Contactless Conductivity Detection Research Articles

Fatty Acid Analysis by Capillary Electrophoresis and Contactless Conductivity Detection for Future Life Detection Missions.

Future life-detection missions will likely search for biosignatures within a wide range of organic compounds, including fatty acids. In order to determine such biosignatures, it is necessary to identify and quantify individual fatty acids present within a sample. In this study, we present a method using capillary electrophoresis coupled to contactless conductivity detection (CE-C4D) for the separation and detection of both saturated and unsaturated fatty acids after derivatization with N,N-diethylethylenediamine, triethylamine, and 2-chloro-1-methylpyridinium iodide at 40°C for 10min. Operating conditions (background electrolyte, separation voltage, and temperature) were optimized to provide maximum separation of fatty acids, thereby allowing their identification and quantification. Using a background electrolyte of 2M acetic acid in 45% acetonitrile, an optimal separation was obtained with a separation voltage of 10kV and a capillary temperature of 15°C. The optimized CE-C4D method was used to analyze samples of the cyanobacterium Spirulina. Multiple fatty acids were detected in the samples, showing the potential of this method for detection of fatty acid biosignatures during future spaceflight missions.

Rapid Determination of Galantamine in Human Plasma by Microchip Electrophoresis With a Highly Integrated Contactless Conductivity Detector.

A novel and rapid method was developed for the determination of galantamine in human plasma by microchip electrophoresis with a highly integrated contactless conductivity detector (CCD). The instrumental parameters affecting the response of the detector, such as excitation frequency and excitation voltage, were examined and optimized. The electrophoresis conditions that influenced the separation and detection of galantamine, including the composition of buffer solution, buffer pH, buffer concentration, additives, injection time, and separation voltage were systematically investigated. Under the optimal conditions, the peak height had a good linear relationship with the concentration of galantamine in human plasma from 10 to 160 µg/L, and the correlation coefficient was 0.9992, the limit of detection reached 1.1 µg/L. The recoveries were between 98.6% and 102.1%. This sensitive, rapid, and convenient method is a good alternative to existing methods for galantamine determination. Also, this highly integrated CCD holds great promise in clinical biochemical analysis.

Simultaneous Determination of Tryptophan and 5-hydroxytryptophan in Dietary Supplements using Capillary Zone Electrophoresis and Capacitively Coupled Contactless Conductivity Detection

Simultaneous Determination of Tryptophan and 5-hydroxytryptophan in Dietary Supplements using Capillary Zone Electrophoresis and Capacitively Coupled Contactless Conductivity Detection

Applications of capillary electrophoresis with capacitively coupled contactless conductivity detector (CE-C4D) for the determination of glucosamine, vitamin B6 and minerals

Capillary electrophoresis with capacitively coupled contactless conductivity detector (CE-C4D) is renowned for its numerous advantages, such as compact equipment, low cost of setup and operation, simplicity in functionality, and minimal use of samples and chemical solvents. This method has been applied across various fields, including environmental analysis, forensic science, biochemistry, pharmaceuticals, and food science. In this study, the CE-C4D method was applied to determine the presence of glucosamine, vitamin B6, and certain minerals in dietary supplements. Notably, glucosamine was simultaneously determined with calcium, and vitamin B6 with magnesium. The method was validated to meet the requirements of AOAC. The detection limits achieved for calcium, glucosamine, vitamin B6 and magnesium were 0.05 ppm; 0.50 ppm; 0.10 ppm and 1.00 ppm, respectively. The concurrent determination of active substances with different properties within a single product is crucial, optimizing analytical efficiency and yielding high accuracy for the analysis.

Rapid Detection of Soil Available Phosphorus using Capacitively Coupled Contactless Conductivity Detection

Background: In China, the traditional method for analyzing soil available phospho-rus is inadequate for large-scale soil assessment and nationwide soil formulation demands. To address this, we propose a rapid and reliable method for soil-available phosphorus detection. The setup includes an on-site rapid pre-treatment device, a non-contact conductivity detection device, and a capillary electrophoresis buffer solution system composed of glacial acetic acid and hydroxypropyl-β-cyclodextrin. Methods: The on-site rapid pre-treatment process includes fresh soil moisture content detec-tion (moisture rapid detector), weighing (handheld weighing meter), stirring (handheld rapid stirrer), and filtration (soil rapid filter) to obtain the liquid sample, and direct injection (capil-lary electrophoresis detector). The phosphate ion detection parameters include capillary size, separation voltage, injection parameters, and electric injection. We used Liaoning brown soil, Henan yellow tidal soil, Heilongjiang black soil, and Anhui tidal soil as standard samples. Additionally, we used mathematical modeling methods and machine learning algorithms to analyze and process research data. Results and Conclusion: Following calibration with standard samples, the experimental blind test samples demonstrated conformity with the national standard method, exhibiting a relative standard deviation of less than 3%. The proposed pre-treatment device and non-contact con-ductivity detector are powered by lithium-ion batteries, rendering them ideal for extended field operations. The non-contact conductivity detector obviates the need for direct contact with test samples, mitigating environmental pollution. Furthermore, the neural network model exhibited the highest level of goodness of fit in chemical data analysis.

Determination of amino acids and peptides without their pre-column derivatization by capillary electrophoresis with ultraviolet and contactless conductivity detection. An overview.

This review provides an overview of recent works focusing on the determination of amino acids (AAs) and peptides using capillary electrophoresis with contactless conductivity detection and ultraviolet (UV) detection, which is the most widespread detection in capillary electromigration techniques, without pre-capillary derivatization. Available options for the UV detection of these analytes, such as indirect detection, complexation with transition metal ions, and in-capillary derivatization are described. Developments in the field of direct detection of UV-absorbing AAs and peptides as well as progress in chiral separation are described. A separate section is dedicated to using on-line sample preconcentration methods combined with capillary electrophoresis-UV.

Development of capillary electrophoresis methods for the detection of microbial metabolites on potential future spaceflight missions.

The search for chemical indicators of life is a fundamental component of potential future spaceflight missions to ocean worlds. Capillary electrophoresis (CE) is a useful separation method for the determination of the small organic molecules, such as amino acids and nucleobases, that could be used to help determine whether or not life is present in a sample collected during such missions. CE is under development for spaceflight applications using multiple detection systems, such as laser induced fluorescence (LIF) and mass spectrometry (MS). Here we report CE-based methods for separation and detection of major polar metabolites in cells, such as amino acids, nucleobases/sides, and oxidized and reduced glutathione using detectors that are less expensive alternatives to LIF and MS. Direct UV detection, indirect UV detection, and capacitvely coupled contactless conductivity detection (C4D) were tested with CE, and a combination of direct UV and C4D allowed the detection of the widest variety of metabolites. The optimized method was used to profile metabolites found in samples of Escherichia coli and Pseudoalteromonas haloplanktis and showed distinct differences between the species.

Pushing the Limits of Capacitively Coupled Contactless Conductivity Detection for Capillary Electrophoresis.

Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has proven to be an efficient technique for the separation and detection of charged inorganic, organic, and biochemical analytes. It offers several advantages, including cost-effectiveness, nanoliter injection volume, short analysis time, good separation efficiency, suitability for miniaturization, and portability. However, the routine determination of common inorganic cations (NH4+, K+, Na+, Ca2+, Mg2+, and Li+) and inorganic anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-) in water quality monitoring typically exhibits limits of detection of about 0.3-1 μM without preconcentration. This sensitivity often proves insufficient for the applications of CE-C4D in trace analysis situations. Here, we explore methods to push the detection limits of CE-C4D through a comprehensive consideration of signal and noise sources. In particular, we (i) studied the model of C4D and its guiding roles in C4D and CE-C4D, (ii) optimized the bandwidth and noise performance of the current-to-voltage (I-V) converter, and (iii) reduced the noise level due to the strong background signal of the background electrolyte by adaptive differential detection. We characterized the system with Li+; the 3-fold signal-to-noise (S/N) detection limit for Li+ was determined at 20 nM, with a linear range spanning from 60 nM to 1.6 mM. Moreover, the optimized CE-C4D method was applied to the analysis of common mixed inorganic cations (K+, Na+, Ca2+, Mg2+, and Li+), anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-), toxic halides (BrO3-) and heavy metal ions (Pb2+, Cd2+, Cr3+, Co2+, Ni2+, Zn2+, and Cu2+) at trace concentrations of 200 nM. All electropherograms showed good S/N ratios, thus proving its applicability and accuracy. Our results have shown that the developed CE-C4D method is feasible for trace ion analysis in water quality control.

Efficient separation of organic anions in beverages using aminosilane-functionalized capillary electrophoresis with contactless conductivity detection

BackgroundCapillary electrophoresis (CE) has the advantage of rapid anion analysis, when employing a reverse electroosmotic flow (EOF). The conventional CE method utilizes dynamic coatings with surfactants like cetyltrimethylammonium bromide (CTAB) in the run buffer to reverse the EOF. However, this method suffers from very slow equilibration leading to drifting effective migration times of the analyte anions, which adversely affects the identification and quantification of peaks. Permanent coating of the capillary surface may obviate this problem but has been relatively little explored. Thus, permanent capillary surface modification by the covalent binding of 3-aminopropyltriethoxysilane (APTES) was studied as an alternative. ResultsThis study investigates the effect of APTES concentration for surface functionalization on EOF mobility, separation efficiency, and reproducibility of anion separation. The performance data was complemented by X-ray photoelectron spectroscopy (XPS) and contact angle (CA) measurements. The XPS measurements showed that the coverage with APTES was dependent on its concentration in the coating solution. The XPS measurements correlated well with the EOF values determined for the capillaries tested. A standard mixture of 21 anions could be baseline separated within 10 min in the capillaries with lower EOF, but not in the capillary with the highest EOF as the residence time of the analytes was too short in this case. Compared to conventional dynamic coating with CTAB, APTES-functionalized capillaries provide faster equilibration and long-term EOF stability. The application of APTES-functionalized capillaries in analyzing different beverages demonstrates the precision, reliability, and specificity in determining organic anions, providing valuable insights of their compositions. SignificanceAPTES coating on capillaries provides a facile approach to achieve a permanent reversal of the stable EOF to determine anions. The control of the coverage via the concentration of the reagent solution allows the tailoring of the EOF to different needs, a faster EOF for less complex samples where resolution is not challenging, while a lower EOF for higher complex samples where the focus is on separation efficiency. This enhancement in efficiency and sensitivity has been applied to analyzing organic acids in several beverages.

Automated analyses of dried blood spots collected by volumetric microsampling devices

BackgroundDried blood spot (DBS) sampling on cellulose cards suffers from varying blood haematocrit levels and from chromatographic effects, which have a direct impact on quantitative DBS analyses. Commercial volumetric microsampling devices were, therefore, introduced to mitigate these effects, however, these devices are not compatible with automated DBS processing systems and must be processed manually. ResultsCapillary electrophoresis (CE) instruments use fused-silica (FS) capillaries for precise and accurate liquid handling as well as for injection, separation, and quantitative analyses of liquid samples. These inherent features of an Agilent 7100 CE instrument were employed for the automated processing (elution and homogenization) of DBSs collected by hemaPEN® volumetric devices (2.74 μL of capillary blood per spot). The hemaPEN® samples were processed directly in CE vials by consecutive transfers of 56 μL of methanol and 14 μL of deionized water through the FS capillary in a sequence of 39 DBSs with repeatability of the liquid transfers better than 1.4 %. The resulting DBS eluates were homogenized by a quick air flush through the capillary and analyzed by the same capillary and CE instrument. Creatinine was selected as a clinically relevant model analyte and its endogenous concentrations in DBSs were determined by CE with capacitively coupled contactless conductivity detection (CE-C4D) in a background electrolyte solution consisting of 50 mM acetic acid and 0.1 % (v/v) Tween 20 (pH 3.0). The overall repeatability of the automated DBS processing and CE-C4D analyses of 39 DBSs was ≤7.1 % (peak areas) and ≤0.6 % (migration times), the calibration curve was linear in the 25–500 μM range (R2 = 0.9993) and covered all endogenous blood creatinine levels, the limit of detection was 5.0 μM, and sample throughput was >12 DBSs per hour. DBS ageing for 60 days and varying blood haematocrit levels (20–70 %) did not affect creatinine quantitative results (≤6.9 % for peak areas). Inter-capillary and inter-instrument repeatability was ≤7.7 % (peak areas) and ≤3.4 % (migration times) and demonstrated an excellent transferability of the proposed analytical concept among laboratories. Significance and noveltyThis contribution is the first-ever report on the use of a single off-the-shelf analytical instrument for fully automated analyses of DBSs collected by commercial volumetric microsampling devices and holds great promise for future unmanned quantitative DBS analyses.

A new green approach to L-histidine and β-alanine analysis in dietary supplements using rapid and simple contactless conductivity detection integrated with high-resolution glass-microchip electrophoresis.

The analysis of dietary supplements is far less regulated than pharmaceuticals, leading to potential quality issues. Considering their positive effect, many athletes consume supplements containing L-histidine and β-alanine. A new microfluidic method for the determination of L-histidine and β-alanine in dietary supplement formulations has been developed. For the first time, capacitively coupled contactless conductivity detection was employed for the microchip electrophoresis of amino acids in real samples. A linear relationship between detector response and concentration was observed in the range of 10-100µmol L-1 for L-histidine (R2 = 0.9968) and β-alanine (R2 = 0.9954), while achieved limits of detection (3 × S/N ratio) were 4.2µmol L-1 and 5.2µmol L-1, respectively. The accuracy of the method was confirmed using recovery experiments as well as CE-UV-VIS and HPLC-UV-VIS techniques. The developed method allows unambiguous identification of amino acids in native form without chemical derivatization and with the possibility of simultaneous analysis of amino acids with metal cations.

A novel portable microchip electrophoresis system for rapid on-site detection of soil nutrient ions

The conventional techniques for soil nutrient ion detection face challenges, including prolonged preparation periods and the necessity for distinct instruments tailored to each specific ion. To address these issues, we have engineered a cutting-edge soil nutrient ion detection apparatus: the Microchip Electrophoresis Soil Nutrient Ion Portable Detection System (ME-SNI-PDS). This system, leveraging microchip electrophoresis with a capacitively coupled contactless conductivity detector (ME-C4D), simplifies the detection process with user-friendly touchscreen controls. Our system is capable of simultaneous detection of key soil nutrient ions—ammonium (NH4 +), calcium (Ca2+), magnesium (Mg2+), potassium (K+), nitrate (NO3 −), and dihydrogen phosphate (H2PO4 −)—in a swift 180 s, facilitated by precise voltage regulation. We have refined the buffer solution, consisting of 20 mM 2-(N-morpholinyl)-ethanesulfonic acid and L-histidine, with the addition of 0.01 mM cetyltrimethylammonium bromide and 10 mM 18-crown-6, to ensure the complete resolution of soil nutrient ions. Following this, we established highly accurate peak height-to-concentration correlations for the six aforementioned ions, each with a coefficient of determination (R2) exceeding 0.99. The detection limits for these ions stand at a remarkably low concentration of 0.05 mM, translating to 0.9 mg l−1 for NH4 +, 2.0 mg l−1 for Ca2+, 1.2 mg l−1 for Mg2+, 1.96 mg l−1 for K+, 3.1 mg l−1 for NO3 −, and 4.85 mg l−1 for H2PO4 −. Subsequent soil leachate analysis via the ME-SNI-PDS has yielded ion content data that, upon comparison with results from continuous flow analyser (CFA) and inductively coupled plasma atomic emission spectrometry, confirm the system’s exceptional integration, compactness, portability, speed, and efficiency. The ME-SNI-PDS shows immense promise for application in precision agriculture and the prevention of surface soil pollution. It is poised to make a significant impact in the realm of crop fertilization and environmental stewardship.

Simple, fast, and simultaneous determination of orthophosphate, pyrophosphate, and tripolyphosphate by capillary electrophoresis with capacitively coupled contactless conductivity detection.

This work describes a novel analytical method using capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C4D) for simultaneous, simple, and rapid determination of three inorganic phosphates (orthophosphate, pyrophosphate, and tripolyphosphate) widely used as food additives and in pharmaceutical formulations. A background electrolyte composed of 0.5mol L-1 acetic acid provided fast separation (around 3.0min) and good separation efficiency and peak resolution. Linearity in the concentration range of 10-500mg L-1 was confirmed by the coefficients of determination (R2) higher than 0.99. The limits of detection varied from 0.41 to 0.58mg L-1. The accuracy of the proposed method was assessed by recovery tests conducted at three concentration levels in tap water samples, food, and personal hygiene products. Recovery values varying from 81% to 118% were achieved, indicating an acceptable accuracy. The proposed CE-C4D successfully determined the three inorganic phosphates in the analyzed samples.

A novel capacitively coupled contactless conductivity detection (C4D) microfluidic chip integrated 3D microelectrodes for on-site determination of soil nutrients

Soil macronutrient nutrients (N, P and K) are critical for crop growth and agricultural production. The rapid and quantitative determination of soil nutrient content is of great importance to guide precise fertilization. To address the difficulty of synchronizing the detection of soil N, P and K with high sensitivity, this paper proposes a novel C4D microfluidic device with integrated 3D microelectrodes, which achieves lower detection limits for nutrients detection. The chip consisted of a crossover-type electrophoretic microchannels system and a 3D microelectrodes C4D system. 3D microelectrodes were constructed through clever design with only a single photolithography process required. The proposed microfluidic chips were used to detect potassium, ammonium, nitrate, and phosphate, with experimental results of standard solutions showing low detection limits of 5.24 × 10−5 g/L, 2.81 × 10−5 g/L, 2.35 × 10−5 g/L and 2.38 × 10−5 g/L. The microfluidic chips showed good reproducibility with relative standard deviations of less than 5 %. Separation experiments were also performed on soil samples with a resolution of K+ and NH4+ greater than 1.1. Accuracy was evaluated by adding 10 mg/L and 50 mg/L standards to the soil samples and results showed that recoveries were maintained at 80–120 %. The microfluidic chip with integrated 3D microelectrodes proposed in this work would effectively address the need for on-site, rapid detection of soil nutrients.

Capillary electrophoresis using triple layer modified capillary facilitating salivary ion analyses: Application to search for potential stress markers induced by cold pressure test

In this study, we introduce a novel approach for the analysis of salivary ions using capillary electrophoresis (CE) with a triple-layer coated capillary. The capillary is sequentially coated with cationic silylating reagents, poly(vinylsulfonate), and polybrene to form a custom designed surface that effectively inhibits adsorption of protein matrix on the capillary inner wall and allows for reproducible ion analysis. For the CE with capacitively coupled contactless conductivity detection, we used suitable background electrolytes (BGEs) for salivary ion analysis. Anions were separated using a mixture of 2-(N-morpholino)ethanesulfonic acid and l-arginine, and cations were separated using that with 18-crown-6. This setup enabled rapid separation, within 4 min, together with sensitive detection. We quantified nine common anions and five cations typically found in saliva samples using this CE method, both before and after a cold pressure test (CPT, a standard stress test). The CE system demonstrated consistent ion separation across 30 consecutive measurements without requiring capillary replacement. Notably, the salivary ion balance remained predominantly anion-rich, regardless of the CPT. Cold water exposure induced greater variation in the total anion concentration than in the total cation concentration. Further analysis using multiple regression analysis revealed strong relationships between nitrate and nitrite, formate and phosphate, and potassium and nitrate, before and after the CPT. Notably, potassium and nitrate ions exhibited variations in response to stress. These results provided a method for assessing salivary ion composition and insights into the potential of salivary ions as biomarkers for stress.

Taylor dispersion analysis using capacitively coupled contactless conductivity detector

Taylor dispersion analysis (TDA) is a simple and absolute method to determine the hydrodynamic radius of solutes that respond to UV or fluorescence detections. To broaden the application range of TDA, it is necessary to develop new detection modes. This study aims to study capacitively coupled contactless conductivity detector (C4D) for the analysis of charged macromolecules. The detection sensitivities and hydrodynamic radii were compared for a C4D detector and a UV detector on positively or negatively charged polymers responding both to UV and C4D (poly-L-lysine and poly(acrylamide-co-2-acrylamido-1-methyl-propanesulfonate). The influence of the composition of the background electrolyte on the detection sensitivity has been studied and optimized for C4D detection. The influence of the molar mass and of the polymer chemical charge density on the C4D and UV sensitivities of detection have been investigated based on well-characterized copolymers samples of different molar masses and charge densities. The advantages and disadvantages compared to UV detection, as well as the range of applicability of C4D detection in TDA were identified. C4D detection can be an alternative method for sizing charged polymers of reasonable molar mass (typically below 105 g mol−1) that do not absorb in UV. A decline in the sensitivity of detection in C4D was observed for higher molar masses.

Numerical-Simulation-Based Buffer Design for Microchip Electrophoresis with Capacitively Coupled Contactless Conductivity Detection

Numerical-Simulation-Based Buffer Design for Microchip Electrophoresis with Capacitively Coupled Contactless Conductivity Detection

Contactless conductivity detector as a tool for improving universality and sensitivity of capillary electrophoresis-frontal analysis: Proof of concept.

Drug binding to plasma proteins influences processes such as liberation, adsorption, disposition, metabolism, and elimination of drugs, which are thus one of the key steps of a new drug development. As a result, the characterization of drug-protein interactions is an essential part of these time- and money-consuming processes. It is important to determine not only the binding strength and the stoichiometry of interaction, but also the binding site of a drug on a protein molecule, because two drugs with the same binding site can mutually affect free drug concentration. Capillary electrophoresis-frontal analysis with mobility shift affinity capillary electrophoresis is one of the most used affinity capillary electrophoresis methods for the characterization of these interactions. In this study, awell-known sensitivity problem of most capillary electrophoresis-frontal analyses using ultraviolet detection is solved by its combination with contactless conductivity detection, which provided sixfold lower limits of quantitation and detection. Binding parameters of the human serum albumin-salicylic acid model affinity pair were evaluated by this newly developed approach and by the classical approach with ultravioletdetection primarily used for their mutual comparison. The results of both approaches agreed well and are also in agreement with literature data obtained using different techniques.

PCB-C4D coupled with paper-based microfluidic sampling for the rapid detection of liquid conductivity.

The detection of liquid electrical conductivity has board applications in food safety testing, water quality monitoring, and agricultural soil analysis. Electrodes used in traditional liquid electrical conductivity detection come into direct contact with liquid, leading to electrode contamination and affecting the accuracy of the detection results. The capacitively coupled contactless conductivity detection (C4D) method effectively addresses this issue. However, impurity particles present in the solution can compromise the consistency and repeatability of detection results. This study combines paper-based microfluidic technology with printed circuit board-capacitively coupled contactless conductivity detection (PCB-C4D) to address this issue. Prior to sample detection, in situ rapid filtration is employed to remove impurity particles from the raw solution sample, significantly enhancing detection consistency and reliability. Simultaneously, Optimization of PCB-C4D parameters, channel size, filtration time, and solution drop rate ensures optimal detection conditions. A compact kit design facilitates reliable assembly of the PCB-C4D electrodes and paper-based channel, enhancing practicality. Practical measurements on the conductivity of orange juice, cucumber, and soil solution further validate the method's accuracy, rapidity, and effectiveness in in situ conductivity detection. This work advances the practical application of PCB-C4D technology.

A compact and high-performance setup of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D).

Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has the advantages of high throughput (simultaneous detection of multiple ions), high separation efficiency (higher than 105 theoretical plates) and rapid analysis capability (less than 5 min for common inorganic ions). A compact CE-C4D system is ideal for water quality control and on-site analysis. It is suitable not only for common cations (e.g. Na+, K+, Li+, NH4+, Ca2+, etc.) and anions (e.g. Cl-, SO42-, BrO3-, etc.) but also for some ions (e.g. lanthanide ions, Pb2+, Cd2+, etc.) that require complex derivatization procedures to be detected by ion chromatography (IC). However, an obvious limitation of the CE-C4D method is that its sensitivity (e.g. 0.3-1 μM for common inorganic ions) is often insufficient for trace analysis (e.g. 1 ppb or 20 nM level for common inorganic ions) without preconcentration. For this technology to become a powerful and routine analytical technique, the system should be made compact while maintaining trace analysis sensitivity. In this study, we developed an all-in-one version of the CE-C4D instrument with custom-made modular components to make it a convenient, compact and high-performance system. The system was designed using direct digital synthesis (DDS) technology to generate programmable sinusoidal waveforms with any frequency for excitation, a kilovolt high-voltage power supply for capillary electrophoresis separation, and an "effective" differential C4D cell with a low-noise circuitry for high-sensitivity detection. We characterized the system with different concentrations of Cs+, and even a low concentration of 20 nM was detectable without preconcentration. Moreover, the optimized CE-C4D setup was applied to analyse mixed ions at a trace concentration of 200 nM with excellent signal-to-noise ratios. In typical applications, the limits of detection based on the 3σ criterion (without baseline filtering) were 9, 10, 24, 5, and 12 nM for K+, Cs+, Li+, Ca2+, and Mg2+, respectively, and about 7, 6, 6 and 6 nM for Br-, ClO4-, BrO3- and SO42-, respectively. Finally, the setup was also applied for the analysis of all 14 lanthanide ions and rare-earth minerals, and it showed an improvement in sensitivity by more than 25 times.