SUMMARY Pheromone responses are highly context-dependent. For example, the C. elegans pheromone ascaroside C9 (ascr#3) is repulsive to wild-type hermaphrodites, attractive to wild-type males, and usually neutral to “social” hermaphrodites with reduced activity of the npr-1 neuropeptide receptor gene. We show here that these distinct behavioral responses arise from overlapping push-pull circuits driven by two classes of pheromone-sensing neurons. The ADL sensory neurons detect C9, and in wild-type hermaphrodites, drive C9 repulsion through their chemical synapses. In npr-1 mutant hermaphrodites, C9 repulsion is reduced by the recruitment of a gap junction circuit that antagonizes ADL chemical synapses. In males, ADL sensory responses are diminished; in addition, a second pheromone-sensing neuron, ASK, antagonizes C9 repulsion. The additive effects of these antagonistic circuit elements generate attractive, repulsive or neutral pheromone responses. Neuronal modulation by circuit state and sex, and flexibility in synaptic output pathways, may permit small circuits to maximize their adaptive behavioral outputs.

A fabrication platform for realizing integrated microfluidic devices is discussed. The platform allows for creating specific microsystems for multistep assays in an ad hoc manner as the components that perform the assay steps can be created at any location inside the device via in situ fabrication. The platform was utilized to create a prototype microsystem for detecting botulinum neurotoxin directly from whole blood. Process steps such as sample preparation by filtration, mixing and incubation with reagents was carried out on the device. Various microfluidic components such as channel network, valves and porous filter were fabricated from prepolymer mixture consisting of monomer, cross-linker and a photoinitiator. For detection of the toxoid, biotinylated antibodies were immobilized on streptavidin-functionalized agarose gel beads. The gel beads were introduced into the device and were used as readouts. Enzymatic reaction between alkaline phosphatase (on secondary antibody) and substrate produced an insoluble, colored precipitate that coated the beads thus making the readout visible to the naked eye. Clinically relevant amounts of the toxin can be detected from whole blood using the portable enzyme-linked immunosorbent assay (ELISA) system. Multiple layers can be realized for effective space utilization and creating a three-dimensional (3-D) chaotic mixer. In addition, external materials such as membranes can be incorporated into the device as components. Individual components that were necessary to perform these steps were characterized, and their mutual compatibility is also discussed.

Resistive switching is observed in silver nitrate solution and synaptic behaviors are evaluated using liquid-based memory devices.

In situ liquid-phase photopolymerization (LP(3)) has been applied to the field of microfluidics to create components within integrated systems. As an extension of LP(3) technology, we present reconfigurable components that utilize the swelling of hydrogels. These components can be conveniently used to enhance microfluidic functions and applications. In order to utilize the swelling characteristic of hydrogels to the fullest, we demonstrate strategies to increase the swelling performance temporally and spatially. To this end, two successful applications using the reconfigurable components were tested: (1) active walls to block or divert flow at different steps in the fabrication or assay process, and (2) delivery pistons to move objects to specific locations within the microchannels after device fabrication.

The pressure required to drive flow through a microfluidic device is an important characteristic of that device. We present a method to measure the flow rate through microfluidic components and systems, including micropumps and microvalves. The measurement platform is composed of two pressure sensors and a glass tube, which provides series resistance. The principle of the measurement is the fluid dynamical equivalent of Ohm's law, which defines the relationship between current, resistance, and voltage that are analogues to flow rate, hydraulic resistance, and pressure drop, respectively. Once the series resistance is known, it is possible to compute the flow rate through a device based on pressure alone. In addition, the dynamic system characteristics of the device-resistance and capacitance-can be computed. The benefits of this method are its simple configuration, capability of measuring flow rate accurately from the more easily measured pressure, and the ability to predict the dynamic response of microfluidic devices.