High-throughput quantification of the interactions between biomolecules and cells with engineered surfaces

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The study of the complex behaviour of biological systems often asks for a large scale experimentation approach, to comprehensively describe their responses to a large variety of perturbation parameters. In the last decades, this large scale experimentation approach has been made possible due to the miniaturisation of biochemical and (more recently) cell-based tests. While these techniques present a certain degree of empirical, `brute force' probing of the systems studied, the ultimate goal of this powerful methodology is the prediction of the behavior of biological systems based on the deciphering the underlying mechanisms, rather than the prediction based on empirical observation. Usually, large scale experimentation has been used for `omics' applications, e.g., genomics, proteomics, metabolomics, for the benefits of drug discovery, but the methodology has been used for other applications, e.g., the discovery of new materials and biomaterials. To this end, the long term objective of the proposed program is to progress the understanding-based prediction of the behavior of hybrid systems comprising biomolecules, in particular proteins; and cells, in particular microorganisms, interfaced with artificial surfaces and structures. This objective will be fulfilled through a programmatic progression from (i) large scale, standardized experimentation yielding comprehensive empirical data; to (ii) construction of semi-empirical correlations between the parameters of the biological component, i.e., biomolecule, cell; and those of the artificial component, i.e., surfaces, micro/nano-structures; to (iii) model-based predictions of the behavior of the systems of interest; thus allowing for engineering-style design, fabrication and operation of hybrid bio-nano-devices.In the short term, the program aims to (i) develop an experimental platform that integrates microfluidics, microarrays, biosensors and MEMS elements for the combinatorial study of interactions of biomolecules and cells with engineered surfaces; (ii) collect data regarding protein adsorption and bioactivity from large scale, standardized experimentation; and find statistical relationships regarding protein adsorption between protein properties; surface properties; and fluid properties; (iii) derive design rules for nano-structured surfaces specifically interfacing individual protein molecules; and (iv) demonstrate the quantification of the motility of biological systems, i.e., cytoskeletal proteins and motile microorganisms, as an ultimate reporter of the bioactivity of the system interfacing artificial structures and surfaces.The program deliverables are linked to various levels of impact. Firstly, the methodological advances will demonstrate the use of the integrated combinatorial-testing device, which will help the standardization and efficiency of relevant studies in the area of microbiology, drug discovery, diagnostics and fundamental molecular biology studies. Second, the fabrication of structures that induce a specific biological behavior, e.g., antifouling, selective adsorption, bioactivity preservation, will impact on areas as diverse as surgical instruments, implants, diagnostic devices, consumer products, food processing, air conditioning equipment, antifouling of ships, etc. Considering biomaterials only (a $8bn market), the possibility of quick "design & test" of personalised biomaterials will greatly amplify the capacity of addressing the patient's, rather than a generic medical condition. Third, the quick and comprehensive quantification of the motility of cytoskeleton filaments and microorganisms, on drug discovery for e.g., cancer, neurodegenerative diseases; or new, virulent hospital-based infectious diseases - a particular problem for Canada.