The Maryland Biochip Collaborative

The goal of our research is to enlist molecular bioengineering to "translate" the communication between biological and microfabricated systems in a manner that embraces the fragility of biology. Our overarching objective is to exploit the recognition and self-assembly capabilities found in biological systems for fabrication.

Nanobiotechnology advocates promote an exciting vision: "nanofactories" that patrol your bloodstream in search of diseases that they can safely arrest. They also envision "smart" microdevices that modulate proteins, cells, and tissues for testing complex biological interactions, or that manufacture designer molecules for personalized medicine.

Biology has a lot to offer to the field of nanobiotechnology: it provides an array of components that can detect (receptors), manufacture (enzymes), and maintain blueprints (DNA) for these components. It also provides devices for assembly (ribosomes) and energy transduction (ATPases) and mechanisms to self-assemble these devices through a hierarchy of structure. Signal transduction processes enable their control. Biology also provides self-contained units (cells) and inter-dependent communities (tissues and biofilms), and it enables their self-replication.

Microfabrication is also crucial: it is capable of generating devices by localizing components of ever-decreasing size. Microfabricated devices can be constructed for near-instantaneous signal processing: to impose stimuli, to detect response, and to transmit information. Microfabricated systems can be of immense complexity, where optical, electrical, magnetic, pneumatic and fluidic systems are all integrated "on-chip" to enable high-throughput massively-parallel operation.

Biology and microfabrication offer complementary capabilities in receiving, processing and transmitting information, and many have predicted that the effective interfacing of biology and microfabrication will enable remarkable advances in medicine, industry and national security. But there is a problem: while both biological and microfabricated systems are expert at receiving and transmitting signals, their communication is often incompatible because they communicate using different "languages."

Microfabricated devices traditionally communicate through electron flow or, more recently, by the transmission of light. Biological systems communicate using ions and small molecules. Moreover, biohybrid devices must be manufactured recognizing the labile nature of their biological components. The goal of this research is to enlist molecular and cellular bioengineering to "translate" the communication between biological and microfabricated systems in a manner that embraces the fragility of biology.

The goal of our research is to enlist molecular bioengineering to "translate" the communication between biological and microfabricated systems in a manner that embraces the fragility of biology.

The traditional method 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). Often, devices are constructed using 2D lithographic techniques where the insertion of biological components into the devices limits design flexibility. The shelf-life of these systems is dictated by the most labile biological component.

We are pursuing a more flexible codesign paradigm in which biological elements are used in the fabrication of the devices and become functional components. 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, in both the means by which materials and devices are fabricated and the components of the subsequent product that can be found in nature. We offer this view of fabrication as a transformational process.

We propose to demonstrate the creation of "biofunctionalized" devices" in which proteins, cells, and cell populations are interrogated on-board and moved between locations based on measured biological responses. We will do so by the systematic study of a complex cell-to-cell communication system that has emerged as a determinant of bacterial pathogenicity. The study of this system requires complex architectures that can be modeled, validated, and that feature biological elements controlled by embedded systems within microelectromechanical systems (MEMS). We will use electrical signals to assemble a two-enzyme biosynthetic pathway, electrical and magnetic signals to recruit cells to specific registries, and optical and mechanical signals to guide cell function and characterize phenotype"“all within prepackaged microfabricated devices.