Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.

An in vitro model of the human kidney glomerulus - the major site of blood filtration - could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes - the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications.

Microfluidic designs and techniques using lab-on-a-chip devices for pathogen detection for point-of-care diagnostics.

Effective pathogen detection is an essential prerequisite for the prevention and treatment of infectious diseases. Despite recent advances in biosensors, infectious diseases remain a major cause of illnesses and mortality throughout the world. For instance in developing countries, infectious diseases account for over half of the mortality rate. Pathogen detection platforms provide a fundamental tool in different fields including clinical diagnostics, pathology, drug discovery, clinical research, disease outbreaks, and food safety. Microfluidic lab-on-a-chip (LOC) devices offer many advantages for pathogen detection such as miniaturization, small sample volume, portability, rapid detection time and point-of-care diagnosis. This review paper outlines recent microfluidic based devices and LOC design strategies for pathogen detection with the main focus on the integration of different techniques that led to the development of sample-to-result devices. Several examples of recently developed devices are presented along with respective advantages and limitations of each design. Progresses made in biomarkers, sample preparation, amplification and fluid handling techniques using microfluidic platforms are also covered and strategies for multiplexing and high-throughput analysis, as well as point-of-care diagnosis, are discussed.