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Adv."],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    larvae provide a powerful model for interrogating genes associated with human muscle and neurological disorders; however, existing genotyping and phenotyping approaches remain low-throughput and often rely on destructive, invasive, or toxic procedures. Here, we present a scalable bioelectronic platform that enables real-time, simultaneous mechano-electrophysiological recording from freely moving\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    larvae in an open three-dimensional (3D) space, allowing high-throughput cross-modal genotype mapping (CMGM). The system integrates conductive and piezoelectric microneedle electrodes into a flexible sensory array that achieves stable, long-term signal acquisition during unrestricted and complex 3D locomotion. By coupling dual-modal signal acquisition with machine-learning-assisted classification, we directly identify muscle defects in unlabeled RNAi-knockdown larvae within 30 minutes, without invasive manipulation or time-consuming sample preparation. Incorporation of both electrophysiological and mechanical waveform features improves overall classification accuracy to 96%, outperforming single-modality approaches. This non-destructive, high-throughput CMGM strategy establishes a generalizable framework for bridging genotype and phenotype in intact, freely behaving organisms, with broad implications for functional genetics and disease modeling.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef7492","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:04:04Z","timestamp":1789754644000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Real-time, cross-modal genotype mapping of free-moving\n                    <i>Drosophila<\/i>\n                    larvae via simultaneous mechano-electrophysiological recording"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5911-4250","authenticated-orcid":true,"given":"Kairu","family":"Dong","sequence":"first","affiliation":[{"name":"Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou 310027, China."},{"name":"State Key Laboratory of Advanced Drug Delivery and Release Systems, School of Pharmacy, Zhejiang University, Hangzhou 310058, China."},{"name":"College of Biomedical Engineering &amp; 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