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Micro and Nano Systems
 
(Faculty Participants: S. Bhansali, L. An, V. Bhetanabotla, A. Malik, S. Samson, J. Kapat, S. Hoath, R. Smallwood, M. Rahman, T. Weller, S. Hariharan, R. Schlaf )
 
We propose to develop, model, test and validate multiple MEMS based approaches to facilitate data collection from the skin and facilitating the development of a seamless transfer system between the MEMS systems and the skin that will enable this exchange. We plan to focus on the following tasks:
 
Development of multifunctional multimode sensors for characterization of cells and tissue
 
Processes and protocols for reliable and repeatable fabrication of (a) microelectrode sensor arrays and (b) micro needle arrays will be investigated. Techniques to fabricate two MEMS based electrical cell analyzers (one semi-invasive and one noninvasive) to measure the bio-impedance profile of individual cells in the skin will be developed using Coherent Porous Si/DRIE and metallization techniques. The ability to differentiate between different layers of the skin as function of both the frequency of the signal and the electrode spacing and electrode depth will be explored. Microneedle arrays will be optimized for penetration into the tissue. The needle array chip will be designed to allow integration of novel electrodes, sensors, and fluidic components to ensure reliable sensor coupling. Modular design approaches that ensure that while the integrated system functions, each sub-system is fully functional independently will also be explored. The electronics, information processing and interfacing issues relevant to this task are discussed in the ASIC and information processing and, bio-interfaces section.
 
Non silicon based MEMS fabrication methodologies for biomedical applications
 
The fundamental research will focus on (i): development of multi-functional polymers and polymer-derived ceramics for bio-MEMS. The approach is based on recently developed chemical-precursor technique that converts a liquid polymer precursor to fully dense Si-based ceramic. Materials and structures developed will be evaluated for both their bio and chemical compatibility and tuned to get the desired properties by designing the precursors needed at the atomic level resulting in designer materials for target applications. (ii) development of micro-stereolithography (m-SL) techniques for the fabrication of MEMS with complex 3-D structures. Techniques to develop complex MEMS structures with multiple materials using photopolymerizable liquid phase polymer precursors will be developed. The basic idea is to repeat the stereolithography step for different precursors prior to the cross-linking and pyrolysis steps.
 
Sol-Gel hybrid organic-inorganic polymeric materials for on-line preconcentration and separation of analytes from skin-environment interface
 
Sol-gel advanced materials can be used either as surface coatings or porous monolithic beds in micro chromatographic columns and/or channels of microfluidic devices. Both sample preconcentration and separation functions will be integrated within the microfluidic channel. The microchannels containing sol-gel stationary phases will be used as a means for preferential enrichment of ultra trace concentrations of target analytes followed by their analysis using capillary/channel electrophoresis (for charged analytes), capillary/channel electrochromatography or electrochemistry based sandwich immunoassays.
 
Analysis of micro- and nano-scale thermo-fluid transport in human-skin smart biological interface
 
We will develop (a) fluid flow and Heat Transfer Models (b) analytical solutions (c) numerical solutions and (d) conduct parametric studies for the processes that occur on the skin/sensor interface: Viz: (1) Thermal transport between the micro sensors and the skin, (2) Fluid flow and heat transfer processes underneath the skin and within the human body that determine the boundary conditions at the outer layer of the skin, (3) Fluid flow and heat transfer in microchannels, and the microfluidic components of the microsystem. (4) Mixing of different fluids, their transport, and thermal cycling in BioMEMS and (5) Thermal radiation and transpiration at the skin surface. The outcome of this task will be the mathematical representation of biophysical processes, which has yet not been accomplished.
 
Electrochemical Sensors
 
We plan to develop an integrated sensor array capable of detecting ions, properties of fluids and dissolved gases that are collected from the skin (from sweat to interstitial fluids). Some of the analytes we plan to detect are pH, Na+, K+, O2, CO2 and NH3. We plan to investigate the development of integrated modular sensor array that uses polymeric membranes, gas permeable membranes and specialty glasses over ion selective microelectrodes to enhance detection limits and improve response times.
 
Acoustic Wave Biosensors
 
Our objective is to produce TSM and SH-SAW biosensors for analyte detection (small molecular or ionic) and for immunoassay coupled to the skin by microfluidics. Specific tasks are: Sensitive TSM device fabrication: The TSM sensor typically operates at 5-20 MHz and is not competitive in sensitivity to some optical sensors. Sensitivity is proportional to at least the square of the operating frequency. Higher fundamental frequencies imply thinner, more fragile plates (typically, quartz). The alternative of working with overtones suffers from attenuation of harmonic resonances, and only a linear increase in sensitivity. The alternative of thinning the central area of a quartz plate (by ion beam or chemical milling) to produce a thick, mechanically stable outer ring with a thinner, higher frequency center area, has been tried by others and shown to produce higher sensitivity. We plan to develop macroscopic (first) and MEMS TSM devices of frequencies up to 100+ MHz by chemical milling. Coatings for analyte detection and immunoassay: Help of the other team members will be utilized in selecting specific immunoassay coatings, and ion selective polymer coatings will be considered for ionic concentration measurements. Sensor system characterization: The fabricated TSMs of various higher frequencies will be characterized in specific analyte and immunoassay applications for sensitivity gains, signal to noise, and stability. Influence of the fluid mechanics of the FIA system will also be investigated. MEMS fabrication: The TSM sensor and FIA components appear amenable to MEMS fabrication techniques. A miniature sensor will be attempted after the above studies.
 
Nanoscale systems and processing
 
We will focus on the investigation of the molecular interaction between functionalized magnetic particles (ferrofluidic core polystyrenes) and their specific target molecules. The goals are to determine the selectivity and the strength of the interaction. Atomic force microscopy (AFM) combines sub-nanometer spatial resolution with a force sensitivity in the nN range. This enables AFM to measure the interaction between single molecules. The AFM probe tip will be coated with functionalized particles by dipping a ferromagnetic AFM probe into a thin film or solution of the magnetic spheres. Spin coating of the target molecules of interest, on the other hand, allows creating matching target molecule model systems for the investigation of the selectivity of the functional ligands. AFM force curves will allow quantifying the strength of the interaction. We will use lithographic techniques to create samples with target molecule patterns.
 
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