Rapid and simultaneous bacterial identification and antimicrobial susceptibility testing based on multidimensional optical and mass spectrometry imaging on microfluidic chip

Project: Research project

Project Details

Description

Antimicrobial resistance (AMR), a phenomenon where microbes become resistant to antibiotics, has become an imminent threat to global public health and the modern society. This natural phenomenon is greatly sped up by misusing of antibiotics in modern healthcare system where empirical prescription has been the norm. On the other hand, development of novel antibiotics stalls—it has been nearly 20 years since new types of antibiotics haven’t been developed. Therefore, preserving effective agents becomes a priority. Meanwhile, studies of the resistance mechanisms should also be accelerated, which would help the development of new antibiotics. Under these circumstances, it is important to carefully look into the situation, as well as the technologies that should help to prevent such a doomsday scenario.

Instead of empirical therapy, optimal treatment would require most suitable drug(s) to be given with the most appropriate dosage and duration. This can be achieved only if key information regarding the specific pathogen’s resistance to different drugs is obtained, like the minimal inhibition concentration (MIC). In microbiology, an MIC is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria, which could be obtained through antimicrobial susceptibility tests (AST). Nevertheless, AST is not widely adopted in practice because of the significant limitations of current methods, such as low speed and low efficiency.

Herein, we are aiming at developing a platform for bacteria investigation, which could not only fulfil the need of clinical AST but also be helpful to study the resistance mechanisms and develop new drugs. This platform is based on hydrogel microfluidic chips developed by our group, with MALDI-TOF imaging mass spectrometry (IMS) as downstream processing. While it is based on a microfluidic device, unconventionally, cells are cultured on the top of the device rather than inside the microchannels as others commonly did. This design make our platform more versatile and user friendly, and closer to current dish culture standard methods, e.g., it eliminates the problem of shear stress to channel-based cultures, and allow easy harvesting of cells. Our design allows reliable generation of stable linear gradient of drugs in 2D fashion. After simple sample treatment, AST of mixed culture can be carried out on this device. Different drug combinations can be tested simultaneously and will spatially separate the cultured bacteria into different regions on the culture surface on the basis of their differences in antimicrobial susceptibilities. This spatial separation could be regarded as a kind of isolation and makes it possible to couple with imaging mass spectrometry (IMS). Therefore, this platform hopes to develop a new paradigm of AST which can realize simultaneous polymicrobial AST and bacteria identification, and becomes a powerful weapon against AMR.

Our device can mimic a physiological environment by adjusting the media used to prepare and feed the devices. Meanwhile, it can support multi-bacteria on one chip and monitor the changes of bacteria growth affected by drug treatment or dynamic environment with the help of microscopic technologies and imaging mass spectrometry. The proposed system could serve to provide rapid and critical data on the infection of patients, which in turn would guide the prescription of antibiotics and promote prudent drug use in the clinical setting. This would not only improve the outcome of treatment for individual patients, but also lower the chance of bacteria developing resistance. The technology can also be used as an efficient, cost effective, and more importantly, reliable way to conduct large-scale screening for drug discovery.

StatusActive
Effective start/end date1/01/2130/06/24

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.