{"doi":"10.1101/2022.08.05.502947","title":"EDoF-Miniscope: pupil engineering for extended depth-of-field imaging in a fluorescence miniscope","abstract":"Abstract Extended depth of field (EDoF) microscopy has emerged as a powerful solution to greatly increase the access into neuronal populations in table-top imaging platforms. Here, we present EDoF-Miniscope, which integrates an optimized thin and lightweight binary diffractive optical element (DOE) onto the gradient refractive index (GRIN) lens of a head-mounted fluorescence miniature microscope, i.e. “miniscope”. We achieve an alignment accuracy of 70 μm to allow a 2.8X depth-of-field extension between the twin foci. We optimize the phase profile across the whole back aperture through a genetic algorithm that considers the primary GRIN lens aberrations, optical property of the submersion media, and axial intensity loss from tissue scattering in a Fourier optics forward model. Compared to other computational miniscopes, our EDoF-Miniscope produces high-contrast signals that can be recovered by a simple algorithm and can successfully capture volumetrically distributed neuronal signals without significantly compromising the speed, signal-to-noise, signal-to-background, and maintain a comparable 0.9-μm lateral spatial resolution and the size and weight of the miniature platform. We demonstrate the robustness of EDoF-Miniscope against scattering by characterizing its performance in 5-μm and 10-μm beads embedded in scattering phantoms. We demonstrate that EDoF-Miniscope facilitates deeper interrogations of neuronal populations in a 100-μm thick mouse brain sample, as well as vessels in a mouse brain. Built from off-the-shelf components augmented by a customizable DOE, we expect that this low-cost EDoF-Miniscope may find utility in a wide range of neural recording applications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300332,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559398,"name":"Yujia Xue","orcid":"0000-0003-0144-3981","position":1,"is_corresponding":false},{"id":319930,"name":"Jeffrey Alido","orcid":"0000-0001-9730-5596","position":2,"is_corresponding":false},{"id":393579,"name":"Alex Matlock","orcid":"0000-0002-4337-2715","position":3,"is_corresponding":false},{"id":862063,"name":"Guorong Hu","orcid":"0009-0006-7446-0140","position":4,"is_corresponding":false},{"id":256592,"name":"Kıvılcım Kılıç","orcid":"0000-0001-7248-8728","position":5,"is_corresponding":false},{"id":450738,"name":"Ian G. Davison","orcid":"0000-0003-0998-7676","position":6,"is_corresponding":false},{"id":374502,"name":"Lei Tian","orcid":"0000-0002-1316-4456","position":7,"is_corresponding":false},{"id":990783,"name":"J. E. Greene","orcid":"0000-0002-7825-4030","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:53.559757Z","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":[]}