A Cellular Array of Three Dimensional Mono- and Polymicrobial Biofilms for High-throughput Drug Discovery and Diagnostics

The development of new antibiotics faces the long and arduous process of drug discovery, in which the search typically begins with High-Throughput Screening (HTS). In HTS, in vitro assays involving libraries of thousands or even hundreds of thousands small molecules are tested to identify "Hits" or effective biomolecules that affect a particular biological process. Unfortunately, the current methods of conventional drug discovery using classical microbiological culture techniques are not compatible with hunger for speed.

Addressing these issues and quenching the thirst of HTS for a rapid screening platform we have developed a chip-based cellular array of single and polymicrobial, nano-scale biofilms of C. albicans, S. aureus and P. aeruginosa; as a model organisms for fungi, gram positive and gram negative bacteria respectively. Briefly, a robotic arrayer will be used to print single or co-culture of microorganisms, with a suitable media and synthetic hydrogel matrix onto a surface-modified glass slide which upon incubation leads to biofilm formation. An array of 1200 identical spots of nano-biofilms can be printed on a microscopic glass slide, making the chip-based platform a "truly" high-throughput screen. Compared to current industry standards (namely the 96-well microtiter plate model of biofilm formation), this biofilm chip has advantages in terms of miniaturization and automation, which combine to cut reagent use and analysis time, minimize or eliminate labor intensive steps, and dramatically reduce assay costs. Such a chip will speed up the drug discovery process by enabling rapid, convenient and inexpensive screening of hundreds-to-thousands of compounds simultaneously.

On the diagnostic front, we have developed a lab-on-a-chip high-throughput platform for rapid detection of antimicrobials that are effective in treating skin and soft-tissue infections; caused by community-acquired Staphylococcus aureus. The High-Throughput-Antimicrobial Susceptibility Testing Chip (HT-ASTChip) is rapid, robust and culture-independent. We believe that the results obtained using this universal platform will ameliorate the prescription of empirical antibiotic therapy.