Sensors based on nanopores show promises
Biomarkers are molecules that offer a measurable indicator of some biological state or condition. The presence of biomarkers in biological samples is used to monitor pathogenic processes. Using nanopore is advantageous because they do not require chemical labelling or complex optics thus allowing easy integration in low-cost, portable and wearable devices.
In collaboration with Portal Biotech, we are currently developing a nanopore based technology for high-throughput sensing of biomarkers.
Metabolite Recognition with Protein Adaptors
Protein Engineering for p
Metabolites are small molecules that are products of metabolism and are an important class of biomarkers.
Proteins can be integrated inside a nanopore and the binding of ligands can be observed by the specific modulation of the ionic current. Metabolites can be identified directly from picoliter blood samples, sweat and other biological liquids.
We are testing the incorporation of many proteins that bind to a variety of metabolites.
Nanofilters for protein biomarkers
Many biomarkers are proteins. Protein biomarkers are recognised by their specific ionic current signature (e.g. thrombin in green and GFP in blue) and quantified by the frequency of the blockades. One of the main challenges is to detect low abundance proteins in a biological sample. We are investigating several methods to selectively recognize a protein biomarker. In one example below, a layer of DNA aptamers was chemically attached to the nanopore to allow selective capture of cognate analyses.
Protein sizing with 15-nm conical biological nanopore YaxAB. ACS Nano (2023). https://doi.org/10.1021/acsnano.3c02847
Specific Detection of Proteins by a Nanobody-Functionalized Nanopore Sensor. ACS Nano (2023). https://doi.org/10.1021/acsnano.2c12733
PlyAB Nanopores Detect Single Amino Acid Differences in Folded Haemoglobin from Blood. Angewandte Chemie (2022) https://doi.org/10.1002/anie.202206227
Automated Electrical Quantification of Vitamin B1 in a Bodily Fluid using an Engineered Nanopore Sensor. Angewandte Chemie (2021). https://doi.org/10.1002/anie.202107807
Blockades of Proteins Inside Nanopores for Real-Time Metabolome Analysis. ACS Nano. (2020) https://doi.org/10.1021/acsnano.9b09434.
Engineering and Modeling the Electrophoretic Trapping of a Single Protein Inside a Nanopore. ACS Nano (2019) doi.org/10.1021/acsnano.8b09137
Direct electrical quantification of glucose and asparagine from bodily fluids using nanopores. Nature Communications (2018) 10.1038/s41467-017-01006-4-Eurekalert - Sciencelinx - PhysOrg - Science News - Science Daily - Canada News - LongRoom - GEN - R&D - Infosurhoy - Bionity - Health Innovations - Bioanalysis - Kennislink - Chemistry World - LabMedica
Real-time conformational changes and controlled orientation of native proteins inside a protein nanoreactor. JACS. (2017). doi: 10.1021/jacs.7b10106.
G. Single-Molecule Analyte Recognition with ClyA Nanopores Equipped with Internal Protein Adaptors. JACS (2015). DOI: 10.1021/jacs.5b01520.
Detection of two isomeric binding configurations in a protein-aptamer complex with a biological nanopore. ACS Nano (2014). DOI: 10.1021/nn506077e.
An engineered ClyA nanopore detects folded target proteins by selective external association and pore entry. Nano Letters (2012). DOI