On-chip Electromembrane Extraction Research Articles

Introduction of an electrospun nanofibrous membrane incorporated by metal-organic framework-199 (MOF-199) with Lewis acid property for efficient extraction of sulfonamides in on-chip electromembrane extraction

In this study, a new supporting polymeric membrane having Lewis acid nature was introduced for immobilizing organic solvent in on-chip electromembrane extraction (on-chip EME). For this aim, a polymeric nanofibrous membrane incorporated by a copper based metal-organic framework (MOF-199), with coordinatively unsaturated metal sites and Lewis acid property, was prepared by electrospinning a mixture of polycaprolactone (PCL) and MOF-199. Based on the field emission scanning electron microscopy images, the obtained polymeric membrane consisted of intertwined nanofibers having empty space between the fibers which could provide a suitable place for immobilizing the organic solvent. To demonstrate remarkable extractability of the proposed membrane (PCL/MOF-199 nanofibers) via executing Lewis acid-base interactions, three sulfonamide drugs was selected as anionic polar analytes with Lewis base feature. The parameters affecting the extraction efficiency of the method were optimized through the experimental design method using the orthogonal and rotatable central composite design (CCD). Under optimum conditions, the extraction recoveries ranging from 35.5 to 71.2%, the relative standard deviations (RSD%) less than 6.45%, and the detection limits in the range of 0.2-0.5 μg L−1 were achieved. The comparison of the extraction efficiency of the on-chip EME method using the electrospun PCL/MOF-199 nanofibers and PCL nanofibers membranes indicated that the proposed membrane was more efficient for extraction of sulfonamides because of the significant Lewis acid-base interactions of sulfonamides with copper uncoordinated open sites in MOF-199. Finally, the performance of the proposed method for extraction and determination of sulfonamides in three real samples was assayed.

The selective extraction of dietary polyamines from chicken breast using the application of a lab-on-a-chip electromembrane and dispersive liquid-liquid microextraction followed by gas chromatography-mass spectrometry.

Excessive dietary polyamines (PAs), including putrescine (PUT), spermine (SPM), and spermidine (SPD), have become a worldwide concern due to their carcinogenicity and reduced shelf life. A modern miniaturized on-chip electromembrane extraction (EME) has been applied to extract these compounds from chicken breast samples. This method is based fundamentally on ionic compounds' electrostatic attraction, diffusion, and solubility in the acceptor phase. The chemical structure of polyamines enables their efficient extraction using an electric driving force on a microchip device. HCl solution (0.1 mol L-1) was applied as an aqueous acceptor solvent. Dispersive liquid-liquid microextraction was performed after EME to facilitate joining three-phase EME to GC-MS and improve the merit figures. The total ranges of 3.77-7.89 μg g-1, 3.48-7.02 μg g-1, and 0.78-2.20 μg g-1 were acquired as PUT, SPM and SPD concentrations in chicken breast, respectively. The results demonstrate that the level of PAs in fresh chicken breast samples is not concerning, but it may reduce the quality of chicken meat over time. This novel analytical technique has several advantages: high recovery, substantial quickness, remarkable selectivity, and good enrichment factors. This emerging method could be generalized to other studies to analyze different foodstuffs.

The application of barcode readable assay and linear regression RGB analysis using a customized smartphone app in on-chip electromembrane extraction for simultaneous determination of heavy metal ions

This paper presents an on-chip electromembrane extraction (OC-EME) followed by RGB analysis with a barcode-readable customized app for the determination of three heavy metal ions; Cr(VI), Ni(ΙΙ), and Cu(ΙΙ) in water samples. First, the OC-EME procedure was performed on a single transparent platform including three divided channels for extraction of analytes and subsequently complex formation with chromogenic reagents. The RGB values of colorful complexes were then analyzed by Photoshop software and green value intensities of all three colors showed the best concentration dependence signal. Effective parameters such as the composition of supported liquid membrane (SLM), the voltage of extraction, the composition of donor and acceptor solutions, sample volume, and flow rate were investigated and optimized. Also, a smartphone app was developed for RGB analysis on a barcode-readable program to detect and quantify the extracted heavy metal(s). A fast, easy, and accurate quantification analysis was offered using principal component analysis (PCA) and a trained linear regression model. Under optimized conditions, good calibration fittings were observed within the ranges of 0.05–1.5 mg l−1 for Cr(VI), 1.0–70.0 mg l−1 for Ni(II), and 0.5–30.0 mg l−1 for Cu(II) via the customized app. Intra- and inter-day RSDs% of the method were obtained less than 6.9 % and 7.8 %, respectively. Finally, the proposed procedure was successfully applied for the analysis of target ions in water samples with relative recoveries between 85.0 % and 116.4 %.

On-chip electromembrane extraction using deep eutectic solvent and red-green-blue analysis by quick-response code readable customized application on a smartphone for measuring salicylic acid in pharmaceutical and plasma samples

The current work presents an on-chip electromembrane extraction (OC-EME) method using deep eutectic solvent followed by QR code-based red-green-blue (RGB) analysis for measuring salicylic acid (SA) in plasma and pharmaceutical samples. The RGB analysis was performed based on forming the SA-Fe3+ complex in the acceptor phase giving a purple solution. The QR code readable customized app provided rapid, easy, and cost-less qualification and quantification of SA with the aid of principal component analysis (PCA). Parameters affecting OC-EME, including the supported liquid membrane (SLM), pH of the donor and acceptor phases, applied voltage, and sample flow rate, were optimized. Also, the concentration of FeCl3, as a chromogenic reagent, and its reaction time with SA were investigated to find the best concentration-dependent signal. Under the optimized conditions, a good relationship was observed between the green intensity and SA concentration within the range of 1.0–100.0 mg l−1 (R2 = 0.9946) in water and 5.0–100.0 mg l−1 (R2 = 0.9902) in plasma. Intra- and inter-day RSDs% were obtained less than 4.7% and 7.7%, respectively. Finally, the method was successfully applied for measuring SA in foot corn treatment, Aspirin medicines, and human plasma, with relative recoveries between 89.0 and 129.2%.

Miniaturized on-chip electromembrane extraction with QR code-based red-green-blue analysis using a customized Android application for copper determination in environmental and food samples

A miniaturized on-chip electromembrane extraction device with QR code-based red–green–blue analysis was designed to determine copper in water, food, and soil. The acceptor droplet consisted of ascorbic acid as the reducing agent and bathocuproine as the chromogenic reagent. The formation of a yellowish-orange complex was a sign of copper in the sample. Then, the qualitative and quantitative analysis of the dried acceptor droplet was done by the customized Android app that was developed based on image analysis concepts. In this application, principal component analysis was performed on the data for the first time to reduce the three dimensions, red, green, and blue, to one dimension. The effective extraction parameters were optimized. The limit of detection and limit of quantification were 0.1 µg mL−1. Intra- and inter-assay relative standard deviations ranged between 2.0 and 2.3 % and 3.1–3.7 %, respectively. The calibration range was studied between 0.1 and 25 µg mL−1 (R2 = 0.9814).

A new microfluidic-chip device followed by sensitive image analysis of smart phone for simultaneous determination of dyes with different acidic–basic properties

In this study, a new microfluidic-chip coupled with micro solid phase extraction (μ-SPE) and a RGB detection system was designed. The method was used for extraction and simultaneous determination of trace amounts of dyes with different acidic–basic properties. Erythrosine (Ery) and Crystal Violet (CV) were selected as acidic and basic model analytes, respectively. The first step of this method is based on the on-chip electromembrane extraction (CEME) of analytes from aqueous solution. The utilized microfluidic system is a single compartment that composed of three polymethyl metacrylate plates (with sandwiched structures) patterned with palm shaped helix channels. The device consisted one pair of platinum electrodes that were embedded in the acceptor phase channels in each side. The middle part was cut and used as the path of the sample. The extracted analytes by CEME were passed through the micro-packed column containing strong cation and anion exchanger sorbents respectively. Two adsorbents were separated by a polypropylene frit and sealed on each side by two polypropylene frites. Following dye adsorption on the sorbents, the colors that emerged were promptly evaluated using RGB colorimetry on a smartphone. Central composite design was used to analyze and optimize the effective parameters on extraction efficiency. The relative standard deviations (RSDs%) based on five replicate measurements were less than 7.8% for RGB and 8.6% for the spectrophotometry technique under ideal conditions. Image analysis using a smartphone yielded LOD values of 15.0 and 10.5 μg L−1 for Ery and CV, respectively. The CEME- μ-SPE -RGB approach produced findings that were equivalent to those obtained by spectrophotometry. Finally, the approach was used to accurately determine Ery and CV in water samples, yielding good relative recoveries (recovery ≥94.0).

Polyaniline-polycaprolactone electrospun nanofibrous mat: new polymeric support with anion exchange characteristic for immobilizing liquid membrane in efficient on-chip electromembrane extraction of polar acidic drugs.

The potential of application of an electrospun nanofiber sheet as new polymeric support for immobilizing the liquid membrane, instead of a common commercial polypropylene sheet, in on-chip electromembrane extraction (EME) of some acidic polar drugs followed by HPLC with ultraviolet detection is presented. The nanofiber sheet was prepared by electrospinning a mixture of polycaprolactone and polyaniline. The successful synthesis of the electrospun nanofiber sheet was confirmed by field emission-scanning electron microscopy, energy-dispersive X-ray spectroscopy, elemental mapping, and atomic force microscopy. Several parameters affecting the efficiency of the microextraction method, including pHs of the donor and acceptor phases, applied voltage, sample flow rate, phosphate content of the acceptor phase, and sample volume, were investigated and optimized. After optimization, the linearity range of 0.5-250.0µg L-1 and detection limits of 0.2-1.0µg L-1 were obtained for the analytes. The extraction recovery values and preconcentration factors were 10.7-55.3% and 16-83, respectively. The presence of polyaniline in the composition of the nanofibers significantly improved the extraction efficiency of the polar acidic drugs due to providing the possibility of various interactions with the target analytes such as hydrogen bonding, π-stacking, andanion exchange. The obtained results demonstrate the excellent efficiency of the synthesized electrospun nanofibrous mat as a novel support membrane for immobilizing 1-octanol and as an interactive substrate for electromembrane extraction of acidic polar drugs. Eventually, the proposed on-chip EME method exhibits acceptable precision (relative standard deviations less than 9.7% (n = 3)) and good accuracy (86-112%) for determining the target analytes in the plasma samples.

On-chip electromembrane extraction of some polar acidic drugs from plasma samples by the development of an active and efficient polymeric support for liquid membrane based on electrospinning process

Electromembrane extraction (EME), despite its high performance in the extraction of highly polar basic analytes, has challenges in extracting polar acidic compounds. This is the result of a lack of access to the suitable supported liquid membrane (SLM) for this group of analytes. Therefore, it would be valuable to provide a suitable solution for this problem. Accordingly, in the present study, a new method based on on-chip EME followed by HPLC with UV detection was developed for the extraction and determination of some polar acidic drugs in order to provide high extraction efficiency. Here, a new polymeric sheet was introduced as a support for SLM immobilization, which is not only used to impregnate 1-octanol as SLM but also enhances extraction recovery by exerting effective interactions with target acidic analytes. The polymeric sheet was composed of nanofibers prepared by electrospinning polycaprolactone blended with a composite of graphene oxide and aluminum polycations. Encapsulation of the composite in polycaprolactone nanofibers improved the extraction efficiency of polar acidic compounds by creating additional interactions with the target analytes, including hydrogen bonding, dipole-dipole, π-π stacking, and anion exchange process. The electrospun nanofiber-based sheet was characterized by FE-SEM, EDX, elemental mapping, TEM, and AFM. The extraction parameters were further optimized with an orthogonal-rotatable central composite design (CCD). Applying CCD determined optimal conditions by minimum experiments, and interactions between the parameters were clarified. Under optimized conditions, the proposed method provided extraction recoveries from 36.5 to 64.1%, relative standard deviations less than 5.7% (n = 4), and detection limits of 0.3–0.5 μg L−1. Furthermore, the proposed method was successfully used for the determination of target analytes in plasma samples, providing good accuracy (87–110%) and precision (3.2–8.8%).

An efficient configuration for simultaneous electromembrane extraction of acidic and basic drugs on a chip

• An effective on-chip electromembrane extraction (CEME) was designed and coupled with HPLC. • This design does not require a syringe pump, so the system is simple and easy to handle. • The method was applied for simultaneous extraction and determination of acidic and basic analytes. • Efficient parameters on CEME of ibuprofen, disopyramide and lidocaine were optimized. • The preconcentration factors higher than 7.4 and RSDs% < 3.9% were obtained. In the present study, a new chip was designed for simultaneous electromembrane extraction (EME) of acidic and basic analytes. The method followed by the HPLC-UV analysis, was used for simultaneous extraction and determination of trace amounts of target analytes with different properties. Ibuprofen (IBU), as an acidic model analyte, and disopyramide (DIS) and lidocaine (LID), as basic model analytes, were selected. The chip was composed of three polymethylmethacrylate (PMMA) plates. The chamber for the sample solution was set in the middle plate. Two other chambers were carved on the other plates and they were acted as two acceptor phases’ reservoirs. Two stainless steel electrodes, which were responsible for applying a DC electrical potential on both sides of the supported liquid membranes (SLMs), were placed in the bottom of acceptor phases chambers and connected to a power supply. The two porous polypropylene membrane sheets, which were impregnated with different organic solvents, were used to separate the plates. Effective parameters such as SLM composition (1-octanol for acidic analyte and NPOE+5%DEHP for basic analytes), pH of donor phase and acceptor phases, applied voltage across SLM, and extraction time were optimized. Under the optimized conditions, the calibration curves were linear with coefficient of determinations (R 2 ) higher than 0.991 in the water, urine, and blood plasma samples. The obtained LODs were less than 5.0 µg L −1 and 1 µg L −1 for the basic and acidic analytes, respectively. The results demonstrated that on-chip EME would be used most effectively for extraction and determination of IBU, DIS, and LID in biofluids. Graphical Abstract .

On-chip electromembrane extraction followed by sensitive digital image-based colorimetry for determination of trace amounts of Cr(vi)

In this work, an on-chip electromembrane extraction coupled with the micro solid phase extraction step was developed for extraction, preconcentration, and determination of trace amounts of chromium(vi) in water samples.

On-chip electromembrane extraction of acidic drugs.

In the present work, a new supported liquid membrane (SLM) has been developed for on-chip electromembrane extraction of acidic drugs combined with HPLC or CE, providing significantly higher stability than those reported up to date. The target analytes are five widely used non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), diclofenac (DIC), naproxen (NAX), ketoprofen (KTP) and salicylic acid (SAL). Two different microchip devices were used, both consisted basically of two poly(methyl methacrylate) (PMMA) plates with individual channels for acceptor and sample solutions, respectively, and a 25µm thick porous polypropylene membrane impregnated with the organic solvent in between. The SLM consisting of a mixture of 1-undecanol and 2-nitrophenyl octyl ether (NPOE) in a ratio 1:3 was found to be the most suitable liquid membrane for the extraction of these acidic drugs under dynamic conditions. It showed a long-term stability of at least 8 hours, a low system current around 20µA, and recoveries over 94% for the target analytes. NPOE was included in the SLM to significantly decrease the extraction current compared to pure 1-undecanol, while the extraction properties was almost unaffected. Moreover, it has been successfully applied to the determination of the target analytes in human urine samples, providing high extraction efficiency.

Simultaneous extraction of acidic and basic drugs via on-chip electromembrane extraction using a single-compartment microfluidic device

In this study, a new chip was designed for simultaneous extraction of acidic and basic drugs by a single chamber on-chip electromembrane extraction (CEME) followed by high performance liquid chromatography. Diclofenac (DIC) and nalmefene (NAL) were selected as acidic and basic model analytes, respectively. In this device, simultaneous extraction of the analytes was carried out using a single compartment. The chip was composed of three PMMA (polymethyl methacrylate) parts with sandwiched structures and carved spiral microfluidic channels in each part. The middle part was cut and an "M" pattern provided interfaces for contact between the sample solution flow and two porous polypropylene sheets on both sides. Two other parts had the same spiral channels dedicated to the corresponding acceptor phases of the acidic and basic analytes and were located at both sides. Each polypropylene sheet was impregnated with the appropriate organic solvent for the acidic and basic analytes. Two platinum electrodes connected to a power supply were mounted at the bottom of the acceptor channels. These electrodes provided the electrical fields across SLMs to extract the analytes from a single sample flow. When the extraction was completed, the acceptor solutions were collected, mixed, and then injected into the chromatographic system. The effective parameters on the extraction efficiency were investigated and optimized. Under the optimal conditions, the calibration curves were linear in the range of 9.0-500 μg L-1 for NAL and 11.0-500 μg L-1 for DIC with the coefficient of determination (R2) higher than 0.9913. The relative standard deviations (RSD%) based on five replicate measurements were less than 6.3%. LOD values were 4.0 and 3.0 μg L-1 for DIC and NAL, respectively. Finally, the method was successfully applied to determine DIC and NAL in the human urine samples and satisfactory results were obtained (recovery ≥90).

Electromembrane extraction of biogenic amines in food samples by a microfluidic-chip system followed by dabsyl derivatization prior to high performance liquid chromatography analysis

In the present research, an on-chip electromembrane extraction coupled with high performance liquid chromatography was developed for monitoring the trace levels of biogenic amines (BAs), including histamine, tryptamine, putrescine, cadaverine and spermidine in food samples. A porous polypropylene sheet membrane impregnated with an organic solvent was placed between the two parts of the chip device to separate the channels. Two platinum electrodes were mounted at the bottom of these channels, which were connected to a power supply, providing the electrical driving force for migration of ionized analytes from the sample solution through the porous sheet membrane into the acceptor phase.BAs were extracted from 2 mL aqueous sample solutions at neutral pH into 50 μL of acidified (HCl 90 mM) acceptor solution. Supported liquid membrane including NPOE containing 10% DEHP was used to ensure efficient extraction. Low voltage of 40 V was applied over the SLMs during extraction time. The influences of fundamental parameters affecting the transport of BAs were optimized. Under the optimized conditions, the relative standard deviations based on four replicate measurements were less than 8.0% and limit of detections were in range of 3.0–8.0 μg L−1. Finally, the method was successfully applied to determinate BAs in the food samples and satisfactory results (recovery > 95.6) were obtained.

Quantitative analysis of clonidine and ephedrine by a microfluidic system: On-chip electromembrane extraction followed by high performance liquid chromatography.

In this work, a microfluidic device was developed for on-chip electromembrane extraction of trace amounts of ephedrine (EPH) and clonidine (CLO) in human urine and plasma samples followed by HPLC-UV analysis. Two polymethylmethacrylate plates were used as substrates and a microchannel was carved in each plate. The microchannel channel on the underneath plate provided the flow pass of the sample solution and the one on the upper plate dedicated to a compartment for the stagnant acceptor phase. A piece of polypropylene sheet was impregnated by an organic solvent and mounted between the two parts of the chip device. An electrical field, across the porous sheet, was created by two embedded platinum electrodes placed in the bottom of the channels which were connected to a power supply. The analytes were converted to their ionized form, passed through the supported liquid membrane, and then extracted into the acceptor phase by the applied voltage. All the effective parameters including the type of the SLM, the SLM composition, pH of donor and acceptor phases, and the quantity of the applied voltage were evaluated and optimized. Several organic solvents were evaluated as the SLM to assess the effect of SLM composition. Other parameters were optimized by a central composite design. Under the optimal conditions of voltage of 74V, flow rate of 28μLmin-1, 100 and 20mM HCl as acceptor and donor phase composition, respectively, the calibration curves were plotted for both analytes. The limits of detection were less than 7.0 and 11μgL-1 in urine and plasma, respectively. The linear dynamic ranges were within the range of 10-450 and 25-500μgL-1 (r2˃0.9969) for CLO, and within the range of 20-450 and 30-500μgL-1 (r2˃0.9907) for EPH in urine and plasma, respectively. To examine the capability of the method, real biological samples were analyzed. The results represented a high accuracy in the quantitative analysis of the analytes with relative recoveries within the range of 94.6-105.2% and acceptable repeatability with relative standard deviations lower than 5.1%.

Simultaneous extraction of acidic and basic drugs via on-chip electromembrane extraction

In the present work, a on-chip electromembrane extraction (CEME) was designed and employed for simultaneous extraction of mefenamic acid (MEF) and diclofenac (DIC), as acidic model analytes, and betaxolol (BET), as a basic model analyte, followed by HPLC-UV. The CEME consists of two polymethyl methacrylate (PMMA) parts which each part consists of two separated microfluidic channels. A polypropylene sheet membrane impregnated with an organic solvent was sandwiched between the parts. One of the parts was used as the flow path for the sample solution and the other one as holder for the acceptor phases. The separated microfluidic channels of the sample solution part were connected to each other using a small piece of a capillary tube and the sample solution was pumped through them by means of a micro-syringe pump. However, the acceptor phases of the acidic and basic analytes were separately kept stagnant in the two microfluidic channels during the extraction process. A d.c. potential was applied for migration of the analytes from sample solution through the organic membrane into the acceptor phases. All effective variables on the extraction efficiency of the analytes were optimized. Under the optimized conditions, preconcentration factors higher than 15 were achieved and the calibration curves were linear in the range of 10–500 μg L−1 (r2 > 0.9982). RSD% values (n = 4) and LODs were less than 7.1% and 5.0 μg L−1. The results demonstrated that CEME could efficiently be used for the simultaneous analysis of acidic and basic analytes in biological samples.

On-chip electromembrane extraction for monitoring drug metabolism in real time by electrospray ionization mass spectrometry.

Sample preparation is an essential step in any bioanalytical procedure and very often the most challenging step in method development. Most of the currently used methods require a relatively large amount of sample and are time consuming. Here, we describe a new approach based on electromembrane extraction (EME) integrated in microfluidic polymer chips. This procedure is fast, requires only small amounts of sample, and may thus be used for monitoring drug metabolism and the formation of metabolites in real time.

Electromembrane Extraction--A Novel Extraction Technique for Pharmaceutical, Chemical, Clinical and Environmental Analysis

Electromembrane extraction (EME) is a novel sample preparation technique in pharmaceutical, chemical, clinical and environmental analysis. This technique uses electromigration across artificial liquid membranes for selective extraction of analytes and sample enrichment from complex matrices. This review focuses on the setup, general procedure and parameters affecting the extraction efficiency of EME. An overview of innovations in EME (on-chip EME, low voltage EME, drop-to-drop EME, pulsed EME and EME followed by low-density solvent based ultrasound-assisted emulsification microextraction) is also presented in this article and attention is focused on the use of EME for pharmaceutical, chemical, clinical and environmental analysis.

On-chip electromembrane extraction for monitoring drug metabolism in real time by electrospray ionization mass spectrometry

A temperature controlled (37 °C) metabolic reaction chamber with a volume of 1 mL was coupled directly to electrospray ionization mass spectrometry (ESI-MS) by the use of a 50 μm deep counter flow micro-chip electromembrane extraction (EME) system. The EME/ESI-MS system was used to study the in vitro metabolism of amitriptyline in real time. There was no need to stop the metabolisms by protein precipitation as in conventional metabolic studies, since the EME selectively extracted the drug and metabolites from the reaction solution comprised of rat liver microsomes in buffer. Compositional changes in the reaction chamber were continuously detected 9 seconds later in the MS. Most of this time delay was due to transport of the purified extract towards the ESI source. The EME step effectively removed the enzymatic material, buffer and salts from the reaction mixture, and prevented these species from being introduced into the ESI-MS system. The on-chip EME/ESI-MS system provided repeatability for the amitriptyline signal intensity within 3.1% relative standard deviation (RSD) (n = 6), gave a linear response for amitriptyline in the tested concentration range of 0.25 to 15 μM, and was found not to be prone to ion-suppression from major metabolites introduced simultaneously into the EME/ESI-MS system. The setup allowed the study of fast reactions kinetics. The half-life, t(1/2), for the metabolism of 10 μM amitriptyline was 1.4 minutes with a 12.6% RSD (n = 6).

On-Chip Electro Membrane Extraction with Online Ultraviolet and Mass Spectrometric Detection

Electro membrane extraction was demonstrated in a microfluidic device. The device was composed of a 25 μm thick porous polypropylene membrane bonded between two poly(methyl methacrylate) (PMMA) substrates, each having 50 μm deep channel structures facing the membrane. The supported liquid membrane (SLM) consisted of 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of the membrane. The driving force for the extraction was a 15 V direct current (DC) electrical potential applied across the SLM. Samples containing the basic drugs pethidine, nortriptyline, methadone, haloperidol, loperamide, and amitriptyline were used to characterize the system. Extraction recoveries were typically in the range of 65-86% for the different analytes when the device was operated with a sample flow of 2.0 μL/min and an acceptor flow of 1.0 μL/min. With the sample flow at 9.0 μL/min and the acceptor flow at 0.0 μL/min, enrichment factors exceeding 75 were obtained during 12 min of operation from a total sample volume of only 108 μL. The on-chip electro membrane system was coupled online to electrospray ionization mass spectrometry and used to monitor online and real-time metabolism of amitriptyline by rat liver microsomes.

On-chip electro membrane extraction

This paper presents the first downscaling of electro membrane extraction (EME) to a chip format. The voltage-controlled extraction for sample preparation on microfluidic devices has several advantages such as selective extraction removing the high ionic strength of biological samples, preconcentration, fast kinetics with exact control of the beginning, and termination of the extraction. The device comprises a 25 μm thick porous polypropylene membrane bonded in-between two polymethyl methacrylate (PMMA) substrates with channel structures toward the membrane. The supported liquid membrane (SLM) was created by locally filling the pores of the membrane with 2-nitrophenyl octyl ether (NPOE). The sample solution, containing five basic model analytes in 10 mM HCl or urine was pumped through the 50 μm deep donor channel on one side of the membrane. With 15 V applied across the membrane, the protonated basic drugs were selectively extracted from the flowing sample solution, into the organic phase SLM, and further into just 7 μl of 10 mM HCl, serving as acceptor solution. Subsequently, the acceptor solution was analyzed by capillary electrophoresis. The electro membrane chip was highly efficient and even with flow rates resulting in the sample being in contact with the SLM for less than 4 s (3 μl min−1), 20–60% of the amount of the respective drugs in the sample was extracted. The large span in recovery was dependent on the physical properties of the drug substances compared to the SLM, and the individual drug substances were extracted with a RSD in the recovery of less than 5%.