In many neural culture studies, neurite migration on a flat, open surface does not reflect the three-dimensional (3D) microenvironment in vivo. With that in mind, we fabricated arrays of semiconductor tubes using strained silicon (Si) and germanium (Ge) nanomembranes and employed them as a cell culture substrate for primary cortical neurons. Our experiments show that the SiGe substrate and the tube fabrication process are biologically viable for neuron cells. We also observe that neurons are attracted by the tube topography, even in the absence of adhesion factors, and can be guided to pass through the tubes during outgrowth. Coupled with selective seeding of individual neurons close to the tube opening, growth within a tube can be limited to a single axon. Furthermore, the tube feature resembles the natural myelin, both physically and electrically, and it is possible to control the tube diameter to be close to that of an axon, providing a confined 3D contact with the axon membrane and potentially insulating it from the extracellular solution.
Accurate and fast enumeration of large, combinatorial search spaces presents a central conceptual challenge in molecular design. To address this challenge, an algorithm is de®eloped that guarantees globally optimal solutions to a mixed-integer nonlinear programming formulation for molecular design. The formulation includes no®el structural feasibility constraints, while the algorithm pro®ides all feasible solutions to this formulation through the implicit enumeration of a single branch-and-reduce tree. This algorithm is used to pro®ide the complete solution set to a refrigerant design problem posedelsewhere. In addition to redisco®ering CFCs, the proposed methodology identifies a number of no®el potential replacements of Freon 12.
High-throughput screening of ion channels is now possible with the advent of the planar patch clamp system. This system drastically increases the number of ion channels that can be studied, as multiple ion channel experiments can now be conducted in parallel. However, due to tedious, usually pressure-driven mechanotransduction techniques, there has been a slow integration of this technology into the field of mechanosensitive ion channels. By implementing a piezoelectric quartz substrate into a planar patch clamp system, we show that the patch clamp substrate itself can be used to mechanically actuate ion channels. The piezoelectric substrate transduces an external, applied electric field into a mechanical tension, so precise actuation of the membrane can be accomplished. By applying this electric field only to the outer edges of the substrate, no ulterior electric field is created in the vicinity of the membrane during actuation. Further, with resonant frequencies ranging from 1 kHz to 200 MHz, quartz substrates can be used to apply a wide range of time-varying tensions to cell membranes. This will allow for new and instructive investigations into the dynamic mechanotransductive properties of ion channels.
We report on a novel method of using an excimer laser to drill ultra-small pores in borosilicate glass membranes. By introducing a thin layer of liquid between sandwiches of two glass slides, we can shrink the pore size and smoothen the surface on the exit side. We are able to push the minimal exit pore diameter down to 90 nm, well below the laser wavelength of 193 nm. This is achieved with substrates over 150 microm thick. Compared to other methods, this technique is fast, inexpensive, and produces high quality smooth pores.
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