Self-driving Gliders for Programmable Routing of Microscopic Cargo

What are you trying to do?We propose self-driving gliders for programmable routing of microscopic cargo on surfaces patterned with dynein motors. We’ll initially focus on two applications: (1) sorting of CAR-T cells to enrich for metabolic fitness and avidity to peptide-MHC targets; (2) DNA-sequence encoded assembly of informational polymers (“makeshift synthetic ribosome”) and subsequent multi-objective evaluation and annotation of functional performance (“Molecular Ninja Warrior”).How is it done today?Current cell sorting methods are limited by the assay of choice. The dominant sorting paradigm is FACS; limitations of FACS include the high cost, medium throughput, and limited capability to assay only for staining efficiency.What is new in your approach?“Molecular Ninja Warrior”: Gliders enable annotation of library members with transit time through each reaction chamber, which could be a proxy for a rich range of functionally interesting behaviorsIf you are successful, what difference will it make?The ability to assess the anti-tumor activity of specific CAR-T variants would facilitate the development of more effective CAR-T immunotherapies to improve patient outcomes. “Molecular Ninja Warrior”: Small molecule compounds can be assembled with specific activity profiles based on time-tracked performance in sequential reaction chambers. Compounds with desired activity profiles can be identified via high-throughput sequencing for personalized medicine. For example, chemotherapeutics with activity profiles that match the mutational profile of a patient tumor can be selected to prevent drug resistance.Cost and timeline?CAR-T cell sorter ($500k per year total cost): Years 1–2 proof-of-principle to demonstrate genotype-specific, DNA-tape-annotated transit times of gliders; Years 3–4 prototyping performance with CAR-T cells; Molecular Ninja Warrior ($500k per year total cost): Years 1–2 proof-of-principle to demonstrate control of genotype-specific routing of gliders for split and combine synthesis; Years 3–4 prototype device for demonstrating library synthesis and functional evaluation.