Samadhan B. Patil, Manuel Vögtli, Ben Webb, Giuseppe Mazza, Massimo Pinzani, Yeong-Ah Soh, Rachel A. McKendry and Joseph W. Ndieyira
London Centre for Nanotechnology, Division of Medicine and Department of Physics and Astronomy, University College London, United Kingdom
HIV and bacterial infections are affecting the wellbeing and quality of life of millions of people each year worldwide. Even so, the road map to effective disease control and termination is far from complete. Affordable and rapid multiplexed portable methodologies in resource–limited countries would be crucial for early tests to improve patient care through appropriate treatment and to prevent spread of disease. The key step is to have ultrasensitive and specific identification of disease biomarkers when target molecules are present in extremely low concentrations. Here, we present stress signal generation mechanism that redefines the limit of biochemical sensing. By introducing an innovative method that exploits receptor concentrations and surface footprint, we optimise mechanical signaling responses even in the presence of competing stress from opposing nanosensor cantilever surfaces, permitting direct capture of molecules at femtomolar concentrations within minutes (Fig 1). In particular, we demonstrate enhanced detection of antibiotics [1,2], and large molecules HIV antigens and coagulation factors, yielding ultrasensitive and reproducible quantitative assays. Our measurements provide novel approach for targeting specificity and sensitivity for direct sample analysis, and utilization of this information could lead to ultrasensitive biodetection systems.
Fig. 1: Exploiting nanomechanics of biochemical–receptor interactions to investigate the impact of optimising mechanical signaling responses for ultrasensitive detection of disease biomarkers even when present in extremely low concentrations. Here the molecules can bind to the surface tethered receptors to form a bound complex with subsequent activation of mechanical signaling, detected optically.
REFERENCES
[1] Ndieyira, J. W. et al. Nature Nanotech. 3, 691 (2008).
[2] Ndieyira, J. W. et al. Nature Nanotech. 9, 225 (2014).