Proteins, including antibodies, are increasingly becoming important as therapeutics. LLNL has developed an in silico antibody design platform based on AI tools. The approach requires experimental evaluation of in silico designed antibodies, which currently takes several weeks. There is a need to overcome this shortcoming and develop an automated and integrated platform that can accomplish this task rapidly.
LLNL inventors have developed a method and device for the high throughput screening of various chemical and biological entities using a novel combination of cell-free protein synthesis (in vitro transcription-translation), microencapsulation and optical interrogation (Figure below). This includes automated sample handling, microemulsions, microfluidics manipulation, machine vision, and fluorescent interrogation. This automated system can be used to partition analytes into thousands of independent microdroplet reactions that are tracked and optically interrogated for assay activity. Since timing of droplet generation and position are known, an n-dimensional pooling strategy can be performed to increase screening throughput over the traditional 1:1 assay method. An optical interrogation method such as fluorescence correlation spectroscopy (FCS) can provide highly quantitative information for each reaction in real time (e.g., affinity constant for novel antibodies), significantly increasing the precision and quality of data that informs future models and experiments. The approach outlined will enable the feedback loop from experimental evaluations to occur in about 3 days rather than 6 weeks, thereby enabling high quality antibody designs in weeks rather than months.
Current stage of technology development: TRL-2
LLNL has filed for patent protection on this invention.
The major advantages of the invention are: (i) integration of making protein (cell-free system), microencapsulation to generate thousands of reactions, and interrogation to characterize interactions into a single device; (ii) rapid turnaround; and (iii) cost saving by using analytes and reagents in small volumes.
The invention has numerous applications such as antibody development, large and small molecule functionality screening, cell-free protein synthesis development and monitoring, protein-small molecule, protein-nucleic acid and protein-protein interactions, directed evolution, cell killing assays, protein production, and stability monitoring.
