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Recent Developments in Instrumentation for Capillary Electrophoresis and Microchip-Capillary Electrophoresis
Abstract
Over the last years, there has been an explosion in the number of developments and applications of CE and microchip-CE. In part, this growth has been the direct consequence of recent developments in instrumentation associated with CE. This review, which is focused on the contributions published in the last 5 years, is intended to complement the articles presented in this special issue dedicated to instrumentation and to provide an overview of the general trends and some of the most remarkable developments published in the areas of high-voltage power supplies, detectors, auxiliary components, and compact systems. It also includes a few examples of alternative uses of and modifications to traditional CE instruments.
... Table 7 displays the fragments obtained for aspart by MS/MS. [α (15)(16)(17)(18)(19)(20)(21) Based on our experience (Fig. 10, 11), it is evident that as the size of the protein increases, so does the strength of CE-UV over CE-MS in terms of detection sensitivity. As a small protein, insulin, with a mass spectra containing a fairly simple isotopic distribution and few charge states, yields comparable LOD values with UV and MS detection. ...
... This phenomenon is referred to as the "siphon effect", which affects all components (proteins) independent of the capillaries (coated or uncoated) utilized. It could, however, be diminished by turning the nebulization pressure in the ESI interface off during sample introduction and the first several minutes of the electrophoretic run(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) s prior to the detection of the first analyte)[108]. ...
... Otherwise, it might result in broad peak widths or peak distor-Nowadays, besides the conventional instruments, numerous microfabricated[18] as well as portable[19] CE counterparts serve as popular fields of research due to their enhanced performance and speed. Unlike CE, in miniachemical, off-capillary mass spectrometry, NMR detectors have been also extensively investigated[21]. High sensitivity, broad dynamic range, rapid response time, low volume detection cells, selective and unselective detection are the key considerations for proper choice of detectors. ...
In my thesis, I achieved the following:
1. Optimization of CZE-UV and CZE-MS parameters for intact protein analysis in BFS, PB-coated, and LPA-coated capillaries, considering the ideal operating conditions for each capillary.
2. Evaluation and comparison of the separation performances of LPA-coated and PB-coated capillaries with BFS capillary for simple and complex protein mixtures.
3. Demonstration of ESI-MS's good detection sensitivity for smaller proteins (M < 25 kDa) and its limited sensitivity for numerous larger proteins (M > 30 kDa).
4. Utilization of CZE-MS for beneficial TDMS examinations of proteins, providing insights into intact proteins (from smaller peptides to large mAbs) and their deamidated isoforms.
... Further merits of sensors based on CE possess the ability to utilise numerous established separation techniques, perform analyses with low power usage, and attain complete electronic control over the system. Currently, CE and miniaturized-CE devices are extensively adopted as versatile analytical platforms in diverse fields such as biomedical research, pharmaceuticals, environmental monitoring, and forensics [35]. Over the past two decades, a thoroughly examined area of research has played a pivotal role in the process of miniaturization. ...
... The cost of traditional optical equipment, the frequent requirement for analysis derivatization, and the constrained portability of LIF have initiated considerable interest in electrochemical (EC) detection. This approach is viewed as a compelling alternative detection method when coupled with M-CE [35]. The enthusiasm for M-CE-EC detection has grown significantly due to the exceptional attributes that EC detection brings to M-CE like remarkable sensitivity, inherent miniaturization and portability, cost-effectiveness, low power demands, and seamless compatibility with microfabrication technologies [82,90]. ...
After a decade of research, development, and instrument commercialization, capillary electrophoresis (CE) has firmly established itself as a recognized analytical technique. CE is a separation method that segregates charged species based on their charge and size. In the field of environmental science, CE instruments have emerged as an ideal choice due to their simplicity, efficiency, affordability, and compact design. Furthermore, CE's equipment requirements are straightforward, making it well-suited for easy miniaturization. This review provides a comprehensive overview of the latest advancements in the CE technology, with a focus on its miniaturization. It delves into portable CE and microchip-based CE, exploring their structural characteristics, advantages, and limitations. Additionally, it investigates a modular approach that consolidates all essential components onto a single board, offering a holistic perspective on the innovative possibilities within the realm of miniature capillary electrophoresis.
... However, it has not yet been systematically discussed how the thickness of microfluidic devices influences the degree of acoustic focusing, because thin microfluidic devices are delicate to use and to produce. Thus, the thickness of microfluidic devices composed of hard materials is usually found to be 1 -2 mm [29,30]. By contrast, we have worked on thinner glass microfluidic devices with a thickness as thin as 0.012 mm [31 -35]. ...
... Representing thicker microfluidic devices commonly used (1-2 mm), devices with a thickness of 1.4-2.8 mm were used to compare the achievable degree of acoustic focusing [29,30]. A piezoelectric transducer was attached to a glass microfluidic device along the length of the straight microchannel. ...
The manipulation of micro/nanoparticles has becomeincreasingly important in biological and industrial fields.As a non-contact method for particle manipulation, acousticfocusing has been applied in sorting, enrichment andanalysis of particles with microfluidic devices. Althoughthe frequency and amplitude of acoustic waves and thedimensions of microchannels have been recognized asimportant parameters for acoustic focusing, the thickness ofmicrofluidic devices has not been considered so far. Here,we report that thin glass microfluidic devices enhanceacoustic focusing of micro/nanoparticles. It was found thatthe thickness of a microfluidic device strongly influencesits ability to focus particles via acoustic radiation, becausethe energy propagation of acoustic waves is affected bythe total mass of the device. Acoustic focusing ofsubmicrometre polystyrene beads andEscherichia coliaswell as enrichment of polystyrene beads were achieved inglass microfluidic devices as thin as 0.4 mm. Modifyingthe thickness of a microfluidic device can thus serve as acritical parameter for acoustic focusing when conventionalparameters to achieve this effect are kept unchanged. Thus,our findings enable new approaches to the design of novelmicrofluidic devices.
... In recent years, capillary electrophoresis (CE) has gained attention of the international scientific community, as an alternative powerful technique for the separation and analysis of compounds of industrial, pharmaceutical, clinical, and environmental interest [1][2][3]. Some of the features that make the CE an analytical technique of great interest are its wide applicability, being possible to analyze different kinds of samples, the low cost, small amount of waste generated, small sample demand, versatility and especially simplicity in handling, and the speed of experiments that may perform the separation of many compounds in minutes or even in a few seconds [4]. According to recent papers published, the development of rapid methods using CE could be based on strategies as the use of reduced capillary length, application of high electric field, injection at the short-end of the capillary closest to the detector, use of multiple injections in a single run, or even the combinations of all of these strategies [5][6][7][8]. ...
... RSD range relative to four peaks injected (P1, P2, P3, and P4) ( = 12). 4 Values referents to a standard and a sample, outside and inside the brackets, respectively. RSD range relative to three levels of concentration tested ( = 9). ...
This paper reports the development of a subminute separation method by capillary zone electrophoresis in an uncoated capillary using multiple injection procedure for the determination of lidocaine in samples of pharmaceutical formulations. The separation was performed in less than a minute leading to doing four injections in a single run. The cathodic electroosmotic flow contributed to reducing the analyses time. The background electrolyte was composed of 20 mmol L
−1
2-amino-2-(hydroxymethyl)-1,3-propanediol and 40 mmol L
−1
2-(
N
-morpholino)ethanesulfonic acid at pH 6.1. The internal standard used was benzylamine. Separations were performed in a fused uncoated silica capillary (32 cm total length, 23.5 cm effective length, and 50
μ
m internal diameter) with direct UV detection at 200 nm. Samples and standards were injected hydrodynamically using 40 mbar/3 s interspersed with spacer electrolyte using 40 mbar/7 s. The electrophoretic system was operated under constant voltage of 30 kV with positive polarity on the injection side. The evaluation of some analytical parameters of the method showed good linearity
(
r
2
>
0.999
)
, a limit of detection 0.92 mg L
−1
, intermediate precision better than 3.2% (peak area), and recovery in the range of 92–102%.
... In microfluidic chip electrophoresis devices, the power supply is ±3kV and 100 µA direct current (DC). It is less than 10 times to capillary electrophoresis [37,38]. For alternating between the injection valve open and closed gate sequences, there are two high-voltage switches, as well as the voltages necessary to operate an injection valve with a gate. ...
The recent development of microfluidics and lab-on-a-chip technology has substantially raised interest in analytical chemistry. Since, they have demonstrated to be extraordinarily adept at precise fluid control, cell manipulation, and signal output, microfluidic chips are a useful tool for quick and in-depth single-cell investigation. This technique is cost-effective, less time-consuming, automatic, high mobility, and fast separation technique. Due to the internal chip sizes, which range from micrometers to millimeters, consumption of the samples and reagents occurs at the nanoliter and picoliter levels. The microfluidic device can fit a variety of functions onto a few centimeter-long chips. In this article, we discussed numerous preparations of microfluidic chip electrophoresis and its recent advancements. This method is useful for the detection of various small amounts of content with less time and greater efficacy. It is also useful in cancer studies, 3D inkjet printing, immunoassay investigation in cell-cell interactions, analysis of nanoparticles, dielectrophoretic particle separation, plant alkaloids, and forensic science applications. This review, therefore, examines the use of various microfluidic chips in electrophoretic separation during 2017–2022. There are various papers found by search, indicating continuous activity in the research area along with studies to explain its material, method, and its efficacy.
... ME allows for integrating multiple functions such as injection, separation, and detection on a single microchip with typical channel lengths of 1-10 cm [20]. ME has been coupled to different detection methods, including laser-induced fluorescence detection [21], mass spectrometric detection, and chemiluminescence [22]. Although the majority of the analytical techniques mentioned above provide high sensitivity, they require derivatization reactions, which are laborious and time consuming. ...
A simple, rapid method using CE and microchip electrophoresis with capacitively coupled contactless conductivity detection has been developed for the separation of four Nonsteroidal anti‐inflammatory drugs (NSAIDs) in the environmental sample. The investigated compounds were ibuprofen (IB), ketoprofen (KET), acetylsalicylic acid (ASA), and diclofenac sodium (DIC). In the present study, we applied for the first time ME with C4D detection to the separation and detection of ASA, IB, DIC, and KET in the wastewater matrix. Under optimum conditions, the four NSAIDs compounds could be well separated in less than 1 min in a BGE composed of 20 mM His/15 mM Tris, pH 8.6, 2 mM HP‐β‐CD, 10% methanol (v/v) at a separation voltage of 1000 ‐ 1200 V. The proposed method showed excellent repeatability, good sensitivity (LODs ranging between 0.156 and 0.6 mg/L), low cost, high sample throughputs, portable instrumentation for mobile deployment, and extremely lower reagent and sample consumption. The developed method was applied to the analysis of pharmaceuticals in wastewater samples with satisfactory recoveries ranging from 62.5% to 118%. This article is protected by copyright. All rights reserved
... The cost of extra reagents makes IFE less affordable [27,31]. CE is an alternative method to gel-based methods (SPEP, IFE) that is based on small-hole (10-100 mm), silica capillary tubes, and microfluidics to separate proteins displayed using a UV detector [33]. However, CE has limited analytical sensitivity, poor solubility and encounters difficulties in communicators [34]. ...
Background:
Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. The diagnosis of Alzheimer's disease according to symptomatic events is still a puzzling task. Developing a biomarker-based, low-cost, and high-throughput test, readily applicable in clinical laboratories, dramatically impacts the rapid and reliable detection of the disease.
Objective:
This study aimed to develop an accurate, sensitive, and reliable screening tool for diagnosing Alzheimer's disease, which can significantly reduce the cost and time of existing methods.
Methods:
We have employed a MALDI-TOF-MS-based methodology combined with a microaffinity chromatogra Results: We observed a statistically significant difference in the kappa light chain over lambda light chain (κLC/LC) ratios between patients with AD and controls (% 95 CI: -0.547 to -0.269, p<0.001). Our method demonstrated higher sensitivity (100.00%) and specificity (71.43%) for discrimination between AD and controls.
Conclusion:
We have developed a high-throughput screening test with a novel sample enrichment method for determining κLC/LC ratios associated with AD diagnosis. Following further validation, we believe our test has a potential for clinical laboratories.
... The hydrophilic molecules do not stay for longer periods and migrate through the solvent, whereas hydrophobic molecules require more time to migrate. In the absence of micelles, neutral species move with the help of EOF and separation does not occur (Fig. 6) [10,11]. ...
Capillary electrophoresis (CE) is widely used for the impurity profiling of drugs that contain stereochemical centers in their structures, analysis of biomolecules, and characterization of biopharmaceuticals. Currently, CE is the method of choice for the analysis of foodstuffs and the determination of adulterants. This article discusses the general theory and instrumentation of CE along with the classification of various CE techniques. It also presents an overview of research on the applications of different CE techniques in the impurity profiling of drugs in the past decade. The review briefly presents a comparison between CE and liquid chromatography methods and highlights the strengths of CE using drug compounds as examples. This review will help scientists, fellow researchers, and students to understand the applications of CE techniques in the impurity profiling of drugs.
... Screening the literature reveals a number of previously reported reviews dealing with either the advancement in the instrumentation of MCE, its different detection techniques or its application as analytical tool in different areas. Felhofer et al. [11] reviewed advancement in the instrumentation of MCE in the period 2005-2010. Another review summarizes microfluidic platforms developments for biochemical assays. ...
Microfluidic capillary electrophoresis (MCE) is the novel technique resulted from the CE mininaturization as planar separation and analysis device. This review presents and discusses various application fields of this advanced technology published in the period 2017 till mid-2019 in eight different sections including clinical, biological, single cell analysis, environmental, pharmaceuticals, food analysis, forensic and ion analysis. The need for miniaturization of CE and the consequence advantages achieved are also discussed including high-throughput, miniaturized detection, effective separation, portability and the need for micro- or even nano-volume of samples. Comprehensive tables for the MCE applications in the different studied fields are provided. Also, figure comparing the number of the published papers applying MCE in the eight discussed fields within the studied period is included. The future investigation should put into consideration the possibility of replacing conventional CE with the MCE after proper validation. Suitable validation parameters with their suitable accepted ranges should be tailored for analysis methods utilizing such unique technique (MCE).
... A voltage of 5 to 30 kV is applied across the two electrodes; its polarity can be reversed to permit a fast separation of anions. [122][123][124][125] An electro-osmotic flow (EOF) is usually created when a high voltage is applied across a fusedsilica capillary tube containing a buffer solution; as a result, the migration is toward the cathode. ...
Nowadays, the management of infectious diseases is especially threatened by the rapid emergence of drug resistance. It has been suggested that the medicine quality assurance combined with good medication adherence may help to reduce this impendence. Moreover, the search for new antimicrobial agents from medicinal plants is strongly encouraged for the exploration of alternatives to existing therapies. In this context, the present work focused on both the quality evaluation of commercialized antimalarial medicines from the Democratic Republic of the Congo and on the phytochemical investigations of a Congolese Ancistrocladus species.
... To examine the effect on optical performance the optical characterization for the flow cell including transparent detection window was performed. Orange G has been commonly used in previous studies as the model analyte for the characterisation of the optical detectors/detection methods [29,30], therefore it was chosen as the test analyte for the characterisation of the newly developed flow cell. ...
Optical detection is the most common detection mode for many analytical assays. Photometric detection systems and their integration with analytical systems usually require several assembly parts and manual alignment of the capillary/tubing which affects sensitivity and repeatability. 3D printing is an innovative technology for the fabrication of integrated complex detection systems. One step multi-material 3D printing has been explored to fabricate a photometric detector flow cell from optically transparent and opaque materials using a dual-head FDM 3D printer. Integration of the microchannel, the detection window and the slit in a single device eliminates the need for manual alignment of fluidic and optical components, and hence improves sensitivity and repeatability. 3D printing allowed for rapid design optimisation by varying the slit dimension and optical pathlength. The optimised design was evaluated by determining stray light, effective path length and the signal to noise ratio using orange G. The optimised flow cell with extended path length of 10 mm and 500 μm slit yielded 0.02% stray light, 89% effective path length and detection limit of 2 nM. The sensitivity was also improved by 80% in the process of optimisation, using a blue 470 nm LED as a light source.
... The separation in terms of repeatability of the migration times and the peak areas can to a large extent depend on the HVPS quality. Three relatively recent review articles provide some information on available HVPSs [11][12][13]. Typically, HVPS can apply up to ±30 kV and ±300 A if designed for standard CE. ...
Open source paradigm is becoming widely accepted in scientific communities and open source hardware is finding its steady place in chemistry research. In this review article we provide the reader with the most up‐to‐date information on open source hardware and software resources enabling the construction and utilization of an “open source capillary electrophoresis“(OSCE) instrument. While capillary electrophoresis (CE) is still underused as a separation technique, it offers unique flexibility, low‐cost, and high efficiency and is particularly suitable for open source instrumental development. We overview the major parts of CE instruments, such as high voltage power supplies, detectors, data acquisition systems and CE software resources, with emphasis on availability of the open source information on the web and in the scientific literature. This review is the first of its kind, revealing accessible blueprints of most parts from which a fully functional open source CE system can be built. By collecting the extensive information on OSCE in this review article, the authors aim at facilitating the dissemination of knowledge on CE within and outside the scientific community, fosters innovation and inspire other researchers to improve the shared CE blueprints.
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... Capillary Electrophoresis Microchips can be used as a versatile tool for ion concentration measurements in liquid samples. Previously investigated applications address medical point of care diagnostics, fast chemical process analytics, environmental analysis and others [1][2]. Recently, applications in soil analysis were reported [3][4] as the technology allows measuring the most important plant nutrients (plant macronutrients) in one miniaturized device. ...
A process suitable for high throughput manufacturing of capillary electrophoresis microchips is presented. The microfluidic channels were produced by imprinting on large area polymer foils. The following steps of inlet cutting, bonding and electrode printing were adapted to large area processing, too. Hence, production of a huge number of chips in parallel without need for complicated single chip handling gets feasible and low chip manufacturing costs get feasible. First chips were produced and used for determination of ion concentrations in soil sample extracts.
... Although several HV sources for multidimensional CE and microchip CE applications were reported [40][41][42], the problem of monitoring V i and its implementation has hardly been discussed [41]. In principle, the following basic aspects have to be taken into consideration: ...
One of the greatest challenges in multi-channel networks for electromigrative separation techniques is the control of the leakage of sample constituents and band broadening at the channel intersections in microfluidic devices or capillary-chip interfaces, which can be achieved using fixed bias or pullback potentials. These may be implemented as the first separation dimension in a 2D setup, where the electric potential at the interface to the second dimension changes with time. Thus, a dynamic control via on-line potential measurement in combination with a feedback system is needed to control electromigration into the side channels. We here present for the first time a prototype for in-channel potential measurements using a low working current in combination with a Si3N4 passivated Ti/Pt electrode at the intersection of the channels in a microfluidic interface. Exemplarily we chose capillary electrophoresis and isotachophoresis as model applications with constant vs. dynamic potential. Parallel on-chip intersection potential measurements were successfully conducted without disturbing capillary zone electrophoretic and isotachophoretic analysis regarding separation and peak performance of amino acids chosen as model analytes. This was possible due to a Si3N4 passivation layer, but also due to an ad-hoc developed high impedance instrumentation, resulting in a very low measuring electric current. Simulations of the detected isotachophoretic cross-section potential allowed a deeper understanding of the potential development during the separation.
... On the other hand, various sensitive detection schemes have been developed and applied in microfluidics , providing a sensitive detection of the non-fluorescent analytes or selective detection based on an affinity [76]. Furthermore, the studies on a development of small/portable instruments for an onsite or point-of-care analysis have been also in progress [77]. In the near future, the author believes that these different approaches will be combined to realize the highly sensitive, effective, highthroughput analysis with a low cost and easy procedure. ...
Microchip electrophoresis (MCE) is one of the versatile separation techniques in microfluidic systems since MCE has remarkable advantages such as high resolution, rapid analysis, small consumptions of samples and reagents, and high integratability to other chemical operations on planer substrate. However, there still remains a significant problem about a poor sensitivity due to a short optical pathlength and extremely small volume of analytes introduced into the separation channel. To overcome this drawback, a lot of on-line sample preconcentration methods have been developed and applied to MCE for improving the sensitivity. In this review, the author highlights recent progresses on combinations of chemical operations integrated onto microfluidic devices for enhancing a detector signal, e.g., solid phase extraction (SPE), affinity capturing, electrokinetic filtrating/trapping, and polymerase chain reaction (PCR) with MCE mainly from 2009. The other integrated techniques and methods which are expected to be combined with MCE are also introduced briefly.
... ME emerged in the early 1990s [56][57][58][59], and has evolved greatly since then. Some of the advantages of microchips over conventional benchtop CE systems include custom design, reduced consumption of reagent and sample, lower waste generation, increased analysis speed, and portability [55,60,61]. In ME, an electric potential difference is applied across a microchannel filled with an electrolyte solution (Fig. 6a). ...
We present a comprehensive discussion of the role that microchip electrophoresis (ME) instrumentation could play in future NASA missions of exploration, as well as the current barriers that must be overcome to make this type of chemical investigation possible. We describe how ME would be able to fill fundamental gaps in our knowledge of the potential for past, present, or future life beyond Earth. Despite the great promise of ME for ultrasensitive portable chemical analysis, to date, it has never been used on a robotic mission of exploration to another world. We provide a current snapshot of the technology readiness level (TRL) of ME instrumentation, where the TRL is the NASA systems engineering metric used to evaluate the maturity of technology, and its fitness for implementation on missions. We explain how the NASA flight implementation process would apply specifically to ME instrumentation, and outline the scientific and technology development issues that must be addressed for ME analyses to be performed successfully on another world. We also outline research demonstrations that could be accomplished by independent researchers to help advance the TRL of ME instrumentation for future exploration missions. The overall approach described here for system development could be readily applied to a wide range of other instrumentation development efforts having broad societal and commercial impact.
... Capillary electrophoresis (CE) is a widely employed analytical technique which presents high versatility. This property leads to a wide variety of instrumental developments [1]. On the one hand, the design of portable CE equipment is a current trend, as it would allow the in situ analysis, useful in some analytical fields such as environmental or forensic sciences [2] [3]. ...
Abstract In this article, we present a microstructured capillary electrophoresis method for the determination of minimal amounts of nitrocellulose in dynamite samples. A 6-hole microstructured capillary (MSC) was selected for the method development. First, the hydrodynamic behaviour of the MSC was studied at varying lengths (31, 41 and 51 cm), which had never been studied before. Next, one of the MSC segments (31 cm) was employed to develop a microstructured capillary electrophoresis method to determine nitrocellulose in dynamite. In a first evaluation, the dynamite derivatization process was investigated to obtain an efficient derivatization yield. Afterward, the instrumental parameters, more specifically voltage and capillary cartridge temperature, were optimized. Afterward, the analytical performance of the developed methodology was assessed. Dynamite analyses during a period of 15 days were performed to establish intra-day (10 analyses) and inter-day (40 analyses) precision, obtaining RSDs lower than 6% and 10%, respectively. Besides, RSDs for migration time (< 0.5%), peak asymmetry (< 3%), resolution (< 3.9%), and S/N (< 9%) were obtained. Finally, a diluted sample of dynamite was analyzed, detecting amounts of nitrocellulose in the order of 220–400 pg.
... Microchip electrophoresis has become a powerful and effective analytical tool in the last years [19,20] due to this unique features [21] and the general trend toward miniaturization. The success of microchip electrophoresis depends not only on a suitable fabrication material, but also on the choice of an adequate detection system. ...
Ionic liquids have been attracting attention as background additives to improve separations in the last years. This work reports about the use of four ionic liquids (ILs): 1-butyl-4-methylpyridinum tetrafluoroborate (BMPyBF4), 1-buty1-3-methylimidazolium tetrafluoroborate (BMIMBF4), 1-buty1-3methylimidazolium hydrogen sulfate (BMIMHSO4) and 1-ethy1-3-methylimidazolium methyl sulfate (EMIMMeSO4) as dynamic modifiers in glass and SU-8 microchip electrophoresis (ME). The influence of varying pH values and ILs concentration on the detection system was investigated. Moreover, ionic liquids with different cations and counterions were evaluated as background additives choosing two catecholamines (dopamine, DA and epinephrine, E) as model analytes. Dynamic modification with ILs proved to be necessary to obtain enhanced mixture separation in both 30 mm glass and SU-8 MEs. Good precision in terms of migration times and resolution was obtained for both kinds of MEs when ILs were employed. In addition, baseline resolution with good reproducibility over time (RSD values of 0.5% and 0.8% for migration times in one experiment and three days, respectively) was achieved in glass MEs with 60 mm effective separation length. (C) 2013 Published by Elsevier B.V.
... Over the last decades technological and scientific achievements have led to huge improvements in the world of analytical chemistry, including CE, where many of the developments have focused on system automation and miniaturization [1,2]. However, studies regarding the capillary have not been reported in a great extent. ...
Two prototypes of micro-structured capillaries (MSCs) were designed, manufactured and used to carry out different experiments. MSC-1 consisted of 6 holes of ≈ 28 μm id whereas MSC-2 consisted of 85 holes of ≈ 7.7 μm id. A fundamental study on the hydrodynamic injection through a commercial CE equipment was made. Experimental times to flush specific volumes were approximately 3 times larger than the theoretical values. Then, the detection of starch was carried out by using the MSCs and conventional capillaries, and the electropherograms were compared on the basis of analytical parameters employed in CE. An improvement in peak asymmetry was obtained for the MSC-1 compared to the conventional capillaries. S/N ratio was 1 order of magnitude increased with the MSC, improving 10 times the sensitivity. Considering this advantage, the separation and detection of nitrostarch was performed as a first application of the MSC-1. Minimal sample amounts of nitrostarch (1.7 μg) were detected. Results present a real interest in forensics since this substance had not been previously detected through CE, leading to new investigations in the design of new capillaries capable of enhancing CE performance.This article is protected by copyright. All rights reserved
... In this regard, our group has recently presented two versatile and inexpensive approaches to either assemble [13] or engrave microfluidic devices [14]. Despite these advances, it is important to stress the limited number of publications related to instrumentation designed for microfluidic devices [2,13,[15][16][17][18]. In turn, this could be attributed to a combination of limited funding opportunities to support such engineering-oriented endeavors, a gap in interest and/or preparation of classic chemistry students in the area of electronic circuits and software, and the cost of traditional platforms such as LabView (National Instruments, http://www.ni.com/ labview/). ...
Understanding basic concepts of electronics and computer programming allows researchers to get the most out of the equipment found in their laboratories. Although a number of platforms have been specifically designed for the general public and are supported by a vast array of on-line tutorials, this subject is not normally included in university chemistry curricula. Aiming to provide the basic concepts of hardware and software, this article is focused on the design and use of a simple module to control a series of PDMS-based valves. The module is based on a low-cost microprocessor (Teensy) and open-source software (Arduino). The microvalves were fabricated using thin sheets of PDMS and patterned using CO2 laser engraving, providing a simple and efficient way to fabricate devices without the traditional photolithographic process or facilities. Synchronization of valve control enabled the development of two simple devices to perform injection (1.6 ± 0.4 μL / stroke) and mixing of different solutions. Furthermore, a practical demonstration of the utility of this system for microscale chemical sample handling and analysis was achieved performing an on-chip acid-base titration, followed by conductivity detection with an open-source low-cost detection system. Overall, the system provided a very reproducible (98%) platform to perform fluid delivery at the microfluidic scale.This article is protected by copyright. All rights reserved
... This problem is exacerbated when the target analytes have low or no absorptivity [2]. Among other examples where improvements in sensitivity could allow a wider application of CE-UV [3] and avoid the use of complex and bulky instrumentation [4,5], biogenic amines [6], environmental pollutants [7], and amino acids [8] are of critical importance. The analysis of primary amines such as putrescine, cadaverine, spermidine, and spermine in food samples is clinically relevant because they can cause a variety of health problems including headaches, nausea, and (in some individuals taking monoamine oxidase inhibitors) severe effects on the cardiovascular and central nervous systems [9,10]. ...
Quality control (QC) is a major concern in the pharmaceutical industry to ensure medicines quality and patient’s safety. QC analysis are currently performed using several well-known separative and spectroscopic techniques. However, current trends are focused on the development of high performance techniques for reducing analysis time and cost and decreasing ecological footprint. In this context, analytical scientists developed microfluidic techniques such as microchip electrophoresis (MCE). This paper provides an overview of MCE system development and applications in perspectives with the requirements of QC analysis. The objective of the present review is to evaluate if MCE could be, now or in the future, a suitable alternative for pharmaceutical quality control. The quantitative performances of published MCE methods are deeply discussed using precision criterion (RSD) as a common thread.
Capillary electrophoresis (CE) is a separation technique employed for the analysis of charged and uncharged species, ranging from small inorganic ions to complex biomolecules. The versatility of CE arises from the many modes of operation such as capillary zone electrophoresis, micellar electrokinetic capillary chromatography, isoelectric focusing, isotachophoresis, capillary electrochromatography and capillary gel electrophoresis. Microchip‐Capillary Electrophoresis (ME) is a miniaturised version of CE where the capillary is replaced by a chip capillary device, which was initially proposed in the early 1990s by Manz and co‐workers. ME offers other potential advantages, particularly for compounds of forensic significance. These include shorter analysis times and lower sample volumes, as well as the potential for creation of disposable devices and automation. Electrochemical detectors (amperometry and conductometry) are commonly used in ME devices due to their high sensitivity and relatively easy implementation.
This paper presents an inexpensive and easy‐to‐implement voltage sequencer instrument for use in microchip capillary electrophoresis (MCE) actuation. The voltage sequencer instrument takes a 0 – 5 V input signal from a microcontroller and produces a reciprocally proportional voltage signal with the capability to achieve the voltages required for MCE actuation. The unit developed in this work features four independent voltage channels, measures 105 × 143 × 45 mm (width × length × height), and the cost to assemble is under 60 USD. The system is controlled by a peripheral interface controller and commands are given via universal serial bus connection to a personal computer running a command line graphical user interface. The performance of the voltage sequencer is demonstrated by its integration with a fluorescence spectroscopy MCE sensor using pinched sample injection and electrophoretic separation to detect ciprofloxacin in samples of milk. This application is chosen as it is particularly important for the dairy industry, where fines and health concerns are associated with the shipping of antibiotic‐contaminated milk. The voltage sequencer instrument presented represents an effective low‐cost instrumentation method for conducting MCE, thereby making these experiments accessible and affordable for use in industries such as the dairy industry.
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High-speed capillary electrophoresis (HSCE) is implemented using a 10 cm total length fused-silica capillary (50 m i.d. by 80 m o.d.) combined with refractive index (RI) detection using back-scatter interferometry (BSI). The short capillary length reduces analysis time while the ultra-thin wall (15 m) efficiently dissipates heat from the separation channel, mitigating the deleterious effects of Joule heating. The separation capillary is mounted on a temperature-controlled heat sink that stabilizes temperature to ± 0.004 oC. This temperature stabilization improves separation efficiency and enhances RI detection. Ohm’s law plots confirm the superior heat dissipation of the HSCE capillary compared to a similarly prepared conventional CE capillary (50 m i.d. by 363 m o.d.). The speed and efficiency of HSCE combined with universal RI detection is illustrated through the separation of K+, Ba2+, Mg2+, Na+, Li+, and Tris+ in approximately 30 s, with efficiencies greater than 500,000 plates/m. Run-to-run repeatability is explored using nine consecutive electrokinetic injections of a K+, Na+, and Li+ mixture. The average migration times and %RSD for K+, Na+, and Li+ were measured to be 22.04 s (1.59%), 26.81 s (1.38%), and 29.80 s (2.21%), respectively. Finally, we show that the BSI signal is sensitive to the separation voltage through the Kerr mechanism. This leads to peaks in the electropherogram from the injection process that are useful for precisely defining the start of each separation and quantifying the amount of sample injected onto the capillary.
We present the application of a smartphone anatomy based technology in the field of liquid phase bioseparations, particularly in capillary electrophoresis. A simple capillary electrophoresis system was built with LED induced fluorescence detection and a credit card sized minicomputer to prove the concept of real time fluorescent imaging (zone adjustable time-lapse fluorescence image processor) and separation controller. The system was evaluated by analyzing under- and overloaded aminopyrenetrisulfonate (APTS)-labeled oligosaccharide samples. The open source software based image processing tool allowed undistorted signal modulation (reprocessing) if the signal was inappropriate for the actual detection system settings (too low or too high). The novel smart detection tool for fluorescently labeled biomolecules greatly expands dynamic range and enables retrospective correction for injections with unsuitable signal levels without the necessity to repeat the analysis.
This chapter gives an overview of chip-based capillary electrophoresis (CE). It includes the factors such as the substrate materials, fabrication technologies, surface modification methods, injection methods, detection techniques, and so on, which influence the performance of the chip-based CE. Moreover, the applications of the chip-based CE are also summarized. In addition, future developments in the related research field have also been discussed.
Gel electrophoresis is one of the most applied and standardized tools for separation and analysis of macromolecules and their fragments in academic research and in industry. In this work we present a novel approach for conducting on-demand electrophoretic separations of DNA molecules in open microfluidic (OM) systems on planar polymer substrates. The approach combines advantages of slab gel, capillary- & chip-based methods offering low consumable costs (<0.1 $) circumventing cost intensive microfluidic chip fabrication, short process times (5 minutes per analysis) and high sensitivity (4 ng/μl dsDNA) combined with reasonable resolution (17 bases). The open microfluidic separation system comprises two opposing reservoirs of 2-4 μl in volume, a semi-contact written gel line acting as separation channel interconnecting the reservoirs and sample injected into the line via non-contact droplet dispensing and thus enabling the precise control of the injection plug and sample concentration. Evaporation is prevented by covering aqueous structures with PCR-grade mineral oil while maintaining surface temperature at 15°C. The liquid gel line exhibits a semi-circular cross section of adaptable width (∼200-600 μm) and height (∼30-80 μm) as well as a typical length of 15-55 mm. Layout of such liquid structures is adaptable on-demand not requiring time consuming and repetitive fabrication steps. The approach was successfully demonstrated by the separation of a standard label-free DNA ladder (100-1000 bp) at 100 V/cm via in-line staining and laser induced fluorescent end-point detection using an automated prototype. This article is protected by copyright. All rights reserved.
We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device.
Soon after capillary electrophoresis (CE) became established as a high-resolution, liquid-phase microseparation, instrumental analysis technique by the end of the 1980s, first efforts were reported to couple CE with mass spectrometry (MS). Electrospray ionization (ESI) has been established as the preferred technique for coupling HPLC with MS. Microchip CE (MCE)-MS is still in a proof-of-principle stage and has remained an active area of research for several groups worldwide. This chapter focuses on developments of MCE-MS published since the middle of the past decade. It first presents the principle of operation of MCE, and then goes on to present reviews on MCE and MCE-MS. The main requirements of MCE-MS include ESI, and the layout of MCE-MS devices. The chapter also discusses MCE-MS by direct off-chip spraying, with connected sprayer, and with integrated sprayer. It ends with a discussion on multidimensional MCE-MS devices.
Electrochemical methods of chemical analysis have been widely used for many years, most especially the trusty pH electrode and conductivity meter, but also in the mass-manufactured glucose test strips which place electrochemical measurements into the hands of non-scientists.
The purpose of this volume is to address advances that will enable new measurement strategies in the future. Surveying research and development advances based on new methods, materials and devices that achieve improved electroanalytical performances, this collection encompasses chip-based systems, through nanodomain approaches and soft interfaces. This book is a vital resource for graduate students and professional analytical chemists.
Precise measurement of nitric oxide (NO) is of great importance to understand the function of NO in liver and the mechanism of liver injury. 8-(3',4'-Diamino phenyl)-3,5-(2-hydroxyphenyl)-dimethylene pyrrole (BOPB), a fluorescent probe in the red region (> 600 nm) newly developed in our group, has good photo-stability and excitation/emission wavelength of 622/643 nm matching well with commercial 635 nm semiconductor laser of capillary electrophoresis with laser induced fluorescence detection (CE-LIF). Therefore, BOPB was used in CE-LIF for the determination of NO in mice liver. Both derivatization and separation conditions were optimized. Derivatization reaction of BOPB and NO was carried out in pH 7.4 PBS buffer at 35 ℃ for 12 min and the separation of NO derivative (BOPB-T) of BOPB was achieved within 7.0 min in pH 9.0 running buffer containing 15 mM H3 BO3 -NaOH and 15 mM SDS. Good linearity was found in the range of 1.0×10(-9) - 5.0×10(-7) M with the limit of detection of 0.02 nM. The proposed method was applied to the analysis of NO in real samples, and NO concentration was increased obviously in acute liver injury of mice. Compared to existing derivatization-based CE-LIF methods for NO, this method has lower LOD and less background interference owing to detection wavelength of BOPB in the red region. This article is protected by copyright. All rights reserved.
We developed an automated direct blotting system that completes the entire process of electrophoresis and electroblotting within 1-2 h. This system has high transfer reproducibility compared with the conventional semi-dry method. We also demonstrated the primary application of direct blotting of two-dimensional separated proteins, providing the expansion of protein spots.
A novel and rapid method was developed for the determination of uric acid in human urine by capillary electrophoresis with an improved electromagnetic induction detector. Electrophoretic parameters affecting the separation efficiency, such as buffer composition, buffer pH, buffer concentration, and electroosmotic flow modifier, were systematically investigated. An electrolyte solution consisting of 8.5 mmol L−1 tris(hydroxymethyl)aminomethane (Tris), 1.5 mmol L−1 citric acid, and 0.2 mmol L−1 cetyltrimethylammonium bromide, pH 8.0, was found to be suitable for sample determination. Uric acid was separated and detected within 2.3 min, with a linear response range from 5 to 400 µg mL−1 and a correlation coefficient of 0.9998. Intraday and interday precision were 1.6 and 2.5 % (n = 6), respectively. The recoveries were between 98.3 and 100.5 %. This simple, effective, and stable method is a good alternative to existing methods for uric acid determination. Also, the improved electromagnetic induction detector holds great promise in clinical analysis.
Microchip capillary electrophoresis (MCE) is becoming an established technique for point-of-care analyses of small samples because of its portability and short analysis times. However, most MCE development has focused on disposable devices for one-sample analyses. An MCE area that has not been actively pursued is the ability to perform continuous, unattended monitoring with a single device over extended timescales of hours, days, or even weeks. Many typical MCE analyses suffer from poor qualitative and quantitative reproducibility at timescales longer than a few minutes. Multiple factors degrade reproducibility at longer times, including surface fouling, background electrolyte depletion, solution volatilization, and changes to bulk flow rates. Additionally, extended monitoring often requires the use of sequential injections, which can be interfered with by late-migrating sample species or system zones from previous injections. This chapter discusses approaches for making MCE a more viable technique for long-term monitoring applications, reviews relevant literature since the inception of capillary
The application of affinity capillary electrophoresis (ACE), a submode of capillary zone electrophoresis, to investigate the interactions between ligands and their substrates is described in this chapter. Using ACE, it is possible to characterize noncovalent molecular interactions (complexation and partition equilibria) of different binding strengths. Resulting association constants (K) provide a measured value of the affinity of a ligand molecule to a substrate. Starting with the background of high-performance capillary electrophoresis (HPCE), in general, and ACE, various possibilities are given how ACE can be used in capillaries or chips. A brief mathematical description of the context between measured parameters (ionic mobility, peak area, or peak height) and evaluated binding parameters (as binding constants and stoichiometry number), as well as various ACE modes and constellations of intermolecular interacting molecules suitable for a wide range of applications are provided. Finally, selected applications are described in detail in terms of the experimental setup and estimation of the binding strength by a suitable mathematical model.Keywords:affinity capillary electrophoresis;binding constant;interaction;biomolecules;receptor ligand;stoichiometry
This chapter is intended as a basic introduction to microchip-based capillary electrophoresis to set the scene for newcomers and give pointers to reference material.
An outline of some commonly used setups and key concepts is given, many of which are explored in greater depth in later chapters.
We report simple and rapid capillary electrophoresis (CE) separation followed by in-channel pulsed amperometric detection (PAD) of three common triazine herbicides: simazine, atrazine and ametryn that are used to control broad leaf weeds and annual grasses. For their detection in soil and groundwater samples, a CE-PAD microfluidic chip was fabricated using standard photolithography methods. Cyclic voltammetry was conducted on these herbicides that exhibited a characteristic cathodic peak at -0.70 V for simazine or atrazine and -0.80 V for ametryn, without any anodic peak at reverse scan, indicating that the cathodic peaks were irreversible electron transfer processes. For effective CE-PAD separation of triazine complex, the capillary was filled with 1.5% agarose. The pulsed amperometric detection of these chemicals ensured better sensor response and low electrode fouling. The average electropherogram of simazine, atrazine and ametryn showed single peaks at 58, 66 and 74 s, respectively at 20 V/cm separation potential. A mixture of all three herbicides showed similar separated peaks. HPLC was also conducted in a soil spiked with these pollutants to compare the method. The results hold the promise of detecting triazines within a very short time. (c) 2012 Elsevier B.V. All rights reserved.
The number of pesticides used in agriculture is increasing steadily, leading to contamination of soil and drinking water. Herein, we present a microfluidic platform to detect the extent of contamination in soil samples. A microchip capillary electrophoresis system with in-channel electrodes was fabricated for label-free electroanalytical detection of triazine herbicides. The sample mixture contained three representative triazines: simazine, atrazine and ametryn. The electropherogram for each individual injection of simazine, atrazine and ametryn showed peaks at 58, 66 and 72 s whereas a mixture of them showed distinct peaks at 59, 67 and 71 s respectively. The technique as such may prove to be a useful qualitative and quantitative tool for the similar environmental pollutants.
The number of pesticides used in agriculture is increasing steadily, leading to contamination of soil and drinking water. Herein, we present a microfluidic platform to detect the extent of contamination in soil samples. A microchip capillary electrophoresis system with in-channel electrodes was fabricated for label-free electroanalytical detection of triazine herbicides. The sample mixture contained three representative triazines: simazine, atrazine and ametryn. The electropherogram for each individual injection of simazine, atrazine and ametryn showed peaks at 58, 66 and 72 s whereas a mixture of them showed distinct peaks at 59, 67 and 71 s respectively. The technique as such may prove to be a useful qualitative and quantitative tool for the similar environmental pollutants.
MicroRNAs (miRNAs) are short noncoding RNAs that conduct important roles in many cellular processes such as development, proliferation, differentiation, and apoptosis. In particular, circulating miRNAs have been proposed as biomarkers for cancer, diabetes, cardiovascular disease, and other illnesses. Therefore, determination of miRNA expression levels in various biofluids is important for the investigation of biological processes in health and disease and for discovering their potential as new biomarkers and drug targets. Capillary electrophoresis (CE) is emerging as a useful analytical tool for analyzing miRNA because of its simple sample preparation steps and efficient resolution of a diverse size range of compounds. In particular, CE with laser-induced fluorescence detection is a promising and relatively rapidly developing tool with the potential to provide high sensitivity and specificity in the analysis of miRNAs. This paper covers a short overview of the recent developments and applications of CE systems in miRNA studies in biological and biomedical areas.
Copyright © 2014 Elsevier B.V. All rights reserved.
A simple and sensitive method for determination of free amino acids in milk by microchip electrophoresis (MCE) coupled with laser-induced fluorescence (LIF) detection was developed. Seven kinds of standard amino acids were derivated with sulfoindocyanine succinimidyl ester (Cy5) and then perfectly measured by MCE-LIF within 150 s. The parameters of MCE separation were carefully investigated to obtain the optimal conditions: 100 mmol·L−1 sodium borate solution (pH 10.0) as running buffer solution, 0.8 kV as injection voltage, 2.2 kV as separation voltage etc. The linear range of the detection of amino acids was from 0.01 µmol·L−1 to 1.0 µmol·L−1 and the detection limit was as low as about 1.0 nmol·L−1. This MCE-LIF method was applied to the measurements of free amino acids in actual milk samples and satisfactory experimental results were achieved.
In this paper, we describe design and fabrication of 3-D silicon microarrays consisting of a wide range of isotropically-etched concave cavities for cell-capturing applications. The microarrays supported rapid and efficient capture of metastatic human breast cancer cells (MDA-MB-231) from single-cell suspensions. Furthermore, the captured cells adhered and were retained within the etched cavities for at least 72 h. Cavity spacing of 30-50 μm was most suitable for capture of the cells within microwells. Cell capture was evident within 1 min and was essentially complete by 20-30 min. Capture of 10 μm beads proceeded with a similar time frame and efficiency. Cell capture was 80%-90% efficient and was independent of cavity diameters tested: 35, 60, 70, and 100 μm. The depth of the microwells ranged from 28 to 54 μm. For single-cell capture, the 35 μm diameter cavity was optimal. The larger cavities contained 3-10 cells and were better suited for applications sensing cell proliferation, cell-cell interactions, stem cell differentiation, and drug responsiveness. The proposed silicon microarrays did not require any chemical coating or surface modification to support micro co-cultures of normal human breast epithelial cells (MCF10A) and MDA-MB-231 after cell trapping. This paper demonstrates that the silicon microarrays efficiently capture individual human breast cancer cells from a mono-culture suspension and in a mixture of excess MCF10A. Therefore the developed silicon platform is suitable for efficient detection and sensing of individual human breast cancer cells.
The integration of simple and robust device components required for the successful adaptation of many analytical methods to multiplexed and field-portable devices often has negative effects on detection sensitivity, such as in the optical detection components in a capillary electrophoresis (CE) system. One of the simplest methods to improve sensitivity in the CE field is known as sample stacking. This method involves preparing the sample in a buffer with a different concentration (and conductivity) than that of the run buffer so that when an electric field is applied the analyte concentration is increased at the boundary between the two different buffer concentrations. Here, we describe a method in which the sample is prepared in a buffer at a lower concentration than the run buffer coupled with a recently described counter-flow electrophoresis method, gradient elution moving boundary electrophoresis (GEMBE), with channel current detection. Because of the continuous sample introduction with GEMBE, we refer to the method as field amplified continuous sample injection (FACSI). This method achieves a significantly greater signal enhancement than expected for sample stacking. For example, we achieve signal enhancement of 110× with a conductivity ratio of 8.21, and using the detection of arsenate in drinking water as a model system, we have achieved an LOD improvement of approximately 60× (LODs with and without FACSI are 200nmol/L and 12µmol/L respectively) with a conductivity ratio of approximately 5.93.
This chapter describes the most important features of capillary electrophoretic equipment. A presentation of the important developments in high voltage power supplies for chip CE is followed by preparation of fused silica capillaries for use in CE. Detection systems that are used in capillary electrophoresis are widely described. Here, UV-Vis absorbance measurements are discussed including different types of detection cells—also those less popular (u-shaped, Z-shaped, mirror-coated). Fluorescence detection and laser-induced fluorescence detection are the most sensitive detection systems. Several LIF setups, such as collinear, orthogonal, confocal, and sheath-flow cuvette, are presented from the point of view of the sensitivity they can provide. Several electrochemical detectors for CE, such as conductivity, amperometric, and potentiometric, are also shown and their constructions discussed. CE-MS and much less known CE (CEC)-NMR systems are also described. The examples of automation and robotized CE systems together with their potential fields of application are also presented.
Carbon nanotubes are among the plethora of novel nanostructures developed since the 1980s. Nanotubes have attracted considerable interest by the scientific community thanks to their extraordinary physical and chemical properties. Research areas have flourished in recent years and now include the nano-electronic, (bio)sensor and analytical field along with many others. This review covers applications of carbon nanotubes in capillary electrophoresis, capillary electrochromatography and microchip electrophoresis. First, carbon nanotubes and a range of electrophoretic techniques are briefly introduced and key references are mentioned. Next, a comprehensive survey of achievements in the field is presented and critically assessed. The merits and downsides of carbon nanotube addition to the various capillary electrophoretic modes are addressed. The different schemes for fabricating electrochromatographic stationary phases based on carbon nanotubes are discussed. Finally, some future perspectives are offered.
Microfluidics concerns the manipulation of small volumes of fluids (typically nanoliters or less) within networks of channels that have dimensions of tens to hundreds of micrometers. Such devices benefit from having small footprints, low volume requirements of samples and reagents, short analysis times, and a large degree of control over processes being performed, allowing miniaturization of single or multiple laboratory-based procedures and giving rise to ‘lab-on-a-chip’ technology. Microfluidic platforms have become powerful tools in a broad range of fields, from chemistry and engineering to the life sciences, and are revolutionizing the way research can be performed and the quality of information that can be gained.
We perform experimental studies of droplet breakup in microfluidic T-junctions in a range of Capillary numbers lying between 4.10-4 and 2 10-1 and for two viscosity ratios of the fluids forming the dispersed and continuous phases. The present paper extends the range of Capillary numbers explored by previous investigators by two orders of magnitude. We single out two different regimes of breakup. In a first regime, a gap exists between the droplet and the wall before breakup occurs. In this case, the break up process agrees well with the analytical theory of Leshansky and Pismen [Phys. Fluids, 21(2), 023303 (2009)]. In a second regime, droplets keep obstructing the T-junction before breakup. Using physical arguments, we introduce a critical droplet extension for describing the breakup process in this case.
The present contribution deals with the use of unmo dified commercial equipment for cross-correlation c apillary electrophoresis (CE). Complex injection sequences have been injected by switching sample and background electrolyte vi als according to a pre- programmed order. Because of the nature of the auto -sampler used, no sequence could be injected in com mercial instrument without high voltage (HV) interruptions. Apparently , this is the main reason why obtained signal-to-no ise (S/N) ratios are lower than theoretical. Specific ways of programming the injection sequence and use of modified injection se quence in the correlation process have been used to overcome the deleterious effect caused by this sample injection. An electro- osmotic flow (EOF) marker was used as a sample to find optimal conditi ons for cross-correlation experiments. Best results demonstrate S/N ratio improvements around 2.8 compared to 4.0 theoretical maximum.
Although H(+) and OH(-) are the most common ions in aqueous media, they are not usually observable in capillary electrophoresis (CE) experiments, because of the extensive use of buffer solutions as the background electrolyte. In the present work, we introduce CE equipment designed to allow the determination of such ions in a similar fashion as any other ion. Basically, it consists of a four-compartment piece of equipment for electrolysis-separated experiments (D. P. de Jesus et at, Anal. Chem., 2005, 77, 607). In such a system, the ends of the capillary are placed in two reservoirs, which are connected to two other reservoirs through electrolyte-filled tubes. The electrodes of the high-voltage power source are positioned in these reservoirs. Thus, the electrolysis products are kept away from the inputs of the capillary. The detection was provided by two capacitively coupled contactless conductivity detectors (CD), each one positioned about 11 cm from the end of the capillary. Two applications were demonstrated: titration-like procedures for nanolitre samples and mobility measurements. Strong and weak acids (pK(a) < 5), pure or mixtures, could be titrated. The analytical curve is linear from 50 mu M up to 10 mM of total dissociable hydrogen (r = 0.99899 for n =10) in 10-nL samples. By including D(2)O in the running electrolyte, we could demonstrate how to measure the mixed proton/deuteron mobility. When H(2)O/D(2)O (9 : 1 v/v) was used as the solvent, the mobility was 289.6 +/- 0.5 x 10(-5) cm(2) V(-1) s(-1). Due to the fast conversion of the species, this value is related to the overall behaviour of all isotopologues and isotopomers of the Zundel and Eigen structures, as well as the Stokesian mobility of proton and deuteron. The effect of neutral (o-phenanthroline) and negatively charged (chloroacetate) bases and aprotic solvent (DMSO) over the H(+) mobility was also demonstrated.
This review reports the progress on the recent development of
micromixers. The review first presents the different micromixer types
and designs. Micromixers in this review are categorized as passive
micromixers and active micromixers. Due to the simple fabrication
technology and the easy implementation in a complex microfluidic system,
passive micromixers will be the focus of this review. Next, the review
discusses the operation points of the micromixers based on
characteristic dimensionless numbers such as Reynolds number Re, Peclet
number Pe, and in dynamic cases the Strouhal number St. The fabrication
technologies for different mixer types are also analysed. Quantification
techniques for evaluation of the performance of micromixers are
discussed. Finally, the review addresses typical applications of
micromixers.
Recent years have seen considerable progress in the development of microfabricated systems for use in the chemical and biological sciences. The term micro total analytical system (µTAS) is now a well-accepted concept. Much development has been driven by a need to perform effective manipulation of chemical and biological liquids with small volumes at micro and/or nano flowrate level in these systems. In this review, the focus will be on the pumping techniques used for delivery and control of liquids, especially those physical-chemical 'continuous dynamic flow micropumps'. The principles of these pumping techniques are mainly based on one or several well-known phenomena such as electrical, light, magnetic, thermal and other actuated mechanisms. Electrokinetically-driven continuous flow pumps such as the electrophoretic pump and electroosmotic pump, surface chemistry based continuous flow micropumps such as the opto-electrowetting-based pump, optically-driven pump, electrochemical pump and constant gravity-driven pump, and combination-driven techniques such as hydrodynamic flow and electrokinetic/gravity/magnetophoretic pumping will be summarized. The focus will be on the research highlights, trends and future of these pump techniques. Finally, mixing techniques on the microscale are briefly reviewed.
We introduce a simple and versatile microfluidic drop-on-demand solution that enables independent and dynamical control of both the drop size and the drop production rate. To do so, we combine a standard microfluidic T-junction and a novel active switching component that connects the microfluidic channel to the macroscopic liquid reservoirs. Firstly, we explain how to make this simple but accurate drop-on-demand device. Secondly, we carefully characterize its dynamic response and its range of operations. Finally, we show how to generate complex two-dimensional drop patterns dynamically in single or multiple synchronized drop-on-demand devices.
We report a prototype protein separator that successfully miniaturizes existing technology for potential use in biocompatible health monitoring implants. The prototype is a liquid chromatography (LC) column (LC mini-column) fabricated on an inexpensive, flexible, biocompatible polydimethylsiloxane (PDMS) enclosure. The LC mini-column separates a mixture of proteins using size exclusion chromatography (SEC) with polydivinylbenzene beads (5–20 µm in diameter with 10 nm pore size). The LC mini-column is smaller than any commercially available LC column by a factor of ~11 000 and successfully separates denatured and native protein mixtures at ~71 psi of the applied fluidic pressure. Separated proteins are analyzed using NuPAGE-gel electrophoresis, high-performance liquid chromatography (HPLC) and an automated electrophoresis system. Quantitative HPLC results demonstrate successful separation based on intensity change: within 12 min, the intensity between large and small protein peaks changed by a factor of ~20. In further evaluation using the automated electrophoresis system, the plate height of the LC mini-column is between 36 µm and 100 µm. The prototype LC mini-column shows the potential for real-time health monitoring in applications that require inexpensive, flexible implant technology that can function effectively under non-laboratory conditions.
Although simple equivalent circuits have been used to explain the basic functioning of a capacitively coupled contactless conductivity detector (C4D), more sophisticated models are required to take into account the effects of the spatial non-homogeneity of the solution conductivity as the electrophoretic zones pass inside the detector. The overshooting phenomenon observed in real electropherograms may be explained by modeling the coupling of the electrodes with the inner capillary with a network of resistors and capacitors and its dependence with the stray capacitance becomes evident. An even more detailed model of the cell based on electrostatics allows one to calculate the stray capacitances. For the typical geometries and materials, this capacitance is on the order of a few to hundreds of femtofarads. It was possible to demonstrate that the ground plane, sometimes used, reduces the capacitance, but does not eliminate it completely. Possible noise sources are also discussed. The electrode tightness minimizes a possible source of mechanical noise due to variation of the coupling capacitances. Thermal control should also be ensured; the calculations showed that a temperature fluctuation as low as 7×10−3 °C induces artifacts as high as the limit of quantification of K+ in a typical electrophoretic condition, for which the technique has one of its highest sensitivities.
This review gives a brief overview of microvalves, and focuses on the actuation mechanisms and their applications. One of the stumbling blocks for successful miniaturization and commercialization of fully integrated microfluidic systems was the development of reliable microvalves. Applications of the microvalves include flow regulation, on/off switching and sealing of liquids, gases or vacuums. Microvalves have been developed in the form of active or passive microvalves employing mechanical, non-mechanical and external systems. Even though great progress has been made during the last 20 years, there is plenty of room for further improving the performance of existing microvalves.
This paper reviews the centrifugal 'Bio-Disk' platform which is based on rotationally controlled, multi-scale liquid handling to fully integrate and automate complex analysis and synthesis protocols in the life sciences. The platform offers the crucial ingredients for a rapid development of applications: a coherent library of fluidic unit operations, a device technology for actuation, liquid interfacing and detection as well as a developer toolbox providing experimental testing, rapid prototyping and simulation capabilities. Various applications in the fields of life science, in vitro diagnostics and micro-process engineering are demonstrated.
This review gives an overview of developments in the field of microchip analysis for clinical diagnostic and forensic applications. The approach chosen to review the literature is different from that in most microchip reviews to date, in that the information is presented in terms of analytes tested rather than microchip method. Analyte categories for which examples are presented include (i) drugs (quality control, seizures) and explosives residues, (ii) drugs and endogenous small molecules and ions in biofluids, (iii) proteins and peptides, and (iv) analysis of nucleic acids and oligonucleotides. Few cases of microchip analysis of physiological samples or other “real‐world” matrices were found. However, many of the examples presented have potential application for these samples, especially with ongoing parallel developments involving integration of sample pretreatment onto chips and the use of fluid propulsion mechanisms other than electrokinetic pumping.
This review gives an overview of developments in the field of microchip analysis for clinical diagnostic and forensic applications. The approach chosen to review the literature is different from that in most microchip reviews to date, in that the information is presented in terms of analytes tested rather than microchip method. Analyte categories for which examples are presented include (i) drugs (quality control, seizures) and explosives residues, (ii) drugs and endogenous small molecules and ions in biofluids, (iii) proteins and peptides, and (iv) analysis of nucleic acids and oligonucleotides. Few cases of microchip analysis of physiological samples or other “real-world” matrices were found. However, many of the examples presented have potential application for these samples, especially with ongoing parallel developments involving integration of sample pretreatment onto chips and the use of fluid propulsion mechanisms other than electrokinetic pumping.
Proteomic research is linked with significant technological challenges such as the high dynamic range and low abundance of biologically interesting proteins. Moreover, there is an increasing need for high-throughput and robustness of routinely performed analyses. Solving these difficulties requires refinements in the capability to fractionate and prepare biological samples as well as improvements in speed, automation, separation power and overall analytical sensitivity.Recent innovations in microfluidic devices with integrated on-chip sample enrichment, liquid chromatography and electrospray emitters and their applicability for specific proteomic applications are presented in this review.:
We have designed and fabricated a polydimethylsiloxane (PDMS) microfluidic device for coupling capillary electrophoresis (CE) and matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). The coupling is advantageous in biological research because CE has the power of separating analytes in a sample based on mobility difference and MALDI-MS provides accurate and sensitive mass analysis of the analytes. The goal is realized by fractionating the separated analytes inside the microfluidic device and pushing the analyte fractions into open reservoirs. Each analyte fraction is then mixed with a matrix solution and deposited on a MALDI target for MALDI-MS. Therefore, a two-step analysis of analytes in the form of CE-MALDI-MS is achieved by using the microfluidic device.
An analytical method was proposed for calculating radiative fluxes incident on a planar circular detector from a volume multiple point chemi- or bio-luminescent source inside a coaxial cylindrical reactor. The method was designed for a cylindrical reactor when the surface reflections were neglected and when chemi- or bio-luminescence reaches a detector embedded in the same homogeneous optical medium as the point emitters of the volume multiple point source model. The radiative fluxes from arbitrarily distributed point emitters were expressed by one generalized quadruple-integral formula. Then some double- and single-integral formulas were obtained for calculating radiative fluxes from identically radiating point emitters uniformly distributed within the reactor. Selected results were computed and illustrated graphically. The obtained formulas are suitable for optimizing and/or calibrating the considered source-detectors systems (optical radiometers or luminometers) and determining radiative fluxes generated by chemical, biological, and physical processes leading to chemi-, bio-, radio-, and sono-luminescence for example.
We report a new electromagnetic induction detector with two vertical inductors for capillary electrophoresis and microfluidic chip capillary electrophoresis. Compared with currently available detection methods, this new detector has several advantages, including simple construction, no complicated elements, ease of assembly and operation, and potential for universal applications. The conditions affecting the response of the detector, including the number of coil turns, the frequency and the effective voltage, were optimized. Its feasibility and performance were demonstrated by analyzing inorganic ions. The new detector showed a well-defined correlation between the ion concentrations and the responses (r=0.993–0.998), with a detection limit of 5.6μmolL−1 for Mn2+, as well as good reproducibility and stability for both CE and microfluidic chip CE.
A versatile programmable eight-path-electrode power supply (PEPS) system for manipulating microfluids of a complex microfluidic chip has been developed. The PEPS system consisted of a single chip microprocessor as a central control unit and a personal computer (PC) as an upper computer, and the program could be operated under Windows98/2000/XP. The voltage output of each electrode was in the range of 0 to +8000V (0.1% precision) while the current output was in the range of 0 to +999μA. The voltage of eight electrodes could be operated either independently or synchronously by random combination of any electrodes through switching. The voltage output modes were “switch-off/floating”, “switch-on” and “grounded” and fast switched at ms-level between these modes, and run time (0.1s precision) of these modes could be controlled as desired. The PEPS system was conveniently for controlling flow rate and direction of electroosmotic flow (EOF) in a chip network. Six electrodes were chosen to control the repeated ‘injection and separation’ of 1.0×10−5M fluorescein isothiocyanate (FITC) in a six-reservoir glass-based chip. The relative standard deviation (R.S.D., n=4, S/N=10) of the repeated operation was 0.9% for the reservation time (tR) and 2.3% for the peak height, respectively.
There is increasing pressure on industry and regulatory bodies to monitor the discharge of trace metals into the aquatic environment. The determination of trace metals can be achieved to parts per billion (ppb) levels using anodic stripping voltammetry (ASV) at screen printed electrodes, controlled using an NMRC potentiostat coupled with software control. The disposable testheads consist of inexpensive materials and allow for low-cost production in batch processes. Voltammetric (the measurement of current as a function of potential) methods of analysis are attractive for the determination of copper, cadmium, lead and zinc. A three electrode set-up is used both in the preparation of the mercury film on a carbon electrode and in the subsequent anodic stripping voltammetric detection step. The performances of the reference electrodes, the screen-printed carbon and the FPGA based unit have been investigated in this paper.
A novel type of voltage-controlled pump based on electro-osmotic flow has been developed that uses massively parallel micromachined microfluidic channels to generate both high flow rates and high pressures. The approximately half-million microchannels have sub-micron cross-sections, and thus also function as a monolithically integrated microfilter with uniform pore size. This first generation device produces pressures of 5.5kPa/V and flow rate of 0.054mL/min/V/cm2. Such a small and light-weight, yet robust pump makes it useful, and often advantageous in a particularly broad array of applications and systems ranging from drug delivery to cooling microchips to filtration.
Miniaturization in analytical chemistry is a clear trend, and has been the subject of an important number of research works. In this article, we present a general overview of the potential of analytical microsystems. Although clear advantages can be pointed out, we offer a critical evaluation based on highlighting strengths and weaknesses. Thinking about the future use of the current analytical microsystems in routine and control analytical laboratories, we discuss the issues involved in the analytical process and the different steps involved in chemical analyses. We identify challenges in applying analytical microsystems to these uses.
The low vapor pressure and the versatility of the physico-chemical properties of ionic liquids make them really attractive as an alternative for conventional molecular solvents. The knowledge of their physico-chemical properties (viscosity, conductivity, miscibility with organic solvents and anion–cation interactions) has appeared mandatory for better targeting their applications, although it is generally still lacking or incomplete.This work promotes capillary electrophoresis instrumentation as an integrated apparatus for measurement of viscosity, conductivity and absorbance of pure ionic liquids and ionic liquid–molecular solvent mixtures. Compared to current conventional techniques, the assets of this instrumentation for this purpose are the combined availability of a pressure delivery system, power supply, diode array absorbance detector and thermoregulation device, allowing unattended, automatic and easy operation, involving minimum sample handling. Most importantly, the required sample volume can be reduced to about 50μL, making this protocol very cost-effective. A protocol was optimized with respect to time, sample consumption and data reliability for the determination of these physico-chemical parameters. Ionic liquids selected for method development and validation differed in the nature of their cation (butyl- and ethyl-methylimidazolium) and anion (trifluoromethanesulfonate and bis(trifluoromethanesulfonyl)imide). Various molecular solvents were mixed with these ionic liquids (acetonitrile, methanol, dimethylformamide and trifluoroethanol) and the same physico-chemical properties were determined by optimized methods. The knowledge of these data should be of great support in various application areas, including the development of new separation media for capillary electrophoresis and chromatographic techniques.
A new detection system for isotachophoresis, the high-frequency contactless conductivity detector, is described. This detector has a high resolving power and gives good reproducibility.
Microsensors and micromachines that are capable of self-propulsion through fluids could revolutionize many aspects of technology. Few principles to propel such devices and supply them with energy are known. Here, we show that various types of miniature semiconductor diodes floating in water act as self-propelling particles when powered by an external alternating electric field. The millimetre-sized diodes rectify the voltage induced between their electrodes. The resulting particle-localized electro-osmotic flow propels them in the direction of either the cathode or the anode, depending on their surface charge. These rudimentary self-propelling devices can emit light or respond to light and could be controlled by internal logic. Diodes embedded in the walls of microfluidic channels provide locally distributed pumping or mixing functions powered by a global external field. The combined application of a.c. and d.c. fields in such devices allows decoupling of the velocity of the particles and the liquid and could be used for on-chip separations.
Miniaturized, portable instrumentation has been gaining popularity in all areas of analytical chemistry. Capillary electrophoresis (CE), due to its main strengths of high separation efficiency, relatively short analysis time and low consumption of chemicals, is a particularly suitable technique for use in portable analytical instrumentation. In line with the general trend in miniaturization in chemistry utilizing microfluidic chips, the main thrust of portable CE (P–CE) systems development is towards chip-based miniaturized CE. Despite this, capillary-based (non-chip) P–CE systems have certain unmatched advantages, especially in the relative simplicity of the regular cylindrical geometry of the CE capillary, maximal volume-to-surface ratio, no need to design and to fabricate a chip, the low costs of capillary compared to chip, and better performance with some detection techniques. This review presents an overview of the state of the art of P–CE and literature relevant to future developments. We pay particular attention to the development and the potential of miniaturization of functional parts for P–CE. These include comp-onents related to sample introduction, separation and detection, which are the key elements in P–CE design. The future of P–CE may be in relatively simple, rugged designs (e.g., using a short piece of capillary fixed to a chip-sized platform on which injection and detection parts can be mounted). Electrochemical detection is well suited for miniaturization, so is probably the most suitable detection technique for P–CE, but optical detection is gaining interest, especially due to miniaturized light sources (e.g., light-emitting diodes).
Miniaturized, battery-powered, high-voltage power supply, electrochemical (EC) detection, and interface circuits designed for microchip capillary electrophoresis (CE) are described. The dual source CE power supply provides +/- 1 kVDC at 380 microA and can operate continuously for 15 h without recharging. The amperometric EC detection circuit provides electrode potentials of +/-2 VDC and gains of 1, 10, and 100 nA/V. The CE power supply power is connected to the microchip through an interface circuit consisting of two miniature relays, diodes, and resistors. The microchip has equal length buffer and separation channels. This geometry allows the microchip to be controlled from only two reservoirs using fixed dc sources while providing a consistent and stable sample injection volume. The interface circuit also maintains the detection reservoir at ground potential and allows channel currents to be measured likewise. Data are recorded, and the circuits are controlled by a National Instruments signal interface card and software installed in a notebook computer. The combined size (4 in. x 6 in. x 1 in.) and weight (0.35 kg) of the circuits make them ideal for lab-on-a-chip applications. The circuits were tested electrically, by performing separations of dopamine and catechol EC and by laser-induced fluorescence visualization.
The design, fabrication, and operation of a radial capillary array electrophoresis microplate and scanner for high-throughput DNA analysis is presented. The microplate consists of a central common anode reservoir coupled to 96 separate microfabricated separation channels connected to sample injectors on the perimeter of the 10-cm-diameter wafer. Detection is accomplished by a laser-excited rotary confocal scanner with four color detection channels. Loading of 96 samples in parallel is achieved using a pressurized capillary array system. High-quality separations of 96 pBR322 restriction digest samples are achieved in <120 s with the microplate system. The practical utility and multicolor detection capability is demonstrated by analyzing 96 methylenetetrahydrofolate reductase (MTHFR) alleles in parallel using a noncovalent 2-color staining method. This work establishes the feasibility of performing high-throughput genotyping separations with capillary array electrophoresis microplates.
An oscillometric detector for capillary electrophoresis (CE) has been described. Two 2-mm silver rings separated by 1 mm were painted over the polyimide coating of a fused-silica capillary (75-μm i.d. and 360-μm o.d.) and used as electrodes for oscillometric measurements. A function generator was used to apply a sinusoidal signal over one of the electrodes; the other one was connected to a current-to-voltage converter. The rectified signal is proportional to the admittance of the cell, which is a function of the inner solution conductivity in the region of the electrodes. Electropherograms of alkaline and alkaline-earth cations showed good signal-to-noise ratio. For typical electrophoretic conditions, the limit of detection for lithium was 1.5 μM, and there was good linearity (R = 0.998 for eight data points) up to 2 mM. Indirect conductivity detection of quaternary ammonium salts was achieved by using potassium acetate running buffer, showing results similar to those from conventional conductometric detectors. Despite the cell length (5 mm), good resolution was obtained in the electropherograms. Equivalent electrical circuits were proposed for the cell. The most simplified model comprises a resistor−capacitor couple in parallel with another capacitor. The resistor stands for the inner solution resistivity, the series capacitor stands for the fused-silica wall dielectric properties in the region between the electrodes and the solution, and the parallel capacitor stands for the leakage through the wall and edge capacitance effects.
The purpose of this work is to demonstrate the usefulness of capillary electrophoresis (CE) instrumentation for determining values of critical micelle concentration (cmc) of surfactants. The approach essentially consists of a CE version of the traditional method of measuring values of cmc by conductivity. Namely, the different conductivities of ionic surfactants in solution depending on their aggregation state, i.e., as monomers or micelles, and the effect on the electrical current as usually measured in a CE apparatus are employed to determine the cmc values. The cmc of sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) is obtained in several media such as water, aqueous solutions containing salts, organosaline solutions, and aqueous solutions containing β-cyclodextrin. The cmc values for SDS and CTAB under these conditions are in good agreement with those reported in the literature. Advantages and drawbacks of this procedure as well as its implications in micellar electrokinetic chromatography are discussed. From our results, it is deduced that the present method can be used with high confidence to determine values of cmc in a fast and easy way.
Following a conventional capillary electrophoresis system with an optical detector, a conductive membrane can be used to connect a second capillary, the terminal end of which is connected to a second power supply, the membrane serving as the common ground for both high-voltage sources. The direction and magnitude of the field applied to the second capillary govern if the bulk flow in the first capillary is augmented, inhibited, or unaffected by the pumping action exerted by the second capillary. The majority of CE applications involve samples of ionic strength lower than that of the running electrolyte and optimum sample stacking is desirable. In such cases, auxiliary pumping of this type can be used to optimize the stacking profile and thus improve the separation efficiencies for charged solutes. This work also compares the characteristics of this type of auxiliary electroosmotic pumping with its hydrostatic counterpart.
This paper characterizes a bi-directional pneumatic diaphragm micropump and presents a model for performance of an integrated fluidic capacitor. The fluidic capacitor is used to convert pulsatile flow into a nearly continuous flow stream. The pump was fabricated in acrylic using a CNC mill. The stroke volume of the pump is ~1 µL. The pump is self-priming, bubble tolerant and insensitive to changes in head pressure and pneumatic pressure within its operating range. The pump achieves a maximum flow rate of 5 mL min−1 against zero head pressure. With pneumatic pressure set to 40 kPa, the pump can provide flow at 2.6 mL min−1 against a head pressure of 25 kPa. A nonlinear model for the capacitor was developed and compared with experimental results. The ratio of the time constant of the capacitor to the cycle time of the pump is shown to be an accurate indicator of capacitor performance and a useful design tool.
This paper presents the integration of interdigitated microelectrodes and a CMOS circuit for electrochemical sensing of the neurotransmitter dopamine. Gold electrodes with a gap of 3 µm are fabricated by the lift-off technique. The CMOS sensing circuit has a current gain of 10, an integrating capacitor of 4 pF, and a measured dynamic range of 60 dB. The applied reduction and oxidation potentials are determined by voltammetry at about −0.2 V and 0.6 V, respectively. The measured collection efficiency can reach up to 84%. The produced oxidation current with respect to dopamine concentration averages 0.44 nA µM−1.
A full-wafer process is presented for fast and simple fabrication of glass microfluidic chips with integrated electroplated electrodes. The process employs the permanent dry film resist (DFR) Ordyl SY300 to create microfluidic channels, followed by electroplating of silver and subsequent chlorination. The dry film resist is bonded directly to a second substrate, without intermediate gluing layers, only by applying pressure and moderate heating. The process of microfluidic channel fabrication, electroplating and wafer bonding can be completed within 1 day, thus making it one of the fastest and simplest full-wafer fabrication processes.
The determination of the critical micelle concentration (CMC) of cationic surfactants by capillary electrophoresis was demonstrated. In this study, tetradecyltrimethylammonium bromide (TTAB) and dodecyltrimethylammonium bromide (DoTAB) were selected as cationic surfactants and propazine was chosen as test solute. In the evolution of the effective electrophoretic mobility of propazine as a function of surfactant concentration, a dramatic change in slope at a particular concentration is a good indication of the CMC of this surfactant. The CMC values determined experimentally were further confirmed by a curve-fitting approach. Simulation of the electrophoretic mobility curves as a function of surfactant concentration in both micellar electrokinetic chromatography and capillary zone electrophoresis using cationic surfactants as an electrolyte modifier was performed for propazine, and the intersection of these two mobility curves allowed us to precisely predict the CMC of the surfactant. The CMC values determined for TTAB and DoTAB are 1.6 ± 0.1 and 11.0 ± 0.1 mM, respectively, in the case of an electrolytic solution consisting of 70 mM phosphate buffer at pH 6.0. Moreover, the applicability of the electroosmotic mobility as a parameter for the determination of the CMC was examined.
Capacitively coupled contactless conductivity detection (C4D) is presented in a progressively detailed approach. Through different levels of theoretical and practical complexity, several aspects related to this kind of detection are addressed, which should be helpful to understand the results as well as to design a detector or plan experiments. Simulations and experimental results suggest that sensitivity depends on: 1) the electrolyte co-ion and counter-ion; 2) cell geometry and its positioning; 3) operating frequency. Undesirable stray capacitance formed due to the close placement of the electrodes is of great importance to the optimization of the operating frequency and must be minimized.
Pulsed electrochemical detection (PED) is an excellent method for detection of analytes that normally foul electrodes. In PED, the detection electrode is first cleaned at a high positive potential, then reactivated at a negative potential dissolving the surface oxide, and finally used to oxidize the analyte at a moderate positive potential. Due to the advantages and versatility of PED, many different variations of the detection waveform can be found in literature. This review focuses on application of PED to CE and in particular, the most commonly used modes: pulsed amperometric detection (PAD) and integrated pulsed amperometric detection (iPAD).
Electrochemistry detection offers considerable promise for capillary-electrophoresis (CE) microchips, with features that include remarkable sensitivity, portability, independence of optical path length or sample turbidity, low cost and power requirements, and high compatibility with modern micromachining technologies. This article highlights key strategies in controlled-potential electrochemical detectors for CE microchip systems, along with recent advances and directions. Subjects covered include the design of the electrochemical detection system, its requirements and operational principles, common electrode materials, isolation from the separation voltage, derivatization reactions, typical applications, and future prospects. It is expected that electrochemical detection will become a powerful tool for CE microchip systems and will lead to the creation of truly portable (and possibly disposable) devices.
We present a microfluidic system with paraffin-actuated microvalves and a thermopneumatic-actuated micropump that are easily integrated on the same substrate using the same fabrication process. The fabrication process of this microfluidic system using polydimethylsiloxane (PDMS), indium tin oxide (ITO) and glass is relatively simple, and its performance is good for the application of the disposable lab-on-a-chip. A maximum pumping rate of about 2.0 μl/min was measured at a duty ratio of 5% and a frequency of 1 Hz. The flow cut-off powers for the microvalves with the channel depth of 220 μm, were 300 and 350 mW for valve seat diameters of 1.5 and 2.0 mm, respectively. The power for flow cut-off depends on the channel depth and the diameter of the valve seat in the microvalves.
Development of a simple and low-cost instrument using a PC sound card for the potentiometric sensors has been reported in this work. It consists of a scanning-DC type data acquisition system which will allow us to acquire an AC signal data corresponding to the scanning-DC signal. Therefore in physical or chemical device characterization it can be used to acquire any DC dependent parameter such as the dielectric constant, capacitance, photocurrent of semiconductor heterostructure, electrochemical parameters, etc. Speaker port of the sound card has been used here to deliver an AC (0 –1 V) that is converted to a corresponding DC voltage externally by a hardware composed of a half-wave precision rectifier (HWPR), a low-pass filter and a level-shifter. The DC voltage can be scanned from +2 to −2 V in any desired steps. The PC sound card Microphone input has been used to collect the AC signal corresponding to the DC voltage steps. For outputting the DC an AC voltage having a frequency of 4000 Hz is sent to the PC sound card Speaker port. The sampling rate for the output voltage is fixed at 8000 sample/s. For collecting the data the configurable sampling rate (>Nyquist rate) depending on the frequency of the input signal has been used. As a test case it has been applied to obtain the AC photocurrent response of a Si3N4/SiO2/Si heterostructure. The experimental results show a good promise for the novel very simple instrument to be used in the potentiometric sensing as well as an important tool for the characterization of physical and chemical devices.
The impedance of a capacitively coupled contactless conductivity detector (C4D) cell was experimentally examined for different cell parameters by alternative current impedance (ACImp). The effect of the gap between the electrodes and the length of the electrodes on the impedance behavior of the C4D cell has been studied. As a result, the impedance of C4D cell is largely defined by the length of the gap between the electrodes and the length of the electrodes. The impedance increases with increasing gap between the electrodes and the length of the electrodes. It could be found that tightly coupling of the electrodes to the outer wall of the capillary is needed. The axial contactless conductometric detector can be effectively described by the simplest possible equivalent circuitry consisting of a capacitor, resistor, a second resister and a Warburg impedance. These results are helpful to understand the impedance characteristics of C4D cell and improve its detective performance.
This paper reports a simple procedure for coating fused-silica capillaries with poly(diallyldimethyl ammonium chloride) and montmorillonite. The coated capillaries were characterized by performing EOF measurements as a function of buffer pH, number of layers of coating, and number of runs (stability). The coated capillaries showed a highly stable μEOF (run-to-run RSD less than 1.5%, n = 20), allowing continuous use for several days without conditioning. The coated capillaries were then used for the effective separation of nine environmentally important phenolic compounds showing a significant improvement in the resolution, when compared to bare fused-silica capillaries. The EOF of the coated capillaries was constant in alkaline solutions (pH ≥ 7), allowing the optimization of the separation conditions of phenolic compounds without significantly affecting the μEOF.
A new portable capillary electrophoresis instrument with capacitively coupled contactless conductivity detection was developed and optimized for the sensitive field measurements of ionic compounds in environmental samples. It is powered by batteries and the high voltage modules are capable of delivering up to 15 kV at either polarity for more than one working day. Inorganic cations and anions, including ions of heavy metals and arsenate, could be determined with detection limits in the range from about 0.2 to 1 μM. The instrument was field tested in a remote region of Tasmania and nitrite and ammonium could be determined on-site at concentrations as low as 10 ppb in presence of other common inorganic ions at concentrations which were 2 to 3 orders of magnitude higher.
This paper deals with the development of state-of-the-art metal oxide semiconductor (MOX) gas sensors based on ultra-low-power (ULP) consumption micro-machined hotplates and targeted to VOC detection at ppb-level. A very simple, single metal, front-side silicon bulk micromachining fabrication technology was conceived and proposed. Several types of ULP devices, differing in shape and size, have been designed and fabricated to assess both the most efficient layout geometry and optimal fabrication process parameters. The ULP hotplates functional behavior was thoroughly investigated, and typical results on measurements of the hotplate temperature vs. applied power are reported. A very satisfactory value of 8.9 mW at 400 °C can be highlighted, for a device featuring an innovative self-insulated layout between heater and sensing layer. Transient temperature responses and evaluation of the hotplate thermal time constant were also carried out. On the center of the suspended hotplate structures a thin film of tin oxide has been deposited by means of modified rheotaxial growth and thermal oxidation (M-RGTO) process. A very controlled amount of gold nanoparticles is finally sputtered onto the sensing layer to enhance its response to VOC by catalytic effect. As expected and confirmed by morphological characterization the tin oxide film is structured in nanoclusters very uniform in size. Results of functional characterizations towards different gases under different working conditions are reported and prove the capability of detecting volatile organic compounds (VOC) down to few parts a per billion (ppb).
The prototype of a field-portable battery-powered capillary electrophoresis instrument described here includes a high voltage supply capable of delivering the standard 30 kV at both polarities. The instrument has dimensions of 340 mm×175 mm×175 mm (w×h×d) and a weight of 7.5 kg. Data acquisition is carried out with a portable laptop or palmtop computer. Electrochemical detection was chosen as the straightforward signal transduction methods are relatively easily implemented. For robustness, the amperometric and potentiometric detection modes are carried out in a fixed wall-jet cell without decoupler. Both methods rely on the electrophoretic ground electrode as reference and counter electrode. For conductometric detection the only recently reported contactless version was implemented. The availability of the three complementary electrochemical detection methods allows for great versatility, which includes the ability to determine inorganic cations and anions as well as many organic species of interest.
Arsenazo III, a metallochromic ligand colorimetrically sensitive to the metal complexation of lanthanide and actinide metal ions, is applied to a capillary electrophoresis microchip for the detection of uranium (VI) and various lanthanide metal ions. The glass microchip contained 100 μm deep by 200 μm wide microchannels etched in a simple cross pattern with an 80 mm separation channel length and an 8 mm injection channel length. Detection of the Arsenazo III metal complexes is achieved using a red light emitting diode (LED) light source and a photodiode array detector. Carbowax 20M is incorporated into the background electrolyte in order to eliminate the electroosmotic flow and prevent dye adsorption on the microchannel walls. Separation of uranium from four lanthanide metal ions is demonstrated in under 2 min. The addition of diethylenetriaminepentaacetic acid (DTPA) to the background electrolyte is found to be an effective means of eliminating any interference from lanthanide, transition and alkaline earth metal ions. Direct load injection of a pre-complexed metal ion mixture onto the microchannel gave a detection limit of 23 ppb uranium (VI) in the presence of seven lanthanide impurities (1.5 ppm each) in under 55 s.
An in-channel configuration for amperometric detection has been adopted in capillary electrophoresis performed in photolithographically microfabricated chips. This electrode alignment, compared with the more conventional end-channel configuration, led to a better peak resolution and a higher sensitivity, because it involves no gap between the channel outlet and the working electrode, thus preventing the dispersion of the analyte band leaving the separation channel into the comparatively large detection reservoir. All details concerning the chip fabrication, as well as injection and detection procedures adopted are carefully described. The performance of this approach was first optimized for the experimental parameters affecting both separation and detection steps and then assayed for the separation of two synthetic food dyes, Green S and Patent Blue, concomitantly present in synthetic samples. Under the optimized conditions thus recognized (background electrolyte: 40 mM aqueous carbonate–bicarbonate buffer at pH = 10.5, separation voltage: 1300 V, amperometric detection at controlled potential of 0.9 V vs. ), a well satisfactory resolution could be achieved within less than 300 s. The recorded peaks were characterized by both a good repeatability (7%) and a linear dependence of their height over a wide concentration range (about 2 orders of magnitude). The detection limit, estimated for a signal-to-noise ratio of three was 10 μM for Patent Blue and 17 μM for Green S. The application of the method to some commercial soft-drinks and candies is also presented.
A miniaturized and robust optical fluorosensor, designed as a portable instrumentation for the in situ analysis of ions in water samples by using optodes has been constructed with low cost discrete optical components. The chemical recognition element of the device consists of a plasticized PVC-based fluorescent optode, which includes a new hexamethine–hemicyanine dye as a fluorophore. The signal can be attributed to a certain analyte depending on the ionophore employed. In this work, a commercial potassium ionophore (valinomycin) has been used to formulate a model membrane selective to potassium. The sensor has been fully characterized using a simple flow injection analysis (FIA) system and analytical parameters such as sensitivity (0.71 mV dec−1), limit of detection (2.2 × 10−5 M K+), repeatability (R.S.D. = 4.2%), reproducibility, lifetime and ionic interferences have been determined. The developed miniaturized system has been applied to the potassium concentration determination in spiked tap water samples. The obtained results have been compared to those acquired by the ICP-OES reference method and the suitability of the experimental setup for the determination of ions in water samples by the miniaturized fluorescence proposal has been demonstrated.
Interest in the development of surface plasmon resonance (SPR) based immunosensors for detection and monitoring of low-molecular-weight analytes of biomedical, food and environmental fields has been rapidly increasing over the last 10 years. By combining the advantages of the specific antigen–antibody immunoreaction and the high sensitivity and reliability of SPR signal transduction, SPR immunoassays offer exceptional performance capabilities with respect to sensitivity, specificity, speed and multianalyte detection in complex analytical matrices. Advancements in the technology of antibody production and the signal transduction provide a promising scope for SPR immunosensors to lead in the next generation biosensors. This review highlights the current state-of-the-art in SPR immunosensors and outlines briefly the important issues with regard to the development of SPR immmunosensors, such as preparation of the biomolecules, sensor fabrication, non-specific adsorption, surface regeneration and detection principles. Particular emphasis is given to the indirect competitive immunoassay principle which is compatible and highly promising for detection of small analytes with enhanced sensitivity. In addition, recent advancements and trends in the application of SPR immunosensors in biomedical, environmental and food-related analyses are discussed.
In this work, a new laser-induced fluorescence (LIF) detection system based on a line laser beam for microfluidic chip electrophoresis analysis was developed. This detection system had the advantages of simple optical structure, compactness, and ease in constructing. Highly sensitive detection was realized by detecting the fluorescence light emitted in the micro-channel through the vertical intersection between the line laser source and micro-channel. The filtered line source was established by a bevel laser beam and a micro-gap which could facilitate the alignment of line laser beam with the microfluidic channel. Both the theoretical analysis and experimental study demonstrated that the detection system with a 0.07 mm-width micro-gap had enough sensitivity and adequate separation efficiency. By this system, a detection limit (S/N > 12) of 1.284 × 10−10 M fluorescein isothiocyanate was obtained, and the plate number could reach to 6100, which were comparable to those of optimized confocal or orthogonal LIF systems for microchip based capillary electrophoresis. The reproductibility of the detection system was evaluated by Sybr Green labeled DNA markers contained five fragments. Finally, the multi-PCR products including 165 bp, 266 bp, 378 bp and 881 bp fragments could be successfully achieved for baseline separation by this system within 4 min. The work undertaken can gear toward a semi-automated handheld system with substantial time and cost saving.