Awards were reserved for single major items of equipment that are at least $200K in total cost, with the expectation that proposals that exceed $600K must also include matching fund mechanisms for the remaining balance. Principal Investigators are also required to assume administrative and scientific oversight responsibility for the shared instrument and be prepared to develop a business plan for the operation and maintenance for the equipment that may involve a cost recovery or “user fee” system.

The ANH is proud to announce the winners of the ANH HEI program. The top two proposals were able to be funded thanks to generous matching-fund contributions from the University of Houston.

Principal Investigators:

Acquisition of Core Equipment to Support NanoHealth-Related Biomedical Research in the Greater Houston Area

Our long-term goal is to develop a core nanofabrication and nanosensing facility for translational biomedical research managed following the Good Manufacturing Practice (GMP) requirements set forth in the Quality System regulation promulgated under section 520 of the Food, Drug and Cosmetic (FD&C) Act. The objective in this grant application is to acquire 1) an Oxford Instruments Plasma Lab ICP (inductively coupled plasma) 180 RIE system for high-rate anisotropic etching of silicon, glass, silicon oxide, silicon nitride, and polymers and 2) a custom-designed NanoLog^® spectrofluorometer system for ultra-high-resolution spectroscopic assessment of nanomaterials and their bioconjugates. The rationale for this proposal is to gain a deep-etch and biosensing and biocharacterization capabilities for in vivo and in vitro drug delivery systems, Lab-on-chip, biofluidic separation, BioMEMS, high throughput multiplex sensing and characterization of macromolecules and proteins, and others. Our team is well-positioned to leverage the proposed instrumentation to enhance the existing research. The PI and ANH team members have extensive expertise in the areas of nanofabrication and nanomaterial research eras, optical imaging research, spectroscopic characterization of nanomaterials, extensive clinical and pre-clinical applications as well as a proven record of securing significant research funding. We propose the following Specific Aims:

Specific Aim #1: To purchase, install in the UH nanofabrication facility, and make available to the Alliance of NanoHealth scientific community (including instrument training) a deep reactive ion etching system.

Specific Aim #2: To purchase, install in the UH BMECRL facility, and make available to the Alliance of NanoHealth scientific community (including instrument training) a custom-designed NanoLog^® spectrofluorometer system enhanced with life-time measurement capability.

Specific Aim #3: To apply the acquired systems to enhance biomedical translational research conducted by the Alliance for NanoHealth members across all Houston research-intensive University including UTHSC, UTMB, BCM, Rice University, Texas A&M, MDACC, and UH.

The acquisition of the proposed instrumentations represents an effective approach to significantly boost the fabrication, characterization, and sensing capabilities available to the Alliance of the NanoHealth members. Significantly, it will enable, for the first time, such fabrication and biosensing capability not only in the Greater Houston, but also in the entire Texas academic community. The impact of the acquisition will be in considerable enhancement of biomedical translational research programs in the Greater Houston area spanning a wide spectrum of areas from drug delivery to rapid drug development to medical diagnostics to lab-on-a-chip applications to in vivo drug delivery systems.

Deep Reactive ion etching system

Schematic diagram of the DRIE.

Reactive Ion etching (RIE) is a dry etching process widely employed in semiconductor industry to remove thin film materials deposited on wafers. RIE uses chemical reactive plasma, generated under low pressure and by an electromagnetic field to physically ion-bombard and chemically react with the materials on substrates. In a typical RIE setting, a silicon wafer is grounded (cathode), and electrically isolated from the rest of the chamber. The reaction gas enters through the small inlets in the top of the chamber and exhaust exists to the vacuum pimp through the bottom. Different gas and flow rates can be adjusted depending on the etch process and applications.

Deep reactive ion etching (DRIE) is a highly anisotropic etch process used to fabricate deep, straight side-wall microstructures and trenches with the aspect ratio of 20:1 or higher. For semiconductors manufacturing, DRIE is often used to fabricate high aspect ratio trench for high-density capacitors for solid-state memory device and various sensors and actuators for micro electromechanical systems (MEMS). In DRIE, an RF powered magnetic field is used to generate high-density plasma (called inductive coupled plasma, ICP), which created directional electrical fields near the substrate to achieve more anisotropic etch profiles and higher etch rate. Two technologies, including Bosch process and cryogenic process, are mainly used for the protection of sidewall and to enable the fabrication of micro/nanostructures with vertical walls.

The Bosch process (or time multiplexed etching process) alternately repeat the process between etch/deposit modules: remove of substrate and passivation of a chemically inert material. During the etch phase, the directional ion will sputter the exposed surface in the bottom of the microstrucutres. Passivation layer is then coated and protects the side-wall from further etch. Each etch/depostion last for several seconds and are repeated many times.

In cryo-DRIE, the wafer is cooled down to -110 °C. The low temperature slows down the chemical reaction that produces isotropic etching. Ions continue to bombard the surfaces and etch them away to yields vertical sidewalls.

The requested Deep Reactive Ion Etching and surface profiling instrumentation will be a major addition to the infrastructure of the ANH and the University. The instrumentation will enable the fabrication and characterization of novel micro-nano building blocks in lab-on-chip, drug delivery system, biosensors, micro/nanoelectronics, photonic, and MEMS research programs, with strong focus on interdisciplinary research, education and applications in biomedical engineering. We expect the requested instrumentation will have broad impact to the research community at Greater Houston area.

High-resolution spectrofluorometer enhanced with life-time measurement capability

Brief schematic diagram of the proposed multimodality for spectroscopic characterization of nanomaterials.

NanoLog® spectrofluorometer (HoribaJobin Yvon Co) that is custom-designed for ultra-high-resolution spectroscopic assessment (spectroscopic resolution below 1 nm) of nanomaterials such as quantum dots, gold nanporticles and nanoshells, and carbon nanotubes is requested in this proposal. This instrument detects fluorescence in the near-IR from 800 to 1700 nm with visible and UV illumination. A complete spectrum can be scanned as fast as a few milliseconds, and a full excitation-emission matrix scan can be taken in as little as seconds. The system will be enhanced with the tunable femtosecond Ti:SAPP laser source (Coherent Co) allowing time-resolved spectroscopic analysis of the nanomaterials.

The acquisition of the enhanced spectrofluorometer represents an effective approach to dramatically improve nanocharacterization, fabrication, and biosensing capabilities at the Greater Houston area. For example, it will allow, for the first time, multiplex time-resolved detection and measurement of molecules and macromolecular structures in biofluids, labeled with nanoparticles, with high specificity and accuracy. One of our ongoing current projects involves investigation of mechanics and physics that underline Quantum Dots (QDs) – protein interactions using combination of analytical, computational and experimental knowledge bases. The attachment of macromolecules and other biological entities will manifest as changes of the surface energy and chemistry of nanoparticles, which in turn alters its band gap (and hence optical emission) through (i) surface energy induced strain---appreciable for small QDs and (ii) changes in surface electronic states. Our preliminary results indicates that surface energy induced strain effects can be significant for sub-5 nm QDs. Therefore, acquisition of the spectroscopic multimodality will be used for direct experimental verification and identification of unique fluorescent features of the coupled structures with high specificity and accuracy and will provide the basis for ultrasensitive biosensings of multiple macromolecules in tissues and blood available to ANH researches.

Cleanroom Core Facility

An array of nano- and microfabrication tools owned and recently acquired by the UH is being installed in the cleanroom facility including e-beam lithography, optical aligner, two reactive ion etching (RIE) systems, sputtering and thermal evaporation deposition systems, several wet-processing stations, etc. The facility is scheduled to open its doors to the Alliance for NanoHealth users in the fall of 2008. The University of Houston has allocated $200k per year for the next two years to support operational expenses in the start-up phase, which includes hiring of the cleanroom manager and a technician. The support will be reduced to $100k per year thereafter, when the user fees are expected to provide the remainder of the necessary operational funds. The users will be offered equipment training and ready access to all the tools on an hourly fee basis. The cleanroom will be run, including setting the policies and the fee structure, by the 4-5 member user committee (representing Alliance for NanoHealth institutions) headed by the Cleanroom Director (Dr. Dmitry Litvinov). The cleanroon facility will be home for the deep reactive ion etching system.

Biomedical Engineering Core Research Laboratory

The BioMedical Engineering Research Core Laboratory (BMERCL) is housed in Engineering Building-1, Room N-181 in the Cullen College of Engineering at the University of Houston. It is approximately a 2,000 square feet laboratory equipped with laboratory benches, a chemical fume hood, common equipment area and a separate autoclave room, cell culture room, microscope room, and radioisotope sample preparation room.

BMERCL will host the high-resolution spectrofluorometer system. BMERCL has adopted interactive Online Scheduling of BMERCL Equipment, as well as equipment availability through VNet. Users will be able to select a List or Calendar View for a given instrument to see available times. Once they have decided on an instrument and time slot, users can select the desired Instrument and schedule the usage time. All the policies regarding equipment-specific associated user fees has been currently developed for all core equipment and will be adapted to support maintenance of the requested high-resolution spectrofluorometer system (http://bmercl.uh.edu/index.html).