Scalable high-throughput acoustophoresis in arrayed plastic microchannels.

Microfluidic acoustophoresis is a label-free technique that isolates a purified product from a complex mixture of cells. This technique is well-studied but thus far has lacked the throughput and device manufacturability needed for many medical and industrial uses. Scale-up of acoustofluidic devices can be more challenging than in other microfluidic systems because the channel walls are integral to the resonant behavior and coupling to neighboring channels can inhibit performance. Additionally, the increased device area needed for parallel channels becomes less practical in the silicon or glass materials usually used for acoustofluidic devices. Here, we report an acoustic separator with 12 parallel channels made entirely from polystyrene that achieves blood cell separation at a flow rate greater than 1 ml/min. We discuss the design and optimization of the device and the electrical drive parameters and compare the separation performance using channels of two different designs. To demonstrate the utility of the device, we test its ability to purify lymphocytes from apheresis product, a process that is critical to new immunotherapies used to treat blood cancers. We process a leukapheresis sample with a volume greater than 100 ml in less than 2 h in a single pass without interruption, achieving greater than 90% purity of lymphocytes, without any prepurification steps. These advances suggest that acoustophoresis could in the future aid in cell therapy bioprocessing and that further scale-up is possible.

Anticoagulant monitoring and neutralization during open heart surgery--a rapid method for measuring heparin and calculating safe reduced protamine doses.

Confident monitoring of heparin during cardiopulmonary bypass and subsequent neutralization by protamine has been hampered by the absence of an accurate, reproducible, rapid, simple, and specific assay for heparin. By using two new instruments in tandem, one of which produced 0.5 ml of plasma in 1 min and one which specifically measures heparin in 3-4 min, heparin levels are available in approximately 5 min. By performing heparin assays at a variety of intervals, it was demonstrated that 76% of patients receiving common doses of heparin during cardiopulmonary bypass may have plasma levels that are potentially too low. Minimum neutralizing doses of protamine may be calculated using the formula: (estimated blood volume + pump prime volume) X (plasma heparin level/100) X 1.1 + 50. These doses were nearly two-thirds of previous doses and were unassociated with increased bleeding, clotting, or clinically significant heparin rebound.