WE-EF-210-07: Development of a Minimally Invasive Photo Acoustic Imaging System for Early Prostate Cancer Detection.
2015; 42 (6): 3684-?
In-vitro bipolar nano- and microsecond electro-pulse bursts for irreversible electroporation therapies
2014; 100: 69-79
Simultaneous electrokinetic flow and dielectrophoretic trapping using perpendicular static and dynamic electric fields
MICROFLUIDICS AND NANOFLUIDICS
2013; 15 (5): 599-609
Investigating dielectric properties of different stages of syngeneic murine ovarian cancer cells
2013; 7 (1)
The objective of this work is to design, implement and characterize a catheter-based ultrasound/photoacoustic imaging probe for early-diagnosis of prostate cancer and to aid in image-guided radiation therapy.The need to image across 6-10cm of tissue to image the whole prostate gland limits the resolution achievable with a transrectal ultrasound approach. In contrast, the urethra bisects the prostate gland, providing a minimally invasive pathway for deploying a high resolution ultrasound transducer. Utilizing a high-frequency (20MHz) ultrasound/photoacoustic probe, high-resolution structural and molecular imaging of the prostate tissue is possible. A custom 3D printed probe containing a high-frequency single-element ultrasound transducer is utilized. The diameter of the probe is designed to fit inside a Foley catheter and the probe is rotated around the central axis to achieve a circular B-scan. A custom ultrasound amplifier and receiver was set up to trigger the ultrasound pulse transmission and record the reflected signal. The reconstructed images were compared to images generated by traditional 5 MHz ultrasound transducers.The preliminary results using the high-frequency ultrasound probe show that it is possible to resolve finely detailed information in a prostate tissue phantom that was not achievable with previous low-frequency ultrasound systems. Preliminary ultrasound imaging was performed on tissue mimicking phantom and sensitivity and signal-to-noise ratio of the catheter was measured.In order to achieve non-invasive, high-resolution, structural and molecular imaging for early-diagnosis and image-guided radiation therapy of the prostate tissue, a transurethral catheter was designed. Structural/molecular imaging using ultrasound/photoacoustic of the prostate tissue will allow for localization of hyper vascularized areas for early-stage prostate cancer diagnosis.
View details for DOI 10.1118/1.4926030
View details for PubMedID 26129328
Multilayer contactless dielectrophoresis: Theoretical considerations
2012; 33 (13): 1938-1946
In this study, the electrical properties of four different stages of mouse ovarian surface epithelial (MOSE) cells were investigated using contactless dielectrophoresis (cDEP). This study expands the work from our previous report describing for the first time the crossover frequency and cell specific membrane capacitance of different stages of cancer cells that are derived from the same cell line. The specific membrane capacitance increased as the stage of malignancy advanced from 15.39 ± 1.54 mF m(-2) for a non-malignant benign stage to 26.42 ± 1.22 mF m(-2) for the most aggressive stage. These differences could be the result of morphological variations due to changes in the cytoskeleton structure, specifically the decrease of the level of actin filaments in the cytoskeleton structure of the transformed MOSE cells. Studying the electrical properties of MOSE cells provides important information as a first step to develop cancer-treatment techniques which could partially reverse the cytoskeleton disorganization of malignant cells to a morphology more similar to that of benign cells.
View details for DOI 10.1063/1.4788921
View details for Web of Science ID 000315597100015
View details for PubMedID 24403991
Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis
2012; 6 (2)
Dielectrophoresis (DEP), the movement of dielectric particles in a nonuniform electric field, is of particular interest due to its ability to manipulate particles based on their unique electrical properties. Contactless DEP (cDEP) is an extension of traditional and insulator-based DEP topologies. The devices consist of a sample channel and fluid electrode channels filled with a highly conductive media. A thin insulating membrane between the sample channel and the fluid electrode channels serves to isolate the sample from direct contact with metal electrodes. Here we investigate, for the first time, the properties of multilayer devices in which the sample and electrode channels occupy distinct layers. Simulations are conducted using commercially available finite element software and a less computationally demanding numerical approximation is presented and validated. We show that devices can be created that achieve a similar level of electrical performance to other cDEP devices presented in the literature while increasing fluid throughput. We conclude, based on these models, that the ultimate limiting factors in device performance resides in breakdown voltage of the barrier material and the ability to generate high-voltage, high-frequency signals. Finally, we demonstrate trapping of MDA-MB-231 breast cancer cells in a prototype device at a flow rate of 1.0 mL/h when 250 V(RMS) at 600 kHz is applied.
View details for DOI 10.1002/elps.201100677
View details for Web of Science ID 000306404700004
View details for PubMedID 22806458
Modeling and development of a low frequency contactless dielectrophoresis (cDEP) platform to sort cancer cells from dilute whole blood samples
BIOSENSORS & BIOELECTRONICS
2011; 30 (1): 13-20
Ovarian cancer is the leading cause of death from gynecological malignancies in women. The primary challenge is the detection of the cancer at an early stage, since this drastically increases the survival rate. In this study we investigated the dielectrophoretic responses of progressive stages of mouse ovarian surface epithelial (MOSE) cells, as well as mouse fibroblast and macrophage cell lines, utilizing contactless dielectrophoresis (cDEP). cDEP is a relatively new cell manipulation technique that has addressed some of the challenges of conventional dielectrophoretic methods. To evaluate our microfluidic device performance, we computationally studied the effects of altering various geometrical parameters, such as the size and arrangement of insulating structures, on dielectrophoretic and drag forces. We found that the trapping voltage of MOSE cells increases as the cells progress from a non-tumorigenic, benign cell to a tumorigenic, malignant phenotype. Additionally, all MOSE cells display unique behavior compared to fibroblasts and macrophages, representing normal and inflammatory cells found in the peritoneal fluid. Based on these findings, we predict that cDEP can be utilized for isolation of ovarian cancer cells from peritoneal fluid as an early cancer detection tool.
View details for DOI 10.1063/1.3699973
View details for Web of Science ID 000305839800015
View details for PubMedID 22536308
High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction
BIOMEDICAL ENGINEERING ONLINE
Contactless dielectrophoresis (cDEP) devices are a new adaptation of dielectrophoresis in which fluid electrodes, isolated from the main microfluidic channel by a thin membrane, provide the electric field gradients necessary to manipulate cells. This work presents a continuous sorting device which is the first cDEP design capable of exploiting the Clausius-Mossotti factor at frequencies where it is both positive and negative for mammalian cells. Experimental devices are fabricated using a cost effective technique which can achieve 50 μm feature sizes and does not require the use of a cleanroom or specialized equipment. An analytical model is developed to evaluate cDEP devices as a network of parallel resistor-capacitor pairs. Two theoretical devices are presented and evaluated using finite element methods to demonstrate the effect of geometry on the development of electric field gradients across a wide frequency spectrum. Finally, we present an experimental device capable of continuously sorting human leukemia cells from dilute blood samples. This is the first cDEP device designed to operate below 100 kHz resulting in successful manipulation of human leukemia cells, while in the background red blood cells are unaffected.
View details for DOI 10.1016/j.bios.2011.07.048
View details for Web of Science ID 000297610200002
View details for PubMedID 21944186
Contactless dielectrophoretic spectroscopy: Examination of the dielectric properties of cells found in blood
2011; 32 (22): 3164-3171
Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.
View details for DOI 10.1186/1475-925X-10-102
View details for Web of Science ID 000299074900001
View details for PubMedID 22104372
Selective concentration of human cancer cells using contactless dielectrophoresis
2011; 32 (18): 2523-2529
The use of non-invasive methods to detect and enrich circulating tumor cells (CTCs) independent of their genotype is critical for early diagnostic and treatment purposes. The key to using CTCs as predictive clinical biomarkers is their separation and enrichment. This work presents the use of a contactless dielectrophoresis (cDEP) device to investigate the frequency response of cells and calculate their area-specific membrane capacitance. This is the first demonstration of a cDEP device which is capable of operating between 10 and 100 kHz. Positive and negative dielectrophoretic responses were observed in red blood cells, macrophages, breast cancer, and leukemia cells. The area-specific membrane capacitances of MDA-MB231, THP-1 and PC1 cells were determined to be 0.01518 ± 0.0013, 0.01719 ± 0.0020, 0.01275 ± 0.0018 (F/m(2)), respectively. By first establishing the dielectrophoretic responses of cancerous cells within this cDEP device, conditions to detect and enrich tumor cells from mixtures with non-transformed cells can be determined providing further information to develop methods to isolate these rare cells.
View details for DOI 10.1002/elps.201100351
View details for Web of Science ID 000298098700012
View details for PubMedID 22102497
Theoretical Considerations of Tissue Electroporation With High-Frequency Bipolar Pulses
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2011; 58 (5): 1474-1482
This work is the first to demonstrate the ability of contactless dielectrophoresis (cDEP) to isolate target cell species from a heterogeneous sample of live cells. Since all cell types have a unique molecular composition, it is expected that their dielectrophoretic (DEP) properties are also unique. cDEP is a technique developed to improve upon traditional and insulator-based DEP devices by replacing embedded metal electrodes with fluid electrode channels positioned alongside desired trapping locations. Through the placement of the fluid electrode channels and the removal of contact between the electrodes and the sample fluid, cDEP mitigates issues associated with sample/electrode contact. MCF10A, MCF7, and MDA-MB-231 human breast cells were used to represent early, intermediate, and late-staged breast cancer, respectively. Trapping frequency responses of each cell type were distinct, with the largest difference between the cells found at 20 and 30 V. MDA-MB-231 cells were successfully isolated from a population containing MCF10A and MCF7 cells at 30 V and 164 kHz. The ability to selectively concentrate cells is the key to development of biological applications using DEP. The isolation of these cells could provide a workbench for clinicians to detect transformed cells at their earliest stage, screen drug therapies prior to patient treatment, increasing the probability of success, and eliminate unsuccessful treatment options.
View details for DOI 10.1002/elps.201100081
View details for Web of Science ID 000295232000013
View details for PubMedID 21922494
Towards the creation of decellularized organ constructs using irreversible electroporation and active mechanical perfusion
BIOMEDICAL ENGINEERING ONLINE
This study introduces the use of high-frequency pulsed electric fields for tissue electroporation. Through the development of finite element models and the use of analytical techniques, electroporation with rectangular, bipolar pulses is investigated. The electric field and temperature distribution along with the associated transmembrane potential development are considered in a heterogeneous skin fold geometry. Results indicate that switching polarity on the nanosecond scale near the charging time of plasma membranes can greatly improve treatment outcomes in heterogeneous tissues. Specifically, high-frequency fields ranging from 500 kHz to 1 MHz are best suited to penetrate epithelial layers without inducing significant Joule heating, and cause electroporation in underlying cells.
View details for DOI 10.1109/TBME.2010.2102021
View details for Web of Science ID 000289807300039
View details for PubMedID 21189230
Electromagnetically Controlled Biological Assembly of Aligned Bacterial Cellulose Nanofibers
ANNALS OF BIOMEDICAL ENGINEERING
2010; 38 (8): 2475-2484
Despite advances in transplant surgery and general medicine, the number of patients awaiting transplant organs continues to grow, while the supply of organs does not. This work outlines a method of organ decellularization using non-thermal irreversible electroporation (N-TIRE) which, in combination with reseeding, may help supplement the supply of organs for transplant.In our study, brief but intense electric pulses were applied to porcine livers while under active low temperature cardio-emulation perfusion. Histological analysis and lesion measurements were used to determine the effects of the pulses in decellularizing the livers as a first step towards the development of extracellular scaffolds that may be used with stem cell reseeding. A dynamic conductivity numerical model was developed to simulate the treatment parameters used and determine an irreversible electroporation threshold.Ninety-nine individual 1000 V/cm 100-μs square pulses with repetition rates between 0.25 and 4 Hz were found to produce a lesion within 24 hours post-treatment. The livers maintained intact bile ducts and vascular structures while demonstrating hepatocytic cord disruption and cell delamination from cord basal laminae after 24 hours of perfusion. A numerical model found an electric field threshold of 423 V/cm under specific experimental conditions, which may be used in the future to plan treatments for the decellularization of entire organs. Analysis of the pulse repetition rate shows that the largest treated area and the lowest interstitial density score was achieved for a pulse frequency of 1 Hz. After 24 hours of perfusion, a maximum density score reduction of 58.5 percent had been achieved.This method is the first effort towards creating decellularized tissue scaffolds that could be used for organ transplantation using N-TIRE. In addition, it provides a versatile platform to study the effects of pulse parameters such as pulse length, repetition rate, and field strength on whole organ structures.
View details for DOI 10.1186/1475-925X-9-83
View details for Web of Science ID 000286045700001
View details for PubMedID 21143979
Selective isolation of live/dead cells using contactless dielectrophoresis (cDEP)
LAB ON A CHIP
2010; 10 (4): 438-445
We have developed a new biofabrication process in which the precise control of bacterial motion is used to fabricate customizable networks of cellulose nanofibrils. This article describes how the motion of Acetobacter xylinum can be controlled by electric fields while the bacteria simultaneously produce nanocellulose, resulting in networks with aligned fibers. Since the electrolysis of water due to the application of electric fields produces the oxygen in the culture media far from the liquid-air boundary, aerobic cellulose production in 3D structures is readily achievable. Five separate sets of experiments were conducted to demonstrate the assembly of nanocellulose by A. xylinum in the presence of electric fields in micro- and macro-environments. This study demonstrates a new concept of bottom up material synthesis by the control of a biological assembly process.
View details for DOI 10.1007/s10439-010-9999-0
View details for Web of Science ID 000279682000001
View details for PubMedID 20300846
Contactless dielectrophoresis: a new technique for cell manipulation
2009; 11 (5): 997-1006
Contactless dielectrophoresis (cDEP) is a recently developed method of cell manipulation in which the electrodes are physically isolated from the sample. Here we present two microfluidic devices capable of selectively isolating live human leukemia cells from dead cells utilizing their electrical signatures. The effect of different voltages and frequencies on the gradient of the electric field and device performance was investigated numerically and validated experimentally. With these prototype devices we were able to achieve greater than 95% removal efficiency at 0.2-0.5 mm s(-1) with 100% selectivity between live and dead cells. In conjunction with enrichment, cDEP could be integrated with other technologies to yield fully automated lab-on-a-chip systems capable of sensing, sorting, and identifying rare cells.
View details for DOI 10.1039/b920590j
View details for Web of Science ID 000274207700005
View details for PubMedID 20126683
Dielectrophoresis (DEP) has become a promising technique to separate and identify cells and microparticles suspended in a medium based on their size or electrical properties. Presented herein is a new technique to provide the non-uniform electric field required for DEP that does not require electrodes to contact the sample fluid. In our method, electrodes are capacitively-coupled to a fluidic channel through dielectric barriers; the application of a high-frequency electric field to these electrodes then induces an electric field in the channel. This technique combines the cell manipulation abilities of traditional DEP with the ease of fabrication found in insulator-based technologies. A microfluidic device was fabricated based on this principle to determine the feasibility of cell manipulations through contactless DEP (cDEP). We were able to demonstrate cell responses unique to the DEP effect in three separate cell lines. These results illustrate the potential for this technique to identify cells through their electrical properties without fear of contamination from electrodes.
View details for DOI 10.1007/s10544-009-9317-5
View details for Web of Science ID 000270679400007
View details for PubMedID 19415498