A functional microengineered model of the human splenon-on-a-chip

Abstract

The spleen is a secondary lymphoid organ specialized in the filtration of senescent, damaged, or infected red blood cells. This unique filtering capacity is largely due to blood microcirculation through filtration beds of the splenic red pulp in an open-slow microcirculation compartment where the hematocrit increases, facilitating the recognition and destruction of unhealthy red blood cells by specialized macrophages. Moreover, in sinusal spleens such as those of humans, blood in the open-slow microcirculation compartment has a unidirectional passage through interendothelial slits before reaching the venous system. This further physical constraint represents a second stringent test for erythrocytes ensuring elimination of those cells lacking deformability. With the aim of replicating the filtering function of the spleen on a chip, we have designed a novel microengineered device mimicking the hydrodynamic forces and the physical properties of the splenon, the minimal functional unit of the red pulp able to maintain filtering functions. In this biomimetic platform, we have evaluated the mechanical and physiological responses of the splenon using human red blood cells and malaria-infected cells. This novel device should facilitate future functional studies of the spleen in relation to malaria and other hematological disorders.

Microfluidic Organ‐on‐a‐Chip Technology for Advancement of Drug Development and Toxicology

“…A "splenon-on-a-chip" design was created by Rigat-Brugarolas et al [ 70 ] This design mimics the red pulp area of the spleen by creating a fast-fl ow layer and a slow-fl ow layer. The fl uid going through the slow-fl ow layer travels through a straight channel representing the 10% of blood that goes through a fi ltration process, where unhealthy red blood cells are destroyed.…”

Splenic Retention of Plasmodium falciparum Gametocytes To Block the Transmission of Malaria

“…Most existing methods to study the deformability of P. falciparum-infected RBC (7,26,27) are not yet compatible with the stringent requirements for high-throughput screening (HTS). A single-sample microsphere filtration (microsphiltration) device to measure the ability of RBC to squeeze between calibrated microspheres, thus mimicking the spleen, has been recently developed (28).…”

Organ-on-a-Chip Platforms for Drug Delivery and Cell Characterization: A Review

“…In addition to major organs, such as the heart, lungs, and liver, kidney (32) -, splenon (77,78) -and breast (79) -on-a-chip devices have been developed. Figure 9 shows the schematics of these three devices.…”

“…This problem is also related to the mathematical analysis of cell properties. Current models focus on a single property of cells or cell behaviors, such as fusion, (80)(81)(82) ECM-cell (78) interactions, (83) and cell-cell interactions. (84) Those simple models require further development to simulate in vivo cell activities precisely.…”