SampleStream: A Radically Simplified Platform for Protein Sample Preparation

Abstract: The rise of the global SARS-CoV-2 pandemic has exposed serious weaknesses in our ability to respond to novelpathogens. Three major areas of improvement include the rapid development of vaccines, therapeutics, andserosurveillence. All three of these areas require tools that accurately assess the immune response across individuals.Vaccine development requires lot-to-lot quality control and requires an antibody test that establishes whether or not aparticular formulation has elicited antibody creation in the patient. Likewise, intimate knowledge of the antibodiescreated in populations with mild disease can provide valuable potential candidates for biologics that can be rapidlyproduced. Finally, the identity and amount of antibodies specific to a pathogen within an individual can indicatewhether or not an individual has been infected, and, importantly, whether or not they have lasting immunity.Integrated Protein Technologies has developed a technology called SampleStream that enables rapid purification andconcentration of large proteins, such as antibodies, prior to delivery to mass spectrometry. Herein, we propose usingthis technology to couple immunoprecipitation to mass spectrometry. Using the KingFisher flex platform from ThermoFisher, 96 serum samples can be processed simultaneously with magnetic beads coated with recombinant spike proteinfrom SARS-CoV-2. The resultant samples will contain the antibodies specific to the virus on a per-individual basis. Massspectral analysis of these antibodies will provide sequence and abundance information. When combined with patientoutcome data, this will enable IPT to identify the set of antibodies that are truly neutralizing in the broader population.Ultimately, these antibodies can serve as drug leads, can aid in vaccine development by ensuring a potent immuneresponse is generated, and enable surveillance and assessment of infection/immunity across the globe.IPT's technology and our "plugin" system enable us to rapidly integrate these platforms and SampleStream uniquelyprovides the high throughput interface with mass spectrometry. We have an opportunity to have a significant impact onthis crisis and template a new technology that will enable more rapid responses to future pathogens.