In this tutorial review aimed at researchers using nanofluidic devices, we summarize the current state of theoretical and experimental approaches to describing concentration polarization (CP) in hybrid microfluidic–nanofluidic systems. We also analyze experimental results for these systems and place them in the context of recent theoretical developments. We then extend the theory to explain the behavior of both positively and negatively charged, low-concentration, analyte species in systems with CP. We conclude by discussing several applications of CP in microfluidics.

Rapid antibody production in response to invading pathogens requires the dramatic expansion of pathogen-derived antigen-specific B lymphocyte populations. Whether B cell population dynamics are based on stochastic competition between competing cell fates, as in the development of competence by the bacterium Bacillus subtilis, or on deterministic cell fate decisions that execute a predictable program, as during the development of the worm Caenorhabditis elegans, remains unclear. Here, we developed long-term live-cell microscopy of B cell population expansion and multiscale mechanistic computational modeling to characterize the role of molecular noise in determining phenotype heterogeneity. We show that the cell lineage trees underlying B cell population dynamics are mediated by a largely predictable decision-making process where the heterogeneity of cell proliferation and death decisions at any given timepoint largely derives from nongenetic heterogeneity in the founder cells. This means that contrary to previous models, only a minority of genetically identical founder cells contribute the majority to the population response. We computationally predict and experimentally confirm nongenetic molecular determinants that are predictive of founder cells’ proliferative capacity. While founder cell heterogeneity may arise from different exposure histories, we show that it may also be due to the gradual accumulation of small amounts of intrinsic noise during the lineage differentiation process of hematopoietic stem cells to mature B cells. Our finding of the largely deterministic nature of B lymphocyte responses may provide opportunities for diagnostic and therapeutic development. Significance This study addresses why splenic B lymphocytes show differential cell proliferation and death decisions, and whether these may be predictable. Biology provides examples of both stochastic decision making and highly deterministic developmental programs. Prior studies of B lymphocytes suggested these cells make stochastic decisions, but the key experiment—long-term tracing of individual cell lineages—has not been done. Overcoming the technical challenges, we found that B cell fate decisions are largely nonstochastic. Using a mathematical model, we found that they are predictable, as long as the state of the molecular network in founder cells is known. That allowed us to identify the molecular determinants of proliferative fate decisions, which potentially constitute novel drug targets and biomarkers for B cell-mediated diseases.