Micro-fabricated perforated polymer devices for long-term drug delivery.

Fabrication techniques have been developed to produce a perforated polymer microtube as a drug delivery device. The technique consists of first forming a silicon platform with trenches and alignment marks to hold the tubes for subsequent processing. Photolithography and reactive ion etching with an inductively coupled plasma source were used to fabricate micro holes on the surface of polyimide tubes. Several materials have been used to form the etching mask, including titanium film deposited by e-beam evaporation and SiO(2) and SiN(x) films deposited by high-density plasma chemical vapor deposition (HDPCVD). Three equidistant holes of 20 µm in diameter were fabricated on polyimide tubes (I.D. = 125 µm). The perforated tubes were loaded with ethinyl estradiol and tested for drug release in phosphate buffered saline (pH = 7.1) at 37°C. Zero order release was observed over a period of 30 days with a potential to be extended to 4 years.

Development and characterization of a scalable microperforated device capable of long-term zero order drug release.

A drug delivery system that consists of microperforated polyimide microtubes was developed and characterized. Two groups of polyimide tubes were used. One set consisted of microtubes (I.D. = 125 microm) with 32.9 +/- 1.7 microm size holes. The second set consisted of larger tubes (I.D. = 1000 microm) with 362-542 microm holes. The number of holes was varied between 1 and 3. The small tubes were loaded with crystal violet (CV) and ethinyl estradiol (EE) and the drug release studies were performed in 0.01 M phosphate buffered saline (PBS) (pH 7.1-7.4) at 37.0 +/- 1.0 degrees C for upto 4 weeks. The large tubes were loaded with CV and the drug release was studied in vitro in PBS and also ex vivo in rabbit's vitreous humor. Linear release rates with R(2) > 0.9900 were obtained for all groups with CV and EE. Release rates of 7.8 +/- 2.5, 16.2 +/- 5.5, and 22.5 +/- 6.0 ng/day for CV and 30.1 +/- 5.8 ng/day for EE were obtained for small tubes. For large tubes, a release rate of 10.8 +/- 4.1, 15.8 +/- 4.8 and 22.1 +/- 6.7 microg/day was observed in vitro in PBS and a release rate of 5.8 +/- 1.8 microg/day was observed ex vivo in vitreous humor.

Controlled formation and resistivity scaling of nickel silicide nanolines.

We demonstrate a top-down method for fabricating nickel mono-silicide (NiSi) nanolines (also referred to as nanowires) with smooth sidewalls and line widths down to 15 nm. Four-probe electrical measurements reveal that the room temperature electrical resistivity of the NiSi nanolines remains constant as the line widths are reduced to 23 nm. The resistivity at cryogenic temperatures is found to increase with decreasing line width. This finding can be attributed to electron scattering at the sidewalls and is used to deduce an electron mean free path of 6.3 nm for NiSi at room temperature. The results suggest that NiSi nanolines with smooth sidewalls are able to meet the requirements for implementation at the 22 nm technology node without degradation of device performance.

Fabrication and characterization of patterned single-crystal silicon nanolines.

This letter demonstrates a method for fabricating single-crystal Si nanolines, with rectangular cross sections and nearly atomically flat sidewalls. The high quality of these nanolines leads to superb mechanical properties, with the strain to fracture measured by nanoindentation tests exceeding 8.5% for lines of 74 nm width. A large displacement burst before fracture was observed, which is attributed to a buckling mechanism. Numerical simulations show that the critical load for buckling depends on the friction at the contact surface.

Nano-opto-mechanical characterization of neuron membrane mechanics under cellular growth and differentiation.

We designed and fabricated silicon probe with nanophotonic force sensor to directly stimulate neurons (PC12) and measured its effect on neurite initiation and elongation. A single-layer pitch-variable diffractive nanogratings was fabricated on silicon nitride probe using e-beam lithography, reactive ion etching and wet-etching techniques. The nanogratings consist of flexure folding beams suspended between two parallel cantilevers of known stiffness. The probe displacement, therefore the force, can be measured through grating transmission spectrum. We measured the mechanical membrane characteristics of PC12 cells using the force sensors with displacement range of 10 mum and force sensitivity 8 muN/mum. Young's moduli of 425 +/- 30 Pa are measured with membrane deflection of 1% for PC12 cells cultured on polydimethylsiloxane (PDMS) substrate coated with collagen or laminin in Ham's F-12K medium. In a series of measurements, we have also observed stimulation of directed neurite contraction up to 6 mum on extended probing for a time period of 30 min. This method is applicable to measure central neurons mechanics under subtle tensions for studies on development and morphogenesis. The close synergy between the nano-photonic measurements and neurological verification can improve our understanding of the effect of external conditions on the mechanical properties of cells during growth and differentiation.