The invention features methods for separating cells from a sample (e.g., separating fetal red blood cells from maternal blood). The method begins with the introduction of a sample including cells into one or more microfluidic channels. In one embodiment, the device includes at least two processing steps. For example, a mixture of cells is introduced into a microfluidic channel that selectively allows the passage of a desired type of cell, and the population of cells enriched in the desired type is then introduced into a second microfluidic channel that allows the passage of the desired cell to produce a population of cells further enriched in the desired type. The selection of cells is based on a property of the cells in the mixture, for example, size, shape, deformability, surface characteristics (e.g., cell surface receptors or antigens and membrane permeability), or intracellular properties (e.g., expression of a particular enzyme).

Microfluidic device for cell separation and uses thereof

Electrokinetics is the study of the motion of bulk fluids or selected particles embedded in fluids when they are subjected to electric fields. With the recent developments in microfabrication, electrokinetics provides effective manipulation techniques in the micro and nano domains, which matches the length scale of various biological objects. The ability to manipulate objects down to molecular levels opens new avenues to exploit biological science and technology. Understanding of the fundamental characteristics and limitations of the forces becomes a crucial issue for successful applications of these force fields. In this paper, we review and examine the range of influence for electrokinetically manipulated biological objects in microdevices, which can lead to interesting applications in biotechnology.

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Electrokinetics in micro devices for biotechnology applications

The present invention provides systems, apparatuses, and methods to detect the presence of fetal cells when mixed with a population of maternal cells in a sample and to test fetal abnormalities, e.g. aneuploidy. The present invention involves labeling regions of genomic DNA in each cell in said mixed sample with different labels wherein each label is specific to each cell and quantifying the labeled regions of genomic DNA from each cell in the mixed sample. More particularly the invention involves quantifying labeled DNA polymorphisms from each cell in the mixed sample.

Rare cell analysis using sample splitting and dna tags

Dielectrophoresis is a noninvasive, nondestructive, inexpensive, and fast technique for the manipulation of bioparticles. Recent advances in the field of dielectrophoresis (DEP) have resulted in new approaches for characterizing the behavior of particles and cells using direct current (DC) electric fields. In such approaches, spatial nonuniformities are created in the channel by embedding insulating obstacles in the channel or flow field in order to perform separation or trapping. This emerging field of dielectrophoresis is commonly termed DC insulator dielectrophoresis (DC-iDEP), insulator-based dielectrophoresis (iDEP), or electrodeless dielectrophoresis (eDEP). In many microdevices, this form of dielectrophoresis has advantages over traditional AC-DEP, including single material microfabrication, remotely positioned electrodes, and reduced fouling of the test region. DC-iDEP applications have included disease detection, separation of cancerous cells from normal cells, and separation of live from dead bacteria. However, there is a need for a critical report to integrate these important research findings. The aim of this review is to provide an overview of the current state-of-art technology in the field of DC-iDEP for the separation and trapping of inert particles and cells. In this article, a review of the concepts and theory leading to the manipulation of particles via DC-iDEP is given, and insulating obstacle geometry designs and the characterization of device performance are discussed. This review compiles and compares the significant findings obtained by researchers in handling and manipulating particles.

https://static.springer.com/sgw/documents/1346328/application/pdf/DC+insulator+dielectrophoretic.pdf

DC insulator dielectrophoretic applications in microdevice technology: a review

The invention features devices and methods for the deterministic separation of particles. Exemplary methods include the enrichment of a sample in a desired particle or the alteration of a desired particle in the device. The devices and methods are advantageously employed to enrich for rare cells, e.g., fetal cells, present in a sample, e.g., maternal blood and rare cell components, e.g., fetal cell nuclei. The invention further provides a method for preferentially lysing cells of interest in a sample, e.g., to extract clinical information from a cellular component, e.g., a nucleus, of the cells of interest. In general, the method employs differential lysis between the cells of interest and other cells (e.g., other nucleated cells) in the sample.

Devices and method for enrichment and alteration of cells and other particles

The dielectric properties of human red cells are strongly affected by the applied electric field, especially the frequency. Under the high frequency, the cells are acted on by positive dielectrophoresis (DEP) force and move to the tip region of the interdigitated electrode where the electric field is strongest. The cells are acted on by negative DEP force and aggregated in the "bay" zone between the neighboring electrode castellation tips and the surface of the electrodes. The patterns formed by DEP force are identical with the distribution of the electric field.

Ming Cao

Papers

Dielectrophoresis of human red cells in microchips.