Drainas AP, McIlwain DR, Dallas A, Chu T, Delgado-González A, Baron M, Angulo-Ibáñez M, Trejo A, Bai Y, Hickey JW, Lu G, Lu S, Pineda-Ramirez J, Anglin K, Richardson ET, Prostko JC, Frias E, Servellita V, Brazer N, Chiu CY, Peluso MJ, Martin JN, Wirz OF, Pham TD, Boyd SD, Kelly JD, Sage J, Nolan GP, Rovira-Clavé X, (2025). High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beadsNature Biomedical Engineering 9, 1117-1128
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 mu l 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.
The intricate interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations to the intestinal tissue environment. Our ability to study these events on the systems level is significantly limited by in situ approaches capable of generating simultaneous insights from both host and microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for simultaneous in situ probing of host and microbiome across multiple spatial modalities. We demonstrate MicroCart by investigating gut host and microbiome changes in a murine colitis model, using spatial proteomics, transcriptomics, and glycomics. Our findings reveal a global but systematic transformation in tissue immune responses, encompassing tissue-level remodeling in response to host immune and epithelial cell state perturbations, bacterial population shifts, localized inflammatory responses, and metabolic process alterations during colitis. MicroCart enables a deep investigation of the intricate interplay between the host tissue and its microbiome with spatial multi-omics.
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