{"doi":"10.1117/12.2038753","title":"Super-nonlinear fluorescence microscopy for high-contrast deep tissue imaging","abstract":null,"journal":"SPIE Proceedings","year":2014,"id":663952,"datarank":0.11211293644084144,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.008140859356849627,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.008140859356849627,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1349780,"name":"Xinxin Zhu","orcid":"0000-0002-5673-9977","position":1,"is_corresponding":false},{"id":1733610,"name":"Zhixing Chen","orcid":null,"position":2,"is_corresponding":false},{"id":275832,"name":"Wei Min","orcid":"0000-0003-2570-3557","position":3,"is_corresponding":false},{"id":1453674,"name":"Lu Wei","orcid":"0000-0002-8065-0956","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Super-nonlinear fluorescence microscopy for high-contrast deep tissue imaging","abstract":"Two-photon excited fluorescence microscopy (TPFM) offers the highest penetration depth with subcellular resolution in light microscopy, due to its unique advantage of nonlinear excitation. However, a fundamental imaging-depth limit, accompanied by a vanishing signal-to-background contrast, still exists for TPFM when imaging deep into scattering samples. Formally, the focusing depth, at which the in-focus signal and the out-of-focus background are equal to each other, is defined as the fundamental imaging-depth limit. To go beyond this imaging-depth limit of TPFM, we report a new class of super-nonlinear fluorescence microscopy for high-contrast deep tissue imaging, including multiphoton activation and imaging (MPAI) harnessing novel photo-activatable fluorophores, stimulated emission reduced fluorescence (SERF) microscopy by adding a weak laser beam for stimulated emission, and two-photon induced focal saturation imaging with preferential depletion of ground-state fluorophores at focus. The resulting image contrasts all exhibit a higher-order (third- or fourth- order) nonlinear signal dependence on laser intensity than that in the standard TPFM. Both the physical principles and the imaging demonstrations will be provided for each super-nonlinear microscopy. In all these techniques, the created super-nonlinearity significantly enhances the imaging contrast and concurrently extends the imaging depth-limit of TPFM. Conceptually different from conventional multiphoton processes mediated by virtual states, our strategy constitutes a new class of fluorescence microscopy where high-order nonlinearity is mediated by real population transfer.","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W1984805718","authors":[],"funders":[],"total_grants":0,"fwci":0.4796,"citation_percentile":0.7887574,"influential_citations":0,"citation_trend":[{"year":2017,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.spiedigitallibrary.org/conference-proceedings-of-spie/8948/894825/Super-nonlinear-fluorescence-microscopy-for-high-contrast-deep-tissue-imaging/10.1117/12.2038753.pdf","host_type":"journal"},{"url":"https://www.spiedigitallibrary.org/conference-proceedings-of-spie/8948/894825/Super-nonlinear-fluorescence-microscopy-for-high-contrast-deep-tissue-imaging/10.1117/12.2038753.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1117/12.2038753","host_type":"journal"},{"url":"https://authors.library.caltech.edu/86928/","host_type":"repository"}],"fields_of_study":["Advanced Fluorescence Microscopy Techniques","Photoacoustic and Ultrasonic Imaging","Spectroscopy Techniques in Biomedical and Chemical Research"],"mesh_terms":[],"keywords":["Microscopy","Fluorescence-lifetime imaging microscopy","Two-photon excitation microscopy","Optics","Photoactivated localization microscopy","Fluorescence microscope","Materials science","Fluorescence","Microscope","Laser","Population","Penetration depth","Super-resolution microscopy","Nuclear magnetic resonance","Physics","Scanning confocal electron microscopy"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-13T00:21:04.428732Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}