This proposal outlines a project geared toward the design of a microfluidic """"""""mouth-on-a-chip"""""""" system to study dental biofilm formation, a process associated not only with tooth decay, but also more serious systemic problems such as heart disease and organ failure if not kept under control through regimented oral hygiene. By varying the input oxygen/nitrogen ratio, sample flow rates, and the attachment substrate structure and composition (sealants, binders), the microfluidic chips will function as very powerful, inexpensive tools to study differential biofilm formation under a matrix of environmental conditions. Once validated, future research with the chips will focus on investigating mechanisms to disrupt the biofilm formation, including modification of the dental sealant composition, and the use of small molecule libraries to block intrabacterial interactions. ? ? ?