NanoCarbaOne - Nano-Structured Sensors for Rapid Point-of-Care Detection of Carbapenemase-producing Bacteria (ERA4Health JTC4)

Antibiotic resistance is a growing global health crisis, particularly with carbapenems, which are often the last line of defense against tough bacterial infections. The rapid spread of carbapenem-resistant bacteria, especially in hospitals, is alarming. Current methods to detect these resistant bacteria are slow and complex. To address this, a group of researchers within NanoCarbaOne, are developing a new diagnostic device that can quickly and accurately detect these resistant bacteria directly from clinical samples. This device uses advanced electrochemical sensors and microfluidics technology to identify key enzymes and their activity, providing crucial information for treatment and infection control. The goal is to eventually create a portable, point-of-care tool that is fast, reliable, and environmentally sustainable, helping to manage and control the spread of antibiotic-resistant infections more effectively in different settings. This innovation has the potential to positively impact healthcare and contribute to the greater social good by mitigating the impact of antibiotic resistance.

Growing resistance to carbapenems, last-line antibiotics for infections caused by multidrug-resistant bacteria, poses a main global health challenge. Of major concern is the rapid spread of carbapenem-resistant Enterobacterales (and other Gram-negatives), increasingly prevalent in the clinical setting. Carbapenem resistance (CR) mainly relies on the production of carbapenem-hydrolysing ß-lactamases, enzymes encoded by plasmids that show high transferability, enabling the widespread transmission of CR. Therefore, there is a critical need for diagnostics to detect carbapenemase-producing bacteria quickly and accurately. Unlike current phenotypic and genotypic methods to detect CR, the diagnostics proposed here will promptly quantify key carbapenemases and total carbapenemase activity directly in clinical samples, providing pivotal information to guide therapy and infection control practices, the latter via regular screenings in outbreak situations, CR carriers and areas with CR prevalence. Specifically, we aim to: - design a point-of-care device combining dispersible sensors to pre-concentrate bacteria, and an array of nano-structured sensors, within a microfluidics chip; - test the device with purified carbapenemases; - and validate its analytical and clinical performance with 1) bacterial isolates of known CR phenotypes, and 2) CR-positive blood, urine and rectal swab samples. The ultra-sensitivity and high specificity, expected by confining the sensing event into the sensing nano-environment, are paramount to escape cell culturing, reduce the analysis time (<15 min), and suppress false negatives. To support technology translation, the sustainability of the materials and their processing will be designed from inception to minimise environmental impact and ease future regulatory endorsement. Key stakeholders leading research and technology development in antimicrobial susceptibility testing, will be engaged as part of the project’s advisory board.