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BACKGROUND Advanced capabilities in genomic sequencing developed in the research sector will soon enter the clinical arena. Issues such as the proportioning of patient specimen material for traditional bright-field microscopic evaluation or dedication for molecular analysis will intensify, particularly in situations of small core biopsies. Microfluidics appears aptly suited as a platform capable of allowing traditional cytologic diagnostics and downstream molecular analysis from the same specimen. However, clarification is needed to determine that forces which act on cells in a fluidic environment do not drastically alter their cytologic features. METHODS Cells were processed for flow-through in a microfluidic channel and evaluated qualitatively and quantitatively for alterations due to fluid-shear stress or anoikis. RESULTS Processing caused separation of cells from cohesive clusters to smaller groups and individual cells, leading to greater variation in parameters associated with the nucleus in nontumor cells but no significant change in tumor cells. These differences were most readily apparent by quantitative measures, and to a lesser extent, qualitative evaluation. Time-dependent processing played a larger role in cytologic alteration than fluid-shear stress for nontumor cells. CONCLUSIONS Passage of cells through a microfluidic channel is a feasible approach that can be integrated into future platforms intent on integrating cytologic assessment of cells with recovery of the same cells for downstream assays. Cancer (Cancer Cytopathol) 2014;122:59–69. © 2013 American Cancer Society.

Advanced capabilities in genomic sequencing developed in the research sector will soon enter the clinical arena. Issues such as the proportioning of patient specimen material for traditional bright-field microscopic evaluation or dedication for molecular analysis will intensify, particularly in situations of small core biopsies. Microfluidics appears aptly suited as a platform capable of allowing traditional cytologic diagnostics and downstream molecular analysis from the same specimen. However, clarification is needed to determine that forces which act on cells in a fluidic environment do not drastically alter their cytologic features.Cells were processed for flow-through in a microfluidic channel and evaluated qualitatively and quantitatively for alterations due to fluid-shear stress or anoikis.Processing caused separation of cells from cohesive clusters to smaller groups and individual cells, leading to greater variation in parameters associated with the nucleus in nontumor cells but no significant change in tumor cells. These differences were most readily apparent by quantitative measures, and to a lesser extent, qualitative evaluation. Time-dependent processing played a larger role in cytologic alteration than fluid-shear stress for nontumor cells.Passage of cells through a microfluidic channel is a feasible approach that can be integrated into future platforms intent on integrating cytologic assessment of cells with recovery of the same cells for downstream assays.