Wenyan Liu

We herein designed a 64-chamber laminar-flow microfluidic chip with independently addressable culture units capable of establishing spatially heterogeneous chemical environments to mimic tissue microenvironments. Stable chemical gradients were successfully generated within the chip through controlled laminar flow, allowing precise spatial modulation of cellular exposure. Using TNF-α as a model stimulus, we observed a clear time delay in NF-κB activation between cells directly exposed to the cytokine and those located on the medium-only side, confirming the establishment of spatially distinct chemical conditions. Notably, even cells not directly exposed to TNF-α eventually responded, indicating that molecular diffusion along the static solid–liquid interface serves as an effective delivery route for bioactive molecules. To further demonstrate the platform’s utility, we constructed a skin-mimetic co-culture model of HaCaT keratinocytes and human skin fibroblasts (HSFs) to assess the diffusion and cytotoxic effects of 5-fluorouracil (5-FU). The results revealed that fibroblasts provided protective effects against 5-FU-induced cytotoxicity, likely via paracrine signaling or direct cell–cell interactions. These findings highlight the platform’s capacity for probing not only spatial drug-delivery dynamics but also intercellular interactions under physiologically relevant conditions. This system offers a powerful and versatile tool for studying spatiotemporal signaling, drug screening, and topical therapeutic development.

Red blood cell (RBC) deformability is a critical biophysical property that enables effective passage of RBCs through microvasculature and ensures proper oxygen delivery. Impairment of this property is associated with various pathological conditions, including type 2 diabetes mellitus (T2DM). In this study, we developed an automated microfluidic platform for high-throughput and real-time assessment of RBC deformability under controlled flow conditions. The device features a structured microchannel design and integrated imaging to quantify individual cell deformation responses. Comparative analyses of RBCs from healthy individuals and T2DM patients revealed significant reductions in deformability in the diabetic group. In vivo validation using a diabetic mouse model further confirmed the progressive decline in RBC deformability under chronic hyperglycemia. This microfluidic approach provides a robust and efficient tool for characterizing RBC mechanical properties, offering potential for disease monitoring and clinical diagnostic applications.