This paper presents a picoliter sample preparation technique utilizing the flow-through principle, allowing on-line coupling of chromatographic systems to be made. The work was performed in order to investigate the characteristics and the physicochemical properties of the sample preparation using typical mobile phase conditions from µ-CLC (column liquid chromatography) separations. The device presented here is a pressure pulse-driven dispenser, formed by two silicon structures processed by conventional micromachining. The pressure pulse is generated in the flow-through channel by a piezoceramic element. Depending on the orifice size, the droplets ejected range between 30 and 200 pL. The maximum ejection frequency is 500 Hz, limited by resonances within the unit. A pyramid-shaped nozzle improves the directivity of the droplets since it reduces the wetting of the orifice front surface area. The risk of particles sticking close to the orifice is also minimized. The analyses of the deposited sample spots were carried out on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer with delayed extraction. It was possible to detect attomole amounts (159-248 amol) of various proteins (cytochrome c, ribonuclease A, lysozyme, and myoglobin) from a single droplet of matrix:analyte 1:1 (drop volume ≈ 110 pL). Additionally, it was found that sample enrichment could be carried out using multiple depositions on the same spot; i.e., 31 nM of insulin was easily detected when more than four depositions were made on the same spot, while no detection was possible without sample enrichment. Size optimization of the MALDI sample spot gave target zones of 100-500-µm diameter that matched the size of the laser focal point and resulted in a considerably increased sample throughput.

The development of a piezoactuated flow-through microdispenser is described. The dispenser can be used for on-line sampling in a continuous-liquid-flow system. A major application area is rapid sample handling in chemical microsystems, e.g. automated high-throughput analysis or screening systems. The microdispenser is constructed of two joined silicon structures forming a flow-through channel. One channel wall couples the impulse movement of a piezoceramic element into the flow channel, generating a pressure pulse. Droplets (of typically 100 picolitres) are ejected from an orifice in the opposite channel wall. The sequential improvements of the dispenser over three generations are presented. The actuation voltage could be lowered from 150 V to approximately 50 V. The final version of the dispenser had an internal volume of 2.6 microlitres. The impact on droplet stability and directivity of introducing a protruding p-n etch-stop-defined nozzle and a means of matching surface properties to the dispensed liquid for improved performance are discussed. The maximum frequency for stable droplet formation was found to be approximately 500 Hz.

The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.

We present an electrode, based on structurally controlled nanowires, as a first step towards developing a useful nanostructured device for neurophysiological measurements in vivo. The sensing part of the electrode is made of a metal film deposited on top of an array of epitaxially grown gallium phosphide nanowires. We achieved the first functional testing of the nanowire-based electrode by performing acute in vivo recordings in the rat cerebral cortex and withstanding multiple brain implantations. Due to the controllable geometry of the nanowires, this type of electrode can be used as a model system for further analysis of the functional properties of nanostructured neuronal interfaces in vivo.