Adhesion-Based Capture and Separation of Cells for Microfluidic Devices
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Adhesion-based capture and separation of cells for microfluidic devices Wesley C. Chang1,3, Luke P. Lee2,3, Dorian Liepmann2,3 1 Department of Mechanical Engineering 2 Department of Bioengineering 3 Berkeley Sensor and Actuator Center, 497 Cory Hall University of California, Berkeley, CA 94720-1774, USA ABSTRACT Cell separation and sorting in micro-assay devices must be performed using minimal sample sizes and few processing steps. To meet these requirements, a biomimetic approach to cell sorting is proposed based on adhesive rolling of cells along surfaces. This type of interaction is mediated by a special class of adhesion proteins on cell membranes and is responsible for localizing cells to particular tissues in vivo. To perform cell capture in a microdevice, raw sample can be flowed through microstructured fluidic channels, which serve as chromatographic “separation columns” and whose surfaces are coated with adhesion proteins. Targeted cells are captured by the flow structures and are permitted to roll slowly under shear from passing fluid. Among captured cells, differences in rolling speed provide the basis for segregating different populations. In this study, two prospective designs for microstructured fluidic channels were coated with E-selectin IgG chimera. The capture and enrichment of HL-60 and U-937 cells from flowing samples were demonstrated. Additionally, the difference in transit speed through one of the fluidic channels indicates that separation of enriched populations of these cells is feasible. INTRODUCTION The goal of miniaturizing biological assay systems (such as lab-on-a-chip) is to shrink the functions of conventional clinical and research laboratories onto devices that integrate various process steps on a single microfluidic platform. This transformation will yield several key advantages both for medical diagnostics and research tools in biotechnology, including the reduction of needed sample sizes to the scale of microliters and acceleration of sample processing speeds, permitting fast turnaround and high throughput [1]. Consequently, the development of these miniaturized systems must focus on manipulating fluids in small volumes, minimizing sample preparation and incubation steps, and virtually eliminating human intervention. In many biological assays, one of the primary steps in preparing raw biological samples (i.e. blood) is separating and isolating different types of cells. In conventional laboratory processes, this function is performed in a variety of ways based on differences in physical or biochemical properties among different cell types [2]. In microfludics, exclusion arrays can be used to separate cells based on size[3] or cell stiffness[4]. These methods, however, function best only when physical differences among different cell types are substantial. More advanced cell separation techniques focus on using biochemical properties and select specific chemical species or antigens on the cell membrane or within the cell. Molecular markers, such as antibodies, target these species a
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