Quadrupole Electrodes Research Articles

Dielectrophoretic profiling of erythrocytes to study the impacts of metabolic stress, temperature, and storage duration utilizing a point-and-planar microdevice

Dielectrophoresis (DEP) is widely utilized for trapping and sorting various types of cells, including live and dead cells and healthy and infected cells. This article focuses on the dielectric characterization of erythrocytes (red blood cells or RBCs) by quantifying DEP crossover frequency using a novel point-and-planar microwell device platform. Numerical simulations using COMSOL Multiphysics software demonstrate that the distribution of the DEP force is influenced by factors such as the shape of the point electrode, spacing between the point and planar electrodes, and the type of bioparticle being investigated. The dependency on electrode spacing is experimentally evaluated by analyzing the DEP crossover response of erythrocytes. Furthermore, the results are validated against the traditional electrical characterization technique called electrorotation, which typically requires laborious fabrication and operation using quadrupole electrodes. Other significant factors, including erythrocyte storage age and the changes in cell properties over time since collection, osmolarity, and temperature, are also assessed to determine the optimal conditions for erythrocyte characterization. The findings indicate a significant difference between fresh and stored erythrocyte samples (up to 4 days), highlighting the importance of maintaining an isotonic medium for cell storage.

Next generation CANCAN focusing for remote stimulation by nanosecond electric pulses

Focusing electric pulse effects away from electrodes is a challenge because the electric field weakens with distance. Previously we introduced a remote focusing method based on bipolar cancellation, a phenomenon of low efficiency of bipolar nanosecond electric pulses (nsEP). Superpositioning two bipolar nsEP into a unipolar pulse canceled bipolar cancellation (“CANCAN” effect), enhancing bioeffects at a distance despite the electric field weakening. Here, we introduce the next generation (NG) CANCAN focusing with unipolar nsEP packets designed to produce bipolar waveforms near electrodes (suppressing electroporation) but not at the remote target. NG-CANCAN was tested in CHO cell monolayers using a quadrupole electrode array and labeling electroporated cells with YO-PRO-1 dye. We routinely achieved 1.5–2 times stronger electroporation in the center of the quadrupole than near electrodes, despite a 3–4-fold field attenuation. With the array lifted 1–2 mm above the monolayer (imitating a 3D treatment), the remote effect was enhanced up to 6-fold. We analyzed the role of nsEP number, amplitude, rotation, and inter-pulse delay, and showed how remote focusing is enhanced when re-created bipolar waveforms exhibit stronger cancellation. Advantages of NG-CANCAN include the exceptional versatility of designing pulse packets and easy remote focusing using an off-the-shelf 4-channel nsEP generator.

Dielectrophoretic detection of electrical property changes of stored human red blood cells.

The ability to transport and store a large human blood inventory for transfusions is an essential requirement for medical institutions. Thus, there is an important need for rapid and low-cost characterization tools for analyzing the properties of human red blood cells (RBCs) while in storage. In this study, we investigate the ability to use dielectrophoresis (DEP) for measuring the storage-induced changes in RBC electrical properties. Fresh human blood was collected, suspended in K2-EDTA anticoagulant, and stored in a blood bank refrigerator for a period of 20 days. Cells were removed from storage at 5-day intervals and subjected to a glutaraldehyde crosslinking reaction to "freeze" cells at their ionic equilibrium at that point in time and prevent ion leakage during DEP analysis. The DEP behavior of RBCs was analyzed in a high permittivity DEP buffer using a three-dimensional DEP chip (3DEP) and also compared to measurements taken with a 2D quadrupole electrode array. The DEP analysis confirms that RBC electrical property changes occur during storage and are only discernable with the use of the cell crosslinking reaction above a glutaraldehyde fixation concentration of 1.0w/v%. In particular, cytoplasm conductivity was observed to decrease by more than 75% while the RBC membrane conductance was observed to increase by more than 1000% over a period of 20 days. These results show that the presented combination of chemical crosslinking and DEP can be used as rapid characterization tool for monitoring electrical properties changes of human RBCs while subjected to refrigeration in blood bank storage.

Organic Photovoltaics Printed via Sheet Electrospray Enabled by Quadrupole Electrodes.

Developing manufacturing methods that are scalable and compatible with a roll-to-roll process with low waste of material has become a pressing need to transfer organic photovoltaics (OPVs) to a viable renewable energy source. For this purpose, various spray printing methods have been proposed. Among them, electrospray (ES) is an attractive option due to its negligible material waste, tunable droplet size, and tolerance to the substrate defects and roughness. Conventional ES with a circular spray footprint often makes the droplets well separated and unlikely to merge, giving rise to "coffee rings" which cause a rough and flawed film morphology. Here, a quadrupole electrode is introduced to generate a compressing electric field that squeezes the conical ES profile into the shape of a thin sheet. The numerical simulation and experimental data of the trajectories of sprayed droplets show that the quadrupole apparatus can effectively increase the long axis to short axis ratio of the oval spray footprint and hence bring droplets closer to each other and make the merging more likely for the deposited droplets. By promoting the merging of droplets, individual coffee rings are also suppressed. Thus, the quadrupole ES offers untapped opportunities for effectively reducing voids and improving the flatness of the ES-printed active layer. The devices with a PM6:N3 active layer printed by the sheet ES exhibited the highest power conversion efficiency (PCE) of up to 15.98%, which is a noticeable improvement over that (14.85%) of counterparts fabricated by a conventional conical ES. This is the highest PCE reported for ES-printed OPVs and is one of the most efficient spray-deposited OPVs so far. In addition, the all-spray-printed devices reached a PCE of 14.55%, which is also among the most efficient all-spray-printed OPVs.

Monitoring of the Electrototation of Cells Stimulated By the Ionophore

Monitoring of the Electrototation of Cells Stimulated By the Ionophore

Cannabinoid Receptor Agonist Inhibits Atrial Electrical Remodeling in a Tachypaced Ex Vivo Rat Model.

Introduction: Atrial fibrillation (AF) leads to rate-dependent atrial changes collectively defined as atrial remodelling (AR). Shortening of the atrial effective refractory period (AERP) and decreased conduction velocity are among the hallmarks of AR. Pharmacological strategies to inhibit AR, thereby reducing the self-perpetual nature of AF, are of great clinical value. Cannabinoid receptor (CBR) ligands may exert cardioprotective effects; CB13, a dual CBR agonist with limited brain penetration, protects cardiomyocytes from mitochondrial dysfunction induced by endothelin-1. Here, we examined the effects of CB13 on normal physiology of the rat heart and development of tachypacing-induced AR. Methods: Rat hearts were perfused in a Langendorff set-up with CB13 (1 µM) or vehicle. Hemodynamic properties of non-paced hearts were examined conventionally. In a different set of hearts, programmed stimulation protocol was performed before and after atrial tachypacing for 90 min using a mini-hook platinum quadrupole electrode inserted on the right atrium. Atrial samples were further assessed by western blot analysis. Results: CB13 had no effects on basal hemodynamic properties. However, the compound inhibited tachypacing-induced shortening of the AERP. Protein expression of PGC1α was significantly increased by CB13 compared to vehicle in paced and non-paced hearts. Phosphorylation of AMPKα at residue threonine 172 was increased suggesting upregulation of mitochondrial biogenesis. Connexin43 was downregulated by tachypacing. This effect was diminished in the presence of CB13. Conclusion: Our findings support the notion that peripheral activation of CBR may be a new treatment strategy to prevent AR in patients suffering from AF, and therefore warrants further study.

Continuous trapping of bacteria in non-Newtonian blood flow using negative dielectrophoresis with quadrupole electrodes

Efficient trapping of bacteria from whole blood is essential for point-of-care diagnostics of sepsis at an early stage in order to reduce morbidity and mortality. However, low bacteria concentration and the presence of blood cells hinder the trapping efficiency of bacteria from whole blood. As red blood cells comprise 94.9% of total blood cells, lysing the red blood cells using saponin could effectively attenuate the influence of the blood component on the bacteria-trapping process. In this situation, long-range bacteria trapping from whole blood using a hybrid electrokinetic based lab-on-a-chip device becomes promising. In this paper, through developing a multi-physical lattice Boltzmann method with Langevin dynamics, the continuous trapping process of S. aureus in a microfluidic channel with quadrupole electrodes under combined alternating-current electrothermal electrohydrodynamic force and negative dielectrophoresis force is numerically investigated and optimized at various parametric conditions. Based on the statistical data, a stable bacteria recovery rate of 68.4%–74.5% is successfully achieved with respect to different bacteria densities under appropriate operational conditions of the designed lab-on-a-chip device. The current work demonstrates the potential of continuous bacteria trapping from whole blood using hybrid electrokinetic phenomena.

Automated Embryo Manipulation and Rotation via Robotic nDEP-Tweezers.

This paper presents a novel and non-invasive technique that can easily manipulate mouse embryos on a polyvinyl chloride (PVC) Petri dish. An inverted microchip with quadrupole electrodes was attached to a micromanipulator to become a robotic dielectrophoresis (DEP) tweezers, and a motorized platform provided additional mobility to the embryos lying on a Petri dish. Vision-based algorithms were developed to evaluate relevant information of the embryos from the image, and to provide feedback signals for precise position and orientation control of the embryo. A series of experiments was conducted to examine the system performance, and the embryo can be successfully manipulated to a specified location with the desired orientation for subsequent processing. This system offers a non-contact, low cost, and flexible method for rapid cell handling. As the DEP tweezers can grasp the embryo without the need for precise alignment, the overall time required to process a large number of embryos can be shortened.

Microchip with Single-Cell Impedance Measurements for Monitoring Osteogenic Differentiation of Mesenchymal Stem Cells under Electrical Stimulation.

Effective induction methods and in situ monitoring are essential for studying the mechanism of biological responses in stem cell differentiation. This article proposes an induction method incorporating electrical stimulation under an inhomogeneous field with single-cell impedance monitoring for studying osteogenic differentiation of mesenchymal stem cells (MSCs) using a microchip. The microchip contains an array of sextupole-electrode units for implementing a combination of controllable electrical stimulation and single-cell impedance measurements. MSCs are inducted to osteogenic differentiation under electrical stimulation using quadrupole electrodes and single-cell impedances are monitored in situ using a pair of microelectrodes at each unit center. The proposed microchip adopts an array design to monitor a number of MSCs in parallel, which improves measurement throughput and facilitates to carry out statistic tests. We perform osteogenic differentiation of MSCs on the microchip with and without electrical stimulation meanwhile monitoring single-cell impedance in real time for 21 days. The recorded impedance results show the detailed characteristic change of MSCs at the single-cell level during osteogenic differentiation, which demonstrates a significant difference between the conditions with and without electrical stimulation. The cell morphology and various staining analyses are also used to validate osteogenesis and correlate with the impedance expression. Correlation analysis of the impedance measurement, cell morphology, and various staining assays proves the great acceleration effect of the proposed electrical stimulation on osteogenic differentiation of MSCs. The proposed impedance method can monitor the dynamic process of cell development and study heterogeneity of stem cell differentiation at the single-cell level.

Numerical simulation of the electric field induced in a contactless dielectrophoretic quadrupole cell separator

PurposeThis study aims to propose a contactless and continuous dielectrophoretic cell-separation device using quadrupole electric field. To examine the separation performance, numerical simulations of the electric field in the cross-section of the glass capillary installed in the center of the quadrupole electrode were conducted.Design/methodology/approachTo estimate the magnitude of the dielectrophoretic force induced on cells, electrostatic analysis was performed by using a boundary-fitted coordinate system.Distribution of the electric field and gradient of the electric field square in the cross-section of the glass capillary were simulated for various ratios of radii of the glass capillary to the electrode rod.FindingsThe distribution of the electric field was found to have a cone-like profile about the center axis of the glass capillary with maximum at the internal surface of the glass capillary. The magnitude of the gradient of electric field square had similar distribution as that of the electric field, but had steeper slope near the internal surface of the glass capillary. The optimal values of the ratio of radii and the applied voltage were also estimated to achieve the local electric field strength suitable for cell separation.Originality/valueOne major advantage of the proposed device is simple and low fabrication cost, in addition to its contactless structure free from cell damage. Derived knowledge is instructive in achieving high-throughput cell separation without the use of devices of complex structure.

Quadrupoles for Remote Electrostimulation Incorporating Bipolar Cancellation.

Introduction: A method that utilizes nanosecond bipolar cancellation (BPC) near a quadrupole electrodes to suppress a biological response but cancels the distal BPC at the quadrupole center, i.e., cancellation of cancellation (CANCAN), may allow for a remote focused stimulation at the quadrupole center. Objectives: The primary object of this study was to outline the requirement of the CANCAN implementation and select an effective quadrupole configuration. Results: We have studied three quadrupole electrode configurations, a rod quadrupole, a plate quadrupole (Plate-Q), and a resistor quadrupole. The pulse shapes of electric fields include monophasic pulses, cancellation pulses, and additive pulses. The Plate-Q appears the best for CANCAN as it shows the highest percentage of cancellation pulses among all pulse shapes, allowing for the best spatial focus. Conclusion: For the region of interest characterized in the Plate-Q configuration, the maximum magnitude of bipolar field is twice as that of the unipolar field, which allows for the CANCAN demonstration that involves membrane electropermeabilization.

Peripherally Restricted Dual Cannabinoid Receptor Agonist Modifies Mitochondrial Signaling and Inhibits Atrial Electrical Remodeling in a Tachypaced Ex Vivo Rat Model

Atrial fibrillation (AF) leads to rate‐dependent changes, which progressively increase the risk for recurrence and persistence of the arrhythmia (collectively defined as atrial remodelling). Atrial effective refractory period (AERP) shortening and conduction velocity prolongation are hallmarks of atrial remodelling markedly promoting AF substrate. The molecular mechanisms underlying atrial remodelling are not fully elucidated and therapeutic strategies to reduce AF burden by preventing atrial remodelling are not yet available. Cannabinoid (CB) receptor ligands exert cardioprotective effects. We hypothesized that CB13, a peripherally restricted dual CB receptor agonist with limited brain penetration, would reduce atrial remodelling.Sprague Dawley (SD) rat hearts were excised and hung on a Langendorff set‐up, and supplemented with CB13 (1μM) or without (control) (paced and non‐paced). Coronary pressure of 60–80 mmHg was maintained. Electrophysiological (EP) parameters were measured by placing a mini‐hook platinum‐iridium quadrupole electrode on the right atrium (RA) for pacing and atrial recording (CB13 n=8; control n=8). RA were tachypaced for 90 min at double diastolic threshold and a cycle length of 5 ms higher than failed 1:1 atrial capture. S1S2 stimulation protocol was used to measure AERP, defined as the longest interval with failed 1:1 capture. The effects of CB13 on atrial refractoriness and AF substrate were assessed by analysis of high resolution electrogram recordings and protein expression via western blot.Post‐tachypacing EP recordings showed reduced AERP in control compared to pre‐tachypacing (54.38±3.05 vs. 44.75±3.67 ms; p<0.01). AERP post‐tachypacing in CB13‐treated hearts remained unchanged compared to pre‐tachypacing (55.25±3.46 vs. 55.50±2.67 ms; ns). Thus, CB13‐treatment resulted in preservation of AERP compared to control (103.6±9.2 vs. 82.3±4.4 % of baseline; p<0.05). Protein expression of PGC1α was significantly increased by CB13 compared to controls (paced and non‐paced). Upregulation of mitochondrial biogenesis may be related to increased phosphorylation of AMPKα at residue threonine 172 (compared to total AMPKα, p=0.12, CB13 vs. control paced). Furthermore, gap junction connexin 43 was significantly downregulated in paced controls vs. non‐paced controls, while CB13 remained upregulated (no significance vs. controls).CB13 exposure during tachypacing prevents AERP reduction and gap junction downregulation probably through mechanisms involving mitochondrial biogenesis. Thus, by inhibiting atrial remodeling CB13 and the subsequent activation of CB receptors may be a viable treatment strategy for AF.Support or Funding InformationThis work was supported by studentships from the Canadian Institutes of Health Research and Mitacs (D.L.)

Compensation of longitudinal entrance and exit gap field effects in RFQ’s of the 4-ROD type

Abstract In case of 4-Rod-type RFQ’s the quadrupole electrodes are excited by a series of coupled RF oscillators. As the contact planes between both electrode pairs differ, there remains an oscillating electric potential along the beam axis. This results in remarkably high longitudinal field components between the electrode ends and the RFQ tank end walls. In contrast, the electrodes of a 4-Vane RFQ are equally charged to ± | V 0 ∕ 2 | and only feature a quadrupole on-axis field. The entrance gap fields were investigated to serve as a longitudinal prebuncher instead of causing additional longitudinal emittance growth. The effects of the entrance gap field have been validated in beam dynamics simulations. The exit fields have to be taken into consideration for a calculation of the exact RFQ output energy.

Digital mass filter analysis in stability zones A and B.

Digitally driven mass filter analysis is an advancing field. This work presents a tutorial of digital waveforms, stability diagrams, and pseudopotential well plots. Experimental results on digitally driven mass filter analysis in stability zones A and B are also shown. This work explains duty cycle manipulation of the waveforms to axially trap and eject ions from linear quadrupoles and how to change and distort the stability diagrams to create mass filters and their effects on the pseudopotential well depth. It discusses the sensitivity and resolution that can be obtained and what limits these benchmarks. It reveals the advantages of mass filter operation without any added direct current potential between the quadrupole electrodes (a=0).

Development of an ion mobility spectrometer using radio-frequency electric field.

This paper describes the development of a new ion mobility spectrometer (IMS) using the radio-frequency (RF) electric field. The proposed IMS has high ion transmission efficiency. Seven connected IMS devices, in which the RF and DC electric fields are created by separate electrodes, are constructed. The ions are confined by the RF electric field and drifted by the DC electric field. The electrodes in each IMS device include short quadrupole electrodes and segmented vane electrodes. The uniform electric field in the IMS is verified by simulated results obtained using SIMION. To measure the exact value of reduced mobility K 0 at low Td (1 Td = 10-17 V cm2), two ion gates are installed in the IMS. By installing the ion gates at suitable positions for eliminating the effect of gas flow, the exact ion velocity through the IMS can be measured. The K 0 values of O2 + and C6H6 + ions are measured as a function of Td. In addition, the K 0 of CH3OCH2 + fragment ions is measured. These K 0 measurement results are consistent with previous results obtained using electrostatic drift tube apparatus. In summary, as our IMS can measure K 0 under low Td conditions, it can be used to better understand the structure of small molecular or fragment ions.

Development of a dielectrophoresis-assisted surface plasmon resonance fluorescence biosensor for detection of bacteria

To detect biological substances such as bacteria speedily and accurately, a dielectrophoresis-assisted surface plasmon resonance (SPR) fluorescence biosensor is being developed. Using Escherichia coli as a target organism, an appropriate voltage frequency to collect E. coli cells on indium tin oxide quadrupole electrodes by dielectrophoresis is analyzed. Then, E. coli is stained with 4′,6-diamidino-2-phenylindole (DAPI). To clearly detect fluorescence signals from DAPI-stained E. coli cells, the sensor is optimized so that we can excite SPR on Al electrodes by illuminating 405 nm photons. As a result, the number of fluorescence signals is increased on the electrodes by the application of a low-frequency voltage. This indicates that E. coli cells with a lower permittivity than the surrounding water are collected by negative dielectrophoresis onto the electrodes where the electric field strength is lowest.

Practical design approach for trapezoidal modulation of a radio-frequency quadrupole

Trapezoidal modulation of quadrupole electrodes offers additional benefits to the concept of a radio-frequency quadrupole (RFQ). Because of the significant increase of the effective shunt impedance, RFQs with trapezoidal modulation have a reduced interelectrode voltage or resonator length as compared to conventional RFQs with sinusoidal modulation. This feature is especially valuable for RFQs operating in cw mode, since it reduces the required rf power. We develop a detailed procedure for the design of RFQ electrodes with trapezoidal modulation. With our design procedure and by properly choosing the trapezoidal cell parameters, we can easily control the peak surface fields in the RFQ to the same level as for sinusoidal cell modulation. The procedure is applied to the design of the electrodes for the ReA3 RFQ at Michigan State University.

Admittance Scanning for Whole Column Detection.

Whole column detection (WCD) is as old as chromatography itself. WCD requires an ability to interrogate column contents from the outside. Other than the obvious case of optical detection through a transparent column, admittance (often termed contactless conductance) measurements can also sense changes in the column contents (especially ionic content) from the outside without galvanic contact with the solution. We propose here electromechanically scanned admittance imaging and apply this to open tubular (OT) chromatography. The detector scans across the column; the length resolution depends on the scanning velocity and the data acquisition frequency, ultimately limited by the physical step resolution (40 μm in the present setup). Precision equal to this step resolution was observed for locating an interface between two immiscible liquids inside a 21 μm capillary. Mechanically, the maximum scanning speed was 100 mm/s, but at 1 kHz sampling rate and a time constant of 25 ms, the highest practical scan speed (no peak distortion) was 28 mm/s. At scanning speeds of 0, 4, and 28 mm/s, the S/N for 180 pL (zone length of 1.9 mm in a 11 μm i.d. column) of 500 μM KCl injected into water was 6450, 3850, and 1500, respectively. To facilitate constant and reproducible contact with the column regardless of minor variations in outer diameter, a double quadrupole electrode system was developed. Columns of significant length (>1 m) can be readily scanned. We demonstrate its applicability with both OT and commercial packed columns and explore uniformity of retention along a column, increasing S/N by stopped-flow repeat scans, etc. as unique applications.

Alignment of Ag nanoparticles by an external electric field proposed for metamaterial applications

The ability to control the DNG properties of metamaterials in the microwave range makes possible many new constructions and practical applications. In addition, since the fabrication of ordered metamaterials with metallic structure arrays is habitually complex, the mass production of these structures is being prevented. For this purpose, a control on spatial structure of random metamaterial at the nanoscale dimensions was performed. Here, we demonstrate the alignment of dispersed Ag nanoparticles subjected to external AC electric field created by quadrupole electrode in refluxing condition at 180 °C. External electric field allows for alignment of the well-dispersed Ag nanoparticles with long-range orientational order. The effects of the AC electric field on the DNG region that obtained in the microwave range can be accompanied with a control on optical performances, even in the plasmonic field for future studies. This achievement provides a new way toward the development of random metamaterial devices.

Electrophoretic and dielectrophoretic trapping of molecular objects in planar quadrupole electrode configuration at room temperature

Recent rapid development of single molecule analysis highly demands the trapping of molecular objects. In this study, we present how stability and random motions vary depending on dielectrophoretic and electrophoretic descriptions for a molecular object in planar quadrupole electrical traps. The object is modeled as a molecular dipole surrounded by a cavity (“molecular dipole cavity”) to introduce the solvent accessible surface of a solute molecule, and the instantaneous electrophoretic and dielectrophoretic force formulations are employed for the rigorous estimation of the deterministic stability which is identified by the equation of motion without random impulse and the random fluctuation that is compared with the trap size for the identification of random stability. The deterministic stability is analyzed with the universal Mathieu equation based theories for Paul trap while the random fluctuation is computed by averaging the multiple trajectories with different random seeds. The results show that the deterministic stabilities are quite similar in dielectrophoretic and electrophoretic descriptions, whereas the random fluctuation is significantly influenced by the type of force description. This study is expected to provide fundamental information in designing a quadrupole trap for molecular objects which is essential in single molecule analysis.