Biomedical Devices
Figure 1 shows some of the proposed applications of biomedical devices. Examples of projects in this area include: Nanocomposites for Implants and Tissue Engineering Scaffolds, Conjugates of Biomolecules and Nanoparticles or Conductive Polymers for Biosensors, Nanofluidic Diagnostic and Gene Therapy Devices, Nanofactory Assembly Line for Making Biomimetic Gene-Lipid Nanoparticles, CD-ELISA Biochips, and Biocapsules for Controlled Drug Delivery . Because of space limitations, we briefly describe only the first three projects.
(a) Nanocomposite Implants and Tissue Engineering Scaffolds One area that is particularly exciting for near-term commercialization of nanoengineered materials for biomedical applications is the substitution of CNT or other nanomaterials to enhance the performance of current biocompatible materials such as Teflon ® , polypropylene and carbon-carbon (C-C) composites. UD has demonstrated that the incorporation of CNF in a host matrix can dramatically improve mechanical and thermal properties for near-term applications. As a mid-term objective, nanostructured filters may be used to prevent blood clot-related deaths due to strokes, heart failure and phlebitis. The high-surface area filter may be implanted in a patient's circulatory system to break up coagulated blood (precursor to a clot) and avoid the formation of clots. Other applications that significantly impact the medical devices market include: facial implants (currently, C-C structures for facial implant do not allow growth of high-quality tissue; insertion of nanoelements into the structure can modify its surface texture and properties, leading to improved tissue growth); heart valves (C-C heart valves have limited useful life due to material chipping; the inclusion of CNT can enhance the valve mechanical strength and durability); hip and other bone implants (most hip replacements are made from a polymer, which wears too rapidly to be a lifetime replacement; the inclusion of CNT can increase the material's strength and lubricity leading to increased comfort and reduced need for replacement). In the long-term, we plan to develop nanoscaled tissue engineering at OSU and UA . ‘Nanofiber nests' produced by electrospinning of slowly biodegradable polymers can be easily formed into cylindrical vessels of almost any size for use as approximations of intestinal grafts. Following the alignment of vascular and intestinal smooth muscle cells in vitro , seeding of the appropriate endothelial cells on the nanofiber nest leads to the formation of 3D biomimetic neotissues ex vivo . Novel 3D scaffolds with biocompatible surfaces and well-defined micro- and nanoscale structures can also be produced using other low-cost polymer nanomanufacturing methods developed in the proposed Center. Dual RF inductively coupled plasma (ICP) technology has been used to deposit biocompatible carbon based films including diamond-like carbon. Diamond-like carbon (DLC) films are known to be smooth, hard, chemically stable, impermeable, and highly lubricating. Biocompatibility of DLC films has been established in non-blood-contacting applications in which a wear-resistant material is required. Several in vitro and in vivo studies have shown that DLC does not illicit a mutagenic response. This technology will be used in the preparation of wear resistant, biocompatible coatings for implantable devices (stents, knees, hips, etc.) and wear resistant, biocompatible coatings for instruments (knives, probes, etc.).
• Conjugates of Biomolecules and Nanoparticles or Conductive Polymers for Biosensors and Lab-on-a-Chips (LOCs) Low-cost and high-sensitivity biosensors and lab-on-a-chips are extremely important for future health care, homeland security and environmental protection. The commercially available biosensors and LOCs mostly rely on optical and radiation methods for detection, which are either too expensive or not sensitive enough for single molecule analysis. At OSU , we plan to use nanoparticles and conductive polymers developed in the other areas to form conjugates with biomolecules for advanced proteomic biosensing applications. One example is to develop micro-sensors based on protein-quantum dot conjugates to take the advantage of their high light-emitting intensity and high sensitivity due to quantum effects. The second example is an electric chemistry-based biosensor design using DNA doping of conductive polymers as the detection technique. This simple and novel design can eliminate the use of bulky and expensive fluorescence or UV detectors in today's genomic biosensors. At UD and UA, conducting polymer nanocontainers have been prepared using nanobubbles as a template for the electrodeposition of conducting polymers on flat conducting plates and aligned carbon nanotube electrodes. The use of the conducting polymer nanocontainers for encapsulation and controlled release of drugs will be explored. Biosensors are being developed, based on ligand-protein-nanofiber interactions that result in electrical signals through the nanofibers. The effects of various environmental factors (such as pH and temperature) on electrical signals and biorecognition are being determined. This technology will be used in the development of high performance electrical-signal-based biosensors for early detection of chemical or biological agents.
• Nanofluidic Diagnostic and Gene Therapy Devices The NSF nanobiotechnology center at OSU will develop a number of nanofluidics-based biomedical devices using functional polymers and nanocomposites. Polymeric materials are chosen because of their low-cost and good processibility for mass-production of disposable devices, and broad chemical, physical and biological properties for the necessary biocompatibility and biofunctionality. Three such devices are described below. A number of start-up biotech firms in Ohio such as BioLOC and iMEDD will work with us on device development and product commercialization, as well as Battelle.
Magnetic protein separator. Protein detection or separation typically uses intrinsic properties of proteins, i.e., size, charge and/or immunological binding to a matrix. Electro/magnetic forces, based on either intrinsic electric/magnetic properties of biomolecules or specific binding of an electro/magnetic carrier (micro- or nanoparticles), have been applied for separating large bodies such as cancer cells (5-10 m m). The same method is not effective for protein separation because of the weak electro/magnetic forces relative to Brownian (or thermal) forces of nano-sized molecules. A large increase in electro/magnetic forces can be achieved by decreasing the distance across the pole pieces of the electrode or magnet to 50-100 nm. A typical application of this passive method would be a simple, handheld device for the separation and detection of infectious prion proteins and molecular separation at high-throughput . Long nanochannel arrays made of disposable electro/magnetic conductive polymers are essential for clinical uses of this device. A design is shown in Figure 2.
Nanonozzle cell patch for low-invasive delivery of genes and macromolecular medicines into cells. Mechanical and electrical methods such as the gene gun and electroporation have been used to deliver genes or macromolecules into cells. However, they are highly invasive. Typical electroporation in cell cultures lyses 30-50% of the cell population. We propose a novel nanonozzle array cell patch made of biocompatible polymers. Genes and polymer-biomolecule conjugates experience electrophoretic stretching through converging channels located in the nanonozzles. We hypothesize that the stretched molecules can effectively permeate the cell membrane through reptation effects and their bioactivity may be retained when the molecules relax to their native coil size. Since the needles are much smaller than the cells, this method should be much less invasive than existing physical gene delivery methods. To facilitate gene delivery, moderate electroporation can be integrated with electrophoretic (EP) stretching by coating the outer surface of the cell patch with conductive polymers. The nanonozzle arrays and the device design shown in Figure 3 are suitable for this application.
Biomolecular nanopumps as synthetic ion channels. Ion channels play a crucial role in the transport of biofluids to and from cells. To keep cells functioning properly, a continuous flux of ions in and out of the cell and the cellular components is needed. The cell is surrounded by a negatively charged plasma membrane permitting selective transfer of ions via membrane protein channels. The protein channels are made up of a polypeptide chain with two polar regions connected by a nonpolar region that associates with the nonpolar region of the phospholipid membrane. Selectivity for transport of ions (e.g. Ca 2+ , Cl - , K + , Na + , H + , Mg 2+ , HCO 3 - , PO 4 2- ) and biomolecules may be achieved in synthetic ion channels or nanopumps by controlling a number of variables including size, charge and conformation of the biomolecule (e.g. a protein), the radius of the pore, and the induced charge on the wall(s) of the pore. The nanopump is effectively a flow device capable of delivering a wide variety of drugs. Because these devices are pumps, they can be used as rapid molecular screening devices capable of interrogating single molecules. Single DNA strands can be analyzed very quickly. Current density profiles can tell us the species and the amount of the biomolecule present. Rapid analysis (minutes ~ hours rather than days) of chemical and bioterrorism agents becomes possible. Nanochannels in this case need to be in the range of 5-50 nm.
Other Research Areas
