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# DNA nanoscopy

DNA nanoscopy or DNA microscopy uses DNA-DNA interactions and then using sequencing to form a visual image of the geometry being studied.

* **Original APR DNA nanoscope** — auto proximity recording using DNA, original publication [Nature](https://www.nature.com/articles/s41467-017-00542-3).
* **Scaling up with a “molecular ruler”** — bioRxiv preprint from the same lab; distance records calibrated on origami, reconstructing patterns with >100 unique features. [bioRxiv](https://www.biorxiv.org/content/10.1101/2020.08.27.271072.full?utm_source=chatgpt.com), [Molecular Systems Lab](https://yin.hms.harvard.edu/publications/2020.nanoscope.pdf?utm_source=chatgpt.com)
* **Primer Exchange Reaction (PER)** — the isothermal DNA synthesis cascade that underpins several recording schemes. Nature Chemistry (2017). [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC5784857/?utm_source=chatgpt.com)
* **DNA microscopy (optics-free)** — original Cell paper: encodes proximities into DNA via a stand-alone reaction + computational reconstruction. [ScienceDirect](https://www.sciencedirect.com/science/article/pii/S0092867419305471?utm_source=chatgpt.com)
* **Volumetric DNA microscopy** — 3D, organism-scale extension; Nature Biotechnology (2025). [Nature](https://www.nature.com/articles/s41587-025-02613-z?utm_source=chatgpt.com), [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC12339006/?utm_source=chatgpt.com)
* **SCOPE** — spatial reConstruction via Oligonucleotide Proximity Encoding; an optics-free 2D array demo inspired by DNA microscopy. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11326233/?utm_source=chatgpt.com)
* **Error-correction/algorithms for DNA microscopy** — a 2024 methods paper focused on reconstruction robustness. [Nature](https://www.nature.com/articles/s43588-023-00589-x?utm_source=chatgpt.com)
* “DNA-GPS” for large-scale optics-free spatial genomics. [ScienceDirect](https://www.sciencedirect.com/science/article/pii/S2405471223002430?utm_source=chatgpt.com)
* Review - *Microscopy-by-sequencing* primer (Trends in Biotechnology, 2019) — great conceptual survey. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6943198/?utm_source=chatgpt.com), [marcottelab.org](https://www.marcottelab.org/paper-pdfs/TIBTech_DNAmicroscopy_2020.pdf?utm_source=chatgpt.com)
* Review - *Imaging-by-sequencing methods* (Nanoscale, 2023) — broader technique landscape & contrasts vs optical ST/PAINT. [RSC Publishing](https://pubs.rsc.org/en/content/articlehtml/2023/nr/d2nr05435c?utm_source=chatgpt.com)

The auto proximity recording paper mentions that probes can be attached via either antibodies or aptamers, which is handy for protein targets you care about. [Nature](https://www.nature.com/articles/s41467-017-00542-3)

DNA-PAINT context (optical, but DNA-programmed): If you’re mixing sequencing-based readout with optical benchmarks, these are handy: a recent **DNA-PAINT** review (2025) and **Ångström-resolution DNA-PAINT** (2023). [RSC Publishing](https://pubs.rsc.org/en/content/articlehtml/2025/nr/d4nr04544k?utm_source=chatgpt.com), [Nature](https://www.nature.com/articles/s41586-023-05925-9?utm_source=chatgpt.com)

# See also

[[fisseq]] and [[in situ sequencing]]