Microfluidic Device For Cell Separation And Uses Thereof

Abstract

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).

What is claimed is: 
     
         1 . A method for manufacturing a device comprising:
 i. providing a first substrate;   ii. creating a pattern of obstacles on said first substrate, and   iii. coating said pattern of obstacles with one or more binding moieties that selectively bind to one or more first cell types in a mixture of cells, wherein said first cell type is a fetal nucleated red blood cell.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the substrate is selected from a silicon-based substrate, a metal-based substrate, or a polymeric-based substrate. 
     
     
         4 . The method of  claim 3 , wherein the silicon-based substrate is a glass substrate, a silicon substrate, or a silicon-on insulator substrate. 
     
     
         5 . The method of  claim 3 , wherein the metal-based substrate is a steel substrate or a nickel substrate. 
     
     
         6 . The method of  claim 3 , wherein the polymeric-based substrate is a charged polymer or an uncharged polymer. 
     
     
         7 . The method of  claim 3 , wherein the polymeric-based substrate is a urethane polymer, an epoxy polymer, an acrylic polymer, or a polymer selected from the group consisting of poly(methylmethacrylate), polycarbonate, polystyrene, polyethylene, poly(dimethylsiloxane) and polyolefins. 
     
     
         8 . The method of  claim 1 , wherein the creating step comprises the use of lithography, micromachining, casting, molding, embossing, wet chemical etch, dry chemical etch, milling, diamond cutting, electroforming, LIGA, or any combination thereof. 
     
     
         9 . The method of  claim 8 , wherein lithography comprises photolithography, soft lithography, stereolithography or x-ray lithography. 
     
     
         10 . The method of  claim 8 , wherein micromachining comprises laser micromachining, thin-film surface micromachining, silicon micromachining or plastic micromachining. 
     
     
         11 . The method of either  claim 8 , wherein molding is injection molding. 
     
     
         12 . The method of either  claim 8 , wherein the dry chemical etch is a deep reactive ion etch. 
     
     
         13 . The method of  claim 1 , wherein the creating step further comprises bonding a second substrate to the first substrate. 
     
     
         14 . The method of  claim 13 , wherein the bonding comprises. the use of clamping, gluing, heating, anodic bonding, wafer bonding, a vacuum, or any combination thereof. 
     
     
         15 . The method of  claim 13 , wherein the second substrate material and the first substrate material are the same. 
     
     
         16 . The method of  claim 15 , wherein the first substrate and the second substrate are made of a polymeric material. 
     
     
         17 . The method of  claim 13 , wherein the second substrate material and the substrate material are different. 
     
     
         18 . The method of  claim 13 , wherein the first substrate is glass and the second substrate is silicon, the first substrate is silicon and the second substrate is glass, the first substrate is glass and the second substrate is plastic, the first substrate is plastic and the second substrate is glass, or the first substrate is plastic and the second substrate a different plastic. 
     
     
         19 . The method of  claim 1 , wherein the height of each obstacle is about 100 μm. 
     
     
         20 . The method of  claim 1 , wherein the shape of each obstacle is circular, semi-circular, oval, trapezoidal, rectangular, a square, or any combination thereof. 
     
     
         21 - 34 . (canceled)