DIAG4AMR

Project description

Antibiotics overuse and broad-spectrum antibiotics misuse have placed antibiotic resistance at the forefront of the most pressing global health issues. In this context, prompt and accurate diagnosis facilitating personalised clinical management of infections to guide antibiotic choice is foreseen as a key driver toward a more effective treatment, protecting patients from antibiotics adverse effects, and dwindling antibiotic resistance. New diagnostics providing quick and accurate infection diagnosis, spanning from host-immune response assessment of pre-symptomatic patients, to pathogen-associated and antibiotic resistance biomarkers identification, and antibiotic levels monitoring, are urgently needed to efficiently support antibiotic stewardship.

DIAG4AMR aims to create a new class of diagnostic tools fit-for-purpose to mitigate challenges and technological gaps in diagnosis, dramatically reducing the time from infection onset to proper drug prescription. High-precision porous silicon and porous alumina fabrication methods, and advances in engineering surface functionalities will set up a tool-box of versatile nanoarchitectures with advanced properties to develop bespoke diagnostics. Advances in generating building blocks, built on or from porous nanostructures, assembled in hierarchical structures, with tuneable surface chemistry, and displayed bioreceptors and stimuli-responsive properties, are strongly intertwined with the materials functions. Gathering a better understanding of the relationship between nanoarchitecture/displayed functionalities, and function, is thus perceived as a key milestone in designing electrochemical sensors able to suit the diagnosis at each stage of the infectious disease by adjusting their properties to the application requirements, i.e. PoC for early diagnosis, monitoring for prognosis, or non-invasive analysis to support therapeutic guidance.

Specifically, DIAG4AMR aims to design: 1. Double-layer porous structures for the sequential quantification of various biomarkers in a single sensing platform, a breakthrough with critical impact on the acquired information. As proof-of-concept of the potential of this unique approach, two electrochemical biosensors will be developed to sequentially detect (a) exosomes and key exosomal miRNAs to support early diagnosis of pre-symptomatic patients, and (b) bacteria and their specific 16SrRNA growth markers to underpin pathogen identification. 2. Porous structures grafted with stimuli-triggered responsive polymers enabling electrochemical sensing mechanisms based on monitoring polymers conformational switch, to deal with ultralow analyte concentrations in complex biological samples. The potential of these sensing platforms to support therapeutic guidance will be demonstrated through the design and optimisation of a porous structure grafted with pH-responsive polymer brushes for the detection of carbapenemases, enzymes driving the main carbapenem-resistance mechanism. 3. Arrays of polymeric micropillars built as replicas from porous structures to be used for non-invasive on-skin diagnostics. Proof-ofconcept of therapeutic drug monitoring of antibiotics in sweat will be demonstrated using gold-coated micropillar arrays. Future validation of these diagnostic tools will place them at the center of a broader action plan, guided by medical and public health needs, to combine infection prevention and efficient antibiotic stewardship with diagnostics.