Microfluidic Platform for Rapid, Low-cost, High-Throughput, Automated Test of Antimicrobial Susceptibility

Antimicrobial resistance (AMR) is a natural phenomenon developed in microorganisms, and is accelerated by misuse of antibiotics. AMR makes the treatment difficult, costly, or even impossible, thus is causing major health threat as well as enormous financial loss worldwide. Hong Kong also faces serious issues of AMR.

Two strategies are effective in addressing AMR issue: (1) use narrow-spectrum antibiotics based on accurate diagnosis, preferentially, using antimicrobial susceptibility test (AST); (2) develop new antibiotics. However, both strategies are challenged by the lack of effective and affordable method to test the response of target microorganisms to drug administration. An AST involves a large number of tests, especially when the minimum inhibitory concentration (MIC) of each drug is desired. Current ASTs are based on observing cell-growth, which is costly, time-consuming, and incapable of dealing with fastidious microorganisms. Similar challenge exists in the drug development which requires large-scale screening. Tremendous efforts have been made to improve AST technology; however, those new strategies, based on PCR, nanoparticles, or dielectrophoresis, are still impractical to be used for real specimens.

Herein we propose a microfluidic platform which could have major contribution to addressing the aforementioned challenges. We are developing a fundamentally new strategy to detect the response of microorganisms to drug treatment, using single-cell- level evidences such as morphological and surface-chemical changes, which arise way before the change of cell population could be detected at macro scale using conventional method. Not relying on proliferation, this method also facilitates study of fastidious organisms and “hard-to-detect” resistance mechanisms. The device will be made of a new material, Teflon, which addresses two major challenges in drug-loaded on-chip culture. Also, the system supports high-throughput operation without massive manipulation such as pipetting, thereby improving the reliability of the assay. Moreover, a special detection scheme will realize fully-automatic data-acquisition without sophisticated instrument (such as microscope) or technician labor; this will help release the system to real market.

Through this project, we expect an inexpensive, user-friendly but quick and reliable method to benefit the control of AMR. As our method is designed to allow maximum accessibility, the broad range of clinics currently could not afford AST would be able to conduct routine test. At the mean time, the unique platform will allow us to obtain important new knowledge about the mechanism of AMR development. Finally, the platform could be implemented to drug discovery and other applications where similar tool is sought for.