Anas Alazzam

Interdigitated comb-like electrodes for continuous separation of malignant cells from blood using dielectrophoresis.

In this paper, a method for continuous flow separation of circulating malignant cells from blood in a microfluidic device using dielectrophoresis is discussed. Separation of MDA231 breast cancer cells after mixing with normal blood cells was achieved with a level of accuracy that enabled precise counting of the malignant cells, separation and eventually, sub‐culturing. MDA231 cells were separated from the blood to a daughter channel using two pairs of interdigitated activated comb‐like electrode structures. All experiments are performed with conductivity adjusted medium samples. The electrode pairs were positioned divergent and convergent with respect to the flow. The AC signals used in the separation are 20 V peak‐to‐peak with frequencies of 10–50 kHz. The separation is based on balance of magnitude of the dielectrophoretic force and hydrodynamic force. The difference in response between circulating malignant cells and normal cells at a certain band of alternating current frequencies was used for rapid separation of cancer cells from blood. The significance of these experimental results is discussed in this paper, with detailed reporting on the suspension medium, preparation of cells, flow condition and the fabrication process of the microfluidic chip. The present technique could potentially be applied to identify incident cancer at a stage and size that is not yet detectable by standard diagnostic techniques (imaging and biochemical testing). Alternatively, it may also be used to detect cancer recurrences.

Microchannel Anechoic Corner for Size-Selective Separation and Medium Exchange via Traveling Surface Acoustic Waves

We demonstrate a miniaturized acoustofluidic device composed of a pair of slanted interdigitated transducers (SIDTs) and a polydimethylsiloxane microchannel for achieving size-selective separation and exchange of medium around polystyrene particles in a continuous, label-free, and contactless fashion. The SIDTs, deposited parallel to each other, produce tunable traveling surface acoustic waves (TSAWs) at desired locations, which, in turn, yield an anechoic corner inside the microchannel that is used to selectively deflect particles of choice from their streamlines. The TSAWs with frequency fR originating from the right SIDT and propagating left toward the microchannel normal to the fluid flow direction, laterally deflect larger particles with diameter d1 from the hydrodynamically focused sample fluid that carries other particles as well with diameters d2 and d3, such that d1 > d2 > d3. The deflected particles (d1) are pushed into the top-left corner of the microchannel. Downstream, the TSAWs with frequency fL, such that fL > fR, disseminating from the left SIDT, deflect the medium-sized particles (d2) rightward, leaving behind the larger particles (d1) unaffected in the top-left anechoic corner and the smaller particles (d3) in the middle of the microchannel, thereby achieving particle separation. A particle not present in the anechoic corner could be deflected rightward to realize twice the medium exchange. In this work, the three-way separation of polystyrene particles with diameters of 3, 4.2, and 5 μm and 3, 5, and 7 μm is achieved using two separate devices. Moreover, these devices are used to demonstrate multimedium exchange around polystyrene particles ∼5 μm and 7 μm in diameter.

Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells

To identify genes affected by single-walled carbon nanotubes (SWCNTs) in human normal lung cells, we compared the gene expression profiles of untreated human normal bronchial epithelial (HNBE) cells to profiles of HNBE cells treated with SWCNTs. A complementary DNA microarray analysis consisting of 54,675 human genes revealed marked changes in the expression of 14,294 genes, with 7,029 genes being upregulated and 7,265 being downregulated. This comprehensive list of genes included those associated with cell cycle, apoptosis, cell survival, cell adhesion and motility, signal transduction, and transcription regulation. Additional analysis of 19 genes using reverse transcription-polymerase chain reaction confirmed the microarray analysis. More specifically, our study demonstrates to our knowledge for the first time, evidence that 9 of the 19 genes (most of which encode cell apoptotic, signal transduction, and transcription regulator products) are upregulated in the SWCNTs-treated HNBE cells as compared with untreated cells, whereas the remaining 10 of the 19 (involved in cell adhesion and motility, cell proliferation, and cell survival) are downregulated in SWCNTs-treated HNBE cells in comparison with untreated controls. These findings provide a large body of information regarding gene expression profiles associated with SWCNTs exposure in human lung bronchial epithelial cells, and also represent a source to investigate the mechanism of the effect of SWCNTs in human normal lung cells. From the clinical editor: In this study, the gene expression profile of human normal bronchial epithelial cells was compared with single-wall carbon nanotubes-treated cells. A cDNA microarray analysis consisting of 54,675 human genes revealed significant changes in the expression of 14,294 genes, with 7,029 genes being up-regulated and 7,265 being down-regulated. This serves as a first step in clarification of mechanisms of action and to investigate toxicity in this model.

Analytical solutions and validation of electric field and dielectrophoretic force in a bio-microfluidic channel

In a microbiological device, cell or particle manipulation and characterization require the use of electric field on different electrodes in several configurations and shapes. To efficiently design microelectrodes within a microfluidic channel for dielectrophoresis focusing, manipulation and characterization of cells, the designer will seek the exact distribution of the electric potential, electric field and hence dielectrophoresis force exerted on the cell within the microdevice. In this paper we describe the approach attaining the analytical solution of the dielectrophoretic force expression within a microchannel with parallel facing same size electrodes present on the two faces of channel substrates, with opposite voltages on the pair electrodes. Simple Fourier series mathematical expressions are derived for electric potential, electric field and dielectric force between two distant finite‐size electrodes. Excellent agreement is found by comparing the analytical results calculated using MATLAB™ with numerical ones obtained by Comsol. This analytical result can help the designer to perform simple design parametric analysis. Bio‐microdevices are also designed and fabricated to illustrate the theoretical solution results with the experimental data. Experiments with red blood cells show the dielectrophoretic force contour plots of the analytical data matched to the experimental results.

Computational Analysis of Enhanced Magnetic Bioseparation in Microfluidic Systems with Flow-Invasive Magnetic Elements

A microfluidic design is proposed for realizing greatly enhanced separation of magnetically-labeled bioparticles using integrated soft-magnetic elements. The elements are fixed and intersect the carrier fluid (flow-invasive) with their length transverse to the flow. They are magnetized using a bias field to produce a particle capture force. Multiple stair-step elements are used to provide efficient capture throughout the entire flow channel. This is in contrast to conventional systems wherein the elements are integrated into the walls of the channel, which restricts efficient capture to limited regions of the channel due to the short range nature of the magnetic force. This severely limits the channel size and hence throughput. Flow-invasive elements overcome this limitation and enable microfluidic bioseparation systems with superior scalability. This enhanced functionality is quantified for the first time using a computational model that accounts for the dominant mechanisms of particle transport including fully-coupled particle-fluid momentum transfer.

Novel microfluidic device for the continuous separation of cancer cells using dielectrophoresis

We describe the design, microfabrication, and testing of a microfluidic device for the separation of cancer cells based on dielectrophoresis. Cancer cells, specifically green fluorescent protein-labeled MDA-MB-231, are successfully separated from a heterogeneous mixture of the same and normal blood cells. MDA-MB-231 cancer cells are separated with an accuracy that enables precise detection and counting of circulating tumor cells present among normal blood cells. The separation is performed using a set of planar interdigitated transducer electrodes that are deposited on the surface of a glass wafer and slightly protrude into the separation microchannel at one side. The device includes two parts, namely, a glass wafer and polydimethylsiloxane element. The device is fabricated using standard microfabrication techniques. All experiments are conducted with low conductivity sucrose-dextrose isotonic medium. The variation in response between MDA-MB-231 cancer cells and normal cells to a certain band of alternating-current frequencies is used for continuous separation of cells. The fabrication of the microfluidic device, preparation of cells and medium, and flow conditions are detailed. The proposed microdevice can be used to detect and separate malignant cells from heterogeneous mixture of cells for the purpose of early screening for cancer.

Lab-on-chip for liquid biopsy (LoC-LB) based on dielectrophoresis

This short communication presents the proof-of-concept of a novel dielectrophoretic lab-on-chip for identifying/separating circulating tumor cells for purposes of liquid biopsy. The device consists of a polydimethylsiloxane layer, containing a microchannel, bonded on a glass substrate that holds two sets of planar interdigitated transducer electrodes. The lab-on-chip is operated at a frequency that enables dielectrophoretic force to sort cells, based on type, along the lateral direction. The operating frequency ensures attraction force toward the electrodes on cancer cells and repulsion force toward the center of the microchannel on other cells. Initial tests for demonstrating proof-of-concept have successfully identified/separated green fluorescent protein-labelled MDA-MB-231 breast cancer cells from a mixture of the same and regular blood cells suspended in low conductivity sucrose/dextrose medium.

Microfluidic Platforms for Bio-applications

This chapter provides a brief overview of three actuation mechanisms that are relevant for biomedical applications of microfluidics. Actuation mechanisms are employed in the field of microfluidics for realizing unit operations such as focusing, switching, and separation. The topics dealt with in this chapter include dielectrophoresis, acoustophoresis, and magnetophoresis. The first section provides an introduction to these and related topics while the second section deals specifically on dielectrophoresis. The third and fourth sections detail acoustophoresis and magnetophoresis, respectively. This chapter concludes by providing a quick comparison of these different actuation methods.

Impact of single-walled carbon nanotubes on the embryo: a brief review

Carbon nanotubes (CNTs) are considered one of the most interesting materials in the 21st century due to their unique physiochemical characteristics and applicability to various industrial products and medical applications. However, in the last few years, questions have been raised regarding the potential toxicity of CNTs to humans and the environment; it is believed that the physiochemical characteristics of these materials are key determinants of CNT interaction with living cells and hence determine their toxicity in humans and other organisms as well as their embryos. Thus, several recent studies, including ours, pointed out that CNTs have cytotoxic effects on human and animal cells, which occur via the alteration of key regulator genes of cell proliferation, apoptosis, survival, cell–cell adhesion, and angiogenesis. Meanwhile, few investigations revealed that CNTs could also be harmful to the normal development of the embryo. In this review, we will discuss the toxic role of single-walled CNTs in the embryo, which was recently explored by several groups including ours.

Dielectrophoresis based focusing in microfluidic devices

This document presents the mathematical model of a microfluidic device employing dielectrophoresis for purposes of 3D-focusing. The electrode configuration consists of multiple interdigitated transducer electrodes on either side of the bottom surface of the microchannel. The model consists of three equations of motion, one for each direction, equation of electric potential and electric field, and Navier-Stokes equation for fluid flow. The model accounts for forces such as inertia, gravity, buoyancy, and dielectrophoresis. The model is used for analyzing the influence of operating and geometric parameters on focusing. It is observed that the electrode configuration can achieve 3D-focusing irrespective of the radius and initial location of the micro-scale entity, volumetric flow rate, and applied voltage.