Biofunctionalized Devices - On Chip Signaling and Rewiring Bacterial Cell-Cell Communication

1. Biofunctionalized Devices - On Chip Signaling and "Rewiring" Bacterial Cell-Cell Communication William E. Bentley, PI, University of Maryland Reza Ghodssi, Co-PI, University of Maryland Gregory Payne, Co-PI, University of Maryland Gary Rubloff, Co-PI, University of Maryland

2. Project Description:The target of this research is the cell-cell communication system mediated by bacterial signaling autoinducers in a process known as �quorum sensing�. We will engineer pathway enzymes with �pro-tags� to allow their activatable assembly onto specified locales within microfluidic channels in response to localized electrical signals (left). Cell-based sensors will be engineered to recognize the products of this pathway, reprogram themselves, and transmit optical signals that will be detected and transmitted through on-chip optical waveguides (middle). Magnetic and electrical signals will drive on-board actuators (switches, valves) that will serve to guide protein synthesis and cell phenotype (morphology and pili formation, right).

3. Expected Transformative Benefits The traditional motivation for integrating biological components into microfabricated devices has been to create biosensors that meld the molecular recognition capabilities of biology with the signal processing capabilities of electronic devices (e.g. DNA microarrays). This theme is not new. Often, devices are constructed using 2D lithographic techniques where the insertion of biological components into the devices limits design flexibility. Furthermore, the shelf-life of these systems is dictated by the most labile biological component. We are pursuing a flexible codesign paradigm in which biological elements are used in the fabrication of the devices and become components of the functional device. This is accomplished by prefabrication of a completed microfluidic device followed by on-demand, programmable insertion of functional biological entities at specific locations to serve the biotechnology application. In this vision, there is promise to dramatically expand the role of biohybrid devices in our society. Our overarching objective is to exploit the recognition and self-assembly capabilities found in biological systems for fabrication. Both (1) the means by which materials and devices are fabricated and (2) the components of the subsequent product can be found in nature. We offer this view of fabrication as a transformational process

4. Overall managementPI � BentleyAdvisory Committee (1-day formal mtg): Dr. Nimish Dalal of Bristol Myers Squibb  Dr. Nicole Bleckwenn of MedImmune  Dr. Tsu-shun Lee of Sanofi Pasteur Dr. Thomas K. Wood of Texas A&M Dr. Ray Adomaitis of the University of MarylandMeetings. We schedule monthly meetings of the full group � faculty, postdocs, and students � and to highlight specific topics through two feature presentations and discussion following them. Asynchronous updating. Asynchronous communication of results and emerging issues is a critical challenge to sustain progress in such a program. While keeping up to date with student progress in individual and group meeting, we increasingly use a regular reporting system, particularly the posting of Powerpoint summaries by each student on a regular basis (e.g., semimonthly). Students and postdocs will post regular dated updates to a central location and send a notification to others that they have done so. Data sharing. We will use our existing and emerging communications and data sharing methods to achieve efficient, effective interactions for the highly cross-disciplinary, integrated research program proposed here. The team currently relies mainly on a dedicated Blackboard site for managing information within its Deutsch Foundation program in next-generation biochips for antimicrobial drug discovery, which supports threaded discussion, file and data sharing, group email, etc. In addition, the Maryland NanoCenter (directed by Rubloff, see www.nanocenter.umd.edu ) has established additional information sharing mechanisms. One is the EZ File Exchange, a file upload/download facility on the NanoCenter�s intranet which enables users to establish password-protected accounts at will, create folders, and share even large files within them.