Microfluidic transport in microdevices for rare cell capture

Abstract

The isolation and capture of rare cells is a problem uniquely suited to microfluidic devices, in which geometries on the cellular length scale can be engineered and a wide range of chemical functionalizations can be implemented. The performance of such devices is primarily affected by the chemical interaction between the cell and the capture surface and the mechanics of cell– surface collision and adhesion. As rare cell capture technology has been summarized elsewhere [1], this article focuses on the fundamental adhesion and transport mechanisms in rare cell capture microdevices, and explores modern device design strategies in a transport context. The biorheology and engineering parameters of cell adhesion are defined; adhesion models and reaction kinetics briefly reviewed. Transport at the microscale, including diffusion and steric interactions that result in cell motion across streamlines, is discussed. The review concludes by discussing design strategies with a focus on leveraging the underlying transport phenomena to maximize device performance.

Characterization of microfluidic shear-dependent epithelial cell adhesion molecule immunocapture and enrichment of pancreatic cancer cells from blood cells with dielectrophoresis

“…4,35,37,39,40,43 We chose to characterize the cell lines Capan-1, PANC-1, and BxPC-3 because of differences in their tumor origin (Capan-1 from liver metastasis; PANC-1 and BxPC-3 from primary pancreatic tumors), differentiation state (Capan-1 is well differentiated; PANC-1 and BxPC-3 are moderately to poorly differentiated), 49 and EpCAM expression as measured by antibodies bound per cell. 20 In addition, although Pethig et al previously measured the membrane capacitance and conductance of pancreatic beta cells 50 and Shim et al recently made DEP crossover frequency measurements of all NCI-60 cell lines, 27 to our knowledge, the DEP response of these pancreatic cancer cells has not been characterized before.…”

“…Captured cells in each pair of 1-mm 2 observation windows were enumerated and compared at a series of observation sites corresponding to a range of shear stresses found in typical immunocapture devices. 4,12,39,43 incubation with 10 lg/ml anti-EpCAM antibody (Clone 158206, R&D Systems) for 1 h. 20 All antibodies were prepared in 1% bovine serum albumin (BSA) in phosphate buffered saline (PBS).…”

Microfluidic Enrichment of Mouse Epidermal Stem Cells and Validation of Stem Cell Proliferation In Vitro

“…In a pillar array, an optimized offset between each row can increase cell-pillar collision rates and result in enhanced rare cell capture. 21,25,26 This study tested two different pillar array designs (Fig. 1) in the functional enrichment of epidermal stem cells.…”

Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture

“…From a technology standpoint, this work was completed with a device that was designed to generate sheardependent adhesion data [46]; we focused on characterization of cell physicochemical response rather than clinical and translational implementation of high-efficiency rare cell capture, which we have reported previously [9]. Our data on shear-dependent cell adhesion with the addition of DEP effects can be incorporated into computational fluid dynamics simulations of cancer and blood cell trajectories in 3D immunocapture devices to better predict capture performance and inform the design of future high-purity CTC capture systems that can facilitate subsequent clinical studies [17,27]. [63].…”

“…Studies that used the epithelial cell-adhesion molecule (EpCAM) to capture lung, prostate, pancreatic, and colorectal CTCs have reported a wide range of capture purities (9-67%) [16,18,19]. Our group has combined immunospecificity with optimization of cell adhesion and transport mechanisms to create Geometrically Enhanced Differential Immunocapture (GEDI) [27], and reported a capture purity of 62% with prostate CTCs by use of a monoclonal antibody, J591, that is highly specific to prostate-specific membrane antigen (PSMA) [17]. The main contributing factor to CTC capture impurities is the nonspecific adhesion of leukocytes to immunocapture surfaces.…”