CCFE - Center for Complex Fluid Engineering - Carnegie Mellon University

We are currently developing a microelectrical mechanical systems (MEMS) based acoustic-wave biosensing device. Our microgravimetric sensor device works by detecting the frequency shifts resulting from the selective binding of target molecules to the surface of a functionalized resonating polymer membrane. Each resonant membrane structures can be operated in a liquid environment for biological applications such as studying protein adsorption and measuring specific ligand-ligate binding events, DNA hybridization, and antibody-antigen interactions. Coupling MEMS technology with gravimetric detection allows for the fabrication and development of a light-weight, miniature, low cost, portable sensor which promises high sensitive due to its high surface area to mass ratio as well as eliminating the need for molecular tagging or expensive external optical equipment.	Figure 1: 4x4 suspended mesh array with surrounding bondpads which serve as a means to apply actuation voltages and measure output signals.
Figure 2: Detection of avidin-FITC via selective immobilization of PHB. We currently have the ability to create feature sizes on the order of 25 microns as well as having the capability to minimize the amount of non-specific adsorption.	The computer-aided design (CAD) of our MEMS microchip involves the layout of each mechanical mesh sensing structure along with the integrated electronic instrumentation and control elements. Each MEMS microchip consists of a 4x4 array of mesh structures. The mesh structures are 150 microns in length and can be electrostatically actuated by applying a voltage between the metal mesh and the underlying silicon substrate. Membrane oscillations are sensed via piezoresistors embedded in the mesh which responds to changes in stress within the resonating structure. Other key design features include: the ability to operate at higher harmonic frequencies, embedded multiplexer circuitry elements used for the electrical logic control of the output signals, and reference membranes which will be used to monitor the occurrence of non-specific molecular adsorption. The electrical coupling of a sensing membrane with a reference structure will enable a self-calibrating differential measurement to be performed.
Adaptation from MEMS microchip to a biosensing device has focused on: (a) modification of the metal oxide mesh with a conformal coating of polystyrene, (b) the photochemical functionalization of the polymer surface with immobilized biotin moieties capable of exploiting ligand-ligate specificity [2], (c) the incorporation of a reservoir for introduction of liquid phase samples to the membrane surface [1], and, (d) the locatization of binding patches on the membrane surface via computer-aided modeling to optimize device sensitivity and flexibility. The photochemical modification of the polystyrene structure using photobiotin (PHB) allows us to uniformly and covalently functionalize the resonant surface and enables the detection of specific target analyte molecules. Using a lithographic mask, this immobilization scheme provides a straightforward method to selectively and spatially deposit receptor molecules on the polymeric surface. This spatially selective functionalization scheme will increase device sensitivity and ultimately allow for simultaneous detection of multiple targets. Current work is focusing on characterizing the bending of the mesh structure through static deflection experiments and determining the structures resonant frequency through dynamic experiments.
[1] Bartkovsky, M.J. and Przybycien, T.M. and Neumann, J.J. and Hauan, S. A First Generation MEMS Membrane based Biosensor. AIChE annual meeting, paper 385e, 2003. [2] Bartkovsky, M.J. and Przybycien, T.M. and Hauan, S. Photochemical modification of a MEMS membrane device for use as a novel gravimetric based biosensor. AIChE annual meeting, Austin, TX, Advances in Biosensors I, paper 36g, 2004.