This paper reviews the interdisciplinary work performed in our group in recent years to develop micro-integrated devices to characterize biological entities. We present the use of electrical and mechanically based phenomena to perform characterization and various functions needed for integrated biochips. One sub-system takes advantage of the dielectrophoretic effect to sort and concentrate cells within a micro-fluidic biochip. Another sub-system measures impedance changes produced by the metabolic activity of cells to determine their viability. A third sub-system is used to detect the mass of bacteria as they bind to micro-mechanical silicon cantilevers. These devices with an electronic signal output can be very useful in producing practical systems for rapid detection and characterization of cells for a wide variety of applications in the food safety and health diagnostics industries.

Characterization of electrical activity of individual neurons is the fundamental step in understanding the functioning of the nervous system. Single cell electrical activity at various stages of cell development is essential to accurately determine in in-vivo conditions the position of a cell based on the procured electrical activity. Understanding memory formation and development translates to changes in the electrical activity of individual neurons. Hence, there is an enormous need to develop novel ways for isolating and positioning individual neurons over single recording sites. To this end, we used a 3x3 multiple microelectrode array system to spatially arrange neurons by applying a gradient AC field. We characterized the electric field distribution inside our test platform by using two dimensiona l finite element modeling (FEM) and determined the location of neurons over the electrode array. Dielectrophoretic AC fields were utilized to separate the neurons from the glial cells and to position the neurons over the electrodes. The neurons were obtained from 0-2-day-old rat (Sprague-Dawley) pups. The technique of using electric fields to achieve single neuron patterning has implications in neural engineering, elucidating a new and simpler method to develop and study neuronal activity as compared to conventional microelectrode array techniques.

The surface functionalization of ultrananocrystalline (UNCD) thin films has been investigated to develop biocomposite materials for use as BioMicroElectroMechanical Systems (BioMEMS). Specifically, hydrophobic, hydrogen-terminated UNCD films have been synthesized using a microwave plasma chemical vapor deposition technique then surface functionalized using a two-step modification procedure. This procedure produces a mixed submonolayer comprised of chloro- and hydroxyl- terminated alkyl chains chemisorbed to the UNCD surface. This surface modification procedure serves to provide functional groups that will allow for the subsequent attachment of a wide variety of biological macromolecules (e.g., proteins, biomembranes) and the ability to tune the hydrophilic nature of the diamond. The resultant materials have been characterized using surface-sensitive spectroscopies (NEXAFS and XPS).

Microfabricated microfluidic devices provide useful platforms for sensing and conducting immunoassays for high throughput screening and drug discovery. Here, Fluorescence Polarization has been used as a technique for probing binding events within 500 micron and smaller microfluidic channels fabricated in poly (dimethyl siloxane) (PDMS). The binding of concanavalin A to a lectin-dextran and a glycoproteinacetylcholinesterase has been used to demonstrate the homogeneous, ratioing format of fluorescence polarization for the quick and accurate determination of extremely low (nanomole) concentrations. Polarization has also been used to sense for a poly-aromatic hydrocarbon (PAH) within a microfluidic channel using binding to an antibody. We have also demonstrated a simple pH sensor based on the change in anisotropy of a pH sensitive fluorophore. The ease of fabrication and measurement using such polarization-based devices make them extremely suitable for micro-sized sensors, assays and total analysis systems.

In view of the superior bio-compatibility of amorphous carbon (a-C) films, a study has been carried out on the fabrication and simulation of free-standing amorphous carbon microcantilevers. The fabrication of micro-structure was carried out by a single photolithography step. A 1.7micro-meter thick, low stress, smooth (Rrms ∼0.75nm) a-C films were deposited by filtered cathodic vacuum arc deposition (FCVA) system, in conjunction with high substrate pulse biasing on patterned n-doped Si >100< substrates. Subsequently, the photoresist was lifted-off in acetone and which is followed by undercutting of the cantilever structures in 40% KOH solution. The deflection of the free-standing cantilever structures was measured using an optical profiler, and the stress in the a-C cantilever structures was independently calculated from the deflection of the cantilever beam and the total tilt angle. This stress value is compared with the stress in the film measured from the film-substrate sandwich by radius of curvature technique. Simulation of the cantilever assembly was carried out to obtain the deflection and stress distribution. The simulated parameters are compared with the experimental results.

The development of sophisticated endoscopic tools and the recent introduction of robotics are expanding the applications of minimally invasive surgery. The lack of tactile feedback in the currently available endoscopic and robotic telemanipulation systems however represents a significant limitation. A need has arisen for the development of surgical instruments having integrated sensors. Current efforts to integrate sensors into or onto surgical tools has focused on fabrication of sensors on silicon, polyimide, or some other substrate and then attaching the sensors to a tool by hand or machine with epoxy, tape, or some other glue layer. Attaching the sensor in this manner has certain deficiencies. In particular, this method of attaching sensors to a surgical tool limits the sensors size, increases its thickness, and further constrains where the sensor can be placed. A method of fabricating tactile sensors on surgical instruments that addresses these deficiencies is discussed.