(5am) Nanoengineering Systems for Targeted Drug Delivery, Cell-Based Therapy, and Microfluidic Biosensors/Chips

Many characteristics of polymers and ease of processing make them attractive for various biomedical applications. Proper combination of functional polymers and a number of manufacturing modules can offer tailored properties for sophisticated technologies used in targeted drug delivery, cell-based therapy, and microfluidic biosensors/chips.

1. Multifunctional delivery systems for oral and implant administrations

Many protein- and DNA-based drugs need to be properly protected and precisely controlled during administration. A robust manufacturing protocol has been developed to produce particulate-like polymeric devices based on functional hydrogels to achieve multi-functionalities, such as drug protection, self-regulated oscillatory release, enhanced mucoadhesion and targeted unidirectional release. The delivery devices will be of great benefit to the advancement of oral administration of existing therapeutic agents. A nanoporous miniature device made of biodegradable poly(lactide-co-glycolide acid) (PLGA) has also been designed based on the integration of a number of micro-manufacturing modules, such as phase inversion, a sacrificial template nano-imprinting, and carbon dioxide (CO2) -assisted bonding. The biocompatibility, biodegradation, and release performance of this device have been evaluated in animal studies. Such devices are able to enhance the bioavailability of existing therapeutic and provide a continuous, pre-designed release profile within the local tumor environment, potentially without the need for surgical implantation.

2. Cell-based delivery systems by micro-/nanofabrication

Cell-based delivery devices holds great promise for applications requiring site-specific and sustainable drug delivery of cell-synthesized molecules. On the other hand, embryonic stem (ES) cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. An integration of ES cells within immunoprotective and biodegradable devices will provide great potential for novel delivery platforms. Our recent work focus on the development of nanoporous PCL-based chambers for immunoisolation of embryonic stem cells. A series of advanced techniques such as composite membrane preparation by phase inversion, surface coating by plasma polymerization, and nitrogen (N2) -assisted bonding, have been combined to improve the device functionalities. Studies described herein also include the interactions of PCL-based substrates with differentiated ES cells in terms of viability, proliferation, and functionality.

3. Design and evaluation of microfludic biochips for Enzyme-Linked Immunosorbent Assay (ELISA)

A polymeric microfluidic biochip has been designed and fabricated for enzyme-linked immunosorbent assays based on the integration of manufacturing modules: polyaniline-based surface modification, the conceptual design with splitters, and the oxygen plasma-PEI-TR protein A modification. The proper flow sequencing was achieved on a CD-like microfluidic chip by integrating the necessary microfluidic functions such as capillary valving treated with polyaniline-based surface modification. It has been successfully demonstrated that the splitters indeed work very well to even distribution of the fluid to branch flows. To enhance the sensitivity of miniature detection area on the PMMA biochips for ELISA immunoassay, a TR-catalyzed protein A antibody immobilization technique was successfully developed. By treating the PMMA surface with this method, not only the antibody binding efficiency, but also the specific capture capacity towards target protein of the antibody was greatly enhanced, leading to a significant improvement of the fluorescence signal ELISA in PMMA chips. The microfluidic biochips we developed here would be applicable to a variety of clinically relevant disease conditions. And the modification technologies in this study can be extensively implemented in lab-on-a-chip systems, drug/gene delivery carriers and other immunoassay biosensor applications.