We describe the fluidFM, an atomic force microscope (AFM) based on hollow cantilevers for local liquid dispensing and stimulation of single living cells under physiological conditions. A nanofluidic channel in the cantilever allows soluble molecules to be dispensed through a submicrometer aperture in the AFM tip. The sensitive AFM force feedback allows controlled approach of the tip to a sample for extremely local modification of surfaces in liquid environments. It also allows reliable discrimination between gentle contact with a cell membrane or its perforation. Using these two procedures, dyes have been introduced into individual living cells and even selected subcellular structures of these cells. The universality and versatility of the fluidFM will stimulate original experiments at the submicrometer scale not only in biology but also in physics, chemistry, and material science.
Quantum structures made from epitaxial semiconductor layers have revolutionized our understanding of low-dimensional systems and are used for ultrafast transistors, semiconductor lasers, and detectors. Strain induced by different lattice parameters and thermal properties offers additional degrees of freedom for tailoring materials, but often at the expense of dislocation generation, wafer bowing, and cracks. We eliminated these drawbacks by fast, low-temperature epitaxial growth of Ge and SiGe crystals onto micrometer-scale tall pillars etched into Si(001) substrates. Faceted crystals were shown to be strain- and defect-free by x-ray diffraction, electron microscopy, and defect etching. They formed space-filling arrays up to tens of micrometers in height by a mechanism of self-limited lateral growth. The mechanism is explained by reduced surface diffusion and flux shielding by nearest-neighbor crystals.
A microchip-based flow confinement method for rapid
delivery of small sample volumes to sensor surfaces is
described. For flow confinement, a sample flow is joined
with a perpendicular makeup flow of water or sample
medium. Under laminar flow conditions, the makeup flow
confines the sample into a thin layer above the sensing
area and increases its velocity. This can benefit mass
transport limited processes such as DNA hybridization
or heterogeneous immunoassays. For proof of concept,
this method was applied to a high-affinity immunoassay
with excess capture antibody. Rabbit IgG was immobilized
onto a silicon nitride waveguide. Cy5-labeled anti-rabbit
IgG was hydrodynamically pumped over the immobilized
zone through an attached 3D-PDMS flow cell with 20-μm-deep microchannels. The degree of confinement was
adjusted through the volume flow rate of the confining
flow. Evanescent field-based fluorescence detection enabled monitoring of the binding event. Assays were
allowed to reach equilibrium to enable sensorgram normalization for inter-run comparison. The corresponding
assay completion times could be reduced from 55 min
for static drop conditions to 13 min for 25:1 flow confinement (ratio of confining to sample flow). For typical
analytical applications, where equilibrium formation is not
required, the faster response should translate to very
short analysis times. Concurrently with the faster binding,
sample consumption was reduced by 96% compared to
conventional whole-channel sample delivery. Diffusional
loss of analyte into the confining layer was identified as
the main limitation of flow confinement, particularly for
long sensing pads.
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