A platinum polymer probe for multiplexed single cell suspension mass cytometry and imaging mass cytometry assays
Bibliographic record
Abstract
• A polymer system carrying pendant dipicolylamine chelators that bind Pt 2+ ions was synthesized. • Isotopically enriched Pt polymers were conjugated to antibodies (Abs) and were investigated as reagents for mass cytometry (MC) applications. • The Pt polymer-Ab conjugates were effective probes for antigen detection on cells by suspension MC. • A Pt-polymer-anti-CD45RA conjugate was effective for imaging tissue sections by imaging mass cytometry. • The Pt polymer was compatible with commercial MC reagents and with other Pt isotopes of the same polymer in multiplex cell assays. Single-cell analysis with mass cytometry has enabled routine detection of ∼ 50 biomarkers per cell with suspension mass cytometry (SMC), and 40 + biomarkers in tissue sections with imaging mass cytometry (IMC). However, biologists have expressed the strong need for additional mass tag reagents. While there has been progress in the development of alternative metal mass tags for SMC, few reagents have been validated for IMC. We report polyacrylamide polymers (DP = 22, 55) carrying dipicolylamine (DPA) chelators effective at binding Pt 2+ ions that serve as effective mass tags with strong signal and low nonspecific binding in both SMC and IMC applications. These polymers were labeled with three Pt isotopes ( 195 Pt, 196 Pt, and 198 Pt) and gave excellent performance in an 11-plex SMC assay on peripheral blood mononuclear cells. We further demonstrated that the 196 Pt-polymer was effective at generating sharp images comparable to commercial lanthanide-based reagents when used in a 5-plex IMC assay on healthy human tonsil tissue. We demonstrate that these Pt polymers serve as versatile mass tags that can be conjugated to various Abs and target their respective biomarkers with high specificity for both cell and tissue samples. Our Pt polymer system has higher sensitivity than existing cisplatin-labeled Abs. and increases the accessible mass channels for both SMC and IMC by three. This work also presents the first Pt probe that is demonstrated to be highly effective for imaging of tissue sections by IMC. Overall, these polymers add three new mass tags to the mass cytometry toolbox, and this work presents a valuable contribution toward the design of new mass tag reagents that are suitable for both SMC and IMC.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".