Significance: Microfluidics is an important in vitro platform to gain insights into mechanics of blood flow and mechanisms of pathophysiology of human diseases. Extraction of 3D fields in microfluidics with dense cell suspensions remains a formidable challenge. We present artificial-intelligence velocimetry (AIV) as a general platform to determine 3D flow fields and a microaneurysm-on-a-chip to simulate blood flow in microaneurysms in patients with diabetic retinopathy. AIV is built on physics-informed neural networks that integrate seamlessly 2D images from microfluidic experiments or in vivo observations with physical laws to estimate full 3D velocity and stress fields. AIV could be integrated into imaging technologies to automatically infer key hemodynamic metrics from in vivo and in vitro biomedical images.

The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC–macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.

Three-dimensional (3D) extrusion-based bioprinting is the most widely used bioprinting technology to fabricate bionic tissue or organ constructs by combining biomaterial ink and living cells for tissue engineering and regenerative medicine. One critical issue of this technique is the selection of suitable biomaterial ink to simulate extracellular matrix (ECM) that provides mechanical support for cells and regulates their physiological activities. Previous studies have demonstrated that it is an enormous challenge to form and maintain reproducible 3D constructs and eventually achieve the balance among biocompatibility, mechanical properties, and printability. This review highlights the properties of extrusion-based biomaterial inks and recent developments as well as details various biomaterial inks classified by their function. Key approaches related to their modification methods according to the functional requirements are also discussed, along with the selection strategies by varying extrusion paths and methods in extrusion-based bioprinting. This systematical review will assist researchers in identifying the most suitable extrusionbased biomaterial inks based on their requirements, as well as in elaborating current challenges and prospects of extrudable biomaterial inks in the field of bioprinting of in vitro tissue models.

Photonic crystal (PC) barcodes are a new type of spectrum-encoding microcarriers used in multiplex high-throughput bioassays, such as broad analysis of biomarkers for clinical diagnosis, gene expression, and cell culture. Unfortunately, most of these existing PC barcodes suffered from undesired features, including difficult spectrum-signal acquisition, weak mechanical strength, and high ontology fluorescence, which limited their development to real applications. To address these limitations, we report a new type of structural color-encoded PC barcodes. The barcodes are fabricated by the assembly of monodisperse polydopamine- (PDA-) coated silica (PDA@SiO ₂ ) nanoparticles using a droplet-based microfluidic technique and followed by pyrolysis of PDA@SiO ₂ (C@SiO ₂ ) barcodes. Because of the templated carbonization of adhesive PDA, the prepared C@SiO ₂ PC beads were endowed with simultaneous easy-to-identify structural color, high mechanical strength, and ultralow ontology fluorescence. We demonstrated that the structural colored C@SiO ₂ barcodes not only maintained a high structural stability and good biocompatibility during the coculturing with fibroblasts and tumor cells capture but also achieved an enhanced fluorescent-reading signal-to-noise ratio in the fluorescence-reading detection. These features make the C@SiO ₂ PC barcodes versatile for expansive application in fluorescence-reading-based multibioassays.