A high-throughput microfluidic device based on controlled incremental filtration to enable centrifugation-free, low extracorporeal volume leukapheresis.

Leukapheresis, the extracorporeal separation of white blood cells (WBCs) from red blood cells (RBCs) and platelets (PLTs), is a life-saving procedure used for treating patients with cancer and other conditions, and as the initial step in the manufacturing of cellular and gene-based therapies. Well-tolerated by adults, leukapheresis poses a significant risk to neonates and low-weight infants because the extracorporeal volume (ECV) of standard centrifugation-based machines represents a particularly large fraction of these patients' total blood volume. Here we describe a novel high-throughput microfluidic device (with a void volume of 0.4 mL) based on controlled incremental filtration (CIF) technology that could replace centrifugation for performing leukapheresis. The CIF device was tested extensively using whole blood from healthy volunteers at multiple hematocrits (5-30%) and flow rates (10-30 mL/min). In the flow-through regime, the CIF device separated WBCs with > 85% efficiency and 10-15% loss of RBCs and PLTs while processing whole blood diluted with saline to 10% hematocrit at a flow rate of 10 mL/min. In the recirculation regime, the CIF device demonstrated a similar level of separation performance, virtually depleting WBCs in the recirculating blood (~ 98% reduction) by the end of a 3.5-hour simulated leukapheresis procedure. Importantly, the device operated without clogging or decline in separation performance, with minimal activation of WBCs and PLTs and no measurable damage to RBCs. Compared to the typical parameters of centrifugation-based leukapheresis, the CIF device had a void volume at least 100-fold smaller, removed WBCs about twice as fast, and lost ~ 2-3-fold fewer PLTs, while operating at a flow rate compatible with the current practice. The hematocrit and flow rate at which the CIF device operated were significantly higher than previously published for other microfluidic cell separation methods. Finally, this study is the first to demonstrate a highly efficient separation of cells from recirculating blood using a microfluidic device. Overall, these findings suggest the feasibility of using high-throughput microfluidic cell separation technology to ultimately enable centrifugation-free, low-ECV leukapheresis. Such a capability would be particularly useful in young children, a vulnerable group of patients who are currently underserved.

Incidence and Effects of Feeding Intolerance in Trauma Patients.

BACKGROUND: Although feeding intolerance is a common complication in trauma patients, the incidence, development, and effects are poorly understood. METHODS: We performed a retrospective study in which trauma patients were classified as having feeding intolerance based on time to reach feeding goal. Subsequently, we sorted patients by gastric residual volumes (GRVs) or symptoms of slowed gastrointestinal motility. RESULTS: One-third of trauma patients experienced delayed time to reach feeding goal after diet initiation. Delayed feeding was associated with prolonged intensive care unit (ICU) stays, increased readmission rates, and increased incidence of sepsis. Patients with elevated GRV (>500 mL) had significantly prolonged ICU and hospital stays and increase incidence of sepsis. Patients with >2 symptoms of slowed gastrointestinal motility had prolonged ICU and hospital stays, delayed time to reach feeding goals, significantly increased readmission rates, increased incidence of infectious and thromboembolic complications and sepsis, decreased serum prealbumin levels, and increased CRP levels. CONCLUSION: Decreased gastrointestinal motility in trauma patients is associated with worse outcomes and increased systemic inflammation.