Contactless Conductivity Detection Research Articles

A novel temperature-controlled open source microcontroller based sampler for collection of exhaled breath condensate in point-of-care diagnostics

Exhaled breath condensate (EBC) is an attractive, non-invasive sample for clinical diagnostics. During EBC collection, its composition is influenced by the collection temperature, a factor that is often not thoroughly monitored and controlled. In this study, we assembled a novel, simple, portable, and inexpensive device for EBC collection, able to maintain a stable temperature at any value between −7 °C and +12 °C. The temperature was controlled using a microcontroller and a thermoelectric cooler that was employed to cool the aluminum block holding the glass tube or the polypropylene syringe. The performance of the novel sampler was compared with the passively cooled RTube™ and a simple EBC sampler, in which the temperature was steadily increasing during sampling. The developed sampler was able to maintain a stable temperature within ±1 °C. To investigate the influence of different sampling temperatures (i.e., +12, −7, −80 °C) on the analyte content in EBC, inorganic ions and organic acids were analyzed by capillary electrophoresis with a capacitively coupled contactless conductivity detector. It was shown that the concentration of metabolites decreased significantly with decreasing temperature. The portability and the ability to keep a stable temperature during EBC sampling makes the developed sampler suitable for point-of-care diagnostics.

Towards a radiation-tolerant contactless conductivity detector for use with capillary electrophoresis systems in spaceflight applications

The simplicity, versatility, and ease of miniaturization of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has led to its application for the analysis of a wide range of inorganic and organic species. While C4D detectors have relatively straightforward electronics, no designs specifically focused on spaceflight applications have been developed. The challenge lies in the limited set of components tolerant to high radiation levels and large temperature ranges when designing electronics for planetary science missions. In this work we present a C4D prototype designed for high radiation environments over the range of 50–300 krad total ionizing dose (TID). The proposed design, including selection of components, compatibility with radiation levels and the main differences compared to an open source version of the detector (OpenC4D) are discussed in detail. This prototype was also designed to allow monitoring of up to three capillaries for measurement redundancy. The Rad Hard C4D was assembled using COTS equivalents of the radiation-hardened counterparts, and its performance was evaluated by comparison to a commercial C4D device. Additionally, the reagents used for an astrobiology focused CE-C4D method developed previously were investigated for long-term storage and compatibility with high radiation levels. No loss in performance was observed for reagents exposed to 300 krad TID and stored for 2 years at room temperature.

Sub-Minute Analysis of Lactate from a Single Blood Drop Using Capillary Electrophoresis with Contactless Conductivity Detection in Monitoring of Athlete Performance.

A simple and fast method for the analysis of lactate from a single drop of blood was developed. The finger-prick whole blood sample (10 µL) was diluted (1:20) with a 7% (w/v) solution of [tris(hydroxymethyl)methylamino] propanesulfonic acid and applied to a blood plasma separation device. The device accommodates a membrane sandwich composed of an asymmetric polysulfone membrane and a supporting textile membrane that allows the collection of blood plasma into a narrow glass capillary in less than 20 s. Separated and simultaneously diluted blood plasma was directly injected into a capillary electrophoresis instrument with a contactless conductivity detector (CE-C4D) and analyzed in less than one minute. A separation electrolyte consisted of 10 mmol/L l-histidine, 15 mmol/L dl-glutamic acid, and 30 µmol/L cetyltrimethylammonium bromide. The whole procedure starting from the finger-prick sampling until the CE-C4D analysis was finished, took less than 5 min and was suitable for monitoring lactate increase in blood plasma during incremental cycling exercise. The observed lactate increase during the experiments measured by the developed CE-C4D method correlated well with the results from a hand-held lactate analyzer (R = 0.9882). The advantage of the developed CE method is the speed, significant savings per analysis, and the possibility to analyze other compounds from blood plasma.

A Low Excitation Working Frequency Capacitively Coupled Contactless Conductivity Detection (C4D) Sensor for Microfluidic Devices.

In this work, a new capacitively coupled contactless conductivity detection (C4D) sensor for microfluidic devices is developed. By introducing an LC circuit, the working frequency of the new C4D sensor can be lowered by the adjustments of the inductor and the capacitance of the LC circuit. The limits of detection (LODs) of the new C4D sensor for conductivity/ion concentration measurement can be improved. Conductivity measurement experiments with KCl solutions were carried out in microfluidic devices (500 µm × 50 µm). The experimental results indicate that the developed C4D sensor can realize the conductivity measurement with low working frequency (less than 50 kHz). The LOD of the C4D sensor for conductivity measurement is estimated to be 2.2 µS/cm. Furthermore, to show the effectiveness of the new C4D sensor for the concentration measurement of other ions (solutions), SO42− and Li+ ion concentration measurement experiments were also carried out at a working frequency of 29.70 kHz. The experimental results show that at low concentrations, the input-output characteristics of the C4D sensor for SO42− and Li+ ion concentration measurement show good linearity with the LODs estimated to be 8.2 µM and 19.0 µM, respectively.

Development of CE-C4D Method for Determination Tropane Alkaloids.

A fast method for the determination of tropane alkaloids, using a portable CE instrument with a capacitively coupled contactless conductivity detector (CE-C4D) was developed and validated for determination of atropine and scopolamine in seeds from Solanaceae family plants. Separation was obtained within 5 min, using an optimized background electrolyte consisting of 0.5 M acetic acid with 0.25% (w/v) β-CD. The limit of detection and quantification was 0.5 µg/mL and 1.5 µg/mL, respectively, for both atropine and scopolamine. The developed method was validated with the following parameters—precision (CV): 1.07–2.08%, accuracy of the assay (recovery, RE): 101.0–102.7% and matrix effect (ME): 92.99–94.23%. Moreover, the optimized CE-C4D method was applied to the analysis of plant extracts and pharmaceuticals, proving its applicability and accuracy.

Analysis of amino acids in cell culture supernatant using capillary electrophoresis with contactless conductivity detection.

CE-C4 D methods for the analysis of amino acids (AAs) are presented. Combining the results from two methods with acetic acid and cyclodextrin-based BGEs, 20 proteinogenic AAs could be analyzed using CE. CE-C4 D was also, for the first time, applied to analyze free AAs in samples of mammalian cell culture supernatant. After dilution as only sample preparation, combining the results of the two CE methods allowed monitoring the concentration changes of 17 AAs in samples taken during the cultivation of CHO cells.

Multimaterial 3D-printed contactless conductivity/laser-induced fluorescence dual-detection cell for capillary electrophoresis

利用多材料3D打印技术研制了用于毛细管电泳(CE)的二合一检测池,实现了电容耦合非接触电导(C4D)与共聚焦激光诱导荧光(LIF)两种检测方法在毛细管柱上同一位置同时检测。3D打印的检测池采用了导电的复合聚乳酸(PLA)材料制作C4D的屏蔽层,采用普通的绝缘PLA材料支撑C4D金属管电极并隔离屏蔽层。两根金属管电极通过“打印-暂停-打印”的方式嵌入到检测池中,两电极被2 mm厚的导电屏蔽层隔开,在屏蔽层中有一直径为1 mm的圆形通孔用于LIF检测。该检测池与带流通式进样接口的自组装CE系统联用,用于同时检测无机离子和异硫氰酸荧光素(FITC)标记的氨基酸。研究优化了C4D激励信号频率与电泳缓冲液浓度,选用的电泳缓冲溶液为10 mmol/L 3-吗啉丙烷-1-磺酸(MOPS)与10 mmol/L二(2-羟乙基)亚氨基三(羟甲基)甲烷(Bis-Tris)的混合溶液,选用C4D激励频率为77 kHz。二合一检测池应用于内径为25 μm的毛细管时,C 4D对Na+、K+和Li+的检出限分别为2.2、2.0和2.6 μmol/L; LIF对荧光素和FITC的检出限分别为7.6和1.7 nmol/L。两种检测方法的相对标准偏差在0.3%至4.5%之间(n=3),工作曲线的相关系数r 2≥0.9904。采用3D打印技术可以在实验室内实现复杂结构的制作,降低了制作的成本,且便于方法的推广和改进。

Monitoring of circulating amino acids in patients with pancreatic cancer and cancer cachexia using capillary electrophoresis and contactless conductivity detection.

Branched chain amino acids (BCAAs), alanine and glutamine are determined in human plasma by capillary electrophoresis with contactless conductivity detection (CE/C4 D). The baseline separation of five amino acids from other plasma components is achieved on the short capillary effective length of 18cm in 3.2mol/L acetic acid with addition of 13% v/v methanol as background electrolyte. Migration times range from 2.01min for valine to 2.84min for glutamine, and LODs for untreated plasma are in the interval 0.7-0.9μmol/L. Sample treatment is based on the addition of acetonitrile to only 15μL of plasma and supernatant is directly subjected to CE/C4 D. Circulating amino acids are measured in patients with pancreatic cancer and cancer cachexia during oral glucose tolerance test. It is shown that patients with pancreatic cancer and cancer cachexia syndrome exhibit low basal circulating BCAAs and glutamine levels and loss of their insulin-dependent suppression.

3D-printed microchip electrophoresis device containing spiral electrodes for integrated capacitively coupled contactless conductivity detection.

In this work, we demonstrate for the first time the design and fabrication of microchip electrophoresis devices containing cross-shaped channels and spiral electrodes around the separation channel for microchip electrophoresis and capacitively coupled contactless conductivity detection. The whole device was prepared in a digital light processing-based 3D printer in poly(ethylene glycol) diacrylate resin. Outstanding X-Y resolution of the customized 3D printer ensured the fabrication of 40-μm cross section channels. The spiral channels were filled with melted gallium to form conductive electrodes around the separation channel. We demonstrate the applicability of the device on the separation of sodium, potassium, and lithium cations by microchip electrophoresis. Graphical abstract.

Characterization of linearly coupled capillaries with various inner diameters in the context of capillary electrophoresis

As a result of continuous instrumental progress, capillary electrophoresis has become an established separation technique. However, the choice of the suitable capillary inner diameter is sometimes difficult due to different instrumental requirements concerning injection, separation, or detection. To overcome this problem, we assembled two capillaries with different inner diameters, meaning that the inner diameter of the capillary at the injection side was different from that at the detection side. Since this was a rather uncommon approach, we focused on the associated effects in this proof-of-concept study. For the experiments, a non-aqueous model system was used, consisting of an acetonitrile-based background electrolyte and the two ferrocene derivates, ferrocenemethanol and decamethylferrocene. Using capillary flow injection analysis hyphenated to capacitively coupled contactless conductivity detection, it could be shown that fragmented capillaries of the same inner diameter had slightly lower volume flow rates than non-fragmented capillaries. With non-aqueous capillary electrophoresis hyphenated to UV detection, it was found that the coupling of capillaries with different inner diameter had a much stronger effect on the capillary electrophoresis flow than combinations with the same inner diameter. Additionally, if the inner diameter of the second capillary was larger than the inner diameter of the first capillary, a higher theoretical plate number and an increased sensitivity were found. Furthermore, it was found that there was no significant peak tailing introduced by the coupling.Graphic abstract

Ultrasensitive determination of underivatized adamantane analogs in biological fluids by capillary electrophoresis with contactless conductivity detection

Separation techniques are promising for the detection of adamantane analogs with various functional groups. The derivatization of adamantane analogs with chromophores or fluorophores should be conducted using a separation technique combined with a common ultraviolet–visible or fluorescence detector. However, limited research has been conducted on underivatized adamantane analogs. Therefore, we present a highly rapid and sensitive method for detecting underivatized adamantane analogs by integrating ultrasound-assisted dispersive liquid–liquid microextraction (UADLLME), field-amplified sample stacking (FASS)-related capillary electrophoresis (CE), and capacitively coupled contactless conductivity detection (C4D). In the proposed system, UADLLME is used for sample clean up and analyte enrichment, whereas FASS-related CE provides on-line concentration of underivatized adamantane analogs during CE separation. A mixture of memantine (MT), amantadine (AT), and rimantadine (RT) was separated at baseline within 8 min through the application of optimized UADLLME (mixing extraction solvent, 50 μL of 1,1,2,2-tetrachloroethane (C2H2Cl4) and dispersive solvent, 200 μL of acetonitrile; mixing solution was injected into 1 mL of the sample solution at pH 12.5), FASS (buffer, 1.5 M acetic acid; additive, 0.05 mM β-cyclodextrin; pH 2.5), and C4D (amplitude, 2 Vpp; frequency, 500 kHz). The calibration curve exhibited acceptable linearity, with a coefficient of determination higher than 0.99. The limits of detection (signal-to-noise ratio of 3) were estimated to be 0.9, 1.0, and 1.2 nM for MT, AT, and RT, respectively. The relative standard deviations of peak areas varied from 8.9% to 9.3% (n = 5), whereas the sensitivity improvement of three underivatized adamantane analogs ranged from 1342 to 1766. The feasibility and accuracy of the present method for the determination of MT, AT, and RT in human serum and urine was satisfactorily confirmed by the excellent recovery and relative error. The proposed method exhibited high enrichment factors and offers excellent precision, high accuracy, and a short analysis time.

Automated Capillary Electrophoresis System Compatible with Multiple Detectors for Potential In Situ Spaceflight Missions.

The in situ search for chemical signatures of life on extraterrestrial worlds requires automated hardware capable of performing detailed compositional analysis during robotic missions of exploration. The use of electrophoretic separations in this search is particularly powerful, enabling analysis of a wide range of soluble organic compounds potentially indicative of life, as well as inorganic compounds that can serve as indicators of habitability. However, to detect this broad range of compounds with a single electrophoresis instrument, a combination of different detection modes is required. For detection of any ionizable species, including organic compounds that do not participate in terrestrial biology (i.e., "unknown unknowns"), mass spectrometry (MS) is essential. Inorganic ions, or any dissolved charged species present, can be analyzed using capacitively coupled contactless conductivity detection (C4D). Additionally, for the trace analysis of compounds of key interest to astrobiology (particularly, amino acids), laser-induced fluorescence (LIF) detection holds unique promise, due to the fact that it has the highest demonstrated sensitivity of any form of detection. Here, we demonstrate a fully automated, portable capillary electrophoresis analyzer that is capable of all these modes of detection. The prototype system developed here addresses the three most significant challenges for doing electrophoretic separations: precise sample injection, HV isolation, and automation of all operational steps. These key challenges were successfully addressed with the use of custom-designed rotor-stator valves with optimized operational sequences incorporating gas purging steps, rinses, and HV application.

Investigation of the Effects of Electrode Geometry on the Performance of C4D Sensor with Radial Configuration.

Electrodes are basic components of C4D (capacitively coupled contactless conductivity detection) sensors, and different electrode structures (the configuration pattern or the electrode geometry) can lead to different measurement results. In this work, the effects of electrode geometry of radial configuration on the measurement performance of C4D sensors are investigated. Two geometrical parameters, the electrode length and the electrode angle, are considered. A FEM (finite element method) model based on the C4D method is developed. With the FEM model, corresponding simulation results of conductivity measurement with different electrode geometry are obtained. Meanwhile, practical experiments of conductivity measurement are also conducted. According to the simulation results and experimental results, the optimal electrode geometry of the C4D sensor with radial configuration is discussed and proposed. The recommended electrode length is 5–10 times of the pipe inner diameter and the recommended electrode angle is 120–160°.

Development of low-cost planar electrodes and microfluidic channels for applications in capacitively coupled contactless conductivity detection (C4 D).

Electrochemical techniques are commonly applied to micro total analysis system (μTAS) devices mainly due to its high sensitivity and miniaturization capacity. Among many electrochemical techniques, capacitively coupled contactless conductivity detection (C4 D) stands out for not requiring direct electrode-solution contact, avoiding several problems such as electrolysis, bubble formation, and metal degradation. Furthermore, the instrumentation required for C4 D measurements is compact, low cost, and easy to use, allowing in situ measurements to be performed even by nonspecialized personal. Contrarily, the production of metallic electrodes and microchannels adequate for C4 D measurements commonly requires specialized facilities and workers, increasing the costs of applying these methods. We propose alternatives to batch manufacture metallic electrodes and polymeric microchannels for C4 D analysis using more straightforward equipment and lower-cost materials. Three devices with different dielectric layer compositions and electrode sizes were tested and compared regarding their analytical performance. The constructed platforms have shown a reduction of more than 64% in cost when compared to traditional techniques and displayed good linearity (R2 ≥ 0.994), reproducibility (RSD ≤ 4.07%, n = 3), and limits of detection (≤0.26mmol/L) when measuring standard NaCl samples. Therefore, the proposed methods were successfully validated and are available for further C4 D applications such as diagnosis of dry-eye syndrome.

Ultra‐rapid capillary zone electrophoresis method for simultaneous determination of arginine and ibuprofen

The combination of arginine and ibuprofen is widely used for pain relief with a faster onset of action than conventional ibuprofen. Therefore, the determination of both compounds in a single run is highly desirable for rapid quality control applications. This paper reports an ultra-fast method (100 injections/h) for simultaneous determination of arginine and ibuprofen using capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation of arginine as cation and ibuprofen as anion was achieved using a background electrolyte composed by an equimolar mixture of 10mmol/L of 2-(cyclohexylamino) ethanesulfonic acid and boric acid with pH adjusted to 8.4 using potassium hydroxide. The limits of detections were 5.3 and 10.0 μmol/L for arginine and ibuprofen, respectively. The proposed method is simple, fast (one analysis every 35 s), environmentally friendly (minimal waste generation) and accurate (recovery values between 95 and 98%).

Tween 20-capped gold nanoparticles for selective extraction of free low-molecular-weight thiols in saliva followed by capillary electrophoresis with contactless conductivity detection

Low-molecular-weight thiols are widely present in human fluids, and are regarded as a kind of potential broad-spectrum evaluation indicators for some clinical diseases. In this work, gold nanoparticles capped with Tween 20 were used for purification and microextraction of the main free thiols (cysteine, homocysteine, glutathione and methionine) in saliva based on Au-S bond formation. Ultrasound further sped up the releasing of the target analytes, and the releasing time needed was only 10 min, and the required sample volume was only 40 µL. The desorption solution could be directly injected for electrophoretic analysis without derivatization, and field-amplified sample stacking of electrophoretic online enrichment technology further improved the detection sensitivity. The synergistic enrichment effect made the enrichment factors of four analytes reach 1119–2067 times. This developed method was applied for the analyses of saliva samples of healthy volunteers. Acceptable sensitivity (LODs: 0.15–1.5 ng mL−1) and recoveries (97.6–116%) were obtained in the saliva sample matrix. This proposed method provides an alternative for the sensitive detection of low-molecular-weight thiols in noninvasive body fluids, which has potential application prospect in the preliminary noninvasive diagnosis of diabetes, cardiovascular diseases, etc.

Advancements in capacitance-to-digital converter-based C4 D technology for detection in capillary electrophoresis using amplified excitation voltages and comparison to classical and open-source C4 Ds.

This work introduces new hardware configurations for a capacitively coupled contactless conductivity detector (C4 D) based on capacitance-to-digital conversion (CDC) technology for CE. The aim was to improve sensitivity, handling, price, and portability of CDC-based C4 D detectors (CDCD) to reach LODs similar to classic C4 Ds with more sophisticated electric circuits. To achieve this, a systematic study on the CDCDs was carried out including a direct comparison to already established C4 D setups. Instrumental setups differing in electrode lengths, measurement modes, and amplification of excitation voltages were investigated to achieve LODs for alkali metal ions of 4 to 12μM, similar to LODs obtained by classic C4 D setups. Lowest LODs were achieved for a setup with two 10mm electrodes at a distance of 0.2mm and an excitation voltage of 24V. The detection head was exceptionally lightweight with only 2.6g and covered only 20mm of the capillary on total. This allowed the use of multiple detectors along the separation path to enable spatial tracking of analytes during separation. The entirely battery-powered detector assembly weighs less than 200g, and the data are transmitted wirelessly for possible portable applications. The freely accessible hardware and software were optimized for fully automated measurements with real time data plotting and allowed handling multidetector setups. The new developments were applied to quantify the potassium salt of glyphosate in its herbicide formulation.

Chip-based separation of organic and inorganic anions and multivariate analysis of wines according to grape varieties

This report describes the use of electrophoresis microchips integrated with contactless conductivity detection for the determination of organic acids and inorganic anions in wine samples and the subsequent classification based on the grape varieties. The best separation was achieved using a buffer composed of 30 mmol L−1 2-(N-morpholino)ethanesulfonic acid, 15 mmol L−1l-histidine and 0.05 mmol L−1 cetyltrimethylammonium bromide (pH 5.8), allowing the determination of chloride, nitrate, sulfate, oxalate, tartrate, maleate, succinate, citrate, acetate, lactate, pyroglutamate and phosphate within ca. 100 s. The relative standard deviations obtained for the migration times were lower than 2%, while the obtained values for peak areas ranged from 2.5 to 8.4%. The limits of detection achieved for all compounds ranged between 3.0 and 12.6 μmol L−1. A total of 18 wines from Brazil and Chile were successfully investigated, including red, white and rosé, and the anionic species were quantified with recovery values between 92 and 117%. A statistical difference has not been observed between the data obtained by using electrophoresis microchips integrated with contactless conductivity detection (ME-C4D) and capillary electrophoresis with ultra-violet detection (CE-UV) and thus the results from newly developed method is validated. Finally, similarities among the anionic profile of wines were investigated by using a multivariate approach, and it was possible to discriminate samples mainly by grapes varieties. Furthermore, the proposed methodology has provided instrumental simplicity and good analytical performance, demonstrating to be useful for routine quality control of wines.

Contactless conductivity sensor as detector for microfluidic paper-based analytical device with application to unique rapid method for quantifying sulfite preservative

Abstract The work presents the latest exploitation of capacitively coupled contactless conductivity detector (C4D) produced from printed-circuit board as durable detector for in-situ headspace microfluidic paper-based analytical devices (μPADs). This is the first reagent-free operating paper-based method for direct determination of sulfite, with storage of acid reagent during μPAD fabrication. In the procedure, the detection zone is first moistened with deionized water, and the μPAD turned over and placed on the C4D sensing area with the moist-zone faced down. Sample is loaded at the top layer of μPAD where it flows into the adjacent covered reaction zone, containing the absorbed acid, forming SO2(g). The gas diffuses through the in-situ headspace in the middle layer and is absorbed into the moist detection zone at the base layer giving a prompt change in the C4D signal due to the change in conductivity from the generated conductive ionic species, viz. H+(aq) and HSO3−(aq). The working range of the C4D-μPAD is 8–100 mg L-1 sulfite, with the limit of detection of 6.61 mg L-1. Compared with other paper-based methods that detect SO2(g), this is the only in-situ method and most rapid method (3.3 min per sample) for fruit juices, white and red wines.

A Rapid and Simple Dual-Channeled Capillary Electrophoresis with Contactless Conductivity Detection Method for the Determination of Adenosine, Cordycepin, and Inosine in Ophiocordyceps sinensis-Based Products

This study aims to propose a tool for food control activities that can be realizable even with a modest infrastructure, using purpose-made capillary electrophoresis (CE) instrumentation with capacitively coupled contactless conductivity detection (C4D). For demonstration of a featured application, we reported herein a simple and inexpensive method for authentication and quality control of Ophiocordyceps sinensis-based products (literally known as “summer grass, winter worm”). This species, originally found on the Tibetan plateau and in the Himalayas, between elevations of 3000–5000 m, is classified as a medicinal mushroom and has been used as a precious component in traditional Chinese and Vietnamese medicine. Due to its high value and rareness, counterfeit products have emerged, leading to the need for quality control activities. For this purpose, a CE-C4D methodology was developed to determine their adenosine, cordycepin, and inosine contents. These compounds were analyzed on two channels of the purpose-made instrument, with the best-achieved detection limits of 11.2–22.0 μg/g using the developed CE-C4D methods. Cross-checking data using the reference method (HPLC-DAD) was provided to prove the reliability of the analytical results obtained with CE-C4D. Good agreement for the two pairs of data was achieved, with the result deviation being less than 12%.