Significance: A major challenge with in vitro investigations of the pathophysiological processes in sickle cell disease (SCD) has been the lack of a well-controlled microenvironment to mimic in vivo circulating conditions. The microfluidic platform developed here provides a quantitative assay of the kinetics of cell sickling, unsickling, and single-cell rheology. The ensuing alterations in the biorheological characteristics of sickle cells under hypoxic conditions show strong correlation with sickle hemoglobin level, hydroxyurea (HU) therapy, and cell density. These analyses provide cell-level perspectives of the clinical manifestations in SCD patients and offer unique diagnostic indicators of vasoocclusion and disease severity. These results could also provide alternative pathways to supplement current clinical practices to evaluate HU therapy.

In this perspective article, we present the state of the microfluidic field regarding current limitations and propose future directions and new approaches for the field to advance lab-on-a-chip technologies closer to translation and clinical use.

The electrical properties of biological cells have connections to their pathological states. Here we present an electric impedance microflow cytometry (EIMC) platform for the characterization of disease states of single cells. This platform entails a microfluidic device for a label-free and non-invasive cell-counting assay through electric impedance sensing. We identified a dimensionless offset parameter δ obtained as a linear combination of a normalized phase shift and a normalized magnitude shift in electric impedance to differentiate cells on the basis of their pathological states. This paper discusses a representative case study on red blood cells (RBCs) invaded by the malaria parasite Plasmodium falciparum. Invasion by P. falciparum induces physical and biochemical changes on the host cells throughout a 48-h multi-stage life cycle within the RBC. As a consequence, it also induces progressive changes in electrical properties of the host cells. We demonstrate that the EIMC system in combination with data analysis involving the new offset parameter allows differentiation of P. falciparum infected RBCs from uninfected RBCs as well as among different P. falciparum intraerythrocytic asexual stages including the ring stage. The representative results provided here also point to the potential of the proposed experimental and analysis platform as a valuable tool for non-invasive diagnostics of a wide variety of disease states and for cell separation.

The human placenta plays a key role in reproduction and serves as a major interface for maternofetal exchange of nutrients. Study of human placenta pathology presents a great experimental challenge because it is not easily accessible. In this paper, a 3D placenta-on-a-chip model is developed by bioengineering techniques to simulate the placental interface between maternal and fetal blood in vitro. In this model, trophoblasts cells and human umbilical vein endothelial cells are cultured on the opposite sides of a porous polycarbonate membrane, which is sandwiched between two microfluidic channels. Glucose diffusion across this barrier is analyzed under shear flow conditions. Meanwhile, a numerical model of the 3D placenta-on-a-chip model is developed. Numerical results of concentration distributions and the convection–diffusion mass transport is compared to the results obtained from the experiments for validation. Finally, effects of flow rate and membrane porosity on glucose diffusion across the placental barrier are studied using the validated numerical model. The placental model developed here provides a potentially helpful tool to study a variety of other processes at the maternal–fetal interface, for example, effects of drugs or infections like malaria on transport of various substances across the placental barrier.

Significance: The mechanisms underlying degradation of biological cells due to mechanical fatigue are not well understood. Specifically, detrimental effects of fatigue on properties and homeostasis of human red blood cells (RBCs), as they repeatedly deform while traversing microvasculature, have remained largely unexplored. We present a general microfluidics method that incorporates amplitude-modulated electrodeformation to induce static and cyclic mechanical deformation of RBCs. Fatigue of RBCs leads to significantly greater loss of membrane deformability, compared to static deformation under the same maximum load and maximum-load duration. These findings establish unique effects of cyclic mechanical deformation on the properties and function of biological cells. Our work provides a means to assess the mechanical integrity and fatigue damage of RBCs in blood circulation.