Client: Targanta Therapeutics
Overview:
The alarming growth of antibiotic-resistant superbugs such as methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, are driving the development of new antibiotics and new technologies to investigate these antibiotics and their modes of action. Researchers affiliated with the Bio Nano Consulting (BNC) have spearheaded the development of the label-free detection of antibiotic-mucopeptide interactions using cantilever arrays, achieving 100 pM sensitivity. In previous work, differential measurements by BNC-associated scientists have quantified binding constants for vancomycin-sensitive mucopeptides and vancomycin-resistant analogues. This technique is now being made available on a commercial basis for the assessment of drug-target interaction for a broad range of other antibiotics and drugs under development.
Nanomechanical Sensors:
Nano-cantilevers are thin (<10µm) strips of silicon which have been manufactured to extremely tight tolerances using techniques from the microchip industry. These can be set up in arrays to allow a number of analytes to be detected at the same time. Each cantilever is functionalised with particular surface coatings (that is, with ligands that bind specifically to a target a analyte).
These highly-sensitive biosensors operate by detecting minute changes of the in-plane surface forces (surface stress) when the drug binds specifically to ligands tethered on a cantilever. The nano-cantilevers can also be operated in the dynamic mode where it has been shown that the added mass of single bacterium can be detected through a change in resonance frequency.
Benefits of this technique:
- Cantilevers require no sample labelling, enabling rapid, single step detection of bio-molecules.
- Cantilever arrays can screen multiple drug-target interactions in parallel at the same time.
- Quantitative ligand-receptor binding constants can be measured on cantilever arrays.
- The nanomechanical signal is not limited by mass, in contrast to other techniques.
- By virtue of their miniaturized dimensions they are portable for point-of-care diagnostics and also amenable to parallelization for high throughput screening applications.