The need for analytical tools, which can assess function by sensing and quantifying intracellular chemical or physical species, has led to the development of a variety of luminescent molecular probes. However, due to the complexity of natural systems, cell signalling and function do not occur as isolated processes. Ideally, to gain truly meaningful insights into intracellular processes and perturbation to such processes induced by diseases, therapy or toxicity, multiple analytes need to be monitored simultaneously in a complex biological environment. Molecular logic sensors offer an elegant way to approach this issue by using parallel and logically connected identification of two or more analytes. A molecular logic gate processes these analytical inputs via a logic operation, producing an optical output signal. The output signal provides distinct information whether none, either of the analytes, or both of them, are present at a certain threshold concentration. Since the introduction of molecular logic gates by the group of de Silva 20 years ago, research approaches have focused on the realization of sensors and advanced drug delivery systems that exploit molecular logic gates. And, whereas the examples show the potential of molecular logic sensing for medical diagnostics, the major obstacle, which is the transfer of this sensing concept from solution to a complex biological environment such as the living cell, has not been tackled to date, but holds promise for future diagnostics.
Such tailor-made diagnostic tools are urgently needed both in fundamental research and clinical routine. As a proof-of-concept, LogicLab will develop a molecular logic sensor platform to diagnose endothelial dysfunction (ED). A dysfunction of the the cells lining our blood vessels is the primary cause of many lifestyle related diseases such as atherosclerosis, which account according to the WHO for 60% of all deaths worldwide in 2005. In atherosclerosis – a chronic medical condition that can remain undetected for decades - so called plaques deposit at the walls of blood vessels leading to stenosis and eventually to serious clinical events such as heart attack or stroke. An early-stage diagnosis of atherosclerosis would allow for intervention long before a high and thus dangerous degree of stenosis is reached. By detection of key biomarkers for ED, such as low wall shear stress and low nitric oxide (NO) concentration, LogicLab aims to develop an analytical platform to diagnose ED and the diseases it possibly provokes at a primary level. The objective of LogicLab is to explore a new concept of molecular logic sensing that can be applied in a biological environment. Not till then, molecular logic sensors will find wide-spread and important application such as in intracellular sensing, critical care diagnostics and high-throughput screening. The approach of LogicLab is a stepwise transfer of the concept from solution to membrane models to real biological environments such as cells and tissue.
