 7 Ω ⋅ kPa -1 ), low hysteresis (2.99 ± 1.37%) over a wide pressure range (0-20 kPa), and fast response (400 Hz). We demonstrate that TRACE sensors can accurately detect and measure the pulse wave velocity (PWV) when skin mounted. Moreover, we show that these tactile sensors when arrayed enabled fast reliable one-touch surface texture classification with neuromorphic encoding and deep learning algorithms., Competing Interests: The authors declare no competing interest.

The human sense of touch is essential for dexterous tool usage, spatial awareness, and social communication. Equipping intelligent human-like androids and prosthetics with electronic skins-a large array of sensors spatially distributed and capable of rapid somatosensory perception-will enable them to work collaboratively and naturally with humans to manipulate objects in unstructured living environments. Previously reported tactile-sensitive electronic skins largely transmit the tactile information from sensors serially, resulting in readout latency bottlenecks and complex wiring as the number of sensors increases. Here, we introduce the Asynchronously Coded Electronic Skin (ACES)-a neuromimetic architecture that enables simultaneous transmission of thermotactile information while maintaining exceptionally low readout latencies, even with array sizes beyond 10,000 sensors. We demonstrate prototype arrays of up to 240 artificial mechanoreceptors that transmitted events asynchronously at a constant latency of 1 ms while maintaining an ultra-high temporal precision of <60 ns, thus resolving fine spatiotemporal features necessary for rapid tactile perception. Our platform requires only a single electrical conductor for signal propagation, realizing sensor arrays that are dynamically reconfigurable and robust to damage. We anticipate that the ACES platform can be integrated with a wide range of skin-like sensors for artificial intelligence (AI)-enhanced autonomous robots, neuroprosthetics, and neuromorphic computing hardware for dexterous object manipulation and somatosensory perception., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

An electrokinetic platform was developed for extracting small-molecule pharmaceuticals from a dried blood spot. Through the exclusion of liquid reagents and use of low field strength (6 V cm -1 ), the electroextraction of a drug from a dried blood spot, deposited on a polymer inclusion membrane (PIM), could be realised while in transit in the mail. In transit sample preparation provides a potential solution to in situ sample degradation and may accelerate the workflow upon arrival of a patient sample at the analytical facility. The electroextraction method was enabled through our discovery of the use of 15-20 μm thin PIMs as electrophoretic separation medium in absence of liquid reagents. Here, a PIM consisting of cellulose triacetate as polymer base, 2-nitrophenyl octyl ether as plasticizer and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide as carrier was used. The PIM, was packaged with two 12 V batteries to supply the separation voltage. A blood spot containing berberine chloride was deposited and dried before the applying the separation potential, allowing for the electroextraction while the packaged device was shipped in internal mail. Upon arrival in the analytical laboratory, the PIM was analysed using a fluorescence microscope with photon multiplier tube, quantifying the berberine extracted away from the sample matrix. This platform represents a new opportunity for processing clinical samples during transport to the laboratory, saving time and manual handling to accelerate the time to result., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new multi-stacking pre-concentration procedure based on field-enhanced sample injection (FESI), field-amplified sample stacking, and transient isotachophoresis was developed and implemented in a compact microchip electrophoresis (MCE) with a double T-junction glass chip, coupled with an on-chip capacitively coupled contactless conductivity detection (C 4 D) system. A mixture of the cationic target analyte and the terminating electrolyte (TE) from the two sample reservoirs was injected under FESI conditions within the two sample-loading channels. At the double T-junction, the stacked analyte zones were further concentrated under field-amplified stacking conditions and then subsequently focused by transient-isotachophoresis and separated along the separation channels. The proposed multi-stacking strategy was verified under a Universal Serial Bus (USB) fluorescence microscope employing Rhodamine 6G as the model analyte. This developed approach was subsequently used to monitor the target quinine present in human plasma samples. The total analysis time for quinine was approximately 200 s with a sensitivity enhancement factor of approximately 61 when compared to the typical gated injection. The detection and quantification limits of the developed approach for quinine were 3.0 μg/mL and 10 μg/mL, respectively, with intraday and interday repeatability (%RSDs, n = 5) of 3.6 and 4.4%. Recoveries in spiked human plasma were 98.1-99.8%., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

One of the most cited limitations of capillary and microchip electrophoresis is the poor sensitivity. This review continues to update this series of biannual reviews, first published in Electrophoresis in 2007, on developments in the field of online/in-line concentration methods in capillaries and microchips, covering the period July 2016-June 2018. It includes developments in the field of stacking, covering all methods from field-amplified sample stacking and large-volume sample stacking, through to isotachophoresis, dynamic pH junction, and sweeping. Attention is also given to online or in-line extraction methods that have been used for electrophoresis., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This work presents the simple and rapid fabrication of a polymer-based microfluidic prototype manufactured by rolling up thin films of polymer. The thin films were fabricated via a casting method and rolled up around a center core with the aid of plasma activation to create a three-dimensional (3D) spiral microchannel, hence reducing the time and cost of manufacture. In this work, rolled-up devices with single or dual fluidic networks fabricated from a single or two films were demonstrated for heat sink or heat exchanger applications, respectively. The experimental results show good heat transfer in the rolled-up system at various flow rates for both heat sink and heat exchanger devices, without any leakages. The rolled-up microfluidic system creates multiple curved channels, allowing for the generation of Dean vortices, which in turn lead to an enhancement of heat and mass transfer and prevention of fouling formation. These benefits enable the devices to be employed for many diverse applications, such as heat-transfer devices, micromixers, and sorters. To our knowledge, this work would be the first report on a microfluidic prototype of 3D spiral microchannel made from rolled-up polymeric thin film. This novel fabrication approach may represent the first step towards the development of a pioneering prototype for roll-to-roll processing, permitting the mass production of polymer-based microchannels from single or multiple thin films.

A sample pre-treatment method based on a dynamic mixed matrix membrane tip extraction followed by capillary electrophoresis with contactless conductivity detection (CE-C 4 D) was evaluated for the determination of tobramycin in human plasma. The extraction tip device consisted of a cellulose triacetate membrane tip wall immobilised with 15% (w/w) of hydrophilic lipophilic balance (HLB) nanoparticles as adsorbent. The extraction was performed dynamically by withdrawing/dispensing the plasma sample through the tip device followed by desorption into 20 μL of acidified aqueous solution at pH 3 prior to the CE-C 4 D analysis. Under the optimum conditions, the detection limit of the method for tobramycin was 10 ng/mL, with intraday and interday repeatability RSDs of 3.5% and 4.5%, respectively. Relative recoveries in spiked human plasma were 99.6%-99.9%. The developed approach was successfully demonstrated for the quantification of tobramycin in human plasma samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A method for on-line matrix elimination to enable selective quantification of ultraviolet absorbing analytes by a flow-injection analysis procedure is described. Selectivity is achieved by electric field driven extraction across a polymer inclusion membrane. The method was demonstrated on the example of the determination of naproxen from spiked human urine. Membranes of 10 μm thickness were employed which consisted of 7.5 mg cellulose triacetate as base polymer, 5 mg of o -nitrophenyl octyl ether as plasticizer and 7.5 mg of Aliquat 336 as cationic carrier. Ten μL of sample was introduced into a continuous stream of background solution consisting of 100 µM aqueous NaClO₄ with a flow rate of 2 μL/min while applying a voltage of 150 V to the extraction cell. The target ion was electrokinetically transported across the membrane and enriched in 1.5 μL of a stagnant acceptor solution. This was subsequently pumped past a flow-through UV detector for quantification. The method showed a linear range from 5 to 200 µM with a correlation coefficient of 0.9978 and a reproducibility of typically 7% ( n = 8). The detection limit of the method for naproxen was 2 µM., Competing Interests: The authors declare no conflict of interest.

Mechanical properties of the extracellular matrix (ECM) have been observed to influence the behavior of cells. Investigations on such an influence commonly rely on using soluble cues to alter the global intrinsic ECM properties in order to study the subsequent response of cells. This article presents an electromagnetic system for inducing a localized force gradient in an ECM, and reports the experimentally observed effect of such a force gradient on in vitro angiogenic sprouting of human microvascular endothelial cells (HMVECs). This force gradient is realized through the induction of magnetic forces on the superparamagnetic microparticle-embedded ECM ( sECM). Both analytical and statistically meaningful experimental results demonstrate the effectiveness of this approach in influencing the behavior of a targeted HMVEC sprout without affecting that of other sprouts nearby. These results suggest the possibility of selectively controlling the in vitro behavior of cells by the induction of a localized force gradient in the ECM.

Point-of-collection (POC) devices aim for a fast, on-site detection for medical and environmental purposes. In this area, microfluidic Paper-based Analytical Devices (μPADs) have recently gained popularity because these are potentially cheap and environmentally friendly to produce, and easy to use. From an analytical perspective, paper is well known for its use as a substrate for chromatography, but less known for its use in electrophoretic separations. With the recent interest in μPADs, most applications are based on rather simple assays with relatively few applications incorporating an analytical separation. The focus of this review is on paper-based electrophoresis, originating with the key developments in the 1940s and 1950s as well as the recent developments of electrophoretic μPADs, and concluding with a critical discussion of the opportunities and challenges for electrophoretic μPADS in the future., (Copyright © 2017. Published by Elsevier B.V.)

A new electric-field driven extraction approach based on the integration of a bubbleless electrode into the electromembrane extraction (EME) across hollow polymer inclusion membranes (HPIMs) was demonstrated for the first time. The bubbleless electrode was prepared based on an in-situ synthesised polyacrylamide within a fused silica capillary. The electrode functions as a salt bridge, which conducts the electrical current between the acceptor phase in the lumen of the HPIM and the acceptor solution in the reservoir connected to a high voltage supply through a platinum electrode. Two types of HPIMs were employed, which consisted of desired proportions of cellulose acetate as base polymer, tris(2-ethylhexyl)phosphate as plasticizer, and di-(2-ethylhexyl)phosphoric acid as anionic carrier or Aliquat 336 as cationic carrier, respectively. The EME strategy was evaluated for the simultaneous determination of cationic quaternary ammonium and anionic chlorophenoxy acetic acid herbicides present in the river water, respectively. The analysis was carried out using capillary electrophoresis coupled with UV and contactless conductivity detection. Under the optimised conditions, enrichment factors in the range of 152-185-fold were obtained from 4mL of river water sample with a 20min extraction time and an applied voltage of 3000V. The proposed method provided good linearity with correlation coefficients ranging from 0.9982 to 0.9997 over a concentration range of 1-1000μg/L. The detection limits of the method for the herbicides were in the range of 0.3-0.4μg/L, with relative standard deviations of between 4.8% and 8.5%. The relative recoveries obtained when analysing the spiked river water ranged from 99.1% to 100%. A comparison was also made between the newly developed approach with the conventional EME setup by placing the platinum electrode directly in the lumen of the HPIMs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A portable microchip electrophoresis (MCE) coupled with on-chip contactless conductivity detection (C 4 D) system was evaluated for the determination of vancomycin in human plasma. In order to enhance the detection sensitivity, a new online multi-stacking preconcentration technique based on field-enhanced sample injection (FESI) and micelle-to-solvent stacking (MSS) was developed and implemented in MCE-C 4 D system equipped with a commercially available double T-junction glass chip. The cationic analytes from the two sample reservoirs were injected under FESI conditions and subsequently focused by MSS within the sample-loading channel. The proposed multi-stacking strategy was verified under a fluorescence microscope using Rhodamine 6G as the model analyte and a sensitivity enhancement factor (SEF) of up to 217 was achieved. The developed approach was subsequently implemented in the aqueous-based MCE, coupled to C 4 D in order to monitor the targeted antibiotic (in this case, vancomycin) present in human plasma samples. The multi-stacking and analysis time for vancomycin were 50s and 250s respectively, with SEF of approximately 83 when compared to typical gated injection. The detection limit of the method for vancomycin was 1.2μg/mL, with intraday and interday repeatability RSDs of 2.6% and 4.3%, respectively. Recoveries in spiked human plasma were 99.0%-99.2%., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A new approach based on the integration of the free liquid membrane (FLM) into electrokinetic supercharging (EKS) was demonstrated to be a new powerful tool used in order to enhance online preconcentration efficiency in capillary electrophoresis (CE). A small plug of water immiscible organic solvent was used as a membrane interface during the electrokinetic sample injection step in EKS in order to significantly enhance the analyte stacking efficiency. The new online preconcentration strategy was evaluated for the determination of paraquat and diquat present in the environmental water samples. The optimised FLM-EKS conditions employed were as follows: hydrodynamic injection (HI) of 20mM potassium chloride as leading electrolyte at 50mbar for 75s (3% of the total capillary volume) followed by the HI of tris(2-ethylhexyl) phosphate (TEHP) as FLM at a 1mm length (0.1% of the capillary volume). The sample was injected at 10kV for 360s, followed by the HI of 20mM cetyl trimethylammonium bromide (CTAB) as terminating electrolyte at 50mbar for 50s (2% of the total capillary volume). The separation was performed in 12mM ammonium acetate and 30mM NaCl containing 20% MeOH at +25kV with UV detection at 205nm. Under optimised conditions, the sensitivity was enhanced between 1500- and 1866-fold when compared with the typical HI at 50mbar for 50s. The detection limit of the method for paraquat and diquat was 0.15-0.20ng/mL, with RSDs below 5.5%. Relative recoveries in spiked river water were in the range of 95.4-97.5%. A comparison was also made between the proposed approach with sole preconcentration of the field-enhanced sample injection (FASI) and EKS in the absence of the FLM., (Copyright © 2016 Elsevier B.V. All rights reserved.)

One of the most cited limitations of capillary (and microchip) electrophoresis is the poor sensitivity. This review continues to update this series of biennial reviews, first published in Electrophoresis in 2007, on developments in the field of on-line/in-line concentration methods in capillaries and microchips, covering the period July 2014-June 2016. It includes developments in the field of stacking, covering all methods from field amplified sample stacking and large volume sample stacking, through to isotachophoresis, dynamic pH junction, and sweeping. Attention is also given to on-line or in-line extraction methods that have been used for electrophoresis., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The low conductivity of separation electrolytes employed in nonaqueous capillary electrophoresis (NACE) limits the use of on-line sample concentration or stacking by field enhancement. Herein, micelle-to-solvent stacking (MSS) was performed by the simple injection of a micellar solution plug prior to electrokinetic injection of sample prepared under field-enhanced stacking conditions (known as field-enhanced sample injection, FESI). The proposed approach allowed a 214-625-fold improvement in peak signals for targeted anticancer drugs (e.g., tamoxifen) and its major metabolites in NACE using 100% methanol-based separation electrolyte that comprised of 7.5mM deoxycholic acid sodium salt, 15mM acetic acid and 1mM 18-crown-6. These improvements yielded tamoxifen and its metabolites with 2-5 times better stacking efficiency as compared to those obtained without micellar solution injection or FESI only. This is comparable to the results typically achieved when FESI is combined with isotachophoresis (electrokinetic supercharging). The FESI-MSS-NACE was tested for the measuring levels of target drugs in plasma. The analytical figures of merit are also reported., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The translation of stacking techniques used in capillary electrophoresis (CE) to microchip CE (MCE) in order to improve concentration sensitivity is an important area of study. The success in stacking relies on the generation and control of the stacking boundaries which is a challenge in MCE because the manipulation of solutions is not as straightforward as in CE with a single channel. Here, a simple and rapid online sample concentration (stacking strategy) in a battery operated nonaqueous MCE device with a commercially available double T-junction glass chip is presented. A multistacking approach was developed in order to circumvent the issues for stacking in nonaqueous MCE. The cationic analytes from the two loading channels were injected under field-enhanced conditions and were focused by micelle-to-solvent stacking. This was achieved by the application of high electric fields along the two loading channels and a low electric field in the separation channel, with one ground electrode in the reservoir closest to the junction. At the junction, the stacked zones were restacked under field-enhanced conditions and then injected into the separation channels. The multistacking was verified under a fluorescence microscope using Rhodamine 6G as the analyte, revealing a sensitivity enhancement factor (SEF) of 110. The stacking approach was also implemented in the nonaqueous MCE with contactless conductivity detection of the anticancer drug tamoxifen as well as its metabolites. The multistacking and analysis time was 40 and 110 s, respectively, the limit of detections was from 10 to 35 ng/mL and the SEFs were 20 to 50. The method was able to quantify the target analytes from breast cancer patients.

An online preconcentration method, namely electrokinetic supercharging (EKS), was evaluated for the determination of tamoxifen and its metabolites in human plasma in nonaqueous capillary electrophoresis with ultraviolet detection (NACE-UV). This method was comprehensively optimized in terms of the leading electrolyte (LE) and terminating electrolyte (TE) injection lengths, as well as electrokinetic sample injection time. The optimized EKS conditions employed were as follows: hydrodynamic injection (HI) of 10mM potassium chloride as LE at 150mbar for 36s (4% of total capillary volume). The sample was injected at 10kV for 300s, followed by HI of 10mM pimozide as TE at 150mbar for 36s (4% of total capillary volume). Separation was performed in 7.5mM deoxycholic acid sodium salt, 15mM acetic acid and 1mM 18-crown-6 in 100% methanol at +25kV with UV detection at 205nm. Under optimized conditions, the sensitivity was enhanced between 160- and 600-fold when compared with our previously developed method based on HI at 150mbar for 12s. The detection limit of the method for tamoxifen and its metabolites were 0.05-0.25ng/mL, with RSDs between 2.1% and 3.5%. Recoveries in spiked human plasma were 95.6%-99.7%. A comparison was also made between the proposed EKS approach and the standard field-amplified sample injection (FASI) technique. EKS proved to be 3-5 times more sensitive than the FASI. The new EKS method was applied to the analysis of tamoxifen and its metabolites in plasma samples from breast cancer patients after liquid-liquid extraction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this study, the potential for carbonaceous nanomaterials to be used as adsorbents for the mixed matrix membrane (MMM) microextraction and preconcentration of organic pollutants was demonstrated. For this method, multiwall carbon nanotubes (MWCNT) and single layer graphene (SLG) nanoparticles were individually incorporated through dispersion in a cellulose triacetate (CTA) polymer matrix to form a MWCNT-MMM and SLG-MMM, respectively. The prepared membranes were evaluated for the extraction of selected polycyclic aromatic hydrocarbons (PAHs) present in sewage pond water samples. The extraction was performed by dipping a small piece of membrane (7 mm × 7 mm) in a stirred 7.5 mL sample solution to initiate the analyte adsorption. This step was followed by an analyte desorption into 60 μL of methanol prior to high performance liquid chromatography (HPLC) analysis. When the optimum SLG-MMM microextraction technique was applied to spiked sewage pond water samples, the detection limit of the method for the PAHs were in the range of 0.02-0.09 ng/mL, with relative standard deviations of between 1.4% and 7.8%. Enrichment factors of 54-100 were achieved with relative recoveries of 99%-101%. A comparison was also made between the proposed approach and standard solid phase extraction using polymeric bonded octadecyl (C18) cartridges., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Micelle to solvent stacking was implemented for the recently established NACE-C(4) D method to determine tamoxifen and its metabolites in standard samples and human plasma of breast cancer patients. For stacking, the standard samples and extract after liquid-liquid extraction (LLE) were prepared in methanol and the resulting sample solution was pressure injected after a micellar plug of SDS. Factors that affected the stacking such as SDS concentration, micelle, and sample plug length were examined. The sensitivity enhancement factor (peak height from stacking/peak height from typical injection of sample in BGE) was 15-22. The method detection limits with LLE were in the range of 5-10 ng/mL, which was lower than the established method (where the LLE extract was also prepared in methanol) with reported method detection limits of 25-40 ng/mL. The intraday and interday repeatability were in the range of 1.0-3.4% and 3.8-6.5%, respectively., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new approach for the quantification of tamoxifen and its metabolites 4-hydroxytamoxifen, N-desmethyltamoxifen, and 4-hydroxy-N-desmethyltamoxifen (endoxifen) in human plasma samples using NACE coupled with contactless conductivity detection (C 4 D) is presented. The buffer system employed consisted of 7.5 mM deoxycholic acid sodium salt, 15 mM acetic acid, and 1 mM 18-crown-6 in 100% methanol. The complete separation of all targeted compounds (including endoxifen racemate) could be achieved within 6 min under optimized conditions. The proposed method was validated and showed good linearity in the range from 100 to 5000 ng/mL with correlation coefficients between 0.9922 and 0.9973, LODs in the range of 25-40 ng/mL, and acceptable reproducibility of the peak area (intraday RSD 2.2-3.1%, n = 4; interday (3 days) RSD 6.0-8.8%, n = 4). The developed method was successfully demonstrated for the quantification of tamoxifen and its metabolites in human plasma samples collected from breast cancer patients undertaking tamoxifen treatment., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, a new variation of the electromembrane extraction (EME) approach employing a hollow polymer inclusion membrane (HPIM) was developed. In this method, a HPIM was prepared by casting a solution of the desired proportions of cellulose acetate (CTA), tris(2-ethylhexyl)phosphate (TEHP) and di-(2-ethylhexyl)phosphoric acid (D2EHPA) in dichloromethane on glass capillary tubing. Three basic drugs namely amphetamine, methamphetamine, and 3,4-methylenedioxy-N-methylamphetamine (MDMA) were selected as model analytes to evaluate the extraction performance of this new approach. The drugs were extracted from human plasma samples, through a 20μm thickness HPIM, to an aqueous acceptor solution inside the lumen of the hollow membrane. Parameters affecting the extraction efficiency were investigated in detail. Under the optimized conditions, enrichment factors in the range of 97-103-fold were obtained from 3mL of sample solution with a 10min extraction time and an applied voltage of 300V across the HPIM. The detection limits of the method for the three drugs were in the range of 1.0-2.5ng/mL (at a signal/noise ratio of three), with relative standard deviations of between 6.4% and 7.9%. When the method was applied to spiked plasma samples, the relative recoveries ranged from 99.2% to 100.8%. Enrichment factors of 103, 99 and 97 were obtained for amphetamine, methamphetamine, and MDMA, respectively. A comparison was also made between the newly developed approach and EME using supported liquid membranes (SLM) as well as standard sample preparation methods (liquid-liquid extraction) used by the Toxicology Unit, Department of Chemistry, Malaysia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

One of the most cited limitations of capillary (and microchip) electrophoresis is the poor sensitivity. This review continues to update this series of biannual reviews, first published in Electrophoresis in 2007, on developments in the field of on-line/in-line concentration methods, covering the period July 2012-July 2014. It includes developments in the field of stacking, covering all methods from field-amplified sample stacking and large-volume sample stacking, through to ITP, dynamic pH junction, and sweeping. Attention is also given to on-line or in-line extraction methods that have been used for electrophoresis., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An automated analyte electroextraction and preconcentration system, which was used as the front end for a liquid chromatography-electrospray mass spectrometry instrument, is described. The extraction was based on driving the anionic analytes across a polymer inclusion membrane by application of a potential of 200 V to the cell. Five milliliters (5 mL) of sample were passed through a flow-through cell at a flow rate of 0.2 mL/min containing a membrane 20 μm thick. This consisted of 75% cellulose triacetate as base polymer, 12.5% of tris(2-ethylhexyl)phosphate as plasticizer, and 12.5% of Aliquat 336 as cationic carrier. The target analytes were enriched in 20 μL of a stagnant acceptor solution prior to online LC/MS analysis. The performance of the system was demonstrated for the determination of chlorinated phenoxyacetic acid herbicides in spiked river water. Enrichment factors of ~200 were achieved with recoveries of typically 99% and precision values of typically 5%. The limit of detection (LOD) values were found to be between 0.03 ng/mL to 0.08 ng/mL.

A flow-through arrangement for electrodriven extraction across a polymer inclusion membrane was developed. Sample introduction into the donor chamber was continuous, while the acceptor solution was stagnant. By adjustment of the total volume of the donor solution pumped through the cell the best compromise between enrichment factor and extraction time can be set. The enriched extract was analyzed by capillary electrophoresis with contactless conductivity detection. Membranes of 20μm thickness were employed which consisted of 60% cellulose triacetate as base polymer, 20% o-nitrophenyl octyl ether as plasticizer, and 20% Aliquat 336. By passing through 10mL of sample at a flow rate of 1mL/min the model analytes glyphosate (a common herbicide) and its major metabolite aminomethylphosphonic acid could be transported from the aqueous donor solution to the aqueous acceptor solution with efficiencies >87% in 10min at an applied voltage of 1500V. Enrichment factors of 87 and 95 and limits of detection down to 43 and 64pg/mL were obtained for glyphosate and aminomethylphosphonic acid, respectively. The intra- and interday reproducibilities for the extraction of the two compounds from spiked river water were about 6 and 7% respectively when new membranes were used for each experiment. For consecutive extractions of batches of river water with a single piece of membrane a deterioration of recovery by about 16% (after 20 runs) was noted, an effect not observed with purely aqueous standards., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The determination of fatty acids by nonaqueous CZE with capacitively coupled contactless conductivity detection was investigated. A new deoxycholate-based BGE, which had previously been found to give significantly improved baseline stability in the determination of lipophilic organic ammonium ions, was found to be similarly beneficial for the determination of the anions. The use of a PVA-coated capillary was required for suppression of the EOF and to obtain well reproducible results. The complete separation of 12 fatty acids could be achieved with 10 mM DOC in methanol within 6 min under optimized conditions. The PVA-coated capillary demonstrated outstanding stability over 300 runs with no sign of depletion of the PVA layer. Method validation showed a good linearity range from 0.75 to 25 μM with correlation coefficients between 0.9949 and 0.9979. The LOD was determined as 0.5 μM for all fatty acids. The developed approach was successfully demonstrated for the separation of free fatty acids in commercial and home-made edible oil., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A simple adsorption/desorption procedure using a mixed matrix membrane (MMM) as extraction medium is demonstrated as a new miniaturized sample pretreatment and preconcentration technique. Reversed-phase particles namely polymeric bonded octadecyl (C18) was incorporated through dispersion in a cellulose triacetate (CTA) polymer matrix to form a C18-MMM. Non-steroidal anti-inflammatory drugs (NSAIDs) namely diclofenac, mefenamic acid and ibuprofen present in the environmental water samples were selected as targeted model analytes. The extraction setup is simple by dipping a small piece of C18-MMM (7 mm × 7 mm) in a stirred 10 mL sample solution for analyte adsorption process. The entrapped analyte within the membrane was then desorbed into 100 μL of methanol by ultrasonication prior to high performance liquid chromatography (HPLC) analysis. Each membrane was discarded after single use to avoid any analyte carry-over effect. Several important parameters, such as effect of sample pH, salting-out effect, sample volume, extraction time, desorption solvent and desorption time were comprehensively optimized. The C18-MMM demonstrated high affinity for NSAIDs spiked in tap and river water with relative recoveries ranging from 92 to 100% and good reproducibility with relative standard deviations between 1.1 and 5.5% (n=9). The overall results obtained were found comparable against conventional solid phase extraction (SPE) using cartridge packed with identical C18 adsorbent., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A study on the separation of lipophilic quaternary ammonium cations in NACE coupled with contactless conductivity detection (NACE-C(4)D) is presented. The suitability of different salts dissolved in various organic solvents as running electrolytes in NACE-C(4)D was investigated. A solvent mixture of methanol/acetonitrile at a ratio of 90%:10% v/v showed the best results. Deoxycholic acid sodium salt as BGE was found to provide exceptional high stability with low baseline noise that leads to highest S/N ratios for the target analytes among all BGEs tested. Under the optimum conditions, capillaries with different internal diameters were examined and an id of 50 μm was found to give best detection sensitivity. The proposed method was validated and showed good linearity in the range from 2.5 to 200 μM, low limits of detection (0.1-0.7 μM) and acceptable reproducibility of peak area (intraday RSD 0.1-0.7%, n = 3; interday RSD 5.9-9.4%, n = 3)., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new approach for the determination of free and total valproic acid in small samples of 140 μL human plasma based on capillary electrophoresis with contactless conductivity detection is proposed. A dispersive liquid-liquid microextraction technique was employed in order to remove biological matrices prior to instrumental analysis. The free valproic acid was determined by isolating free valproic acid from protein-bound valproic acid by ultrafiltration under centrifugation of 100 μL sample. The filtrate was acidified to turn valproic acid into its protonated neutral form and then extracted. The determination of total valproic acid was carried out by acidifying 40 μL untreated plasma to release the protein-bound valproic acid prior to extraction. A solution consisting of 10 mM histidine, 10 mM 3-(N-morpholino)propanesulfonic acid and 10 μM hexadecyltrimethylammonium bromide of pH 6.5 was used as background electrolyte for the electrophoretic separation. The method showed good linearity in the range of 0.4-300 μg/mL with a correlation coefficient of 0.9996. The limit of detection was 0.08 μg/mL, and the reproducibility of the peak area was excellent (RSD=0.7-3.5%, n=3, for the concentration range from 1 to 150 μg/mL). The results for the free and total valproic acid concentration in human plasma were found to be comparable to those obtained with a standard immunoassay. The corresponding correlation coefficients were 0.9847 for free and 0.9521 for total valproic acid., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A capillary electrophoresis method with contactless conductivity detection was evaluated as a new approach for quantification of creatine and phosphocreatine in human quadriceps femoris biopsy samples. The running buffers employed consisted of 1 M acetic acid at a pH of 2.3 for the determination of creatine and 50 mM 3-(N-morpholino)propanesulfonic acid/30 mM histidine at a pH of 6.4 for the determination of phosphocreatine in the centrifuged muscle extracts. The limits of detection for creatine and phosphocreatine were found to be 2.5 and 1.0 μM, respectively. Creatine and phosphocreatine were determined in six human muscle biopsy samples and the results were found comparable to those of a standard enzymatic assay. The procedures developed for creatine and phosphocreatine also allow the determination of creatinine as well as adenosine diphosphate and adenosine triphosphate., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The use of a cationic carrier-mediated polymer inclusion membrane (PIM) for extraction and preconcentration of anionic model analytes driven by an electric field directly into an aqueous acceptor solution is demonstrated. The optimized membrane was 20 μm thick and consisted of 60% cellulose triacetate as base polymer, 20% o-nitrophenyl octyl ether as plasticizer, and 20% Aliquat 336 as cationic carrier in the perchlorate form. By applying voltages of up to 700 V across the membrane, the lipophilic model analytes propanesulfonate, octanesulfonate, and decanesulfonate could be transported from the aqueous donor solution to the aqueous acceptor solution with efficiences >90% within 5 to 20 min. A preconcentration factor of 26, defined by the volume ratio between donor and acceptor compartments of the current cell design, could be achieved. The utility of the method for analytical applications is demonstrated by extraction of the herbicide glyphosate and its breakdown product aminomethylphosphonic acid from spiked river water, followed by quantification with capillary electrophoresis using contactless conductivity detection. Limits of detection of 0.8 and 1.5 ng/mL were obtained for glyphosate and aminomethylphosphonic acid, respectively.

A dynamic supported liquid membrane tip extraction (SLMTE) procedure for the effective extraction and preconcentration of glyphosate (GLYP) and its metabolite aminomethylphosphonic acid (AMPA) in water has been investigated. The SLMTE procedure was performed in a semi-automated dynamic mode and demonstrated a greater performance against a static extraction. Several important extraction parameters such as donor phase pH, cationic carrier concentration, type of membrane solvent, type of acceptor stripping phase, agitation and extraction time were comprehensively optimized. A solution of Aliquat-336, a cationic carrier, in dihexyl ether was selected as the supported liquid incorporated into the membrane phase. Quantification of GLYP and AMPA was carried out using capillary electrophoresis with contactless conductivity detection. An electrolyte solution consisting of 12 mM histidine (His), 8 mM 2-(N-morpholino)ethanesulfonic acid (MES), 75 microM cetyltrimethylammonium bromide (CTAB), 3% methanol, pH 6.3, was used as running buffer. Under the optimum extraction conditions, the method showed good linearity in the range of 0.01-200 microg/L (GLYP) and 0.1-400 microg/L (AMPA), acceptable reproducibility (RSD 5-7%, n=5), low limits of detection of 0.005 microg/L for GLYP and 0.06 microg/L for AMPA, and satisfactory relative recoveries (90-94%). Due to the low cost, the SLMTE device was disposed after each run which additionally eliminated the possibility of carry-over between runs. The validated method was tested for the analysis of both analytes in spiked tap water and river water with good success., (Copyright 2010 Elsevier B.V. All rights reserved.)

A novel microextraction technique termed solid phase membrane tip extraction (SPMTE) was developed. Selected triazine herbicides were employed as model compounds to evaluate the extraction performance and multiwall carbon nanotubes (MWCNTs) were used as the adsorbent enclosed in SPMTE device. The SPMTE procedure was performed in semi-automated dynamic mode and several important extraction parameters were comprehensively optimized. Under the optimum extraction conditions, the method showed good linearity in the range of 1-100 microg/L, acceptable reproducibility (RSD 6-8%, n=5), low limits of detection (0.2-0.5 microg/L), and satisfactory relative recoveries (95-101%). The SPMTE device could be regenerated and reused up to 15 analyses with no analyte carry-over effects observed. Comparison was made with commercially available solid phase extraction-molecular imprinted polymer cartridge (SPE-MIP) for triazine herbicides as the reference method. The new developed method showed comparable or even better results against reference method and is a simple, feasible, and cost effective microextraction technique., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Rapid and direct online preconcentration followed by CE with capacitively coupled contactless conductivity detection (CE-C(4)D) is evaluated as a new approach for the determination of glyphosate, glufosinate (GLUF), and aminophosphonic acid (AMPA) in drinking water. Two online preconcentration techniques, namely large volume sample stacking without polarity switching and field-enhanced sample injection, coupled with CE-C(4)D were successfully developed and optimized. Under optimized conditions, LODs in the range of 0.01-0.1 microM (1.7-11.1 microg/L) and sensitivity enhancements of 48- to 53-fold were achieved with the large volume sample stacking-CE-C(4)D method. By performing the field-enhanced sample injection-CE-C(4)D procedure, excellent LODs down to 0.0005-0.02 microM (0.1-2.2 microg/L) as well as sensitivity enhancements of up to 245- to 1002-fold were obtained. Both techniques showed satisfactory reproducibility with RSDs of peak height of better than 10%. The newly established approaches were successfully applied to the analysis of glyphosate, glufosinate, and aminophosphonic acid in spiked tap drinking water.

A new sample pre-treatment technique termed cone-shaped membrane liquid phase microextraction (CSM-LPME) was developed and combined with micro-liquid chromatography (micro-LC) for the determination of selected pesticides in water samples. Four pesticides (hexaconazole, procymidone, quinalphos and vinclozolin) were considered as target analytes. Several important extraction parameters such as types of extraction solvent, agitation rate, pH value, total exposure time and effect of salt and humic acids were optimized. Enrichment factors of > 50 folds were easily achieved within 20 min of extraction. The analytical data demonstrated relative standard deviations for the reproducibility of the optimized CSM-LPME method ranging from 6.3 to 7.5%. The correlation coefficients of the calibration curves were at least 0.9995 across a concentration range of 2-100 microg/L. The detection limits for all the analytes were found to be in the range of 1.1-1.9 microg/L.

High temperature liquid chromatography using water-rich and superheated water eluent is evaluated as a new approach for the separation of selected triazole fungicides, hexaconazole, tebuconazole, propiconazole, and difenoconazole. Using a polybutadiene-coated zirconia column at temperatures of 100-150 degrees C, clear separations were achieved when 100% purified water was utilized as organic-free eluent. Excellent limits of detection down to pg level were obtained for the separation of the triazole fungicides under optimum conditions. Van't Hoff plots for the separations were linear suggesting that no changes occurred in the retention mechanism over the temperature range studied.