Ultrastructural brain abnormalities and associated behavioral changes in mice after low-intensity blast exposure.

Explosive blast-induced mild traumatic brain injury (mTBI), a "signature wound" of recent military conflicts, commonly affects service members. While past blast injury studies have provided insights into TBI with moderate- to high-intensity explosions, the impact of primary low-intensity blast (LIB)-mediated pathobiology on neurological deficits requires further investigation. Our prior considerations of blast physics predicted ultrastructural injuries at nanoscale levels. Here, we provide quantitative data using a primary LIB injury murine model exposed to open field detonation of 350 g of high-energy explosive C4. We quantified ultrastructural and behavioral changes up to 30 days post blast injury (DPI). The use of an open-field experimental blast generated a primary blast wave with a peak overpressure of 6.76 PSI (46.6 kPa) at a 3-m distance from the center of the explosion, a positive phase duration of approximate 3.0 milliseconds (ms), a maximal impulse of 8.7 PSI × ms and a sharp rising time of 9 × 10-3 ms, with no apparent impact/acceleration in exposed animals. Neuropathologically, myelinated axonal damage was observed in blast-exposed groups at 7 DPI. Using transmission electron microscopy, we observed and quantified myelin sheath defects and mitochondrial abnormalities at 7 and 30 DPI. Inverse correlations between blast intensities and neurobehavioral outcomes including motor activities, anxiety levels, nesting behavior, spatial learning and memory occurred. These observations uncover unique ultrastructural brain abnormalities and associated behavioral changes due to primary blast injury and provide key insights into its pathogenesis and potential treatment.

3D hydrodynamic focusing microfluidics for emerging sensing technologies.

While the physics behind laminar flows has been studied for 200 years, understanding of how to use parallel flows to augment the capabilities of microfluidic systems has been a subject of study primarily over the last decade. The use of one flow to focus another within a microfluidic channel has graduated from a two-dimensional to a three-dimensional process and the design principles are only now becoming established. This review explores the underlying principles for hydrodynamic focusing in three dimensions (3D) using miscible fluids and the application of these principles for creation of biosensors, separation of cells and particles for sample manipulation, and fabrication of materials that could be used for biosensors. Where sufficient information is available, the practicality of devices implementing fluid flows directed in 3D is evaluated and the advantages and limitations of 3D hydrodynamic focusing for the particular application are highlighted.

Two simple and rugged designs for creating microfluidic sheath flow.

A simple design capable of 2-dimensional hydrodynamic focusing is proposed and successfully demonstrated. In the past, most microfluidic sheath flow systems have often only confined the sample solution on the sides, leaving the top and bottom of the sample stream in contact with the floor and ceiling of the channel. While relatively simple to build, these designs increase the risk of adsorption of sample components to the top and bottom of the channel. A few designs have been successful in completely sheathing the sample stream, but these typically require multiple sheath inputs and several alignment steps. In the designs presented here, full sheathing is accomplished using as few as one sheath input, which eliminates the need to carefully balance the flow of two or more sheath inlets. The design is easily manufactured using current microfabrication techniques. Furthermore, the sample and sheath fluid can be subsequently separated for recapture of the sample fluid or re-use of the sheath fluid. Designs were demonstrated in poly(dimethylsiloxane) (PDMS) using soft lithography and poly(methyl methacrylate) (PMMA) using micromilling and laser ablation.

Target delivery in a microfluidic immunosensor.

A study is presented that examines the effect of microfluidic mixing elements on direct and sandwich assays performed in microchannels. Patterned grooves were embossed in the top of microchannels made in PDMS using soft lithography. The grooves redirected the fluid flowing in the channel, enhancing delivery of the target from the bulk fluid to the surface and preventing the formation of a depletion layer at the surface. Comparing assays in grooved and plain channels demonstrated that the mixers improved assay results by 26-46%. A computational flow analysis showed that the grooves caused virtual particles in the bulk flow to come close to the surface ( approximately 11 microm) which is consistent with the signal increase seen experimentally. Direct assays for several concentrations of CY5-labeled biotin were performed in the microchannels. The mixers also improved signal intensity in sandwich assays for botulinum toxin which required mixing of the reagents as well as the direction of the target to the surface.

Toolbox for the design of optimized microfluidic components.

A computational "toolbox" for the a priori design of optimized microfluidic components is presented. These components consist of a microchannel under low-Reynolds number, pressure-driven flow, with an arrangement of grooves cut into the top and bottom to generate a tailored cross-channel flow. An advection map for each feature (i.e., groove of a particular shape and orientation) predicts the lateral transport of fluid within the channel due to that feature. We show that applying these maps in sequence generates an excellent representation of the outflow distribution for complex designs that combine these basic features. The effect of the complex three-dimensional flow field can therefore be predicted without solving the governing flow equations through the composite geometry, and the resulting distribution of fluids in the channel is used to evaluate how well a component performs a specified task. The generation and use of advection maps is described, and the toolbox is applied to determine optimal combinations of features for specified mixer sizes and mixing metrics.

A microfluidic mixer with grooves placed on the top and bottom of the channel.

A new microfluidic mixer is presented consisting of a rectangular channel with grooves placed in the top and bottom. This not only increases the driving force behind the lateral flow, but allows for the formation of advection patterns that cannot be created with structures on the bottom alone. Chevrons, pointing in opposite directions on the top and bottom, are used to create a pair of vortices positioned side by side. Stripes running the width of the channel generate a pair of vertically stacked vortices. Computational fluid dynamics (CFD) simulations are used to model the behavior of the systems and provide velocity maps at cross-sections within the mixer. Experiments demonstrate the mixing that results when two segregated species enter the mixer side-by-side and pass through two cycles of the mixer (i.e., two alternating sets of four stripes and four chevrons).

Design and evaluation of a Dean vortex-based micromixer.

A mixer, based on the Dean vortex, is fabricated and tested in an on-chip format. When fluid is directed around a curve under pressure driven flow, the high velocity streams in the center of the channel experience a greater centripetal force and so are deflected outward. This creates a pair of counter-rotating vortices moving fluid toward the inner wall at the top and bottom of the channel and toward the outer wall in the center. For the geometries studied, the vortices were first seen at Reynolds numbers between 1 and 10 and became stronger as the flow velocity is increased. Vortex formation was monitored in channels with depth/width ratios of 0.5, 1.0, and 2.0. The lowest aspect ratio strongly suppressed vortex formation. Increasing the aspect ratio above 1 appeared to provide improved mixing. This design has the advantages of easy fabrication and low surface area.