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.

Rapid prototyping and parametric optimization of plastic acoustofluidic devices for blood-bacteria separation.

Acoustic manipulation has emerged as a versatile method for microfluidic separation and concentration of particles and cells. Most recent demonstrations of the technology use piezoelectric actuators to excite resonant modes in silicon or glass microchannels. Here, we focus on acoustic manipulation in disposable, plastic microchannels in order to enable a low-cost processing tool for point-of-care diagnostics. Unfortunately, the performance of resonant acoustofluidic devices in plastic is hampered by a lack of a predictive model. In this paper, we build and test a plastic blood-bacteria separation device informed by a design of experiments approach, parametric rapid prototyping, and screening by image-processing. We demonstrate that the new device geometry can separate bacteria from blood while operating at 275% greater flow rate as well as reduce the power requirement by 82%, while maintaining equivalent separation performance and resolution when compared to the previously published plastic acoustofluidic separation device.

Nanomechanical motion of Escherichia coli adhered to a surface.

Nanomechanical motion of bacteria adhered to a chemically functionalized silicon surface is studied by means of a microcantilever. A non-specific binding agent is used to attach Escherichia coli (E. coli) to the surface of a silicon microcantilever. The microcantilever is kept in a liquid medium, and its nanomechanical fluctuations are monitored using an optical displacement transducer. The motion of the bacteria couples efficiently to the microcantilever well below its resonance frequency, causing a measurable increase in the microcantilever fluctuations. In the time domain, the fluctuations exhibit large-amplitude low-frequency oscillations. In corresponding frequency-domain measurements, it is observed that the mechanical energy is focused at low frequencies with a 1/fα -type power law. A basic physical model is used for explaining the observed spectral distribution of the mechanical energy. These results lay the groundwork for understanding the motion of microorganisms adhered to surfaces and for developing micromechanical sensors for bacteria.

Crossover from hydrodynamics to the kinetic regime in confined nanoflows.

We present an experimental study of a confined nanoflow, which is generated by a sphere oscillating in the proximity of a flat solid wall in a simple fluid. Varying the oscillation frequency, the confining length scale, and the fluid mean free path over a broad range provides a detailed map of the flow. We use this experimental map to construct a scaling function, which describes the nanoflow in the entire parameter space, including both the hydrodynamic and the kinetic regimes. Our scaling function unifies previous theories based on the slip boundary condition and the effective viscosity.

The "low-dose" concept and the paradoxical effects of prolactin on grooming and sexual behavior.

The effects of prolactin on animal behavior include the stimulation of novelty-induced grooming in rats. This effect has been demonstrated in hyperprolactinaemic animals bearing pituitary homografts under the kidney capsule or after intracerebroventricular (i.c.v.) administration of prolactin. Since plasma prolactin levels in hyperprolactinaemic rats are similar to those of animals injected with low doses of rat prolactin, we studied the effects of this hormone injected subcutaneously (s.c.) in a dose range of 5-50 microg/kg. Novelty-induced grooming was enhanced only in rats injected with 5 or 10 microg/kg rat prolactin, whereas no effect was observed after the s.c. injection of the higher dose. The sexual behavior of male rats is also affected by prolactin. Male rats with normal mating activity showed enhanced sexual behavior when injected s.c. with rat prolactin (5, 10 or 50 microg/kg). In animals with poor sexual performance or in impotent rats, prolactin (5 or 10 microg/kg, but not 50 microg/kg) restored the full pattern of sexual behavior. An increased lordosis quotient was also observed in ovariectomized rats treated with prolactin 5 or 10 microg/kg. These results suggest that, besides the duration of hyperprolactinaemia, the effective level of plasma prolactin is important for the expression of the behavioral effects of this hormone.