Considering drug discovery, since the golden era in the mid 1900's there has been a drastic decrease in the number of novel and useful compounds discovered from environmental samples. Furthermore, due to diminishing returns there has been even less success in discovering broad spectrum anti-microbial and anti-fungal compounds of clinical relevance. Although technology advancements in robotics have improved the process for finding novel compounds, financing conventional multi-well plate assays have become economically infeasible. Furthermore, new methods for drug discovery such as rational drug design, investigation of "unculturables", and next generation sequencing have shown promise, but lack the ability for robustly analyzing samples and churning out "hits". With the addition of resistant strains of bacteria/fungi, prevalence of new pathogens, and the natural evolution of these pathogens, we have found ourselves on the losing side of a war against virulent pathogens. In lieu of these facts, it is more pertinent than ever that we revolutionize and advance our methods for discovering and combating select agents before we reach a point of no return. In our pursuit for developing a large-scale versatile comprehensive fully integrated screening system, we have developed a Microfluidic Based High-throughput Analysis Platform for the Study of Polymicrobial Interactions, termed the Poly-chip. This highly complex fully integrated system is comprised of fundamental functionalities necessary for conducting continuous large volume-based screening assays for the discovery of novel compounds. Utilizing all prior capabilities exhibited in previous works and a novel process for fabrication and realization of an integrated bottom-up 16 to 21-layer Poly-chip screening system, the Poly-chip platform is a pivotal step toward revolutionizing the current state of drug discovery. With the integration of: on-chip droplet generation, large-volume bottom-up first-in first-out culture chambers, on-the-fly generation/synchronization, three-dimensional liquid metal injected electrodes for merging/shielding/sorting, multi-parallel culture chambers, on-the-fly laser based detection, high speed electric-field based sorting, a novel basket trapping structure, automated valve controls, and a comprehensive LabView-based graphical interface, the Poly-chip system is a ground breaking technology for the discovery of novel compounds. The Poly-chip system is not only the first fully integrated droplet microfluidic system, but integrating these functionalities improves the platform stability by eliminating the need for tubing which often leads to issues in droplet merging or splitting at the interface of adjacent devices. In addition, this full integration allows for the use of imbedded valves at each stage of operation, providing precise control of fluidic components and automated control using a graphical user interface (GUI). Considering that current conventional droplet screening assays are conducted on several tethered chips or conducted partially on-chip followed by conventional off-chip fluorescence-activated cell sorting, the Poly-chip is an innovative comprehensive platform with a novel fabrication process that can pave the way for future highly complex multi-layer droplet screening systems for a variety of applications.
