This article also applies to CUT&Tag, meCUT&RUN and Multiomic CUT&RUN.
EpiCypher’s CUTANATM Wash Buffer Enhancers (EpiCypher 14-1803) are optional, optimized additives for all CUTANATM assays that reduce sample clumping, a frequent cause of poor sequencing performance. They help maintain uniform suspension of cells/nuclei and magnetic beads, minimizing aggregation and sample loss. By improving bead resuspension and magnetic separation (Figure 1), these enhancers enable smoother handling and more consistent reagent access throughout the workflow, resulting in reduced technical variability and improved data quality.
Wash Buffer Enhancers are included in CUT&RUN and CUT&Tag kits produced from late 2025 onward (versions 6.0 and 4.0, respectively) and can be purchased as a standalone for use with previous kit versions, meCUT&RUN kits, or DIY CUT&RUN and CUT&Tag. While they are intended to improve sample handling and assay performance, they may not be appropriate for all cell types. Omitting them will not cause adverse effects unless your sample type is known to be prone to clumping or sticking. (Adherent cells, primary cells, and tissue-derived cells/nuclei may be especially prone to this.) You may not need the Wash Buffer Enhancers if:
You have used previous versions of our kits (v5 and earlier for CUT&RUN, or v3 and earlier for CUT&Tag) with the same cell/sample type without issue
Your cell type is particularly fragile
You have used this cell/sample type in other single-cell assays and have not observed clumping, lysing, or extracellular debris
On the other hand, if you have not used Wash Buffer Enhancers and are struggling with sample clumping, difficulty in handling, or poor sequencing results, you might consider adding the Wash Buffer Enhancers in your next round of experiments. We would recommend running a small pilot on a representative sample before incorporating them into your standard protocol. For best results, this pilot should include reactions prepared with Wash Buffer Enhancers and reactions (of the same sample and with the same antibody) prepared without the Wash Buffer Enhancers. For CUT&RUN kit users working with v5.0+, see Table 1 (below) for instructions on preparing buffers with the Wash Buffer Enhancers incorporated.
Figure 1. Comparison in CUT&Tag with and without Wash Buffer Enhancers shows more defined pellet formation, reduced supernatant cloudiness, and decreased sample adherence to tube walls when using the Wash Buffer Enhancer Set.
Table 1. Combine reagents as instructed in the table to prepare CUT&RUN buffers. Calculations are for 8 and 16 reactions are provided. All buffers include 20% extra volume to account for pipetting error—no additional overage is needed.
† Optional