Transparent, patterned graphene oxide films with tunable electrical conductivity using thermal, chemical, and photoreduction techniques for lab-on-a-chip applications.

This work demonstrates the fabrication of electrically tunable films of graphene oxide (GO). GO thin films were deposited and micropatterned on a cyclic olefin copolymer (COC) substrate using a plasma-enhanced liftoff technique. This article discusses thermal, chemical, and photoreduction methods for controlling the electrical conductivity of the patterned film. The patterned graphene oxide films were used to manipulate cells after embedding them in a microfluidic channel. Cells were manipulated under dielectrophoresis (DEP) using patterned reduced graphene oxide (rGO) films with varying electrical conductivities. The non-uniform electric field required for DEP was created either by arranging and shaping a set of electrodes (eDEP) or by simply implementing low conductivity rGO as an insulator between two metal electrodes (iDEP).

Cases from a Community Hospital JCHIMP Series #1: 55-Year-Old Male with Acute PE Who Developed Persistent Epistaxis.

This is the first in a new series of case reports that will present real scenarios from our community hospital. The cases are chosen to highlight clinical dilemmas and offer review and perspective on what is currently known about the topic. We present the case of a 55-year-old Caucasian male who presented to the emergency department of our community hospital for worsening dyspnea. Evaluation in the Emergency department revealed a diagnosis of extensive pulmonary emboli in the pulmonary vasculature. The patient was admitted to the ICU. A clinical decision was made to initiate treatment with low-dose tissue plasminogen activator (tpa) followed by intravenous heparin infusion. Several hours later the patient developed significant epistaxis. A decision was made to stop the heparin infusion. Later that day, the patient had abrupt clinical deterioration with subsequent cardiac arrest and did not recover. We discuss the classification and treatment of acute pulmonary embolism, the management of epistaxis in an anticoagulated patient, and the clinical conundrum of balancing active bleeding in patient requiring anticoagulation.

Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest.

The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2-4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs.

Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147-150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.

Randomised trial of epinephrine dose and flush volume in term newborn lambs.

OBJECTIVES: Neonatal resuscitation guidelines recommend 0.5-1 mL saline flush following 0.01-0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest. DESIGN: Forty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored. RESULTS: Ten lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush. CONCLUSIONS: 0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

Glucose Levels during the First 24 Hours following Perinatal Hypoxia.

OBJECTIVE: Hypoglycemia is a significant risk factor for perinatal brain injury and adverse outcomes, particularly in infants requiring resuscitation following hypoxic ischemic (HI) insult. We aimed to study blood glucose (BG) levels in physiologically stressed infants in the presence or absence of epinephrine (Epi) administration at resuscitation in the first 24 hours after birth. STUDY DESIGN: A retrospective chart review of all infants with heart rate (HR) < 100/min at 1 minute requiring positive pressure ventilation (PPV) at birth was performed. Infants were classified into two groups as follows: (1) PPV group: infants' HR improved with PPV only at resuscitation, and Epi group: infants received Epi at resuscitation for persistent bradycardia. Serial measurements of BG levels collected and glucose infusion rate (GIR) calculated at 24 hours. RESULTS: By design, infants in the Epi group had lower cord pH and higher base deficit. BG was significantly lower overtime in premature infants ≤32 weeks of gestation in the Epi group. The BG was markedly higher in near-term and term infants in the Epi group compared with the PPV group. Hypoglycemia was more common despite administration of higher GIR in premature infants ≤32 weeks of gestation. CONCLUSION: In the presence of physiological stress, premature infants are more at risk for hypoglycemia than term infants.

Dielectrophoretic Microfluidic Device for Separating Microparticles Based on Size with Sub-Micron Resolution.

This article details the mathematical model of a microfluidic device aimed at separating any binary heterogeneous sample of microparticles into two homogeneous samples based on size with sub-micron resolution. The device consists of two sections, where the upstream section is dedicated to focusing of microparticles, while the downstream section is dedicated to separation of the focused stream of microparticles into two samples based on size. Each section has multiple planar electrodes of finite size protruding into the microchannel from the top and bottom of each sidewall; each top electrode aligns with a bottom electrode and they form a pair leading to multiple pairs of electrodes on each side. The focusing section subjects all microparticles to repulsive dielectrophoretic force, from each set of the electrodes, to focus them next to one of the sidewalls. This separation section pushes the big microparticles toward the interior, away from the wall, of the microchannel using repulsive dielectrophoretic force, while the small microparticles move unaffected to achieve the desired degree of separation. The operating frequency of the set of electrodes in the separation section is maintained equal to the cross-over frequency of the small microparticles. The working of the device is demonstrated by separating a heterogeneous mixture consisting of polystyrene microparticles of different size (radii of 2 and 2.25 µm) into two homogeneous samples. The mathematical model is used for parametric study, and the performance is quantified in terms of separation efficiency and separation purity; the parameters considered include applied electric voltages, electrode dimensions, outlet widths, number of electrodes, and volumetric flowrate. The separation efficiencies and separation purities for both microparticles are 100% for low volumetric flow rates, a large number of electrode pairs, large electrode dimensions, and high differences between voltages in both sections.

Optimal Oxygen Targets in Term Lambs with Meconium Aspiration Syndrome and Pulmonary Hypertension.

Optimal oxygen saturation as measured by pulse oximetry (SpO2) in neonatal lung injury, such as meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of newborn (PPHN), is not known. Our goal was to determine the SpO2 range in lambs with MAS and PPHN that results in the highest brain oxygen delivery (bDO2) and pulmonary blood flow (Qp) and the lowest pulmonary vascular resistance and oxidative stress. Meconium was instilled into endotracheal tubes in 25 near-term gestation lambs, and the umbilical cord was occluded to induce asphyxia and gasping, causing MAS and PPHN. Lambs were randomized into four groups and ventilated for 6 hours with fixed fraction of inspired oxygen (FiO2) = 1.0 irrespective of SpO2, and three groups had FiO2 titrated to keep preductal SpO2 between 85% and 89%, 90% and 94%, and 95% and 99%, respectively. Tissues were collected to measure nitric oxide synthase activity, 3-nitrotyrosine, and 8-isoprostanes. Throughout the 6-hour exposure period, lambs in the 95-99% SpO2 target group had the highest Qp, lowest pulmonary vascular resistance, and highest bDO2 but were exposed to higher FiO2 (0.5 ± 0.21 vs. 0.29 ± 0.17) with higher lung 3-nitrotyrosine (0.67 [interquartile range (IQR), 0.43-0.73] ng/mcg protein vs. 0.1 [IQR, 0.09-0.2] ng/mcg protein) and lower lung nitric oxide synthase activity (196 [IQR, 192-201] mMol nitrite/mg protein vs. 270 [IQR, 227-280] mMol nitrite/mg protein) compared with the 90-94% target group. Brain 3-nitrotyrosine was lower in the 85-89% target group, and brain/lung 8-isoprostane levels were not significantly different. In term lambs with MAS and PPHN, Qp and bDO2 through the first 6 hours are higher with target SpO2 in the 95-99% range. However, the 90-94% target range is associated with significantly lower FiO2 and lung oxidative stress. Clinical trials comparing the 90-94% versus the 95-99% SpO2 target range in term infants with PPHN are warranted.

Modeling a Dielectrophoretic Microfluidic Device with Vertical Interdigitated Transducer Electrodes for Separation of Microparticles Based on Size.

This article conceptualizes and mathematically models a dielectrophoretic microfluidic device with two sets of interdigitated transducer vertical electrodes for separation of a binary heterogeneous mixture of particles based on size; each set of electrodes is located on the sidewalls and independently controllable. To achieve separation in the proposed microfluidic device, the small microparticles are subjected to positive dielectrophoresis and the big microparticles do not experience dielectrophoresis. The mathematical model consists of equations describing the motion of each microparticle, fluid flow profile, and electric voltage and field profiles, and they are solved numerically. The equations of motion take into account the influence of phenomena, such as inertia, drag, dielectrophoresis, gravity, and buoyancy. The model is used for a parametric study to understand the influence of parameters on the performance of the microfluidic device. The parameters studied include applied electric voltages, electrode dimensions, volumetric flow rate, and number of electrodes. The separation efficiency of the big and small microparticles is found to be independent of and dependent on all parameters, respectively. On the other hand, the separation purity of the big and small microparticles is found to be dependent on and independent of all parameters, respectively. The mathematical model is useful in designing the proposed microfluidic device with the desired level of separation efficiency and separation purity.

Simulation of a microfluidic device employing dielectrophoresis for liquid biopsy.

This article details simulation based study of cell separation in a dielectrophoretic microfluidic device. The device consists of a narrow microchannel connected to a wide microchannel with several finite sized planar interdigitated transducer electrodes protruding into the narrow microchannel from one of its sidewalls. In the narrow microchannel, the circulating tumor cells are subjected to positive dielectrophoresis while the regular cells are subjected to negative dielectrophoresis to achieve separation and as all cells move in to the wide microchannel, the physical distance between the two types of cells increases thereby making their collection from the device easier. Equations describing motion, fluid field, electric field, and electric potential form the mathematical model and accounts for forces related to inertia, drag, and dielectrophoresis. Applied electric potential, electrode/gap length, and tumor cell diameter have a positive effect on the performance metrics while velocity of the medium and microchannel width have negative effect on the performance metrics. The model presented in this article is beneficial in realizing liquid biopsy with the desired performance metrics using the proposed microfluidic device.

Nozzle-Shaped Electrode Configuration for Dielectrophoretic 3D-Focusing of Microparticles.

: An experimentally validated mathematical model of a microfluidic device with nozzle-shaped electrode configuration for realizing dielectrophoresis based 3D-focusing is presented in the article. Two right-triangle shaped electrodes on the top and bottom surfaces make up the nozzle-shaped electrode configuration. The mathematical model consists of equations describing the motion of microparticles as well as profiles of electric potential, electric field, and fluid flow inside the microchannel. The influence of forces associated with inertia, gravity, drag, virtual mass, dielectrophoresis, and buoyancy are taken into account in the model. The performance of the microfluidic device is quantified in terms of horizontal and vertical focusing parameters. The influence of operating parameters, such as applied electric potential and volumetric flow rate, as well as geometric parameters, such as electrode dimensions and microchannel dimensions, are analyzed using the model. The performance of the microfluidic device enhances with an increase in applied electric potential and reduction in volumetric flow rate. Additionally, the performance of the microfluidic device improves with reduction in microchannel height and increase in microparticle radius while degrading with increase in reduction in electrode length and width. The model is of great benefit as it allows for generating working designs of the proposed microfluidic device with the desired performance metrics.

Dielectrophoresis Multipath Focusing of Microparticles through Perforated Electrodes in Microfluidic Channels.

This paper presents focusing of microparticles in multiple paths within the direction of the flow using dielectrophoresis. The focusing of microparticles is realized through partially perforated electrodes within the microchannel. A continuous electrode on the top surface of the microchannel is considered, while the bottom side is made of a circular meshed perforated electrode. For the mathematical model of this microfluidic channel, inertia, buoyancy, drag and dielectrophoretic forces are brought up in the motion equation of the microparticles. The dielectrophoretic force is accounted for through a finite element discretization taking into account the perforated 3D geometry within the microchannel. An ordinary differential equation is solved to track the trajectories of the microparticles. For the case of continuous electrodes using the same mathematical model, the numerical simulation shows a very good agreement with the experiments, and this confirms the validation of focusing of microparticles within the proposed perforated electrode microchannel. Microparticles of silicon dioxide and polystyrene are used for this analysis. Their initial positions and radius, the Reynolds number, and the radius of the pore in perforated electrodes mainly conduct microparticles trajectories. Moreover, the radius of the pore of perforated electrode is the dominant factor in the steady state levitation height.

Continued Enteral Feeding Is Beneficial in Hypoglycemic Infants Admitted to Intensive Care for Parenteral Dextrose Therapy.

There is variability in practice among care providers on feeding infants admitted with neonatal hypoglycemia (NH) for parenteral dextrose. We compared clinical outcomes in infants who were fed (NH-Fed) and hypoglycemic infants who were kept nothing per os (NPO) (NH-NPO) at the time of initiation of intravenous (IV) dextrose. We performed a retrospective review of all newborn infants admitted to the neonatal intensive care unit with NH for IV dextrose. Infants were grouped as per the feeding approach at initiation of IV dextrose: NH-Fed or NH-NPO infants. We found that infants in the NH-Fed group had lower maximum glucose infusion rate, less duration of glucose infusion therapy compared with the NH-NPO group, and significantly less number of days of hospital stay compared with the NH-NPO group (5.87 ± 1.4 days vs 4.9 ± 1.4 days, P < .006). In conclusion, feeding infants with hypoglycemia who require IV dextrose offers tangible benefits of shorter duration of parenteral dextrose and shorter length of hospitalization.

Oxygenation and Hemodynamics during Chest Compressions in a Lamb Model of Perinatal Asphyxia Induced Cardiac Arrest.

The current guidelines recommend the use of 100% O2 during resuscitation of a neonate requiring chest compressions (CC). Studies comparing 21% and 100% O2 during CC were conducted in postnatal models and have not shown a difference in incidence or timing of return of spontaneous circulation (ROSC). The objective of this study is to evaluate systemic oxygenation and oxygen delivery to the brain during CC in an ovine model of perinatal asphyxial arrest induced by umbilical cord occlusion. Pulseless cardiac arrest was induced by umbilical cord occlusion in 22 lambs. After 5 min of asystole, lambs were resuscitated with 21% O2 as per Neonatal Resuscitation Program (NRP) guidelines. At the onset of CC, inspired O2 was either increased to 100% O2 (n = 25) or continued at 21% (n = 9). Lambs were ventilated for 30 min post ROSC and FiO2 was gradually titrated to achieve preductal SpO2 of 85-95%. All lambs achieved ROSC. During CC, PaO2 was 21.6 ± 1.6 mm Hg with 21% and 23.9 ± 6.8 mm Hg with 100% O2 (p = 0.16). Carotid flow was significantly lower during CC (1.2 ± 1.6 mL/kg/min in 21% and 3.2 ± 3.4 mL/kg/min in 100% oxygen) compared to baseline fetal levels (27 ± 9 mL/kg/min). Oxygen delivery to the brain was 0.05 ± 0.06 mL/kg/min in the 21% group and 0.11 ± 0.09 mL/kg/min in the 100% group and was significantly lower than fetal levels (2.1 ± 0.3 mL/kg/min). Immediately after ROSC, lambs ventilated with 100% O2 had higher PaO2 and pulmonary flow. It was concluded that carotid blood flow, systemic PaO2, and oxygen delivery to the brain are very low during chest compressions for cardiac arrest irrespective of 21% or 100% inspired oxygen use during resuscitation.

Bioavailability of endotracheal epinephrine in an ovine model of neonatal resuscitation.

BACKGROUND: Distressed infants in the delivery room and those that have completed postnatal transition are both resuscitated according to established neonatal resuscitation guidelines, often with endotracheal (ET) epinephrine at the same dose. We hypothesized that ET epinephrine would have higher bioavailability in a post-transitional compared to transitioning newborn model due to absence of fetal lung liquid and intra-cardiac shunts. METHODS: 15 term fetal (transitioning newborn) and 6 postnatal lambs were asphyxiated by umbilical cord and ET tube occlusion respectively. Lambs were resuscitated after 5 min of asystole. ET epinephrine (0.1 mg/kg) was administered after 1 min of positive pressure ventilation (PPV) and chest compressions, and repeated 3 min later, followed by intravenous (IV) epinephrine (0.03 mg/kg) every 3 min until return of spontaneous circulation (ROSC). Serial plasma epinephrine concentrations were measured. RESULTS: Peak plasma epinephrine concentrations were lower in transitioning newborns as compared to postnatal lambs: after a single ET dose (145.36 ±â€¯135.5 ng/ml vs 553.54 ±â€¯215 ng/ml, p < 0.01) and after two ET doses (443 ±â€¯192.49 ng/ml vs 1406 ±â€¯420.8 ng/ml, p < 0.01). The rates of ROSC with a single ET dose were similar in both groups (40% vs 50% in newborn and postnatal respectively, p > 0.99). There was a higher incidence of post-ROSC tachycardia and increased carotid blood flow in the postnatal group. CONCLUSIONS: In the postnatal period, ET epinephrine at currently recommended doses resulted in higher peak epinephrine concentrations, post-ROSC tachycardia and cerebral reperfusion without significant differences in incidence of ROSC. Further studies evaluating the optimal dose of ET epinephrine during the postnatal period are warranted.

Physical examination score predicts need for surgery in neonates with necrotizing enterocolitis.

OBJECTIVE: To evaluate the utility of a standardized physical exam score (PE-NEC) in predicting need for surgery or death in neonates with necrotizing enterocolitis (NEC). METHODS: This prospective, multicenter, observational study was conducted from 3/1/14 to 2/29/16 with three regional perinatal centers in upstate New York. Infants with NEC Bell's Stage ≥ 2 had physical exams and laboratory data recorded at 12-24 h intervals for 48 h following diagnosis. PE-NEC score was comprised of seven components: bowel sounds, capillary refill time, abdominal wall erythema, girth, discoloration, induration, and tenderness. Surgical timing was determined by surgeons blinded to the PE-NEC score. Optimal sensitivity and specificity of PE-NEC score for surgery/death (primary outcome) was determined by receiver operating characteristic curve analysis. RESULTS: Of 100 infants with NEC, 5 had pneumoperitoneum at diagnosis and were excluded yielding 95 for analyses. Of those, 35 infants experienced the primary outcome: 3 died from NEC prior to surgery and 32 had surgery (30 laparotomies, 2 drains). The PE-NEC score was found to be sensitive and specific for need for surgery/death (AUC = 0.89, 95% CI 0.82-0.97); a score of ≥3 had a sensitivity of 0.88 (95% CI 0.72-0.97), specificity of 0.81 (95% CI 0.69-0.90). All components of the PE-NEC score were more likely to be present among infants with surgical NEC or who died. CONCLUSION: PE-NEC score is sensitive and specific in predicting need for surgery in infants with NEC and should be validated as a clinical decision-making tool.

Dielectrophoresis-based 3D-focusing of microscale entities in microfluidic devices.

This article presents a validated mathematical model of a dielectrophoresis (DEP)-based microfluidic device capable of 3D-focusing microscale entities at any lateral location inside the microchannel. The microfluidic device employs planar, independently controllable, interdigitated transducer (IDT) electrodes on either side of the microchannel. The developed model is used for understanding the influence of different geometric and operating parameters on 3D focusing, and it comprises of motion equation, Navier-Stokes equation, continuity equation, and electric potential equation (Laplace equation). The model accounts for forces associated with inertia, gravity, buoyancy, virtual mass, drag, and DEP. The model is solved using finite difference method. The findings of the study indicate that the 3D focusing possible with the proposed microfluidic device is independent of microscale entity's size and initial position, microchannel height, and volumetric flow rate. In contrast, 3D focusing achievable with the microfluidic device is dependent on the applied electric potential, protrusion width of electrodes, and width of electrode/gap. Additionally, the lateral position of 3D focused can be controlled by varying the applied electric potential. The advantage of the proposed microfluidic device is that it is simple to construct while capable of achieving 3D focusing at any lateral location inside the microchannel.

Microfluidics Based Magnetophoresis: A Review.

Magnetophoresis, the manipulation of trajectory of micro-scale entities using magnetic forces, as employed in microfluidic devices is reviewed at length in this article. Magnetophoresis has recently garnered significant interest due to its simplicity, in terms of implementation, as well as cost-effectiveness while being efficient and biocompatible. Theory associated with magnetophoresis is illustrated in this review along with different sources for creating magnetic field gradient commonly employed in microfluidic devices. Additionally, this article reviews the state-of-the-art of magnetophoresis based microfluidic devices, where positive- and negative-magnetophoresis are utilized for manipulation of micro-scale entities (cells and microparticles), employed for operations such as trapping, focusing, separation, and switching of microparticles and cells. The article concludes with a brief outlook of the field of magnetophoresis.

Lateral fluid flow fractionation using dielectrophoresis (LFFF-DEP) for size-independent, label-free isolation of circulating tumor cells.

This short communication introduces a continuous-flow, dielectrophoresis-based lateral fluid flow fractionation microdevice for detection/isolation of circulating tumor cells in the presence of other haematological cells. The device utilizes two sets of planar interdigitated transducer electrodes micropatterned on top of a glass wafer using standard microfabrication techniques. A microchannel with a single inlet and two outlets, realized in polydimethylsiloxane, is bonded on the glass substrate. The two sets of electrodes slightly protrude into the microchannel. Both of the electrode sets are energized with signals at different frequencies and different operating voltages ensuring that the cancer cells experience positive dielectrophoretic force from one set of the electrodes and negative dielectrophoretic force from the other array. Normal cells experience unequal negative dielectrophoretic forces from opposing sets of electrodes. The resultant dielectrophoretic forces on cancer and normal cells push them to flow towards their designed outlets. Successful isolation of green fluorescent protein-labelled MDA-MB-231 breast cancer cells from regular blood cells, both suspended in a sucrose/dextrose medium, is reported in this work.