Printable bioelectronics to investigate functional biological interfaces for ultra-high performing biosensors

c5tc02737c-f3_hi-resAutore del lavoro candidato: Luisa Torsi

SINTESI CONTENENTE UNA BREVE DESCRIZIONE DEL LAVORO SVOLTO E DEI RISULTATI OTTENUTI: Thin-film transistors interfaced to biological systems can result in highly performing bioelectronic devices capable to accomplish tasks such as sense bio-species as well as transduce the electrical activity of cells or even organs such as the brain. The scientific activity of Luisa Torsi is developed within this exciting and fast developing field, and has been centered on the use of organic transistors as sensitive and selective biosensors. Besides the applications, she has always paid attention to the fundamental understanding of the sensing mechanisms. In the past five years along with her group, she has shown how organic, as well as other printable transistors, can integrate functional biological recognition elements resulting in extremely highly performing low-cost bioelectronic sensors that hold the potential to revolutionize the present approa ch to point-of-care testing and well-being. Among the device structures studied and developed in her group, interesting are the electrolyte-gated thin-film transistors. These are field-effect devices gated through an ionic conductor rather than a dielectric. Due to the high capacitance of the charge double layers generated upon gate biasing, they can be operated as capacitance-modulated transistors. Specifically, it is the bio-layer capacitance, being the lower in a series of capacitors, that controls the device output current. Such an occurrence allows for extremely high sensitivity detections even towards very weak interactions. A proof-of-principle of this novel sensing concept has been provided with an electrolyte gated transistor integrating odorant binding proteins. The device has been proven to accomplish chiral differential detection of carvone molecules with an extraordinary large enantiomeric discrimination factor and accurate estimate of interaction energies as low as few kJ per mol. This is a unique tool with general applicability that allows neutral ligand detection in the pico-molar concentration range. The results have been published early this year in Nature Communications with Torsi being the corresponding author. In nine months the paper has been downloaded already more than 3.000 times leading to an impressive Altmetric score: 96 percentile (ranked 5.127th) of the 131,108 tracked articles of a similar age in all journals and 76 percentile (ranked 131st) of the 556 tracked articles of a similar age in Nature Communications. In the elicited work the binding curves modelling provides information on the electrochemical free-energies derived from the dissociation constants while the electrostatic component is isolated from the threshold voltage shifts. These can be combined with the chemical free-energies gathered from the complex formation in solution, overall providing a very comprehensive picture of the energy balances for a surface bound protein-carvone complex undergoing chiral interactions. The computation of the relative decrease in capacitance upon binding provides strong support to the hypothesis of odorant binding proteins undergoing a conformational change when binding only to one of the two carvone enantiomers. This study shows also that such an ultra-sensitive detection system can be achieved with an organic bio-electronic device fabricated on a flexible substrate with low-cost, printing compatible technology. This has been shown to hold true, not only to detect neutral odor molecules, but more generally to accomplish label-free detection of biomarkers for inflammatory diseases with ultra-high sensitivity. For instance commercially available antibodies against C-reactive protein have been integrated in a transistor proving how such a biological recognition layer can selectively capture its target biomarker directly in blood serum or saliva. Very recent and still unpublished results prove that femto-molar detection limits can be reached in this technologically relevant case of study.

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