Prof. Kai Johnsson, Max-Planck-Institute for Medical Research; Dr Qiuliyang Yu, Max-Planck-Institute for Medical Research; Dr Rudolf Griss, Ecole Polytechnique Federale de Lausanne; Dr Alberto Schena, Ecole Polytechnique Federale de Lausanne; Dr Olivier Sallin, Ecole Polytechnique Federale de Lausanne; Dr Luc Reymond, Ecole Polytechnique Federale de Lausanne
We aim at performing therapeutic drug monitoring (TDM) and metabolic profiling at the point-of-care using a single drop of blood in minutes.
We developed a class of colour-changing bioluminescent sensor proteins named Snifits. These engineered proteins emit light, whose colour changes from blue to red upon specific binding of a given analyte.
TDM and metabolic profiling nowadays require either liquid chromatography coupled to mass spectrometry (LC-MS), colorimetric enzymatic assays or antibody-based immunoassays. All methods require large amounts of blood, are time-consuming and labour-intensive, and require expensive equipment, restricting their use to the central laboratories of the largest hospitals. Our sensor proteins however allow fast and reliable quantification of multiple analytes from tiny amounts of blood with minimal equipment and reduced price, enabling new point-of-care diagnostics opportunities.
Sensors for several drugs requiring TDM (methotrexate, tacrolimus, sirolimus, cyclosporin A, topiramate and digoxin) and metabolites (NADPH and NAD+) have been developed. The sensors for metabolites also allow the quantification of a large range of small molecules (including aminoacids, sugars, lipids) and enzymes (including aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase), routinely measured in central laboratories. This is performed by coupling the sensor with other biochemicals without increasing assay complexity. All these assays have been proven to work on a paper-test format, require only single-microliter volumes of whole blood collected by a simple fingerprick, and are performed within minutes.
3 patents cover the technology:
PCT / EP2013 / 065223 : filed on 18.7.2013; granted in Europe, the USA and AU; still under examination: China, India and Canada. General coverage of the technology.
PCT / EP2016 / 053280 : first application 16 February 2015 granted in US, EP and JP; covers specifically the NAD+ sensor.
PCT / EP2018 / 064076 : first filing on May 30, 2017; covers specifically the NADPH sensor.
All these patents are now exploited by the Max-Planck-Innovation GmbH.
Griss et al., Nature Chemical Biology 2014, 598;
Xue et al., Angewandte Chemie 2017, 7112;
Yu et al. Science 2018, 1122;
Yu et al. Nature Metabolism 2019, 1219.