Yanting Zhang

Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels

The dielectrophoresis (DEP) phenomenon is used to separate platelets directly from diluted whole blood in microfluidic channels. By exploiting the fact that platelets are the smallest cell type in blood, we utilize the DEP‐activated cell sorter (DACS) device to perform size‐based fractionation of blood samples and continuously enrich the platelets in a label‐free manner. Cytometry analysis revealed that a single pass through the two‐stage DACS device yields a high purity of platelets (∼95%) at a throughput of ∼2.2×104 cells/second/microchannel with minimal platelet activation. This work demonstrates gentle and label‐free dielectrophoretic separation of delicate cells from complex samples and such a separation approach may open a path toward continuous screening of blood products by integrated microfluidic devices.

Numerical Simulation of an Electroosmotic Micromixer

We present a micromixer fabricated using MEMS technology which takes advantage of electroosmosis to mix fluids. A time dependent electric field is applied and the resulting electroosmosis perturbs the low Reynolds number flow. It is shown that the electric field can be deemed quasi-steady and the electroosmotic slip boundary condition can be applied when the incompressible Navier Stokes equation is solved. Both the electric field and the electroosmotic flow are simulated numerically. Study of the particle traces shows folding and stretching of material lines, and a positive Lyapunov exponent is found which indicates chaotic-like mixing.

Titanium-based dielectrophoresis devices for microfluidic applications.

To date, materials selection in microfluidics has been restricted to conventional micromechanical materials systems such as silicon, glass, and various polymers. Metallic materials offer a number of potential advantages for microfluidic applications, including high fracture toughness, thermal stability, and solvent resistance. However, their exploitation in such applications has been limited. In this work, we present the application of recently developed titanium micromachining and multilayer lamination techniques for the fabrication of dielectrophoresis devices for microfluidic particle manipulation. Two device designs are presented, one with interdigitated planar electrodes defined on the floor of the flow channel, and the other with electrodes embedded within the channel wall. Using these devices, two-frequency particle separation and Z-dimensional flow visualization of the dielectrophoresis phenomena are demonstrated.

TITANIUM BULK MICROMACHINING FOR BIOMEMS APPLICATIONS: A DEP DEVICE AS A DEMONSTRATION

Titanium has been widely used as a biomedical material in orthopedics, dentistry, cardiology, and cardiovascular surgery due to the excellent biostability and biocompatibility that results from its spontaneous formation of a highly passivating oxide layer in air and blood. However, little research has been done on the development of titanium for bioMEMS applications. This is likely due to the immaturity of titanium bulk micromachining technology to date. Here we report the application of new high-aspect-ratio bulk titanium micromachining techniques recently developed within our group towards the fabrication of a titanium-based multifrequency traveling wave dielectrophoresis (DEP) device targeted for the separation of bioparticles. The device serves to illustrate the potential of these techniques for enabling the realization of novel bioMEMS devices with enhanced functionality and capability.

Affinity reagent technology development and application to rapid immunochromatographic pathogen detection

Immunochromatography is a rapid, reliable, and cost effective method of detecting biowarfare agents. The format is similar to that of an over-the-counter pregnancy test. A sample is applied to one end of a cassette and then a control line, and possibly a sample line, are visualized at the other end of the cassette. The test is based upon a sandwich assay. For the control, a line of Protein A is immobilized on the membrane. Gold nanoparticle bound IgG flows through the membrane and binds the Protein A, creating a visible line on the membrane. For the sample, one epitope is immobilized on the membrane and another epitope is attached to gold nanoparticles. The sample binds gold bound epitope, travels through the membrane, and binds membrane bound epitope. The two epitopes are not cross-reactive, therefore a sample line is only visible if the sample is present. In order to efficiently screen for binders to a sample target, a novel, Continuous Magnetic Activated Cell Sorter (CMACS) has been developed on a disposable, microfluidic platform. The CMACS chip quickly sorts E. coli peptide libraries for target binders with high affinity. Peptide libraries, are composed of approximately ten million bacteria, each displaying a different peptide on their surface. The target of interest is conjugated to a micrometer sized magnetic particle. After the library and the target are incubated together to allow binding, the mixture is applied to the CMACS chip. In the presence of patterned nickel and an external magnet, separation occurs of the bead-bound bacteria from the bulk material. The bead fraction is added to bacterial growth media where any attached E. coli grow and divide. These cells are cloned, sequenced, and the peptides are assayed for target binding affinity. As a proof-of-principle, assays were developed for human C-reactive protein. More defense relevant targets are currently being pursued.

Experimental Study of Two-frequency Dielectrophoresis Effects on a Linear Electrode Array

Dielectrophoresis is a powerful tool for the manipulation of particles and biological cells. The magnitude and direction of the DEP force is determined by the comparative conductivity and permeability of the medium and the particle. Most previous work has focused on single frequency studies. In this paper, we present the work of two frequency dielectrophoresis effects on a linear electrode array. We show results where the advantage of applying two frequencies is to separate particles having similar dielectric properties. In addition, we report the first experimental data on breaking of DEP trapping zone by adding a low frequency signal to the main frequency signal. The phenomenon is due to a system disturbance by electro-hydrodynamic effect and has potential applications in DEP mixing and advanced control of particles

Controlled Separation and Trapping of Particles Using Two-frequency DEP

We present numerical simulations and experiments on dielectrophoretic (DEP) separation and trapping performed in a titanium-based microchannel linear electrode array. The use of electric fields and in particular dielectrophoresis (DEP) have a great potential to help miniaturize and increase the speed of biomedical analysis. Precise control and manipulation of micro/nano/bio particles inside those miniaturized devices depend greatly on our understanding of the phenomena induced by AC electric fields inside microchannels and how we take advantage of them. The studied DEP devices are composed of two parts: the inter-digitated titanium electrodes and the channel. The electrode substrate is constituted of two layers to form 4-phase traveling wave. Each electrode is 20 μm wide and separated from the other by a gap of 20 μm. The channel is 200 μm wide, 50 μm deep and 6 mm long. The device is designed to generate inhomogeneities in electric-field magnitude. This allows positive and negative DEP (p-DEP and n-DEP). Moreover, it can also produce inhomogeneities in electric-field phase, hence authorizing traveling wave DEP (twDEP). It is also capable of inducing two-frequency DEP, in contrast with most of the previous, single-frequency, designs. The advantages of two-frequency DEP were shown by theoretical work (Chang et al. 2003) and permit precise and optimal control of particles movements. We show that fluid flow effects are substantial and can affect the particle motion in a positive (enhanced trapping) and negative (trapping when separation is desired) way. We discuss the effects of AC-electroosmosis, electrothermal and dielectrophoresis combined. We discuss the advantages of two-frequency dielectrophoretic handling of bioparticles. We investigate the limits of particle size that can be accurately controlled.Copyright