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High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads
Alexandros P Drainas1,2, David R McIlwain3,4,5, Alec Dallas6,7
1Department of Pediatrics, Stanford University, Stanford, CA, USA. drainas@stanford.edu.
Insights
Mass cytometry enables high-throughput serology testing using isotopically barcoded beads. This cost-effective method allows simultaneous detection of multiple antibodies in small sample volumes, aiding infectious disease outbreak management.
Area of Science:
- Immunology
- Biotechnology
- Analytical Chemistry
Background:
- Traditional serology testing is often slow, expensive, and requires individual sample analysis.
- There is a need for scalable, cost-effective serology methods capable of parallel measurements using minimal sample volumes.
Purpose of the Study:
- To demonstrate the utility of mass cytometry for high-throughput, multiplexed serology.
- To develop a method for simultaneously detecting multiple immunoglobulin G (IgG) and immunoglobulin M (IgM) responses against SARS-CoV-2 antigens.
Main Methods:
- Utilized mass cytometry with polystyrene beads uniformly loaded with stable isotopes for unique barcoding.
- Generated 18,480 unique isotopically barcoded beads to create a multiplexed assay.
- Tested 924 serum samples to detect IgG and IgM levels against 19 SARS-CoV-2 proteins.
Main Results:
- Successfully performed 36,960 tests in a small volume (400 nl sample, 30 μl reaction volume).
- Demonstrated the capability of mass cytometry for simultaneous, high-throughput antibody detection.
- Achieved a rapid, cost-effective serological testing approach.
Conclusions:
- Mass cytometry offers a scalable solution for multiplexed serology.
- This technique can significantly accelerate diagnostics during public health emergencies.
- The developed method is rapid, high-throughput, and cost-effective for infectious disease surveillance.
Abstract:
In serology, each sample is typically tested individually, one antigen at a time. This is costly and time consuming. Serology techniques should ideally allow recurrent measurements in parallel in small sample volumes and be inexpensive and fast. Here we show that mass cytometry can be used to scale up multiplexed serology testing by leveraging polystyrene beads uniformly loaded with combinations of stable isotopes. We generated 18,480 unique isotopically barcoded beads to simultaneously detect, in a single tube with 924 serum samples, the levels of immunoglobulins G and M against 19 proteins from SARS-CoV-2 (a total of 36,960 tests in 400 nl of sample volume and 30 μl of reaction volume). As a rapid, high-throughput and cost-effective technique, serology by mass cytometry may contribute to the effective management of public health emergencies originating from infectious diseases.
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