{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:50:18Z","timestamp":1782949818766,"version":"3.54.5"},"posted":{"date-parts":[[2026,4,20]]},"group-title":"Bioengineering","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The rapid convergence of optical innovation and machine intelligence is reshaping biological imaging by enabling platforms that jointly advance image formation and computational reconstruction for highspeed, high-resolution volumetric microscopy. However, broadly accessible three-dimensional imaging at high spatiotemporal resolution remains limited by the reliance of existing supervised methods on large modality-matched training datasets, the computational burden of conventional iterative reconstruction, and sensitivity to optical mismatch arising from small deviations in the spatial-angular point spread functions. Here, we introduce HYPER-Net, a physics-conditioned self-supervised framework for Fourier light-field microscopy that integrates scan-free volumetric acquisition with fast, robust three-dimensional reconstruction. HYPER-Net incorporates experiment-specific point-spread functions into the learning process in two complementary roles: as the forward operator that enforces measurement consistency and as a conditioning signal that adaptively modulates intermediate feature representations. This design reduces reliance on paired experimental ground-truth volumes, improves robustness to system variation, and enables generalizable reconstruction across diverse biological contexts. Using human colon organoids, embryonic\n                  <jats:italic>Xenopus<\/jats:italic>\n                  laevis hearts, hiPSC-derived cardiac spheroids, and freely moving\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  , we demonstrate high-fidelity volumetric imaging of tissue morphology, cardiac function, calcium-contraction coupling, and locomotion-associated neural and muscular dynamics. These results position HYPER-Net as a versatile framework for rapid volumetric imaging and quantitative analysis of dynamic biological systems across basic research and biomedical applications.\n                <\/jats:p>","DOI":"10.64898\/2026.04.14.718527","type":"posted-content","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:30:14Z","timestamp":1776706214000},"source":"Crossref","is-referenced-by-count":0,"title":["HYPER-Net: Physics-Conditioned Self-Supervised Reconstruction for Fourier Light-Field Microscopy"],"prefix":"10.64898","author":[{"given":"Zhi","family":"Ling","sequence":"first","affiliation":[{"name":"Laboratory for Systems Biophotonics, Georgia Institute of Technology, Atlanta, Georgia, USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA,"},{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA"},{"name":"George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5946-0808","authenticated-orcid":false,"given":"Xuanwen","family":"Hua","sequence":"additional","affiliation":[{"name":"Laboratory for Systems Biophotonics, Georgia Institute of Technology, Atlanta, Georgia, USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory for Systems Biophotonics, Georgia Institute of Technology, Atlanta, Georgia, USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory for Systems Biophotonics, Georgia Institute of Technology, Atlanta, Georgia, USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucinda M","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvin","family":"Forghani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Pierce","sequence":"additional","affiliation":[{"name":"School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge-Ah R","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Takayama","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA,"},{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Nie","sequence":"additional","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA"},{"name":"School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Xu","sequence":"additional","affiliation":[{"name":"Wallace H. 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