Harvard Offers License for Universal Platform for Drug Delivery Via Vertical Silicon Nanowires

Vertical silicon nanowires as a universal platform for highly efficient delivery of bioactive molecules into living cells have been developed by Harvard scientists Hongkun Park,  Marsela Jorgolli, JinSeok Lee, Jacob Robinson, Alex Shalek, Amy A Sutton,  EunGyeong Yang, and Myung-Han Yoon and are offered for license by the University Office of Technology Development.

This platform consists of an array of surface-modified vertical silicon nanowires that have been chemically grown or etched on a wafer and to which virtually any kind of bioactive species (drug, protein, nucleic acid, nanoparticles) may be attached by covalent or electrostatic means. When cells are plated on the surface of the array, they are penetrated by the functionalized nanowires, and the bioactive material is thus efficiently delivered into the cytosol of the cells. Since the cells remain viable after penetration, the effects of the delivered material on the cells can be monitored over time.

Existing strategies for delivering exogenous materials into cells (e.g., viral vectors, physio-chemical means, or microinjection) are limited either by the range of chemical and biological species that each can deliver, or by the efficiency or throughput of the delivery. While there have been previous efforts to use nanostructured materials to introduce bioactive species into cells, they too have been inefficient and generally limited to the delivery of genetic material.

The potential to deliver a wide range of molecules at sites of one’s choosing lends itself to a broad variety of implementations, including the following:

1. Massive, parallel screening for drug discovery: the cellular effects of many proteins (proteomics), siRNAs (knockdown efficacy), and small molecules (drug/antibiotic resistance) may be assayed simultaneously, either singly or in combinations; by perturbing different elements of a particular cellular pathway, the causal relationships between those elements can be discovered.

2. Cell-based ADME/Tox assays: the concentration-dependent effects of a particular protein, drug, and/or combinations can be studied in cell-based assays.

3. Derivation of induced pluripotent stem (iPS) cells: the platform is suitable for efficiently delivering (and discovering) molecules capable of reprogramming adult cells into iPS cells.

4. Designer cell networks and disease models: the platform can be used to construct complex cellular systems, such as synaptic pairs of differentially perturbed neurons for modeling neurodegenerative diseases.

5. Assays of epigenetic factors: the platform could be used to discover molecules that usefully affect the differentiation and development of any set of cells (e.g., stem cells, iPS cells, or differentiated tissues), and then further used to generate cells of a particular lineage for use in cell-based therapies.

By optimizing the cell-nanowire interface through the use of novel surface chemistry and the precise control over nanowire density, diameter, and height, investigators in the laboratory of Chemistry and of Physics Professor Professor Hongkun Park at Harvard University have created a platform suitable for delivering a wide range of materials (including small molecules, nanoparticles, siRNAs, and proteins) into living cells in a highly efficiently, massively parallel, arrayed fashion. There are three general steps involving to implement the procedure:

1. The nanowires are fabricated by either growing them from a precursor material on the surface of a patterned substrate, or by etching the structures out of a substrate material from the top down.

2. The surface of the nanowires is then chemically treated to facilitate their electrostatic linkage to the compound of interest. (Covalent linkage strategies may also be employed.)

3. The compound of interest is then tethered to the nanowire by pipetting a few uLs of a solution containing the compound atop the nanowires. Microarraying techniques may also be used for the multiplex deposition of an assortment of molecular species. Once the solvent evaporates, the nanowire wafer may be used immediately or stored until needed.

4. Cells are then plated on the nanowire surface. As they settle, they are impaled by the wires (typically within an hour) and the electrostatically linked agent detaches from the wires and is thus released into the cell cytosol.

This single platform has been shown to be able to deliver small molecules, nanoparticles, RNAs, peptides, and proteins, into a number of primary and clonal cell with an efficiency greater than 95%. It should be noted that the Park laboratory has been able to mass-produce the wires on six-inch silicon wafers using a technique that could easily be implemented by any semiconductor foundry. The high-throughput, low-cost production of these silicon wafer arrays using widely available semiconductor processing should enable the wide adoption and rapid commercialization of this technology.

Intellectual Property Status: A patent application is pending.

Publications:

"Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells," A. Shalek, J. T. Robinson, E. S. Karp, J. S. Lee, D-R. Ahn, M-H. Yoon, A. Sutton, M. Jorgolli, R. S. Gertner, T. S. Gujral, G. MacBeath, E. G. Yang, H. Park, submitted (2009).

For further information, please contact:

Bob Benson, Director of Business Development

(617) 496-3830

Email: robert_benson(at)harvard.edu, Harvard Reference: 3211

Taiwan Scientists Use Nanoparticles to Solve Lifetime Problem for Dye-Sensitized Solar Cells

Atomic Energy Council - Institute of Nuclear Energy Research (Taoyuan, TW) scientists have fabricated a longlife Dye-Sensitized Solar Cell using nanoparticles of InN(indium nitride)/TiO2 (titanium oxide) to create a novel photosensitized electrode. It is comprised  of an indium tin oxide (ITO) substrate, a TiO2 film and an InN photosensitive layer.   The photosensitized electrode can be fabricated at a low cost and with long lifetime in a solar cell device with enhanced absorbing ability.  The solar cell is an InN/TiO2 photosensitized electrode, where a lifetime issue of the dye for a Dye-Sensitized Solar Cell (DSSC) is solved; an optical absorption efficiency is enhanced; a production procedure is simplified; and a production cost is reduced to 1/5 to 1/10 of current manufacturing processes, say inventors Ming-Chang Lin, Yen-Chang Tzeng, Shan-Ming Lan, Yuan-Pern Lee, Wei-Guang Diau, Tsong-Yang Wei, Jyh-Perng Chiu, Li-Fu Lin, Der-Jhy Shieh and Ming-Chao Kuo in U.S. Patent 7,622,397.

The substrate can also be a fluorine tin oxide (FTO) glass or other transparent conductive substrate.  The TiO2 film has a nanoparticle structure, where nanoparticles are evenly distributed in the  film and where each nanoparticle has a diameter between 7 nm (nanometer) and 50 nm. The TiO2 film has a thickness between 100 nm and 100,000 nm and is made of a metal oxide with a high band-gap.  The InN photosensitive layer is made through a chemical vapor deposition (CVD), a physical vapor deposition (PVD) or other epitaxial film growth method. The InN photosensitive layer is coated on the TiO2 film. The InN photosensitive layer has a thickness between 1 nm and 10000 nm. When a light penetrates through the substrate of the photosensitized electrode into the photosensitive layer, an electron is injected into the TiO2 film from the InN photosensitive layer and then the electron is conducted to an outside circuit from the substrate, where the InN photosensitive layer absorbs an optical wavelength between 390 nm and 800 nm.

FIG 2. shows a simplified schematic for production of Dye-Sensitized Solar Cell developed at Taiwan's Institute of Nuclear Energy Research.

Step (a): A substrate coated with a TiO2 film is placed into a reaction chamber  where the TiO2 film is coated on the substrate through a CVD or a PCD.

Step (b): A hydrazoic acid (HN3) and a compound containing indium  is introduced into the reaction chamber 2, where the ratio of HN3 to the compound containing indium is between 1 and 10. The compound containing indium is a trimethylindium, a triethylindium, a indium-containing metallo-organic precursor or a combination of indium-containing metallo-organic precursors. The process uses the HN3 and the compound containing indium as precursors; and the HN3 can be replaced with a compound containing nitrogen.

Step (c) The substrate is then illuminated with an ultraviolet (UV) light, where the UV light is obtained from a continuous UV lamp, an excimer laser, a semiconductor laser, a gas laser, a solid-state laser, a liquid laser, a chemical laser or a free-electron laser, and where the TiO2 film bears a temperature between 600.degree. C. (Celsius degree) and 900.degree. C.

Step (d): An InN photosensitive layer is obtained on the TiO2 film. Thus, an InN photosensitized electrode is obtained through the above steps, where the total process time is between 1 hr and 8 hr.

Ciba Specialty Reveals Process to Improve Polymers with Nanoclays

Ciba Specialty Chemicals Corporation (Tarrytown, NY) developed cationic alkoxyamines as polymerization initiators/regulators in a controlled stable free radical polymerization process to produce intercalated and/or exfoliated nanoparticles from natural or synthetic clays. The process results in improved nanocomposites and nanocomposite compositions for use in paints, inks, coatings, sealants, caulks, adhesives, reactive diluents and as plastic additives for thermoplastic materials, according to U.S. Patent 7,595,359.

One way of improving polymer properties is by adding a natural or synthetic clay material to polymers to form composite materials. However, incorporating clays into polymers may not provide a desirable improvement in the physical properties, particularly mechanical and optical properties of the polymer may be adversely affected. Nanocomposite compositions containing finely dispersed natural or synthetic clay with at least partially intercalated and/or exfoliated layers and mixtures of ethylenically unsaturated monomers and/or polymers have attracted much interest in recent years. According to Ciba inventors Andreas Muhlebach, Peter Nesvadba and Andreas Kramer, nanoclay materials combine the desired effects of dispersed clay bu avoid the negative influence on the mechanical or optical properties. The nanocomposite compositions can be optically almost transparent, indicating the fine distribution, on the nanometer scale, of the clay.

Ciba provides alkoxyamines, which can be anchored to natural or synthetic clays by a cationic anchor group and which have a high reactivity towards acrylates, methacrylates, styrene and other monomers resulting in a controlled molecular weight with narrow molecular weight distribution. With these compounds polymerization leads to high monomer to polymer conversions in short times and at relatively low temperatures. In contrast to conventional radical polymerization, controlled radical polymerization permits the adjustment of the molecular weight of all growing chains almost uniformly to a predetermined length (low polydispersity), resulting in an almost ideal dispersion of the intercalated and/or exfoliated clay particles.