IMPORTANCE Prokaryotes are social organisms capable of coordinated group behaviors, including the abilities to construct antibiotic-resistant biofilms and to communicate with small signaling molecules (quorum sensing [QS]). While there has been significant effort devoted to understanding biofilm formation and QS, few studies have examined these processes in high-density/low-cell-number populations. Such studies have clinical significance, as many infections are initiated by small bacterial populations (<105) that are organized into dense clusters. Here, we describe a technology for studying such bacterial populations in picoliter-sized porous cavities (referred to as bacterial “lobster traps”) capable of capturing a single bacterium and tracking growth and behavior in real time. We provide evidence that small changes in the size of the bacterial cluster as well as flow rate of the surrounding medium modulate QS in Pseudomonas aeruginosa. We also demonstrate that as few as ~150 confined bacteria are needed to exhibit an antibiotic-resistant phenotype similar to biofilm bacteria.