ArticleACS nano2014
Next-generation in situ hybridization chain reaction: higher gain, lower cost, greater durability.
Article in ACS nano, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
275 citing papers in PubMed.
- Immunophenotyping by Spatial Biology.Methods in molecular biology (Clifton, N.J.) · 2027Article
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- Behavioral genomics identifies Creld1 as a cross-modal regulator of somatosensation.Nature neuroscience · 2026Article
- Anatomical and functional organisation of the cholinergic nervous system in the tunicatebioRxiv : the preprint server for biology · 2026Article
- Multiplexed gene expression analysis in dissociated and intact planarian flatworm tissues using in situ hybridization chain reaction.Biology open · 2026Article
- Full-length single-cell spatial transcriptomics reveals spatial and cell-type-specific transcript isoforms in the primate brain.Nature methods · 2026Article
- Ultrasensitive miRNA-21 biosensing: a metal-free photoinduced ROMP strategy via 3'-end oxidation.Analytical and bioanalytical chemistry · 2026Article
- Single-cell detection and quantification of the microbiota by MicFLY.Cell host & microbe · 2026Article
- Lineage Tracing Reveals atoh7-Positive and Negative Retinal Ganglion Cell Populations in the Zebrafish Retina.Investigative ophthalmology & visual science · 2026Article
- Recent advances in nanozyme assisted miRNA biosensing for disease diagnosis.Mikrochimica acta · 2026Review
- Hydrostatic pressure shapes and canalizes semicircular canal morphology to ensure vestibular function.bioRxiv : the preprint server for biology · 2026Article
- Multivalent Aptamers: Contemporary Engineering Strategies and Biomedical Applications.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Whole-organ spatial transcriptional analysis at cellular resolution using TRISCO.Nature protocols · 2026Review
- Prenatal acoustic communication triggers adaptive vascular programming in the developing avian brain.The Journal of experimental biology · 2026Article
- Two neuropeptides that promote blood feeding ineLife · 2026Article
- Single-molecule mitochondrial DNA imaging reveals heteroplasmy dynamics shaped by developmental bottlenecks and selection in vivo.Developmental cell · 2026Article
- Methodological framework for chromogenic mRNA detection using in situ hybridization chain reaction.Histochemistry and cell biology · 2026Article
- A Guide for Spatial Omics Technologies: Innovation, Evaluation, and Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- High Sensitivity Cardiac Troponin I Detection via MP-Locked Aptamer and Multimeric DNAzyme-Coupled Hyperbranched Hybridization Chain Reaction.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Modern RNA Quantification Methods: From RT-qPCR to Advanced Microscopy.The journal of physical chemistry. B · 2026Review
215 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Hybridization chain reaction (HCR) provides multiplexed, isothermal, enzyme-free, molecular signal amplification in diverse settings. Within intact vertebrate embryos, where signal-to-background is at a premium, HCR in situ amplification enables simultaneous mapping of multiple target mRNAs, addressing a longstanding challenge in the biological sciences. With this approach, RNA probes complementary to mRNA targets trigger chain reactions in which metastable fluorophore-labeled RNA hairpins self-assemble into tethered fluorescent amplification polymers. The properties of HCR lead to straightforward multiplexing, deep sample penetration, high signal-to-background, and sharp subcellular signal localization within fixed whole-mount zebrafish embryos, a standard model system for the study of vertebrate development. However, RNA reagents are expensive and vulnerable to enzymatic degradation. Moreover, the stringent hybridization conditions used to destabilize nonspecific hairpin binding also reduce the energetic driving force for HCR polymerization, creating a trade-off between minimization of background and maximization of signal. Here, we eliminate this trade-off by demonstrating that low background levels can be achieved using permissive in situ amplification conditions (0% formamide, room temperature) and engineer next-generation DNA HCR amplifiers that maximize the free energy benefit per polymerization step while preserving the kinetic trapping property that underlies conditional polymerization, dramatically increasing signal gain, reducing reagent cost, and improving reagent durability.
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Registered trials
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