(1387-D) Towards a plasmonic nanosieving device for the automated selection of cancer-relevant peptides targeted by T-cell receptor-mimic antibodies
Tuesday, February 6, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: This work presents the initial steps towards the development of a plasmonic nanosieving device for the automated identification and sorting of antibody-antigen complexes resulting from mixing a test antibody with a heterogeneous antigen solution. At the core of this device exists a plasmonic nanopore sensor that traps optically single proteins or protein complexes and subjects them to a series of AC pulses to deduce multiple electrical signatures from each trapped molecular entity. The electrical data are acquired through a nanopore that is located immediately below the plasmonic optical trap. Concurrently with the electrical data form the nanopore, optical data are also acquired based on light scattering from the optically trapped entities. A curated library optical and electrical data has been compiled to train a machine learning algorithm for real-time molecule classification i.e., whether the molecular entity inside the optical trap is an antibody, an antigen, or an antibody-antigen complex. Results from ongoing work will be presented to showcase our device and data analysis workflow for the specific example of a peptide presented by Major Histocompatibility Complex type-I (pMHC) receptors targeted by a T-cell receptor-mimic antibody developed against them, in the presence of non-specific peptide targets. In the next step of this work, our team will develop an automated DAQ protocol that, upon molecule classification by the sensor, will repel it back towards the solution if it is an antibody, antigen or agglomerate, and force it through the nanopore into a separate reservoir if it is classified as an antibody-peptide complex with specific binding. In future work multiple antibodies tagged with DNA barcodes will be mixed into a heterogeneous antigen mixture so as to further multiplex this assay, or alternatively, we will explore coupling our nanosensor with a mass-spectrometry system for the detailed characterization of the peptides selected through our nanosieving device.