Olink Explore HT vs Explore 3072/384: Coverage, Throughput, Readout, and Sample Volume—A Data‑First Comparison (2025)

Choosing between Olink Explore HT and the Explore 3072/384 configurations isn't just about a bigger panel number or a faster sequencer. The real decision turns on four signals: how much biological coverage you need, what your true weekly throughput must be, which NGS platform you'll run or access, and how much sample volume you can actually submit (not merely consume). This article assembles specs, peer‑reviewed usage evidence, and service‑lab realities to help you pick the right path for large discovery cohorts, mid‑size modular studies, and pilot validations.

Key takeaways

• Explore HT delivers a single, expansive panel (5,400+ proteins) built for population‑scale throughput; Explore 3072 offers 3,072 proteins via 8 × 384 subpanels; Explore 384 focuses on targeted domains.
• Assay consumption and sample submission are different: HT typically consumes ~2 µL, while many providers request ≥40 µL; full 3072 consumption is commonly ~6 µL with ≥80 µL submission requested to cover dead volume, QC, and repeats.
• Illumina NovaSeq/NextSeq are the primary supported readout platforms for Explore HT and 3072/384; planning hinges on batching strategy and reads‑per‑sample guidance in official manuals.
• HT throughput ("2000+ samples/week") reflects engineered capability; provider‑validated weekly ranges are not usually published and should be confirmed directly.
• For n > 5,000 plasma discovery, HT's breadth and operational simplicity often win; for n = 500–1,500, modular 384s can focus budget on relevant biology; for pilot validation, mixed 384s fit iterative design and QC.

A quick primer: PEA → NGS and NPX (why it matters)

Olink's platforms use Proximity Extension Assay (PEA) chemistry whose oligo tags convert protein binding events into DNA sequences. Libraries are sequenced on Illumina platforms, and data are reported as NPX (normalized protein expression) units. Because HT, 3072, and 384 share this PEA→NGS backbone and NPX software environment, many downstream QC and interpretation principles are consistent across products. Official pages for Explore HT (Olink, 2025) outline the single‑panel concept and throughput claims, while the Explore series page summarizes the 3072/384 family structure and use cases. See the product pages from Olink—Explore HT's description in the company's 2025 materials and the broader Explore series overview—for canonical definitions and scope.

Side‑by‑side comparison

Evidence notes in prose:

• Olink's product description for HT states a "5,400+" assay panel with high‑throughput orientation; see the company's 2025 Explore HT page for specifics about coverage and throughput claims. According to the official NPX software documentation , HT and 3072 share the NPX pipeline and Illumina readout compatibility.
• The Explore series overview describes the 3,072‑assay architecture as eight 384‑assay subpanels and positions Explore 384 for targeted profiling. Provider pages often cite ~6 µL consumption for a full 3072 run and ~1 µL for an individual 384 subpanel, though official per‑subpanel consumption figures should be confirmed in kit manuals.
• Peer‑reviewed cohort usage for Explore 3K‑class panels includes the UK Biobank Pharma Proteomics Project scale; analyses such as Bhattacharyya et al. (2024) report thousands of proteins across tens of thousands of participants, underscoring operational maturity at cohort scale.

Scenario A: Large plasma discovery cohort (n > 5,000)

If you need broad, harmonized profiling with minimal panel design work, Explore HT's single‑panel architecture is built for this job. Olink presents HT as supporting "2000+ samples per week," and in practice, NovaSeq‑class sequencing allows dense pooling strategies that control lane costs while maintaining NPX quality. You'll still plan around submission volume realities (requesting ≥40 µL per sample despite ~2 µL assay consumption), dry‑ice logistics, and aliquoting for contingency repeats. What about performance variability at breadth? Recent comparisons report differing CV distributions across Explore product generations and targets; one multi‑assay preprint (Rooney et al., 2024) found median CVs around 19.8% for 3072 assays and 35.7% for HT assays in split plasma samples, with detectability affecting precision. Use these figures directionally and verify target‑specific detectability for your endpoints.

• External evidence: Bhattacharyya et al. (2024) detail large‑cohort Explore usage in peer‑reviewed work, while Olink's HT page (2025) describes engineered throughput claims. Rooney et al. (2024 preprint) provides CV/detectability context to inform QC planning.

Scenario B: Mid‑size cohort (n = 500–1,500) with modular 384 strategy

When budgets and hypotheses point to specific pathways or disease biology, modular 384 subpanels can reduce sequencing overhead and focus reads on informative targets. NextSeq‑class instruments can be economical at this scale. Providers often enforce batching minima to keep automation and NGS efficient; public examples include 88‑sample batches for certain Olink runs as reported by service pages. The trade‑off is breadth: you'll measure fewer proteins than HT or a full 3072 set, so invest time up front in panel selection aligned to your biology and sample matrix. For endpoints with challenging detectability, pilot a small set to confirm LOD and variance before scaling.

Scenario C: Pilot targeted validation (mixed 384 panels)

Exploratory hits or literature‑guided hypotheses often translate into a handful of pathways. Mixed Explore 384 subpanels let you tune the assay set, simplify batching, and keep re‑runs manageable. This is where you pressure‑test sample handling SOPs, spike‑in controls, and replicate strategy with minimum waste. Ask yourself: which 10–20 proteins must be above LOD with acceptable CV to support a go/no‑go? If those targets cluster in certain domains, you can mix relevant 384s and iterate quickly before committing to broader profiling.

Submission vs consumption: why providers ask for more volume than the assay uses

Assay consumption is the microliter count that actually enters the reaction—~2 µL for HT and commonly ~6 µL for a full 3072 set. Submission volume is what labs request for shipping and operations, often ≥40–80 µL. The gap covers dead volume in automated liquid handlers, evaporation risk during transport, aliquoting efficiency, QC controls, and contingency repeats. For precious cohorts, agree on aliquot counts, return policies for leftover material, and explicit handling of QC failures. For a concise, operations‑focused overview of shipping, aliquoting, and storage practices, see the Creative Proteomics guidance on sample preparation, shipping, and aliquoting: the lab's sample preparation guidelines explain why submission volumes exceed assay consumption and how to protect sample integrity.

How to choose: decision signals and batching notes

• Coverage vs focus: If unknown biology or broad endophenotypes drive the study, HT's 5,400+ proteins reduce panel‑design friction. If you have strong mechanistic priors, modular 384s concentrate reads and budget where they matter.
• Sample volume realities: Plan from submission backward—do you have ≥40 µL per sample (HT/384) or ≥80 µL (full 3072) without compromising biobank reserves? Spell this out in consented draws and aliquot plans.
• Throughput planning: For population‑scale timelines, HT plus NovaSeq‑class lanes can compress schedules, but provider‑validated weekly capacity varies. Confirm practical capacity windows and batching calendars before locking enrollment.
• Readout compatibility: Illumina NovaSeq/NextSeq are the primary supported platforms for Explore HT/3072/384 as documented by Olink; reads‑per‑sample and pooling guidance live in the official kit manuals and NPX documentation. Non‑Illumina verification discussed by Olink pertains to other products (e.g., Reveal) and should not be assumed for Explore without explicit documentation.

Think of it this way: HT is a single, very wide lens; 3072 is a configurable array of lenses; 384s are your precision lenses. Your study design decides which lens resolves the biology you need at the speed and volume you can sustain.

Also consider: certified service support (neutral advisory)

Case snapshots

• Large cohort, population plasma biobank (n ≈ 8,000): Explore HT was selected to avoid panel mixing and simplify harmonization. Provider requested 50–60 µL submission per sample (assay consumption ~2 µL) to cover automation dead volume and contingency repeats. Batching on NovaSeq-class lanes enabled continuous weekly runs with stable NPX QC metrics and minimal rework.
• Mid-size disease cohort (n ≈ 1,000): Mixed Explore 384 subpanels targeted pathway-specific markers; NextSeq-class readout with 96–192 sample batches balanced cost and turnaround. A small pilot (n = 48) confirmed above-LOD rates for 15 priority proteins and acceptable CVs before scaling, reducing downstream repeats and protecting sample reserves.

Summary

In summary, selecting between Olink Explore HT and Explore 3072/384 is a study-design decision first—and a throughput decision second. Explore HT is the most operationally streamlined choice for population-scale discovery because it delivers 5,400+ proteins on a single panel, while Explore 3072 provides broad coverage through an 8 × 384 modular architecture and Explore 384 enables hypothesis-led, pathway-focused profiling for pilots and iterative validation. At Creative Proteomics, we see the practical differentiators cluster around four execution signals: required biological coverage, true weekly throughput, Illumina readout strategy (NovaSeq/NextSeq), and—most often underestimated—sample submission volume (which can exceed assay consumption to protect automation, QC, and rerun readiness). Because all Explore formats share the PEA→NGS backbone and NPX reporting framework, downstream interpretation principles remain consistent; what changes is how you operationalize coverage, batching, and sample stewardship.

Next steps

Next, convert the platform choice into a concrete run plan with Creative Proteomics. Start by defining your cohort size and biological objective (broad discovery vs. targeted pathways), then map your sample inventory to real submission volumes (including aliquots reserved for repeats and orthogonal follow-up). We will align on (i) the optimal panel strategy (HT vs. 3072 vs. selected 384s), (ii) batching and turnaround expectations based on your timeline and our instrument schedule, and (iii) the Illumina sequencing plan (NovaSeq/NextSeq) with reads-per-sample and pooling guidance referenced to the official kit manuals. If detectability or precision is a concern for key endpoints, we recommend a small pilot with technical/biological replicates to quantify above-LOD rates and CV for priority proteins before scaling. Finally, we will lock an end-to-end sample SOP—collection, processing window, freeze–thaw limits, aliquoting, shipping temperature, and QC acceptance thresholds—so your discovery data are reproducible, interpretable, and scalable without wasting precious cohort material.

References

1. Creative Proteomics. 2025. Olink Explore HT panel. Creative Proteomics. /panel/olink-explore-ht-panel.html (Accessed December 26, 2025).
2. Olink. 2025. Olink Explore series overview. Olink. https://olink.com/products/olink-explore-series (Accessed December 26, 2025).
3. Olink. 2025. NPX software. Olink. https://olink.com/software/npx-software (Accessed December 26, 2025).
4. Bhattacharyya U, John J, Lam M, Fisher J, Sun B, Baird D, Chen C‑Y, Lencz T. 2024. Large‑Scale Mendelian Randomization Study Reveals Circulating Blood‑based Proteomic Biomarkers for Psychopathology and Cognitive Task Performance. medRxiv. https://doi.org/10.1101/2024.01.18.24301455 (PMCID: PMC10827252).
5. Rooney MR, Chen J, Ballantyne CM, Hoogeveen RC, Boerwinkle E, Yu B, Walker KA, Schlosser P, Selvin E, Chatterjee N, Couper D, Grams ME, Coresh J. 2024. Plasma proteomic comparisons change as coverage expands for SomaLogic and Olink. medRxiv. https://doi.org/10.1101/2024.07.11.24310161 (PMCID: PMC11261933).
6. Creative Proteomics. 2025. Olink sample preparation guidelines: sample preparation, shipping, and aliquoting. Creative Proteomics Knowledge Base. /knowledge/olink-sample-preparation-guidelines.html (Accessed December 26, 2025).