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 novel pathogens. Three major areas of improvement include the rapid development of vaccines, therapeutics, and serosurveillence. 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 a particular formulation has elicited antibody creation in the patient. Likewise, intimate knowledge of the antibodies created in populations with mild disease can provide valuable potential candidates for biologics that can be rapidly produced. Finally, the identity and amount of antibodies specific to a pathogen within an individual can indicate whether 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 and concentration of large proteins, such as antibodies, prior to delivery to mass spectrometry. Herein, we propose using this technology to couple immunoprecipitation to mass spectrometry. Using the KingFisher flex platform from Thermo Fisher, 96 serum samples can be processed simultaneously with magnetic beads coated with recombinant spike protein from SARS-CoV-2. The resultant samples will contain the antibodies specific to the virus on a per-individual basis. Mass spectral analysis of these antibodies will provide sequence and abundance information. When combined with patient outcome 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 immune response 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 uniquely provides the high throughput interface with mass spectrometry. We have an opportunity to have a significant impact on this crisis and template a new technology that will enable more rapid responses to future pathogens.Narrative: This application seeks to leverage Integrated Protein Technologies’ SampleStream platform to integrate immunoprecipitation of antibodies from human serum directly to mass spectrometry with a throughput that enables a meaningful number of samples to be processed daily in the face of SARS-CoV-2. The completed system will affinity purify SARS-CoV-2-specific antibodies from human serum using the spike protein and deliver them for mass spectrometric interrogation with a throughput of 1 min per sample, enabling the collection of a wealth of information not possible by any current methods. The platform will have an immediate impact on the current global pandemic, but the same platform can be deployed against any existing or new pathogen, including seasonal flu.